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Background photo on cover by James Lockey, M.D.: Photomicrograph of a rat lung in inhalation studies with airborne fibers.
Inset photo on cover, courtesy of Kevin H. Dunn: NIOSH industrial hygienist performing air sampling to evaluate engineering controls in simulated work ac-tivities using RCF materials.
Criteria for a Recommended Standard
Occupational Exposure to Refractory Ceramic Fibers
DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention
National Institute for Occupational Safety and Health
ii Refractory Ceramic Fibers
This document is in the public domain and may be freely copied or reprinted.
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DHHS (NIOSH) Publication No. 2006–123
May2006
Safe • Healthier • PeopleTM
Refractory Ceramic Fibers iii
Foreword
WhentheU.S.CongresspassedtheOccupationalSafetyandHealthActof1970(PublicLaw91–596),itestablishedtheNationalInstituteforOccupationalSafetyandHealth(NIOSH).ThroughtheAct,CongresschargedNIOSHwithrecommendingoccupationalsafetyandhealthstandardsanddescribingexposurelimitsthataresafeforvariousperiodsofemployment.Theselimitsin-cludebutarenotlimitedtotheexposuresatwhichnoworkerwillsufferdiminishedhealth,func-tionalcapacity,orlifeexpectancyasaresultofhisorherworkexperience.Bymeansofcriteriadocuments,NIOSHcommunicatestheserecommendedstandardstoregulatoryagencies(includ-ingtheOccupationalSafetyandHealthAdministration[OSHA]),healthprofessionalsinacademicinstitutions,industry,organizedlabor,publicinterestgroups,andothersintheoccupationalsafetyandhealthcommunity.Criteriadocumentscontainacriticalreviewofthescientificandtechni-calinformationabouttheprevalenceofhazards,theexistenceofsafetyandhealthrisks,andtheadequacyofcontrolmethods.
Thiscriteriadocumentisderivedfromreviewsof informationfromhumanandanimalstudiesofthetoxicityofrefractoryceramicfibers(RCFs)andisintendedtodescribethepotentialhealtheffectsofoccupationalexposuretoairbornefibersofthismaterial.RCFsareamorphoussyntheticfibersproducedbythemeltingandblowingorspinningofcalcinedkaolinclayoracombinationofalumina,silica,andotheroxides.RCFsbelongtotheclassofsyntheticvitreousfibers(SVFs)—ma-terialsthatalsoincludefibersofglasswool,rockwool,slagwool,andspecialtyglass.RCFsareusedincommercialapplicationsrequiringlightweight,high-heatinsulation(e.g.,furnaceandkilninsu-lation).CommercialproductionofRCFsbeganinthe1950sintheUnitedStates,andproductionincreaseddramaticallyinthe1970s.DomesticproductionofRCFsin1997totaledapproximately107.7millionlb.Currently,totalU.S.productionhasbeenestimatedat80millionlbperyear,whichconstitutes1%to2%ofSVFsproducedworldwide.IntheUnitedStates,approximately31,500workershavethepotentialforoccupationalexposuretoRCFsduringdistribution,handling,installation,andremoval.Morethan800oftheseworkersareemployeddirectlyinthemanufactur-ingofRCFsandRCFproducts.WithincreasingproductionofRCFs,concernsaboutexposurestoairbornefiberspromptedanimalinhalationstudiesthathaveindicatedanincreasedincidenceofmesotheliomasinhamstersandlungcancerinratsfollowingexposuretoRCFs.StudiesofworkerswhomanufactureRCFshaveshownapositiveassociationbetweenincreasedexposuretoRCFsandthedevelopmentofpleuralplaques,skinandeyeirritation,andrespiratorysymptomsandcon-ditions(includingdyspnea,wheezing,andchroniccough).Inaddition,currentandformerRCFproductionworkershaveshowndecrementsinpulmonaryfunction.
Afterevaluatingthisevidence,NIOSHproposesarecommendedexposurelimit(REL)forRCFsof0.5fiberpercubiccentimeter (f/cm3)ofairasa time-weightedaverage(TWA)concentra-tionforuptoa10-hrworkshiftduringa40-hrworkweek.LimitingairborneRCFexposurestothisconcentrationwillminimizetheriskfor lungcancerandirritationoftheeyesandupper
iv Refractory Ceramic Fibers
respiratorysystemandisachievablebasedonareviewofexposuremonitoringdatacollectedfromRCFmanufacturersandusers.However,becausearesidualriskofcancer(lungcancerandpleuralmesothelioma)maystillexistattheREL,continuedeffortsshouldbemadetowardreducingexpo-surestolessthan0.2f/cm3.Engineeringcontrols,appropriaterespiratoryprotectionprograms,andotherpreventivemeasuresshouldbeimplementedtominimizeworkerexposurestoRCFs.NIOSHurgesemployerstodisseminatethisinformationtoworkersandcustomers.NIOSHalsorequeststhatprofessionalandtradeassociationsandlabororganizationsinformtheirmembersaboutthehazardsofexposuretoRCFs.
JohnHoward,M.D.Director,NationalInstituteforOccupationalSafetyandHealthCentersforDiseaseControlandPrevention
Foreword
Refractory Ceramic Fibers v
Executive Summary
lungcancer.However,studiesofworkerpopu-lationswithoccupationalexposuretoairborneRCFshaveshownanassociationbetweenex-posure and the formation of pleural plaques,increasedprevalenceofrespiratorysymptomsand conditions (dyspnea, wheezing, chroniccough),decreasesinpulmonaryfunction,andskin,eye,andupperrespiratorytractirritation[Lemastersetal.1994,1998;Lockeyetal.1996].Increased decrements in pulmonary functionamongworkersexposedtoRCFswhoarecur-rent or former cigarette smokers indicate anapparent synergistic effect between smokingandRCFexposure[Lemastersetal.1998].Thisfindingisconsistentwithstudiesofotherdust-exposed populations. The implementation ofimprovedengineeringcontrolsandworkprac-ticesinRCFmanufacturingprocessesandenduseshaveledtodramaticdeclinesinairbornefiberexposureconcentrations[Riceetal.1996,1997;Maximetal.2000a],whichinturnhavelowered the risk of symptoms and health ef-fectsforexposedworkers.
In2002,theRefractoryCeramicFibersCoali-tion(RCFC)establishedtheProductSteward-ship Program (PSP), which was endorsed bythe Occupational Safety and Health Admin-istration(OSHA).ContainedinthePSPwererecommendationsforanRCFexposureguide-lineof0.5fiberpercubiccentimeter(f/cm3)ofairasatime-weightedaverage(TWA)basedonthecontentionthatexposuresat thisconcen-tration could be achieved in most industriesthatmanufacturedorusedRCFs.Atthistime,the available health data do not provide suf-ficientevidence forderivingaprecisehealth-based occupational exposure limit to protect
TheNationalInstituteforOccupationalSafetyandHealth(NIOSH)hasrevieweddatachar-acterizing occupational exposure to airbornerefractoryceramicfibers(RCFs)andinforma-tion about potential health effects obtainedfromexperimentalandepidemiologicstudies.Fromthisreview,NIOSHdeterminedthatoc-cupationalexposuretoRCFsisassociatedwithadverserespiratoryeffectsaswellas skinandeyeirritationandmayposeacarcinogenicriskbasedontheresultsofchronicanimalinhala-tionstudies.
In chronic animal inhalation studies, expo-suretoRCFsproducedanincreasedincidenceofmesotheliomas inhamsters [McConnell etal. 1995] and lung cancer in rats [Mast et al.1995a,b].Thepotentialroleofnonfibrouspar-ticulatesgeneratedduringinhalationexposuresintheanimalstudiescomplicatestheissueofdeterminingtheexactmechanismsanddosesassociatedwiththetoxicityofRCFsinproduc-ingcarcinogeniceffects[Mastetal.2000].Theinductionofmesotheliomasand sarcomas inrats and hamsters following intrapleural andintraperitoneal implantation of RCFs pro-videdadditionalevidenceforthecarcinogenicpotential of RCFs [Wagner et al. 1973; Davisetal.1984;Smithetal.1987;Pottetal.1987].Lung tumors have also been observed in ratsexposed to RCFs by intratracheal instillation[ManvilleCorporation1991].
IncontrasttothecarcinogeniceffectsofRCFsobservedinexperimentalanimalstudies,epide-miologicstudieshavefoundnoassociationbe-tweenoccupationalexposuretoairborneRCFsandanexcessrateofpulmonaryfibrosisor
Executive Summary
vi Refractory Ceramic Fibers
against lung cancer. However, given what isknown from the animal and epidemiologicaldata, NIOSH supports the intent of the PSPand concurs that a recommended exposurelimit(REL)of0.5f/cm3asaTWAforuptoa10-hrworkshiftduringa40-hrworkweekwilllowertheriskfordevelopinglungcancer.Keeping exposures below the REL should re-duce the risk of lung cancer to estimates be-tween0.073/1,000and1.2/1,000(basedonex-trapolationsof riskmodels fromMoolgavkaretal.[1999]andYuandOberdörster[2000]).KeepingworkerexposuresbelowtheRELwillalsoreducetheriskofirritationoftheeyesandupperrespiratorysystem.
The risk for mesothelioma at 0.5 f/cm3 is notknown but cannot be discounted. Evidencefromepidemiologicstudiesshowedthathigherexposuresinthepastresultedinpleuralplaquesinworkers,indicatingthatRCFsdoreachpleu-raltissue.BothimplantationstudiesinratsandinhalationstudiesinhamstersshowthatRCFscancausemesothelioma.Becauseoflimitationsin thehamsterdata, the riskofmesotheliomacannotbequantified.However,thefactthatnomesotheliomahasbeen found inworkers andthatpleuralplaquesappear tobe less likely inworkerswithlowerexposuressuggestsa lowerriskformesotheliomaattheREL.
Because residual risks of cancer (lung cancerandpleuralmesothelioma)andirritationmaystill exist at the REL, NIOSH further recom-mends that all reasonable efforts be made toworktowardreducingexposurestolessthan0.2f/cm3.Atthisconcentration,therisksoflung
cancerareestimatedtobebetween0.03/1,000and0.47/1,000(basedonextrapolationsofriskmodelsfromMoolgavkaretal.[1999]andYuandOberdörster[2000]).
MaintainingairborneRCFconcentrationsbe-low the REL requires a comprehensive safetyand health program that includes provisionsforthemonitoringofworkerexposures,instal-lationandroutinemaintenanceofengineeringcontrols,andthetrainingofworkers ingoodworkpractices.Industry-ledeffortshavelike-wise promoted these actions by establishingthePSP.NIOSHbelievesthatmaintainingex-posures below the REL is achievable at mostmanufacturingoperationsandmanyuserap-plications, and that the incorporation of anactionlevel(AL)of0.25f/cm3intheexposuremonitoringstrategywillhelpemployersdeter-minewhenworkplaceexposureconcentrationsareapproachingtheREL.TheALconcepthasbeenanintegralelementofoccupationalstan-dardsrecommendedinNIOSHcriteriadocu-ments and in comprehensive standards pro-mulgatedbyOSHAand theMineSafetyandHealthAdministration(MSHA).
NIOSHalsorecommendsthatemployersim-plementadditionalmeasuresunderacompre-hensive safety and health program, includinghazardcommunication,respiratoryprotectionprograms, smoking cessation, and medicalmonitoring. These elements, in combinationwitheffortstomaintainairborneRCFconcen-trationsbelowtheREL,willfurtherprotectthehealthofworkers.
Refractory Ceramic Fibers vii
Contents
Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iiiExecutiveSummary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vAbbreviations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiGlossary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xivAcknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii
1 Recommendations for a Refractory Ceramic Fiber (RCF) Standard . . . 11.1RecommendedExposureLimit(REL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2DefinitionsandCharacteristics.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2.1NaturallyOccurringMineralFibers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2.2RCFs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21.2.3SVFs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.3SamplingandAnalysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21.4ExposureMonitoring. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.4.1SamplingSurveys. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.4.2ActionLevel. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.5HazardCommunication.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41.6Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41.7ProductFormulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41.8EngineeringControlsandWorkPractices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.8.1EngineeringControls. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51.8.2WorkPractices.................................................. 5
1.9RespiratoryProtection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.9.1RespiratoryProctectionProgram. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61.9.2RespiratorSelection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.10SanitationandHygiene. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71.11MedicalMonitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.11.1OversightoftheProgram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91.11.2ElementsoftheMedicalMonitoringProgram . . . . . . . . . . . . . . . . . . . . . . 9
1.12LabelingandPosting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111.13SmokingCessation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
2 Background and Description of RCFs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132.1Scope............................................................... 13
viii Refractory Ceramic Fibers
Contents
2.2Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132.3ChemicalandPhysicalPropertiesofRCFs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.3.1FiberDimensions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142.3.2FiberDurability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
3 RCF Production and Potential for Worker Exposure . . . . . . . . . . . . . . . . . 183.1Production. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183.2PotentialforWorkerExposure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183.3RCFManufacturingProcess. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183.4RCFProductsandUses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
3.4.1ExamplesofProducts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203.4.2ExamplesofApplications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
4 Assessing Occupational Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224.1AirSamplingandAnalyticalMethods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224.2SamplingforAirborneFibers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
4.2.1NIOSHFiber-CountingRules. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224.2.2EuropeanFiber-CountingRules. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
4.3SamplingforTotalorRespirableParticulates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234.4SamplingforAirborneSilica . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244.5IndustrialHygieneSurveysandExposureAssessments. . . . . . . . . . . . . . . . . . . . . . 24
4.5.1UniversityofPittsburghSurveyofExposuresDuringRCFManufacturing 254.5.2UniversityofCincinnatiStudyofExposuresDuringRCFManufacturing. 254.5.3RCFC/EPAConsentAgreementMonitoringData . . . . . . . . . . . . . . . . . . . . 264.5.4ExposuresDuringInstallationandRemovalofRCFFurnaceInsulation. . 314.5.5International(Canadian,Swedish,andAustralian)SurveysofRCFExposure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334.5.6JohnsHopkinsUniversityIndustrialHygieneSurveys. . . . . . . . . . . . . . . . . 344.5.7NIOSHHHEsandAdditionalSourcesofRCFExposureData. . . . . . . . . . 344.5.8Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
5 Effects of Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385.1HealthEffectsinAnimals(InVivoStudies). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
5.1.1Intrapleural,Intraperitoneal,andIntratrachealStudies. . . . . . . . . . . . . . . . 385.1.2ChronicInhalationStudies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425.1.3DiscussionofRCFStudiesinAnimals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535.1.4LungOverloadArgumentRegardingInhalationStudiesinAnimals . . . . . 56
5.2CellularandMolecularEffectsofRCFs(InVitroStudies). . . . . . . . . . . . . . . . . . . 585.3HealthEffectsinHumans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
5.3.1MorbidityandMortalityStudies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605.3.2RadiographicAnalyses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
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5.3.3RespiratoryConditionsandSymptomAnalyses. . . . . . . . . . . . . . . . . . . . . . 765.3.4PulmonaryFunctionTesting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 775.3.5MortalityStudies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 785.3.6NIOSHHHEs.................................................. 805.3.7Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
5.4CarcinogenicityRiskAssessmentAnalyses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
5.4.1DECOS[1995] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 835.4.2Fayerweatheretal.[1997].. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 855.4.3Moolgavkaretal.[1999] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 855.4.4Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
6 Discussion and Summary of Fiber Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . 896.1SignificanceofStudieswithRCFs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 896.2FactorsAffectingFiberToxicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
6.2.1FiberDose. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 916.2.2FiberDimensions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 916.2.3FiberDurability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
6.3SummaryofRCFToxicityandExposureData. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
7 Existing Standards and Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . 96
8 Basis for the Recommended Standard . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 998.1Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 998.2RationalefortheREL. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
8.2.1CarcinogenesisinAnimalStudies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1018.2.2HealthEffectsStudiesofWorkersExposedtoRCFs. . . . . . . . . . . . . . . . . . . 1068.2.3CarcinogenicRiskinHumans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1078.2.4ControllingRCFExposuresintheWorkplace. . . . . . . . . . . . . . . . . . . . . . . . 109
8.3Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
9 Guidelines for Protecting Worker Health . . . . . . . . . . . . . . . . . . . . . . . . . . . 1139.1InformingWorkersaboutHazards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
9.1.1SafetyandHealthTrainingProgram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1139.1.2LabelingandPosting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
9.2HazardPreventionandControl. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
9.2.1EngineeringControls. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1149.2.2ProductReformulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1179.2.3WorkPracticesandHygiene. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1179.2.4PersonalProtectiveEquipment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1189.2.5RespiratoryProtection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
9.3ExposureMonitoring. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
x Refractory Ceramic Fibers
Contents
9.3.1WorkplaceExposureMonitoringProgram . . . . . . . . . . . . . . . . . . . . . . . . . . 1199.3.2ActionLevel. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1219.3.3SamplingStrategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
9.4MedicalMonitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
9.4.1ObjectivesofMedicalMonitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1229.4.2CriteriaforMedicalScreening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1229.4.3WorkerParticipation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1239.4.4MedicalMonitoringProgramDirector . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1239.4.5RecommendedProgramElements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 9.4.6WrittenReportstotheWorker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1269.4.7WrittenReportstotheEmployer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1279.4.8EmployerActions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
9.5SurveillanceofHealthOutcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1279.6SmokingCessation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
10 Research Needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
AppendicesA.AirSamplingMethods.................................................. 147B.FunctionalJobCategoriesforRCFWorkers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179C.CellularandMolecularEffectsofRCFs(InVitroStudies) . . . . . . . . . . . . . . . . . . . . 183
Refractory Ceramic Fibers xi
Abbreviations
ACGIH AmericanConferenceofGovernmentalIndustrialHygienistsACS AmericanCancerSocietyAl aluminumAL actionlevelA1
2O
3alumina
Al2Si
2O
5[OH]
4siliceouskaolin
AM arithmeticmeanAPF assignedprotectionfactorATSDR AgencyforToxicSubstancesDiseaseRegistryB
2O
3boronoxide
BAL bronchoalveolarlavage°C degree(s)CelsiusCaO calciumoxideCFR CodeofFederalRegulationsCI confidenceintervalDECOS DutchExpertCommitteeonOccupationalStandardsdG 2-deoxyguanosineDNA deoxyribonucelicacidEDXA energydispersiveX-rayanalyzere.g. forexampleEID EducationandInformationDivisionEPA U.S.EnvironmentalProtectionAgency°F degree(s)Fahrenheitf/cm3 fiberspercubiccentimeterofairFe ironFEF
25–75 forcedexpiratoryflow(liter/second)between25%and75%ofthe
forcedvitalcapacityFe
2O
3 ferricoxide
FEV1 forcedexpiratoryvolumeinonesecond
FEV1/FVC ratioofforcedexpiratoryvolumeinonesecondtoforcedvital
capacityFJC functionaljobcategoryFVC forcedvitalcapacityg/cm3 gramspercubicmeterofairGM geometricmean
xii Refractory Ceramic Fibers
Abbreviations
GMD geometricmeandiameter
GML
geometricmeanlengthGSD geometricstandarddeviationGSH glutathioneγ-GT γ-glutamyltransferaseHEPA high-efficiencyparticulateairHHE HealthHazardEvaluationhr hour(s)HTE hamstertrachealepithelialIARC InternationalAgencyforResearchonCanceri.e. thatisIgG immunoglobulinIJT industryjobtitleILO InternationalLaborOfficeILs interleukinsK
2O potassiumoxide
lb pound(s)LDH lactosedehydrogenaseLOAEL lowestobservableadverseeffectlevelLOD limitofdetectionMAC maximumachievableconcentrationMAN ManvilleRCFmg/m3 milligramspercubicmeterMgO magnesiumoxidemin minute(s)ml milliliter(s)MLE maximumlikelihoodestimatemm millimeter(s)MMC metalmatrixcompositesMMMF man-mademineralfiberMMVF man-madevitreousfiberMSDS materialsafetydatasheetMSHA MineSafetyandHealthAdministrationMTD maximumtolerateddoseMVK Moolgavkar-Venzon-Knudsonn numberNa
2O sodiumoxide
ng nanogram(s)NIEHS NationalInstituteofEnvironmentalHealthSciencesNIOSH NationalInstituteforOccupationalSafetyandHealth
Refractory Ceramic Fibers xiii
Abbreviations
nl nanoliter(s)NOAEL noobservableadverseeffectlevelNTP NationalToxicologyProgramODC ornithinedecarboxylaseOM OsborneMendelOR oddsratioOSHA OccupationalSafetyandHealthAdministrationP probabilityPA posteroanteriorPCM phasecontrastopticalmicroscopyPEL permissibleexposurelimitPFT pulmonaryfunctiontestPG prostaglandinPPE personalprotectiveequipmentPSP ProductStewardshipProgramRCF refractoryceramicfiberRCFC RefractoryCeramicFibersCoalitionREL recommendedexposurelimitROM reactiveoxygenmetaboliteROS reactiveoxygenspeciesRPM rodentpleuralmesothelialSAED selectedareaelectrondiffractionSD standarddeviationSEM scanningelectronmicroscopySi siliconSiO
2silicondioxide
SMR standardizedmortalityratioSVF syntheticvitreousfiberTEM transmissionelectronmicroscopyTIMA ThermalInsulationManufacturersAssociationTiO
2titaniumdioxide
TLV thresholdlimitvalueTNF tumornecrosisfactorTWA time-weightedaverageUCL upperconfidencelimitUICC UnionInternationaleContreleCancerUJT uniformjobtitlesWHO WorldHealthOrganizationZrO
2 zirconiumdioxide
µm micrometer
xiv Refractory Ceramic Fibers
Glossary
Action level (AL):Astatisticallyderivedconceptusedtopermitanemployertohaveconfidence(e.g.,95%)thatifameasuredexposureconcentrationisbelowtheAL,thenonlyasmallprobabilityexiststhattheactualconcentrationisabovetheexposurelimit. Oftenestablishedashalfoftheexposurelimit,theALshouldbedesignatedfordeterminingwhenadditionalcontrolsareneededoradminis-trativeactionsshouldbetakentoreduceexposures.Thepurposeofusingthisreferenceistoindicatewhenworkerexposurestohazardoussubstancesmaybeapproachingtheexposurelimit.
After-service refractory ceramic fiber (RCF):RCFthathasbeensubjectedtogreaterthan1,800oF(~1,000oC)andhaspartiallyconvertedtothesilicapolymorphcristobalite.Inexperimentalstud-ies,thisfiberisalsocalledRCF4.
Aspect ratio:Thelengthtowidthratioofafiber.
Costophrenic angle:Locationonachestradiographwheretheribsandthediaphragmappeartomeet.
Dyspnea grade 1:Shortnessofbreathonexertion,classifiedaslessseverethangrade2.
Dyspnea grade 2:Shortnessofbreathonexertion,excludingshortnessofbreathassociatedwithhurryingonthelevelorwalkingupaslighthill,andclassifiedasmoreseverethandys-pneagrade1.
FEF25–75
:Forcedexpiratoryflow(liter/second) that isbetween25%and75%of the forcedvitalcapacity.
FEV1:Forcedexpiratoryvolumeinonesecond,orthemaximumvolumeofairthatcanbeforcibly
expiredduringthefirstsecondofexpirationfollowingamaximalinspiration.
Fiber counting rules:Criteriaforidentifyingandcountingfibersduringairsamplingandexposureassessment.Thethreemainconventions forfibercountingaredescribedbelow(and inSection4.2.1andAppendixA).
■ NIOSH “A” rules—anyparticle>5µmlongwithanaspectratio(lengthtowidth)greaterthan3:1isconsideredafiber.
■ NIOSH “B” rules—anyparticle>5µmlongwithanaspectratioequaltoorgreaterthan5:1andadiameter<3µmisconsideredafiber.
■ World Health Organization (WHO) reference method for man-made mineral fiber—anyparticle>5µmlongwithanaspectratioequaltoorgreaterthan3:1andadiameter<3µmisconsideredafiber.
Refractory Ceramic Fibers xv
Glossary
FVC:Forcedvitalcapacityorthemaximumvolumeofair(inliters)thatcanbeforciblyexpiredfromthelungsfollowingamaximalinspiration.
High-efficiency particulate air (HEPA) filter:Adry-typefilterusedtoremoveairborneparticleswithanefficiencyequaltoorgreaterthan99.97%for0.3-µmparticles.Thelowestfilteringeffi-ciencyof99.97%isassociatedwith0.3-µmparticles,whichisapproximatelythemostpenetratingparticlesizeforparticulatefilters.
Inspirable dust:Thefractionofairborneparticlesthatwouldbeinspiredthroughthemouthandnoseofaworker.
MAN:ArefractoryceramicfiberproducedbytheJohnsManvilleCompany.
Occupational medical monitoring (incorporating medical screening, surveillance):Theperiodicmedicalevaluationofworkerstoidentifypotentialhealtheffectsandsymptomsrelatedtooccupa-tionalexposuresorenvironmentalconditionsintheworkplace.Anoccupationalmedicalmonitor-ingprogramisasecondarypreventionmethodbasedontwoprocesses,screeningandsurveillance.Occupationalmedicalscreeningfocusesonearlydetectionofhealthoutcomesforindividualwork-ers.Screeningmayinvolveanoccupationalhistoryassessment,medicalexamination,andmedicalteststodetectthepresenceoftoxicantsorearlypathologicchangesbeforetheworkerwouldnor-mallyseekclinicalcareforsymptomaticdisease.Occupationalmedical surveillanceinvolvestheongoingevaluationofthehealthstatusofagroupofworkersthroughthecollectionandanalysisofhealthdataforthepurposeofdiseasepreventionandforevaluatingtheeffectivenessofinterven-tionprograms.
Pleural plaques:Discreteareasofthickeningthataregenerallyontheparietalpleuraandaremostcommonly locatedat themidcostalandposteriorcostalareas, thedomeof thediaphragm,andthemediastinalpleura.Presenceofplaquesisanindicationofexposuretoafibroussilicate,mostfrequentlyasbestos.
Radiographic opacity:AshadowonachestX-rayfilmgenerallyassociatedwithafibrogenicre-sponsetodustretainedinthelungs[Morgan1995].Opacitiesareclassifiedbysize,shape,location,andprofusionaccordingtoguidelinesestablishedbytheInternationalLaborOffice[ILO2000]www.ilo.org/public/english/support/publ/books.htm).
Refractory ceramic fiber (RCF):Anamorphous,syntheticfiber(ChemicalAbstractsServicesNo.142844–00–6)producedbymeltingandblowingorspinningcalcinedkaolinclayoracombina-tionofalumina(Al
2O
3)andsilicondioxide(SiO
2).Oxidesmaybeaddedsuchaszirconia,ferric
oxide,titaniumoxide,magnesiumoxide,calciumoxide,andalkalies.Thepercentage(byweight)ofcomponentsisasfollows:alumina,20%to80%;silicondioxide,20%to80%;andotheroxidesinsmalleramounts.
Respirable-sized fiber:Particles>5µmlongwithanaspectratio>3:1anddiameter≤1.3µm.
Shot:NonfibrousparticulatethatisgeneratedduringtheproductionofRCFsfromtheoriginalmeltbatch.
xvi Refractory Ceramic Fibers
Glossary
Standardized mortality ratio (SMR):Theratiooftheobservednumberofdeaths(fromaspecifiedcause)totheexpectednumberofdeaths(fromthatsamecause)thathasbeenadjustedtoaccountfordemographicdifferences(e.g.,age, sex, race)betweenthestudypopulationandthereferentpopulation.
Synthetic vitreous fiber (SVF):Anyofanumberofmanufacturedfibersproducedbythemeltingandsubsequentfiberizationofkaolinclay,sand,rock,slag,etc.Fibrousglass,mineralwool,ceramicfibers,andalkalineearthsilicatewoolsarethemajortypesofSVF,alsocalledman-mademineralfiber(MMMF)orman-madevitreousfiber(MMVF).
Thoracic-sized fiber:Particles>5µmlongwithaspectratio>3:1andadiameter<3to3.5µm.Thoracicreferstoparticlespenetratingtothethorax(50%cutat10-µmaerodynamicdiameter).Mineralandvitreousfiberswithdiameters3to3.5µmhaveanaerodynamicdiameterofapproxi-mately10µm.
Refractory Ceramic Fibers xvii
Acknowledgments
ThisdocumentwaspreparedbytheEducationandInformationDivision(EID),PaulSchulte,Ph.D.,Director.ThomasLentz,Ph.D.;KathleenMacMahon,D.V.M.;RalphZumwalde;andClaytonDoakweretheprincipleauthorsofthisdocument.OthermembersoftheDocumentDevelopmentBranch,inparticularMarieHaringSweeney,Ph.D.,wereextremelyhelpfulinprovidingtechnicalreviewsandcomments.
Forcontributionstothetechnicalcontentandreviewofthisdocument,theauthorsgratefullyac-knowledgethefollowingNIOSHpersonnel:
Education and Information Division
HeinzAhlers,J.D.JohnBailer,Ph.D.JeffBryantDavidDankovic,Ph.D.JeromeFleschCharlesGeraci,Ph.D.StephenGilbertG.KentHatfield,Ph.D.EileenKuempel,Ph.D.BonitaMalit,M.D.RichardNiemeier,Ph.D.RonaldSchulerJohnSheehy,Ph.D.RandallSmithLeslieStayner,Ph.D.DavidVotawJoannWessJohnWhalen
Division of Applied Research and Technology
PaulBaron,Ph.D.KevinH.DunnJosephFernbackLaurenceReedLloydStettler,Ph.D.MarkToraason,Ph.D.
Division of Surveillance, Hazard Evaluations, and Field Studies
MitchellSingal,M.D.
Division of Respiratory Disease Studies
DonaldCampbellRobertCastellan,M.D.DanielHewettPaulHewett,Ph.D.MarkHoover,Ph.D.PaulMiddendorf,Ph.D.ErnestMoyer,Ph.D.JohnParker,M.D.LeePetsonk,M.D.
Health Effects Laboratory Division
VincentCastranova,Ph.D.DanLewisKennethWeber,Ph.D.
Pittsburgh Research Laboratory
AndrewCecala
Office of the Director
FrankHearl,P.E.AnitaSchill,Ph.D.RosemarySokas,M.D.
xviii Refractory Ceramic Fibers
Acknowledgments
TheauthorswishtothankSusanAfanuh,VanessaBecks,GinoFazio,AnneHamilton,andJaneWeber for theireditorial supportandcontributions to thedesignand layoutof thisdocument.Clerical support in preparing this document was provided by Judith Curless, Pamela Graydon,RosmarieHagedorn,NormaLouHelton,andKristinaWasmund.
Finally,specialappreciationisexpressedtothefollowingindividualsandorganizationsforservingasindependentexternalreviewersandprovidingcommentsthatcontributedtothedevelopmentofthisdocument:
ChrisBurleyEuropeanCeramicFibresIndustryAssociationParis,France
JohnCherrie,Ph.D.LibertySafeWorkResearchCentreAberdeen,UnitedKingdom
JohnDement,Ph.D.DukeUniversityMedicalCenterDurham,NC
WilliamKojolaAFL-CIO,SafetyandHealthDepartmentWashington,DC
DavidLai,Ph.D.OfficeofPollutionPreventionandToxicsU.S.EnvironmentalProtectionAgencyWashington,DC
GraceLeMasters,Ph.D.UniversityofCincinnati,CollegeofMedicineCincinnati,OH
MortonLippmann,Ph.D.NewYorkUniversity,SchoolofMedicineTuxedo,NY
JamesLockey,M.D.UniversityofCincinnati,CollegeofMedicineCincinnati,OH
PeterMcClure,Ph.D.SyracuseResearchCorporationNorthSyracuse,NY
EugeneMcConnell,D.V.M.ToxPathRaleigh,NC
NationalInsulationAssociationAlexandria,VA
DennisO’Brien,Ph.D.UnitedAutomobile,AerospaceandAgriculturalImplementWorkersofAmericaDetroit,MI
RefractoryCeramicFibersCoalitionWashington,DC
CarolRice,Ph.D.UniversityofCincinnati,CollegeofMedicineCincinnati,OH
JolandaRijnkels,Ph.D.HealthCounciloftheNetherlandsDenHaag,TheNetherlands
ScottSchneiderLaborers’HealthandSafetyFundofNorthAmericaWashington,DC
JayTurim,Ph.D.SciencesInternational,Inc.Alexandria,VA
CindyFraleighWheelerOfficeofPollutionPreventionandToxicsU.S.EnvironmentalProtectionAgencyWashington,DC
Refractory Ceramic Fibers 1
1 Recommendations for a Refractory Ceramic Fiber (RCF) Standard
mesothelioma, and other adverse respiratoryhealth effects (including irritation and com-promisedpulmonaryfunction)associatedwithexcessiveRCFexposureintheworkplace.Lim-itingexposureswillalsoprotectworkers’eyesandskinfromthemechanicalirritationasso-ciatedwithexposuretoRCFs.Inmostmanu-facturingoperations,itiscurrentlypossibletolimitairborneRCFconcentrationsto0.5f/cm3orless.ExceptionsmayoccurduringRCFfin-ishing operations and during the installationandremovalofRCFproducts,whenthenatureof jobactivitiespresentsachallengetomeet-ing the REL. For these operations, additionalprotective measures are recommended. Engi-neeringandadministrativecontrols,respiratoruse,andotherpreventivemeasuresshouldbeimplementedtominimizeexposuresforwork-ers in RCF industry sectors where airborneRCF concentrations exceed the REL. NIOSHurgesemployers todisseminate this informa-tiontoworkersandcustomers,andRCFman-ufacturers should convey this information todownstream users. NIOSH also requests thatprofessional and trade associations and labororganizationsinformtheirmembersaboutthehazardsofexposuretoRCFs.
1.2 Definitions and Characteristics
1.2.1 Naturally Occurring Mineral Fibers
Manytypesofmineralfibersoccurnaturally.Asbestos is the most prominent of these fi-bersbecauseofitsindustrialapplication.The
TheNationalInstituteforOccupationalSafetyand Health (NIOSH) recommends that expo-suretoairbornerefractoryceramicfibers(RCFs)becontrolledintheworkplacebyimplementingthe recommendations presented in this docu-ment.Theserecommendationsaredesignedtoprotectthesafetyandhealthofworkersforuptoa10-hrworkshiftduringa40-hrworkweekovera40-yearworkinglifetime.Observanceoftheserecommendationsshouldpreventorgreatlyre-ducetherisksofeyeandskinirritationandad-verserespiratoryhealtheffects(includinglungcancer) in workers with exposure to airborneRCFs. Preventive efforts are primarily focusedon controlling and minimizing airborne fiberconcentrations to which workers are exposed.Exposuremonitoring,hazardcommunication,training, respiratoryprotectionprograms, andmedical monitoring are also important ele-mentsofacomprehensiveprogramtoprotectthehealthofworkers exposed toRCFs.Theseelements are described briefly in this chapterandingreaterdetailinChapter9.
1.1 Recommended Exposure Limit (REL)
NIOSHrecommendsthatoccupationalexpo-surestoairborneRCFsbelimitedto0.5fiberpercubiccentimeter(f/cm3)ofairasa time-weightedaverage(TWA)concentrationforuptoa10-hrworkshiftduringa40-hrworkweek,measured according to NIOSH Method 7400(Brules)[NIOSH1998].
This recommended exposure limit (REL) isintended to reduce the risk of lung cancer,
2 Refractory Ceramic Fibers
1 ■Recommendations for a Refractory Ceramic Fiber Standard
asbestosmineralsincludeboththeserpentineasbestos(chrysotile)andtheamphibolemin-eral fibers, including actinolite, amosite, an-thophyllite, crocidolite, and tremolite [Petersand Peters 1980]. Since ancient times, min-eralfibershavebeenminedandprocessedforuseasinsulationbecauseoftheirhightensilestrength, resistance to heat, durability in ac-idsandotherchemicals,andlightweight.Thepredominant forms of asbestos mined andused today are chrysotile (~95%), crocidolite(<5%),andamosite(<1%).
For thepurposesof thisdocument,naturallyoccurring mineral fibers are distinguishablefromsyntheticvitreousfibers(SVFs)basedonthecrystallinestructureofthemineralfibers.Thispropertycausesthemineralfiberstofrac-turelongitudinallywhensubjectedtomechan-ical stresses, thereby producing more fibersofdecreasingdiameter.By contrast, SVFsareamorphousandfracturetransversely,resultingin more fibers of decreasing length until thesegmentsarenolongerofsufficientlengthtobeconsideredfibers.Naturallyoccurringmin-eralfibersaregenerallymoredurableandlesssoluble than SVFs, a property that accountsfor thebiopersistenceandtoxicityofmineralfibersinvivo.
1.2.2 RCFs
RCFsarea typeofSVF; theyareamorphoussynthetic fibers produced from the meltingand blowing or spinning of calcined kaolinclayoracombinationofalumina(Al
2O
3)and
silicondioxide(SiO2).Oxidessuchaszirconia,
ferric oxide, titanium oxide, magnesium ox-ide,calciumoxide,andalkaliesmaybeadded.Thepercentageofcomponents(byweight) isasfollows:alumina,20%to80%;silicondiox-ide,20%to80%;andotheroxides insmalleramounts. Like the naturally occurring min-eral fibers, RCFs possess the desired qualities
of heat resistance, tensile strength, durability,and light weight. On a continuum, however,RCFsarelessdurable(i.e.,moresoluble)thantheleastdurableasbestosfiber(chrysotile)butmoredurablethanmostfibrousglassandoth-ertypesofSVFs.
1.2.3 SVFs
SVFsincludeanumberofmanmade(notnatu-rallyoccurring)fibersthatareproducedbythemeltingandsubsequentfiberizationofkaolinclay,sand,rock,slag,andothermaterials.ThemajortypesofSVFsarefibrousglass,mineralwool(slagwool,rockwool),andceramicfibers(includingRCFs).SVFsarealsofrequentlyre-ferredtoasmanmademineralfibers(MMMFs)ormanmadevitreousfibers(MMVFs).
1.3 Sampling and Analysis
Employers shall perform air sampling andanalysistodetermineairborneconcentrationsofRCFsaccordingtoNIOSHMethod7400(Brules)[NIOSH1998],providedinAppendixAofthisdocument.
1.4 Exposure Monitoring
Employersshallperformexposuremonitoringasfollows:
■ Establishaworkplaceexposuremonitor-ing program for worksites where RCFsorRCFproductsaremanufactured,han-dled,used,installed,orremoved.
■ Includeinthisprogramroutineareaandpersonal monitoring of airborne fiberconcentrations.
■ Designamonitoringstrategythatcanbeusedto
Refractory Ceramic Fibers 3
1 ■Recommendations for a Refractory Ceramic Fiber Standard
—evaluateaworker’sexposuretoRCFs,
—assesstheeffectivenessofengineeringcontrols, work practices, and otherfactors in controlling airborne fiberconcentrations,and
—identify work areas or job tasks inwhichworkerexposuresareroutinelyhigh and thus require additional ef-fortstoreducethem.
1.4.1 Sampling Surveys
Employersshallconductexposuremonitoringsurveystoensurethatworkerexposures(mea-suredbyfull-shiftsamples)donotexceedtheREL.BecauseadverserespiratoryhealtheffectsmayoccurattheREL,itisdesirabletoachievelowerconcentrationswheneverpossible.Whenworkers are potentially exposed to airborneRCFs,employersshallconductexposuremon-itoringsurveysasfollows:
■ Collect representative personal samplesovertheentireworkshift[NIOSH1997a].
■ Perform periodic sampling at least an-nually and whenever any major processchangetakesplaceorwheneveranotherreason exists to suspect that exposureconcentrationsmayhavechanged.
■ Collect all routine personal samples inthebreathingzonesoftheworkers.
■ Ifworkersareexposedtoconcentrationsabove the REL, perform more frequentexposure monitoring as engineeringchanges are implemented and until atleast two consecutive samples indicatethatexposuresnolongerexceedtheREL[NIOSH1977a].
■ Notifyallworkersofmonitoringresultsandofanyactionstakentoreducetheirexposures.
■ Whendevelopinganexposuresamplingstrategy,considervariationsinworkandproduction schedules as well as the in-herentvariabilityinmostareasampling[NIOSH1995a].
1.4.1.1 Focused sampling
WhensamplingtodeterminewhetherworkerRCF exposures are below the REL, a focusedsamplingstrategymaybemorepracticalthanarandomsamplingapproach.Afocusedsam-pling strategy targetsworkersperceived tobeexposedtothehighestconcentrationsofahaz-ardoussubstance[LeidelandBusch1994].Thisstrategyismostefficientforidentifyingexpo-sures above the REL if maximum-risk work-ersandtimeperiodsareaccuratelyidentified.Short tasks involving high concentrations ofairbornefibers could result in elevatedexpo-sureoverfullworkshifts.
SamplingstrategiessuchasthoseusedbyCornandEsmen[1979],Riceetal.[1997],andMax-imetal.[1997]havebeendevelopedandusedspecificallyinRCFmanufacturingfacilitiestomonitorairbornefiberconcentration.Inthesestrategies, representative workers are selectedfor sampling and are grouped according todust zones, uniform job titles, or functionaljobcategories.Theseapproachesareintendedtoreducethenumberofrequiredsamplesandincreasetheconfidenceofidentifyingworkersatsimilarrisk.
1.4.1.2 Area sampling
Areasamplingmaybeusefulinexposuremon-itoringtodeterminesourcesofairborneRCFsand to assess the effectiveness of engineeringcontrols.
1.4.2 Action Level
Anactionlevel(AL)athalftheREL(0.25f/cm3)shall be used to determine when additional
4 Refractory Ceramic Fibers
1 ■Recommendations for a Refractory Ceramic Fiber Standard
controls are needed or when administrativeactionsshouldbetakentoreduceexposuretoRCFs.ThepurposeofanAListoindicatewhenworkerexposurestohazardoussubstancesmaybe approaching the REL. When air samplescontainconcentrationsatorabovetheAL,theprobability is high that worker exposures tothehazardoussubstanceexceedtheREL.
TheALisastatisticallyderivedconceptpermit-tingtheemployertohaveconfidence(e.g.,95%)thatifresultsfrompersonalairsamplesarebe-lowtheAL,theprobabilityissmallthatworkerexposuresareabovetheREL.NIOSHhascon-cluded that theuseof anALpermits the em-ployer to monitor hazardous workplace expo-sureswithoutdaily sampling.TheALconcepthasservedasthebasisfordefiningtheelementsof an occupational standard in NIOSH crite-ria documents and comprehensive standardspromulgated by the Occupational Safety andHealthAdministration (OSHA) and the MineSafetyandHealthAdministration(MSHA).
1.5 Hazard CommunicationEmployersshalltakethefollowingmeasurestoinformworkersaboutRCFhazards:
■ Establish a safety and health trainingprogram for all workers who manufac-ture,use,handle,install,orremoveRCFproductsorperformotheractivitiesthatbringthemintocontactwithRCFs.
■ Inform employees and contract work-ers about hazardous substances in theirworkareas.
■ Instructworkersabouthowtogetinfor-mation frommaterial safetydata sheets(MSDSs)forRCFsandotherchemicals.
■ Provide MSDSs onsite and make themeasilyaccessible.
■ Inform workers about adverse respira-tory health effects associated with RCFexposures.
■ Inworkinvolvingtheremovalofrefrac-tory insulation materials, make workersaware of the potential for exposure torespirablecrystallinesilica,thehealthef-fectsrelatedtothisexposure,andmeth-odsforreducingexposures.
■ Make workers who smoke cigarettesor use other tobacco products aware oftheir increased risk of developing RCF-inducedrespiratorysymptomsandcon-ditions(seeSections1.12and9.6forrec-ommendationsaboutsmokingcessationprograms).
1.6 TrainingEmployersshallprovidethefollowingtrainingforworkersexposedtoRCFs:
■ Trainworkerstodetecthazardoussitua-tions.
■ Inform workers about practices or op-erations that may generate high air-bornefiberconcentrations(e.g.,cuttingandsandingRCFboardsandotherRCFproducts).
■ Trainworkershowtoprotectthemselvesby using proper work practices, engi-neeringcontrols,andpersonalprotectiveequipment(PPE).
1.7 Product FormulationOne factor recognized as contributing to thetoxicity of an inhaled fiber is its durabilityand resistance to degradation in the respira-torytract.ChemicalcharacteristicsplaceRCFsamongthemostdurableSVFs.Asaresult,an
Refractory Ceramic Fibers 5
1 ■Recommendations for a Refractory Ceramic Fiber Standard
inhaledRCFthatisdepositedinthealveolarre-gionofthelungwillpersistlongerinthelungsthan a less durable fiber. Therefore, NIOSHrecommends substituting a less durable fiberfor RCFs or reformulating the chemistry ofRCFstowardthisendtoreducethehazardforexposedworkers.Aspartofproductsteward-shipefforts,severalRCFproducerswithintheRefractory Ceramic Fibers Coalition (RCFC)havedevelopednewand lessbiopersistentfi-berstermedalkalineearthsilicatewools[Max-imetal.1999b].Newlydevelopedfibersshouldundergo industry-sponsored testing beforetheirselectionandcommercialusetoexcludepossibleadversehealtheffectsfromexposure.
1.8 Engineering Controls and Work Practices
1.8.1 Engineering Controls
Employersshalluseandmaintainappropriateengineeringcontrolstokeepairborneconcen-trationsofRCFsat orbelow the RELduringthe manufacture, use, handling, installation,and removal of RCF products. EngineeringcontrolsforcontrollingRCFsincludethefol-lowing:
■ Localexhaustventilationordustcollec-tion systems at or near dust-generatingsystems
—BandsawsusedinRCFmanufactur-ing and finishing operations havebeen fitted with such engineeringcontrols to capture fibers and dustduring cutting operations, therebyreducingexposuresforthebandsawoperator[Venturin1998].
—Discsandersfittedwithsimilar localexhaustventilationsystemseffectivelyreduce airborne RCF concentrations
duringthesandingofvacuum-formedRCFproducts[Dunnetal.2004].
■ Enclosed processes used during manu-facturing to keep airborne fibers con-tainedandseparatedfromworkers
■ Water knives, which are high-pressurewaterjetsthateffectivelycutandtrimtheedgesofRCFblanketwhile suppressingdust and limiting thegenerationof air-bornefibers
1.8.2 Work Practices
Employers shall implementappropriateworkpracticestohelpkeepworkerexposuresatorbelowtheRELforRCFs.The followingworkpractices are recommended to help reduceconcentrationsofairbornefibers:
■ Limittheuseofpowertoolsunlesstheyareequippedwith localexhaustordustcollectionsystems.
—Beawarethatmanuallypoweredhandtoolsgeneratelessdustandfewerair-borne fibers, but they often requireadditional physical effort and timeandmayincreasetheriskofmuscu-loskeletaldisorders.
—Theadditionalphysicaleffortrequiredby hand tools may also increase therateanddepthofbreathingandcon-sequently affect the inhalation rateanddepositionoffibersinthelungs.
■ Use ergonomically correct tools andproperworkstationdesigntoreducetheriskofmusculoskeletaldisorders.
■ Usehigh-efficiencyparticulateair-filtered(HEPA-filtered)vacuums.
6 Refractory Ceramic Fibers
1 ■Recommendations for a Refractory Ceramic Fiber Standard
■ Use wet sweeping to suppress airbornefiber and dust concentrations duringcleanup.
■ Whenremovingafter-serviceRCFprod-ucts,dampeninsulationwithalightwa-terspraytopreventfibersanddustfrombecoming airborne. (However, use cau-tion when dampening refractory linings during installation,sincewatercandam-age refractory-lined equipment, causingthegenerationofsteamandpossibleex-plosionduringheating.)
■ CleanworkareasregularlyusingaHEPA-filteredvacuumorwetsweepingtomini-mizeaccumulationofdebris.
■ Ensure that workers wear long-sleevedclothing,gloves,andeyeprotectionwhenperforming potentially dusty activitiesinvolving RCFs or RCF products. Forsome activities, disposable clothing orcoverallsmaybepreferred.
1.9 Respiratory ProtectionRespirators shall be used while performingany task for which the exposure concentra-tion is unknown or has been documented tobehigherthantheNIOSHRELof0.5f/cm3asaTWA.However,respiratorsshallnotbeusedastheprimarymeansofcontrollingworkerex-posures.
When possible, use other methods for mini-mizingworkerexposurestoRCFs:
■ Productsubstitution
■ Engineeringcontrols
■ Changesinworkpractices
Use respirators when available engineeringcontrolsandworkpracticesdonotadequately
control worker exposures below the REL forRCFs.NIOSHrecognizes that controllingex-posurestoRCFsisaparticularchallengeduringthefinishingstagesofRCFproductmanufac-turingandduringtheinstallationandremovalofrefractorymaterials
1.9.1 Respiratory Protection Program
When respiratory protection is needed, em-ployers shall establishacomprehensiverespi-ratoryprotectionprogramasdescribedintheOSHA respiratory protection standard [29CFR*1910.134].Elementsofarespiratorypro-tection program must be established and de-scribedinawrittenplanthatisspecifictotheworkplace.Theplanmustincludethefollow-ingelements:
■ Proceduresforselectingrespirators
■ Medicalevaluationsofworkersrequiredtowearrespirators
■ Fit-testingprocedures
■ Routine-use procedures and emergencyrespirator-useprocedures
■ Procedures and schedules for cleaning,disinfecting,storing,inspecting,repairing,discarding,andmaintainingrespirators
■ Procedures for ensuring adequate airqualityforsupplied-airrespirators
■ Traininginrespiratoryhazards
■ Training in the proper use and mainte-nanceofrespirators
■ Programevaluationprocedures
■ Proceduresforensuringthatworkerswhovoluntarily wear respirators (excludingfilteringfacepiecesknownasdustmasks)
*Code of Federal Regulations.SeeCFRinreferences.
Refractory Ceramic Fibers 7
1 ■Recommendations for a Refractory Ceramic Fiber Standard
complywiththemedicalevaluationandcleaning, storing, and maintenance re-quirementsofthestandard
■ Adesignatedprogramadministratorwhoisqualifiedtoadministertherespiratoryprotectionprogram
Employersshallupdatethewrittenprogramasnecessarytoaccountforchangesinthework-place that affect respirator use. In addition,employers are required to provide at no costtoworkersallequipment,training,andmedi-calevaluationsrequiredundertherespiratoryprotectionprogram.
1.9.2 Respirator Selection
WhenconditionsofexposuretoairborneRCFsexceedtheREL,properrespiratoryprotectionshallbeselectedasfollows:
■ Select, at a minimum, a half-mask, air-purifyingrespiratorequippedwitha100series particulate filter. This respiratorhasanassignedprotectionfactor(APF)of10.
■ Provideahigherlevelofprotectionandprevent facial or eye irritation fromRCF exposure by using a full-facepiece,air-purifying respirator equipped witha 100-series filter; or use any powered,air-purifyingrespiratorequippedwithatight-fittingfacepiece(full-facepiece).
■ Consider providing a supplied-air res-piratorwitha full facepiece forworkerswhoremoveafter-serviceRCFinsulation(e.g., furnace insulation) and are there-fore exposed to high and unpredictableconcentrations of RCFs. These respira-torsprovideagreaterlevelofrespiratoryprotection.Usethemwhenevertheworktaskinvolvespotentiallyhighconcentra-tionsofairbornefibers.
■ Always perform a comprehensive as-sessmentofworkplaceexposures tode-termine the presence of other possiblecontaminants(suchassilica)andtoen-surethatproperrespiratoryprotectionisused.
■ UseonlyrespiratorsapprovedbyNIOSHandMSHA.
Forinformationandassistanceinestablishingarespiratoryprotectionprogramandselectingappropriaterespirators,seetheOSHARespira-tory Protection AdvisorontheOSHAWebsiteat www.osha.gov. Additional information isalso available from theNIOSH Respirator Se-lection Logic[NIOSH2004],theNIOSH Guide to Industrial Respiratory Protection [NIOSH1987b],andtheNIOSH Guide to the Selection and Use of Particulate Respirators Certified un-der 42 CFR 84[NIOSH1996].
1.10 Sanitation and Hygiene
EmployersshalltakethefollowingmeasurestoprotectworkerspotentiallyexposedtoRCFs:
■ Donotpermitsmoking,eating,ordrink-inginareaswhereworkersmaycontactRCFs.
■ Provide showering and changing areasfree fromcontaminationwhereworkerscan store work clothes and change intostreet clothes before leaving the worksite.
■ Provide services for laundering workclothessothatworkersdonottakecon-taminatedclotheshome.
■ Protect laundry workers handling RCF-contaminatedclothesfromairbornecon-centrationsthatareabovetheREL.
8 Refractory Ceramic Fibers
1 ■Recommendations for a Refractory Ceramic Fiber Standard
Workers shall take the following protectivemeasures:
■ Donotsmoke,eat,ordrinkinareaspo-tentiallycontaminatedwithRCFs.
■ Iffibersgetontheskin,washwithwarmwaterandmildsoap.
■ Applyskin-moisturizingcreamorlotionas needed to avoid irritation caused byfrequentwashing.
■ Wear long-sleeved clothing, gloves, andeyeprotectionwhenperformingpoten-tiallydustyactivitiesinvolvingRCFs.
■ VacuumthisclothingwithaHEPA-filteredvacuumbeforeleavingtheworkarea.
■ Do not use compressed air to clean theworkareaorclothinganddonotshakeclothingtoremovedust.Theseprocesseswill create a greater respiratory hazardwithairbornedustandfibers.
■ Donot wearwork clothes orprotectiveequipment home. Change into cleanclothesbeforeleavingtheworksite.
1.11 Medical Monitoring
Medical monitoring (in combination withresulting intervention strategies) representssecondarypreventionand shouldnot replaceprimarypreventioneffortstocontrolairbornefiber concentrations and worker exposuresto RCFs. However, compliance with the RELfor RCFs (0.5 f/cm3) does not guarantee thatallworkerswillbefreefromtheriskofRCF-induced respiratory irritation or respiratoryhealth effects. Therefore, medical monitoringis especially important, and employers shallestablishamedicalmonitoringprogramasfol-lows:
■ Collect baseline data for all employeesbeforetheybeginworkwithRCFs.
■ Continue periodic medical screeningthroughouttheirlifetime.
■ Usemedicalsurveillance,whichinvolvesthe aggregate collection and analysis ofmedical screening data, to identify oc-cupations,activities,andworkprocessesinneedofadditionalprimarypreventionefforts.
■ Include all workers potentially exposedto RCFs (in both manufacturing andend-use industries) in an occupationalmedicalmonitoringprogram.
■ Provideworkerswithinformationaboutthepurposesofmedicalmonitoring,thehealth benefits of the program, and theproceduresinvolved.
■ Include the following workers (whocould receive the greatest benefits frommedicalscreening)inthemedicalmoni-toringprogram:
—Workers exposed to elevated fiberconcentrations (e.g., all workers ex-posed to airborne fiber concentra-tionsabove theALof0.25F/cm3,asdescribedinSection9.3)
—Workers in areas or in specific jobsandactivities(regardlessofairbornefiberconcentration)inwhichoneormoreworkershavesymptomsorre-spiratory changes apparently relatedtoRCFexposure
—Workers who may have been previ-ously exposed to asbestos or otherrecognized occupational respiratoryhazards that place them at an in-creasedriskofrespiratorydisease
Refractory Ceramic Fibers 9
1 ■Recommendations for a Refractory Ceramic Fiber Standard
1.11.1 Oversight of the Program
Assign oversight of the medical monitor-ingprogramtoaqualifiedphysicianorotherqualifiedhealthcareprovider (asdeterminedbyappropriateStatelawsandregulations)whoisinformedandknowledgeableaboutthefol-lowing:
■ Administering and managing a medicalmonitoring program for occupationalhazards
■ Establishing a respiratory protectionprogram based on an understanding ofrequirements of the OSHA respiratoryprotection standard and types of respi-ratoryprotectiondevicesavailableattheworkplace
■ Identifying and managing work-relatedrespiratoryeffectsorillnesses
■ Identifying and managing work-relatedskindiseases
1.11.2 Elements of the Medical Monitoring Program
Include the following elements in a medicalmonitoring program for workers exposed toRCFs:(1)aninitialmedicalexamination,(2)pe-riodicmedicalexaminationsatregularlysched-uled intervals, (3) more frequent and detailedmedicalexaminationsasneededonthebasisofthefindingsfromtheseexaminations,(4)work-ertraining,(5)writtenreportsofmedicalfind-ings,(6)qualityassurance,and(7)evaluation.These elements are described in the followingsubsections.
1.11.2.1 Initial (baseline) examination
Performaninitial(baseline)examinationasnearaspossibletothedateofbeginningemployment(within3months)andincludethefollowing:
■ A physical examination of all systemswithanemphasisontherespiratorysys-temandtheskin
■ Aspirometric test (note thatanyonead-ministeringspirometrictestingaspartofthemedicalmonitoringprogramshouldhavecompletedaNIOSH-approvedtrain-ingcourseinspirometryorotherequiva-lenttraining)
■ AchestX-ray(allchestX-rayfilmsshouldbe interpreted by a certified NIOSH BReader using the standard International Classification of Radiographs of Pneumo-conioses [ILO 2000, or the most recentequivalent])
■ Othermedicaltestsasdeemedappropri-atebytheresponsiblehealthcareprofes-sional
■ Astandardizedrespiratorysymptomques-tionnaire,suchastheAmericanThoracicSociety respiratory questionnaire [Ferris1978,orthemostrecentequivalent]
■ Astandardizedoccupationalhistoryques-tionnaire thatgathers informationaboutallpastjobswith(1)specialemphasisonthosewithpotentialexposuretodustandmineralfibers,(2)adescriptionofalldu-tiesandpotentialexposuresforeachjob,and (3) a description of all protectiveequipmenttheworkerhasused
1.11.2.2 Periodic examinations
Administer periodic examinations (includ-ing a physical examination of the respiratorysystemandtheskin,spirometrictesting,are-spiratorysymptomupdatequestionnaire,andanoccupationalhistoryupdatequestionnaire)atregularintervalsdeterminedbythemedicalmonitoring program director. Determine the
10 Refractory Ceramic Fibers
1 ■Recommendations for a Refractory Ceramic Fiber Standard
frequency of the periodic medical examina-tionsaccordingtothefollowingguidelines:
■ Forworkerswithfewerthan10yearssincefirst exposure toRCFs, conductperiodicexaminationsatleastonceevery5years.
■ Forworkerswith10ormoreyearssincefirstexposuretoRCFs,conductperiodicexaminationsatleastonceevery2years.
AchestX-rayandspirometrictestingareim-portant on initial examination and may alsobeappropriatemedicalscreeningtestsduringperiodic examinations for detecting respira-tory system changes, especially in workerswithmorethan10yearssincefirstexposuretoRCFs.Aqualifiedhealthcareprovidershouldconsultwiththeworkertodeterminewhetherthe benefits of periodic chest X-rays warranttheadditionalexposuretoradiation.
1.11.2.3 More frequent evaluations
Workersmayneedtoundergomorefrequentanddetailedmedicalevaluationsiftheattend-ingphysiciandeterminesthatheorshehasanyofthefollowingindications:
■ Neworworseningrespiratorysymptomsorfindings(e.g.,chroniccough,difficultbreathing,wheezing,reducedlungfunc-tion,orradiographicindicationsofpleu-ralplaquesorfibrosis)
■ Historyofexposuretootherrespiratoryhazards(e.g.,asbestos)
■ Recurrentorchronicdermatitis
■ Othermedicallysignificantreason(s)formoredetailedassessment
1.11.2.4 Worker training
Provide workers with sufficient training torecognize symptoms associated with RCF
exposures(e.g.,chroniccough,difficultbreath-ing,wheezing,skinirritation).Instructwork-erstoreportthesesymptomstothedesignatedmedicalmonitoringprogramdirectororotherqualifiedhealthcareprovider forappropriatediagnosisandtreatment.
1.11.2.5 Written reports of medical findings
Followinginitialandperiodicmedicalexami-nations,thephysicianorotherqualifiedhealthcareprovidershallgiveeachworkerawrittenreportcontaining
—resultsofanymedicaltestsperformedontheworker,
—a medical opinion in plain languageabout any medical condition thatwould increase the worker=s risk ofimpairment from exposure to air-borneRCFs,
—recommendations for limiting theworker=s exposure to RCFs (whichmay include the use of appropriatePPE,aswarranted),and
—recommendations for further evalu-ation and treatment of any medicalconditionsdetected.
Followinginitialandperiodicmedicalexami-nations,thephysicianorotherqualifiedhealthcareprovidershallalsogiveawrittenreporttotheemployercontaining
—occupationally pertinent results ofthemedicalevaluation,
—a medical opinion about any medi-calconditionthatwouldincreasetheworker=sriskofimpairmentfromex-posuretoairborneRCFs,
—recommendations for limiting theworker=s exposure to RCFs or other
Refractory Ceramic Fibers 11
1 ■Recommendations for a Refractory Ceramic Fiber Standard
agents in the workplace (which mayincludetheuseofappropriatePPEorreassignmenttoanotherjob),and
—astatementtoindicatethatthework-er has been informed about the re-sultsofthemedicalexaminationandabout any medical condition(s) thatshould have further evaluation ortreatment.
Findings,testresults,ordiagnosesthathavenobearing on the worker=s ability to work withRCFsshallnotbeincludedinthereporttotheemployer.Safeguardstoprotecttheconfiden-tiality of the worker=s medical records shallbe enforced inaccordancewithall applicableregulationsandguidelines.
1.11.2.6 Quality assurance
Employersshalldothefollowingtoensuretheeffective implementation of a medical moni-toringprogram:
■ Ensurethatworkersfollowthequalifiedhealthcareprovider’srecommendedex-posure restrictions for RCFs and otherworkplacehazards.
■ EnsurethatworkersuseappropriatePPEif they are exposed to RCF concentra-tionsabovetheREL.
■ Encourageworkers toparticipate in themedicalmonitoringprogramandtore-portanysymptomspromptlytothepro-gramdirector.
■ Provideanymedicalevaluationsthatarepartofthemedicalmonitoringprogramatnocosttotheworkers.
■ When implementing job reassignmentsrecommended by the medical programdirector,ensurethatworkersdonotlosewages,benefits,orseniority.
■ Ensurethatthemedicalmonitoringpro-gram director communicates regularlywith the employer’s safety and healthpersonnel (e.g., industrialhygienists) toidentifyworkareasthatmayrequirecon-trol measures to minimize exposures toworkplacehazards.
1.11.2.7 Evaluation
Employers shallevaluate theirmedicalmoni-toringprogramsasfollows:
■ Periodically have standardized medicalscreeningdataaggregatedandevaluatedby an epidemiologist or other knowl-edgeable person to identify patterns ofworkerhealththatmaybelinkedtoworkactivities and practices requiring addi-tionalprimarypreventiveefforts.
■ Combine routine aggregate assessmentsof medical screening data with evalu-ations of exposure monitoring data toidentifyneededchangesinworkareasorexposureconditions.
1.12 Labeling and Posting
Employersshallpostwarninglabelsandsignsasfollows:
■ PostwarninglabelsandsignsdescribingthehealthrisksassociatedwithRCFsatentrancestoworkareasandinsideworkareas where airborne concentrations ofRCFsmayexceedtheREL.
■ Depending on work practices and theairborne concentrations of RCFs, stateonthesignstheneedtowearprotectiveclothingandtheappropriaterespiratoryprotectionforRCFexposuresabovetheREL.
12 Refractory Ceramic Fibers
1 ■Recommendations for a Refractory Ceramic Fiber Standard
■ Ifrespiratoryprotectionisrequired,postthefollowingstatement:
Employersshallencouragesmokingcessation
amongRCF-exposedworkersasfollows:
■ Establishsmokingcessationprogramsto
informworkersabouttheincreasedhaz-
ards of cigarette smoking and exposure
toRCFs.
■ Provide assistance and encouragement
forworkerswhowanttoquitsmoking.
■ Prohibitsmokingintheworkplace.
■ Disseminate information about health
promotion and the harmful effects of
smoking.
■ Offer smoking cessation programs to
workersatnocosttoparticipants.
■ Encourageactivitiesthatpromotephysi-
cal fitness and other healthy lifestyle
practices affecting respiratory and car-
diovascularhealth(e.g.,throughtraining
programs,employeeassistanceprograms,
andhealtheducationcampaigns).
NIOSH recommends that all workers who
smoke and are potentially exposed to RCFs
participateinsmokingcessationprograms.
RESPIRATORY PROTECTION REQUIRED IN THIS AREA
■ PrintalllabelsandwarningsignsinbothEnglish and the predominant languageofworkerswhodonotreadEnglish.
■ Verbally informworkers about thehaz-ardsandinstructionsprintedonthe la-belsandsignsiftheyareunabletoreadthem.
1.13 Smoking CessationNIOSHrecognizesasynergisticeffectbetweenexposuretoRCFsandcigarettesmoking.Thiseffectincreasestheriskofadverserespiratoryhealth effects induced by RCFs. In studies ofworkersexposedtovariousairbornecontami-nants, combined exposures to smoking andairbornedusthavebeenshowntocontributeto the increased risk of occupational respira-tory diseases, including chronic bronchitis,emphysema, and lung cancer [Morgan 1994;Barnhart1994].
Refractory Ceramic Fibers 13
2 Background and Description of RCFs
2.1 ScopeInformationaboutRCFswascollectedandre-viewedforthisdocumenttoassessthehealthhazardsassociatedwithoccupationalexposuretothisairbornefiber.Chapter2describesthebackground for studying thehealtheffectsofworkplace exposures to RCFs. Informationis presented about the physical and chemicalproperties of RCFs, including the morphol-ogy,dimensions, anddurabilityoffibers thatmake up RCF-containing products. Chapter3 discusses the production and uses of RCFsasahigh-temperatureinsulationmaterial;thechapteralsodescribesthenumberofworkerswithpotentialforexposuretoRCFs.Chapter4presentsareviewoftheliteratureonpotentialworkplaceexposurestoairborneRCFsduringmanufacturingandendusesofRCFproducts.Chapter5describestheeffectsofexposuretoRCFs—firstwithreviewsofanimalstudiesandthenwithadescriptionofepidemiologicstud-ies of RCFs, focusing on U.S. and Europeanworkers in the RCF manufacturing industry.Recent quantitative risk assessments of RCFsare also summarized in this chapter. Chapter6containsadiscussionoffibercharacteristicsandtheparameters(dose,dimensions,anddu-rability)thatdeterminefibertoxicity.Chapter7summarizesexistingstandardsandguidelinesfor occupational exposure to RCFs. Chapter 8providesthebasisandrationalefortheNIOSHREL. Chapters 1 and 9 provide recommenda-tionsandguidelinesforminimizingexposuresto airborne fibers of RCFs in the workplace.Finally, Chapter 10 discusses futureareas for
researchrelatingtofibertoxicityandoccupa-tionalexposures.
2.2 Background
In 1977, NIOSH reviewed health effects dataonoccupationalexposuretofibrousglassanddeterminedtheprincipaladversehealtheffectstobeskin,eye,andupperrespiratorytractir-ritationaswellasthepotentialfornonmalig-nantrespiratorydisease.AtthattimeNIOSHrecommendedthefollowing:
Occupationalexposuretofibrousglassshallbecontrolledsothatnoworkerisexposedatanairborneconcentrationgreaterthan3,000,000fiberspercubicmeterofair(3fiberspercubiccentimeterofair);...airborneconcentrationsdeterminedastotalfibrousglassshallbelim-itedtoaTWAof5milligramspercubicmeterofair[NIOSH1977].
NIOSH also stated that until more informa-tion became available, this recommendationshouldbeappliedtootherMMMFs,alsocalledSVFs.Sincethen,additionaldatahavebecomeavailablefromstudiesinanimalsandhumansexposedtoRCFs.ThepurposeofthisreportistoreviewandevaluatethesestudiesandotherinformationaboutRCFs.
2.3 Chemical and Physical Properties of RCFs
RCFs(ChemicalAbstractsServiceNo.142844–00–6)areamorphousfibersthatbelongtothe
14 Refractory Ceramic Fibers
2 ■Background and Description of RCFs
largerclassofSVFs,whichalsoincludesfibersof glass wool, mineral wool, slag wool, andspecialtyglass.SVFsvaryaccordingtochemi-cal and physical properties, making themsuitable for different uses. Like the naturallyoccurring mineral fibers defined in Section1.2,RCFspossessdesiredqualitiesofheatre-sistance, tensile strength, durability, and lightweight. The maximum end-use temperatureforRCFsranges fromapproximately1,050to1,425oC(1,920to2,600oF),dependingontheexact chemistry of the fiber. Unlike naturallyoccurring mineral fibers, however, SVFs suchasRCFsandfibrousglassarenoncrystallineinstructure and fracture transversely, retainingthesamediameterbutcreatingshorterfibers.Incontrast,thecrystallinestructureofmineralfiberssuchasasbestoscausesthefiberstofrac-ture along the longitudinal plane under me-chanicalstresses,resultinginmorefiberswiththesame lengthbut smallerdiameters.Thesedifferences in morphology and cleavage pat-ternssuggestthatworkwithSVFsislesslikelytogeneratehighconcentrationsofairbornefi-bers thanworkwith asbestos for comparableoperations, since large-diameter fibers settleout in the air faster than small-diameter fi-bers[AssuncaoandCorn1975;Cherrieetal.1986;Lippmann1990].During themanufac-turingofRCFs,approximately50%ofproduct(byweight)isgeneratedasfiber,and50%isabyproductmadeupofnonfibrousparticulatematerial called shot. Selectedphysical charac-teristicsofRCFsarepresentedinTable2–1.
RCFsareproducedbytheblowingorspinningoffurnace-meltedsiliceouskaolin(Al
2Si
2O
5[OH]
4)
clayorblendsofkaolin,silica,andzircon.RCFsarealsoreferredtoasalumina-basedorkaolin-basedceramicfibersbecausetheyareproducedfrom a 50:50 mixture of alumina and silica[IARC 1988]. Other oxides (including thoseofboron,titanium,andzirconium)areaddedasstabilizerstoalterthephysicalpropertiesof
RCFs [RCFC 1996]. The addition of stabiliz-ersandbindersalters thepropertiesofdura-bilityandheatresistanceforRCFs.Generally,three typesofRCFsaremanufactured, andafourth after-service fiber (often recognized intheliterature)isdistinguishedaccordingtoitsuniquechemistryandmorphology.Table2–2presentsthechemistriesofthefourfibertypes,numberedRCF1throughRCF4.RCF1isaka-olin fiber; RCF2 is an alumina/silica/zirconiafiber; RCF3 is a high-purity (alumina/silica)fiber;andRCF4isanafter-servicefiber,charac-terizedbydevitrification(i.e.,formationofthesilica polymorph cristobalite), which occursduring product use over an extended periodof time at temperatures exceeding 1,050 to1,100oC(>1,900oF).AnotherfibersubcategoryisRCF1a,preparedfromcommercialRCFsus-ingalessaggressivemethodthanthatusedtoprepare RCF1 for animal inhalation studies[Brown et al. 2000]. RCF1a is distinguishedfromRCF1usedinchronicanimalinhalationstudies,theformerhavingagreaterconcentra-tionoflongerfibersandfewernonfibrouspar-ticles.Thelowerratioofrespirablenonfibrousparticles to fibers in RCF1a compared withRCF1 has been shown to affect lung deposi-tionandclearanceinanimalinhalationstudies[Brownetal.2000;Bellmanetal.2001].Chap-ter5presentsadditionaldiscussionofanimalstudiesandtestfibercharacteristics.
2.3.1 Fiber Dimensions
Fibersofbiologicalimportancearethosethatbecomeairborneandhavedimensionswithininhalable,thoracic,andrespirablesizeranges.Thoracic-sizedfibers (<3 to3.5μmindiam-eter) and respirable-sized fibers (<1.3 μm indiameter) with lengths up to 200 μm [Tim-brell 1982; Lippmann 1990; Baron 1996] arecapable of reaching the portion of the respi-ratory system below the larynx. Respirable-sized fibers are of biological concern because
Refractory Ceramic Fibers 15
2 ■Background and Description of RCFs
theyarecapableofreachingthelowerairwaysandgasexchangeregionsofthelungswhenin-haled.Longerorthickerairbornefibersgener-allysettleoutofsuspensionor,ifinhaled,aregenerally filtered out in the nasal passage ordepositedintheupperairways.Thoracic-sizedfibersthatareinhaledanddepositedintheup-perrespiratorytractaregenerallyclearedmorereadilyfromthelung,buttheyhavethepoten-tialtocauseirritationandproducerespiratory
symptoms.Fiberdimensionsarea significantfactor indetermining theirdepositionwithinthelung,biopersistence,andtoxicity.
RCFsandotherSVFsaremanufacturedtomeetspecifiednominaldiametersaccordingtothefi-bertypeandintendeduse.RCFsareproducedwithnominaldiametersof1.2to3μm[Esmenetal.1979;Vu1988;TIMA1993].Typicaldi-ametersforanindividualRCF(asmeasuredin
Table 2–1 . Selected physical characteristics of RCFs
Characteristic Description
Softeningpoint 1,700to1,800˚C
Refractiveindex 1.55to1.57
Specificgravity(density) 2.6to2.7g/cm3
Shotcontent(nonfibrousparticulate) 20%to50%byweight
Nominaldiameter(bulk) 1.2to3μm
Length(bulk) 2to254μm
Dissolutionrate(atpH=7.4) 1to10ng/cm2/hr
Sources:RCFC[1996],TIMA[1993],andIARC[1988].
Table 2–2 . The chemistry of stock RCFs (% oxide)
Oxide component RCF1 RCF2 RCF3 RCF4
Silicondioxide(SiO2) 47.7 50 50.8 47.7
Alumina(Al2O
3) 48 35 48.5 48
Ferricoxide(Fe2O
3) 0.97 <0.05 0.16 0.97
Titaniumdioxide(TiO2) 2.05 0.04 0.02 2.05
Zirconiumdioxide(ZrO2) 0.11 15 0.23 0.11
Calciumoxide(CaO) 0.07 0.05 0.04 0.07
Magnesiumoxide(MgO) 0.98 0.01 <0.01 0.08
Sodiumoxide(Na2O) 0.54 <0.3 0.19 0.54
Potassiumoxide(K2O) 0.16 <0.01 <0.01 0.16
AdaptedfromMastetal.[1995a].
16 Refractory Ceramic Fibers
2 ■Background and Description of RCFs
RCF-containing products) range from 0.1 to20μm,with lengthsrangingfrom5to200μm[IARC1988].InbulksamplestakenfromthreeRCF blanket insulation products, more than80% of the fibers counted by phase contrastopticalmicroscopy(PCM)were<3μmindi-ameter[Brown1992].Thisresultisconsistentwith those from another study of bulk sam-ples of RCF insulation materials [Christensenetal.1993],whichfoundthefiberstohavegeo-metric mean diameters (GM
D) ranging from
1.5 to 2.8 μm (arithmetic mean [AM] diam-eter range=2.3 to 3.9 μm; median diameterrange=1.6to3.3μm).
Studies of airborne fiber size distributions inRCF manufacturing operations indicate thatthesefibersmeetthecriteriaforthoracic-andrespirable-sizedfibers.OneearlystudyofthreedomesticRCFproductionfacilitiesfoundthatapproximately 90% of airborne fibers were<3μmindiameter,and95%ofairbornefiberswere <4 μm in diameter and <50 μm long[Esmen et al. 1979]. The study showed thatdiameterandlengthdistributionsofairbornefibers in the facilities were consistent, with aGM
Dof0.7μmandageometricmeanlength
(GML) of 13 μm.Another study [Lentz et al.
1999] used these data in combination withmonitoring data from two additional studies[MacKinnon et al. 2001; Maxim et al. 1997]at RCF manufacturing plants to review char-acteristicsoffiberssizedfrom118airsamplescovering20years(1976–1996).Fiberswithdi-ameters <1 μm (n=3,711) were measured bytransmission electron microscopy (TEM). Ofthese, 52%haddiameters<0.4μm,75%haddiameters<0.6 μm, and 89% had diameters<0.8μm.Fiberlengthsrangedfrom<0.6to>20μm,with68%offibersmeasuring2.4to20μmlongand19%of thefibers>20μmlong.OnthebasisoftheresultsofTEManalysisof3,357RCFsobservedon98airsamplescollectedinRCFmanufacturingsites,Allshouse[1995]re-
portedthat99.7%ofthefibershaddiameters<3μmand64%hadlengths>10μm.Measure-mentsofairbornefibersintheEuropeanRCFmanufacturingindustryarecomparable:Rood[1988] reported that all fibers observed wereinthethoracicandrespirablesizerange(i.e.,di-ameter<3to3.5μm),with median diametersrangingfrom0.5to1.0μmandmedianlengthsfrom8to23μm.
Cheng et al. [1992] analyzed an air sampleforfibersduringremovalofafter-serviceRCFblanketinsulationfromarefineryfurnace.Fi-berdiametersrangedfrom0.5to6μm,withamediandiameterof1.6μm.Thelengthoffi-bers ranged from 5 to 220 μm. Of 100 fibersrandomly selected and analyzed from the airsample,87%werewithinthethoracicandre-spirablesizerange.Anotherstudyofexposuresto airborne fibers in industrial furnaces dur-inginstallationandremovalofRCFmaterialsfoundGM
Dvaluesof0.38and0.57μm,respec-
tively[Perraultetal.1992].
2.3.2 Fiber Durability
Fiberdurabilitycanaffectthebiologicactivityoffibersinhaledanddepositedintherespira-torysystem.Durablefibersaremorebiopersis-tent,therebyincreasingthepotentialforcaus-ingabiologicaleffect.Durabilityofafiber ismeasured by the amount of time it takes forthefibertofragmentmechanicallyintoshort-erfibersordissolve inbiologicalfluids.RCFstested in vitro with a solution of neutral pH(modified Gamble’s solution) had a dissolu-tionrateof1to10ng/cm2perhr[Leineweber1984].Thistestisbiologicallyrelevantbecauseofthesimilarityofthesolutiontothecondi-tions of the pulmonary interstitial fluid. Bycomparison,otherSVFs(glassandslagwools)aremoresoluble,withdissolutionratesinthe100s of ng/cm2 per hr [Scholze and Conradt1987].Along a continuum of fiber durability
Refractory Ceramic Fibers 17
2 ■Background and Description of RCFs
determinedintestsusingsimulatedlungflu-idsatpH7.4,theasbestosfibercrocidolitehasadissolutionrateof<1ng/cm2perhr,RCF1andMMVF32(Eglass)havedissolutionratesof1to10ng/cm2perhr,MMVF21hasadis-solutionrateof15to25ng/cm2perhr,otherfibrousglassandslagwoolshavedissolutionratesintherangeof50to400ng/cm2perhr,andthealkalineearthsilicatewoolshavedis-solution rates ranging from approximately60to1,000ng/cm2perhr[Christensenetal.1994;Maximetal.1999b;Mooreetal.2001].
Chrysotile,whichisconsideredthemostsol-ubleformofasbestos,hasadissolutionrateof<1to2ng/cm2perhr.
RCFsdissolvemorerapidlythanchrysotile,eventhoughRCFshaveathickerdiameter(byanor-derofmagnitude)thanchrysotile.Therateofdissolutionisanimportantfibercharacteristicthat affects the clearance time and biopersis-tenceofthefiberinthelung.Thesignificanceoffiberdimension,clearance,anddissolution(i.e.,breakage,solubility)isdiscussedinChapter6.
18 Refractory Ceramic Fibers
3 RCF Production and Potential for Worker Exposure
3.1 Production
RCF production in the United States beganin 1942 on an experimental basis, but RCFswere not commercially available until 1953.SalesofRCFsweremodestinitially,buttheybegantoexpandwhenthematerialgainedac-ceptanceasaneconomicalalternativeinsula-tionforhigh-temperaturekilnsandfurnaces.CommercialproductionofRCFsfirstreachedsignificantlevelsinthe1970sasoilshortagesnecessitated reductions in energy consump-tion.ThegrowingdemandforRCFshasalsobeenstrongly influencedbytherecognitionofhealtheffectsassociatedwithexposuretoasbestos-containingmaterialsandtheincreas-inglystringentregulationoftheseproductsintheUnitedStatesandmanyothercountries.
AnnualdomesticproductionofRCFswasanestimated85.7millionlbin1990;in1997,pro-duction of RCFs in the United States totaled107.7million lbannually [RCFC1998].Cur-rently,totalU.S.productionisestimatedtobe80millionlbperyear,representingabout1%to 2% of the worldwide production of SVFs[RCFC2004].RCFsarealsoproducedinMex-ico, Canada, Brazil, Venezuela, South Africa,Australia, Japan, China, Korea, Malaysia, Tai-wan, and several countries in Europe [RCFC1996]. In the United States and Puerto Rico,the primary producers of RCFs include A.P.Green Industries (Pryor, OK), Unifrax Cor-poration (NiagaraFalls,NY, formerlyCarbo-rundum), Thermal Ceramics (Augusta, GA),
and Vesuvius (King of Prussia, PA, formerlyPremierRefractoriesandChemicals).Thelat-ter three producers account for an estimated90%ofdomesticproductionandaremembersoftheRCFC,whichhasbeenactiveinmoni-toringexposures,developingproductsteward-shipprograms,andfundingresearchtostudyRCFhazardsandsafeworkpracticesforRCFmanufacturinganduse.
3.2 Potential for Worker Exposure
Approximately 31,500 workers in the UnitedStatesarepotentiallyexposedtoRCFsduringmanufacturing,processing,orenduse.Asimi-larnumberofworkersarepotentiallyexposedtoRCFsinEurope.Oftheseworkers,about800(3%)areemployedintheactualmanufactur-ingofRCFsandRCFproducts[Maximetal.1997;RCFC2004].
3.3 RCF Manufacturing Process
ThemanufactureofRCFs(Figure3–1)beginsbyblendingrawmaterials,whichmayincludekaolin clay, alumina, silica, and zirconia ina batch house. The batch mix is then trans-ferred either manually or automatically to afurnacetobemeltedattemperaturesexceed-ing1,600oC.Onreachingaspecifiedtemper-atureandviscosityinthefurnace,themolten
Refractory Ceramic Fibers 19
3 ■RCF Production and Potential for Worker Exposure
Fibers are producedby blowing or spinningmolten materials drainedfrom furnace.
Bulk fiber is packaged.
Felt or blanket is curedin tempering oven.
Product is shipped,stored, or fabricatedinto specialty product.
Figure 3–1. Process flow chart for RCF production.
Batch is melted in furnace at >1600˚C.
Lubricants are addedand fibers are processedby needle-felting machine.
Fibers settle intocollection chamber.
Blanket is cut tospecificationsand packaged.
Raw materials (AI2O3,SiO2, TiO2, MgO, CaO,Na2O, K2O, etc.) areadded to batch mix.
20 Refractory Ceramic Fibers
3 ■RCF Production and Potential for Worker Exposure
batchmixturedrainsfromthefurnaceandisfiberized,eitherthroughexposuretopressur-izedairorbyflowingthroughaseriesofspin-ningwheels[Hill1983].Fansareusedtocreateapartialvacuumthatpullsthefibersintoacol-lectionorsettlingchamber.RCFsmaythenbeconveyedpneumatically toabaggingarea forpackagingasbulkfiber.Somebulkfibermaybeuseddirectlyinthisform,oritmaybepro-cessed to formtextiles, felts,boards,cements,and other specialty items. Other RCFs areformedintoblanketsasbulkfiberinthecollec-tionchambersettlesontoaconveyorbelt.Theblanket passes through a needle felting ma-chinethatinterlocksthefibersandcompressestheblankettoaspecifiedthickness.Fromtheneedler, the blanket is conveyed to a temper-ingoventoremove lubricants thatwereadd-edinthesettlingchamber.Thelubricantsareburnedoff,andtheblanketiscuttodesiredsizeandpackaged.Aswiththebulkfiber,theRCFblanketmayundergoadditionalfabricationtocreate other specialty products. Many of theprocessesareautomatedandaremonitoredbymachine operators. Postproduction processessuchascutting,sanding,packaging,handling,andshippingaremorelaborintensive,butthepotentialexistsforexposuretoairbornefibersthroughoutproduction.
3.4 RCF Products and UsesRCFsmaybeusedinbulkfiberformorasoneof theRCF specialtyproducts in the formofmats, paper, textiles, felts, and boards [RCFC1996].Becauseofitsabilitytowithstandtem-peratures exceeding 1,000 °C, RCFs are usedpredominantly in industrial applications, in-cluding insulation, reinforcement, and ther-mal protection for furnaces and kilns. RCFscan also be found in automobile catalyticconverters, in consumer products that oper-ateathightemperatures(e.g.,toasters,ovens,
woodstoves), and in space shuttle tiles. RCFshavebeenformedintonoise-controlblankets[Thorntonetal.1984]andusedasareplace-ment for refractory bricks in industrial kilnsand furnaces[RCFC1996].RCFshave foundincreasing application as reinforcements inspecialized metal matrix composites (MMC),especially in the automotive and aerospaceindustries [Stacey 1988].A summary of RCFproductsandapplicationsareprovidedhere.
3.4.1 Examples of Products
■ Blankets—high-temperature insulationproducedfromspunRCFsintheformofamatorblanket
■ Boards—high-temperatureinsulationpro-ducedfrombulkfibersintheformofacompressed rigid board (boards havea higher density than blankets and areusedascorematerialorinsandwichas-semblies)
■ Bulk RCFs—fiberswithqualitiesofhigh-temperatureresistancetobeusedasfeed-stockinmanufacturingprocessesorotherapplicationsforwhichproductconsisten-cyiscritical—typicallyinthemanufactureofotherceramic-fiber-basedproducts
■ Ropes and braids—high-temperature in-sulation produced by textile operationsand used for packing, seals, and wickingapplications
■ Woven textiles—high-temperature in-sulationproducedbytextileprocessesintheformofcloth,tape,orsleeves
■ Papers and felts—flexiblehigh-temper-atureinsulationproducedbypapermak-ingprocessesandusedforseals,gaskets,andotherautomotiveandaerospaceap-plications
Refractory Ceramic Fibers 21
3 ■RCF Production and Potential for Worker Exposure
■ Vacuum cast shapes—high-temperatureinsulationproducedbyformingspecial-izedshapesonprefabricatedmoldswithwetfibersandthendryingthembyvacu-umandheat,therebytransformingbulkfiberintorigid,shapedproducts
■ Specialties—forms(i.e.,mixes,cements,and caulking compounds) that containwet, inorganic binder and are used asprotective coating putties as well as ad-hesivesandheatandfirebarriersinhigh-temperatureapplications
■ Modules—packagedfunctionalassemblyof blanket insulation with hardware forattachingtothesurfacesof furnacesandkilns
3.4.2 Examples of Applications
■ Insulationliningsofhigh-temperaturein-dustrialfurnacesandrelatedequipment
■ Hot spot repair of industrial furnacelinings
■ Industrial furnacecurtains,gaskets,andseals
■ Insulationofpipes,ducts,andcablesas-sociated with high-temperature indus-trialfurnaces
■ Fire protection for industrial processequipment
■ Aircraftandaerospaceheatshields
■ Commercialandconsumerappliancescon-sistingofprefabricatedchimneys,pizzaov-ens,self-cleaningovens,andwood-burningstoves
■ Automobile applications consisting ofbrakepads,clutchfacings,catalyticcon-verters, air bags, shoulder belt controls,andpassengercompartmentheatshields
22 Refractory Ceramic Fibers
4 Assessing Occupational Exposure
4.1 Air Sampling and Analytical Methods
The conventional method used to assess thecharacteristics and concentrations of expo-sures to airborne fibers is to collect personalandenvironmental(area)airsamplesforlabo-ratoryanalysis.
Personalsamplesarethepreferredmethodforestimating the exposure characteristics of aworkerperformingspecifictasks.Forpersonalsampling, a worker is equipped with the airsampling equipment, and the collection me-diumispositionedwithintheworker’sbreath-ingzone.Areasamplingisperformedtoevalu-ateexposurecharacteristicsassociatedwithanareaorprocess.Samplingequipmentforareasamplingisstationary,incontrasttopersonalsampling,whichallowsformobilitybyaccom-panying theworker throughout the samplingperiod.
4.2 Sampling for Airborne Fibers
ThetwoNIOSHmethodsforthesamplingandanalysisofairbornefibersofasbestosandoth-erfibrousmaterialsareasfollows:
■ Method7400describesairsamplingandanalysisbyPCM
■ Method7402describesairsamplingandanalysisbyTEM
Both methods (listed in the NIOSH Manual of Analytical Methods[NIOSH1998]andpro-videdinAppendixA)involveusinganairsam-plingpumpconnected toacassette.Thecas-sette consists of a conductive cowl equippedwitha25-mmcelluloseestermembranefilter(0.45-to1.2-µmporesize).Thepumpisusedtodrawairthroughthesamplingcassetteataconstantflowratebetween0.5and16L/min.Airborne fibers and other particulates aretrappedonthefilterforanalysisusingmicro-scopicmethods.Methods7400and7402canbe used to count the number of fibers (andthereforecalculateconcentrationbasedonthevolumeofairsampled)andmeasurethefiberdimensions.Fiberconcentrationisreportedasthe number of fibers per cubic centimeter ofair(f/cm3).Althoughthetwomethodsdifferinpreparationofthesamplingmediaforanaly-sis,themajordistinctionbetweenthemistheresolvingcapabilitiesofthemicroscope.WithPCM,0.25µmisapproximately thediameterofthethinnestfibersthatcanbeobserved[De-mentandWallingford1990].TEMhasalowerresolutionlimitwellbelowthediameterofthesmallestRCF(~0.02 to0.05µm) [Middleton1982]. TEM also allows for qualitative analy-sis of fibers using an energy-dispersive X-rayanalyzer(EDXA)todetermineelementalcom-positionandselectedareaelectrondiffraction(SAED) for comparing diffraction patternswithreferencepatternsforidentification.
4.2.1 NIOSH Fiber-Counting Rules
TheappendixtoNIOSHMethod7400speci-fies two setsoffiber-counting rules thatvary
Refractory Ceramic Fibers 23
4 ■Assessing Occupational Exposure
accordingtotheparametersusedtodefineafi-ber.UndertheArules,anyparticle>5µmlongwithanaspectratio(lengthtowidth)>3:1isconsidered a fiber. No upper limit exists onthefiberdiameter intheAcountingrules.IntheB rules,afiber isdefinedasbeing>5µmlongwithanaspectratio≥5:1andadiameter<3µm.Theupper-diameterlimitintheBrulesrestrictsthemeasurementtothoracicandre-spirablefibers.Itisimportanttonotewhichsetoffiber-countingcriteriaisusedwhenreport-inganalyticalresults.NIOSHrecommendsus-ing Method 7400 with the B rules for evalu-ating exposures to airborne RCFs. NIOSHMethod7402specifiesuseoftheA rules,withalower-diameterlimitof0.25µmtoallowcom-parison with results obtained from NIOSHMethod7400.Method7402canalsobeusedtocompare fiber counts obtained from Method7400(Brules).TEMpermitstheidentificationandcountingoffibers<0.25µmindiameter;0.25µmistheapproximateresolutionlimitforPCM.
4.2.2 European Fiber-Counting Rules
In Europe, a slightly different fiber-countingconventionisused.TheWorldHealthOrgani-zation(WHO)referencemethodforMMMFs[WHO/EUROTechnicalCommitteeforMon-itoringandEvaluatingAirborneMMMF1985]recognizesafiberas>5µmlongwithadiameter<3µmandanaspectratio≥3:1.Severalstudiescomparing fiber counts determined with dif-ferentcountingconventionshavefoundgoodagreementinairsamplingforRCFexposures.Buchtaetal.[1998]comparedfibercountsofairsamplesforRCFexposuresasanalyzedus-ing theNIOSHA andB rules;bothmethodsproduced similar results, with no statisticallysignificantdifferenceinfiberdensitymeasure-ments on sample filters. Maxim et al. [1997]found that fiber counts made using NIOSHMethod7400Brulesareequaltoapproximately
95%ofthecountsdeterminedusingtheWHOreferencemethod.InstudieswithotherSVFs,Lees et al. [1993] also found that fiber expo-sure estimates were slightly higher using theA rulesbutwerecomparabletothevaluesob-tainedusingB rules.Breysse et al. [1999] re-portedasimilarfindingwhencomparingRCFfibercountsdeterminedbybothAandBrules:theratioofAtoBcountswas1.33.Thesere-sultssuggestthatforairborneRCFexposures,mostfiberswitha>3:1aspectratioalsomeetthe≥5:1aspectratiocriterionandare<3µmindiameter.
4.3 Sampling for Total or Respirable Airborne Particulates
Airborne exposures generated during workwithRCFsmayalsobeestimatedbysamplingforgeneraldustconcentrations.Samplingforparticulates not otherwise regulated is de-scribedinNIOSHMethod0500fortotaldustconcentrations and in NIOSH Method 0600fortherespirablefraction[NIOSH1998].Bothmethods(alsoincludedinAppendixA)useasamplingpumptopullairthroughafilterthattrapssuspendedparticulates.NIOSHMethod0600 uses a size-selective sampling apparatus(cyclone)toseparatetherespirablefractionofairbornematerialfromthenonrespirablefrac-tion.Themassofairborneparticulatesonthefilter is measured using gravimetric analysis,and airborne concentration is determined astheratiooftheparticulatemasstothevolumeofairsampled,reportedasmg/m3(orµg/m3).Thismethoddoesnotdistinguishfibersfromnonfibrousairborneparticles.NoNIOSHRELexistsforeithertotalorrespirableparticulatesnot otherwise regulated. The OSHA permis-sibleexposurelimit(PEL)forparticulatesnototherwiseregulatedis15mg/m3fortotalpar-ticulatesand5mg/m3forrespirableparticulates
24 Refractory Ceramic Fibers
4 ■Assessing Occupational Exposure
as 8-hr TWA concentrations. The AmericanConference of Governmental Industrial Hy-gienists(ACGIH)thresholdlimitvalue(TLV)forparticles(insolubleorpoorlysoluble)nototherwise specified is10mg/m3 for inhalableparticlesand3mg/m3 for respirableparticlesas8-hrTWAconcentrations[ACGIH2005].
4.4 Sampling for Airborne Silica
BecausesilicaisamajorconstituentofRCFs,thepotentialexistsforexposuretosilicadur-ingworkwithRCFs(e.g.,inmanufacturingorduring removal of after-service RCF furnaceinsulation). As with sampling for respirableparticulates, sampling for respirable silica in-volves using a pump to draw air through acyclone before collecting respirable airborneparticlesonafilter.Qualitativeandquantita-tive analysis of the sample for silica contentcanbeperformedusingthefollowinganalyti-calmethods:
■ X-raypowderdiffraction(NIOSHMeth-od7500)
■ Visible absorption spectrophotometry(NIOSHMethod7601)
■ Infrared absorption spectrophotometry(NIOSHMethod7602)
TheNIOSHRELforrespirablecrystallinesili-cais0.05mg/m3asaTWAforupto10hr/dayduringa40-hrworkweek[NIOSH1974].TheACGIHTLVforcrystallinesilicais0.05mg/m3asan8-hrTWA[ACGIH2005].
4.5 Industrial Hygiene Surveys and Exposure Assessments
Assessments of occupational exposures, in-cludingquantitativemeasurementofairborne
fiberconcentrationsassociatedwithmanufac-turing, handling, and using RCFs, have beenperformed using industrial hygiene surveysandairsamplingtechniquesatmultiplework-sites.Sourcesofmonitoringdatathatcharac-terizeoccupationalexposurestoRCFsincludethefollowing:
■ UniversityofPittsburghstudiesofexpo-suresatRCFmanufacturingsites in the1970s[CornandEsmen1979;Esmenetal.1979]
■ An ongoing University of Cincinnatiepidemiologic study with exposure as-sessmentsthatusehistoricalmonitoringdata and current monitoring strategies[Riceetal.1994,1996,1997]
■ A5-yearconsentagreementbetweentheRCFCand theU.S.EnvironmentalPro-tectionAgency(EPA)tomonitorworkerexposures inRCFmanufacturingplantsandinsecondaryusersofRCFsandRCFproducts [RCFC 1993; Everest 1998;Maximetal.1994,1997,2000a]
■ Studies of exposure to airborne fibersduring the installation and removal ofRCF insulation in industrial furnaces[Gantner 1986; Cheng et al. 1992; vandenBergenetal.1994;SweeneyandGil-grist1998;Maximetal.1999b]
■ International (Canadian, Swedish, Aus-tralian)industrialhygienesurveysofoc-cupational exposures to RCFs [Perraultetal.1992;Krantzetal.1994;Rogersetal.1997]
■ Astudyofend-userexposurestoRCFin-sulationproductsbyresearchersatJohnsHopkinsUniversity[Cornetal.1992]
■ NIOSHHealthHazardEvaluations(HHEs)ofoccupationalexposurestoRCFs
Refractory Ceramic Fibers 25
4 ■Assessing Occupational Exposure
4.5.1 University of Pittsburgh Survey of Exposures During RCF Manufacturing
Inthemid1970s,researchersfromtheUniver-sity of Pittsburgh conducted environmentalmonitoringtoassessworkerexposurestoair-borne fibers at domestic RCF manufacturingfacilities. This research effort was one of thepioneeringstudiesintheuseofworkplaceex-posuregroupingsordust zonesforestablishinga sampling strategy [Corn and Esmen 1979].Inaseriesofindustrialhygienesurveys,Esmenetal.[1979]collected215full-shiftairsamplesatthreeRCFmanufacturingplants.Table4–1summarizes the sampling data for the threefacilities (A, B, and C) by fiber concentra-tion of total airborne dust. Although a widerangeofvaluesforindividualsamplesexisted(<0.01to16f/cm3),average(AM)concentra-tionsrangedfrom0.05to2.6f/cm3.Thehigh-estexposureconcentrationsweremeasuredinmanufacturing and finishing operations dur-ingwhichsanding,cutting,sawing,anddrill-ingoperationswereperformedandventilationwas lacking. A large number of these opera-tionswerenotedinplantA,whichisreflectedby theelevatedfiberanddust concentrationsfor this plant.When data were compared forsimilar operations and dust zones, exposureconcentrations were consistent across plants.Analysesofairsamplesalsoincludedmeasure-mentoffiberdimensions.Approximately95%
oftheairbornefibersmeasuredwere<4.0µmindiameterand<50µmlongwithaGM
Dof
0.7µmandaGMLof13µm.
4.5.2 University of Cincinnati Study of Exposures During RCF Manufacturing
In1987,researchersfromtheUniversityofCin-cinnati initiated an industry-wide epidemio-logicstudyofworkerswhomanufactureRCFs.OneaimofthestudywastocharacterizecurrentandformerexposurestoRCFsandsilicainU.S.RCFmanufacturingfacilities.Datafrominitialsurveys conducted at five RCF manufacturingplants indicated airborne RCFs with a GM
D
rangingfrom0.25to0.6µmandaGMLranging
from3.8 to11.0µm[Lockeyetal.1990].Theairborne TWA fiber concentrations for thesefiveplantsrangedfrom<0.01to1.57f/cm3.Af-terthefirsttworoundsofquarterlysampling,Riceetal.[1994]hadcollecteddatafrom484fibercountsamples(382sampleswithvaluesgreater than the analytic limit of detection[LOD], 39overloaded samples, 36 sampleswith values below the LOD, and 27 samplesvoidedbecauseoftamperingorpumpfailure).They also collected 35 samples from personsworkingwithrawmaterialsthatwereanalyzedquantitatively and qualitatively for respirablemassandforsilicapolymorphs(quartz,tridy-mite,andcristobalite).Asamplingstrategywasdeveloped by identifying more than 100job
Table 4–1 . Industrial hygiene survey data for three RCF* manufacturing plants†
AM total airborne dust AM fiber concentration
Plant No . samples mg/m3 Range f/cm3 Range
A 76 6.05 0.37–100.00 2.6 0.02–16.0
B 67 1.6 0.19–9.73 0.63 0.04–6.7
C 72 0.85 0.05–2.34 0.05 <0.01–0.29
Source:Esmenetal.[1997].*Abbreviations:AM=arithmeticmean;RCF=refractoryceramicfiber.†Fibersweredefinedashavinganaspectratio>3:1.Transmissionelectronmicroscopywasusedtomeasurefibers≤1 µmindiameter.
26 Refractory Ceramic Fibers
4 ■Assessing Occupational Exposure
functions across 5 facilities. These job func-tionswereconsolidatedintoindustryjobtitlesbasedonsimilaritiesoffunction,proximitytocertainprocesses,andexposurecharacteristicswithindesignateddustzones.Table4–2pres-entsmedianTWAexposurestoairbornecon-centrationsofRCFsbyjobtitleatplantssam-pledin1987.TWAfiberconcentrationsrangedfrombelowtheanalyticalLODto1.04f/cm3forworkersin20differentindustryjobtitles.Fiberconcentrationsobtainedbyrinsingthewallsofthesamplingcowl,whereasignificantnumberof fibers accumulated during sampling [Cor-nettetal.1989;Breysseetal.1990],rangedfrombelowtheanalyticalLODto1.54f/cm3.Ofthe35samplesanalyzedforthesilicapolymorphs,quantifiablesilicawasfoundin5samples:4ofthe samples contained cristobalite in concen-trationsrangingfrom20to78µg/m3,and1ofthe samples contained 70 µg/m3 quartz. Themeasurable silica exposures occurred amongworkersemployedasrawmaterialhandlersandfurnaceoperators.
As the studyprogressed,approximately1,820work history interviews were conducted andevaluated to refine uniform job titles and toidentify dust zones according to the meth-odofCornandEsmen[1979].Fouryearsofsamplingdata(1987–1991)weremergedwithhistoric sampling data to construct exposureestimatesfor81jobtitlesin7facilitiesforspec-ified time periods [Rice et al. 1997]. Overallexposuresdecreased.Themaximumexposureestimatedwas10f/cm3inthe1950sforcardingin a textile operation; subsequent changes inengineering, process, and ventilation reducedexposureestimatesforall20jobtitlestonearorbelow1f/cm3[Riceetal.1996,1997].Thestudyreportedthatatmorerecentoperations(1987–1991),exposureestimatesrangedfrombelowtheanalyticLODto0.66f/cm3.
Subsequently,Riceetal.[2005]publishedtheresultsfromananalysisofexposureestimates
for10yearsoffollow-upsampling(1991−2001)at5of7facilities(2facilitieshadclosedbefore1991).Theresearchersfoundthefollowinges-timatesfor122jobtitlesstillactivein2001:
Number and % Exposure estimate of job titles (f/cm3)
97(79%) . . . . . . . . . . ≤0.2517(14%) . . . . . . . . . . >0.25to0.58(7%)........... >0.5
Thestudyshowsthatexposuresdecreasedfor25% of job titles, remained stable for 53%,and increased for22%.Of the job titleswithincreasedexposureestimates,9estimateswere>0.1f/cm3(range=0.1to0.21f/cm3),and19estimates were <0.1 f/cm3. The exposure es-timates for this study do not include adjust-mentsforrespiratoruse.
4.5.3 RCFC/EPA Consent Agreement Monitoring Data
In1993,theRCFCandtheEPAenteredintoane-gotiated5-yearconsentagreementtodeterminethemagnitudeofRCFexposuresintheprimaryRCF manufacturing industry and in secondaryRCF-use industries [RCFC 1993; Maxim et al.1994, 1997; Everest 1998]. Another purpose ofthisconsentagreementwastodocumentchangesinRCFexposuresduringthe5yearsoftheagree-ment(1993–1998).TheQualityAssuranceProj-ectPlan in theconsentagreementcontains theanalytical protocols, statistical design, descrip-tionoftheprogramobjectives,andtimetablesformeetingtheobjectives[RCFC1993].
During each year of the consent agreement, aminimum of 720 personal air samples (mea-sured as 8-hr TWAs) were collected accordingtoa stratifiedrandomsamplingplan.Of these,320 samples were collected in RCF manufac-turing and processing (primary) facilities. Theremaining 400 samples were collected in RCF
Refractory Ceramic Fibers 27
4 ■Assessing Occupational Exposure
Tabl
e 4–
2 . M
edia
n T
WA
exp
osu
res
to a
irb
orn
e co
nce
ntr
atio
ns
of R
CFs
* by
ind
ust
ry jo
b ti
tle
at p
lan
ts s
amp
led
in 1
987†
Pla
nt 1
Pla
nt 2
Pla
nt 3
Pla
nt 4
Pla
nt 5
No .
sa
mp
les
Med
ian
TW
AN
o .
sam
ple
s
Med
ian
TW
AN
o .
sam
ple
s
Med
ian
TW
AN
o .
sam
ple
s
Med
ian
TW
AN
o .
sam
ple
s
Med
ian
TW
A
Ind
ust
ry jo
b ti
tle
f/cm
3SD
f/cm
3 S
D f
/cm
3SD
f/cm
3SD
f/cm
3SD
Bla
nke
tlin
e6
0.03
0.01
210.
150.
062
0.01
0.01
20.
020.
019
1.04
0.28
En
gin
eer
(non
prod
uct
ion
)—
——
——
—1
0.02
——
——
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4].
* Abb
revi
atio
ns:
RC
F=re
frac
tory
cer
amic
fibe
r;S
D=
stan
dard
dev
iati
on;T
WA
=ti
me-
wei
ghte
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erag
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bers
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eda
sh
avin
gan
asp
ect
rati
oof
≥5:
1 an
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ifs
ized
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ng
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smis
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ctro
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copy
.For
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nn
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opy,
fibe
rsw
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defi
ned
w
ith
th
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ect
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ngt
h>
5µm
.I Fo
reis
th
ear
eao
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epl
ant
befo
ret
he
furn
ace.
28 Refractory Ceramic Fibers
4 ■Assessing Occupational Exposure
customer facilities referred to as end-use (sec-ondary)facilities.Theresearcherscollectedato-talof4,576samples.Anumberofend-usefacili-tieswererandomlyselectedfromalistofknownpurchasersofRCFproducts.Theremaindercon-sistedoffacilitiesthatvolunteeredforsamplingoncetheylearnedoftheconsentagreement.Thestratafromwhichthe720sampleswerecollectedconsistofeightfunctionaljobcategoriesderivedsothatresultscouldbeaggregatedforcompari-son across industries, facilities, and similar jobfunctions[RCFC1993].Thiscategorizationwasbased on the approach instituted by Corn andEsmen[1979].AppendixBlistsdefinitionsandmajor work tasks for each functional job cat-egory.TWAandtask-lengthaverageairsamplingdataweregatheredaccordingtoNIOSHMeth-od7400(Brules)andanalyzedusingPCMandTEM.Dataonrespiratoruse(bytype)werealsocollected[Maximetal.1998].
As background for the consent agreementmonitoringplan,baseline(nowreferredtoashistorical) information about airborne fiberconcentrationswasobtainedthroughpersonalsampling of workers at RCF manufacturingfacilitiesfromJanuary1989toMay1993.Ex-posuremonitoringstrategiesusedduring thebaseline period (1989–1993) provided theframeworkfor theconsentagreement(1993–1998) monitoring protocol. Table 4–3 pres-entsAM and geometric mean (GM) concen-trations of RCF exposures determined fromhistoricaldata(1989–1993)by functional jobcategory. Table 4–4 contains these summarystatisticsforall5yearsofRCFconsentagree-mentmonitoringdata.Table4–5summarizesdata from samples collected during the 5thyearoftheconsentagreementonly(June1997toMay1998).Table4–6presents theaverageairbornefiberconcentrations for thebaseline(1989–1993)andconsentagreementmonitor-ing(1993–1998)periodsbymanufacturingandend-usesectors.
Acomparisonofvalues fromTables4–4,4–5,and4–6withthoseinTable4–3indicatesthataverageairborneconcentrationsfor1993–1998were lower than those for theprecedingbase-line sampling period (1989–1993). However,acomparisonofvalues inTables4–5and4–6showsthataverageconcentrationsfortheentire5-year consent agreement monitoring period(1993–1998) are equal to those of year 5 (i.e.,nochange).
Afterthefirst3years(1993–1996)ofthecon-sentagreementmonitoringperiod,Maximetal.[1997]performedinterimanalysesofthesedatacombinedwithhistoricaldatafromthebaselinemonitoringperiod(1989–1993).Thefollowingconclusions about RCF exposures were basedon these analyses of data from 1,600 baselinesamplesand3,200consentagreementsamples:
■ Airborne concentrations of RCFs aregenerallydecreasingintheworkplace.
■ Ninety percent of airborne concentra-tionsofRCFsintheworkplacearebelow1f/cm3.
■ RCF concentrations have an approxi-matelylog-normaldistribution.
■ Significantdifferencesexistinworkplaceconcentrationsbyfacility.
■ Workplaceconcentrationsvarywithfunc-tionaljobcategory.
■ Respiratorusagevarieswiththeworker’sfunctional job category and the associ-atedaveragefiberconcentration.
■ Workplacesampleshavealowerratioofrespirable nonfibrous particles to fibersthansamplesusedininitialanimalinha-lation studies [Mast et al. 1995a,b; Mc-Connelletal.1995].
Functionaljobcategorieswiththehighestaver-ageTWAfiberconcentrationsincluderemoval(AM=1.2f/cm3),finishing(AM=0.8f/cm3),and
Refractory Ceramic Fibers 29
4 ■Assessing Occupational Exposure
Table 4–3 . TWA* concentrations of airborne RCFs in personal samples collected during the baseline sampling period (1989–1993),† by functional job category
Functional job category
Manufacturing (primary production) End use (secondary processing)
No . samples
AM GM No . samples
AM GM
f/cm3 SD f/cm3 GSD f/cm3 SD f/cm3 SD
Assembly 120 0.5 0.92 0.22 3.94 130 0.29 0.36 0.13 4.08
Auxiliary 119 0.15 0.18 0.07 4.01 26 1.1 2.26 0.2 6.33
Fiber 438 0.52 0.79 0.22 4.17 — — — — —
Finishing 127 0.76 0.63 0.49 3.11 84 1.57 5.72 0.47 4.18
Installation — — — — — 201 0.69 1.09 0.3 4.31
Mixingforming 89 0.27 0.34 0.15 3.23 47 0.41 0.55 0.17 4.71
Other 129 0.33 0.86 0.09 4.25 57 0.38 0.69 0.14 4.88
Removal — — — — — 49 1.36 2.97 0.28 6.48
Total 1,022 0.46 0.74 0.19 4.37 594 0.75 2.49 0.23 4.85
*Abbreviations:AM=arithmeticmean;GM=geometricmean;GSD=geometricstandarddeviation;RCF=refractoryceramicfibers;SD=standarddeviation;TWA=time-weightedaverage.†DatacollectedfromAugust1989toMay1993[RCFC1993].
Table 4–4 . TWA* concentrations of airborne RCFs in personal samples collected during the 5-year consent agreement monitoring period, 1993–1998,† by functional job category
Functional job category
Manufacturing (primary production) End use (secondary processing)
No . samples
AM GMNo .
samples
AM GM
f/cm3 SD f/cm3 GSD f/cm3 SD f/cm3 GSD
Assembly 362 0.28 0.27 0.18 2.76 369 0.31 0.4 0.14 4.1
Auxiliary 237 0.12 0.19 0.05 3.87 311 0.19 0.37 0.07 4.68
Fiber 421 0.26 0.47 0.14 3.27 — — — — —
Finishing 359 0.65 0.56 0.47 2.44 622 0.99 2.09 0.35 4.5
Installation — — — — — 456 0.42 0.51 0.2 3.83
Mixingforming 379 0.28 0.27 0.17 2.96 332 0.31 0.47 0.17 3.07
Other 167 0.14 0.21 0.07 3.22 385 0.17 0.46 0.04 4.66
Removal — — — — — 176 1.92 2.85 0.82 4.22
Total 1,925 0.31 0.42 0.16 3.65 2,651 0.56 1.39 0.16 5.22
Source:Maximetal.[1999a].*Abbreviations:AM=arithmeticmean;GM=geometricmean;GSD=geometricstandarddeviation;RCF=refractoryceramicfibers;
SD=standarddeviation;TWA=time-weightedaverage.†DatacollectedfromJune1993toMay1998.
30 Refractory Ceramic Fibers
4 ■Assessing Occupational Exposure
installation(AM=0.4f/cm3).TheremainderofthefunctionaljobcategorieshadaverageTWAconcentrations near or below 0.3 f/cm3. Al-thoughdifferentjobsandactivitiesareassoci-atedwiththethreehigherexposurefunctionaljobcategories,similaritiesexistthatcontributetoexposureconcentrations.First,removalandinstallationactivitiesareperformedatremotejobsiteswhereimplementingfixedengineeringcontrolsmaybedifficultorimpracticalforre-ducingairbornefiberconcentrations.Removalrequires more mechanical energy and mayinvolve fracturing the structure of the RCFproduct, resulting in fiber release and higherconcentrations of airborne fibers. Finish-ingactivitiesareperformedatfixed locationswhereitispossibletoimplementengineeringcontrols,buttheyalsoinvolvemechanicalen-ergytoshapeRCFproductsbydrilling,sand-ing,andsawing.Theseprocessesalsoresultinthedispersalofairbornefibers.
Regardingparticle-to-fiberratio,Maximetal.[1997] found average workplace values to bemuch lower(0.53;n=10;rangenotreported)thantheaverageratio(9.1;n=7)inthesamplesused in a series of animal inhalation toxicitystudieswithRCFs [Mast et al. 1995a,b,2000;McConnelletal.1995].
Monitoringperformedduringthebaselinepe-riod(August1989–May1993)andthe5-yearconsent agreement period (June 1993–May1998)provideddatafromnearly6,200airsam-ples in thedomesticRCF industry.Table4–6presents the summary statistics of workplaceRCFexposureconcentrationsforthebaseline(historical) and consent agreement monitor-ingdata.Thedatasuggestthat(1)theAMsandGMs of RCF concentrations were higher forworkersduringthebaselineperiodthandur-ingthemorerecent(consentmonitoringdata)period,and(2)AMandGMexposureconcen-trationswerelowerforworkersinmanufactur-ingfacilitiesthanatend-usesites.
Table 4–5 . TWA* concentrations of airborne RCFs in personal samples collected during year 5 of the consent agreement monitoring period, June 1997 to May 1998
Functional job category
Manufacturing (primary production) End use (secondary processing)
No . samples
AM GM No . samples
AM GM
f/cm3 SD f/cm3 GSD f/cm3 SD f/cm3 GSD
Assembly 78 0.28 0.25 0.19 2.48 92 0.28 0.39 0.1 5.32
Auxiliary 44 0.16 0.21 0.08 4.05 89 0.18 0.36 0.06 4.98
Fiber 85 0.29 0.29 0.18 2.85 — — — — —
Finishing 77 0.6 0.57 0.44 2.11 126 0.93 1.49 0.37 4.43
Installation — — — — — 81 0.34 0.49 0.17 3.54
Mixingforming 75 0.23 0.24 0.14 2.78 69 0.28 0.31 0.18 2.65
Other 39 0.22 0.34 0.12 3 70 0.05 0.12 0.02 3.07
Removal — — — — — 39 2.3 3.9 0.58 6.15
Total 398 0.31 0.37 0.18 3.12 566 0.54 0.14 0.13 5.83
Source:Maximetal.[1999a].*Abbreviations:AM=arithmeticmean;GM=geometricmean;GSD=geometricstandarddeviation;RCF=refractoryceramic
fibers;SD=standarddeviation;TWA=time-weightedaverage.
Refractory Ceramic Fibers 31
4 ■Assessing Occupational Exposure
4.5.4 Exposures During Installation and Removal of RCF Furnace Insulation
To evaluate exposures to airborne dust as-sociated with removing RCF furnace insula-tion,Gantner[1986]conductedsurveyswithair sampling at five sites. The surveys wereperformed at sites where workers removedmodules or blanket-type insulation manu-allyusingknivesor trowels.Duringremovalactivities,workersworedisposable,single-userespirators,disposableprotectiveclothingortheir own personal clothing, and (in somecases) goggles or other protective eyewear.Personal sampling was performed for totaldustconcentrationaswellas respirabledustconcentration using a cyclone.Area sampleswere collected in the center of work zones(industrial furnaces) at 9 ft above the floor,whichwasat thebreathingzone levelof theworkers,whowereonscaffolding.Atotalof24 air samples were collected, including 14personal samples (9 for respirable dust and5 for total dust concentrations) and 10 area
samples (3 for respirable dust and 7 for to-tal dust concentrations). Bulk samples of theinsulation materials were analyzed for cristo-balitecontent,whichrangedbetween0%and21%. In area air samples, cristobalite contentranged from 4% to 15%. Personal respirabledust concentrations averaged 4.99 mg/m3(range=0.12to16.9mg/m3),andpersonaltotaldustsamplesaveraged13.95mg/m3(range=0.31to35.8mg/m3).Concentrationsinareasampleswere lower,averaging1.61mg/m3(range=0.1to3.4mg/m3)forrespirabledustand8.98mg/m3(range=0.96to36.2mg/m3)fortotaldust.Asexpected, the highest cristobalite concentra-tions inbulksampleswere foundonthe faceof insulation materials closest to high tem-peratures in furnaces (threshold temperaturenear1,700oF).Resultsofthesurveysindicatedthat concentrations of respirable cristobaliteexceeded theACGIH TLV (then [10mg/m3]/[%SiO
2 + 2]/2) in 75% of the samples, al-
thoughallsamplingtimeswereshortbecausetheremovaltasklastsonly26to183min.TheTLVforcristobalitehassincebeenloweredto0.05mg/m3asan8-hrTWA[ACGIH2005].
Table 4–6 . TWA* concentrations RCFs in personal samples collected at manufacturing facilities and end-use site during the baseline (1989–1993) monitoring periods
Type of site No .
samples
Baseline data (1989–1993)†
No . samples
Consent monitoring data (1993–1998)‡
AM GM AM GM
f/cm3 SD f/cm3 GSD f/cm3 SD f/cm3 GSD
Manufacturing(primaryproduction)
1,022 0.46 0.74 0.19 4.37 1,527 0.31 0.42 0.16 3.65
End-use(secondaryprocessing)
594 0.75 2.49 0.23 4.85 2,085 0.56 1.39 0.16 5.22
Total 1,616 0.56 1.63 0.2 4.56 4,576 0.46 1.1 0.16 4.53
Sources:RCFC[1993]andMaximetal.[1999a].*Abbreviations:AM=arithmeticmean;GM=geometricmean;GSD=geometricstandarddeviation;RCFs=refractoryceramic
fibers;SD=standarddeviation;TWA=time-weightedaverage.†DatacollectedfromAugust1989toMay1993[RCFC1993].§DatacollectedfromJune1993toMay1998[Maximetal.1999a].
32 Refractory Ceramic Fibers
4 ■Assessing Occupational Exposure
Chengetal.[1992]studiedexposurestoRCFsduring the installation and removal of RCFinsulation in13 furnacesat6refineriesand2chemical plants. Air samples were collectedand analyzed according to NIOSH Method7400 (A rules); sampling times ranged from15 to 300 min. Samples collected during mi-normaintenanceand inspectiontasks(n=27)showedGMconcentrationsof0.08to0.39f/cm3(range=0.02to17f/cm3).Samplingperformedduring installation of RCF insulation (n=59)revealed GM concentrations of 0.14 to 0.62f/cm3 (range=0.02 to 2.6 f/cm3). The highestexposures were observed in samples collect-ed during removal of RCF insulation (n=32),withGMconcentrationsof0.02 to1.3 f/cm3(range=<0.01 to 17f/cm3). Workers work-ingoutsideofenclosedspaces(furnaces)wererarely exposed to more than 0.2 f/cm3. Onesample of after-service RCF insulation wasanalyzedforfiberdiameterandlength:mediandiameterwasreportedas1.6µm(range=0.5to6µm),and length ranged from5 to220µm.Of100fibersrandomlyselectedandanalyzedfromtheairsample,87%werewithinthere-spirablesizerange.Fourpersonalsampleswerecollectedduringremovalofafter-serviceRCFmodulesandfirebricksandwereanalyzedforrespirablecrystallinesilica(cristobalite).Sam-ples revealed concentrations ranging from0.03mg/m3to0.2mg/m3(GM=0.06mg/m3).
AtaDutchoil refinery,vandenBergenetal.[1994]performedpersonalairmonitoringforairbornefiberstoassessworkerexposuresdur-ingtheremovalofRCFinsulationfromexpan-sionseamsinaheat-treatingfurnace.The8-hrTWAexposuresfor5workerssampledrangedfrom 9to 50 f/cm3 (GM=16 f/cm3). SweeneyandGilgrist[1998]alsomonitoredworkerex-posurestoairborneRCFsandrespirablesilicaduring the removal of RCF materials fromfurnaces. Personal samples from two work-ers taken during the removal of after-service
RCFinsulationrevealedexposuresof0.15and0.16f/cm3.Exposurestototalparticulate(18.3and22.4mg/m3as8-hrTWAs)wereabovetheOSHAPELof15mg/m3.Exposureconcentra-tionsforrespirabledustcontainingcrystallinesilica (2.4% and 4.3%) were also above theOSHA PEL. The elevated concentrations ofrespirableandtotaldustwereassociatedwithremovalof conventional refractory liningus-ing jackhammers, crowbars, and hammers.AworkerperformingroutingtoinstallnewRCFinsulation was exposed at 1.29 f/cm3 (8-hrTWA).PersonalsamplesfromanotherworkerusingabandsawtocutnewRCFinsulationre-vealedconcentrationsof1.02f/cm3asan8-hrTWA.
In theRCF industry,workerexposures to re-spirable crystalline silica (including quartz,cristobalite,andtridymite)mayoccurduringtheuseofsilicainmanufacturing,removalofafter-service insulation, and waste disposal.Focusing on exposures of workers who in-stall,use,orremoveRCFinsulation,Maximetal.[1999a]collected158personalairsamplesanalyzedforrespirablequartz,cristobalite,andtridymite over the RCFC/EPA 5-year consentagreementmonitoringperiod(1993–1998).Atotalof42removalprojectsweresampled.Forsmall jobs, all workers engaged in insulationremoval were sampled; for larger jobs, work-erswereselectedatrandomforsampling.Airsamplingandanalysiswereperformedaccord-ingtoNIOSHMethod7500forcrystallinesili-cabyX-raydiffraction;samplingtimesrangedfrom37 to588min (AM=260min, standarddeviation[SD]=129min).Shortsamplingtimesreflected theshortdurationofRCF insulationremovaltasks(abenefitovertime-intensivere-moval of conventional refractories). RemovalofRCFblanketsandmodulesisperformedbyusingknives,pitchforks,rakes,andwaterlanc-es, or by hand-peeling. The study noted thatmost (>90%) workers wear respirators (with
Refractory Ceramic Fibers 33
4 ■Assessing Occupational Exposure
protectionfactorsfrom10to50ormore)whenremoving insulation.Analysisof158 samplesfoundthefollowing:
■ Fourteen samples had task-time respi-rablequartzconcentrationsrangingfrom0.01to0.44mg/m3(equivalent8-hrTWArange=0.004to0.148mg/m3);theremain-derofsampleswerebelowtheLOD.
■ Threesampleshaddetectableconcentra-tionsofcristobalite thatwerebelowtheNIOSHRELof0.05mg/m3.
■ Onesamplecontainedtridymite(0.2mg/m3)ataconcentrationexceedingtheNIOSHRELof0.05mg/m3.
4.5.5 International (Canadian, Swedish, and Australian) Surveys of RCF Exposure
Perrault et al. [1992] reported on the charac-teristicsoffiberexposuresthatoccurredduringtheuseofsyntheticfiberinsulationmaterialsonconstructionsitesinCanada.Fiberdimensionsweremeasuredfrombulksamplesofinsulationmaterialsusedatfiveconstructionsites.Areaairsampleswerealsocollectedduringtheinstalla-tionof compositeRCFandglasswool insula-tion,glasswoolalone, rockwool (bothblownandsprayedon),andRCFsalone.
Respirable fiber concentrations were highestduringremovalandinstallationofRCFs(0.39to 3.51 f/cm3) compared with concentrationsmeasured during installation of rock wool(0.15to0.32f/cm3),compositeRCFandglasswool(0.04f/cm3),andglasswoolalone(0.01f/cm3).Diametersoffibersinbulksamplesdif-feredsignificantlyfromdiametersinairbornefibers.RCFshadthesmallestGM
Doffibersin
bulksamples(0.38to0.55µm)comparedwithglasswool(0.93µm)androckwool(1.1to3.9
µm). For airborne fibers, rock wool (sprayedon)hadaGM
Dof2.0µm, followedbyRCFs
(1.1µm),compositeRCFsandglasswool(0.71µm),glasswool(0.5µm)andblownrockwool(0.5µm).Elementalanalysisandcomparisonof bulk samples with air samples revealed agreaterconcentrationoffiberswithoxidesofsiliconandaluminuminairsamples.Forsiteswitheitherglasswoolorrockwoolinsulation,airborne samples contained fewer fibers withsiliconoxideasthesoleconstituentthanbulksamples.Theauthorsconcludedthatairbornefiberconcentrationswereaffectedbythetypeof fiber material used and the confinementofworksites.Theauthorsalsoconcludedthatcharacterizationoffibersinbulksamplesisnotagoodrepresentationofphysicalandchemicalparametersoftheairbornefibers.
A report by the Swedish National Institutefor Occupational Health [Krantz et al. 1994]describes exposure to RCFs in smelters andfoundriesbasedonindustrialhygienesurveysand sampling at 4 facilities: a specialty steelfoundry (2,500 workers), a metal smeltingplant (1,500workers), an aluminum foundry(450workers),andanironfoundry(450work-ers).RCFproductswereusedintheseplantsinladles, tapping spouts, holding furnaces, heattreatmentfurnaces,andspillprotectionmats.Workersandcontractorswereplacedintothreeexposure categories, depending on their po-tentialforexposure(asdeterminedbydistancefromafibersource).Thehighestexposurestoairborneceramicfibers(category1)hadmedi-anconcentrationsof0.26to1.2f/cm3andin-volvedabout3%(n=160)oftheworkersattheplantssurveyed.Secondaryexposures(catego-ries2and3)involvedanother33%(n=1,650)oftheworkersandhadmedianconcentrationsof0.03to0.24f/cm3.Duringcertainopera-tionssuchasremovalordemolitionofRCFmaterials in enclosed spaces, concentrationsofupto210f/cm3weremeasured.Totaldust
34 Refractory Ceramic Fibers
4 ■Assessing Occupational Exposure
concentrations increased with fiber concen-trationandwereashighas600mg/m3duringdemolitionand60mg/m3duringreinsulation.Medianfiberdiametersfrombulksamplesan-alyzedbyelectronmicroscopyrangedfrom0.6to1.5µm,whichwascomparabletothediametersofairbornefibers.Onthebasisofairsamplingdata,fiber dose(assumingaworkinglifetimeof40years[fiberconcentration×exposuretimeperyear×40years])wasestimatedfor8oc-cupationswithcategory1exposures.Dosees-timatesrangedfrom0.05fiber-years/cm3foracleanerto85fiber-years/cm3forabricklayerorcontractor.Doseestimatesforthe6otheroc-cupations ranged from 0.6 fiber-years/cm3 to3.1fiber-years/cm3.
Researchersat theAustralianNationalOccupa-tionalHealthandSafetyCommissionestablishedatechnicalworkinggrouptoinvestigatetypi-calexposuresinSVFmanufacturinganduserindustries[Rogersetal.1997].TheRCFman-ufacturing industry isrelativelysmall inAus-tralia:2plantsemployingroughly40workershavebeenmanufacturingRCFssince1976and1977. Since the plants began manufacturingRCFs,152personshavebeeninvolvedwithpro-duction.Airbornefiberconcentrationsinbothplantsdecreasedovertimeasaresultof(1)theintroductionof anational exposure standardof0.5f/cm3forsyntheticfibersandasecond-arystandardof2mg/m3forinspirabledust,(2)theuseofvariouscontrolsandhandlingtech-nologies,and(3) increasedawarenessofdustsuppressionbytheworkforce.GMconcentra-tions of airborne fibers before implementa-tion of the synthetic fiber exposure standard(1983–1990) measured 0.52f/cm3 (geometricstandarddeviation[GSD]=3.9)and0.29f/cm3(GSD=2.5) for plants1and 2, respectively.GMconcentrationsforthesubsequentperiod(1991–1996)droppedto0.11f/cm3(GSD=4.1)atplant1and0.27f/cm3(GSD=3.3)atplant2.
4.5.6 Johns Hopkins University Industrial Hygiene Surveys
AreportofRCFend-userexposuredatapre-pared for the Thermal Insulation Manufac-turers Association (TIMA) showed that us-ing blanket, bulk, and vacuum-formed RCFsduring certain operations resulted in high fi-berconcentrations[Cornetal.1992].Forex-ample,25personalairsamplescollectedfromworkers installing RCF blanket modules hadanAM,8-hrTWAconcentrationof1.36f/cm3(SD=1.15).Thefiberswerecollectedandana-lyzed using NIOSH Method 7400 (B rules).Seventeen vacuum formers had AM expo-sure concentrations of 0.71 f/cm3 (SD=0.83)whileusingbulkRCFproducts.Twenty-eightworkerswiththejobtitlevacuum-formed RCF cast finisher had AM exposures of 1.55f/cm3(SD=1.51). Table 4–7 summarizes exposuredatacollectedforthe17occupationssampledduring the study. Scanning electron micros-copy(SEM)wasusedtomeasuredimensionsofapproximately3,500fibersfromselectedairsamplesofthe17occupations.GMfiberdiam-etersrangedfrom0.9to1.5µm,andGMfiberlengthsrangedfrom20.4to36.1µm.Fiberas-pectratiosbasedonthesedatarangedbetween16:1and30:1.
4.5.7 NIOSH HHEs and Additional Sources of RCF Exposure Data
NIOSHhasconductedHHEsinvolvingpoten-tial exposures to RCFs at the following workplaces:anRCFmanufacturingfacility[Lyman1992], a steel foundry [O'Brien et al. 1990],a power plant [Cantor and Gorman 1987], afoundry [Gorman 1987], and a railroad carwheel and axle production facility [Hewett1996].Table4–8summarizesdataonairbornefiber concentrations and dimensions fromthesestudies.
Refractory Ceramic Fibers 35
4 ■Assessing Occupational Exposure
Table 4–7 . Summary of 8-hr TWA* RCF exposures for workers using RCF insulation products
PCM (f/cm3) SEM (f/cm3)Gravimetric
(mg/m3)
RCF product Occupation n AM SD n AM SD n AM SD
RCFblanket Modulefabricator 5 0.44 0.4 7 0.54 0.8 4 6.26 6.5
Moduleinstaller 25 1.36 1.15 23 1.19 0.8 11 14.2 18.7
Blanketinstaller 8 0.37 0.29 9 0.33 0.24 4 1.42 1.2
Investmentcaster 20 0.73 0.88 18 0.65 0.57 6 3.59 3.75
Generalfabricator 20 0.55 0.55 19 0.46 0.55 7 0.86 0.49
Fabricationmaintenance — — — — — — — — —
RCFbulk Vacuumformer 17 0.71 0.83 13 0.6 0.57 7 1.1 0.7
Vacuummaintenance — — — — — — — — —
Vacuumwarehouse — — — — — — — — —
Sprayer 1 1.53 — 1 1.15 — — — —
Sprayfeeder 1 0.24 — 1 0.21 — — — —
Vacuum-formedRCFs Generalfabricator 2 0.52 0.58 2 0.2 0.05 2 0.57 0.35
Paperfabricator — — — — — — — — —
Paperfinisher — — — — — — — — —
Castfinisher 28 1.55 1.51 32 1.17 1.17 8 4.05 5.42
Finishingmaintenance 1 0.12 — 2 0.07 0.01 1 0.75 —
Boardinstaller 9 0.78 0.84 9 0.66 0.67 1 6.09 —
Source:Cornetal.[1992].*Abbreviations:AM=arithmeticmean;PCM=phasecontrastmicroscopy;RCF-refractoryceramicfiber;SD=standarddeviation;SEM=scanningelectronmicroscopy;TWA=time-weightedaverage.
36 Refractory Ceramic Fibers
4 ■Assessing Occupational Exposure
Table 4–8 . NIOSH Health Hazard Evaluations involving investigation of exposures to RCFs*
Reference Worksite
Samples Concentration
Fiber dimensionNo . Type f/cm3 SD
Lyman[1992] RCFmanufacturing 286 Breathingzone 0.69 — —
4 Breathingzone 4.02 1.82 —
126 Breathingzone 0.81 — AMD=0.6µm
— — AML=13.8µm
24 Breathingzone 1.65 — —
O’Brienetal.[1990] Steelfoundry 48 Fibersinaninsu-latingblanket
— — D=<1.5µm(81%offibers)
— — L=4-64µm(77%offibers)
54 Fibersinsettleddust
— — D=<0.5µm(73%offibers)
— — L=4-64µm(62%offibers)
CantorandGorman[1987]
Powerplant 4 Breathingzone 0.26 0.08 D=0.5-2.0µm(73%offibers)
2 Area 0.08 0.01 L=>20µm(60%offibers)
Gorman[1987] Foundry 7 Breathingzone 0.1 0.06 D=<2µm(96%offibers)
5 Area 0.4 0.26 L=<20µm(80%offibers)
Hewett[1996] Railroadcarwheelandaxlemanufac-turer
6 Breathingzonenearheattreatmentplant
0.024 0.012
—
14 BreathingzoneduringRCFremoval
1.44 0.84—
1 Breathingzone 3.04† — —
1.7‡ — MeanD=0.71(SD=0.44)
— — MeanL=11.9(SD=11.3)
*Abbreviations:AMD=arithmeticmeandiameter;AML=arithmeticmeanlength;D=diameter;L=length;RCFs=refractoryceramicfibers;SD=standarddeviation.†Measuredbyphrasecontrolopticalmicroscopy(PCM).‡Measuredbytransmissionelectronmicroscopy(TEM).
Refractory Ceramic Fibers 37
4 ■Assessing Occupational Exposure
4.5.8 Discussion
Recentandhistoricalenvironmentalmonitor-ingdata[Esmenetal.1979;CantorandGor-man1987;Gorman1987;O=Brienetal.1990;Chengetal.1992;Brown1992;Cornetal.1992;Lyman1992;Allshouse1995;Hewett1996]in-dicate that airborne concentrations of RCFsinclude fibers in the thoracic and respirablesizerange(<3.5µmindiameterand<200µmlong [Timbrell 1982; Lippmann 1990; Baron1996]).Workersareexposedtotheseconcen-trations during primary RCF manufacturing,secondary manufacturing or processing, andend-use activities such as RCF installationand removal. Sampling data from studies ofdomestic primary RCF manufacturing sitesindicatethataverageairbornefiberconcentra-tionshavesteadilydeclinedbynearly2ordersofmagnitudeoverthepast2decades.Riceetal. [1997] reportanestimatedmaximumair-borne concentration of 10 f/cm3 associatedwith an RCF manufacturing process in the1950s.Esmenetal.[1979]recognizedaverageexposureconcentrationsrangingfrom0.05to2.6 f/cm3 in RCF manufacturing facilities inthemid-tolate-1970s.Duringthelate1980s,Riceetal. [1994,1996,1997]calculatedaver-ageairborneconcentrationsinmanufacturingfacilitiesthatrangedfrom<LODto0.66f/cm3.Maxim et al. [1994, 1997, 2000a] report thatfromthelate1980sthrough1997,concentra-tionsrangedfromanAMof<0.3to0.6f/cm3(GM0.2f/cm3).
For many RCF manufacturing processes, re-ductions in exposure concentrations havebeen realized through improved ventilation,engineering or process changes, and prod-uct stewardship programs [Rice et al. 1996;Maxim et al. 1999b]. Several functional jobcategories continue to be associated with fi-ber concentrations that exceed the average;these include finishing operations during
manufacturing, removal operations, and in-stallation performed by end users.Activitiesin these three categories require additionalmechanical energy in handling RCF prod-ucts(e.g., sawing,drilling,cutting,sanding),which increases the generation of airbornefibers.Removalandinstallationactivitiesareperformedatremotesiteswhereconventionalengineering strategies and fixed controls aremoredifficulttoimplement.Forcertainoper-ationsinwhichairbornefiberconcentrationsaregreater(suchasremovalofRCFproductsfromfurnaces),jobsareperformedforshortperiodsandalmostuniversallywiththeuseofrespiratoryprotection[Maximetal.1998].
One additional consideration during workinvolving RCF exposure is the potential forexposure to respirable silica in the forms ofquartz, tridymite, and cristobalite. Althoughthe potential for such exposure exists in pri-marymanufacturing(becausesilicaisamajorcomponentofRCFs),monitoringdataindicatethattheseexposuresaregenerallylow[Riceetal. 1994]. Maxim et al. [1999a] reported thatmany airborne silica samples collected to as-sessexposuresduringinstallationandremovalofRCFproductscontainconcentrationsbelowtheLOD,withaverageconcentrationsofrespi-rable silica ranging from 0.01 to 0.44 mg/m3(equivalent 8-hr TWA range=0.004 to 0.148mg/m3).Otherstudiesindicateagreaterpoten-tialforexposuretorespirablesilica(especiallyintheformofcristobalite)duringremovalofafter-service RCF materials [Gantner 1986;Chengetal.1992;Perraultetal.1992;vandenBergenetal.1994;SweeneyandGilgrist1998].Processesassociatedwithhighconcentrationsofairbornefibersgenerallygeneratehighcon-centrationsoftotalandrespirabledustaswell[Esmenetal.1979;Krantzetal.1994].
38 Refractory Ceramic Fibers
5 Effects of Exposure
Animalstudiesreporttheconcentration(s)towhichtheanimalswereexposed.Thedistinc-tion between administered exposure concen-tration and received dose is important whenanalyzingthesestudies.Thedoseaffectingthetargettissuesisknownonlywhentheamountof fiber present in the lung is measured andreported.Toanalyze the resultsofRCFstud-ies,thenumberoffibersperexposure,theirdi-mensions,durabilities,andthedelivereddoseshouldbeconsideredformakingcomparisonsandconclusionsregardingpotentialandrela-tivetoxicity.
5.1.1 Intrapleural, Intraperitoneal, and Intratracheal Studies
Instillation and implantation studies deliverfibersdirectlytothetrachea,pleuralcavity,orperitonealcavity,bypassingsomeofthedefenseandclearancemechanismsthatactoninhaledfibers. Implantation of fibers into either thepleuralorabdominalcavitiesdeliversfibersdi-rectlytothepleuralorabdominalmesothelium,bypassingsomeorallofthenormaldefenseandclearancemechanismsoftherespiratorytract.Intratrachealinstillationdeliversfibersdirectlytothetrachea,bypassingtheupperrespiratorytract. These exposure methods do not mimicanoccupationalinhalationexposureofseveralhours per day for several days per week overan extended period. However, one advantageof these studies is that they allow the admin-istrationofaprecisedoseoffibersthatcanbereplicated between animals. They also permittheadministrationofhigherdosesthanmaybeobtainablebyinhalationexposure.
5.1 Health Effects in Animals (In Vivo Studies)
ThehealtheffectsofRCFexposureshavebeenevaluated inanimal studiesusing intrapleural,intraperitoneal, intratracheal, and inhalationroutesofexposure.Alloftheserouteshavedem-onstrated the carcinogenic potential of RCFs.Chronicinhalationstudiesprovideinformationthatismostrelevanttotheoccupationalrouteofexposureandhumanriskassessment.Mech-anisticinformationaboutfibertoxicitymayalsobederivedfromothertypesofstudies.StudiesinvestigatingthecellulareffectsofRCFsinvitroarereviewedinSection5.2andAppendixC.
Whencomparingtheeffectsofafiberdose inanimalstudies, it ispossible tocomparefibersonagravimetricbasis (effectperunitweight)or a fiber basis (effect per number of fibers).The same gravimetric dose of different fibertypesmaycontainvastlydifferentnumbersoffibers because of differences in their dimen-sions.RCF1isarelativelythickfibercomparedwithmanytypesofasbestos,suchaschrysotile,afibercommonlyusedasapositivecontrolinpulmonarycarcinogenesisexperiments inani-mals (see Table 2–2 for descriptions of RCF1,RCF2,RCF3,andRCF4).AgravimetricdoseofRCF1usuallycontainsfarfewerfibersthanthesamegravimetricdoseofchrysotileasbestosfi-bers,makingadirectcomparisonoftheireffectsdifficult when the number of fibers per unitweight isnot reported.Comparisononaper-fiberbasis rather thanaweightbasisprovidesinformation most applicable to occupationalriskassessment.
Refractory Ceramic Fibers 39
5 ■Effects of Exposure
Although the results of implantation and in-stillationstudiesmaynotbedirectlyapplicableto occupational exposure and human healtheffects, they provide important informationabout the potential toxicity of RCFs. Experi-mentsthatcontrolfiberdimensionsandothervariablesprovideinformationaboutthephysi-ological characteristics relevant to fiber tox-icity. They provide a less expensive, quickermeanstoscreenthepotentialtoxicityofafiberthaninhalationstudies.
Manyoftheimplantationandinstillationstud-iesreviewedherereporttheadministeredfiberdoseonagravimetricbasisratherthanonaper-fiber basis. Some studies assess the toxicity ofboth RCFs and asbestos independently, whichallows for thecomparisonof thesefibersonagravimetricbasisbutnotonaper-fiberbasis.
5.1.1.1 IntraperitonealImplantationStudies
Inintraperitonealstudies,fibersareimplanteddirectly into the abdominal cavity, bypassingthe respiratory system defense and clearancemechanisms that act on inhaled fibers. Al-thoughtheimplantedfibersactonsomeofthesametargetcelltypesasthefibersofaninhala-tionexposure(suchas themesothelium), theeffectselicitedintheabdominalmesotheliumcannot be assumed to be identical to the re-sponseofthepleuralmesothelium.Table5–1summarizestheresultsofthreeRCFintraperi-tonealimplantationstudies[Davisetal.1984;Smithetal.1987;Pottetal. 1987].Abriefde-scriptionofthesestudiesfollows.
Davisetal.[1987]dosedWistarratswith25mgceramic aluminum silicate dust by intraperi-tonealinjection.Tumorswereinducedin3of32rats:2fibrosarcomasand1mesothelioma.Smith et al. [1987] dosed Osborne Mendel(OM) rats and Syrian hamsters with 25 mgRCFs by intraperitoneal injection. Abdomi-nal mesothelioma induction rates were 83%
(19/23)inOMratsand13%(2/15)and24%(5/21) in two groups of male hamsters. Cro-cidoliteasbestosat25mginducedabdominalmesotheliomasin80%(20/25)ofOMratsand32%(8/25)ofhamsters.Thedifferenceintu-morincidencereportedbyDavisetal.[1984]andSmithetal.[1987]maybeexplainedinpartbydifferencesinfiberlength.Eighty-threeper-centofRCFfibersusedbySmithetal.[1987]had a length >10 µm; 86% had a diameter<2.0µm.Ninetypercentoftheceramicalumi-numsilicatematerialusedbyDavisetal.[1984]hadalength<3µmandadiameter<0.3µm.
Pottetal.[1987]dosedfemaleWistarratsbyintraperitonealinjectionwith9or15mg/weekfor 5weeks with 2ceramic (aluminum sili-cate)woolfibers,Fibrefrax(RCFs),andMAN(ManvilleRCFs);totaldosesof45and75mgwere administered, respectively. Fifty percentofFibrefraxfibershada length<8.3µmanddiameter<0.91µm.Exposure toFibrefraxfi-bers induced abdominal tumors (sarcomas,mesotheliomas,orcarcinomas)in68%oftherats.FiftypercentofMANfibershadalength<6.9µmanddiameter<1.1µm.Thenumberoffibersindifferentlengthcategorieswasnotreported.ExposuretoMANfibersinducedab-dominaltumorsin22%oftherats.Chrysotile(UICC/B)injectedintraperitoneallyatasingledoseof0.05,0.25,or1.00mginducedabdomi-nal tumors in 19%, 62%, or 86% of rats, re-spectively.Fiftypercentofchrysotilefibershadalength<0.9µmanddiameter<0.11µm.Thenumberoffibersperdosewasnotreportedfortheceramicfibersandasbestos.Salineinducedtumorsin2%ofrats.
5.1.1.2 Intrapleural Implantation Studies
Intrapleural implantation studies permit theinvestigation of the effect of RCFs directlyonthepleuralmesotheliumwhilecontrollingvariablessuchasinhalationkineticsandtrans-location.
40 Refractory Ceramic Fibers
5 ■Effects of Exposure
Tabl
e 5–
1 . I
ntr
aper
iton
eal i
mp
lan
tati
on s
tud
ies
of R
CFs
* in a
nim
als
Ref
eren
ce
Spec
ies
Nu
mb
er a
nd
sex
p
er g
rou
p
Fib
er d
ose
Fib
er d
imen
sion
s (µ
m)
Tu
mor
inci
den
ce
Dav
ise
tal
.
[198
4]W
ista
rra
ts
32,s
exu
nsp
ecifi
ed25
mg
cera
mic
fibe
rs
(a
lum
inu
ms
ilica
teg
lass
)
L=90
%<
3
D=
90%
<0.
31
mes
oth
elio
ma
2fi
bros
arco
mas
Firs
ttu
mor
occ
urr
ed8
50d
ays
p
osti
nje
ctio
n.
Pott
et
al.
[1
987]
Wis
tar
rats
47
,fem
ale
54
,fem
ale
36
,fem
ale
102,
fem
ale
9m
g(×
5)=
45m
gR
CFs
(Fib
refr
ax)
15m
g(×
5)=
75m
gM
anvi
lle
R
CFs
(M
AN
)
1m
gU
ICC
/Bc
hry
soti
le
2
mls
alin
e(×
5)=
10m
l
L=
50%
<8.
3
D=
50%
<0.
91
L=50
%<
6.9
D
=50
%<
1.1
L=
50%
<0.
9
D=
50%
<0.
11
N
A
32m
esot
hel
iom
as,s
arco
mas
,or
ad
enom
aso
fth
eab
dom
inal
ca
vity
12m
esot
hel
iom
as,s
arco
mas
,or
ad
enom
aso
fth
eab
dom
inal
ca
vity
31m
esot
hel
iom
as,s
arco
mas
,or
ad
enom
aso
fth
eab
dom
inal
cav
ity
2m
esot
hel
iom
as,s
arco
mas
,or
aden
omas
of
the
abdo
min
al
cavi
ty
Smit
he
tal
.
[1
987]
Osb
orn
e
Men
delr
ats
23
,fem
ale
25m
gR
CFs
(Fi
bref
rax)
G
ML=
25.0
L=83
%>
10
G
MD=
0.9
D
=80
%<
2
20a
bdom
inal
mes
oth
elio
mas
See
foot
not
esa
ten
dof
tab
le.
(Con
tin
ued
)
Refractory Ceramic Fibers 41
5 ■Effects of Exposure
Tabl
e 5–
1 (C
onti
nu
ed) .
In
trap
erit
onea
l im
pla
nta
tion
stu
die
s of
RC
Fs*
in a
nim
als
Ref
eren
ceSp
ecie
sN
um
ber
an
d s
ex
per
gro
up
Fib
er d
ose
Fi
ber
dim
ensi
ons
(µ
m)
Tum
or in
cid
ence
Smit
he
tal
.[
1987
](
con
tin
ued
)
25,f
emal
e25
,fem
ale
125,
fem
ale
25m
gU
ICC
cro
cido
lite
0.5
mlp
hysi
olog
ical
sal
ine
Cag
eco
ntr
ols
Mea
nL
=3.
1(S
D,1
0.2)
L=95
%≤
5N
A N
A
20a
bdom
inal
mes
oth
elio
mas
0
abdo
min
alm
esot
hel
iom
as 0
abdo
min
alm
esot
hel
iom
as
Syri
an
go
lden
ham
ster
s
15,m
ale
25m
gR
CF
(Fib
refr
ax)
L=83
%>
10G
ML=
25.0
D=
80%
<2
GM
D=
0.9
2ab
dom
inal
mes
oth
elio
mas
21,m
ale
25m
gR
CFs
GM
L=25
.0L=
83%
>10
GM
D=
0.9
D=
80%
<2
5ab
dom
inal
mes
oth
elio
mas
25,m
ale
25m
gU
ICC
cro
cido
lite
Mea
nL
=3.
1(S
D,1
0.2)
L=
95%
≤5
8ab
dom
inal
mes
oth
elio
mas
25,m
ale
112,
mal
e
0.5
mlp
hysi
olog
ical
sal
ine
Cag
eco
ntr
ols
NA
NA
0ab
dom
inal
mes
oth
elio
mas
0ab
dom
inal
mes
oth
elio
mas
* Abb
revi
atio
ns:
D=
diam
eter
;GM
D=
geom
etri
cm
ean
dia
met
er;G
ML=
geom
etri
cm
ean
len
gth
;L=
len
gth
;NA
=n
ota
pplic
able
;RC
Fs=
refr
acto
ryc
eram
icf
iber
s;
SD
=st
anda
rdd
evia
tion
;UIC
C=
Un
ion
In
tern
atio
nal
eC
ontr
ele
Can
cer;
UIC
C/B
=U
nio
nI
nte
rnat
ion
ale
Con
tre
leC
ance
r/Ty
pe
B.
42 Refractory Ceramic Fibers
5 ■Effects of Exposure
Table 5–2 summarizes the results of the in-trapleural study of Wagner et al. [1973]. In-trapleuralinjectionof20mgofceramicfiber(unspecified type) or 20 mg for each of twosamplesofchrysotileproducedmesotheliomasin10%(3/31),64%(23/36),and66%(21/32)ofWistarrats,respectively.Themeanceramicfiberdiameterwas0.5to1.0µm.Thelengthsofthechrysotilefibersweremostly<6µm.Thechrysotilefiberdiameter,RCFfiberlength,andnumberoffibersperdosewerenotreported,making a direct comparison of the samplesdifficult.
5.1.1.3 Intratracheal Instillation Studies
Thetechniqueofintratrachealinstillationhastheadvantageofaffectingthesametargettis-sues (other than the upper respiratory tract)as an inhalation exposure. Other advantages,compared with inhalation exposure, includeasimplertechnique,lowercost,accuratedos-ing, and theability todelivermaterials (suchas long fibers) that may not be respirable torodents[Driscolletal.2000].The fasterdoserateandbolusdeliveryoftrachealinstillationmay affect the response of the lung defensemechanisms, resulting indifferences inclear-anceandbiopersistence relative toan inhala-tion exposure. Intratracheal instillation mayalsoproduceaclumpingoffiberswitharesult-ing effect on fiber distribution and clearance[Davisetal.1996;Driscolletal.2000].Intra-tracheal instillationresults inaheavier,morecentralizeddistributionpattern;inhalationex-posureresultsinamoreevenlyandwidelydis-tributedpattern[Brainetal.1976].Table5–3summarizes the results of two RCF intratra-cheal instillation studies [Smith et al. 1987;Manville 1991]. A brief description of thesestudiesfollows.
In the study by Smith et al. [1987], SyriangoldenhamstersandOMratsweredosedwith2mgofRCFssuspendedinsaline(Fibrefrax)
by intratracheal instillation once a week for5weeks(10mgtotal).Theanimalsweremain-tainedfortherestoftheirlives.Approximately50%oftheRCFswere<20µmlongwithameanfiberdiameterof1.8µm.Noprimarylungtu-morsdevelopedinRCF-exposedanimals.Theseanimalsdidnothaveanincreasedincidenceofpulmonaryfibrosisortumorproductioncom-paredwithcontrols;however,theratshadasta-tisticallysignificantincreaseinbronchoalveolarmetaplasia. The median lifespan was 479 daysfor hamsters and 736 days for rats. Hamsters(median lifespan 657 days) and rats (medianlifespan663days)exposedtothesamedosingschedule with 2 mg crocidolite asbestos had astatisticallysignificantincreaseinbronchoalve-olarlungtumorsin20of27(74%)and2of25(8%) animals, respectively. The fiber numbersperdosewerenotreported.
Manville[1991]reportedastatisticallysignifi-cantincreaseinlungtumorsinFischerratsex-posedintratracheallyto2mgofRCF1,RCF2,RCF3,andRCF4insaline[Manville1991].An-imals were terminally sacrificed at 128 weekswithinterimsacrificesat13,26,52,78,and104weeks.RCF1,RCF2,RCF3,andRCF4exposureresulted in adenomas or adenocarcinomasin6of109(5.5%),4of107(3.7%),4of109(3.7%),and7of108(6.5%)rats,respectively.Onemesotheliomawasidentifiedinaratex-posedtoRCF2.Exposureto0.66mgchrysotileasbestosresultedin8primarylungtumorsin8of55rats(14.5%).Thefiberdimensionsandnumbersperdosewerenotreported.
5.1.2 ChronicInhalationStudies
In animal bioassays, administering RCFs bychronic inhalation most closely mimics theoccupational route of exposure. Exposure toRCFsoveratimeperiodthatapproximatesthelifespanoftheanimalprovidesthemostaccu-ratepredictionof thepotentialpathogenicityandcarcinogenicityofthesefibersinanimals.
Refractory Ceramic Fibers 43
5 ■Effects of Exposure
Table 5–2 . Intrapleural study of RCFs* in animals
Reference SpeciesNumber
per group† Fiber doseFiber dimensions
(µm) Tumor incidence
Wagneretal. [1973]
Wistarrats 31
35
35
35
36
32
20mgceramicfibers (aluminumsilicate)
20mgaluminumoxide20mgfiberglass20mgglasspowder20mgCanadianchrysotile20mgCanadianchrysotile
D=0.5–1.0 AreaD=<10 L=60%>20 D=55%2.5–7 AreaD=<8 L=92%<6 L=92%<6
3mesotheliomas1mesothelioma0mesotheliomas1mesothelioma23mesotheliomas21mesotheliomas
*Abbreviations:D=diameter;L=length;RCFs=refractoryceramicfibers.†Thesexratioforallgroupswasapproximately2maleratsto1femalerat.
44 Refractory Ceramic Fibers
5 ■Effects of Exposure
Tabl
e 5–
3 . I
ntr
atra
chea
l stu
die
s of
RC
Fs* in
an
imal
s
Ref
eren
ce
Spec
ies
Nu
mb
er a
nd
se
x p
er g
rou
pFi
ber
dos
eFi
ber
dim
ensi
ons
(µm
)Tu
mor
inci
den
ce
Man
ville
[
1991
]Fi
sch
er3
44r
ats
109,
mal
e
107,
mal
e
109,
mal
e
108,
mal
e
55,
mal
e
118,
mal
e
2m
gR
CF1
(0.2
mlo
fa
10-m
g/m
lsu
spen
sion
) 2
mg
RC
F2
(0
.2m
lof
a10
-mg/
mls
usp
ensi
on)
2m
gR
CF3
(0.2
mlo
fa
10-m
g/m
lsu
spen
sion
) 2
mg
RC
F4
(0
.2m
lof
a10
-mg/
mls
usp
ensi
on)
0.66
mg
Can
adia
nc
hry
soti
le
(0
.2m
lof
a3.
3-g/
mls
usp
ensi
on)
0.2
ml
(v
ehic
len
ots
pec
ified
)
NR
NR
NR
NR
NR
NR
6lu
ng
aden
omas
4lu
ng
tum
ors:
3ad
enom
as
1
carc
inom
a
1m
esot
hel
iom
a
4
lun
gtu
mor
s:
2
aden
omas
2ca
rcin
omas
7lu
ng
aden
omas
8lu
ng
tum
ors:
4ad
enom
as
4
carc
inom
as
0
lun
gtu
mor
s
See
foot
not
esa
ten
dof
tab
le.
(Con
tin
ued
)
Refractory Ceramic Fibers 45
5 ■Effects of Exposure
Tabl
e 5–
3 (C
onti
nu
ed) .
In
trat
rach
eal s
tud
ies
of R
CFs
* in a
nim
als
Ref
eren
ce
Spec
ies
Nu
mb
er a
nd
sex
per
gro
up
Fi
ber
dos
eFi
ber
dim
ensi
ons
(µm
)
Tum
or in
cid
ence
Smit
he
tal
.
[198
7]O
sbor
ne
Men
delr
ats
22
,fem
ale
25
,fem
ale
25
,fem
ale
12
5,fe
mal
e
10m
gR
CFs
(Fi
bref
rax)
(2m
g/w
eek
×5
=10
mg)
10m
gU
ICC
* cro
cido
lite
(2
mg/
wee
k×
5=
10m
g) Sa
line
con
trol
s C
age
con
trol
s
GM
L=25
.0
GM
D=
0.9
L=3%
>10
D
=80
%<
2 L=
95%
≤5
mea
nL
=3.
1(S
D,1
0.2)
NA
NA
0lu
ng
tum
ors
2br
onch
oalv
eola
rtu
mor
s 0
lun
gtu
mor
s 0
lun
gtu
mor
s
Syri
ang
olde
nh
amst
ers
25
,mal
e
27,m
ale
24
,mal
e
112,
mal
e
10m
gR
CFs
(Fi
bref
rax)
(2m
g/w
eek
×5
=10
mg)
10m
gU
ICC
cro
cido
lite
(2m
g/w
eek
×5
=10
mg)
Salin
eco
ntr
ols
Cag
eco
ntr
ols
GM
L=25
.0
GM
D=
0.9
L=
83%
>10
D
=80
%<
2
mea
nL
=3.
1(S
D,1
0.2)
L=
95%
≤5
N
A N
A
0lu
ng
tum
ors
20b
ron
choa
lveo
lar
tum
ors
0lu
ng
tum
ors
0lu
ng
tum
ors
* Abb
revi
atio
ns:
D=
diam
eter
;GM
D=
geom
etri
cm
ean
dia
met
er;G
ML=
geom
etri
cm
ean
len
gth
;L=
len
gth
;NA
=n
ota
pplic
able
;NR
=n
otr
epor
ted;
RC
Fs=
refr
acto
ry
c
eram
icfi
bers
;SD
=st
anda
rdd
evia
tion
;UIC
C=
Un
ion
In
tern
atio
nal
eC
ontr
ele
Can
cer.
46 Refractory Ceramic Fibers
5 ■Effects of Exposure
The effects seen in animals may be used topredict the effects of these fibers in humans,although interspecies differences exist in re-spiratoryanatomy,physiology,andtissuesen-sitivity.Chronicinhalationstudiesprovidethebestmeanstopredictthecriticaldiseaseend-pointsofcancerinductionandnonmalignantrespiratorydiseasethatmayoccurinhumansbecause of fiber exposure [McConnell 1995;Vuetal.1996].
FivechronicRCFinhalationstudieshavebeenconducted on rats or hamsters [Davis et al.1984;Smithetal.1987;Mastetal.1995a,b;Mc-Connelletal.1995].Thesestudiesaresumma-rizedinTables5–4and5–5andaredescribedbelow.
Davis et al. [1984] exposed Wistar rats bywhole-bodyinhalationto10mg/m3(95f/cm3)ceramic (aluminum silicate glass) dust for7 hr/day, 5 days/week for 12 months. Ninetypercentoftheexposurefiberswereshort(<3µm)andthin(<0.3µm).Theparticleratioofnonfibrousparticulatetofiberswas4:1.Eightof 48 exposed rats (17%) developed pulmo-naryneoplasms:1adenoma,3bronchialcarci-nomas,and4histiocytomas.Interstitialfibro-siswasobserved.Nopulmonarytumorswereobservedincontrolanimals.
Smithetal.[1987]exposedOMratsandSyr-ian golden hamsters by nose-only inhala-tion to 10.8±3.4 mg/m3 (200 f/cm3) ceramicfiber(Fibrefrax)for6hr/day,5days/weekfor24months.Theratioofnonfibrousparticulateto fibers was 33:1. Exposure to RCFs did notinduce pulmonary tumors in rats. One RCF-exposedratandonechambercontrol ratde-velopedprimarylungtumors.RatsexposedtoRCFshadmoreseverepulmonarylesionsthanhamsters,andagreaterpercentageofratshadfibrosisthanhamsters(22%versus1%,respec-tively).Undersimilarconditions,exposure to7 mg/cm3 (3,000 f/cm3) crocidolite asbestosproduced pulmonary tumors in 3 of 57 rats,
including 1 mesothelioma and 2 bronchoal-veolar tumors. No pulmonary tumors wereobservedincrocidolite-exposedhamsters.Ex-posure to slag wool at 10 mg/m3 (200f/cm3)andseveralfibrousglassesatsimilargravimet-ricconcentrationsdidnotresultinpulmonaryneoplasms(notshowninTable5–4).
Mast et al. [1995a] exposed Fischer 344 ratsbynose-onlyinhalationto30mg/m3(187±53WHOf/cm3RCF1,220±52WHOf/cm3RCF2,182±66 WHO f/cm3 RCF3, 153±49 WHOf/cm3RCF4)ofoneoffourtypesofRCFsfor6hr/day,5days/weekfor24monthsandhelduntilsacrificeat30months.Groupsof3to6animals were sacrificed at 3, 6, 9, 12, 15, 18,and24monthstoexaminelesionsanddeter-minefiber lungburdens.Otheranimalswereremoved from exposure at the same timepoints and held until sacrifice at 24 months.Positivecontrolratswereexposedto10mg/m3(1.06±1.14×104WHOf/cm3)chrysotileundersimilarexposureconditions.RCFfiberswithameandiameterof1µmandmeanlengthof20to30µmwereselected.Aparticleratioofnon-fibrousparticulatetofiberof1.02–1.88:1wasreported.Interstitialfibrosiswasfirstobservedat6monthswithRCF1,RCF2,andRCF3andat 12 months with RCF4 exposure. Pleuralfibrosis was first observed at 9 months withRCF1,RCF2,andRCF3andat12monthswithRCF4exposure.Aprogression in the severityofpleuralfibrosiswasseeninanimalsexposedto30mg/m3for24monthsandexaminedat6monthspostexposure.Theincidenceoftotallung tumors was significantly increased fromcontrols after exposure to RCF1, RCF2, andRCF3butnotRCF4.Neoplasticdisease,includ-ingadenomasandcarcinomas,wasobservedinalltreatmentgroups:withRCF1,in16of123rats(13%);RCF2,9of121(7.4%);RCF3,19of121(15.7%);RCF4,4of118(3.4%);andchrys-otile, 13 of 69 (18.5%). Mesotheliomas wereinducedinsomeratsinalltreatmentgroups:2withRCF1;3withRCF2;2withRCF3;1with
Refractory Ceramic Fibers 47
5 ■Effects of Exposure
Tabl
e 5–
4 . C
hro
nic
inh
alat
ion
stu
die
s of
RC
Fs* in
an
imal
s
Ref
eren
ce
Spec
ies
Nu
mb
er a
nd
sex
p
er g
rou
pFi
ber
dos
eFi
ber
dim
ensi
ons
(µm
)Tu
mor
inci
den
ce
Dav
ise
tal
.
[198
4]W
ista
rra
ts48
,sex
un
spec
ified
10m
g/m
3 cer
amic
fibe
rs
(a
lum
inu
ms
ilica
teg
lass
)95
fibe
rs/c
m3
L~90
%<
3D
~90
%<
0.3
8pu
lmon
ary
tum
ors:
1
aden
oma
3
bron
choa
lveo
lar
ca
rcin
omas
4h
isti
ocyt
omas
16n
onpu
lmon
ary
tum
ors:
8
ben
ign
8
mal
ign
ant
1
per
iton
eal
m
esot
hel
iom
a40
,sex
un
spec
ified
Con
trol
NA
No
pulm
onar
ytu
mor
s
Non
pulm
onar
ytu
mor
s:
11b
enig
n
9m
alig
nan
t
Mas
tet
al.
[1
995a
]Fi
sch
er3
44r
ats
123,
mal
e29
.1(
SD,5
.2)
mg/
m3 R
CF1
234
(SD
,35)
tota
lf/c
m3
187
(SD
,53)
WH
O† f/
cm3
mea
nL
=22
.3(
SD,1
7.0)
mea
nD
=0.
98(
SD,0
.61)
16lu
ng
tum
ors:
8
aden
omas
8
carc
inom
as
2
pleu
ralm
esot
hel
iom
as12
1,m
ale
28.9
(SD
,4.5
)m
g/m
3 RC
F226
8(
SD,4
5)to
talf
/cm
3
220
(SD
,52)
WH
Of/
cm3
mea
nL
=18
.7(
SD,1
5.5)
mea
nD
=1.
07(
SD,0
.69)
9lu
ng
tum
ors:
4ad
enom
as
5
carc
inom
as
3
pleu
ralm
esot
hel
iom
as
See
foot
not
esa
ten
dof
tab
le.
(Con
tin
ued
)
48 Refractory Ceramic Fibers
5 ■Effects of Exposure
Tabl
e 5–
4 (C
onti
nu
ed) .
Ch
ron
ic in
hal
atio
n s
tud
ies
of R
CFs
* in
an
imal
s
Ref
eren
ce
Spec
ies
Nu
mb
er a
nd
sex
p
er g
rou
p
Fib
er d
ose
Fi
ber
dim
ensi
ons
(µm
)
Tum
or in
cid
ence
121,
mal
e29
.2(
SD,7
.0)
mg/
m3 R
CF3
213
(SD
,44)
tota
lf/
cm3
182
(SD
,66)
WH
Of/
cm3
mea
nL
=24
.2(
SD,1
7.9)
mea
nD
=1.
05(
SD,0
.7)
19lu
ng
tum
ors:
10
ade
nom
as
9
carc
inom
as
2
pleu
ralm
esot
hel
iom
as
118,
mal
e30
.1(
SD,7
.8)
mg/
m3 R
CF4
206
(SD
,48)
tota
lf/c
m3
153
(SD
,49)
WH
Of/
cm3
mea
nL
=12
.7(
SD,9
.9)
mea
nD
=1.
38(
SD,0
.7)
4lu
ng
tum
ors:
2ad
enom
as
2ca
rcin
omas
1pl
eura
lmes
oth
elio
ma
13
0, m
ale
Air
on
lyN
A2
lun
gad
enom
as
Mas
tet
al.
[19
95b]
Fisc
her
344
rat
s13
1, m
ale
3.0
(SD
,0.4
)m
g/m
3 RC
F136
(SD
,17)
f/cm
3
26(
SD,1
2)W
HO
f/cm
3
mea
nL
=19
.88
(SD
,17
.93)
mea
nD
=1.
03(
SD,0
.73)
2lu
ng
aden
omas
134,
mal
e8.
8(S
D,0
.7)
mg/
m3
91(
SD,3
4)f/
cm3
75(
SD,3
5)W
HO
f/cm
3
mea
nL
=20
.54
(SD
,17.
08)
mea
nD
=1.
04(
SD,0
.72)
5lu
ng
tum
ors:
4ad
enom
a
1ca
rcin
oma
1
mes
oth
elio
ma
132,
mal
e16
.5(
SD,1
.1)
mg/
m3 R
CF
162
(SD
,37)
f/cm
3
120
(SD
,35)
WH
Of/
cm3†
mea
nL
=20
.11
(SD
,16.
87)
mea
nD
=1.
06(
SD,0
.72)
2lu
ng
tum
ors:
1ad
enom
a
1ca
rcin
oma
132,
mal
eA
iro
nly
NA
1lu
ng
aden
oma
See
foot
not
esa
ten
dof
tab
le.
(Con
tin
ued
)
Refractory Ceramic Fibers 49
5 ■Effects of Exposure
Tabl
e 5–
4 (C
onti
nu
ed) .
Ch
ron
ic in
hal
atio
n s
tud
ies
of R
CFs
* in a
nim
als
Ref
eren
ce
Spec
ies
Nu
mb
er a
nd
sex
p
er g
rou
pFi
ber
dos
eF
iber
dim
ensi
ons
(µm
)
Tum
or in
cid
ence
McC
onn
elle
tal
.
[199
5]Sy
rian
gol
den
h
amst
ers
102,
mal
e30
mg/
m3 R
CF1
256
(SD
,58)
f/cm
3
215
(SD
,56)
WH
Of/
cm3
mea
nL
=22
.12
(SD
,6.7
)m
ean
D=
0.94
(SD
,0.6
3)42
ple
ura
lmes
oth
elio
mas
49, m
ale
10m
g/m
3 ch
ryso
tile
,Can
adia
n8.
4(S
D,9
.0)×
104 f/
cm3
3.0
(SD
,1.4
)×10
3 WH
Of/
cm3
mea
nL
=1.
68(
SD,2
.71)
mea
nD
=0.
09(
SD,0
.06)
Non
e
106,
mal
eN
egat
ive
con
trol
sN
AN
one
Smit
he
tal
.
[1
987]
Osb
orn
e-M
ende
l
ra
ts
55
, fem
ale
10.8
mg/
m3R
CFs
(Fi
bref
rax)
,
200
f/cm
3
GM
L=
25G
MD=
0.9
Non
e
57, f
emal
e7
mg/
m3 U
ICC
cro
cido
lite,
3,
000
f/cm
3
L=95
%≤
51
mes
oth
elio
ma
2br
onch
oalv
eola
rtu
mor
s
59, f
emal
eC
ham
ber
con
trol
sN
AN
one
125,
fem
ale
Roo
mc
ontr
ols
NA
Non
e
Syri
ang
olde
n
ham
ster
s70
,mal
e10
.8m
g/m
3 RC
Fs(
Fibr
efra
x),
20
0f/
cm3
GM
L=25
GM
D=
0.9
1m
esot
hel
iom
a
58,m
ale
7m
g/m
3 UIC
Cc
roci
dolit
e,
3,00
0f/
cm3
L=91
%≤5
Non
e
58,m
ale
Ch
ambe
rco
ntr
ols
NA
1br
onch
oalv
eola
rtu
mor
112,
mal
eR
oom
con
trol
sN
AN
one
* Abb
revi
atio
ns:
D=
diam
eter
;GM
D=
geom
etri
cm
ean
dia
met
er;
GM
L=ge
omet
ric
mea
nle
ngt
h;L
=le
ngt
h;N
A=
not
app
licab
le,R
CFs
=re
frac
tory
cer
amic
fibe
rs;
U
ICC
=U
nio
nI
nte
rnat
ion
ale
Con
tre
leC
ance
r;W
HO
=W
orld
Hea
lth
Org
aniz
atio
n.
† W
HO
fibe
rsh
ave
diam
eter
s<
3µm
,len
gth
s>
5µm
,an
das
pec
tra
tios
>3:
1[W
HO
198
5].
50 Refractory Ceramic Fibers
5 ■Effects of Exposure
Tabl
e 5–
5 . N
ontu
mor
lun
g ef
fect
s in
an
imal
s ex
pos
ed to
RC
Fs* b
y in
hal
atio
n
Ref
eren
ceSp
ecie
s
Fib
rosi
s
Lun
g ch
ange
s
Lu
ng
fib
er b
urd
en
Dav
ise
tal
.
[198
4]W
ista
rra
ts
Min
imal
per
ibro
nch
iola
r
fibr
osis
Inte
rsti
tial
fibr
osis
at
fin
al
sacr
ifice
Mea
n%
of
lun
gar
ea
(n=
6ra
ts)=
5.0%
Ran
ge=
0.2%
–14.
5%
Larg
ear
eas
ofa
lveo
lar
pr
otei
nos
is
Foam
yan
dag
greg
ated
m
acro
phag
es
Mea
n=
4,13
0µg
n=
4ra
ts
R
ange
=2,
800–
6,80
0µg
Mas
tet
al.
[1
995a
]Fi
sch
er3
44r
ats
Inte
rsti
tial
fibr
osis
see
na
t
3m
onth
s(R
CFs
)
6m
onth
s(R
CF2
,RC
F3)
12
mon
ths
(RC
F4)
Ple
ura
lfibr
osis
see
na
t
9m
onth
s(R
CF1
,RC
F2,R
CF3
)
12m
onth
s(R
CF4
)
Alv
eola
rbr
onch
ioliz
atio
n,
mic
rogr
anu
lom
as,c
olla
gen
depo
siti
on,a
nd
alve
olar
m
acro
phag
ede
posi
tion
w
ere
seen
at
6
mon
ths
(RC
F1)
9
mon
ths
(RC
F2,R
CF3
)
12m
onth
s(
RC
F4)
3.70
×10
5 RC
F1fi
bers
/mg
dry
lun
g9.
58×
105 R
CF2
fibe
rs/m
gdr
ylu
ng
2.57
×10
5 RC
F3fi
bers
/mg
dry
lun
g5.
95×
105 R
CF4
fibe
rs/m
gdr
ylu
ng
See
foot
not
eat
en
dof
tab
le.
(C
onti
nu
ed)
Refractory Ceramic Fibers 51
5 ■Effects of Exposure
Tabl
e 5–
5 (C
onti
nu
ed) .
Non
tum
or lu
ng
effe
cts
in a
nim
als
exp
osed
to R
CFs
* by
inh
alat
ion
R
efer
ence
Spec
ies
Fibr
osis
Lu
ng
chan
ges
Lun
g fi
ber
bu
rden
Mas
tet
al.
[199
5b]
Fisc
her
344
rat
sR
ever
sibl
ein
ters
titi
al
fi
bros
iss
een
at
12m
onth
s
in
16-
mg/
m3 g
rou
p
Ple
ura
lfibr
osis
was
min
imal
Inte
rsti
tial
fibr
osis
pro
gres
sed
in1
6-m
g/m
3 gro
up
such
that
itw
asir
reve
rsib
le
Ple
ura
lan
din
ters
titi
al
fibr
osis
wer
eir
reve
rsib
lea
t
fin
als
acri
fice
.
Mic
rogr
anu
lom
asin
16-m
g/m
3 dos
egr
oup
at
3m
onth
s
Sim
ilar
but
less
sev
ere
in
ot
her
dos
egr
oups
Pro
gres
sion
ina
ll3
grou
ps
at
6m
onth
s
Alv
eola
rbr
onch
ioliz
atio
nin
16-m
g/m
3 gro
up
Dos
e-a
nd
tim
e-de
pen
den
t
in
crea
ses
occu
rred
inlu
ng
and
lu
ng/
body
wei
ghts
.
RC
Fsw
ere
clea
red
quic
kly
from
lun
gso
fan
imal
sw
ith
lon
g
re
cove
ryp
erio
ds.
McC
onn
elle
tal
.
[199
5]Sy
rian
gol
den
ham
ster
sP
leu
ralfi
bros
isp
late
aued
af
ter
12m
onth
sas
dif
-
fu
sed
thic
ken
ing
tor
aise
d
nod
ule
s.
Fibr
osis
see
nb
etw
een
12a
nd
18m
onth
ssh
owed
incr
ease
dse
veri
ty.
Alv
eola
rbr
onch
ioliz
atio
n,
m
icro
gran
ulo
mas
,an
d
colla
gen
dep
osit
ion
;
alve
olar
mac
roph
age
aggr
egat
ion
RC
Fbu
rden
sle
vele
dof
fbe
twee
n
9an
d12
mon
ths.
Rec
over
yan
imal
ssh
owed
dec
reas
ed
R
CF
burd
ens
wit
hd
ecre
asin
g
le
ngt
hs
and
wid
ths.
Smit
he
tal
.
[1
987]
Osb
orn
e-M
ende
l
rat
s12
/55=
22%
Bro
nch
oalv
eola
rm
etap
lasi
a,
1/5
5=2%
2.18
±0.
99×
104 fi
bers
Syri
ang
olde
n
h
amst
ers
1/70
=1%
Bro
nch
oalv
eola
rm
etap
lasi
a,
2/6
9=3%
0.86
±0.
45×
104 fi
bers
* Abb
revi
atio
n: R
CFs
=re
frac
tory
cer
amic
fibe
rs.
52 Refractory Ceramic Fibers
5 ■Effects of Exposure
RCF4;and1inthechrysotileexposuregroup.Allmesotheliomasweredetectedatorafter24monthsofexposure.MostRCFfibersrecoveredinthelungwere5to10µmlongregardlessofexposuretimeandrecoverytime.An80%re-ductioninfiber lungburdenwasseeninratsallowedtorecover for21monthsfollowing3monthsofRCFexposure.
Mastetal.[1995b]exposedFischer344ratsbynose-onlyinhalationto0(air),3,9,or16mg/m3(0,26±12,75±35,or120±35WHOf/cm3)RCF1for 6 hr/day, 5 days/week for 24 months andheldthemuntilsacrificeat30months.FiberswereselectedbysizeasinMastetal.[1995a].Aparticleratioofnonfibrousparticulatetofi-bersof0.9–1.5:1wasreported.Groupsof3to6animalsweresacrificedat3,6,9,12,18,and24months toexamine lesionsanddeterminefi-berlungburdens.Otheranimalswereremovedfromexposureatthesametimepointsandhelduntilsacrificeat24months.Interstitialfibrosiswasobservedafter12monthsofexposureinthe9-and16-mg/m3exposuregroups.Pulmonaryfibrosiswasfirstobservedafter12monthswith16mg/m3exposureandafter18monthswith9mg/m3exposure.ThemeanWagnergradesofpulmonarycellularchangeandfibrosisinratsexposedto0,3,9,16,and30mg/m3ofRCFsfor24monthswere1.0,3.2,4.0,4.2,and4.0,respectively.Ratsexposedatthesamerangeofdosesfor24monthsandallowedtorecoverfor6monthshadmeanWagnergradesof1.0,2.9,3.8,4.0,and4.3.Theseverityofinterstitialandpleuralfibrosiswassimilarbetweenthoseani-malssacrificedat24monthsandthoseallowed6monthsofrecoveryfollowingthe24monthsofexposure.Theincidenceofpulmonaryneo-plasmswasnotstatisticallydifferentfromthecontrols in all exposure groups. One pleuralmesothelioma was observed in the 9-mg/m3exposure group. A dose-related increase oc-curredinfiberlungburden.Fiberlengthsof5to10µmweremostprevalentinthelungfibersrecoveredafter3monthsofexposurefollowed
by21monthsofrecovery,after12monthsofexposure,andafter24monthsofexposuretoalldosesofRCFs.Animalsexposedfor3or6monthsandthenallowedtorecoveruntilsac-rificeat24monthshadlungburdensreducedby96%to97%comparedwithanimalsnotal-lowedrecoverytime.
McConnelletal.[1995]exposedSyriangoldenhamstersbynose-onlyinhalationto30mg/m3RCF1 (256±58 WHO f/cm3) for 6 hr/day, 5days/weekfor18monthsandheldthemuntilsacrificeat20months.Positivecontrolanimalswereexposedto10mg/m3(8.4±9.0×104WHOf/cm3) chrysotile asbestos. Groups of 3 to 6animals were sacrificed at 3, 6, 9, 12, 15, and18months to examine lesions and determinefiber lung burdens. Other animals were re-movedfromexposureatthesametimepointsandhelduntilsacrificeat20months.Intersti-tialandpleuralfibrosiswerefirstobservedafter6 months of exposure in RCF-exposed ham-sters. No pulmonary neoplasms developed.Forty-two of 102 (41.2%) RCF-exposed ani-mals developed pleural mesotheliomas. Mostmesotheliomas developed after 18 months ofexposure. Animals exposed to chrysotile de-velopedamoresevere interstitialfibrosisandpleural fibrosis than those exposed to RCFs.No neoplasms were observed in the lungs orpleuraofthechrysotile-exposedoraircontrolanimals. The greatest percentage of retainedfibershad lengthsof5 to10µmanddiam-eters<5µminthelungsafter6monthsofex-posurefollowedby12monthsofrecovery.
McConnelletal.[1999]conductedamultidosechronicstudyoftheeffectsofamositeinhala-tion in hamsters. The data can be comparedwiththeeffectsofRCF1.Syriangoldenham-sterswereexposedto0.8(36±23WHOf/cm3),3.7(165±61WHOf/cm3),or7mg/m3(263±90WHOf/cm3)amositeasbestos.Pleuralmeso-theliomaincidencesof3.6%,25.9%,and19.5%,respectively,werereported.Theaerosolmean
Refractory Ceramic Fibers 53
5 ■Effects of Exposure
diameteroftheamositeasbestoswas0.60µm±0.25; its aerosol mean length was 13.4 µm±16.7. The dimensions of this asbestos fiberweremoresimilartothoseoftheRCFsusedinthechronicinhalationstudiesofMcConnelletal.[1995]thanthechrysotileasbestosusedasthepositivecontrolinthatsamestudy.
NIOSH[Dankovic2001]analyzedthehamsterdatafromtheRCF[McConnelletal.1995]andamositestudies[McConnelletal.1999].Adose-responsemodelwasdevelopedforamositeandwasusedtopredicttheamositeresponseattheoneandonlydoseatwhichRCFsweretestedinhamsters.Themodeledamositeresponsewascompared with the observed RCF response.TheseresultsarepresentedinFigures5–1and5–2. Log-probit, log-logistic, multistage, andunrestricted Weibull models were analyzed.The transformation for the log-probit andlog-logistic models was log (fibers/cm3 +1).ThedosemetricofthemultistageandWeibullmodelswasfibers/cm3,astheydidnotrequirealog-transformation.Resultsofthelog-probitmodel analysis of these data indicated RCF/amositerelativepotencyestimatesof1.85and1.19,usingWHOfibersandfibers>20µmasthe dose metric, respectively. The model fitswerepoorwhentheamositehigh-dosegroupand20µm-fiberdosewereincluded.Sensitivityanalysesinwhichthehigh-doseamositegroupwasdroppedsuggestthattherelativepotencyof RCFs to amosite could be as low as 0.66based on the log-probit model. Results usingthelog-logistic,multistage,andWeibullmod-els were similar to those using the log-probitmodel,withanoverall rangeofRCF/amositerelative potency estimates from these modelsusingall fouramositedosegroupsof1.03 to1.89.Althoughnocleartoxicologicbasisexistsfor disregarding the high-dose amosite data,sensitivity analyses based on excluding thesedatasuggestthatthepotencyofRCFsrelativetoamositecouldbeaslowas0.47,basedonthemultistagemodel.Thesemodels indicatethat
the plausible carcinogenic potency estimatesforRCFsrelativetoamosite,basedonhamstermesotheliomas,rangefromabouthalftonear-lytwicethecarcinogenicityofamosite.
5.1.3 DiscussionofRCFStudiesinAnimals
Theintrapleural,intraperitoneal,andintratra-chealRCFstudieshavedemonstratedthecar-cinogenicityofRCFs.Becauseofthenonphysi-ologicdeliveryoffibersbythesemethods,itisdifficult to compare their results with thoseof an inhalation exposure. Although trachealinstillation may result in different distribu-tionpatternsthananinhalationexposure,thisrouteofexposure isusefulasascreeningtestforrelativetoxicityandtocomparethetoxicityof new materials with the toxicity of materi-alsforwhichdataalreadyexist[Driscolletal.2000].Trachealinstillationalsoisusefulwhentestingfibersrespirablebyhumansbutnotro-dents.Chronic inhalationstudiesprovide thedatamostrelevanttooccupationalexposuretoRCFs.
The RCF chronic animal inhalation studiesdescribed above allow for the comparison ofhealtheffectsofexposuretodifferentdosesofRCF1,different typesofRCFs,and the inter-speciessusceptibilityoftheratandhamstertoRCFexposure.
Results of the multidose chronic inhalationtestingofRCF1 inrats indicate thepathogen-icpotentialofRCFsathighdoses[Mastetal.1995a,b]. The incidence of total lung tumorswas significantly increased from controls afterexposureto30mg/m3RCF1,RCF2,andRCF3butnotRCF4.Adose-responserelationshipwasdemonstrated for nonneoplastic pulmonarychangesinratsexposedto3,9,and16mg/m3
RCFs.Theseverityofinterstitialandpleuralfi-brosiswassimilarbetweenthoseanimalssacri-ficedat24monthsandthoseallowed6months
54 Refractory Ceramic Fibers
5 ■Effects of Exposure
Exposure concentration (f/cm3)
Exposure concentration (f/cm3)
Figure 5–1 .ProportionofhamsterswithmesotheliomasfollowingexposuretoamositeorRCFs.Con-centrationsarebasedonfibers>20µmlong.The95%confidencelimitsarebasedonassumingabi-nomialdistribution.Dashedlinesrepresentthelog-probitmodelfittedtotheamositedata[Dankovic2001].(Source:McConnelletal.[1995,1999].)
Figure 5–2 .ProportionofhamsterswithmesotheliomasfollowingexposuretoamositeorRCFs.Con-centrationsarebasedonWHOfiberdimensioncriteria.The95%confidencelimitsarebasedonas-sumingabinomialdistribution.Dashedlinesrepresentthelog-probitmodelfittedtotheamositedata[Dankovic2001].(Source:McConnelletal.[1995,1999].)
Refractory Ceramic Fibers 55
5 ■Effects of Exposure
ofrecoveryfollowingthe24-monthexposure.Spontaneousprimarypulmonarymesothelio-masarerareinrats[AnalyticalSciencesIncor-porated1999].Therefore,thepresenceofanymesotheliomaintreatedanimalsisbiologicallysignificantandwarrantscaution.
Comparing the chronic effects of RCF1 withitspositivecontrol,chrysotileasbestos, inthehamster isdifficultbecauseof thedifferencesindose,dimensions,anddurabilityofthetwofiberstested[McConnelletal.1995].Morere-cent dose-response data on amosite asbestosprovide a comparison because these amositefiberdimensionsmorecloselyresemblethoseof RCF1 [McConnell et al. 1999]. The meanlengths of the RCFs and amosite asbestos fi-bers were 22.1 (±16.7) and 13.4(±16.7) µm,respectively. Forty-three percent of RCF fi-bers and ~26% of amosite asbestos fiberswerelongerthan20µm.Themeandiametersof theRCFsandamositeasbestosfiberswere0.94(±0.63)and0.60(±0.25)µm,respectively.Interstitialandpleuralfibrosiswereseenmuchearlier with amosite exposure than with RCFexposure. RCF exposure at 215 (±56) WHOf/cm3resulted inmesotheliomas in42of102(41%)hamsters.Amositeasbestosexposureat263(±90)WHOf/cm3resultedinmesothelio-mas in 17 of 87 (19.5%) hamsters. Modelingof these data indicates that the plausible car-cinogenicpotencyestimates forRCFsrelativetoamosite,basedonhamstermesotheliomas,rangefromabouthalftonearlytwicethecar-cinogenicityofamosite[Dankovic2001].Dif-ferences in the physical characteristics andbiopersistence of RCF1 and amosite asbestosmustbeconsideredbeforeextrapolatingtheseanimaldatatohumanrisk.
Hamsters showed a greater susceptibility tomesotheliomainductionafterRCF1exposurethan did rats under similar exposure condi-tions[Mastetal.1995a;McConnelletal.1995].Chronicinhalationstudiesofamositeasbestosinhamstersshowednopulmonaryneoplasms,
buthighincidencesofmesotheliomaoccurredatdosesof125and250f/cm3[McConnelletal.1999].Manyofthemesotheliomasinthemorerecenthamsterstudieswereidentifiedonlyonmicroscopic examination [Mast et al. 1995a;McConnelletal.1995,1999].Previousstudiesreportingmesotheliomasonlybymacroscopicidentification may have underestimated themesothelioma incidence. Recent, short-terminhalation studies indicate that hamster me-sothelial cells may have a more pronouncedinflammatory and proliferative response toRCF1exposurethanthoseofrats[Everitt1997;Gelzleichteretal.1996a,b,1999].ThereasonsforthisspeciesdifferenceinresponsetoRCFshavenotbeenexplained.Theresultsof theseanimalstudiesindicatetheneedfortheinclu-sionofthehamsterasasensitivetestspeciesinthosestudiesinwhichpleuralmesotheliomaisanendpointofconcern.
Results fromMastetal.[1995a] indicatethatunder the conditions studied, exposure toRCF4 may have a less pronounced effect onpulmonarypathologythanexposuretoRCF1,RCF2, and RCF3. Rats exposed to RCF4 didnothaveasignificantincreaseintotallungtu-mors compared with controls; those exposedto RCF1, RCF2, and RCF3 did. Exposure toRCF4producedalessseverefibrosisthanwasseenintheotherRCFexposuregroups.Differ-encesinthedimensionsorphysicalpropertiesof RCF4 may explain its different respiratoryeffects from RCF1, RCF2, and RCF3. RCF4was produced by heating RCF1 in a furnaceat2,400ºFfor24hr.ThisAafter-service@fibercontained approximately 27% free crystal-line silica. Silicotic nodules were observed inthe RCF4-exposed animals. RCF4 fibers wereshorter (~34% between 5 and 10 µm ) andthicker(~35%<0.5µm)thanthoseofRCF1,RCF2,andRCF3.
Theparticlecontentof theRCF testmaterialmayhavebeenresponsibleforsomeofthere-spiratorypathologyobservedinthesestudies.
56 Refractory Ceramic Fibers
5 ■Effects of Exposure
However,ananalysisoftheratioofnonfibroustofibrousparticulatesinthereviewedstudiesdoes not indicate a correlation between theparticulatecontentandobservedeffects.Smithetal.[1987]performedtestingwiththehigh-est particulate to fiber ratio at 33:1 and didnot report a high tumor incidence. Compar-ing studies based on the ratio of nonfibrousparticulatestofibersiscomplicatedbydiffer-encesamongthestudies infiberpreparation,doses tested, fiber dimensions, and methodsof fiber analysis. The techniques used to de-tectandmeasurenonfibrousparticulateshaveimprovedovertimesothatthecomparisonofrecentandolder studiesmayreflect these in-consistencies.
ThesechronicRCFinhalationstudiesindicatetheabilityofRCFstoinducecancerintwolab-oratory species—mesotheliomas in hamstersandpulmonarytumorsinrats.ThelateonsetoftumorsindicatestheimportanceofchronicstudiesontheeffectsofRCFexposure.Short-termintraperitoneal,intrapleural,intratrache-al, and inhalation studies provide importantinformationabouttheactionoffibers,thefi-bercharacteristicsassociatedwithtoxicity,andpotentialtoxicity.CurrentlyitisonlythroughlifespantoxicologictestingofanimalsthattherespiratoryandotherchronichealtheffectsofRCFscanbeaccuratelyassessed.
5.1.4LungOverloadArgumentRegardingInhalationStudiesinAnimals
Mastetal.[2000]publishedareviewinterpret-ingtheresultsofchronicinhalationstudiesofRCF1inratsandhamsters[Mastetal.1995a,b;McConnelletal.1995].Inthereview,theau-thorssuggestthepossibilitythatthemaximumtolerateddose(MTD)mayhavebeenexceededandthatlungoverloadmayhavecompromisedthe pulmonary clearance mechanisms of test
animals.Buildingontheconceptoflungover-load (first advanced by Bolton et al. [1983]),Mastetal.[2000]consideredparticulatecoex-posure(i.e.,nonfibrousparticulateorshot)tobeaconfounding factor thatmayhavehadamajor effecton theobservedchronic adverseeffects.TheauthorsproposethattheMTDwasexceededatthehighestexposureconcentrationof30mg/m3forRCF1intheratbioassay.
The concept of pulmonary overload in theFischer344ratsisbasedontherecognitionthatexcessive particulate exposures (>1,500 µg/rat,according to Bolton et al. [1983]) eventuallyreducetheclearanceeffectivenessofthelungs,causingthenormallinearclearancekineticstofollowanonlinearpattern.Onacellular level,the overload conditions may result in alveolarmacrophages becoming engorged with par-ticulate, pulmonary and alveolar inflamma-tion,increasedtranslocationofparticlestotheinterstitiumandlymph,granulomaformation,pulmonaryfibrosis,andlungtumors,depend-ing on the time and severity of the overload[Mastetal.2000].Ambiguityaboutthedefini-tionofMTDforchronicinhalationstudieswithanimalswasalsoaconcernexpressedbytheau-thors.Onereference[Morrow1986]recognizesthe MTD as that which causes “a significantfunctionalimpairmentoflungclearance.”AtaNationalToxicologyProgram(NTP)workshoponestablishingexposureconcentrationsforin-halation studies in animals, it was concludedthatthehighestexposureconcentrationshouldproduceonlyminimalchangesinlungdefensemechanisms as measured by clearance [Lewisetal.1989].AtasimilarworkshopconvenedbytheEPA,itwasproposedthattheMTDforfi-berinhalationstudiesisequivalenttothelungdoseproducedatthemaximumachievablecon-centration (MAC) [Vu et al. 1996]. The MACiscalculatedasthehighestfiberconcentrationbasedona90-daystudythatresultsinsignifi-cant changes in alveolar macrophage clear-ancerates,lungburdennormalizedtoexposure
Refractory Ceramic Fibers 57
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concentration,cellproliferation,inflammation,lungweight,andothermeasures.
ThemethodologydescribedfortheRCFchron-icinhalationstudiesinvolvedprocedures(i.e.,wetcycloneseparationtechnology)forremov-ing the nonfibrous particulate fraction fromthecommercialfiber(RCF1)usedforthe in-halationexposures[Mastetal.1995a,b2000;McConnell etal.1995].Thisprocess resultedinanaerosolwitha9.1:1particle-to-fiberratio[Maximetal.1997;Mastetal.2000],comparedwithastudybySmithetal.[1987],whichre-ported 33 nonfibrous particles per fiber inairborneexposures.ResultsfromEsmenetal.[1979]indicatethatdespiteapoorcorrelationbetweenmassoftotalairbornedustandfiberconcentrationinRCFsmeasuredinmanufac-turing,fibersgenerallyconstituteonlyasmallportionofthetotaldust.Thisfindingiscon-sistentwithotherreportedmeasuresofoccu-pational exposures to airborne RCFs [Krantzet al. 1994; Trethowan et al. 1995]. However,Maxim et al. [1997] reported an averageparticle-to-fiber ratio of 0.53:1 (n=10, rangenotreported),orroughly1particleto2fibersinRCFmanufacturingfacilities.
MuhleandBellmann[1996]conducteda5-dayinhalationstudywithFischer344ratstomea-surethebiopersistenceofRCF1(withthe9:1particulate-to-fiber ratio) and RCF1a (RCF1that is further processed to reduce particu-latemass).Thestudyshoweda1.5-foldlongertime-weightedhalf-lifeforRCF1(t
1/2=78days)
compared with RCF1a (t1/2
=54 days). Thatstudyalsoinvolveda3-weekinhalationexperi-mentwithFischer344rats,inwhichtheclear-anceofRCF1(t
1/2=103days)wasalmosttwice
aslongasthatofRCF1a(t1/2
=54days).
In a follow-up study by Brown et al. [2000],femaleWistarratswereexposedtoRCF1andRCF1abyinhalationfor3weeksandfollowedfor12monthstoevaluatealveolarmacrophageclearance and inflammation. The exposure
concentrationswere130fibers/ml>20µmforRCF1 and 125 fibers/ml >20 µm for RCF1a.ThenonfibrouscontentofRCF1wasapproxi-mately 25%, whereas the nonfibrous contentofRCF1awas2%.Themeandiameterofthenonfibrousparticleswas2to3µm.Theaero-solexposuretoRCF1containedtwiceasmanyshortfibers(<20µm)asRCF1aandtwicetheamountofdust(fibersandnonfibrousdust/mg·m3)asRCF1a(51versus25.8mg/m3).Attheendoftheinhalationperiod,animalsexposedtoRCF1ahadahigherpulmonaryconcentra-tionoflongfibersbutlowerconcentrationsofshortfibersandnonfibrousparticles.Thedif-ferenceinparticlecontentwasenhancedinthelungs—15timesmoreparticleswerefoundinthe lungs of the RCF1-exposed animals thaninthoseexposedtoRCF1a.Intheaerosolex-posure,onlyaneightfolddifferencewasfoundinthenumberofparticlesbetweenRCF1andRCF1a. The RCF1a-exposed animals had ahalf-timealveolarclearanceof80days(71–91)compared with 60 days (49–77) for the con-trols; clearance half-time for exposed RCF1animals was 1,200 days (573-infinity) com-pared with 66 (58–88) for the correspondingcontrols. To evaluate respiratory inflamma-tion, bronchoalveolar lavage (BAL) measure-ments(lactosedehyrdogenase[LDH],γ-gluta-myltransferase[γ–GT],totalprotein,reducedglutathione [GSH]) were taken at the end ofthe3-weekstudyperiodandatsubsequentin-tervalsoverthenext12months.Immediatelyfollowingthe3-weekinhalationstudy,allBALmeasurements were statistically elevated inbothRCF1andRCF1aanimals.However,after91daysofrecovery,theBALmeasurementsforRCF1aanimalsreturnedtonormal.Indicationsof inflammation continued for RCF1 throughtheentireobservationperiod.ThegreaterandmorepersistentinflammationseenwithRCF1wasattributedtothegreatermassofmaterialortoincreasedactivityofthenonfibrouspar-ticles,althoughthehighconcentrationofshortfibers in RCF1 (twice that of RCF1a) could
58 Refractory Ceramic Fibers
5 ■Effects of Exposure
have contributed to the observed impedanceinalveolarmacrophageclearanceandinflam-mation.
Tranetal. [1997]examinedhowoverloadingthealveolarmacrophagedefensesystemaffectstheclearanceoffibersversusthatofnonfibrousparticles. Modeling was performed based ondataforratsexposedbyinhalationtotitaniumdioxide (TiO
2) at 1, 10, and 50 mg/m3 or to
glasswool(MMVF10)at3,16,and30mg/m3.Lung burdens and clearance kinetics duringexposure(0to100weeks)werecomparedwiththoseat3,10,and38dayspost-exposure.Themodelsshowedthatoverloadingofthelungbyfibersornonfibrousparticlesaresimilarwhenfibers are short (<15µm). This observationisplausible,asnonfibrousparticlesandshortfiberssmallerthanthediameterof thealveo-larmacrophagearemostreadilyengulfedandcleared via the macrophages. When this de-fense isoverwhelmed(lungburden≥10mg),these particles are cleared less effectively. Forfiberslongerthan15µm,phagocytosisbyalve-olarmacrophageisreduced.Asfiberlengthin-creases,fiberstendtobeclearedbydissolutionand disintegration of long fibers into shorterfibers or fragments. Therefore, clearance oflongfibersisnotaffectedbytheoverloadingofmacrophage-mediated defenses with shorterfibersornonfibrousparticles.
The exposure concentrations for the RCFchronic inhalation bioassays were measuredandreportedasmassinmg/m3.Monitoringofexposuresasperformedbygravimetricanaly-sisdoesnotdistinguishfibersfromnonfibrousparticulate, although fiber concentration anddimensionswerealsocheckedbyphasecontrastandelectronmicroscopy[Mastetal.1995a,b].Consequently,theparticulatefractionwasin-cluded in the dose measurements. This factdoescomplicateeffortstocomparetherelativetoxicity of fibers, nonfibrous particulate, andtotal combined particulate, especially regard-ingthelungoverloadhypothesis.Duringpro-
ductionofRCFsandRCFproducts,however,the nonfibrous particulate fraction is associ-atedwiththefiber,asshowninTable2–1(i.e.,20%to50%ofRCFsbyweightisnonfibrousparticulate). This suggests that occupationalexposurestoairborneRCFsnecessarilyinvolvecoexposures to a fraction of nonfibrous par-ticulate,asuggestionthathasbeensupportedby exposure assessment studies [Esmen et al.1979;Krantzetal.1994;vandenBergenetal.1994;Trethowanetal.1995;Maximetal.1997;Mastetal.2000].
5.2CellularandMolecularEffectsofRCFs(In VitroStudies)
ThecellularandmoleculareffectsofRCFex-posureshavebeen studiedwith twodifferentobjectives.Onepurposeoftheseinvitrostud-iesistoprovideaquicker,lessexpensive,andmorecontrolledalternativetoanimaltoxicitytesting.Theseexperimentsarebest interpret-edbycomparingtheirresultswiththoseofinvivo experiments. The second objective of invitrostudies is toprovidedata thatmayhelpto explain the pathogenesis and mechanismsofactionofRCFsatthecellularandmolecu-lar levels.Thesecytotoxicityandgenotoxicitystudiesarebest interpretedbycomparingtheeffectsofRCFswiththoseofotherSVFsandasbestosfibers.Invitrostudiesserveasscreen-ingtoolsandprovideinsightsintothemolecu-larmechanismsoffibers.Theyareanimpor-tantcomplementtoanimalstudies.CurrentlyitisnotpossibletousethesedatatoderivetheNIOSHRELforRCFs.For thisreason,adis-cussionofinvitrostudiesisincludedhere,butthemorecomprehensivesummariesofstudiesareincludedinAppendixC.
The toxicity of fibers has been attributed totheirdose,dimensions,anddurability.Anytest
Refractory Ceramic Fibers 59
5 ■Effects of Exposure
systemthatisdesignedtoassessthepotentialtoxicity of fibers must address these factors.Durability is difficult to assess using in vitrostudies because of their acute time course.However,invitrostudiesprovideanopportu-nity tostudy theeffectsofvaryingdosesanddimensions of fibers in a quicker, more effi-cientmethodthananimaltesting.Theydonotcurrentlyprovidedatathatcanbeextrapolatedtooccupationalriskassessment.
Theassociationbetweenfiberdimensionandtoxicity has been documented and reviewed[Stanton et al. 1977, 1981; Pott et al. 1987;Warheit1994].RCFsmayhavedifferenttoxici-ties,dependingon thefiber lengthrelative tomacrophagesize.Longerfibersaremoretoxic.Fiberlengthhasbeencorrelatedwiththecyto-toxicityofglassfibers[Blakeetal.1998].Man-ville code 100 (JM–100) fiber samples withaveragelengthsof3,4,7,17,and33µmwereassessedfortheireffectsonLDHactivityandratalveolarmacrophagefunction.Thegreatestcytotoxicitywasreportedinthe17-and33-µmsamples, indicating that length is an impor-tantfactorinthetoxicityofthisfiber.Multiplemacrophages were observed attached alongthelengthoflongfibers.Relativelyshortfibers(<20 µm) were usually phagocytized by onerat alveolar macrophage [Luoto et al. 1994].Longer fibers were phagocytized by two ormore macrophages. Incomplete or frustratedphagocytosismayplayarole inthe increasedtoxicity of longer fibers. Long fibers (17 µmaveragelength)wereamorepotentinduceroftumor necrosis factor (TNF) production andtranscription factor activation than shorterfibers (7 µm average length) [Ye et al. 1999].Thesestudiesdemonstratetheimportantroleoflengthinfibertoxicityandsuggestthatthecapacityformacrophagephagocytosismaybeacriticalfactorindeterminingfibertoxicity.
Several of the in vitro RCF studies (summa-rizedinAppendixC)reportedadirectassocia-tionbetweenalongerfiberlengthandgreater
cytotoxicity. Hart et al. [1992] reported theshortestfiberstobetheleastcytotoxic.Brownet al. [1986] reportedanassociationbetweenlength,butnotdiameter,andcytotoxicactivity.Wrightetal.[1986]reportedthatcytotoxicitywascorrelatedwithfibers>8µmlong.Yeglesetal.[1995]reportedthatthelongestandthickestfiberswerethemostcytotoxic.ThefourmostcytotoxicfibershadGMlengths≥13µmandGMdiameters>0.5µm.Theproductionofab-normal anaphases and telophases was associ-atedwithStantonfiberswitha length>8µmanddiameter<0.25µm.Hartetal.[1994]re-portedthatcytotoxicityincreasedwithincreas-ing average fiber lengths from 1.4 to 22 µm,butdidnotincreasewithaveragelengthsfrom22to31µm.
Additional studies assessing the cytotoxicityofspecificRCFfiberlengthsareneeded.Suchstudieswillhelptodescribetheassociationbe-tween fiber length and toxicity for RCFs andmayallowdeterminationofathresholdlengthabove which toxicity increases significantly.Inaddition toprovidingdataon thecorrela-tionbetweenfiberlengthandtoxicity,invitrostudieshaveprovideddataontherelativetox-icity of RCFs compared with other fibers, al-thoughsomeuncertaintiesremainintheinter-pretationofthesestudiesbecauseofdifferencesin fiber doses, dimensions, and durabilities.RCFs have direct and indirect effects on cellsandalter gene function in similarways.Theyarecapableofinducingenzymereleaseandcellhemolysis.Theymaydecreasecellviabilityandinhibit proliferation. RCFs affect the produc-tionofTNFandreactiveoxygenspecies(ROS)andaffectcellviabilityandproliferation.Theyinducenecrosisinratpleuralmesothelialcells.They may also induce free radicals, micronu-clei, polynuclei, chromosomal breakage, andhyperdiploidcellsinvitro.
Invitrostudiesprovideanexcellentopportu-nityforinvestigatingthepathogenesisofRCFs.However, comparisons are difficult to make
60 Refractory Ceramic Fibers
5 ■Effects of Exposure
between in vitro studies based on differencesin fiber doses, dimensions, preparations, andcompositions. Important information suchas fiber length distribution is not always de-termined. Even when comparable fibers arestudied,thecelllineorconditionsunderwhichtheyaretestedmayvary.Muchoftheresearchtodatehasbeendoneinrodentcelllinesandincellsthatarenotrelatedtotheprimarytar-get organ. In vitro studies using human pul-monarycelllinesshouldprovidepathogenesisdatamostrelevanttohumanhealthriskassess-ment.
Short-term in vitro studies cannot take intoaccounttheinfluenceoffiberdissolutionandfiber compositional changes that may occurover time. In an in vivo exposure, fibers arecontinually modified physically, chemically,andstructurallybycomponentsofthelungen-vironment. This complex set of conditions isdifficulttorecreateinvitro.Justasitisunlikelythatonlyonefactorisanaccuratepredictoroffibertoxicity,itisunlikelythatanyoneinvitrotestisabletopredictfibertoxicity.
5.3 Health Effects in Humans5.3.1 Morbidity and Mortality Studies
Twomajorresearcheffortsevaluatedthemor-bidityofRCF-exposedworkers—oneconduct-edinU.S.plantsandoneinEuropeanplants.Table 5–6 describes the populations analyzedforbothstudies.Theobjectiveoftheseresearcheffortswastoevaluatetherelationshipbetweenoccupational exposure to RCFsandpotentialadverse health effects. These studies includedstandardizedrespiratoryandoccupationalhis-tory questionnaires, chest radiographs, andpulmonary function tests (PFTs) of workers,aswellasairsamplingtoestimateworkerex-posures.ThestudiesofEuropeanplantsbeganin1986.Studysubjects includedonlycurrentworkers at seven RCF manufacturing plants
[Rossiter et al. 1994; Trethowan et al. 1995;Burgeetal.1995].Afollowupcross-sectionalstudy conducted in 1996 evaluated the samemedicalendpointsinworkersfromsixoftheseseven European manufacturing plants (oneplanthadceasedoperation)[Cowieetal.1999,2001]. Current and former workers were in-cludedasstudysubjectsinthefollowupstudy.The studiesofU.S.plantsbegan in1987andinvolvedevaluationsofcurrentworkersatfiveRCFmanufacturingplantsandformerwork-ersattwoRCFmanufacturingplants[Lemas-tersetal.1994,1998;Lockeyetal.1993,1996,1998,2002].
In the United States, the earliest commercialproductionofRCFsandRCFproductsbeganin1953;inEurope,RCFproductionbeganin1968. The demographics of the U.S. and Eu-ropean populations were similar at the timethey were studied, although the average ageof U.S. workers was slightly higher than thatof the workforce in the 1986 European stud-iesbecauseof theearlierdevelopmentof thisindustry in the United States. The mean agefortheEuropeanRCFworkerswas37.7inthe1986 study [Trethowan et al. 1995] and 42.0for males and 39.4 for female workers in the1996 study [Cowie et al. 1999]. In the U.S.RCFmanufacturing industry, theaverageageis 40for current workers and 45 for formerworkers[Lemastersetal.1994].Themeandu-rationofemploymentintheEuropeancohortwas10.2years(range7.2to13.8years)in1986[Trethowanetal.1995]and13.0yearsin1996[Cowieetal.1999].TheU.S.studyreportsthemeandurationofemploymentfor23workerswithpleuralplaquesas13.6years (±9.8); themedian is 11.2 years (range 1.4 to 32.7) [Le-mastersetal.1994].
The following text and Table 5–7 summarizefindingsfromtheU.S.andEuropeanresearchefforts, organized according to results fromradiographicexaminations,respiratorysymp-toms, and PFTs. Discussion of two related
Refractory Ceramic Fibers 61
5 ■Effects of Exposure
Table 5–6 . Cited studies of populations with occupational exposures to RCFs*
Population analyzed Outcome measures
Study DesignEmployment
status Number% male workers
% female workers Radiography PFT Symptoms
European:
Burgeetal.1995‡ Cross-sectional Current§ 532 100 0 N Y Y
Rossiteretal.1994‡ Cohortmorbidity Current** 543 100 0 Y N N
Trethowanetal.1995‡ Cross-sectional Current 628 91 9 Y Y Y
Cowieetal.1999†† Cross-sectional Current 695 90 10 Y Y Y
Former 79 85 15
United States:‡‡
Lemastersetal.1994 Cross-sectional Current 627 83 17 Y N N
Lemastersetal.1994 Cross-sectional Former§§ 220 91 9
Lockeyetal.1993: Cohortmortality Currentandformer
684(including46deceasedand5losttofollowup)***
100 0 N N N(Causeofdeath)
Cohortmorbidity Currentandformer
801(par-ticipants;99%providedrespiratoryhistory,94%providedPFTs,and90%providedchestX-rays[radi-ography])
85 15 Y Y Y
Lockeyetal.1996 Cohortmorbidity Current 370 NA NA Y N N
Former 282††† NA NA NA NA NA
Nestedcase-control
Both(17caseswith3controlseachmatchedoncurrentversusformerstatus)
NA NA Y Y N N
Lockeyetal.1998 Cross-sectionalandlongitudinal
Current 361‡‡‡ 100 0 N Y N
Seefootnotesonnextpage.
62 Refractory Ceramic Fibers
5 ■Effects of Exposure
*Abbreviations:N=number;NA=notavailablefrompublishedcitation;PFT=pulmonaryfunctiontest;RCFs=refractoryceramicfibers;Y=yes.
†Currentversusformer(andleaver)workerstatusatanRCFmanufacturingplantasdeterminedattimeofsurvey.‡StudyincludedcurrentworkersatsevenceramicfibermanufacturingplantsinthreeEuropeancountries.
§Fromapossible708currentworkers,628eligibleparticipantswereidentifiedand596hadchestX-rayexaminations;51femaleworkersand13unexplainedotherswereexcludedfromanalysis.
**Fromapossible708currentworkers,628eligibleparticipantswereidentifiedand596hadchestX-rayexaminations;2unreadablefilmsandthoseof51femaleworkerswereexcludedfromtheanalysis.
††StudyincludedcurrentworkersatsixceramicfibermanufacturingplantsinthreeEuropeancountriesaswellasleaversfromthefirstthreeEuropeanstudies[Burgeetal.1995;Rossiteretal.1994;Trethowanetal.1995](oneofthesevenplantsin-cludedearlierhadceasedoperation).
‡‡StudiesincludedcurrentandformerworkersatfiveRCFmanufacturingplantsintheUnitedStates.§§Fromapossible1,030eligiblecurrentandformerworkers,183wereeitherdeceased,notlocated,ordidnotagreetochestX-
rayexaminations.***Fromapossible729eligiblecurrentandformerworkersat2plantsitesforwhomindividualworkhistorieswereavailable,45wereexcludedonthebasisofinsufficientexposurestofibersorinsufficientdataregardingfiberexposures.
†††Fromapossible868eligiblecurrentandformerworkersat2plantsites,148wereeliminatedforlackofexposurecharacterizationdataandlosstofollowup.Oftheremaining720workers,68didnotagreetochestX-rayexaminations.‡‡‡Fromapossible963eligiblecurrentworkersatfiveplantsites,209femaleworkerswereexcludedaswellas393maleworkers
withfewerthan5PFTsessions.
mortality studies is also presented in Sec-tion 5.3.5 [Lockey et al. 1993; Lemasters etal.2003].TwoHHEsofworkplacesinvolvingworkersexposedtoRCFsarealsodescribedinSection5.3.6[Kominsky1978;Lyman1992].
5.3.2 Radiographic Analyses
In both the European and U.S. studies citedin Table 5–6, the study populations includ-edworkers atmultipleplants involved in themanufactureofRCFsorRCFproducts.Aspartoftheinvestigationofpotentialeffectsofexpo-suretoairborneRCFs,chestradiographywasperformed. In all studies, chest radiographswere read independentlyby three readersus-ingtheInternationalLabourOffice(ILO)1980 International Classification of the Radiographs of Pneumoconioses [ILO 1980]. Identifiers onfilmsweremaskedtoensureablindreviewbyreaders,andqualitycontrolmeasuresandtestsof agreement were used to check consistencyamongthereaders.Foreachtypeofabnormal-ityanalyzed,themedianofthethreereadingsforeachfilmwasused.
5.3.2.1 Pleural abnormalities
Inthe1986studyofEuropeanRCFworkers,re-sultsofthechestradiographyindicatedapreva-lenceof2.8%(15/543) forpleuralabnormali-tiesamongmaleworkers[Rossiteretal.1994].Of the 15 cases with pleural abnormalities, 4hadbilateraldiffusethickening(1withcalcifi-cation),1showedbilateralpleuralcalcificationonly,7presentedwithunilateraldiffuse thick-ening,and3showedcostophrenicangleblunt-ingonly.Thepossibilityforconfoundingeffectswas recognized because of other exposures:52% of workers reported previous employ-ment industy jobs, including4.5%withpriorasbestosexposuresand7%withpriorMMMFexposures.Whenfemaleworkerswereincludedinthesamepopulation,Trethowanetal.[1995]reported a prevalence of 2.7% (16/592) forpleuralabnormalities.Twocaseswereknowntohavepreviousexposuretoasbestos,andthepos-sibilityforexposuretootherrespiratoryhazardswasacknowledgedforotherpersonswithpleuralabnormalities.Cowieetal.[1999,2001]reportedpleural abnormalities in 10% (78/774) and
Refractory Ceramic Fibers 63
5 ■Effects of Exposure
Tabl
e 5–
7 . U
.S .
and
Eu
rop
ean
mor
bid
ity
stu
die
s w
ith
RC
Fs*
Ref
eren
ceSt
udy
des
ign
an
d p
opu
lati
onEv
alu
atio
n m
eth
ods
Res
ult
sC
omm
ents
Lem
aste
rs
et
al.1
994
(U.S
.stu
dy)
Cro
ss-s
ecti
onal
stu
dy:
1,03
0cu
rren
tan
dfo
rmer
wor
kers
at
five
U
.S.R
CF
prod
uct
ion
fa
cilit
ies
empl
oyed
10
/87–
8/89
.Mal
ew
orke
rs:a
tle
ast
1ye
ar
ofe
mpl
oym
ent
in
fibe
rdi
visi
on.F
emal
ew
orke
rs:a
tle
ast
1ye
ar
ofe
mpl
oym
ent
in
fibe
rdi
visi
ona
nd
≥4h
rp
erw
eek
in
prod
uct
ion
.
Post
eroa
nter
iorc
hest
X-r
aye
xam
ina-
tions
wer
epe
rfor
med
for8
47w
ork-
ers.
Occ
upat
iona
land
resp
irat
ory
heal
thh
istor
ies
wer
eob
tain
edu
sing
stan
dard
ized
que
stio
nnai
re.S
tand
ard-
ized
mea
sure
sofp
ulm
onar
yfu
nctio
n
(FEV
1,FV
C,a
ndF
EF25
–75)w
ere
used
.
Rad
iogr
aph
ic a
nal
yses
: P
leu
ral c
han
ges
Pleu
ralc
hang
esw
ere
seen
in3
.4%
ofp
rodu
ctio
n
wor
kers
(23/
686)
and
in0
%o
fnon
prod
uctio
nw
orke
rs
(0/1
61);
91.
3%o
fple
ural
cha
nges
wer
ecl
assi
fied
as
pleu
ralp
laqu
es.N
oir
regu
laro
paci
tiesw
ere
obse
rved
.
Mu
ltip
lelo
gist
icr
egre
s-si
onfo
un
da
stat
is-
tica
llys
ign
ifica
nt
asso
ciat
ion
bet
wee
n
pleu
ralp
laqu
esa
nd
tim
esi
nce
firs
tR
CF
prod
uct
ion
job
(>20
ye
ars)
aft
era
dju
st-
men
tfo
rkn
own
as
best
ose
xpos
ure
an
da
stat
isti
cally
si
gnifi
can
tas
soci
a-ti
onb
etw
een
ple
ura
lpl
aqu
esa
nd
dura
tion
(>
20y
ears
)of
RC
Fex
pos
ure
. (Con
tin
ued
)
Ple
ura
l ch
ange
s
P
reve
lan
ce
Ite
m
(%)
OR
95
% C
I
Year
sof
late
ncy
:†
>0–
10
1.3
1.0
—>
10–2
03.
62.
9‡,§
0.8,
9.7
>20
11
.4
7.7‡,
§ 2.
0,2
9.1
Year
sof
RC
F
ex
posu
re:
>0–
10
1.9
1.0
—>
10–2
04.
32.
5**,†
† 0.
9,7
.0>
20
20.7
8.
8**,†
† 2.
6,3
0.1
* Abb
revi
atio
ns:
CI=
con
fide
nce
inte
rval
;FE
F 25–7
5=fo
rced
exp
irat
ory
flow
bet
wee
n2
5%a
nd
75%
of
the
FVC
;FE
V1=
forc
ede
xpir
ator
yvo
lum
ein
1s
econ
d;F
VC
=fo
rced
vit
al
c
apac
ity;
OR
=od
dsr
atio
;RC
Fs=
refr
acto
ryc
eram
icfi
bers
. † La
ten
cy:t
ime
sin
cefi
rst
RC
Fex
posu
re.
‡ Com
pare
dw
ith
>0–
10y
ears
of
late
ncy
.§ A
dju
sted
for
year
sof
late
ncy
an
dye
ars
ofa
sbes
tos
exp
osu
re.
**C
ompa
red
wit
h>
0–10
yea
rso
fR
CF
expo
sure
.††
Adj
ust
ed(
con
fou
ndi
ng
vari
able
sn
otd
escr
ibed
).
64 Refractory Ceramic Fibers
5 ■Effects of Exposure
Tabl
e 5–
7 (C
onti
nu
ed) .
U .S
. an
d E
uro
pea
n m
orb
idit
y st
ud
ies
wit
h R
CFs
*
Ref
eren
ceSt
udy
des
ign
an
d p
opu
lati
onEv
alu
atio
n m
eth
ods
Res
ult
sC
omm
ents
Lem
aste
rs
et
al.1
998
(U.S
.stu
dy)
Cro
ss-s
ecti
onal
stu
dy:
742
of7
53a
ctiv
ew
orke
rs(
597
mal
e;
145
fem
ale)
at
five
R
CF
man
ufa
ctu
rin
gsi
tes
wh
op
arti
ci-
pate
din
occ
upa
tion
al
his
tory
inte
rvie
ws
be
twee
n1
987
and
1989
.
Med
ical
Eva
luat
ion
:
Mod
ified
Am
eric
anT
hor
acic
So
ciet
y(A
TS)
qu
esti
onn
aire
.Sp
irom
etri
cev
alu
atio
n(
pul-
mon
ary
fun
ctio
n)
att
ime
ofA
TS
inte
rvie
w.M
easu
res
incl
ude
dFE
V1,F
VC
,an
dFE
F 25%
–75%
.
Exp
osu
re a
sses
smen
t:
Occ
upa
tion
alh
isto
ryin
ter-
view
Pro
du
ctio
n w
ork:
Defi
ned
as
spen
din
g≥4
hr/
wee
k(1
0%o
fw
ork
tim
e)in
pr
odu
ctio
na
reas
.
Sym
pto
m a
nal
ysis
P
reva
len
ce (
%)
N
onp
ro-
Pro
du
c-
du
ctio
n
ti
on
S
ymp
tom
w
orke
rs
wor
kers
O
R†
95%
CI
Mal
ew
orke
rs
n=
80
n
=51
7—
—
Dys
pnea
1
2.5
15.7
7.3‡
1.7,
30.
5D
yspn
ea2
0.
04.
8
—
P
=0.
03‡
Wh
eezi
ng
3.8
10.3
2.
50.
8,8
.5A
sth
ma
2.5
2.3
1.0
0.2,
4.7
Ch
ron
icc
ough
5.
07.
41.
00.
3,3
.0C
hro
nic
ph
legm
3.
85.
81.
20.
4,4
.6P
leu
riti
cpa
in
0.0
1.6
—
P=
0.31
On
eor
mor
e
sym
ptom
s11
.3
29.6
2.
9‡ 1.
4,6
.2
Fem
ale
wor
kers
n
=59
n=
86
—
—
Dys
pnea
1
18.6
25
.6
1.3
0.6,
3.2
Dys
pnea
2
0.0
10.5
—
P=
0.00
1‡
Wh
eezi
ng
1.7
7.0
3.9
0.4,
38.
8A
sth
ma
0.0
3.5
—
P=
0.21
Ch
ron
icc
ough
1.
79.
35.
40.
6,4
6.9
Ch
ron
icp
hle
gm
1.7
9.3
3.8
0.4,
33.
5P
leu
riti
cpa
in
0.0
3.5
—
P=
0.21
On
eor
mor
e
sym
ptom
s20
.3
40.7
2.
4‡ 1.
1,5
.3
Pre
vale
nce
of
resp
ira-
tory
sym
ptom
s(e
xcep
tfor
as
thm
a)w
asa
ppro
xim
atel
y2-
to5
-fol
dhi
gher
in
prod
ucti
onw
orke
rsth
anin
n
onpr
oduc
tion
wor
kers
.
(Con
tinu
ed)
*Abb
revi
atio
ns:
AT
S=
Am
eric
anT
hor
acic
Soc
iety
;CI
=c
onfi
den
cein
terv
al;F
EF 25
%−
75%
=F
orce
dex
pira
tory
flow
bet
wee
n2
5%a
nd
75%
of
the
FVC
;FE
V1=
forc
ede
xpir
ator
y
volu
me
in1
sec
ond;
FV
C=
forc
edv
ital
cap
acit
y;n
=n
um
ber;
OR
=o
dds
rati
o; P
=p
roba
bilit
y;R
CFs
=r
efra
ctor
yce
ram
icfi
bers
.† A
dju
sted
for
age,
sm
okin
g(c
ateg
ory
and
pack
yea
rs),
an
dye
ars
ofp
ossi
ble
asbe
stos
exp
osu
rein
alo
gist
icr
egre
ssio
nm
odel
.‡ St
atis
tica
llys
ign
ific
ant
(P<
0.05
).
Refractory Ceramic Fibers 65
5 ■Effects of Exposure
Ta
ble
5–7
(C
onti
nu
ed) .
U .S
. an
d E
uro
pea
n m
orb
idit
y st
ud
ies
wit
h R
CF
s*
Ref
eren
ceSt
udy
des
ign
an
d p
opu
lati
onEv
alu
atio
n m
eth
ods
Res
ult
sC
omm
ents
Lem
aste
rs
et
al.1
998,
c
onti
nu
ed
(U.S
.stu
dy)
Mu
ltip
le
regr
essi
on
anal
ysis
† of
chan
gein
vo
lum
e(m
l)
ofh
eigh
t-ad
just
ed
spir
omet
ric
mea
sure
s(9
5%C
I)
asso
ciat
ed
wit
hR
CF
emp
loym
ent
dura
tion
.C
ontr
olle
d
for
smok
ing
stat
us.
Pulm
unar
y fu
ncti
on
Δ v
olum
e in
(ml)
Item
C
urre
nt sm
oker
s Pa
st sm
oker
s N
ever
smok
ers
Mal
ew
orke
rs
n=
245
n=
174
n=
173
[FV
C]
year
sof
RC
F
emp
loym
ent
–165
.4‡ (
–279
.8,–
51.0
)–1
55.5
‡ (–30
1.9,
–9.
1)
–40.
6(–
175.
1,19
3.8)
[FE
V1]
year
sof
RC
F
emp
loym
ent
–134
.9‡ (
–231
.3,–
38.5
)–7
2.5
(–19
5.9,
50.
9)
–20.
4(–
133.
7,9
2.9)
Fem
ale
wor
kers
n
=56
n
=20
n
=68
[FV
C]
year
sof
RC
F
emp
loym
ent
–110
.8(
–411
.5,1
90.0
)–3
30.5
(–8
72.1
,211
.1)
–350
.3‡ (
–692
.0,8
.7)
[FE
V1]
year
sof
RC
F
emp
loym
ent
13.9
(–2
18.7
,246
.5)
–321
.4(
–740
.2,9
7.4)
–2
23.5
(–4
87.7
,40.
7)
Year
sof
RC
F
prod
uct
ion
em
plo
ymen
tw
ere
sign
ifi-
can
tly
rela
ted
to
volu
me
decl
ine
in(
1)F
VC
for
mal
ecu
rren
tan
d
pas
tsm
oker
s,
(2)
FEV
1inm
ale
curr
ent
smok
-er
s,a
nd
(3)
FV
C
for
fem
ale
nev
er
smok
ers.
* Abb
revi
atio
ns:
CI=
con
fide
nce
inte
rval
;FE
V1=
forc
ede
xpir
ator
yvo
lum
ein
1s
econ
d;F
VC
=fo
rced
vit
alc
apac
ity;
n=
nu
mbe
r;O
=od
dsr
atio
;RC
Fs=
refr
acto
ryc
eram
icfi
bers
.† V
aria
bles
incl
ude
din
mod
el:s
mok
ing
cate
gory
,in
tera
ctio
nte
rmfo
rdu
rati
ono
fR
CF
prod
uct
ion
an
dsm
okin
gca
tego
ry,i
nte
ract
ion
term
for
pack
-yea
rsa
nd
s
mok
ing
cate
gory
,wei
ght,
and
plan
tlo
cati
on.
‡ Stat
isti
cally
sig
nif
ican
t(P
≤0.0
5).
(Con
tin
ued
)
66 Refractory Ceramic Fibers
5 ■Effects of Exposure
Tabl
e 5–
7 (C
onti
nu
ed) .
U .S
. an
d E
uro
pea
n m
orb
idit
y st
ud
ies
wit
h R
CFs
*
Ref
eren
ceSt
udy
des
ign
and
pop
ula
tion
Eval
uat
ion
met
hod
sR
esu
lts
Com
men
ts
Lock
ey
et
al.1
996
(U.S
.stu
dy)
Coh
ort s
tudy
:6
52w
orke
rs(
a)w
how
ere
em-
plo
yed
betw
een
10/8
7
and
12/
91o
rw
ho
had
≥1
year
ofe
m-
plo
ymen
tin
the
RC
F
div
isio
nat
one
oft
wo
p
lant
site
s,
and
(b)
who
com
plet
eda
n
o
ccup
atio
nalh
isto
ry
a
ndp
rovi
ded
post
erio
r-
an
teri
ora
ndtw
o
obl
ique
che
stX
-ray
s.
Nes
ted
case
-con
trol
st
udy:
17
case
sof
ple
ural
pla
que
mat
ched
to
3c
ontr
ols
bys
exa
nd
em
ploy
men
tsta
tus
(
curr
ento
rfo
rmer
w
orke
r;p
rodu
ctio
nor
n
onpr
oduc
tion
)
Hea
lth
: O
ccup
atio
nal
his
tory
inte
rvie
w,
i
nfo
rmat
ion
abo
utw
ork/
hom
e
asb
esto
sex
posu
re;c
hest
X-r
ays.
Exp
osu
re:
Est
imat
edc
once
ntr
atio
ns
of
fibe
rex
posu
refo
rea
chjo
bus
ing
h
isto
rica
lpla
ntp
roce
ss,d
esig
n
an
den
gin
eeri
ng
con
trol
s,a
nd
s
ampl
ing
data
plu
sw
orke
r
in
terv
iew
s[R
ice
eta
l.19
94,1
996]
.
Exp
osu
re:
Con
trol
san
dca
ses
rein
terv
iew
ed
wit
had
diti
onal
que
stio
ns
rega
rd-
in
gas
best
ose
xpos
ure
(app
lica-
t
ion
,man
ipul
atio
n,a
nd
dist
ance
f
rom
exp
osur
e).A
sbes
tos
expo
-s
ure
cate
gori
zed
(rat
ing
inde
x=
h
igh,
med
ium
,low
)fr
omin
ter-
v
iew
dat
a.
Rad
iogr
aph
ic a
nal
yses
Int
he
coh
ort
stu
dy,
20c
ases
of
pleu
ral
plaq
ue
wer
eid
enti
fied
int
he
coh
ort:
18
prod
uc-
tion
wor
kers
an
d2
non
prod
uct
ion
w
orke
rs.
Int
hre
elo
gist
ic
regr
essi
onm
odel
s,
pleu
ralp
laqu
es
wer
eas
soci
ated
(P
<0.
001)
wit
h
year
ssi
nce
firs
t
RC
Fpr
odu
ctio
n
job,
du
rati
ono
fR
CF
prod
uct
ion
jo
bs,a
nd
cum
ula
-ti
vefi
ber-
mon
ths/
cm3 .
18o
f20
cas
esw
ere
rein
terv
iew
ed;1
7w
ere
incl
ude
din
th
eca
se-c
ontr
ol
stu
dy.O
ne
was
de
ceas
ed,o
ne
refu
sed
inte
rvie
w,
and
one
wit
h
asbe
stos
exp
osu
re
was
exc
lude
d.
Pla
que
pre
vale
nce
Ite
m
(%)
OR
† 95
% C
I
Year
ssi
nce
firs
tR
CF
pr
odu
ctio
njo
b:0‡
0.9
1.0
—
>0–
10
1.7
1.4
0.
2,1
0.3
>
10–2
02.
82.
20.
4,1
1.2
>
20
12.5
9.
51.
9,4
8.2
Year
sof
RC
F
empl
oym
ent:
0
0.9
1.0
—
>0–
10
1.4
1.1
0.2,
6.1
>
10–2
07.
46.
11.
2,2
9.7
>
20
26.3
22
.3
3.6,
137
.0C
um
ula
tive
fi
ber-
mon
ths/
cm3 :
>
0–15
0.
31.
0—
>
15–4
55.
315
.4
1.9,
125
.4
>45
-135
6.
421
.3
2.6,
176
.2
>13
57.
824
.2
2.6,
224
.9C
ase-
con
trol
s:
Year
ssi
nce
firs
tRC
F
pro
duct
ion
job
—
1.2
1.0,
1.5
Cum
ulat
ive
RC
F
fi
ber-
mon
ths/
cm3 (
log)
:
Adj
uste
dfo
rye
ars
sin
cefi
rsta
sbes
tos
exp
osur
e—
2.
81.
3,5
.8
Adj
uste
dfo
ras
best
os
r
atin
gin
dex
—
3.8
1.5,
9.9
* Abb
revi
atio
ns:
CI=
con
fide
nce
inte
rval
;P=
prob
abili
ty;O
R=
odds
rat
io;R
FCs=
refr
acto
ryc
eram
icfi
bers
.† A
llbu
tla
ste
ntr
yar
ead
just
edfo
rye
ars
sin
cefi
rst
asbe
stos
exp
osu
re.L
ast
entr
yis
adj
ust
edfo
ras
best
osr
atin
gin
dex,
as
indi
cate
d.‡ N
onpr
odu
ctio
nw
orke
rs.
(Con
tin
ued
)
Refractory Ceramic Fibers 67
5 ■Effects of Exposure
Tabl
e 5–
7 (C
onti
nu
ed) .
U .S
. an
d E
uro
pea
n m
orb
idit
y st
ud
ies
wit
h R
CFs
*
Ref
eren
ceSt
udy
des
ign
an
d p
opu
lati
onEv
alu
atio
n m
eth
ods
Res
ult
sC
omm
ents
Lock
ey
et
al.1
998
(U.S
.stu
dy)
Cro
ss-s
ecti
onal
an
d
l
ongi
tud
inal
stu
dy:
Of
apo
ssib
le7
54m
ale
wor
kers
,th
e
stu
dyin
clu
ded
361
w
ho
(1)
wer
eh
ired
b
efor
e6/
30/9
0,
(
2)w
ere
empl
oyed
≥1
mon
tha
ton
eof
five
U.S
.RC
F
man
ufa
ctu
rin
g,
fac
iliti
es,a
nd
(3)
par
tici
pate
din
at
l
east
five
(of
ap
os-
sib
les
even
)P
FTs
es-
sio
ns
betw
een
6/8
7
an
d6/
94.
Med
ical
eva
luat
ion
:Ye
arly
spi
rom
etri
c
ev
alu
atio
n(
pulm
onar
y
fun
ctio
n)
betw
een
19
87a
nd
1994
.M
easu
res
incl
ude
dFV
C
and
FEV
1.
Exp
osu
re a
sses
smen
t:Pe
riod
an
djo
b-gr
oup-
spec
ific
ex-
posu
rec
once
ntr
atio
ns;
est
imat
ed
for
each
of
five
RC
Fm
anu
fact
ur-
ing
faci
litie
san
das
sign
edto
eac
h
wor
ker
base
don
job
his
tory
.
Cum
ulat
ive
RC
Fex
posu
re(
fibe
r-
mon
ths/
cm3 )
esti
mat
edfr
om
date
of
firs
tP
FT(
1987
)th
rou
gh
fin
alP
FTd
ate.
Pre
-198
7da
tao
nfi
ber
con
cen
trat
ion
sfr
omtw
opl
ants
pe
rmit
ted
calc
ulat
ion
of
cum
ula-
tive
fibe
rco
nce
ntr
atio
ns
from
fi
rstd
ate
ofR
CF
expo
sure
for
wor
kers
att
hese
pla
nts
on
ly.
Pu
lmon
ary
fun
ctio
n: c
ross
-sec
tion
al a
nal
ysis
of
i
nit
ial p
ulm
onar
y fu
nct
ion
test
for
522
wor
kers
Reg
ress
ion
coe
ffici
ent
RC
F p
rod
uct
ion
ye
ars
FV
C†,
‡ F
EV
1†,‡
≤7§
–65.
6(0
.44)
–8
0.6
(0.2
5)
>7§
–219
.4(
<0.
01)
–205
.2(
<0.
01)
193
mal
ew
orke
rs
wer
eex
clu
ded
from
th
ean
alys
isb
ecau
se
they
did
not
par
tici
-pa
tein
at
leas
tfi
ve
PFT
ses
sion
s.O
n
aver
age,
non
par-
tici
pan
tsw
ere
olde
r,sm
oked
an
dw
eigh
ed
mor
e,a
nd
had
low
er
hei
ght-
adju
sted
an
dp
erce
nta
ges
ofp
re-
dict
edlu
ng
fun
ctio
n
valu
es.
(Con
tin
ued
)
* Abb
revi
atio
ns:
FE
V1=
forc
ede
xpir
ator
yvo
lum
ein
1s
econ
d;F
VC
=fo
rced
vit
alc
apac
ity;
PFT
=pu
lmon
ary
fun
ctio
nte
st;R
CFs
=re
frac
tory
cer
amic
fibe
rs.
† Inm
illili
ters
.‡ H
eigh
t-ad
just
ed;v
aria
bles
incl
ude
din
th
ean
alys
isw
ere
age,
cat
egor
ical
RC
Fpr
odu
ctio
ny
ears
(0,
≤7
year
s,>
7ye
ars
[fir
stte
st])
,sm
okin
gca
tego
ry,
pac
kye
ars,
wei
ght,
and
plan
tlo
cati
on.
§ Com
pare
dw
ith
non
prod
uct
ion
wor
kers
.
68 Refractory Ceramic Fibers
5 ■Effects of Exposure
Tabl
e 5–
7 (C
onti
nu
ed) .
U .S
. an
d E
uro
pea
n m
orb
idit
y st
ud
ies
wit
h R
CFs
*
Ref
eren
ce
Stu
dy d
esig
n
and
pop
ula
tion
Eval
uat
ion
met
hod
sR
esu
lts
Com
men
ts
Lock
eye
tal
.199
8(
Con
tinue
d)
(U.S
.stu
dy)
Pu
lmon
ary
fun
ctio
n: l
ongi
tud
inal
an
alys
is
(Con
tin
ued
)
R
egre
ssio
n c
oeffi
cien
t
Item
F
VC
†,‡
FEV
1 †,‡
Cu
mu
lati
ve e
xpos
ure
:In
itia
lRC
Fpr
odu
ctio
nc
ateg
ory,
≤7
year
s‡,§..
....
....
....
....
....
....
..–5
5.2
–38.
9
Init
ialR
CF
prod
uct
ion
cat
egor
y,
>
7ye
ars‡,
§..
....
....
....
....
....
....
.–1
68.3
**
–99.
6
Follo
wu
pcu
mu
lati
veR
CF
expo
sure
(fi
ber-
mon
ths/
cm3 )‡,
§..
....
....
....
0.7
+0.
5
Pro
du
ctio
n e
mp
loym
ent d
ura
tion
:In
itia
lRC
Fpr
odu
ctio
ny
ears
,≤7
year
s‡,§..
...
–66.
3–3
7.6
Init
ialR
CF
prod
uct
ion
yea
rs,>
7ye
ars‡,
§..
..–1
71.0
**
–100
.3
Follo
wu
pR
CF
prod
uct
ion
yea
rs§ ,
††.
....
....
.+
5.3
+0.
2
Cu
mu
lati
ve fi
ber
exp
osu
re:
Init
ialc
um
ula
tive
RC
Fex
posu
re,
>15
–60
fibe
r-m
onth
s/cm
3 ,‡‡
...
....
....
..–3
6.2
–100
.2
Init
ialc
um
ula
tive
RC
Fex
posu
re,
>60
fibe
r-m
onth
s/cm
3 ,‡‡
....
....
....
....
–156
.0
–104
.7
Fo
llow
up
cum
ula
tive
RC
Fex
posu
re,
fi
ber-
mon
ths/
cm3 ,
‡‡..
....
....
....
....
..+
0.8**
+
0.2
* Abb
revi
atio
ns:
FE
V1=
forc
ede
xpir
ator
yvo
lum
ein
1s
econ
d;F
VC
=fo
rced
vit
alc
apac
ity;
P=
prob
abili
ty;R
CFs
=re
frac
tory
cer
amic
fibe
rs.
† In
mill
ilite
rsfo
rm
ale
wor
kers
test
edfi
veto
sev
ent
imes
.‡ H
eigh
t-ad
just
ed;v
aria
bles
incl
ude
din
th
ean
alys
isw
ere
age,
cat
egor
ical
RC
Fpr
odu
ctio
ny
ears
toin
itia
ltes
t,fo
llow
up
cum
ula
tive
RC
Fex
posu
re,p
ack
year
sat
init
ialt
est,
d
ich
otom
ized
sm
okin
gat
eac
hte
st,w
eigh
tat
init
ialt
est,
wei
ght
chan
gea
nd
plan
tlo
cati
on.
§ Com
pare
dw
ith
non
prod
uct
ion
wor
kers
.**
P<
0.05
.††
Hei
ght-
adju
sted
;var
iabl
esin
clu
ded
int
he
anal
ysis
wer
eag
e,c
ateg
oric
alR
CF
prod
uct
ion
yea
rsto
init
ialt
est,
follo
wu
pR
CF
prod
uct
ion
yea
rs,p
ack
year
sat
in
itia
ltes
t,di
chot
omiz
eds
mok
ing
att
he
tim
eof
eac
hte
st,w
eigh
tat
init
ialt
est,
wei
ght
chan
ge,p
lan
tlo
cati
on.
‡‡H
eigh
t-ad
just
ed;v
aria
bles
incl
ude
din
th
ean
alys
isw
ere
age,
cat
egor
ical
cu
mu
lati
veR
CF
exp
osu
reto
init
ialt
est,
follo
wu
pcu
mu
lati
veR
CF
expo
sure
,pac
k
yea
rsa
tin
itia
ltes
t,di
chot
omiz
eds
mok
ing
ate
ach
test
,wei
ght
atin
itia
ltes
t,w
eigh
tch
ange
,pla
nt
loca
tion
.
Refractory Ceramic Fibers 69
5 ■Effects of Exposure
Tabl
e 5–
7 (C
onti
nu
ed) .
U .S
. an
d E
uro
pea
n m
orb
idit
y st
ud
ies
wit
h R
CFs
*
Ref
eren
ceSt
udy
des
ign
an
d p
opu
lati
onEv
alu
atio
n m
eth
ods
Res
ult
sC
omm
ents
Bu
rge
eta
l.19
95
(Eu
rop
ean
stu
dy)
Cro
ss-s
ecti
onal
stu
dy:
From
ap
ossi
ble
708
cur -
ren
tw
orke
rs,6
28e
ligib
le
part
icip
ants
wer
eid
enti
fied
,an
d59
6of
th
ese
had
ch
est
X-r
aye
xam
inat
ion
s.A
fter
ex -
clu
sion
of
51fe
mal
ew
orke
rs
and
13u
nex
plai
ned
oth
ers,
da
taw
ere
avai
labl
efr
om
pulm
onar
yfu
nct
ion
test
sfo
r53
2m
ale
wor
kers
ins
even
E
uro
pea
nR
CF
prim
ary
prod
uct
ion
pla
nts
.
Hea
lth
: W
orke
rsw
ere
eval
uate
dby
as
elf-
adm
inis
tere
dex
pan
ded
resp
ira -
tory
que
stio
nn
aire
that
incl
uded
qu
esti
ons
rega
rdin
gsp
ecifi
csy
mpt
oms.
Pul
mon
ary
fun
ctio
n
test
ing
was
als
ope
rfor
med
.
Exp
osu
re:
Who
le-s
hift
per
son
ala
irs
ampl
es
wer
eco
llect
edfr
omr
ando
mly
se
lect
edw
orke
rsfr
omr
epre
sen
-ta
tive
job
cate
gori
esin
eac
hof
se
ven
RC
Fpr
oduc
tion
pla
nts
.Sa
mpl
esw
ere
colle
cted
an
dan
alyz
eda
ccor
din
gto
aW
HO
/E
UR
O[
1985
]re
fere
nce
met
hod
for
MM
MFs
too
btai
nd
ata
on
insp
irab
lea
nd
tota
lmas
san
dre
spir
able
fibe
rco
nce
ntr
atio
n.
Stat
isti
cal a
nal
ysis
:O
dds
rati
os(
wit
h95
%C
I)
adju
sted
for
plan
t,se
x,s
mok
-in
g,a
nd
age
wer
eca
lcul
ated
fo
rsy
mpt
oms
(i.e
.,dr
yco
ugh,
ch
ron
icb
ron
chit
is,w
heez
e,d
yp-
snea
≥2,s
tuff
yn
ose,
eye
an
dsk
in
irri
tati
on)
and
curr
ente
xpos
ure
cate
gori
esu
sin
gm
ulti
ple
logi
stic
re
gres
sion
.M
ulti
ple
linea
rre
gres
sion
coe
ffici
ents
for
lun
gfu
nct
ion
rel
ated
toc
umul
ativ
eex
posu
res
con
trol
led
for
the
effe
cts
ofr
espi
rabl
efi
ber
and
insp
irab
lem
ass
sepa
rate
lya
nd
toge
ther
.
Sym
pto
m a
nal
yses
E
xpos
ure
E
ffec
t
Cu
rren
t con
cen
trat
ion
s of
insp
irab
le m
ass:
† <
2.5
mg/
m3
Bas
elin
e2.
5to
<3
mg/
m3
Eye
irri
tati
on
[2.2
5(1
.43,
2.2
3)]‡
3m
g/m
3 D
ryc
ough
[3.4
2(1
.41,
8.3
3)]
D
yspn
ea ≥
2
[5
.84
(2.2
5,1
5.26
)]
Stu
ffy
nos
e
[2
.01
(1.1
3,3
.57)
]
Eye
irri
tati
on
[4
.78
(2.6
6,8
.6)]
Sk
inir
rita
tion
[3.3
(1.
8,6
.05)
]C
urr
ent c
once
ntr
atio
ns
of r
esp
irab
le fi
ber
s:†
<0.
2f/
cm3
Bas
elin
e0.
2to
<0.
6f/
cm3
Dry
cou
gh
[2
.53
(1.2
5,5
.11)
]
Stu
ffy
nos
e
[2
.06
(1.2
5,3
.39)
]
Eye
irri
tati
on
[2
.16
(1.3
2,3
.54)
]
Skin
irri
tati
on
[1
.25
(0.7
4,2
.11)
]≥0
.6f/
cm3
Dry
cou
gh
[2
.01
(1.0
5,3
.84)
]
Dys
pnea
2
[2
.66
(1.3
1,5
.42)
]
Eye
irri
tati
on
[2
.63
(1.7
,4.0
8)]
Sk
inir
rita
tion
[3.1
8(2
.01,
5.0
3)]
Cu
rren
tex
posu
res
tob
oth
insp
irab
led
ust
an
dre
spir
able
fi
bers
wer
ere
late
dto
dry
co
ugh
,stu
ffy
nos
e,e
yea
nd
skin
irri
tati
on,a
nd
brea
thle
ss-
nes
s.N
oan
alys
iso
fcu
mu
la-
tive
exp
osu
res
was
per
form
ed
wit
hr
esp
ect
tos
ympt
oms.
Ch
ange
sin
lun
gfu
nct
ion
wer
em
ore
stro
ngl
yre
late
dto
cu
mu
lati
vee
xpos
ure
tofi
bers
th
anto
cu
mu
lati
vee
xpos
ure
to
insp
irab
lem
ass.
Dec
re-
men
tsin
lun
gfu
nct
ion
wer
elim
ited
toc
urr
ent
smok
ers
and
form
ers
mok
ers,
su
gges
t -in
gth
ate
xpos
ure
tofi
bers
pr
omot
esr
espi
rato
rye
ffec
tso
fsm
okin
g.
(Con
tin
ued
)
* Abb
revi
atio
ns:
CI=
con
fide
nce
inte
rval
;MM
MFs
=m
an-m
ade
min
eral
fibe
rs;R
CFs
=re
frac
tory
cer
amic
fibe
rs.
† Sepa
rate
logi
stic
reg
ress
ion
mod
els
(adj
ust
edfo
rag
e,s
ex,s
mok
ing,
an
dpl
ant)
.‡ Fi
gure
sin
bra
cket
s=[O
R(
95%
CI)
].
70 Refractory Ceramic Fibers
5 ■Effects of Exposure
Tabl
e 5–
7 (C
onti
nu
ed) .
U .S
. an
d E
uro
pea
n M
orb
idit
y st
ud
ies
wit
h R
CFs
*
Ref
eren
ceSt
udy
des
ign
and
pop
ula
tion
Eval
uat
ion
met
hod
sR
esu
lts
Com
men
ts
Bu
rge
eta
l.19
95,
con
tin
ued
(Eu
rop
ean
stu
dy)
Sym
pto
m a
nal
yses
, con
tin
ued
E
xpos
ure
E
ffec
t
Cur
ren
t con
cen
trat
ion
s
of in
spir
able
mas
s:§
2.5
to<
3m
g/m
3Ey
eir
rita
tion
[1.
90(
1.15
,3.1
5)]**
≥3m
g/m
3 D
yspn
ea≥
2[4
.74
(1.5
6,1
4.4)
]
Eye
irri
tati
on[
3.31
(1.
62,6
.77)
]C
urre
nt c
once
ntr
atio
ns
of r
espi
rabl
e fi
bers
:§
0.2
to<
0.6
f/cm
3 N
one
stat
isti
cally
sig
nific
ant
≥0.
6f/
cm3
Skin
irri
tati
on[
2.67
(1.
52,4
.70)
]
Pul
mon
ary
fun
ctio
n‡‡
Cum
ulat
ive
insp
irab
le
mas
s ex
posu
re:‡‡
Form
ers
mok
ers
FVC
–8
.7m
l/m
g@ m
3pe
rye
ar
FEV
1–6
.4m
l/m
g@ m
3pe
rye
arC
umul
ativ
e re
spir
able
fi
ber
expo
sure
:‡‡
Cur
rent
sm
oker
sFE
V1
–32
ml/
f @cm
3pe
rye
ar
FEF 25
–75–
63m
l/s
per
f @cm
3pe
rye
ar
Form
ers
mok
ers
FEV
1–3
7m
l/f @c
m3pe
rye
ar
Cum
ulat
ive
resp
irab
le
fibe
r ex
posu
re:§§
Cur
rent
sm
oker
sFE
V1
–36
ml/
f @cm
3pe
rye
ar
Exp
osur
e
Mea
n c
urre
nt i
nsp
irab
le m
ass:
Prim
ary
prod
ucti
on
1.7
to3
.4m
g/m
3
Seco
ndar
ypr
oduc
tion
1.
8to
11.
2m
g/m
3
Mea
n c
urre
nt r
espi
rabl
e
fibe
r co
nce
ntr
atio
n:
Prim
ary
prod
ucti
on
0.2
to0
.88
f/cm
3
Seco
ndar
ypr
oduc
tion
0.
49to
1.3
6f/
cm3
Mea
n c
umul
ativ
e ex
posu
re:
Insp
irab
lem
ass
28.2
4m
g/m
3Ay
ear
Res
pira
ble
fiber
s3.
84f/
cm3Ay
ear
(Con
tin
ued
)
§M
ult
iple
logi
stic
reg
ress
ion
(ad
just
edfo
rag
e,s
ex,s
mok
ing,
an
dpl
ant)
of
sym
ptom
pre
vale
nce
by
curr
ent
resp
irab
lefi
bers
an
dcu
rren
tin
spir
able
mas
sas
inde
pen
den
tva
riab
les
afte
rad
just
men
tfo
rth
eot
her
.*
* Figu
res
inb
rack
ets=
[OR
(95
%C
I)].
†† O
nly
sta
tist
ical
lys
ign
ific
ant
asso
ciat
ion
s(P
<0.
05)
are
show
n.
‡‡ Li
nea
rre
gres
sion
mod
elin
gof
cu
mu
lati
vee
xpos
ure
sto
insp
irab
lem
ass
and
resp
irab
lefi
bers
sep
arat
ely
(adj
ust
edfo
rag
e,h
eigh
t,an
dsm
okin
g).
§§ Li
nea
rre
gres
sion
mod
elin
gw
ith
bot
hc
um
ula
tive
exp
osu
rev
aria
bles
int
he
sam
em
odel
(ad
just
edfo
rag
e,h
eigh
t,an
dsm
okin
g).
Refractory Ceramic Fibers 71
5 ■Effects of Exposure
Ta
ble
5–7
(Con
tin
ued
) . U
.S . a
nd
Eu
rop
ean
mor
bid
ity
stu
die
s w
ith
RC
Fs*
Ref
eren
ceSt
udy
des
ign
an
d p
opu
lati
onEv
alu
atio
n m
eth
ods
Res
ult
sC
omm
ents
Ros
site
ret
al.
1994
(Eu
rop
ean
stu
dy)
Coh
ort m
orb
idit
y
stu
dy:
628
cu
rren
tly
wor
k-in
gem
ploy
ees
in
seve
nE
uro
pea
n
RC
Fpr
odu
ctio
n
plan
ts.5
43m
ale
wor
kers
wh
oh
ad
read
able
ch
est
radi
ogra
phs
wer
ein
clu
ded
int
he
anal
ysis
(59
6of
62
8w
orke
rs[
95%
]h
adc
hes
tra
dio-
grap
hs;
51
wom
en
and
2u
nre
adab
le
film
sw
ere
ex-
clu
ded)
.
Hea
lth:
Che
str
adio
grap
hsa
nd
ques
tion
nair
ew
ere
adm
inis
tere
d.D
ata
for
14d
escr
iptiv
ev
ari-
able
sw
ere
colle
cted
fo
rea
chw
orke
ras
fo
llow
s:p
rodu
ctio
n
plan
t;ag
e;y
ears
sin
ce
first
em
ploy
men
tat
plan
t;ye
ars
sinc
efir
st
expo
sed
toR
CFs
;yea
rs
ofe
mpl
oym
enti
nth
e
plan
t;cu
rren
tres
pi-
rabl
efib
ere
xpos
ure;
cu
rren
tnon
resp
irab
le
fiber
exp
osur
e;c
ur-
rent
insp
irab
lem
ass
expo
sure
;cum
ula-
tive
resp
irab
lefi
ber
expo
sure
;cum
ulat
ive
nonr
espi
rabl
efib
er
expo
sure
;cum
ulat
ive
insp
irab
lem
ass
exp
o-su
re;n
umbe
rof
jobs
at
the
plan
twit
has
best
os
expo
sure
;pri
ora
sbes
-to
sex
posu
re.
Rad
iogr
aph
ic a
nal
ysis
Eff
ect
Pre
vale
nce
Ple
ura
lch
ange
s2.
8%(
15/5
43)
Larg
eop
acit
ies
0Sm
allo
paci
ties
7.
0%(
38/5
43)
Irre
gula
r5.
5%R
oun
ded
3.5%
Mix
ed
5.2%
Stat
isti
cal a
nal
ysis
:
Prev
alen
ce o
f ple
ural
cha
nges
(n=
15)
as-
soci
ated
with
age
(χ2 =
18.8
5, P
=0.
0008
).
Prev
alen
ce o
f cas
es o
f sm
all o
paci
ty p
rofu
-si
on (
n=38
) re
late
d to
prod
ucti
onp
lant
(χ2 =
22.
10,P
<0.
0001
);
smok
ing
year
ssi
nce
first
em
ploy
men
t,ye
ars
ofe
mpl
oym
ent,
prio
ras
best
ose
xpos
ure,
cu
rren
tnon
resp
irab
lefi
ber
expo
sure
(no
χ2
repo
rted
, P≤0
.05)
.
Prev
alen
ce o
f cas
es w
ith m
ostly
rou
nded
op
acit
ies (
n=23
) re
late
d to
heav
ysm
okin
g(χ
2 =2.
18,P
=0.
14);
asb
esto
sex
posu
rew
ithi
nth
eR
CF
plan
ts
(χ2 =
3.08
wit
hco
ntin
uity
cor
rect
ion,
P=
0.08
);b
utn
ota
ge(
χ2 =1.
25,P
=0.
87)
or
prod
ucti
onp
lant
(χ2 =
5.1
3,P
=0.
53).
Prev
alen
ce o
f cas
es w
ith m
ostly
irre
gula
r op
acit
ies (
n=15
) re
late
d to
age
(χ2 =
38.
9,P
<0.
0001
);c
urre
ntn
on-
resp
irab
lefi
ber
leve
ls(
χ2 =5.
2,P
=0.
07);
ye
ars
sinc
efir
stR
CF
empl
oym
ent(
χ2 =8.
16,
P=0.
09);
yea
rso
fR
CF
empl
oym
ent
(χ2 =
8.70
,P=
0.07
);b
utn
otp
lant
(P=
0.23
).
Ple
ural
cha
nge
s(n
=15
)in
clud
ed
four
cas
esw
ith
bila
tera
ldif
fuse
thic
ken
ing
(on
ew
ith
calc
ifica
-ti
on);
on
ew
ith
bila
tera
lple
u-
ralc
alci
fica
tion
on
ly;s
even
wit
h
unila
tera
ldif
fuse
thic
ken
ing;
th
ree
wit
hco
stop
hren
ica
ngl
ebl
unti
ng
only
.Pre
vale
nce
of
pleu
ralc
han
ges
was
ass
ocia
ted
wit
hag
e.
Irre
gula
rop
acit
ies
wer
ere
late
dto
ag
e,c
urre
ntn
onre
spir
able
fibe
rco
nce
ntr
atio
ns,
an
ddu
rati
on
and
late
ncy
of
RC
Fe
mpl
oy-
men
t.O
vera
ll,a
slig
hta
ssoc
ia-
tion
was
not
edfo
rpr
eval
ence
of
smal
lopa
citi
esa
nd
wor
kin
gin
ce
ram
icfi
ber
prod
ucti
on(
i.e.,
RC
Fem
ploy
men
tlat
ency
an
ddu
rati
on).
The
res
earc
hers
con
-cl
uded
itw
asu
nlik
ely
that
fibe
rex
posu
rew
asth
em
ain
cau
seo
fra
diog
raph
ica
bnor
mal
itie
s.
The
pos
sibi
lity
for
con
foun
din
gef
fect
sdu
eto
oth
ere
xpos
ures
is
rec
ogn
ized
:52%
of
wor
kers
re
port
edp
revi
ous
empl
oym
ent
inin
dust
ries
wit
hpo
ten
tial
ex
posu
reto
dus
ts,i
ncl
udin
gas
best
os(
5%),
sto
ne
quar
ryin
g(2
%),
iron
/ste
elfo
undr
ies
(6%
),
refr
acto
ryb
rick
wor
k(1
0%),
an
dm
an-m
ade
min
eral
fibe
rs(
8%).
(Con
tinu
ed)
* Abb
revi
atio
ns.
N=
nu
mbe
r;P
=pr
obab
ility
;RC
Fs=
refr
acto
ryc
eram
icfi
bers
.
72 Refractory Ceramic Fibers
5 ■Effects of Exposure
Tabl
e 5–
7 (C
onti
nu
ed) .
U .S
. an
d E
uro
pea
n M
orb
idit
y st
ud
ies
wit
h R
CFs
*
Ref
eren
ceSt
udy
des
ign
an
d p
opu
lati
onEv
alu
atio
n m
eth
ods
Res
ult
sC
omm
ents
Tret
how
an
eta
l.19
95
(Eu
rop
ean
stu
dy)
Cro
ss-s
ecti
onal
resp
ira-
tory
mor
bidi
ty st
udy:
628
curr
ent
wor
kers
in
sev
enE
uro
pea
n
RC
Fm
anu
fact
uri
ng
plan
ts.
Mea
na
ge=
37.
7ye
ars.
Mea
nd
ura
tion
of
empl
oym
ent
=1
0.2
year
s.
91%
wer
em
ale
wor
kers
an
d9%
w
ere
fem
ale
wor
kers
.
44%
wer
ecu
rren
tsm
oker
s.
Hea
lth
:A
sel
f-ad
min
iste
red
que
stio
nn
aire
w
asu
sed
too
btai
nin
form
atio
n
abou
tres
pira
tory
,nas
al,e
ye,a
nd
skin
sym
ptom
s,p
lus
deta
ilso
fsu
b -je
cts=
occ
upat
ion
alh
isto
ry.P
FTw
as
also
per
form
ed,a
nd
ches
tX-r
ays
wer
eob
tain
edfr
om5
92s
ubje
cts.
Exp
osu
re a
sses
smen
t:14
0jo
bsw
ere
iden
tifi
eda
nd
clas
si-
fied
into
sev
enm
ain
gro
ups.
Full-
shif
tp
erso
nal
air
sam
ples
wer
eco
llect
edfo
rra
ndo
mly
sel
ecte
dw
orke
rsin
eac
ho
fth
ese
ven
mai
n
grou
ps.
Insp
irab
led
ust
mon
itor
ing
was
p
erfo
rmed
acc
ordi
ng
toa
nA
CG
IH
met
hod
.
Res
pira
ble
fibe
rco
nce
ntr
atio
nw
as
mea
sure
dac
cord
ing
toa
WH
O/
EU
RO
[19
85]
refe
ren
cem
eth
odfo
rM
MM
Fs.
(Res
pira
ble
fibe
ris
de -
fin
eda
s<
5µm
lon
gw
ith
an
asp
ect
rati
o>
3:1
and
adi
amet
er ≤
3µm
.)
Stat
isti
cal a
nal
ysis
:P
ulm
onar
yfu
nct
ion
indi
ces
wer
eco
mpa
red
for
cum
ula
tive
exp
osu
re
grou
ps.S
ympt
oms
wer
ein
vest
i -ga
ted
bylo
gist
icr
egre
ssio
n,a
nd
pulm
onar
yfu
nct
ion
by
linea
rre
gres
sion
.Mod
els
wer
eco
ntr
olle
dfo
ref
fect
sof
age
,sex
,sm
okin
gh
abit
s,a
nd
prev
iou
sex
pos
ure
to
resp
irat
ory
haz
ards
.
Rad
iogr
aph
ic a
nal
ysis
E
ffec
t P
reva
len
ce
Ple
ura
lch
ange
s2.
7%(
16/5
92)
Larg
eop
acit
ies
0Sm
allo
paci
ties
13
%Ir
regu
lar
5.1%
Rou
nde
d3.
2%M
ixed
4.
7%
Sym
pto
m a
nal
yses
Cu
rren
t re
spir
able
f/cm
3 E
ffec
t [O
R† (
95%
CI)
]
<0.
2B
asel
ine
0.2
to<
0.6
Dry
cou
gh
[2.5
3(1
.25,
5.1
1)]
St
uff
yn
ose
[2.0
6(1
.25,
3.3
9)]
E
yeir
rita
tion
[2
.16
(1.3
2,3
.54)
]≥0
.6
Dry
cou
gh
[2.0
1(1
.05,
3.8
4)]
D
yspn
ea ≥
2[2
.66
(1.3
1,5
.42)
]
Eye
irri
tati
on
[2.6
3(1
.7,4
.08)
]
Skin
irri
tati
on[
3.18
(2.
01,5
.03)
]
Pre
vale
nce
of
smal
lopa
citi
esin
crea
sed
wit
ha
ge,s
mok
-in
g,a
nd
prev
iou
sex
posu
reto
as
best
os,b
ut
not
wit
hc
um
ula
-ti
vee
xpos
ure
sto
cer
amic
fi
bers
.No
desc
ript
ion
of
this
an
alys
isis
pro
vide
d.Sy
mpt
oms
pres
ent
int
he
stu
dyp
opu
lati
onw
ere
rela
ted
toe
xpos
ure
tor
espi
rabl
efi
bers
.St
atis
tica
llys
ign
ifica
nt
incr
eas -
esw
ere
not
edin
th
epr
eval
ence
of
dys
pnea
(bo
thg
rade
s)w
ith
in
crea
sin
gcu
mu
lati
vefi
ber
expo
sure
gro
ups
.Lu
ng
fun
ctio
nte
sts
show
eda
sign
ifica
nt
rela
tion
bet
wee
nin
-cr
easi
ng
cum
ula
tive
exp
osu
re
tor
espi
rabl
efi
bers
an
dde
cre -
men
tsin
FE
V1a
nd
FEF 25
-75in
cu
rren
tsm
oker
s,a
nd
FEV
1in
form
ers
mok
ers.
Am
ong
nev
ers
mok
ers,
an
incr
ease
(n
ots
tati
stic
ally
sig
nifi
can
t)
occu
rred
inp
ulm
onar
yfu
nc -
tion
mea
sure
sw
ith
incr
easi
ng
cum
ula
tive
fibe
rex
posu
re.
Ove
rall,
19%
of
the
popu
lati
onh
adw
orke
din
du
sty
occu
pati
ons
outs
ide
the
prod
uct
ion
of
cera
mic
fibe
rs.
Not
e:I
nc
alcu
lati
ng
cum
ula
tive
ex
posu
res,
th
ere
sear
cher
sas
-su
me
past
exp
osu
rec
once
ntr
a -ti
ons
wer
eeq
ual
toc
urr
ent
expo
sure
con
cen
trat
ion
s.
* Abb
revi
atio
ns:
AC
GIH
=A
mer
ican
Con
fere
nce
of
Gov
ern
men
talI
ndu
stri
alH
ygie
nis
ts;C
I=
con
fide
nce
inte
rval
;MM
MFs
=m
an-m
ade
min
eral
fibe
rs;O
R=
odd
sra
tio;
PFT
=pu
lmon
ary
fun
ctio
nte
st;R
CFs
=re
frac
tory
cer
amic
fibe
rs.
† Adj
ust
edfo
rth
eef
fect
sof
age
,sex
,sm
okin
g,a
nd
prev
iou
sex
pos
ure
sto
res
pira
tory
haz
ards
.(C
onti
nu
ed)
Refractory Ceramic Fibers 73
5 ■Effects of Exposure
Ta
ble
5–7
(Con
tin
ued
) . U
.S . a
nd
Eu
rop
ean
mor
bid
ity
stu
die
s w
ith
RC
Fs*
Ref
eren
ceSt
udy
des
ign
and
pop
ula
tion
Eval
uat
ion
met
hod
sR
esu
lts
Com
men
ts
Tret
how
ane
tal
.199
5,
con
tin
ued
(Eu
rop
ean
stu
dy)
Logi
stic
reg
ress
ion
was
use
dto
an
alyz
eth
etr
end
betw
een
sy
mpt
omp
reva
len
cea
nd
incr
easi
ng
cum
ula
tive
res
pi-
rabl
efi
ber
expo
sure
.Li
nea
rre
gres
sion
was
use
dto
anal
yze
the
tren
dbe
twee
n
pulm
onar
yfu
nct
ion
mea
-su
res
and
incr
easi
ng
cum
ula
-ti
ver
espi
rabl
efi
ber
expo
sure
.
Sym
pto
m A
nal
yses
(C
onti
nu
ed)
% w
orke
rs w
ith
var
iou
s re
spir
ator
y sy
mp
tom
s by
fib
er e
xpos
ure
Cu
mu
lati
ve r
esp
irab
le fi
ber
exp
osu
re (
f/cm
3 • ye
ar)
Sym
ptom
<
11
to<
22
to<
44
to<
8>
8
Dys
pnea
≥2
69
13
17
20D
yspn
ea≥
31
35
410
Wh
eeze
15
11
20
20
25
Bro
nch
itis
13
9
12
14
10
Pu
lmon
ary
fun
ctio
n (
mea
n %
of
pre
dic
ted
val
ues
)
Cu
mu
lati
ve r
esp
irab
le fi
ber
exp
osu
re (
f/cm
3 • ye
ar)
Fu
nct
ion
inde
x<
11
to<
22
to<
44
to<
8>
8
FVC
11
2.0
110.
211
1.5
109.
211
0.3
FEV
1† 10
6.5
105.
510
6.0
102.
310
2.1
FEF 25
-75†
89.0
90
.1
85.3
79
.7
74.4
Pu
lmon
ary
fun
ctio
n
(Δm
l/[f
/cm
3 @ y
r])
wit
h c
um
ula
tive
exp
osu
re‡ )
Fun
ctio
n in
dex
N
ever
sm
oker
Fo
rmer
sm
oker
C
urr
ent s
mok
er
FVC
+
7-3
4-2
5FE
V1†
+14
-3
7† -3
2†
FEF 25
-75†
+28
-5
1-6
3†
Exp
osu
res
Sub
ject
s
Exp
osu
re c
once
ntr
atio
ns
Nu
mb
er
%
Cu
rren
tex
posu
re(
f/cm
3 ):<
0.2
294
46.8
0.2
to<
0.6
123
19.6
0.6
to<
120
031
.8≥1
11
1.
8C
um
ula
tive
exp
osu
re§ (
f/cm
3•y
):<
111
918
.91
to<
210
616
.92
to<
416
826
.84
to<
816
626
.4>
869
11
.0(C
onti
nu
ed)
* Abb
revi
atio
ns:
RC
Fs=
refr
acto
ryc
eram
icfi
bers
.† St
atis
tica
llys
ign
ific
ant
(P<
0.05
).‡ A
dju
sted
for
the
effe
cts
ofa
ge,h
eigh
t,se
x,s
mok
ing,
an
dpa
ste
xpos
ure
toR
CFs
,asb
esto
s,a
nd
refr
acto
ryw
ork.
§ Ran
ge=
0to
22.
9f/
cm3 ·
year
.
74 Refractory Ceramic Fibers
5 ■Effects of Exposure
Tabl
e 5–
7 (C
onti
nu
ed) .
U .S
. an
d E
uro
pea
n m
orb
idit
y st
ud
ies
wit
h R
CFs
*
Ref
eren
ceSt
udy
des
ign
an
d p
opu
lati
onEv
alu
atio
n m
eth
ods
Res
ult
sC
omm
ents
Cow
iee
tal
.199
9,2
001
(Eu
rop
ean
stu
dy)
Cow
iee
tal
.199
9,2
001
Res
pira
tory
hea
lth
as
sess
men
t
Gro
ate
tal
.199
9E
xpos
ure
ass
essm
ent
Cro
ss-s
ecti
onal
stu
dy:
774
wor
kers
:69
5cu
rren
tw
orke
rs(
90%
re -
spon
ser
ate)
ins
ixE
uro
pea
n
RC
Fm
anu
fact
uri
ng
plan
ts
79fo
rmer
wor
kers
(37
%
resp
onse
rat
e)w
ho
had
bee
n
incl
ude
din
th
efi
rst
Eu
rop
ean
su
rvey
[B
urg
eet
al.
1995
,R
ossi
ter
eta
l.19
94,T
reth
ow-
ane
tal
.199
5]b
ut
had
sin
ce
left
th
ein
dust
ry
89%
mal
ew
orke
rsa
nd
11%
fe
mal
ew
orke
rs
Mea
n a
ge:
Mal
ew
orke
rs,4
2.0
year
sFe
mal
ew
orke
rs,3
9.4
year
s
Smok
ing
his
tory
:M
ale
wor
kers
:N
onsm
oker
s35
%C
urr
ent
smok
ers
38%
Ex-
smok
ers
27%
Fem
ale
wor
kers
:N
onsm
oker
s57
%C
urr
ent
smok
ers
29%
Ex-
smok
ers
13%
Mea
n ti
me
wor
ked
at th
e pl
ants
:13
.0y
ears
Hea
lth
eva
luat
ion
:C
hes
tra
diog
raph
s,n
=76
0(9
8%)
Lun
gfu
nct
ion
:Sp
irom
etry
Sin
gle
brea
thg
ast
ran
sfer
Alv
eola
rvo
lum
e
Qu
esti
onn
aire
s:R
espi
rato
rys
ympt
oms
Mod
ified
Am
eric
anT
hor
acic
So
ciet
yqu
esti
onn
aire
Occ
upa
tion
alh
isto
ry
Exp
osu
re a
sses
smen
t:46
4sh
ift
con
cen
trat
ion
sw
ere
sam
pled
(>
4h
r)
Mea
sure
men
tsin
clu
ded
(1)
resp
irab
leH a
nd
non
resp
irab
le
fibe
rco
nce
ntr
atio
n(
phas
eco
ntr
asto
ptic
alm
icro
scop
y),
(2)
resp
irab
led
ust
an
dcr
ysta
llin
esi
lica
con
cen
trat
ion
s,(3
)fi
ber
con
cen
trat
ion
san
dfi
ber
size
(sc
ann
ing
elec
tron
m
icro
scop
y),a
nd
(4)
mas
sco
nce
ntr
atio
ns
ofto
tal
inh
alab
led
ust
.
Stat
isti
cal a
nal
yses
:R
egre
ssio
na
nal
yses
wer
ep
erfo
rmed
:R
adio
grap
hic
dat
a Clo
gist
icr
egre
s-si
ona
dju
sted
for
age
and
smok
ing
Lun
gfu
nct
ion
dat
a Clin
ear
regr
es-
sion
adj
ust
edfo
rag
e,p
hysi
que,
an
dsm
okin
gR
espi
rato
rys
ympt
oms C
logi
stic
re
gres
sion
adj
ust
edfo
rag
e,s
ex,
smok
ing,
an
dco
un
try.
Rad
iogr
aph
ic a
nal
ysis
:P
leu
ralc
han
ges,
11%
Ple
ura
lpla
ques
,5%
51/6
82m
ale
wor
kers
had
RC
Fex
po-
sure
bef
ore
1971
:10
/51
had
cate
gory
1/0
+o
paci
ties
8/10
wer
eex
pose
dto
asb
esto
s3
wer
ecu
rren
tsm
oker
s,
6ex
-sm
oker
s
Sym
pto
m a
nal
yses
:R
ecu
rren
tch
est
illn
ess
was
ass
ocia
ted
wit
he
stim
ated
cu
mu
lati
vee
xpos
ure
to
res
pira
ble
fibe
rs[
OR
=1.
48,9
5%
CI=
1.11
,1.9
6]a
nd
resp
irab
led
ust
[O
R=
1.32
,95%
CI=
1.00
,1.7
5].
Pu
lmon
ary
fun
ctio
n a
nal
ysis
:M
ale
wor
kers
:FE
V1a
nd
FVC
de-
crea
sed
wit
hin
crea
sin
gex
posu
re
toR
CFs
inc
urr
ent
smok
ers
only
;st
ron
gest
ass
ocia
tion
was
wit
h
esti
mat
edc
um
ula
tive
exp
osu
reto
re
spir
able
fibe
rs.
Fem
ale
wor
kers
:FE
V1d
ecre
ased
wit
h
incr
easi
ng
cum
ula
tive
exp
osu
reto
fi
bers
an
ddu
st;s
tron
gest
ass
ocia
-ti
onw
asw
ith
cu
mu
lati
vee
xpos
ure
to
tota
ldu
st.
Exp
osu
re a
sses
smen
t:C
urr
ent
expo
sure
con
cen
trat
ion
s:R
espi
rabl
efi
bers
:P
rodu
ctio
n,0
.09 B
0.39
f/cm
3
Con
vers
ion/
finish
ing,
0.0
3B1.
25f/
cm3
Res
pira
ble
dust
,0.0
8–0.
42m
g/m
3
On
ly1
4fe
mal
ew
orke
rsh
ads
mal
lop
acit
ies
ofp
rofu
-si
on0
/1;r
adio
grap
h
stat
isti
cala
nal
yses
w
ere
rest
rict
edto
m
ale
wor
kers
.
Ple
ura
lch
ange
sw
ere
asso
ciat
edw
ith
age
an
dex
posu
reto
as
best
os;u
nad
just
ed
for
age,
th
ere
isa
n
asso
ciat
ion
bet
wee
n
pleu
ralc
han
ges
and
nu
mbe
rof
yea
rsa
tth
epl
ant.
Res
pira
tory
sym
ptom
san
alyz
edin
clu
ded
chro
nic
bro
nch
itis
,br
eath
less
nes
s,r
e -cu
rren
tch
est
illn
ess,
an
dpl
euri
tic
ches
tpa
in.
Th
eav
erag
ees
tim
ated
de
crea
sed
FEV
1an
dFV
Cin
mal
esm
ok-
ers
was
~10
0m
l.
* Abb
revi
atio
ns:
RC
Fs=
resp
irab
lec
eram
icfi
bers
;FE
V=
forc
ede
xpir
ator
yvo
lum
ein
1s
econ
d;F
VC
=fo
rced
vit
alc
apac
ity.
† Res
pira
ble
fibe
rsin
clu
ded
effe
ctiv
ely
no
asbe
stos
fibe
rsv
ias
can
nin
gel
ectr
onm
icro
scop
y(S
EM
)ch
arac
teri
zati
on.
Asb
esto
sex
posu
rew
asju
dged
not
tow
arra
nt
spec
ific
sam
plin
g.
Refractory Ceramic Fibers 75
5 ■Effects of Exposure
pleuralplaquesin5%(40/774)ofstudypartic-ipants.IntheU.S.study,23caseswithpleuralabnormalities (all production workers) wereidentified from847maleand femaleworkers(686production,161nonproduction)[Lemas-tersetal.1994].Theprevalenceofpleuralab-normalities amongallworkerswas2.7%andforproductionworkersonly,3.4%.Ofthecas-es,21wereclassifiedashavingpleuralplaquesand 2 as having diffuse pleural thickening.Oneworkerreportedhavingpreviouslydiag-nosedkaolinosisfromprioremploymentinakaolinmine.Lockeyetal.[1996]conductedafollowupreportbasedonreviewof652chestfilmsfromcurrentandformerworkersattwooftheU.S.plants.Theyreportedaprevalenceofpleuralchangesof3.1%(n=20), including19pleuralplaquecasesand1withdiffusepleu-ralthickening.Pleuralplaqueswerepresentin18 (4.1%) production workers and 2 (0.9%)nonproductionworkers.Thetwononproduc-tionworkerswithpleuralplaqueshadworkedwith RCFs as laboratory technicians. Fromstatistical analyses of pleural abnormalities,Rossiter et al. [1994] reported an associationwith age [χ2=18.85, P=0.0008]. However, noattemptwasmade toassesswhetheranasso-ciation existed between pleural abnormalitiesandRCFexposure.Trethowanetal.[1995]alsonoted that pleural abnormalities were relatedtoagebutnotindependentlytoceramicfiberexposures.Cowieetal. [1999,2001]reportedpleural abnormalities to be associated withage, exposure to asbestos, and body mass in-dex(weightdividedbyheightsquared).Whenthedatawereunadjusted for age, an associa-tionexistedbetweenpleuralchangesandyearsworked at the plant. Lemasters et al. [1994]foundthatpleuralabnormalitieswereassoci-atedwithtimesincefirstRCFexposure(RCFlatency)afteradjustingfordurationofasbes-tosexposureandtimesincefirstasbestosexpo-sure(oddsratio [OR]=2.9[95%CI=0.8–9.7]for >10 to 20 years of RCF latency, and 7.7[95% CI=2.0–29.1] for >20 years of RCF
latency,whencomparedwithworkershaving<10yearsofRCFlatency).Pleuralabnormali-tiesremainedstatisticallysignificant(P<0.001)withtimesincefirstRCFexposure(latency)af-teradjustmentfortheeffectsofsmoking,bodyweight, and latency and duration of asbestosexposure.Thepositiveassociationpersistedaf-ter exclusion of workers exposed to asbestos.Inmultiplelogisticregressionanalyses,anas-sociation between duration of RCF exposureandpleuralabnormalitiesremainedsignificant(χ2=7.75, P=0.005)afteradjustmentforasbes-toslatency,asbestosduration,andage[Lemas-ters et al. 1994]. In subsequent analyses withadjustmentforage,researchersfoundthatas-sociations persisted between pleural plaquesand latency and duration of RCF exposure[Lockeyetal.1996].Inthreeseparateanalyses,Lockey etal. [1996] found that prevalence ofpleuralplaquesrelatedtothefollowing:
■ >20yearsofRCFlatency(OR=9.5[95%CI=1.9–48.2])
■ >20yearsRCFexposuredurationinpro-duction jobs (OR=22.3 [95% CI=3.6–137.0])
■ CumulativeRCFexposureinthehighestexposure category (>135 fiber-months/cm3)(OR=24.2[95%CI=2.6–224.9])
Results of a nested case-control study of the20 workers with pleural plaques (matched to3controlsbasedonsex,RCFemploymentsta-tus,andproduction/nonproductioncategory)support the associations of pleural changeswith RCF latency, RCF exposure duration,and cumulative RCF exposure [Lockey et al.1996].Alatencyvalidityreviewwasalsocon-ducted, involving analysis of 205 historicalchest radiographs available for workers withpleural changes. The purpose of the reviewwas to confirm that for persons with pleuralplaques,abiologicallyplausiblelatencyperiod(≥5 years) existed between initial RCF expo-sureandappearanceofapleuralplaque.Of18pleuralplaquecasesforwhichhistoricalchest
76 Refractory Ceramic Fibers
5 ■Effects of Exposure
radiographswereavailable,only1hadalatencyperiodof<5yearsfrominitialRCFproductiontorecognitionofapleuralplaque.
AsubsequentanalysisbyLockeyetal.[2002]included chest radiographs for 625 currentworkersobtainedevery3yearsat5RCFman-ufacturing sites and 383 former workers at2 of the 5 sites. Pleural changes were seen in27workers(2.7%),ofwhich19werebilateralplaques (70%) and 3 were unilateral plaques(11%).CumulativeRCFexposure(>135fiber-months/cm3)wassignificantlyassociatedwithpleuralchanges(OR=6.0,95%CI=1.4,31.0).Theresearchersnotedanincreasingbutnon-significanttrendinvolvinginterstitialchangesand RCF exposure duration in a productionjobandcumulativeRCFexposure.
5.3.2.2 Parenchymal Opacities
In the 1987 European study, Rossiter et al.[1994]foundthat7%(38/543)ofthecurrentmale workers had small parenchymal opaci-tieswithmedianprofusionof1/0ormore.Nolarge parenchymal opacities were observed.Bothpredominantlyrounded(n=23,or4.2%)andpredominantlyirregular(n=15,or2.8%)small parenchymal opacities were identified.Prevalence of rounded, small opacities wasnot associated with age (P=0.87) or produc-tionplant(P=0.53).However,withprevalenceofopacities,strongerassociationsexistedwithasbestos exposure in RCF production plants(P=0.08)andheavysmoking(P=0.14)[Rossit-eretal.1994].Predominantlyirregular,smallopacitieswereassociatedwithage(P<0.0001)but not with production plant (P=0.23). Af-terallowingforage,associationswithcurrentnonrespirablefiberconcentrations,yearssincefirst RCF employment, and duration of RCFemployment approached statistical signifi-cance(P=0.07to0.09).Inasubsequentanaly-sisofsmallopacitiesforbothmaleandfemaleworkers,Trethowanetal.[1995]notedthatthe
prevalence of small opacities increased withage,smoking,andpreviousexposuretoasbes-tosbutnotwithcumulativeRCFexposure.Nodescriptionoftheanalysiswasprovided.Cow-ieetal.[1999]reportedthat10of51(19.6%)menwithRCFexposurebefore1971hadsmallopacities of category 1/0 or greater. Eight ofthese10hadbeenexposedtoasbestos,and9wereeithercurrentorex-smokers.IntheU.S.study,noanalyseswereperformedtoassesstherelationshipbetweensmallopacitiesandRCFexposurebecauseofthesmallnumberofcas-es (n=4) identified by Lemasters et al. [1994,1996].
5.3.3 Respiratory Conditions and Symptom Analyses
Using respiratory health questionnaires, theU.S.andEuropeanstudiessoughttoidentifyre-spiratoryconditionsandsymptomsthatcouldbe associated with exposure to RCFs. Lockeyet al. [1993] administered to 717 subjects astandardized respiratory symptomsquestion-naire that included questions about the fol-lowing symptoms and conditions: chroniccough, chronic phlegm, dyspnea grades 1and2(describedintheDefinitionssectionofthis document), wheezing, asthma, pleurisy,and pleuritic chest pain. Logistic regressionanalyses were adjusted for age, sex, smoking(pack years), duration of asbestos exposure,durationofproductionemployment,durationof other hazardous occupational respiratoryexposure, and time since last RCF employ-ment.Withtheexceptionofasthma,forwhichself-selectionoutofproductionjobsmayhaveoccurred,adjustedORsforrespiratorysymp-tomsweresignificantlyelevatedinproductionworkerscomparedwithnonproductionwork-ers.Resultsofasubsequentanalysiswith742RCFworkersbyLemasters et al. [1998] indi-catedthattheprevalenceofrespiratorysymp-tomsandconditions(except forasthma)wasapproximately twofold to fivefold higher in
Refractory Ceramic Fibers 77
5 ■Effects of Exposure
production than in nonproduction workers.The most frequently reported symptom formaleproductionworkerswasdyspneagrade1(15.7%,comparedwith2.5%fornonproduc-tion),followedbywheezing(10.3%,comparedwith3.8% fornonproduction).Prevalenceofone or more respiratory symptoms and con-ditionsamongfemaleproductionworkerswas40.7%,comparedwith20.3%fornonproduc-tionworkers.
Trethowanetal.[1995]examinedtherelation-shipofdrycough,chronicbronchitis,dyspnea(twogrades),wheeze,stuffynose,eyeirritation,andskin irritationtocurrentandcumulativeRCF exposure estimates among 628 workers.Current exposures were based on air sam-plingmeasurementstakeninassociationwiththerespiratoryhealth survey.Theresearchersnotedeyeandskinirritationwerefrequentinall plants and increased significantly, as diddyspnea and wheeze, with increasing currentexposure concentrations (i.e., 0.2 to 0.6 and≥0.6 f/cm3)aftercontrolling forage, sex,andsmoking habits. The most frequent symp-tom, nasal stuffiness (in 55% of the group),showed no clear association with increasingcurrent exposure. Chronic bronchitis, with aprevalenceof12%amongallworkers,alsoap-pearedunaffectedbyincreasingcurrentexpo-sureconcentration.Drycough,eye irritation,and skin irritation all seemed to be associat-ed with increasing exposure, especially at thehighest exposure concentration (≥0.6 f/cm3).Analysesofcumulativeexposuretorespirablefibers showed statistically significant associa-tions with dyspnea but no apparent associa-tionwithchronicbronchitisandwheeze.Inaseparateanalysisofthesamecohort,Burgeetal.[1995]investigatedtherelativeimportanceof respirable RCF exposure versus inspirabledustexposureinpredictingrespiratorysymp-tomsandconditions.Thestudy foundwork-ers=currentexposurestobothinspirabledustandrespirablefiberswererelated(P<0.05)to
drycough,stuffynose,eyeandskinirritation,andbreathlessness(dyspnea)afteradjustmentfortheeffectsofsmoking,sex,age,andplant.Only skin irritation was significantly associ-ated with current RCF exposure after con-trollingforexposuretoinspirabledust.Burgeetal. [1995] did not analyze the relationshipbetween symptoms and cumulative exposureindices.Cowieetal.[1999,2001]reportedthatrecurrentchestillnesswasassociatedwithesti-matedcumulativeexposuretorespirablefibersbutwasnotsignificantlyassociatedwithrecentexposure.
5.3.4 Pulmonary Function Testing
Trethowan et al. [1995] analyzed spirometrytest results from 600 of 628 current workerswhoparticipatedat7EuropeanRCFproduc-tionplants.Inseparatemultiplelinearregres-sionanalysesformaleworkersineachsmokingcategory(current,former,never),theauthorscontrolledforage,height,andpastexposurestovariousrespiratoryhazards(includingprevi-ousemploymentinotherceramicfiberplants).Results associated cumulative RCFs with sta-tistically significant (P<0.05) decrements inFEV
1inbothcurrentandformersmokersand
withdecreases inFEF25-75
incurrent smokers.Inneversmokers(n=154),allregressioncoef-ficientsofcumulativeRCFexposureinrelationtolungfunctionweresmall,positive,andnotstatisticallysignificant.
Aswiththesymptomsdata,Burgeetal.[1995]further analyzed the spirometry data fromthe European study to discern whether theobserved effects were more highly associatedwith current respirable RCF exposure thanwithconcurrentinspirabledustexposure.Inamultiplelinearregressionmodelthatexcludedcumulative inspirable dust exposure, statisti-cally significant (P<0.05) decreases in FEV
1
andFEF25-75
amongcurrentsmokersandFEV1
among former smokers were associated with
78 Refractory Ceramic Fibers
5 ■Effects of Exposure
cumulative exposure to respirable RCFs. In amultiplelinearregressionmodelthatincludedvariables for cumulative dust and cumulativerespirable RCFs, the only statistically signifi-cant (P<0.05) association for these variableswas for the decrease in FEV
1 among current
smokersassociatedwithcumulativerespirableRCFexposure.Nocumulativedust-associatedcoefficients remained statistically significantafteradjustingfortheeffectofcumulativeRCFexposure.Thus,theinvestigatorsattributedtheadversepulmonaryfunctioneffectobservedinsmokers to the fiber component of occupa-tional dust exposures at RCF manufacturingplants.
Cowieetal. [1999,2001]observedthatRCF-exposed male workers (n=692) showed adecrease in FEV
1 and FVC only for current
smokers, the strongestassociationbeingwithestimated cumulative exposure to respirablefibers.TheaverageestimateddecreaseinFEV
1
andFVCwasmild,approximately100ml.Fe-maleRCF-exposedworkers(n=82)hadade-creased FEV
1 with increasing cumulative ex-
posuretorespirablefibersandrespirableandtotaldust.Amongthefemaleworkers,cumu-lativeexposuretototaldustwasmoststronglyassociatedwithdecreasedpulmonaryfunctionmeasurements.
Lemastersetal.[1998]anaylzedPFTdatafor736 male and female current workers at fiveU.S. RCF plants. They reported decreases inthe percentage of predicted FVC and FEV
1
withevery10yearsofRCFproductionwork.Although the decreases were greatest amongcurrentmalesmokersandformermalesmok-ers,theyweregreaterthandecreasesassociatedwith smoking alone. No significant changeswerenotedinpulmonaryfunctionofRCFpro-ductionworkerswhoneversmoked.AseparatestudybyLockeyetal.[1998]involvedlongitu-dinalanalysisofdatafromacohortof361cur-rent male RCF workers hired before June 30,1990,whohadparticipatedinatleastfivePFT
sessionsbetween1987and1994.Bycompari-son,nonparticipantswhowereexcludedfromthe analysis according to the criteria abovewereonaverageolder,smoked,weighedmore,and had lower height-adjusted and percent-predictedlungfunctionvalues.Cross-sectionalanalysisoftheinitialpulmonaryfunctionses-sion in a regression model included coeffi-cients for age, ≤7 versus >7 RCF productionyears,smokingstatus(packyears,currentver-susformersmoker),weight,andplantlocation(categorical).Theanalysis founddecreases inFVCandFEV
1forworkersemployed>7years
inproductioncomparedwithnonproductionworkers. In longitudinal analysesof followupproductionyears(i.e.,frominitialPFTtofinalPFT)andfollowupcumulativeexposure(i.e.,frominitialPFTtofinalPFT),neitherofthesevariableshadaneffectonFVCorFEV
1.These
results led theauthors toconclude thatmorerecent exposure concentrations during 1980–1994 had no adverse effect on the longitudi-nal trend of pulmonary function [Lockey etal.1998].DecrementsinFVCandFEV
1noted
in initial cross-sectionalanalysesofPFTdatawerebelievedtoberelatedtoearlierhigherex-posureconcentrations.
5.3.5 Mortality Studies
Table5–8presentsfindingsfromacohortmor-talitystudyoftwoU.S.RCFproductionplantsreportedbyLockeyetal.[1993].Thestudyisbasedonacohortof684maleworkersattwoRCF production plants who were employedforatleast1yearbetweenJanuary1,1950,andJune1,1988.Fiveworkerswerelosttofollow-upand46weredeceased.Becausethisisarela-tivelynew industry (40years at the timeofthestudy)thathasexperiencedrecentgrowthoftheworkforceattheplantsstudied,person-years at risk were limited at higher latencies(for example, only 126.37 person-years with>30yearssincefirstRCFjob).Usingstandard-izedmortalityratios(SMRs),theauthorsfound
Refractory Ceramic Fibers 79
5 ■Effects of Exposure
Tabl
e 5–
8 . M
orta
lity
stu
dy w
ith
RC
Fs*
Ref
eren
ceSt
udy
des
ign
an
d p
opu
lati
onEv
alu
atio
n m
eth
ods
Res
ult
sC
omm
ents
Lock
eye
tal
.199
3
(U.S
.stu
dy)
Coh
ort m
orta
lity
stud
y:
Cu
rren
tan
dfo
rmer
m
ale
wor
kers
at
two
plan
tsi
tes
empl
oyed
at
leas
tly
ear
int
he
man
-fa
ctu
reo
fR
CFs
bet
wee
n
10/1
/50
and
6/1/
88.O
fth
e68
4w
orke
rsw
ho
met
th
ecr
iter
ia,6
33
(92.
5%)
wer
eal
ive,
46
(6.7
%)
wer
ede
ceas
ed,
and
5(0
.7%
)w
ere
lost
to
follo
wu
p.
Cau
se-s
pec
ific
SMR
s
w
ere
calc
ula
ted
usi
ng
the
tota
lU.S
.mal
e
po
pula
tion
as
the
refe
ren
cep
opu
la-
ti
on.P
erso
n-y
ears
wer
est
rati
fied
by
age,
race
,cal
enda
rti
me,
late
ncy
,an
dcu
mu
la-
ti
ved
ura
tion
.
Dem
ogra
phic
s:
62
4C
auca
sion
s
60n
on-C
auca
sion
s
Wor
ker
dis
trib
uti
on
Yea
rss
ince
firs
tP
erso
n-y
ears
RC
Fjo
b
atr
isk
Stat
istic
ally
sign
ifica
ntin
crea
se
ind
eath
sfro
mth
efo
llow
-in
g:(
1)p
neum
ocon
iose
san
dot
herr
espi
rato
ryd
isea
se
fort
hec
ateg
ory
ofC
auca
-si
anm
ale
wor
kers
with
>
30y
ears
ofR
CF
late
ncy
(n=
2,S
MR
=2,
614
[95%
C
I=24
6–7,
490]
);(2
)can
cers
of
the
dige
stiv
eor
gans
an
dpe
rito
neum
forn
on-
Cau
casi
anm
ale
wor
kers
(n
=2,
SM
R=
913
[95%
C
I=11
0–3,
295]
);(3
)can
cers
of
the
urin
ary
orga
nsfo
rm
ale
wor
kers
with
>15
–20
year
sofR
CF
late
ncy
(n=
2,
SMR
=3,
306
[95%
CI=
311–
9,47
1]).
The
pow
erto
det
ecta
sign
ifi-
cant
incr
ease
inm
orta
lity
for
any
spec
ific
caus
ew
aslo
w
beca
use
ofth
esm
alln
umbe
rof
dea
thsi
nth
eco
hort
.
1to
5
3,39
0>
5to
10
3,15
5>
10to
15
2,51
2>
15to
20
1,19
7>
20to
25
518
>25
to3
027
7>
30
126
Tota
l11
,175
C
ause
of
deat
h
SMR
(95
%C
I)
All
cau
ses:
40C
auca
sion
s97
(69
–132
)
6n
on-C
auca
sion
s12
6(4
6–27
4)
All
can
cers
:
11C
auca
sion
s12
1(6
0–21
6)
2
non
-Cau
casi
ons
263
(32–
950)
4lu
ng
can
cers
† 11
4(3
1–29
1)
2ca
nce
rso
fth
eu
rin
ary
or
gan
s† 46
7(5
7–1,
687)
6
can
cers
of
the
dige
stiv
e
or
gan
s† 25
9(9
4–56
3)
2pn
eum
ocon
iose
san
dot
her
resp
irat
ory
dise
ase†
205
(25–
740)
* Abb
revi
atio
ns:
CI=
con
fide
nce
inte
rval
;RC
Fs=
refr
acto
ryc
eram
icfi
bers
;SM
R=
stan
dard
ized
mor
talit
yra
tio.
† Com
bin
edr
ace
coh
ort.
80 Refractory Ceramic Fibers
5 ■Effects of Exposure
the combined-race cohort to have no signifi-cant elevations associated with specific causesofdeath,includingcancersofthelung,digestiveorgans and peritoneum, urinary organs, andpneumoconiosesandotherrespiratorydisease.The authors noted that the power to detect asignificantincreaseinmortalityforanyspecificcausewaslowbecauseofthesmallnumberofdeathsinthecohortandgenerallyshortlaten-cies.However,astatisticallysignificantincreaseindeaths frompneumoconiosesandotherre-spiratory disease occurred in Caucasian maleswith>30yearsRCF latency (n=2,SMR=2,614[95%CI=246–7,490]).Astatisticallysignificantelevation in deaths from cancers of the diges-tive organs and peritoneum also occurred fornon-Caucasian males (n=2, SMR=913 [95%CI=110–3,295]).Inaddition,astatisticallysig-nificant elevation occurred in the number ofdeaths from cancers of the urinary organs formaleworkerswith>15to20yearsofRCF la-tency(n=2,SMR=3,306[95%CI=311–9,471]).
Lemastersetal.[2003]publishedasubsequentanalysisofcurrentandformermaleworkersemployedbetween1952and2000atthetwoRCF manufacturing facilities (942 subjects)investigating a possible excess in mortality.Themortalityanalyticmethodsincluded(1)standardizedmortalityratioscomparingthiscohortwiththegeneralandStatepopulationsand(2)aproportionalhazardsmodelthatre-latesriskofdeathtothe lifetimecumulativefiber-months/cm3 exposure among the RCFcohort,adjustedforageathireandforrace.Theanalysisfoundnoexcessmortalityrelat-ed to all deaths, all cancers, or malignanciesordiseasesoftherespiratorysystem(includ-ing mesothelioma) but found a statisticallysignificant association with cancers of theurinaryorgans[SMR=344.8(95%confidencelimits of 111.6, 805.4)]. Based on the smallsize of the cohort, the young average age(51 years), and a mean latency of 21 years,the researchers concluded that the findings
warrantcontinuedsurveillanceofthecohortmortalityregistry.
Walker et al. [2002] used the same cohort ofmaleRCFproductionworkersdescribedbyLe-mastersetal.[2003].Walkeretal.performedariskanalysiscomparingthelungcancerandme-sotheliomainthecohort’saccumulatedmortal-ity experience to that which would have beenexpected if RCFs had a carcinogenic potencyapproximating various forms of asbestos. TheauthorsreportedthatdeathsfromlungcancerintheRCFcohortwerestatisticallysignificantlybelow that which would be expected if RCFshadthepotencyofeithercrocidoliteoramosite.Themortalitywasalsolowerthanwouldbeex-pected if RCFs had the potency of chrysotile,butthedifferenceisnotstatisticallysignificant.For mesothelioma, the authors concluded theanticipated numbers of deaths under hypoth-esesofasbestos-likepotencyaretoosmalltoberejectedby thezerocases seen in theRCFco-horts [Walkeretal.2002].NIOSHresearchersnotedthatthisanalysisbyWalkeretal.wasnotbasedon themostcurrentupdateof theRCFcohort.Inaddition,theasbestosriskassessmentmodelsusedbyWalkeretal.[2002]werefittedto studies with longer followup periods thanthecohortofRCFworkers.Becausethesemod-elsdonot specify lengthof followup, it isnotpossibletoadjust forthesedifferences.Conse-quently,itislikelythattheRCFcohorthasnotbeenfollowedforasufficientlengthoftimetodemonstratetherisksthatwereobservedintheasbestos cohorts. NIOSH believes the mortal-itystudybyLemastersetal.[2003]andtheriskanalysisbyWalkeretal.[2002]haveinsufficientpower fordetecting lungcancer riskbasedonwhatwouldbepredictedforasbestos.
5.3.6 NIOSH HHEs
Aspartofitsmissionasapublichealthagen-cy, NIOSH performs HHEs at the request ofworkers,employers,or labororganizations toinvestigate occupational hazards associated
Refractory Ceramic Fibers 81
5 ■Effects of Exposure
withaworkplaceorwork-relatedactivity.Onesuch HHE involved evaluating worker expo-surestoceramicfibersatacompanymanufac-turingsteel forgings[Kominsky1978].Atthefacility, furnaces for heat-treating steel ingotswerelinedwithRCFfeltandbatting,andthislining required regular maintenance and re-placement. Among the workers interviewedweresixbricklayersinvolvedinfurnaceliningmaintenance.Fourofthebricklayersreportedhavingexperienced irritationofexposedskinareas and of the throat during the handlingandinstallationoftheRCF-containinginsula-tion. On the basis of the reported symptomsand their consistency with known effects ofRCFs,thesymptomsofirritationwereattrib-utedtoRCFexposure.Noattemptwasmadetomeasureairbornefiberconcentrations.Anoth-erNIOSHHHE[Lyman1992] resulted fromanOSHAinspectionthatidentified18casesofoccupationallungdiseaserecordedin1yearataplantmanufacturingfirebricks,ceramicfiberproducts, and other thermal insulation com-ponentsfromkaolin.About600workerswerepotentiallyexposedtorespiratoryhazardsthatincluded not only RCFs but also kaolin dust,crystalline silica dust, and (for maintenanceworkers) asbestos. A total of 38workers hadbeen referred to a pulmonary physician forevaluation based on 2 rounds of chest X-rayscreeningoftheworkforce in1980and1986.Diagnoses were related to pleural thickening(n=10),pleuralplaques(n=3),diffusepulmo-naryfibrosis(n=21),mesothelioma(n=1),andothermiscellaneousconditions.Atleast20ofthese cases were classified as work-related bythe pulmonologist who evaluated the cases.The nonoccupational classification of someoftheremaining18caseswasquestionedbyaNIOSHphysicianwhoperformedaretrospec-tive record review. The 38 cases were reclas-sified on the basis of job histories into thosewhowerelikelytohavebeenexposedtoRCFs(n=19,including4withpleuralabnormalitiesand8withdiffusefibrosis)andthoseunlikely
tohavebeenexposedtoRCFs(n=19,including9withpleuralabnormalities,13withfibrosis,and 1 with mesothelioma). However, no at-temptwasmadetoanalyzefurtherforanas-sociationof thecaseswithexposuretoRCFs.Thereportimpliedthatoccupationalexposuretokaolindustandtoasbestoscausedmanyorallofthejob-relatedconditions.
5.3.7 Discussion
TheradiographicanalysesoftheU.S.and1996Europeanworkergroups suggest anassocia-tionbetweenpleuralabnormalities,includingpleural plaques, and RCF exposure [Lemas-ters et al. 1994;Lockey et al. 1996;Cowie etal.1999].FromRossiteretal.[1994]itislessapparentwhethersuchanassociationwasin-vestigated.Trethowanetal.[1995]reportthatpleuralabnormalitieswerenotindependentlyrelatedtoRCFexposure.Differencesbetweenthefindingsof theU.S. studiesand thoseoftheinitialEuropeanstudiesmayberelatedtothelonglatencybeforepleuralabnormalitiesare detectable, in particular, pleural plaquesfollowingRCFexposure.Workersexposedtoasbestos developed asbestos-associated pleu-ralplaquesafteralatencyperiodofmorethan15yearsafterinitialexposure[Hillerdal1994]andinsomecases,after30to57years[Beginetal.1996].TheEuropeanRCFindustryde-velopedmorethanadecadeaftertheU.S.in-dustry.Asaresult,workersintheU.S.groupare slightly older with a longer average em-ploymentdurationinRCFmanufacturingandtime since first exposure to RCFs. Historicalairsamplingdataalso indicatethatairbornefiber concentrations were much higher inearlyU.S.RCFmanufacturing.These factorsmight explain thefindingofRCF-associatedpleuralabnormalitiesintheU.S.workersbutnot intheEuropeanworkers.Afurtherpos-sible explanation may involve differences intheradiographicsurveillancemethodologies.BoththeU.S.andtheEuropeanstudiesused
82 Refractory Ceramic Fibers
5 ■Effects of Exposure
the1980ILOclassificationsystemsforpneu-monoconiosestoreviewposteroanteriorviewchestradiographsforstudysubjects.However,Lockeyetal.[2002]begantosupplementtheseviewswithleftandright45oobliqueviewfilmsasastandardpracticeforradiographicsurveil-lance.Thismethodology,knownasafilmtri-ad,wasevaluatedagainsttheposteroanterior-only view to determine reliability, sensitivity,andspecificityofeachmethod[Lawsonetal.2001]. The evaluation, involving 652 subjectsin the RCF study, showed the film triad hadconsiderably higher interreader reliabil-ity (κ=0.59) than the posteroanterior-onlymethod(κ=0.44).Theauthorsconcludedthatthe film triad method provides an optimumapproach.
The U.S. and 1986 European studies yieldedlittleevidenceofanassociationbetweenradio-graphicparenchymalopacitiesandRCFexpo-sure.IntheU.S.study,smallopacitieswererare[Lockeyetal.1996].Smallopacitiesofprofu-sioncategory1/0orgreaterweremorefrequentinthe1986Europeanstudy[Trethowanetal.1995],butexposurestosilicaandotherdustswere believed to account for many of thesecases. The results of statistical analyses didnotimplicateRCFexposure[Trethowanetal.1995]oryieldedresultsonlyslightlysuggestiveofanRCFexposureeffect[Rossiteretal.1994].Inthe1996evaluationoftheEuropeancohort,smallopacitiesofcategory1/0orgreaterwerepositivelyassociatedwithRCFexposuresthatoccurredbefore1971[Cowieetal.1999].Tenofthe51(19.6%)maleworkersexposedbefore1971developedcategory1/0orgreateropaci-tiesC8hadalsobeenexposedtoasbestosand9wereeithercurrentorex-smokers.
BoththeU.S.[Lockeyetal.1993;Lemastersetal.1998]andtheEuropean[Trethowanetal.1995;Burgeetal.1995;Cowieetal.1999]studies found that occupational exposuretoRCFsisassociatedwithvariousreportedrespiratorysymptomsandconditions,after
adjustingfortheeffectsofage,sex,andsmok-ing. Exposure to RCF concentrations in therange of 0.2 to 0.6 f/cm3 was associated withstatistically significant increases in eye irrita-tion(OR=2.16,95%CI=1.32–3.54),stuffynose(OR=2.06,95%CI=1.25–3.39),anddrycough(OR=2.53,95%CI=1.25–5.11)comparedwithexposureconcentrations lowerthan0.2f/cm3[Trethowanetal.1995]. IncreasingORsweredemonstrated for RCF exposure concentra-tionsgreaterthan0.6f/cm3comparedwithex-posure concentrations <0.2 f/cm3 for wheeze(P<0.0001), dyspnea (P<0.05), eye irritation(P<0.0001),skinirritation(P<0.0001),anddrycough(P<0.05)butnotstuffynoseorchronicbronchitis [Trethowan et al. 1995]. Lockey etal.[1993]foundthatdyspneawassignificantlyassociatedwithexposureto>15fiber-months/cm3(that is,>1.25fiber-years/cm3)relativetoexposure to ≤15 fiber months/cm3 (dyspneagrade 1COR=2.1, 95% CI=1.3–3.3; dyspneagrade2—OR=3.8,95%CI=1.6–9.4).Lockeyetal.[1993]alsofoundstatisticallysignificantas-sociations between cumulative RCF exposureandchroniccough(OR=2.0,95%CI=1.0–4.0)andpleurisy(OR=5.4,95%CI=1.4–20.2).Le-masters et al. [1998] also noted associations(P<0.05) between employment in an RCFproduction job and increased prevalence ofdyspnea and the presence of at least one re-spiratory symptom or condition. RecurrentchestillnessintheEuropeancohortwasasso-ciatedwithcumulativeexposuretorespirablefibers and was most strongly associated withcumulativeexposuretorespirabledust[Cowieetal.1999].
In cross-sectional analyses involving spiro-metric testing, both the U.S. [Lockey et al.1998;Lemastersetal.1998]and1986Europe-an[Trethowanetal.1995;Burgeetal.1995]studiesfoundthatcumulativeRCFexposurewasassociatedwithpulmonaryfunctiondec-rements among current and former smok-ers. The 1996European study demonstrated
Refractory Ceramic Fibers 83
5 ■Effects of Exposure
decrementsincurrentsmokersonly[Cowieetal.1999].Theobserveddecreasedpulmonaryfunction in the European workers remainedsignificantly associated with cumulative RCFexposure, even after controlling for cumula-tive exposure to inspirable dust [Burge et al.1995]. A longitudinal analysis of data frommultiplePFTsbyLockeyetal. [1998] led theresearcherstoconcludethatexposurestoRCFsbetween 1987 and 1994 were not associatedwithdecreasedpulmonaryfunction.Thefind-ingsfromtheU.S.andEuropeanstudiessug-gest that decrements in pulmonary functionobservedincurrentandformersmokersresultfrom an interactive effect between smokingandRCFexposure.
5.4 Carcinogenicity Risk Assessment Analyses
Theliteraturecontainsthreesignificant inde-pendent risk analyses of occupational expo-sure to RCFs and potential health effects. Ineachof theseanalyses,healtheffectsdatade-rived from multidose and MTD studies withratswereusedwithmodelstoextrapolaterisksto human populations. The modeling of ef-fectsobservedinexperimentalanimalstudieswasnecessitatedby the lackofadequatedataonadversehealtheffects inhumanswithoc-cupationalexposurestoRCFs.Thethreestud-ies,describedindetailbelowandinTable5–9,include the following studies: Dutch ExpertCommittee on Occupational Standards (DE-COS) [1995], Fayerweather et al. [1997], andMoolgavkaretal.[1999].
5.4.1 DECOS [1995]
In1995,DECOS(aworkgroupof theHealthCounciloftheNetherlands)publishedareportevaluating the health effects of occupationalexposure to SVFs. The purpose of the reportwas to establish health-based recommended
occupationalexposurelimitsforspecifictypesof SVFs.As one of the criteria for determin-ingtheairborneexposurelimitsforsixdistincttypesofSVFs,riskassessmentswereperformedfor each fiber type, including RCFs. The riskanalysisforRCFswasbasedontheassumptionthatRCFsareapotentialhumancarcinogenasindicatedbythepositiveresultsofcarcinoge-nicitytestingwithanimals.Ahealth-basedrec-ommended occupational exposure limit wasdeterminedusingthefollowingrationale:
1.If the carcinogenic potential of RCFs iscaused by a nongenotoxic mechanism,an occupational exposure limit of 1 re-spirablef/cm3asan8-hrTWAshouldberecommended based on an NOAEL of25f/cm3andasafetyfactorof25.
2.If the carcinogenic potential of RCFs islinkedtoagenotoxicmechanism,amod-elassumingalinearrelationshipbetweendoseandtheresponse(cancer)shouldbeusedtoestablishtheoccupationalexpo-surelimit.
Themodelindicatedthatanexcesscancerriskof4×10-3 isassociatedwithaTWAexposureto5.6respirablef/cm3basedon40yearsofoc-cupationalexposure.Acancerriskof4×10-5isassociated with exposure to 0.056 f/cm3, anda linear extrapolation indicated that occupa-tionalexposureto1respirablef/cm3asan8-hrTWA for 40 years is associated with a cancerriskof7×10-4.
TheDECOSanalysisreliedonthedatafromalong-term multidose study with rats exposedtokaolinceramicfibers[Bunnetal.1993;Mastet al. 1995b]. These data showed that expo-sure by inhalation to 25 f/cm3 (3 mg/m3) for24 months produced a negligible amount offibrosis (mean Wagner score of 3.2). Conse-quently,theDutchcommitteeviewed25f/cm3as the NOAEL for fibrosis. The report alsonotesthatat thetimeofpublication,nodata
84 Refractory Ceramic Fibers
5 ■Effects of Exposure
Tabl
e 5–
9 . R
isk
asso
ciat
ed w
ith
exp
osu
re to
RC
Fs* a
t 1 f/
cm3 (
TW
A)
as d
eter
min
ed b
y th
ree
ind
epen
den
t an
alys
es
St
udy
An
imal
dat
aE
xtra
pol
atio
n m
odel
Occ
up
atio
nal
exp
osu
re
scen
ario
Exc
ess
life
tim
e ri
sk o
f lu
ng
can
cer–
ML
E
DE
CO
S
19
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Refractory Ceramic Fibers 85
5 ■Effects of Exposure
existedfromretrospectivecohortmortalityormorbidityandcase-controlstudiesofpersonswithoccupationalexposurestoRCFs.Thelin-earmodelingapproach in thisanalysisof theexposure-responserelationshipusingtheani-maldatadoesnottakeintoconsiderationpos-sibledifferencesindosimetryandlungburdenbetweenratsandhumans.
5.4.2 Fayerweather et al. [1997]
Fayerweather et al. [1997] conducted a studyprimarily focusing on the risk assessment ofoccupational exposures for glass fiber insula-tion installers. They performed risk analyseswith several other types of SVFs, includingRCFs.OnlytheanalysiswithRCFsispresent-ed here. This analysis applied an EPA linear-ized multistage model (representing a linearnonthresholddose-response)todatafromratmultidoseandMTDchronicinhalationbioas-says[Mastetal.1995a,b] todetermineexpo-suresatwhichAnosignificantrisk@occurs;i.e.,nomore thanoneadditional cancer caseper100,000 exposed persons. Nonlinear modelswere also used for comparison: the Weibull1.5-hitnonthresholdmodel(representingthenonlinear,nonthresholddose-responsecurve)andWeibull2-hitthresholdmodel(represent-ing the nonlinear, threshold dose-responsecurve). Fiber inhalation by rats was equatedto humans by determining the fibers/day·kgof body weight for the animals and using anexposurescenarioof4hr/day(consistentwithinsulationinstallationworkers=schedules),for5days/weekand50weeks/yearover40work-ingyearsofa70-yearlifespan.RCFCinterpret-edtheresultsoftheanalysiswiththelinearizedmultistagemodeltorepresentariskof3.8×10-5for developing lung cancer over the work-ing lifetime at an exposure concentration of1 f/cm3 [RCFC 1998]. Using the nonlinearmodels, estimates of nonsignificant expo-sures(i.e.,aworkinglifetimeexposureassoci-ated with no more than 1 additional cancer
case/100,000 exposed persons) were 2 and 3orders of magnitude higher. Conversely, therisk estimates for exposure to 1f/cm3 for aworkinglifetimewerelowerusingtheWeibull1.5-hitnonthresholdandWeibull2-hitthresh-oldmodels.
5.4.3 Moolgavkar et al. [1999]
Thisreportdescribesaquantitativeassessmentof theriskof lungcancerassociatedwithoc-cupational exposure to RCFs [Moolgavkar etal.1999].Amajorpremiseunderlyingtheriskassessmentisthathumansareequallysuscep-tibletoRCFsasrats,atthetissuelevel.Theriskanalysis was performed using data from twochronic inhalationbioassaysofRCFs inmaleFischer344rats[Mastetal.1995a,b].Dosim-etryintheriskassessmentwasbasedonafiberdepositionandclearancemodeldevelopedbyYuetal.[1996]thatwasusedtoestimatethelung burdens of fibers in humans. The dose-response model used for the risk assessmentwasthetwo-mutationclonalexpansionmodel,commonlyreferredtoastheMoolgavkar-Ven-zon-Knudson(MVK)model.TheMVKmodelwasfittedtotheratbioassaydatatoestimatetheproportionalincreaseintheratlungtumorinitiationrateinRCF-exposedrats,relativetothebackgroundinitiationrateinnonexposedrats.An MVK model for human lung cancerwas then created by fitting the model to theage-specificlungcancerincidenceforeitheroftwo human cohorts. Finally, the human lungcancer rate for a given tissue dose was esti-matedby increasingthetumorinitiationrateinthehumanmodelbythesameproportionalamountthatanidenticaltissuedosewouldin-creasetheinitiationrateintheMVKmodelforrats. The assumption was made that, for anygiventissuedose,theproportionalincreaseinthe lung tumor initiationrate(relative to thebackgroundrate)isthesameinhumansasinrats.Thetwohumancohortsusedforthehu-manmodelingwereanonsmokingAmerican
86 Refractory Ceramic Fibers
5 ■Effects of Exposure
CancerSociety(ACS)cohort[Petoetal.1992]andacohortofworkersfromthesteelindustry(notexposedtocokeovenemissions)believedtoberepresentativeofindustrialworkers.Be-cause of the difference in the baseline lungcancer risk, risk estimates based on the SteelIndustry cohort were approximately 4 timeshigher than those based on the ACS cohort.Both central estimates (maximum likelihoodestimates[MLEs])and95%upperconfidencelimits (UCLs) were developed. Three equa-tions were tested to describe the relationshipbetween initiation rate for lung cancer andlungburden:
I=Aexp(Bd) (exponential)I=A+Bd2 (quadratic)I=A+Bd (linear)
whered=lungburdeninfiberspermilligramoflung(whichcanvarywithtime)andAandB are constants (different for each model).With each equation, calculations were madetodeterminetheexcessriskforaworkeraged20 to 50 to develop lung cancer by age 70whenexposedtoRCFsataconcentrationof1.0fiber/cm3for8hr/day,5days/week.
Usingtheexponentialmodel,theexcessriskoflungcancerassociatedwith1.0f/cm3wasesti-matedtobe3.7×10-5(MLE)and4.9×10-5(95%UCL),basedontheACScohort.Forthesameconditionstheriskoflungcancerwas1.5×10-4(MLE)and1.8×10-4(95%UCL)basedontheSteelIndustrycohort.Usingaquadraticequa-tion,theresearchersreportedslightlyloweres-timates of excess risk of 4.1×10-6 (MLE) and1.2×10-5(95%UCL)fortheACScohort,and1.4×10-5 (MLE) and 4.3×10-5 (95% UCL) forthe Steel Industry cohort. The highest esti-matesofexcessriskresultedwithalinearequa-tion:2.7×10-4(MLE)and1.5×10-3(95%UCL)for theACScohort,and1.1×10-3(MLE),and5.8×10-3(95%UCL)fortheSteelIndustryco-hort.Additionalriskestimateswerecalculatedaccording to the conditions described above
(i.e.,ACScohortversusSteelIndustrycohort;MLEand95%UCLforexponential,quadratic,andlinearmodels)butwithdifferentexposureconcentrations.Theexcessriskwasalsocalcu-latedforexposureconcentrationsof0.75f/cm3,0.5f/cm3,and0.25f/cm3.TheseriskestimatesarepresentedinTable5–10.
AsshowninTable5–10,thehighestriskesti-mates at each of the three exposure concen-trationsare associatedwith the linearmodel,followedbytheexponentialmodel.Thelowestriskestimatesareassociatedwiththequadraticmodel.Ateachexposureconcentration,moreconservativeriskestimatesareobtainedfortheACScohortthantheSteelIndustrycohort.
Attherecommendedexposureguidelineestab-lishedbytheRCFC(0.5f/cm3),thehighestriskestimate(linearmodel,SteelIndustrycohort)is the MLE of 5.3×10-4 or 5.3/10,000 (95%UCL=2.9×10-3).At0.5f/cm3,theriskestimatesforthesteelindustrycohortareroughly1orderofmagnitude(factorof10)lowerwiththeex-ponentialmodel (MLE=7.3×10-5, 95%UCL=9.1×10-5), and 2 orders of magnitude lowerusing the quadratic model (MLE=3.5×10-6,95% UCL=1.1×10-5). At the lowest exposureconcentration (0.25 f/cm3), the highest riskestimate(SteelIndustrycohort,linearmodel)wastheMLEof2.7×10-4(95%UCL=1.4×10-3).Again,onaverage,theriskestimatesfromthe3modelsusingthesteelindustrycohortare3to4timeshigherthanforcorrespondingmodelvalueswiththeACScohort.
The authors concluded that the risk estimatesbasedonthetwocohorts“representboundsonriskslikelytobeseeninoccupationalcohorts.”However,anoccupationalcohortisunlikelytosharethenonsmokingstatusoftheACScohort.Therefore,ofthetwohumanpopulationsusedformodelfittingintheMoolgavkaretal.[1999]risk assessment, the steel industry cohort maybe the preferable cohort to use for estimatingtherisksfromoccupationalexposurestoRCFs.
Refractory Ceramic Fibers 87
5 ■Effects of Exposure
TheMoolgavkaretal.[1999]reportalsoindi-cates airborne fiber concentrations estimatedtoresultinexcesslifetimeriskforcancerof10-4(1in10,000)basedontheapproachesusedbyDECOS[1995]andFayerweatheretal.[1997]and using the MVK model for both theACScohort and the steel industry cohort. Withthe DECOS [1995] linearized, nonthresholdmodelapproach,anexcesslifetimecancerriskof 10-4 was calculated to result from a fiberconcentrationof0.14f/cm3.Usingthelinear-ized,multistagemodelapproachdescribedinFayerweather et al. [1997], a fiber concentra-tionof2.6f/cm3wasestimatedtocorrespondtotheexcesslifetimecancerriskof10-4.WiththeMVKexponentialmodel,anexcesslifetimecancer risk of 10-4 was determined for fiberconcentrations of 0.7 f/cm3 for the Steel In-dustrycohortand2.7f/cm3fortheACScohort[Moolgavkaretal.1999].
5.4.4 Discussion
Theestimatedlungfiberburdenfordosimetryin theanalysisbyMoolgavkaret al. [1999] is
a methodological improvement over the riskassessment for RCFs by Fayerweather et al.[1997],whichwasbasedsolelyontheinhaledfiberconcentration.Modelinglungburdendo-simetryshould,intheory,compensatefortheknown differences between rats and humansinfiberdepositionandclearance.Similarly,us-inganMVKmodelfordose-responseestima-tion could compensate for differences in cellmutation and proliferation rates in rats andhumans. However, some key parameter val-ues in the MVK and lung dosimetry modelsarepoorlyknown.Forexample,thedosimetrymodel for humans has been validated withonly three human tissue samples taken fromworkers whose exposures to RCFs were notmeasured[Yuetal.1997].
A review and comparison of risk modelingapproaches for RCFs by Maxim et al. [2003]describesthethreemodelshereaswellasad-ditionalmoresophisticatedvariationsofquan-titativeriskanalysesforRCFs.Usingapproach-essuchasbenchmarkdosemodeling,Maximetal.[2003]producedRCFunitpotencyvaluesrangingfrom1.4×10-4to7.2×10-4.
Table 5–10 . Estimates (MLE* and 95% UCL) of excess risk of lung cancer at three exposure concentrations using exponential, quadratic, and linear models for an ACS cohort and a steel industry cohort
Exposure
ACS cohort Steel industry cohort
Exponential Quadratic Linear Exponential Quadratic Linear
0.75 f/cm3:MLE
2.8×10-5
2.3×10-6
2.0×10-4
1.1×10-4
7.9×10-6
8.0×10-4
95%UCL 3.7×10-5 6.8×10-6 1.1×10-3 1.4×10-4 2.4×10-5 4.3×10-3
0.5f/cm3:MLE
1.8×10-5
1.0×10-6
1.3×10-4
7.3×10-5
3.5×10-6
5.3×10-4
95%UCL 2.5×10-5 3.0×10-6 7.3×10-4 9.1×10-5 1.1×10-5 2.9×10-3
0.25 f/cm3:MLE
9.2×10-6
2.5×10-7
6.7×10-5
3.6×10-5
8.8×10-7
2.7×10-4
95%UCL 1.2×10-5 7.5×10-7 3.6×10-5 4.6×10-5 2.7×10-6 1.4×10-3
AdaptedfromMoolgavkaretal.[1999].*Abbreviations:ACS=AmericanCancerSociety;MLE=maximumlikelihoodestimate;UCL=95%upperconfidencelimit.
88 Refractory Ceramic Fibers
5 ■Effects of Exposure
A common weakness among all three of therisk analyses stems from uncertainty aboutpossibledifferencesinthesensitivityofhumanlungstofibers,ascomparedwithratlungs.ThepossibilityofsuchadifferenceisacknowledgedinthereportbyMoolgavkaretal.[1999],buttheeffectof thisuncertaintyon theriskesti-matesisnotexploredquantitatively.Asanex-ample,Pottetal.[1994]estimatedthatinthecase of asbestos fibers, humans are approxi-mately 200-fold more sensitive than rats, onthebasisoffiberconcentrationinair.Pottetal.[1994]furthernotedthatacrocidoliteinhala-tionstudythatwasnegativeintheratresultedinaratlungfiberconcentrationthatwasmorethan1,000-foldgreaterthanthefiberconcen-trationsinthelungsofasbestosworkerswithmesotheliomas.Insupportofthisanalysis,re-sultsofastudybyRödelspergerandWoitowitz[1995]ledtheauthorstoconcludethathumansareatleast6,000timesmoresensitivethanratstoagiventissueconcentrationofamphibolefi-bers.Althoughamphiboleasbestosfibershavephysicochemical characteristics which differfromthoseofRCFs,thesefindingsraiseques-tionsaboutusingexperimentalanimaldataforpredicting human health effects and assum-ingthattargettissues inhumansandratsareequallysensitivetoRCFtoxicity.
ThelungcancerriskestimatesforRCFsderivedbyMoolgavkaretal.[1999]mayalsobeunder-estimatedforoccupationallyexposedworkersbecause of several basic assumptions madein the lung tissue dosimetry. Tissue dosim-etrymodelingintheMoolgavkaretal.[1999]
risk assessment is based on the assumptionthataworkerisexposedtoRCFsfor8hr/day,5days/week,52weeks/year,fromage20to50[Moolgavkaretal.1999].Analternativeanaly-sis, inwhichtheassumptionwaschangedto8hr/day,5days/week,50weeks/yearfromage20to60,wasalsodescribedbutnotpresentedindetail. Inbothcases, thebreathingrateforlightworkwasassumedtobe13.5liters/min-ute. Additional information might be gainedfromassuminganexposureperiodof8hr/day,5days/week,50weeks/year,fromage20to65,with a breathing rate matching the Interna-tionalCommissiononRadiologicalProtection“Reference Man” value for light work, whichis 20 liters/minute [ICRP 1994]. In addition,thecumulativeexcessriskof lungcancerwascalculatedonlythroughage70[Moolgavkaretal.1999].Thispracticemayunderestimatethelifetimeriskoflungcancerintheexposedco-hort,sinceasubstantialfractionofthecohort maybeexpectedtosurvivebeyondage70.Theexcessriskmightalsobecalculatedinacom-peting-risks frameworkusingactuarialmeth-odsuntilmostorallofthecohortispresumedtohavediedbecauseofcompetingrisks(gener-ally85years).Finally,riskestimatesderivedbyMoolgavkaretal.[1999]werebasedsolelyondatafromstudies withrats,ignoringdatafromstudies of hamsters [McConnell et al. 1995].Because42%ofthehamsters inthesestudiesdevelopedmesotheliomas,usingthisdatabasefortheriskassessmentwouldproducehigherestimatesofriskthantheanalysisbasedontheratdata.
Refractory Ceramic Fibers 89
6 Discussion and Summary of Fiber Toxicity
comparativemeasuresoftoxicityfordifferentagents. RCFs implanted into the pleural andabdominal cavities of various strains of ratsand hamsters have produced mesotheliomas,sarcomas,andcarcinomasatthesitesoffiberimplantation[Wagneretal.1973;Davisetal.1984; Pott et al. 1987]. Similar tumorigenicresponseshavebeenobservedfollowingintra-tracheal instillation of RCFs [Manville Cor-poration1991].ThesedataprovideadditionalevidenceofthecarcinogeniceffectsofRCFsinexposedlaboratoryanimals.
Epidemiological data have not associated oc-cupationalexposuretoRCFsundercurrentex-posureconditionswithincreasedincidenceofpleuralmesotheliomaor lungcancer[Lockeyet al. 1993; Lemasters et al. 1998]. However,in epidemiologic studies of workers in RCFmanufacturingfacilities[Lemastersetal.1994;Lockey et al. 1993, 1996; Rossiter et al. 1994;Trethowanetal.1995;Burgeetal.1995;Cowieetal.1999],increasedexposurestoairbornefi-bershavebeenlinkedtopleuralplaques,smallradiographicparenchymalopacities,decreasedpulmonary function, respiratory symptomsandconditions(pleurisy,dyspnea,cough),andskinandeyeirritation.
Manyoftherespiratoryeffectsshowedastatis-tically significantassociationwithRCFexpo-sureaftercontrollingoradjustingforpotentialconfounders,includingcigarettesmokingandexposure tononfibrousdust.Yet inPFTs, theinteractive effect between smoking and RCFexposure was especially pronounced, basedon the finding that RCF-associated decreases
6.1 Significance of Studies with RCFs
Three major sources of data contributing tothe literature on RCFs are (1) experimentalstudieswithanimalsandinvitrobioassays,(2)epidemiologicstudiesofpopulationswithoc-cupational exposure to RCFs (primarily dur-ingmanufacturing), and (3) exposureassess-ment studies that provide quantitative andqualitativemeasurementsofexposuresaswellasthephysicalandchemicalcharacteristicsofairborneRCFs.Eachofthesesourcesofinfor-mation is considered integral to this criteriadocument for providing a more comprehen-sive evaluation of occupational exposure toRCFsandtheirpotentialhealthconsequences.
Datafrominhalationstudieswithanimalsex-posedtoRCFshavedemonstratedstatisticallysignificant increases in the induction of lungtumorsinratsandmesotheliomasinhamsters[Mast et al. 1995a,b; McConnell et al. 1995].Other inhalation studies with RCFs haveshownpathobiologic inflammatoryresponsesin lungandpleural tissues[Gelzleichteretal.1996a,b].Implantationandinstillationmeth-ods have also been used in animal studieswith RCFs to determine the potential effectsofthesefibersontargettissues.Thesestudieshaverecognizedlimitationsforinterpretingre-sults because the exposure techniques bypassthenaturaldefenseandclearancemechanismsassociatedwiththenormalrouteofexposure(i.e., inhalation).However,theyareusefulfordemonstrating mechanisms of toxicity and
90 Refractory Ceramic Fibers
6 ■Discussion and Summary of Fiber Toxicity
in pulmonary function were limited to cur-rentand former smokers [Lockeyetal.1998;Lemasters et al. 1998; Trethowan et al. 1995;Burge et al. 1995]. The interactive effect be-tween exposure to airborne fibers and ciga-rette smokehasbeenpreviouslydocumented(e.g., Selikoff et al. [1968] ). However, unlikemaleworkers,nonsmokingfemaleworkersdidshowstatistically significantdecreases inPFTresultsassociatedwithRCFexposure[Lemas-tersetal.1998].AnalysesofdatafrommultiplePFTsessions[Lockeyetal.1998]haveledre-searcherstoconcludethatdecreasesinpulmo-nary function were more strongly influencedbythehigherexposurestoairborneRCFsthatoccurred in the past. This conclusion seemsplausible,sincehistoricalair-samplingdatain-dicatethatairbornefiberconcentrationsweremuchhigherinthefirstdecadesofRCFmanu-facturingandthatformerworkershadpoten-tiallyhigherexposures.
Multiplestudieshavebeenperformedtochar-acterizetheconcentrationsandcharacteristicsof airborne exposures to RCFs in the work-place. Current and historical environmentalmonitoring data [Esmen etal. 1979; CantorandGorman1987;Gorman1987;O’Brienetal.1990;Chengetal.1992;Brown1992;Cornetal.1992;Lyman1992;Allshouse1995;Hewett1996]indicatethatairborneexposurestoRCFsincludefibersintherespirablesizerange(<3.5μmindiameterand<200μmlong[Timbrell1965; Lippmann 1990; Baron 1996]). TheseexposuresoccurinprimaryRCFmanufactur-ingaswellas insecondary industries suchasRCF installation and removal. Sampling datafromstudiesofdomestic,primaryRCFmanu-facturing sites indicate that average airbornefiberconcentrationshavesteadilydeclinedbynearly 2 orders of magnitude over the past 2decades.Forexample,Riceetal.[1997]reportamaximumexposureestimateof10f/cm3as-sociatedwithanRCFmanufacturingprocessinthe1950s,andEsmenetal.[1979]measured
averageexposureconcentrationsrangingfrom0.05to2.6f/cm3inRCFfacilitiesinthemiddletolate1970s.Riceetal.[1994,1996,1997]sug-gestaverageconcentrationsinmanufacturingranging from<LODto0.66 f/cm3 in the late1980s, and Maxim et al. [1994, 1997, 2000a]reportthatconcentrationsfromthelate1980sthrough1997ranged fromanAMof<0.3 to0.6f/cm3(GM0.2f/cm3).Formanymanufac-turingprocesses,evengreaterreductionsinex-posureshavebeenrealizedthroughimprovedventilation, engineering or process changes,andproductstewardshipprograms[Riceetal.1996;Maximetal.1999b].
Althoughthepotentialexistsforexposuretore-spirablecrystallinesilicaintheformsofquartz,tridymite, and cristobalite during work withRCFs, exposure monitoring data indicate thatthese exposures are generally low [Rice et al.1994].Maximet al. [1999b] report thatmanyairborne samples of crystalline silica collectedduring the installation and removal of RCFproducts contain concentrations below theLOD,withaverageconcentrationsofrespirablecrystalline silica per measurable task rangingfrom0.01to0.44mg/m3(equivalent8-hrTWArange=0.004 to 0.148mg/m3). Other studieshaveshowngreaterpotentialforexposuretore-spirablecrystallinesilica(especiallyintheformof cristobalite) during the removal of after-serviceRCFmaterials[Gantner1986;Chengetal.1992;Perraultetal.1992;vandenBergenetal.1994;SweeneyandGilgrist1998].Forpro-cessesassociatedwithhigherconcentrationsofairbornerespirablefibers,therearealsogeneral-lygreaterconcentrationsoftotalandrespirabledusts[Esmenetal.1979;Krantzetal.1994].
6.2 Factors Affecting Fiber Toxicity
To accurately interpret the results of experi-mentalandepidemiologicstudieswithRCFs,
Refractory Ceramic Fibers 91
6 ■Discussion and Summary of Fiber Toxicity
it is important toconsiderrecognized factorsthatcontribute tofiber toxicity forRCFsandother SVFs in general. The major determi-nantsoffiber toxicityhavebeen identifiedasfiberdose(oritssurrogate,airbornefiberex-posure),fiberdimensions(lengthanddiame-ter),andfiberdurability(especiallyasitaffectsfiber biopersistence in the lungs) [Bignon etal.1994;Bunnetal.1992;BenderandHadley1994;Christensenetal.1994;LockeyandWi-ese1992;Mooreetal.2001].
6.2.1 Fiber Dose
Themeasurementofairbornefiberconcentra-tions is frequentlyusedasa surrogate foras-sessingdoseandhealthrisktoworkers.Analy-sesofhistoricalandcurrentairsamplingdataindicate that occupational exposure concen-trationsofairborneRCFshavedecreaseddra-maticallyinthemanufacturingsector[Maximetal.1997;Riceetal.1997].Inchronicinhala-tionstudiesofRCFs[Mastetal.1995a,b;Mc-Connell et al. 1995], both rats and hamsterswereexposedtoarangeofsize-separatedRCFconcentrationsinanose-onlyinhalationpro-tocol.WhenairborneRCFsaregenerated,halformoreof theaerosol is composedof respi-rableparticlesofunfiberizedmaterialthatwasformerlyacomponentofthefiber[Mastetal.1995a,b].Becauseofthenatureofthismixedexposure, it isdifficult todetermine the rela-tive contributions of the airborne fibers andnonfibrous particulates to the adverse effectsobservedinhumansandanimals.Ithasbeenpostulatedthatthenonfibrousparticulatesmayhave contributed to an overload effect in theMastetal.[1995a,b]animalstudieswithRCFs[Yuetal.1994;Mastetal.1995a,b;Maximetal.1997;Brownetal.2000].Burgeetal.[1995]have suggested that the health effects seen inRCF-exposed workers are a consequence ofcombinedparticulateandfiberexposure,butthe decrements in lung function are more re-latedtofiberexposurecombinedwithsmoking.
Other studies have shown that for processesassociated with higher concentrations of air-borne respirablefibers, there is alsoagreaterconcentrationoftotalandrespirabledust[Es-menetal.1979;Krantzetal.1994].
6.2.2 Fiber Dimensions
Throughout the literature, studies supportthe theory that fiber toxicity is related to fi-ber dimensions [Timbrell 1982, 1989; HarrisandTimbrell1977;Stantonetal.1977,1981;Lippmann 1988]. Initially, fiber dimensions(lengthanddiameter)playasignificantroleindeterminingthedepositionsiteofafiberinthelungs.Longerandthicker(>3.5µmindiam-eter)fibersarepreferentiallydeposited in theupper airways by the mechanisms of impac-tion[Yuetal.1986]orinterception.Timbrell[1965]suggestedthatdirectinterceptionplaysan importantrole in thedepositionoffibers,asthefibercomesintocontactwiththeairwaywallandisdeposited.Fibersbeingdepositedinthelargerciliatedairwaysaregenerallyclearedvia the mucociliary escalator. Thinner fiberstendtomaneuverpastairwaybifurcationsintosmallerandsmallerairwaysuntiltheirdimen-sions dictate deposition either by sedimenta-tionordiffusion[AsgharianandYu1989].An-otherfactorthatmayenhancedepositionistheelectrostaticchargeafibercanaccumulatedur-ingdust-generatingprocessesinoccupationalsettings[Vincent1985].Thefiberchargemayaffectitsattractiontothelungsurface,causingthefiber tobedepositedbyelectrostaticpre-cipitation.
Althoughthedimensionalcharacteristicsandgeometry of a fiber influence its depositionintherespiratorytract,thefiber’slengthandchemicalpropertiesdictate its clearanceandretention once it has been deposited withinthealveolarregion.Forthefiberthattraversestherespiratoryairwaysandisdepositedinthegas exchange region, possible fates include
92 Refractory Ceramic Fibers
6 ■Discussion and Summary of Fiber Toxicity
dissolution,clearanceviaphagocyticcells(al-veolar macrophages) in the alveoli, or trans-location through membranes into interstitialtissues. Both test animals and workers havebeenexposedtoRCFsofsimilarlengthanddi-ameter[Allshouse1995],andtheseexposuresinclude fibers of respirable dimensions [Es-menetal.1979;Lockeyetal.1990;Chengetal.1992].Sinceratsandotherrodentsareobligatenasalbreathers,fibersgreaterthanabout1µmindiameteraretoolargefordepositionintheiralveoli [Jones1993].Bycomparison,humanscaninhaleanddepositfibersupto3.5µmindiameterinthethoracicandgasexchangere-gionsofthelung.Thisphysiologicaldifferencepreventstheevaluationoffiberswithdiametersofabout1 to3.5µm(whichwouldhavehu-manrelevance)inrodentinhalationstudies.
Theroleoffibersizeininducingbiologicalef-fects iswelldocumentedandreviewed in theliterature[Stantonetal.1977,1981;Pottetal.1987;Warheit1994].Stantonetal.[1977]hy-pothesized thatglassfibers longer than8µmwithdiametersthinnerthan0.25µmhadhighcarcinogenicpotential.Inareviewofthesig-nificanceoffibersizetomesotheliomaetiol-ogy,Timbrell[1989]concludedthatthethin-ner fibers with an upper diameter limit of0.1µmaremorepotentforproducingdiseasesoftheparietalpleura(e.g.,mesotheliomaandpleuralplaques)thanthickerfibers.ThatvalueforfiberdiameteriscitedbyLippmann[1988]inhisasbestosexposure indices formesothe-lioma. Oberdörster [1994] studied the effectsofbothlong(>10–16μm)andshort(<10μm)fibersonalveolarmacrophagefunctions,con-cludingthatbothwillleadtoinflammatoryre-actions—although a distinct difference existsinthelong-termeffectsbecauseofdifferentialclearance of fibers of different sizes. Alveolarmacrophagesconstitutethefirstlineofdefenseagainstparticlesdepositedinthealveoli; theymigratetositeswherefibersaredepositedandphagocytizethem.Theengulfedfibersarethen
movedbythemacrophagestowardthemuco-ciliaryescalatorandremoved fromthe respi-ratory tract. The ability of the macrophagesto clear fibers is size-dependent. Short fibers(<15 µm long) can usually be phagocytizedby one rat alveolar macrophage [Luoto et al.1994; Morgan et al. 1982; Oberdörster et al.1988,Oberdörster1994],whereaslongerfibersmaybeengulfedbytwoormoremacrophages.Blakeetal.[1998]havesuggestedthatincom-pleteorfrustratedphagocytosismayplayaroleintheincreasedtoxicityoflongerfibers.Fiberlengthhasbeencorrelatedwiththecytotoxicityofglassfibers[Blakeetal.1998],withgreatestcytotoxicityforfibers17and33µmlongcom-pared with shorter fiber samples. Long fibers(17μmaveragelength)tendtobeamorepo-tentinducerofTNFproductionandtranscrip-tion factoractivationthanshortfibers(7μmaveragelength)[Yeetal.1999].
Whencomparingthedimensionsofairbornefiberswiththosefoundinthe lungs, it is im-portant to consider the preferential clearanceof shorterfibersaswellas theeffectsoffiberdissolutionandbreakage.Yuetal.[1996]eval-uated these factors in a study that led to thedevelopmentofaclearancemodelforRCFsinratlungs.Resultsofthatstudyconfirmedthatfibers10to20µmlongareclearedmoreslowlythanthose<10µmlongbecauseoftheincom-plete phagocytosis of long fibers by macro-phages.Thepreferentialclearanceofshorterfi-bershasalsobeendocumentedinstudieswithchrysotileasbestosandothermineralfibers,inwhichtheaveragelengthofretainedfibersin-creasedduringadiscreteperiodfollowingde-position[Coinetal.1992;Churg1994].Thisincrease might also be explained by the lon-gitudinal cleavage pattern of asbestos fibers,which results in longer fibers of decreasingdiameters[Coinetal.1992].Bycontrast,anybreakageofRCFswouldoccurperpendicularto the longitudinalplane,resulting inshorterfibersofthesamediameter.Fortheclearance
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6 ■Discussion and Summary of Fiber Toxicity
model developed by Yu et al. [1996], the ef-fect of fiber breakage was also assessed fromexperimental data and incorporated into themodel.Theauthorsconcludedthatthesimul-taneouseffectoffiberbreakageanddifferentialclearanceleadsonlytoasmallchangeinfibersize distribution in the lung. This result sug-geststhatthedimensionsoffibersinthelungarecloselyrelatedtothedimensionsoffibersmeasured in the airborne samples (adjustedfordeposition);thus,mostshortfibersinthelungsoriginatedasshortfibersinairborneex-posures.
The dimensions of airborne fibers have alsobeen characterized for workers with occupa-tionalexposuretoRCFs.Onestudyofdomes-ticRCFmanufacturingfacilitiesfoundthatap-proximately90%ofairbornefiberswere<3μmindiameter,and95%ofairbornefiberswere<4μmindiameterand<50μmlong[Esmenet al. 1979]. The study showed that diameterand lengthdistributionsof airbornefibers inthefacilitieswereconsistentwithaGM
Dof0.7
μmandaGMLof13μm.Anotherairsampling
studyofdomesticRCFmanufacturingsitesre-portedthat99.7%ofthefibershaddiametersof<3μmand64%hadlengths>10μm[Alls-house1995].MeasurementsofairbornefibersintheEuropeanRCFmanufacturingindustryarecomparable:Rood[1988]reportedthatallfibersobservedwereinthethoracicandrespi-rable size range (i.e., diameter <3μm), withmedian diameters ranging 0.5 to 1.0 μm andmedian lengths from 8 to 23 μm. During re-moval of RCF products, Cheng et al. [1992]foundthat87%ofairbornefiberswerewithintherespirablesizerange,withfiberdiametersranging from 0.5 to 6 μm (median diame-ter=1.6μm)andfiberlengthsrangingfrom5to220μm.Anotherstudy[Perraultetal.1992]of airborne fiber dimensions measured dur-inginstallationandremovalofRCFmaterialsinindustrialfurnacesreportedGM
Dvaluesof
0.38and0.57μm,respectively.
6.2.3 Fiber Durability
Biopersistence (and specifically the retentiontime of the fiber in the lungs) is consideredtobeanimportantpredictoroffibertoxicity.Fiber solubility affects the biopersistence offibers deposited within the lung and is a keydeterminantoffibertoxicity.BenderandHad-ley[1994]suggestthatsomeoftheimportantconsiderations of fiber durability include thefollowing:
■ Fiber size—particularly length as it re-lates to the dimensions of the alveolarmacrophages
■ Fiberdissolutionrate
■ Mechanical properties of the fibers, in-cludingpartiallydissolvedand/ordigest-edfibers
■ Overloading of the normal clearancemechanismsofthelung
Bignonetal.[1994]arguethatfibersthatarebiopersistentinvivoandinvitroaremorebio-logicallyactivethanlessdurablefibers.
ThedurabilityofRCFs[Hammadetal.1988;Luotoetal.1995]providesabasisforsuggest-ingthatthesefibersmightpersistlongenoughtoinducebiologicaleffectssimilartothoseofasbestos. In vitro durability tests have shownRCFstobehighlyresistanttodissolutioninbi-ologically relevantmixtures suchasGamble’ssolution[ScholzeandConradt1987].Theper-sistenceofRCFsinboththeperitonealcavity[Bellmanetal.1987]andthelung[Hammadetal.1988]hasbeenrecognizedinexperimen-tal studies. Hammad et al. [1988] sacrificedrats exposed to either slag wool or ceramicfibers via inhalation at 5, 30, 90, 180, or 270daysafterexposure.Thelungsoftheanimalswere ashed in a low-temperature asher, andthefibercontentofthelungswasevaluatedbyPCM.Theresearchers foundthat24%of the
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6 ■Discussion and Summary of Fiber Toxicity
deposited RCFs persisted in the lungs of ratssacrificed270daysfollowingexposure.Inthesame study, the lungs of rats exposed to slagwoolcontainedonly6%oftheslagwoolfibers270daysafterexposurecomparedwith thosesacrificed 5 days following inhalation. Fromthese results, itwasconcluded thatRCFs fol-low a clearance pattern of relatively durablefibersthatpersist,translocate,orareremovedby some mechanism other than dissolution.Similar results were obtained in the study byMast et al. [1995b], which shows that RCFsarepersistent in the lungsof rats exposedbyinhalation.Specifically,comparedwiththefi-berburdeninthelungsofanimalssacrificed3monthsafterexposure(recovery),thelungsofanimalssacrificedafter21monthsofrecoverycontainedapproximately20%ofthedepositedfibers. Of the retained fibers (measured withbothSEMandTEMtechniques)54%to75%had diameters <0.5 µm, and more than 90%were5to20µmlong.
Researchershavesuggestedthatfibersdepos-ited in the gas exchange region with lengthsless thanthediameterofanalveolarmacro-phage are phagocytized and cleared via themucociliary system or the lymph channels.DissolutionoffiberswithintheAlMoccursifthefibersarenotresistanttotheacidicintra-cellularconditionsorapH~5[Nybergetal.1989].Fibersthatarenotengulfedbyalveo-larmacrophagesaresubjectedtoapHof7.4intheextracellularfluidofthelung.AstudyofSVFdurabilityinratalveolarmacrophagesreportsthatRCFsaremuchlesssolublethanglasswoolandrockwoolfibersbasedontheamounts of silicon (Si) and iron (Fe) dis-solved from the fibers in vitro [Luoto et al.1995].RCFs in ratalveolarmacrophagecul-turedissolved less than10mgSi/m2offibersurfaceareaandlessthan1mgFe/m2offibersurfacearea.Glasswooldissolvedmorethan50mgSi/m2,androckwooldissolvednearly2mgFe/m2whenmeasuredovercomparable
timeperiods.However,degradationanddis-solution of deposited RCFs may still occur,based on the findings of higher dissolutionofaluminum(Al)fromRCFs(0.8to2.4mgAl/m2) in alveolar macrophages than fromtheotherSVFs[Luotoetal.1995].Inanotherstudy,SEManalysisoffibersrecovered fromthelungsofrats6monthsafterinhalationofRCFsrevealedanerodedappearance,causingthe researchers to conclude that dissolutionof Si in the fibers is a plausible mechanismfor long-term fiber clearance [Yamato et al.1994].
SVFsingeneralarelessdurablethanasbestosfibers.RCFsaremoredurablethanmanyotherSVFs,withadissolutionratesomewhathigherthanchrysotileasbestos.Undertheextracellu-larconditionsinthelung,chrysotile—themostsolubleformofasbestos—hasadissolutionrateof<1to2ng/cm2/hr.RCFshaveasimilardis-solutionrateofabout1to10ng/cm2/hrunderconditionsexperiencedinpulmonaryintersti-tialfluid.OthermoresolubleSVFscanbe10to1,000timeslessdurable[ScholzeandCon-radt 1987; Christensen et al. 1994; Maxim etal.1999b;Mooreetal.2001].Atthemeasuredsolubilityrate,anRCFwitha1-µmdiameterwould take more than 1,000 days to dissolvecompletely[Leineweber1984].
6.3 Summary of RCF Toxicity and Exposure Data
In addition to the main determinants of fi-bertoxicity(dose,dimension,anddurability),other factors such as elemental composition,surface area, andcompositioncanalso influ-encethetoxicityofthefiber.Thus,itisdifficulttopredictafiber’spotentialforhumantoxicitybasedsolelyoninvitroorinvivotests.Basedon consideration of these factors, the majorfindings from the RCF animal and humanstudiesareasfollows:
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6 ■Discussion and Summary of Fiber Toxicity
■ Toxicologicevidence fromexperimentalinhalation studies indicates that RCFsare capable of producing lung tumorsinlaboratoryratsandmesotheliomasinhamsters [Mast et al. 1995a,b; McCon-nell et al. 1995]. However, interpretingthesestudieswithregardtoRCFpotencyanditsimplicationforoccupationallyex-posedhumanpopulationsiscomplicatedbythe issueofcoexposuretofibersandnonfibrousrespirableparticulate.
■ ThedurabilityofRCFscontributestothebiopersistenceofthesefibersbothinvivoandinvitro[Bellmannetal.1987;Schol-zeandConradt1987;LockeyandWiese1992].
■ Cytotoxicityandgenotoxicitystudiesin-dicatethatRCFs
—are capable of inducing enzyme re-leaseandcellhemolysis[Wrightetal.1986;Fujinoetal.1995;Leikaufetal.1995;Luotoetal.1997],
—affectmediatorrelease[Morimotoetal.1993;Ljungmanetal.1994;Fujinoetal.1995;Leikaufetal.1995;Hilletal.1996;Cullenetal.1997;Gilmouretal.1997;Luotoetal.1997;Wangetal.1999],
—may decrease cell viability and in-hibitproliferation[Yeglesetal.1995;Okayasuetal.1999;Hartetal.1992],
—affect cell viability and proliferation[Hartetal.1992],and
—may induce free radicals, micronu-clei,polynuclei,chromosomalbreak-age,andhyperdiploidcells[Brownetal.1998;Doppetal.1997;Hartetal.1992].
■ Exposure monitoring results indicatethatairbornefibersmeasuredinboththemanufacturing and end-use sectors ofthe RCF industry have dimensions thatfall within the thoracic and respirablesizeranges[Esmenetal.1979;Lockeyetal.1990;Chengetal.1992].
■ Epidemiologicstudiesofworkers intheRCF manufacturing industry report anassociationbetweenincreasedexposuresto airborne fibers and the occurrenceof pleural plaques, other radiographicabnormalities, respiratory symptoms,decreased pulmonary function, and eyeandskinirritation[Lemastersetal.1994,1998;Lockeyetal.1996;Trethowanetal.1995;Burgeetal.1995].Currentoccupa-tionalexposures toRCFshavenotbeenlinked to decreases in pulmonary func-tionofworkers[Lockeyetal.1998].
■ WorkerexposuretoairbornefiberintheRCF industry over the past 20 years ormore have decreased substantially, re-portedlyastheresultofincreasedhazardawarenessandthedesignandimplemen-tationofengineeringcontrols[Riceetal.1997;Maximetal.1997].
These observations warrant concern for thecontinued control and reduction of occupa-tionalexposurestoairborneRCFs.
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7 Existing Standards and Recommendations
lengths≥10µmforup to10hr/dayduringa40-hr workweek. NIOSH also recommendedthatairborneconcentrationsdeterminedasto-talfibrousglassbelimitedtoa5mg/m3ofairasaTWA.Atthattime,NIOSHconcludedthatexposure to glass fibers caused eye, skin, andrespiratory irritation.NIOSHalso stated thatuntilmoreinformationbecameavailable,thisrecommendation should be applied to otherSVFs.
TheAgencyforToxicSubstancesandDiseaseRegistry (ATSDR) calculated an inhalationminimal risk concentration of 0.03 f/cm3 forhumans based on extrapolation from animalstudies[ATSDR2002].TheAgencyusedmac-rophageaggregation,themostsensitiveindica-torofinflammationfromRCFs,asthebasisforthisvalue.Calculationofthisvalueisbasedonexposureassumptionsforgeneralpublichealththatdifferfromthoseusedinmodelsfordeter-miningoccupationalexposurelimits.
ACGIHproposedaTLVof0.1f/cm3asan8-hrTWA for RCFs under its notice of intendedchangestothe1998TLVs[ACGIH1998].Onfurtherreview,thisconcentrationwasrevisedto0.2f/cm3[ACGIH2000].ACGIHalsoclas-sifies RCFs as a suspected human carcinogen(A2designations)[ACGIH2005].Ontheba-sis of a weight-of-evidence carcinogenic riskassessment,theEPA[1993]classifiedRCFsasaGroupB2carcinogen(probablehumancar-cinogenbasedonsufficientanimaldata).
ACGIH and EPA designations are consistentwith thatof the InternationalAgency forRe-search on Cancer (IARC), which classified
Standardsandguidelinesforcontrollingwork-erexposurestoRCFsvaryintheUnitedStates.Othergovernmentsandinternationalagencieshavealsodevelopedrecommendationsandoc-cupationalexposurelimitsthatapplytoRCFs.Table7–1presentsasummaryofoccupationalexposure limit standards and guidelines forRCFs.
Within the United States, the RCFC formallyestablished a recommended exposure guide-lineof0.5 f/cm3asanelementof itsproductstewardship program known as PSP 2002,whichwasendorsedbyOSHAasa5-yearvol-untaryprogram[OSHA2002].Aspartofthatprogram,theRCFCrecommendsthatworkerswearrespiratorswhenevertheworkplacefiberconcentration is unknown or when airborneconcentrationsexceed0.5f/cm3.ThisexposureguidelinewasestablishedbytheRCFConOc-tober 31, 1997, and replaces the previous ex-posureguidelineof1f/cm3setbytheRCFCin1991.
Beforethisagreement,theOSHAGeneralIn-dustryStandardwasmostapplicabletoRCFs,requiringthataworker’sexposuretoairbornedust containing <1% quartz and no asbestosbelimitedtoan8-hrPELof5mg/m3forrespi-rabledustand15mg/m3fortotaldust[29CFR1910.1000].
NIOSH has not previously commented onoccupational exposure to RCFs. However, inaddressing health hazards for another SVF(fibrousglass),NIOSH[1977] recommendedanexposurelimit(REL)of3f/cm3asaTWAfor glass fibers with diameters ≤3.5 µm and
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7 ■Exisiting Standards and Recommendations
Table 7–1 . Occupational exposure limits and guidelines pertaining to RCFs*, by country
Country Regulated substance Exposure limit†
Australia Syntheticmineralfibers 0.5f/cm3
Inspirabledust 2mg/m3
Austria Totaldust(listssuperfinefibersassuspectedcarcinogen) 10mg/m3
Canada RCFs 0.5f/cm3
Denmark Manmademineralfibers 1f/cm3
Totaldust(nonstationaryworksite) 5mg/m3
Finland Glasswoolandmineralwool 10mg/m3
France Generaldust,mineralwool 10mg/m3
Germany Syntheticvitreousfibers 0.5f/cm3
Netherlands RCFs 1f/cm3
NewZealand Syntheticmineralfibers 1f/cm3
Norway Syntheticmineralfibers 1f/cm3
Poland Glasswool 2f/cm3
Totaldust 4mg/m3
Sweden Syntheticinorganicfibers 1f/cm3
UnitedKingdom[HSE2004] Machine-mademineralfibers(exceptRCFsandspecial-
purposefibers)
2f/cm3
RCFs 1f/cm3
Totaldust(gravimetriclimit) 5mg/m3
UnitedStates:ACGIH RCFs 0.2f/cm3
ATSDR[2002]‡ RCFs 0.03f/cm3
NIOSH§ RCFs 0.5f/cm3
Glassfibers,otherSVFs[NIOSH1977] 3f/cm3
Totalfibrousglass 5mg/m3
OSHA[2002] RCFs 0.5f/cm3
Respirabledust(<1%quartz,noasbestos) 5mg/m3
Totaldust(<1%quartz,noasbestos) 15mg/m3
Source:AdaptedandupdatedfromU.S.Navy[DOD1997].*Abbreviations:ACGIH=AmericanConferenceofGovernmentalIndustrialHygienists;ATSDR=AgencyforToxicSubstancesDisease
Registry;NIOSH=NationalInstituteforOccupationalSafetyandHealth;OSHA=OccupationalSafetyandHealthAdministration;
RCFs=refractoryceramicfibers;REL=recommendedexposurelimit;TWA=time-weightedaverage.†8-hrTWAunlessotherwisespecified.‡Inhalationminimalrisklevelbasedongeneralpublichealthassumptions,notoccupationalexposure.
§TheNIOSHRELisestablishedasaTWAforuptoa10-hrworkshiftina40-hrworkweek.
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7 ■Exisiting Standards and Recommendations
ceramicfibers,includingRCF,as“possiblycar-cinogenictohumans(Group2B)”[IARC1988,2002]. The IARC characterization was basedon“sufficientevidenceforthecarcinogenicityofceramicfibersinexperimentalanimals”andalackofdataonthecarcinogenicityofceramicfiberstohumans[IARC1988,2002].DECOS[1995]determinedthat“RCFsmayposeacar-cinogenic risk forhumans,” and set ahealth-based recommended occupational exposurelimitof1f/cm3.
TheGermanCommissionfortheInvestigationofHealthHazardsofChemicalCompoundsinthe Work Area published a review of fibrous
dusts[Pott1997]classifyingRCFsascategoryIIIA2,citing“positiveresults(forcarcinogenic-ity) from inhalation studies (often supportedbytheresultsofotherstudieswithintraperito-neal,intrapleural,orintratrachealadministra-tion).”
IntheUnitedKingdom,theHealthandSafetyCommissionof theHealthandSafetyExecu-tivehasestablishedamaximumexposurelimitforRCFsof1.0f/mlofair,withtheadditionaladvisory toreduceexposures to the lowestasreasonably practicable concentration basedonthecategory2carcinogenclassificationforRCFs[HSE2004].
Refractory Ceramic Fibers 99
8 Basis for the Recommended Standard
ditions(includingdyspnea,wheezing,coughing,andpleurisy)observed inRCFworkers tobeadversehealtheffectsassociatedwithexposuretoairborneRCFs[Lemastersetal.1998;Lock-eyetal.1993;Trethowanetal.1995;Burgeetal.1995;Cowieetal.1999].
AnassociationbetweeninhalingRCFsandfi-brotic or carcinogenic effects has been docu-mented in animals, but no evidence of sucheffectshasbeenfoundinworkers intheRCFmanufacturing industry. The lack of such anassociation could be influenced by the smallpopulationofworkersinthisindustry,thelonglatency period between initial exposure anddevelopmentofmeasurableeffects,thelimitednumber of persons with extended exposureto elevated concentrations of airborne fibers,anddecliningoccupational exposureconcen-trations. However, the evidence from animalstudies suggests that RCFs should be consid-eredapotentialoccupationalcarcinogen.ThisclassificationisconsistentwiththeconclusionsofACGIH,EPA,DECOS,andIARC.(Seedis-cussioninChapter7.)
Given these considerations, the NIOSH ob-jective in developing an REL for RCFs is toreduce the possible risk of lung cancer andmesothelioma. In addition, maintaining ex-posuresbelowtheRELwillalsohelptopre-ventotheradverseeffects,includingirritationoftheskin,eyes,andrespiratorytract inex-posedworkers.ToestablishanRELforRCFs,NIOSHtookintoaccountnotonlytheanimaland human health data but also exposure
8.1 BackgroundIntheOccupationalSafetyandHealthActof1970(PublicLaw91–96),CongressmandatedthatNIOSHdevelopandrecommendcriteriaforidentifyingandcontrollingworkplacehaz-ardsthatmayresultinoccupationalillnessorinjury. In fulfillingthismission,NIOSHcon-tinues to investigate the potential health ef-fects of exposure to naturally occurring andsynthetic airborne fibers. This interest stemsfrom the results of research studies confirm-ingasbestosfibersashumancarcinogens.Sig-nificant increases in the production of RCFsduringthe1970sandconcernsaboutpotentialhealth effects led to experimental and epide-miologicalstudiesaswellasworkerexposuremonitoring. Chronic animal inhalation stud-iesdemonstratedthecarcinogenicpotentialofRCFs,withastatisticallysignificantincreaseintheincidenceoflungcancerormesotheliomain two laboratory species—ratsandhamsters[Bunnetal.1993;Mastetal.1995a;McConnellet al. 1995]. Evidence of pleural plaques ob-servedinpersonswithoccupationalexposuresto airborne RCFs is clinically similar to thatobservedinasbestos-exposedpersonsaftertheinitial years of their occupational exposuresto asbestos [Hourihane et al. 1966; Becklakeetal.1970;Dementetal.1986].NIOSHcon-sidersthediscoveryofpleuralplaquesinU.S.studies of RCF manufacturing workers to beasignificantfindingbecausetheplaqueswerecorrelatedwithRCFexposure[Lemastersetal.1994;Lockeyetal.1996].Inaddition,NIOSHconsiders therespiratorysymptomsandcon-
100 Refractory Ceramic Fibers
8 ■Basis for the Recommended Standard
information describing the extent to whichRCF exposures can be controlled at differ-ent workplaces. On the basis of this evalua-tion, NIOSH considers an REL of 0.5 f/cm3(asaTWAforupto10hr/dayduringa40-hrworkweek) to be achievable for most work-placeswhereRCFsorRCFproductsareman-ufactured,used,orhandled.Maintainingex-posuresattheRELwillminimizetheriskforlungcancerandreduce theriskof irritationoftheeyesandupperrespiratorysystem.Theresidual risks of lung cancer at the REL areestimated tobe0.073 to1.2per1,000basedonextrapolationsofriskmodelsfromMool-gavkaretal. [1999]andYuandOberdörster[2000].
The risk for mesothelioma at the REL of0.5 f/cm3 is not known but cannot be dis-counted.Evidencefromepidemiologicstudiesshowed that higher exposures in the past re-sultedinpleuralplaquesinworkers,indicatingthatRCFsdoreachpleuraltissue.Bothimplan-tationstudiesinratsandinhalationstudiesinhamstershaveshownthatRCFfiberscancausemesothelioma. Because of limitations in thehamsterdata,theriskofmesotheliomacannotbequantified.However,thefactthatnomeso-theliomahasbeenfoundinworkersandthatpleuralplaquesappear tobe less likely tooc-curinworkerswithlowerexposuressuggestsalowerriskformesotheliomaattheREL.
Because residual risks of cancer (lung can-cer and pleural mesothelioma) and irrita-tion may exist at the REL, NIOSH furtherrecommends that all reasonable efforts bemadetoworktowardreducingexposurestolessthan0.2f/cm3.Atthisconcentration,therisksoflungcancerareestimatedtobe0.03to 0.47 per 1,000 based on extrapolationsof risk models from Sciences International[1998],Moolgavkaretal.[1999],andYuandOberdörster[2000].
MaintainingairborneRCFconcentrationsatorbelowtheRELrequirestheimplementationofacomprehensivesafetyandhealthprogramthatin-cludesroutinemonitoringofworkerexposures,installationandroutinemaintenanceofengi-neeringcontrols,andworkertrainingingoodwork practices. To ensure that worker expo-suresareroutinelymaintainedbelowtheREL,NIOSHrecommendsthatanALof0.25f/cm3bepartoftheworkplaceexposuremonitoringstrategytoensurethatallexposurecontrolef-forts(e.g.,engineeringcontrolsandworkprac-tices) are inplaceandworkingproperly.ThepurposeoftheAListoindicatewhenworkerexposures to RCFs may be approaching theREL.ExposuremeasurementsatorabovetheALindicateahighdegreeofcertaintythatcon-centrations of RCFs exceed the REL. TheALisastatisticallyderivedconceptpermittingtheemployer to have confidence (e.g., 95%) thatif exposure measurements are below the AL,only a small probability exists that the expo-sureconcentrationsareabovetheREL.Whenexposures exceed the AL, employers shouldtake immediate action (e.g., determine thesourceofexposure,identifymeasuresforcon-trollingexposure)toensurethatexposuresaremaintainedbelowtheexposurelimit.NIOSHhasconcludedthatanALallowsfortheperi-odic monitoring of worker exposures in theworkplacesothatresourcesdonotneedtobedevoted to conducting daily exposure mea-surements.TheALconcepthasbeenaninte-gral element of recommended occupationalstandards in NIOSH criteria documents andin comprehensive standards promulgated byOSHAandMSHA.
8.2RationalefortheRELTherecommendationtolimitoccupation-alexposurestoairborneRCFstoaTWAof0.5f/cm3isbasedondatafromanimalandhuman studies, risk assessments, and the
Refractory Ceramic Fibers 101
8 ■Basis for the Recommended Standard
availabilityofmethodstocontrolRCFex-posures at the REL in many workplaces.EstablishingtheRELforRCFsisconsistentwith the mission of NIOSH mandated intheOccupationalSafetyandHealthActof1970. This Act states that NIOSH is obli-gatedto“developcriteriadealingwithtoxicmaterialsandharmfulphysicalagentsandsubstances which will describe exposurelevels that are safe for various periods ofemployment, includingbutnot limited tothe exposure levels at which no employeewill suffer impaired health or functionalcapacitiesordiminishedlifeexpectancyasaresultofhisworkexperience.”Thecarci-nogenicityfindingsfromthechronicnose-onlyinhalationassaysofRCF1inratsandhamsters [Mast et al. 1995a,b; McConnellet al. 1995] warrant concern about pos-sible health effects in workers exposed toRCFs. Although no increase in lung can-cer or mesothelioma mortality has beenobserved in worker populations exposedtoRCFs,radiographicanalysesindicateanassociation between pleural changes (in-cluding pleural plaques) and RCF expo-sure [Lemasters et al. 1994; Lockey et al.1996; Cowie et al. 1999, 2001]. Both theU.S. [Lockey et al. 1993; Lemasters et al.1998]and theEuropean[Trethowanetal.1995;Burgeetal.1995;Cowieetal.1999,2001] studies have found RCF-associatedrespiratory symptoms, pulmonary func-tionreductions,andpleuralabnormalitiesamongRCFproductionworkers.
Severalindependentevaluationshavequantita-tivelyestimatedtheriskoflungcancerforwork-ersexposedtoRCFsatvariousconcentrations[DECOS1995;Fayerweatheretal.1997;Mool-gavkaretal.1999].NIOSHevaluatedthesestud-iestodeterminewhetheranappropriatequali-tativeorquantitativeassessmentoflungcancerrisk could be achieved. In addition, exposureinformation was collected during the 5-year
monitoringperiodcoveredundertheconsentagreementbetweenRCFCandEPA[Maximetal. 1994,1997,1998].NIOSHused the expo-sure informationtoevaluate the feasibilityofcontrolling workplace exposures at manufac-turingandend-use facilitieswhereRCFsandRCFproductsarehandled.
8.2.1 Carcinogenesis in Animal Studies
ChronicinhalationstudieswithRCFsdemon-stratesignificantincreasesintheincidenceofmesotheliomainhamstersandlungcancerinrats.Tables8–1through8–4presentasynop-sisofthemajorfindingsofthesestudies[Mastetal.1995a,b;McConnelletal.1995].Resultsfrom chronic animal inhalation studies withchrysotileandamositearealsopresented(i.e.,results for the positive control groups); thesedataprovideareferencepointfordeterminingtherelativetoxicityofRCFs[Mastetal.1995a;McConnelletal.1999].
Chronic inhalation exposure to RCF1 at30 mg/m3 (187 WHO f/cm3) induced a13%(16/123)incidenceoflungtumorsinF344rats[Mastetal.1995a].Theincidenceoflungcancerat lowerdosesdidnotshowastatisti-callysignificantdifferencefromtheunexposedcontrolgroup.Lungfiberburdensinthemulti-dosechronicratstudyrevealedadose-responserelationship [Mast et al. 1995b]. In the rat,16 mg/m3 (120 WHO f/cm3) appeared tobe the NOAEL for lung cancer and 3 mg/m3
(26WHO f/cm3) appeared to be the NOAELfor fibrosis. Although it has been suggestedthatfibrosisinanimalsisaprecursortocarci-nogenesis,adefinitelinkhasnotbeenshownforRCFsorotherfibers.NolungcancerswerefoundinhamstersexposedtoRCF1[McCon-nelletal.1995].
102 Refractory Ceramic Fibers
8 ■Basis for the Recommended Standard
Table 8–1 . Doses and dimensions of RCFs* in chronic inhalation studies with F344 rats
Dose
(mg/m3)
WHO Total % Fibers >20 µm
long
Mean fiber diameter†
Mean fiber length†
Reference Fiber type
f/cm3 SD
f/cm3 SD
µm SD µm SD
Mastetal.
1995a
RCF1
30
187 53
234 35
43
0.98 0.61
22.3 17.0
Mastetal.
1995b
RCF1 6
9
3
0
120 35
75 35
26 12
0 —
162 37
91 34
36 17
0 —
43
—
—
—
0.98 0.61
——
——
——
22.3 17.0
——
——
——
Mastetal.
1995a
Chrysotile
asbestos
10 1.06+1.14×10
4 1×10
5 NR 0.10 0.15 2.2 3.0
*Abbreviations:NR=notreported;RCFs=refractoryceramicfibers;SD=standarddeviation;WHO=WorldHealthOrganization.†Arithmeticmean.
Table 8–2 . Results of RCF* chronic inhalation studies with F344 rats
Dose
(mg/m3)
Time of first
occurrence (months) Lung
neoplasms
Pleural
mesotheliomasWHO Interstitial
fibrosis
Pleural
fibrosisReference Fiber type f/cm3 SD Number % Number %
Mastetal.
1995a
RCF1
30
187 53
6
9
16/123 13
2/123 1.6
Mastetal.
1995b
RCF1 16
9
3
0
120 35
75 35
26 12
0 —
12
12
None
None
12
18
None
None
2/124 1.6
5/127 3.9
2/123 1.6
1/129 0.8
0—
1/127 0.8
0 —
0 —
Mastetal.
1995a
Chrysotile
asbestos
10 1.06+1.14×104 3 9 13/69 18.8 1/69 1.4
*Abbreviations:RCF=refractoryceramicfiber;SD=standarddeviation;WHO=WorldHealthOrganization.
Refractory Ceramic Fibers 103
8 ■Basis for the Recommended Standard
Table 8–3 . Doses and dimensions of RCF* in chronic inhalation studies with Syrian golden hamsters
Dose
(mg/m3)
WHO Total% Fibers
>20 µm longMean fiber diameter†
Mean fiber length†
Reference Fiber type f/cm3 SD f/cm3 SD % f/cm3 SD µm SD µm SD
McConnell etal.1995
RCF1
30
215 56
256 58
43 — —
0.940.63
22.1 16.7
McConnell etal.1995
Chrysotile asbestos
10 3.0×103 1.4×10
3 8.4×1049.0×10
4 NR — — 0.090.06 1.68 2.71
McConnell etal.1999
Amosite asbestos
7.1
3.7
0.8
263 90
165 61
36 23
NR —
— —
— —
~26 69 24
~233814
~28106
0.600.25
——
——
13.4 16.7
——
——
*Abbreviations:NR=notreported;RCFs=refractoryceramicfibers;SD=standarddeviation;WHO=WorldHealthOrganization.†Arithmeticmean.
Table 8–4 . Results of RCF* chronic inhalation studies with Syrian golden hamsters
Time of first occurrence
Dose
(mg/m3)
WHO Interstitial
fibrosis
Pleural
fibrosis
Hamsters with pleural mesotheliomas†
Reference Fiber type f/cm3 SD Number %
McConnell etal.1995
RCF1
30
215 56
6months
6months
42/123 41.6
McConnell etal.1995
Chrysotile asbestos
10
3.0×10
3 1.4×10
3
3months
6months
0 —
McConnell
Amosite
7.1
263 90
13weeks
13weeks
17/87 19.5 etal.1995 asbestos 3.7 165 61 13weeks 13weeks 22/85 25.9
0.8 36 23 13weeks 13weeks 3/83 3.6
*Abbreviations:RCF=refractoryceramicfiber;SD=standarddeviation;WHO=WorldHealthOrganization.†Nolungneoplasmsweredetected.
104 Refractory Ceramic Fibers
8 ■Basis for the Recommended Standard
Chronic inhalation exposure to RCF1 at30 mg/m3 induced a 41% (42/102) incidenceof mesotheliomas in Syrian golden ham-sters [McConnell et al. 1995]. Determininga dose-response relationship for inducingmesotheliomaisnotpossiblebasedoncurrent-lyavailabledatabecauseofthesingleexposuredosetestedinthehamsterandbecauseofthelow, sporadic occurrence of mesothelioma intheexposedrats[Mastetal.1995a].Yettheoc-currenceofmesotheliomasintheratandthehighincidenceinthehamsterarebiologicallysignificantbecausethespontaneousincidenceofmesotheliomasinratsandhamstershashis-toricallybeenverylow[AnalyticalSciencesIn-corporated1999].
Toassessthesignificanceofthemesotheliomaincidence observed in RCF-exposed ham-sters, these results were compared with thoseobtainedfromhamstersthatwereexposedtochrysotile asbestos and were used as positivecontrolsforthestudy[McConnelletal.1995](seeTables8–3and8–4).However,thechrysotile-exposedhamstersfailedtodevelopanytumorsand therefore could not be considered truepositivecontrols.Basedontheseresults,apo-tencyrankingcouldnotbeassignedforRCFsrelativetochrysotile,sincethecarcinogenicre-sponserateforthelatterwaszerointhisstudy.Thetwofiberstestedalsodifferedwithregardtotheirdoseandfiberdimension.
TheMcConnelletal.[1999]studyofhamstersexposed to amosite asbestos provides dose-responsedata for comparisonwith theRCF1dataofMcConnelletal.[1995](SeeTables8–3and8–4.).TheseseparatestudiesexaminedtheeffectsofRCF1oramositeasbestosinhamstersusing relatively similar exposure conditions,experimentalconditions,andfiberdimensions[McConnell et al. 1995, 1999]. Exposure to263 WHO f/cm3 and 165 WHO f/cm3 ofamosite asbestos induced pleural mesothe-liomas in 20% and 26% of the hamsters,
respectively[McConnelletal.1999].Aconcen-trationof215RCF1WHOf/cm3inducedme-sotheliomasin41%ofhamsters[McConnelletal.1995].Interstitialandpleuralfibrosiswerefirst observed at 13 weeks following amositeasbestos exposure and at 6 months followingRCF1exposure.Althoughaveragefiberdimen-sionsfortheRCF1andamositeasbestossam-plesweresimilar,theRCF1samplecontainedahigherpercentageoffiberslongerthan20μm[McConnell et al. 1995, 1999]. Longer fibershavebeenassociatedwithincreasedtoxicityinexperimentalanimalstudies[Davisetal.1986;Pottetal.1987;DavisandJones1988;Warheit1994;Blakeetal.1998].
Resultsfromadose-responseanalysisusingthemesotheliomadatafromtheRCFandamositeasbestoshamsterstudies[McConnelletal.1995,1999] indicated that the carcinogenic potencyestimates for RCFs ranged from about half totwotimesthecarcinogenicpotencyestimatesforamositeasbestos[Dankovic2001](seeSection5.1.2).Thisanalysismaynotpredictthemeso-theliomariskinhumans,sinceRCF1containedagreaterpercentageoffiberslongerthan20µmand because of differences in fiber durability.Amositeasbestosisamoredurablefiberwithalongerinvivohalf-lifethanRCF1[Maximetal.1999b;Hesterbergetal.1993](seeTable8–5).YetRCFsaremoredurableandlesssolublethanmanyothertypesofSVFsthathavenotdemon-stratedcarcinogenicityinexperimentalstudies.Thischaracteristicissignificant,asthedurabil-ityofasbestosandSVFs(includingRCFs)maybelinkedtotheriskoflungcancerinanimalschronicallyexposedtothesefibers[Bignonetal.1994;BenderandHadley1994;Hammadetal.1988;Luotoetal.1995].Becauseofthelongla-tencyperiodforthedevelopmentofmesothelio-masinhumans,Berry[1999]hypothesizedthatfibersofsufficientdurabilityareneededtocausethisdiseaseinhumans.ExtrapolationoftheRCFdose-responsedata for lungcancerandmeso-thelioma inexposedrodents should take into
Refractory Ceramic Fibers 105
8 ■Basis for the Recommended Standard
Table 8–5 . Dissolution constant (Kdis
) and weighted in vivo half-life (t0 .5
) of amosite asbestos and RCF1
Fiber type Kdis
(ng/cm2 per hr) t0 .5
(days)
RCF1
7.6
89.6
Amositeasbestos 1.3 418.0
Source:AdaptedfromMaximetal.[1999].*Abbreviation:RCF=refractoryceramicfiber.
account the durability of RCFs in humans.Someevidenceindicatesthatratsarelesssen-sitivethanhumanstothedevelopmentoflungcancerandmesotheliomafromexposuretoas-bestosandmaythereforerepresentaninappro-priatemodelforhumanriskassessment.Pottetal.[1994]hypothesizedthatinchronicinhala-tionstudies,ratsmayhavealowersensitivitytoinorganicfibertoxicitythanhumans.Thelungcancerriskfrominhalingasbestosmaybetwoordersofmagnitudelowerinratsthaninhu-mans,andthemesotheliomariskfrominhalingasbestosmaybethreeordersofmagnitudelow-erforrats.RödelspergerandWoitowitz[1995]measured amphibole fiber concentration inthelungtissuesofhumanswithmesotheliomaand compared the results with fiber burdensreported inrats.Asignificantly increasedOR(OR=4.8, 95%; CI=1.05–21.7) for mesothe-lioma was seen in humans with amphiboleconcentrations between 0.1 and 0.2 fiber/μgof dried lung tissue. The lowest tissue con-centration reported to produce a significantcarcinogenic response in rat inhalation stud-iesofamphiboles(specificallycrocidolite)was1,250fibers/μgofdriedlungtissue.Bycompar-ingtheseresults,RödelspergerandWoitowitz[1995]estimatedthathumansareatleast6,000timesmoresensitivethanratstoagiventissueconcentrationofamphibolefibers.
This work is refuted by other scientists whofavortheratasanappropriatemodelforeval-uating the risk evaluation of lung cancer inhumans[MaximandMcConnell2001].Limi-tations of the Rödelsperger and Woitowitz[1995]andPott[1994]analyses(discussedear-lier)includethelackofadose-responseanaly-sis, analysis of only one epidemiologic study,inadequatecomparisonsofexposureduration,lackofaccountingforthepotentiallymultipli-cativeeffectofsmokingandasbestosexposure,lackofconsiderationoflatencyandclearance,anddifferentfibermeasurementtechniques.
In summary, multiple factors affecting thecomparabilityofdifferentfibertypesandani-malmodelsreportedintheliteraturemakeitdifficulttodeterminewhetherthecarcinogen-icpotencyofRCFsinanimalsissimilartothatin humans. Extrapolation of the animal datatohumansisfurthercomplicatedbyalimitedunderstandingofthemechanismsoffibertox-icity. Consequently, any extrapolation of thecancerriskfoundinanimalsexposedtoRCFsmustaccountfordifferencesbetweenhumansand rodents with regard to fiber depositionandclearancepatterns,uncertaintyabout theroleofRCFdurabilityforpotentiatinganad-verseeffect,andpossiblespeciesdifferencesinsensitivitytofibers.
106 Refractory Ceramic Fibers
8 ■Basis for the Recommended Standard
8.2.2 Health Effects Studies of Workers Exposed to RCFs
Two major research efforts evaluated themorbidityofworkersexposedtoairbornefi-bersintheRCFmanufacturingindustry.OnestudywasconductedintheUnitedStatesandtheotherinEurope.Theobjectiveofeachwastoevaluatetherelationshipbetweenoccupa-tional exposure to RCFs and potential ad-verse health effects. These studies containedmultiplecomponentsincludingstandardizedrespiratory and occupational history ques-tionnaires, chest radiographs, pulmonaryfunctiontestsofworkers,andairsamplingtoestimate worker exposures. The first studiesof European plants were conducted in 1986and included current workers at seven RCFmanufacturing plants [Rossiter et al. 1994;Trethowan et al. 1995; Burge et al. 1995]. Afollowup cross-sectional study conducted in1996 evaluated the same medical endpointsinworkersfromsixofthesesevenEuropeanmanufacturing plants (one plant had ceasedoperation) [Cowie et al. 1999, 2001]. Cur-rentaswellasformerworkerswereincludedas study subjects in the followup study. ThestudiesofU.S.plantsbegan in1987and in-volvedevaluationsofcurrentworkersatfiveRCFmanufacturingplantsandformerwork-ersattwooftheplants[Lemastersetal.1994,1998, 2003; Lockey et al. 1993, 1996, 1998,2002].IntheUnitedStates,theearliestcom-mercial production of RCFs and RCF prod-uctsbeganin1953. InEurope,RCFproduc-tionbeganin1968.ThedemographicsoftheU.S. and European populations were similarat the time they were studied, but the aver-ageageanddurationofemploymentfortheU.S.workerswereslightlyhigherthanfortheworkforce in the 1986 European studies be-cause of the earlier development of this in-dustryintheUnitedStates.
8.2.2.1 Pleural changes in humans
TheradiographicanalysesoftheU.S.and1996European populations in RCF manufactur-ing detected an association between pleuralchanges and RCF exposure [Lemasters et al.1994; Lockey et al. 1996; Cowie et al. 1999,2001]. In the initial European studies, Tre-thowanetal.[1995]foundpleuralabnormali-ties in a small number of RCF workers whohad other confounding exposures that didnot include asbestos. Differences observed inpleural abnormalities between the U.S. andEuropeanworkerpopulationsmaybe relatedto the latency of exposure required to causespecificpleuralchanges[Hillerdal1994;Beginetal.1996],especially the formationofpleu-ralplaques,whichwerefirstobservedinstud-ies of the U.S. RCF manufacturing industry,with its longer latency period. Historical airsamplingdataalsoindicatethatairbornefiberconcentrationsweremuchhigherinearlyU.S.RCF manufacturing. Therefore, in additionto their longeroverall latency,RCFmanufac-turing workers in the United States probablyhad generally higher exposures in the earlyyearsoftheindustrythandidtheirEuropeancounterparts.ThesefactorsmightexplaintheappearanceofRCF-associatedpleuralplaquesin the U.S. studies before their detection intheEuropean studies.TheU.S. and1986Eu-ropeanstudiesyieldedlittleevidenceofanas-sociation between radiographic parenchymalopacitiesandRCFexposure.IntheU.S.study,smallopacitieswererare,withonlythreecasesnoted in one report [Lockey et al. 1996] andonly one case (with small rounded opacitiesofprofusioncategory3/2attributabletopriorkaolinminework)notedintheother[Lemas-ters et al. 1994]. Small opacities of profusioncategory1/0orgreaterweremorefrequentintheEuropeanstudybyTrethowanetal.[1995],but confounding exposures were believedto account for many of these cases. The re-sultsofstatisticalanalysesindicatedeitherno
Refractory Ceramic Fibers 107
8 ■Basis for the Recommended Standard
associationwithRCFexposure[Trethowanetal. 1995] or an association slightly suggestiveofanRCFexposureeffect[Rossiteretal.1994].InamorecomprehensiveevaluationoftheEu-ropean study population, small opacities ofcategory1/0orgreaterwerepositivelyassoci-atedwithRCFexposuresthatoccurredbefore1971[Cowieetal.1999].
8.2.2.2 Respiratory symptoms, irritation, and other conditions in humans
InboththeU.S.[Lockeyetal.1993;Lemastersetal.1998]andtheEuropean[Trethowanetal.1995;Burgeetal.1995;Cowieetal.1999,2001]stud-ies,occupationalexposuretoRCFswasassociatedwith various reported respiratory conditions orirritationsymptomsafteradjustingfortheeffectsofsmoking.WorkerexposuretoRCFsatconcen-trations of 0.2 to 0.6 f/cm3 was associated withstatistically significant increases in eye irritation(OR=2.16, 95% CI=1.32–3.54), stuffy nose(OR=2.06, 95% CI=1.25–3.39), and dry cough(OR=2.53, 95% CI=1.25–5.11) compared withexposuretoconcentrationslowerthan0.2f/cm3[Trethowanet al. 1995].Between the0.2 to0.6 f/cm3and>0.6f/cm3RCFexposuregroups,a statistically significant increase occurred inORs for wheezing (P<0.0001), grade 2 dyspnea(P<0.05),eye irritation(P<0.0001),andskinir-ritation(P<0.0001)—butnotforstuffynose[Tre-thowanetal.1995].Lockeyetal.[1993]foundthatdyspneawassignificantlyassociatedwithcumula-tiveexposureto>15fiber-months/cm3(i.e.,>1.25fiber-year/cm3)relativetocumulativeexposureto≤15fiber-months/cm3(dyspneagrade1–OR=2.1,95%CI1.3–3.3;dyspneagrade2–OR=3.8,95%CI1.6–9.4)afteradjustingforsmokingandotherpotential confounders. Lockey et al. [1993] alsofound a statistically significant association be-tween cumulative RCF exposure and pleurisy(OR=5.4,95%CI=1.4–20.2),andanelevatedbutnonsignificant association between cumulativeRCF exposure and chronic cough (OR=2.0,95%CI=1.0–4.0).Lemastersetal.[1998]also
noted associations (P<0.05) between employ-mentinanRCFproductionjobandincreasedprevalence of dyspnea and the presence of atleast one respiratory symptom after adjustingthedataforconfounders.Recurrentchestillnessin the European study population was associ-atedwiththeestimatedcumulativeexposuretothoracic-sizedfibersbutwasmorestronglyas-sociatedwithestimatedcumulativeexposuretothoracic-sizeddust[Cowieetal.1999,2001].
Incross-sectionalanalyses,boththeU.S.[Lock-ey et al. 1998; Lemasters et al. 1998] and the1986European[Trethowanetal.1995;Burgeetal.1995]studiesfoundthatcumulativeRCFexposure is associated with pulmonary func-tion decrements among current and formersmokers. Lemasters et al. [1998] also foundstatistically significant deficits in pulmonaryfunction measures for nonsmoking femaleworkers. The decreased pulmonary functionin the European study population remainedsignificantly associated with cumulative RCFexposure,evenaftercontrollingforcumulativedust exposure [Burge et al. 1995]. The 1996European study found pulmonary functiondecrements only in current smokers [Cowieet al. 1999, 2001]. In a longitudinal analysisofdatafrommultipleserialpulmonaryfunc-tiontests,Lockeyetal.[1998]concludedthatthemorerecentRCFconcentrationsoccurringafter1987werenotassociatedwithdecreasedpulmonaryfunction;rather,decreases inpul-monaryfunctionweremorecloselyrelatedtotypically higher concentrations that occurredbeforethistimeperiod.TheU.S.andEuropeanstudiessuggestthatdecrementsinpulmonaryfunction observed primarily in current andformersmokersareevidenceofaninteractiveeffectbetweensmokingandRCFexposure.
8.2.3 Carcinogenic Risk in Humans
Moolgavkaretal.[1999]derivedriskestimatesforlungcancerinhumansonthebasisofthe
108 Refractory Ceramic Fibers
8 ■Basis for the Recommended Standard
resultsfromthetwochronicbioassaysofRCFsinmaleFischer344rats[Mastetal.1995a,b].Several models (linear, quadratic, exponen-tial)wereusedtoestimateandcomparerisksusing reference populations comprised of ei-theranonsmokingACScohortoracohortofsteelworkersnotexposedtocokeovenemis-sions (seeTable5–10 for riskestimates).Theexponentialmodelprovidedthebeststatisticalfitofthedata.Thelinearmodelprovidedthehighestestimatesofhuman lungcancer risksfrom exposure to RCFs when used with thereferent steel workers cohort (considered tobemostrepresentativeofworkersexposedtoRCFs because it includes blue collar workerswhosmoke).Lungcancerriskestimateswerecalculatedusingeachmodelatexposurecon-centrationsof0.25f/cm3,0.5f/cm3,0.75f/cm3,and1.0f/cm3.TheRCF-relatedlungcancerriskdeterminedfromthelinearmodelforthelow-estconcentration(0.25 f/cm3)was0.27/1,000forthecohortofsteelworkerscomparedwith0.036/1,000using theexponentialmodel and0.00088/1,000 for the quadratic model whenusingthesamereferentpopulation.
The risk estimates incorporated multiple as-sumptions, includingahumanbreathingrateof 13.5L/min (considered light work) andmultiple criteria for defining the length oftimeaworkercouldbeexposedtoRCFsoveraworkinglifetime.Higherriskestimatescouldbe expected if the assumptions more closelyrepresentedthoseusedbyNIOSHandOSHA:(1) a human breathing rate of 20 L/min and(2) a worker exposure duration of 8 hr/day,5days/wk, 50 wk/yr, from age 20 to 65 withtheriskcalculatedbeyondage70(e.g.,toage85).Furthermore,thecalculatedriskestimatescouldbeanunderestimationofthelungcancerrisk to humans because the models assumedthatthetissuesensitivitytoRCFsintheratisequal to that in humans. Although the lungcancerriskestimatesderivedfromtheratdataare reason for concern, estimates of human
riskformesotheliomafromthehighincidence(41%)ofmesotheliomainhamsterscannotbeappropriatelymodeledsinceonlyasingleex-posurewasadministeredinthestudy.Primar-ily on the basis of chronic animal inhalationstudies [Mastetal.1995a,b;McConnell etal.1995],NIOSHconcludesthatRCFsareapo-tentialoccupationalcarcinogen.Furthermore,theevidenceofpleuralplaques [Lemastersetal.1994;Lockeyetal.1996]observed inper-sonswithoccupationalexposurestoairborneRCFsisclinicallysimilartothatobservedinas-bestos-exposedpersonsaftertheinitialyearsoftheiroccupationalasbestosexposures[Houri-haneetal.1966;Becklakeetal.1970;Dementetal.1986].NIOSHconsidersthediscoveryofpleuralplaquesinU.S.studiesofRCFmanu-facturing workers to be a significant findingbecausetheplaqueswerecorrelatedwithRCFexposure [Lemasters etal. 1994; Lockey et al.1996]. In addition, NIOSH considers the re-spiratorysymptomsandconditions(includingdyspnea,wheeze,cough,andpleurisy)[Lemas-tersetal.1998;Lockeyetal.1993;Trethowanetal.1995;Burgeetal.1995;Cowieetal.1999]inRCFworkerstobeadversehealtheffectsthathavebeenassociatedwithexposuretoairbornefibersofRCFs.
Insufficient evidence exists to document anassociation between fibrotic or carcinogeniceffectsandtheinhalationofRCFsbyworkersin the RCF manufacturing industry thoughthese effects have been demonstrated in ani-mal studies.The lackofanobservedassocia-tion between RCF exposure and these effectsamong workers could be affected by one ormorefactors, includingseveralrelatingtothestudy population: the relatively small cohort,the proportion of workers with short tenurerelativetowhatmightbeexpected(ontheba-sisofanasbestosanalogy)intermsofdiseaselatency, and workers with limited cumulativeexposurestoRCFs.
Refractory Ceramic Fibers 109
8 ■Basis for the Recommended Standard
8.2.4 Controlling RCF Exposures in the Workplace
Table 8–6 summarizes exposure monitoringdata collected by the RCFC under a consentagreementwiththeEPA[Everest1998;Maximetal.1997].Thesedataindicatethatexposuresto RCFs during 1993–1998 had an AM fiberconcentration of about 0.3 f/cm3 for manu-facturing and nearly 0.6 f/cm3 for end users.Maximetal.[1997,1999a]reportedresultsforboth manufacturing and end-use sectors inwhich airborne fiber concentrations through1997werereducedtoanAM<0.3–0.6f/cm3.
Theexposuremonitoringdatacollectedaspartof theRCFC/EPAconsentagreementprovideassurance that when appropriate engineeringcontrolsandworkpracticesareused,airborneexposuretoRCFscanbemaintainedformostfunctionaljobcategories(FJCs)attheRELof0.5f/cm3.Formanymanufacturingprocesses,reductionsinexposureshaveresultedfromtheimproved ventilation, engineering or processchanges, and product stewardship programs[Rice et al. 1996; Maxim et al. 1999b]. ThesedataprovidethebasisfortheNIOSHdetermi-nationthataRELof0.5f/cm3asaTWAcanbeachieved.
AlthoughmanyRCFmanufacturingandend-userjobtaskshaveexposurestoRCFsatcon-centrations below 0.5 f/cm3, exposure moni-toringdataalsoindicatethatnotallFJCsmaybe able to achieve these RCF concentrationsconsistently. FJCs that currently experienceairborneAM fiber concentrations >0.5 f/cm3includefinishing(manufacturingandenduse)andremoval(enduse).Typicalprocessingdur-ingfinishingoperations(e.g.,sawing,drilling,cutting, sanding) often requires high-energysourcesthattendtogeneratelargerquantitiesofairbornedustandfibers.ForRCFinsulationremoval, activities are performed at remotesiteswhereconventionalengineeringcontrolsandfixedventilationsystemsaremoredifficult
to implement. For some operations, such asremovalofRCFinsulationtilesfromfurnaces,the release of high airborne fiber concentra-tionscanoccur.However,removalofRCFin-sulationtilesisnotroutineandisgenerallyac-complishedinashortperiodoftime.Workersalmost universally wear PPE and respiratoryprotectionduringthesejobtasks[Maximetal.1997,1998].
NIOSHacknowledgesthatthefrequentuseofPPE, including respirators, may be requiredforsomeworkershandlingRCFsorRCFprod-ucts.ThefrequentuseofPPEmayberequiredduring job tasks forwhich(1)routinelyhighairborne concentrations of RCF (e.g., finish-ing,insulationremoval)exist,(2)theairborneconcentration of RCF is unknown or unpre-dictable,and(3)jobtasksareassociatedwithhighly variable airborne concentrations be-causeofenvironmentalconditionsortheman-ner inwhichthe jobtask isperformed.InallworkenvironmentswhereRCFsorRCFprod-uctsarehandled,controlofexposurethroughtheengineeringcontrolsshouldbethehighestpriority.
8.3SummaryThe following summarize the relevant infor-mationusedasthebasisfortheNIOSHassess-mentofoccupationalexposurestoRCFs:
■ Airborne concentrations of RCFs havebeen characterized as containing fibersofdimensionsinthethoracicandrespi-rable size ranges. RCFs are among themost durable types of SVFs. In tests ofsolubility,RCFsarenearlyasdurableaschrysotile asbestos but significantly lessdurable than amphibole asbestos fiberssuchasamosite.
■ Chronic, nose-only inhalation studieswithRCFsinanimalsshowastatistically
110 Refractory Ceramic Fibers
8 ■Basis for the Recommended Standard
Table 8–6 . Airborne fiber concentrations in the RCF* industry during 1993–1998, by functional job category and production status† (f/cm3 as TWA)
Functional job category
and production status
Minimum
value
First
quartile Median
Geometric
mean
Arithmetic
mean
Third
quartile
Maximum
value
Total:
Manufacturing
Enduse
0.001
0.002
0.070
0.052
0.186
0.173
0.16
0.16
0.313
0.560
0.407
0.524
7.700
30.000
Assembly:
Manufacturing
Enduse
0.001
0.002
0.110
0.050
0.208
0.159
0.18
0.14
0.281
0.316
0.366
0.402
2.154
2.837
Auxiliary:
Manufacturing
Enduse
0.001
0.002
0.019
0.021
0.038
0.066
0.05
0.07
0.112
0.198
0.132
0.198
1.347
2.678
Fiber:
Manufacturing
Enduse
0.004
—
0.063
—
0.145
—
0.14
—
0.257
—
0.299
—
7.700
—
Finishing:
Manufacturing
Enduse
0.004
0.006
0.316
0.124
0.488
0.383
0.47
0.35
0.663
0.991
0.803
0.986
4.044
30.000
Installation:
Manufacturing
Enduse
—
0.003
—
0.084
—
0.236
—
0.20
—
0.434
—
0.559
—
3.371
Mixing/forming:
Manufacturing
Enduse
0.004
0.010
0.090
0.074
0.184
0.159
0.17
0.17
0.292
0.319
0.364
0.369
1.445
4.109
Other:
Manufacturing
Enduse
0.007
0.003
0.027
0.013
0.070
0.030
0.07
0.04
0.112
0.194
0.177
0.102
1.900
6.400
Removal:
Manufacturing
Enduse
—
0.010
—
0.373
—
1.914
—
0.82
—
1.816
—
2.340
—
16.000
Source:AdaptedfromEverest[1998].*Abbreviations:RCF=refractoryceramicfiber;TWA=time-weightedaverage.†Fiberconcentrationsweredeterminedduringmonitoringperformedovera5-yearperiod(1993–1998)undertheRefractoryCeramicFibersCoalition/EnvironmentalProtectionAgency(RCFC/EPA)consentagreement.ConcentrationsweredeterminedbyNIOSHmethod7400“B”countingrules.
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significant increased incidence of lungtumors in rats and pleural mesothelio-masinhamsters.ThesedatasupporttheNIOSH determination that RCFs are apotentialoccupationalcarcinogen.
■ Epidemiologicstudiesofworkers intheRCF manufacturing industry show anincreased incidence of pleural plaques,respiratory symptoms (dyspnea andcough), skin and eye irritation, and de-creased pulmonary function related toincreasing exposures to airborne fibers.Some of these conditions are docu-mentedforexposureconcentrationsinarangeaslowas0.2to0.6f/cm3.StudiesofworkersexposedtoairborneRCFsshownoevidenceofexcessriskforlungcancerormesothelioma.However,theinabilitytodetectsuchanassociationcouldbebe-causeof(1)thelowstatisticalpowerfordetectinganeffect,(2)theshortlatencyperiod for most workers occupationallyexposed,and(3)thehistoricallylowanddecreasingfiberexposuresthathaveoc-curredinthisindustry.
■ Riskassessmentanalysesusingdatafromchronic inhalation studies in rats indi-cate that the excess risk of developinglungcancerwhenexposed toRCFsataTWAof0.5f/cm3foraworkinglifetimeis 0.073 to 1.2/1,000. However, on thebasisoftheassumptionsusedintheriskanalyses,NIOSHconcludesthatthisriskestimateismorelikelytounderestimatethan to overestimate the risk to RCF-exposedworkers.Reductionof theRCFTWA concentration to 0.2 f/cm3 wouldreducetheriskforlungcancerto0.03to0.47/1,000. OSHA attempts to set PELsforcarcinogensthatreflectanestimatedriskof1/1,000butislimitedbyconsider-ationsoftechnologicandeconomicfea-sibility.
■ RCFexposuredatagatheredunderacon-sent agreement between RCFC and EPA,whichincludeda5-yearcomprehensiveairmonitoring program (1993–1998), indi-catethatairborneexposureconcentrationstoRCFshavebeendecreasing.Monitoringresults showthat75%to>95%ofTWAexposureconcentrationmeasurementsinallFJCs(withoneexception)werebelow1.0f/cm3.InallbuttwooftheeightFJCs,>70%ofTWAmeasurementswerebelowtheRCFCrecommendedexposureguide-line of 0.5 f/cm3. On the basis of the re-viewofthesedata,NIOSHhasconcludedthattheRELof0.5f/cm3canbeachievedinmostworkplaceswhereRCFsorRCFproductsaremanufacturedorused.
■ The combined effect of mixed exposurestofibersandnonfibrousparticulatesmaycontributetoincreasedirritationofthere-spiratorytract,skin,andeyes.Engineeringcontrols and appropriate work practicesusedtokeepairborneRCFconcentrationsbelowtheRELshouldhelptominimizeair-borneexposurestononfibrousparticulatesaswell.Becausetheratiooffiberstonon-fibrous particulate in airborne exposuresmayvaryamongjobtasks,exposuremoni-toringshouldincludeeffortstocharacterizeparticulatecompositionandtocontrolandminimize airborne fibers and nonfibrousparticulateaccordingly.
From the assessment described above andthroughoutthisdocument,NIOSHconcludesthat on a continuum of fiber toxicity, RCFsrelatemorecloselytoasbestosthantofibrousglassandotherSVFsandshouldbehandledac-cordingly.NIOSHconsidersallasbestostypesto be carcinogens and has established a RELof0.1 f/cm3 forairborneasbestosfibers.Thisvaluewasdeterminedonthebasisofextensivehumanandanimalhealtheffectsdataandtherecognizedlimitsofanalyticalmethods.
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RecognizingthatRCFsarecarcinogensinani-malstudiesandgiventhelimitationsinderiv-inganexposurevaluethatreflectsnoexcessriskof lung cancer or mesothelioma for humans,NIOSHrecommendsthateveryeffortbemadetokeepexposuresbelowtheRELof0.5f/cm3asaTWAforupto10hr/dayina40-hrwork-week.Theseeffortswillfurtherreducetheriskfor malignant respiratory disease and protectworkers from conditions and symptoms de-rivingfromirritationof therespiratorytract,skin,andeyes.
From the analysis of historical exposure data(seeChapter4)andtheexposuredatacollect-edaspartoftheRCFC/EPAconsentagreementmonitoringprogram(Table8–6),NIOSHhasdeterminedthatcompliancewiththeRELforRCFsisachievableinmostmanufacturingandend-use job categories. Although routine at-tainment of TWA exposures below the RELmaynotcurrentlyoccuratalljobtasks,itdoesrepresent a reasonable objective that can beachievedthroughmodificationofthejobtaskortheintroductionorimprovementofventi-lationcontrols.
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■ Establish procedures for reporting haz-ards and giving feedback about actionstakentocorrectthem.
■ Instruct workers about using safe workpracticesandappropriatePPE.
■ Informworkersaboutpracticesoroper-ationsthatmaygeneratehighconcentra-tionsofairbornefibers(suchascuttingand sanding of RCF boards and otherRCFproducts).
■ Makeworkerswhoremoverefractoryin-sulationmaterialsawareofthefollowing:
—Theirpotentialforexposuretorespi-rablecrystallinesilica
—Healtheffectsrelatedtothisexposure
—Methodsforreducingtheirexposure
—Types of PPE that may be required(includingrespirators)
9.1.2 Labeling and Posting
Althoughworkersshouldhavereceivedtrain-ingaboutRCFexposurehazardsandmethodsforprotectingthemselves,labelsandsignsserveasimportantremindersandprovidewarningstoworkerswhomaynotordinarilyworkinthearea.Employersshoulddothefollowing:
■ PostwarninglabelsandsignsaboutRCF-associated health risks at entrances andinsideworkareaswhereairborneconcen-trationsofRCFsmayexceedtheREL.
Thefollowingguidelinesforprotectingworkerhealth and minimizing worker exposures toRCFs are considered minimum precautionsthatshouldbeadoptedasapartofasite-specificsafetyandhealthplantobedevelopedandover-seenbyappropriateandqualifiedpersonnel.
9.1 Informing Workers about Hazards
9.1.1 Safety and Health Training Program
Employersshouldestablishasafetyandhealthtraining program for all workers who manu-facture, use, handle, install, or remove RCFproductsorperformotheractivitiesthatbringthem into contact with RCFs.As part of thistraining program, employers should do thefollowing:
■ Informallpotentiallyexposedworkers(in-cluding contract workers) about RCF-associated health risks such as skin, eye,andrespiratoryirritationandlungcancer.
■ ProvideMSDSsonsite:
—Make MSDSs readily available toworkers.
—Instructworkershowtointerpretin-formationfromMSDSs.
■ Teach workers to recognize and reportadverserespiratoryeffectsassociatedwithRCFs.
■ Trainworkerstodetecthazardoussitua-tions.
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■ Statetheneedtowearappropriaterespi-ratoryprotectionandprotectiveclothinginareaswhereairborneRCFsmayexceedtheREL.
■ Ifrespiratoryprotectionisrequired,postthefollowingstatement:
9.2.1 Engineering Controls
Engineering controls should be the principalmethod for minimizing exposure to RCFs intheworkplace.
9.2.1.1 Ventilation
Achieving reduced concentrations of air-borneRCFsdependsonadequateengineeringcontrolssuchaslocalexhaustventilationsys-temsthatareproperlyconstructedandmain-tained.Localexhaustventilationsystemsthatemployhoodsandductworktoremovefibersfrom the workplace atmosphere have beenusedbyRCFmanufacturers.Oneexampleisa slotted-hooddustcollectionsystemplacedoveramixingtanksothatairbornefibersarecaptured and collected in a bag house withHEPAfilters[RCFC1996].Othertypesoflo-calexhaustventilationordustcollectionsys-temsmaybeusedatorneardust-generatingsystemstocaptureairbornefibers.BandsawsusedinRCFmanufacturingandfinishingop-erationshavebeenfittedwithsuchengineer-ingcontrolstocapturefibersanddustduringcuttingoperationsandtherebyreduceexpo-sures for the band saw operator [Venturin1998]. Disc sanders fitted with similar localexhaust ventilation systems are effective inreducing airborne RCF concentrations dur-ingsandingofvacuum-formedRCFproducts[Dunnetal.2004].Forqualitycontrollabora-toriesorlaboratorieswhereproductionsam-plesarepreparedforanalyses,exhaustventi-lationsystemsshouldbedesignedtocaptureandcontaindust.Forguidance indesigninglocal exhaust ventilation systems, see Indus-trial Ventilation—A Manual of Recommended Practice, 25th edition [ACGIH 2005], Rec-ommended Industrial Ventilation Guidelines[HagopianandBastress1976],andtheOSHAventilationstandard[29CFR1910.94].
RESPIRATORS REQUIRED IN THIS AREA.
■ PrintalllabelsandwarningsignsinbothEnglish and the predominant languageofworkerswhodonotreadEnglish.
■ If workers are unable to read the labelsand signs, inform them verbally aboutthehazardsandinstructionsprintedonthelabelsandsigns.
9.2 Hazard Prevention and Control
Proper use and maintenance of engineeringcontrols,workpractices,andPPEareessentialfor controlling concentrations of airborne fi-bersduringthemanufacturing,use,andhan-dling of RCF products. Minimizing exposuretoRCFsmaybeaccomplishedthroughacom-bination of the following work practices andcontrols:
■ Engineeringcontrolsandventilation
■ Productreformulation
■ Workerisolation
■ PPE (such as protective clothing andequipmentandrespirators)
■ Proper decontamination and waste dis-posal
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Additional engineering controls have beenevaluated by the Bureau of Mines for mini-mizingairbornedustinundergroundminingoperationsandatindustrialsandplants.Thesecontrols may also have applications for RCFfinishing,installation,andremovaloperations.Theuseofairshowers(alsoknownasacanopyaircurtainoranoverheadairsupplyisland)in-volvespositioninganairsupplyovertheheadofaworkertoprovideaflowofclean,filteredair to the worker’s breathing zone [Volkweinet al. 1982, 1988]. Proper design and evalua-tion are critical for ensuring that filtration isadequate to remove airborne fibers from theairsupply.Also,selectionoftheairsupplyflowrateisimportanttomakesurethatthevelocitydeliveredtotheworker’sbreathingzoneissuf-ficienttoovercomecrossdraftsandmaintainacleanairflow.
9.2.1.2 Tool selection and modification
TheRCFChasreportedthatusinghandtoolsinstead of powered tools can significantly re-duce airborne concentrations of dust. How-ever,handtoolsoftenrequireadditionalphysi-caleffortandtime,andtheymayincreasetherisk of musculoskeletal disorders. Employersshould therefore use ergonomically correcttoolsandproperworkstationdesign toavoidergonomichazards.
The additional physical effort required tousehandtoolsmayalsoincreasetherateanddepthofbreathingandmayconsequentlyaf-fect the inhalation and deposition of fibers.Foroperationssuchascutting,sawing,grind-ing,drilling,andsanding,thehighlevelofme-chanicalenergyappliedtoRCFproductswithpowertoolsincreasesthepotentialforelevatedconcentrations of airborne fiber. Examples[Carborundum 1992] of how airborne fiberconcentrationsareaffectedby theequipmentusedtoprocessRCFproductsincludethefol-lowing:
■ A testofhand sawingversus theuseofapoweredjigsawshowedan81%reduc-tion in concentrations of airborne dustgenerated.
■ A comparison of hand sanding versuspowersandingshoweda90%reductionin concentrationsof airbornedustgen-erated.
■ Whenalightwatermistisappliedtothesurface of a vacuum-formed board be-fore sanding, airborne dust concentra-tionisreducedby89%forhandsandingand88%forpoweredsanding.
■ Theuseofacorkbore(coredrill)versusanelectricdrillwithatwistbitforcuttingholes in RCF product forms reduces air-bornedustconcentrationsbyabout85%.
9.2.1.3 Engineering controls for RCF finishing operations
ResearchersatNIOSHhavebeenworkingwithindustrial hygienists at RCFC member facili-ties to study the effectiveness of engineeringcontrolsdesignedandappliedtoRCFfinishingoperations.Becausehandtoolsarenotalwaysapracticalsolutiontomanufacturingandend-use facilities requirements, engineering con-trolsarebeingdesignedandevaluatedforusewithpoweredtools.
AjointprojectbetweenNIOSHandRCFCwasinitiatedin1998andinvolvedinvestigatingen-gineeringcontrolsforusewithapedestalbelt/disc sander [Dunn et al. 2000, 2004]. Theseunits are frequently used by the manufactur-ersaswellasthecustomerfacilitiestoproducevacuum-formed boards sized to the requireddimensions.Acontinuousmistingnozzleandsimple local exhaust ventilation system wereintegratedforuseonthepedestalsandingunit.Themisterconsistedofastandardatomizationnozzlethatwassetforalow-waterflowrateto
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minimizepartdegradation.Thelocalexhaustventilation system used two hoods or pickuppointswithatotalairflowof700ft3/min.
Duringproductionofvacuum-formedboards,these two controls reduced fiber concentra-tionsinthebreathingzoneasfollows:
% decrease in airborne fibers:
Discsandingusingwatermist . . . . . . . 88
Discsandingusinglocalexhaustventilation . . . . . . . . . . . . . . . . . 99
Beltsandingusingwatermist . . . . . . .50
Beltsandingusinglocalexhaustventilation . . . . . . . . . . . . . . . . . 99
Thesestudieshighlight thepotential forsig-nificantreductionsinworkerexposureusingwell designed and maintained engineeringcontrols, but their effectiveness needs to bevalidatedinthefield.
9.2.1.4 Wet methods for dust suppression
Fibercountsare lower inmorehumidatmo-spheres. Examples of using water to suppressdustconcentrationsaredescribedasfollows:
■ At one RCF textile facility, misters havebeenaddedabovebroadloomsandtapeloomstodecreasefiberconcentrations.
■ Waterknivesarehigh-pressurewaterjetsthatareusedtocutandtrimedgesofRCFblanketwhilesuppressingdustandlimit-ingthegenerationofairbornefibers.
■ DuringtheinstallationofRCFmodulesin a furnace, a procedure called tamp-ingistypicallyperformed.Aftermodulesareputinplaceonthefurnacewall,themodules are compressed by placing a
1-ft length of 2- by 4-ft lumber againstthe modules and tapping it lightly withahammer.TheprocesshelpsensurethattheRCFmodulesareinstalledtightlyinplace.Whenalightwatersprayisappliedto the surface of the modules beforetamping,airbornefiberconcentrationisreduced by about 75% [Carborundum1993]. The water is applied with a gar-den-type sprayer that is setonmistus-ingabout1galofwater/100ft2ofsurfacearea.However,cautionisadvisedregard-ing thedampeningof refractory-liningsduring installation. The introductionof water can damage refractory-linedequipmentduringheatingwithexplosivespallingfromthegenerationofsteam.
■ After-service RCF insulation removedfrom furnaces may be wetted to reducethereleaseoffibers.
9.2.1.5 Isolation
Some manufacturing processes may be en-closed to keep airborne fibers contained andseparatedfromworkers.
■ Whenpossible, isolateworkersfromdi-rect contact with RCFs by using auto-matedequipmentoperatedfromaclosedcontrolboothorroom.
■ Maintainthecontrolroomatgreaterairpressurethanthatsurroundingthepro-cessequipmentsothatairflowsoutrath-erthanin.
■ Make sure workers take special precau-tions (such as using PPE) when theymustenterthegeneralworkareatoper-formprocesschecks,adjustments,main-tenance,assembly-linetasks,andrelatedoperations.
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9.2.2 Product Reformulation
One factor that contributes to the toxicity ofan inhaled fiber is the durability of the fiberanditsresistancetodegradationintherespira-torytract.ThechemicalcharacteristicsofRCFsmake themoneof themostdurable typesofSVFs.Asaresult,aninhaledRCFofspecificdi-mensionswillpersistlongerinthelungs.Mod-ifying the physical characteristics of RCFs orreformulatingtheirchemistrytoproduce lessdurable fibers are recommended options forreducingthehazardforexposedworkers.SuchanapproachhasbeentakenbyoneRCFmanu-facturerindevelopingtwomoresolubletypesofSVF[Maximetal.1999b].However,cautionisadvisedfordevelopinganddistributingsuchmodifiedfibers.Possibleadversehealtheffectsofnewlydevelopedfibersshouldbeevaluatedbefore introducing them intocommerce.Ap-propriatetestingofthesefibersshouldbeper-formedtoprovideinformationaboutthefibertoxicologyandpotentialadversehealtheffectsassociatedwithexposuretothesefibers.
9.2.3 Work Practices and Hygiene
Usegoodworkpracticestohelpreduceexpo-suretoairbornefibers.Thesepracticesincludethefollowing:
■ Limittheuseofpowertoolsunlesstheyareequippedwith localexhaustordustcollection systems. When possible, usehandtools,whichgeneratelessdustandfewerairborneparticles.
■ UseHEPA-filteredvacuums,wetsweeping,oraproperlyenclosedwetvacuumsystemforcleaningupdustcontainingRCFs.
■ DuringremovalofRCFproducts,damp-eninsulationwithalightwaterspraytokeepfibersanddustfrombecomingair-borne.
■ Clean work areas regularly with HEPA-filtered vacuums or with wet sweepingmethods to minimize the accumulationofdebris.
■ LimitaccesstoareaswhereworkersmaybeexposedtoairborneRCFs:permitonlyworkerswhoareessentialtotheprocessoroperation.
Use good hygiene and sanitation to protectworkers as well as people outside the work-place who might be contaminated with take-homedustandfibers:
■ Do not allow workers to smoke, eat, ordrink in work areas where they contactRCFs.
■ IfRCFsgetontheskin,washwithwarmwaterandmildsoap.
■ Applyskinmoisturizingcreamasneededto avoid dryness or irritation from re-peatedwashing.
■ Vacuum contaminated clothes with aHEPA-filteredvacuumbeforeleavingtheworkarea.
—Do not use compressed air to cleantheworkareaorclothing.
—Donotshakeclothestoremovedust.
■ Donotwear contaminatedclothesout-sidetheworkarea.Instead,takethefol-lowingmeasures toprevent takingcon-taminantshome:
—Changeintostreetclothesbeforego-inghome.
—Leave contaminated clothes at theworkplacetobelaunderedbytheem-ployer.
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—Store street clothes in separate areasof the workplace to keep from con-taminatingthem.
■ Provideworkerswith showersandhavethemshowerbeforeleavingwork.
■ Prohibitremovalofcontaminatedclothesorotheritemsfromtheworkplace[NIOSH1995b].
9.2.4 Personal Protective Equipment
Wear long sleeves, gloves, and eye protectionwhen performing dusty activities involvingRCFs.
9.2.5 Respiratory Protection
NIOSHrecommendsusingarespiratorforanytaskinvolvingRCFexposuresthatareunknownorhavebeendocumentedtobehigherthantheNIOSHRELof0.5 f/cm3(TWA).Respiratorsshould not be used as the primary means ofcontrollingworkerexposures.Instead,NIOSHrecommends using other exposure-reductionmethods, such as product substitution, engi-neering controls, and changes in work prac-tices. However, respirators may be necessarywhenavailableengineeringcontrolsandworkpracticesdonotadequatelycontrolworkerex-posuresbelowtheRELforRCFs.NIOSHrec-ognizesthiscontroltobeaparticularchallengeinthefinishingstagesofRCFproductmanu-facturingaswellasduringtheinstallationandremovalofRCFinsulationmaterials.
If respiratory protection is needed, the em-ployer should establish a comprehensive re-spiratory protection program as described inthe OSHA respiratory protection standard[29CFR1910.134].Elementsofarespiratoryprotectionprogramshouldbeestablishedanddescribed in a written plan that is specific tothe workplace. This respirator program mustincludethefollowing:
■ Proceduresforselectingrespirators
■ Medicalevaluationsofworkersrequiredtowearrespirators
■ Fittestingprocedures
■ Routine use procedures and emergencyrespiratoruseprocedures
■ Procedures and schedules for cleaning,disinfecting, storing, inspecting, repair-ing,discarding, andmaintaining respi-rators
■ Procedures for ensuring adequate airqualityforsupplied-airrespirators
■ Traininginrespiratoryhazards
■ Training in the proper use and mainte-nanceofrespirators
■ Programevaluationprocedures
■ Procedures for ensuring that workerswhovoluntarilywearrespirators(exclud-ingfilteringfacepiecerespiratorsknownas dust masks) comply with the medi-calevaluationandcleaning,storing,andmaintenance requirements contained inAppendix D of the OSHA respiratoryprotectionstandard
■ Adesignatedprogramadministratorwhoisqualifiedtoadministertherespiratoryprotectionprogram
The written respiratory protection programshouldbeupdatedasnecessarytoaccountforchangesintheworkplacethataffectrespiratoruse.Allequipment,training,andmedicaleval-uationsrequiredundertherespiratoryprotec-tionprogramshouldbeprovidedatnocosttoworkers.Workers should use only respiratorsthathavebeencertifiedbyNIOSH[2002].
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WhenairborneRCFconcentrationsexceedtheREL,NIOSHrecommendsthefollowingrespi-ratoryprotection:
■ At a minimum, use a half-mask, air-purifying respirator equipped with a100 series particulate filter (this res-piratorhasanassignedprotectionfactor(APF)of10.
■ For a higher level of protection and forprevention of facial or eye irritation, usea full-facepiece, air-purifying respirator(equippedwitha100 seriesfilter)or anypowered,air-purifyingrespiratorequippedwithatight-fittingfullfacepiece.
■ For greater respiratory protection whenthe work involves potentially high air-borne fiber concentrations (such as re-moval of after-service RCF insulationsuch as furnace insulation), use a sup-plied-airrespiratorequippedwitha fullfacepiece, since airborne exposure toRCFscanbehighandunpredictable.
Acomprehensiveassessmentofworkplaceex-posuresshouldalwaysbeperformedtodeter-minethepresenceofotherpossiblecontami-nants (such as silica) and to ensure that theproperrespiratoryprotectionisused.Table9–1providesadditionalguidanceforselectingap-propriaterespiratoryprotectionwithregardtoairbornefiberconcentrationsandtheNIOSHRELforRCFs.
Workersmayvoluntarilychoosetouserespi-ratory protection even when airborne fiberconcentrations are below the NIOSH RELor other applicable Federal or State stan-dards.Whenrespiratorsareusedvoluntarilybyworkers,employersneedtoestablishonlythose respiratory protection program ele-mentsnecessarytoassurethattherespiratoritselfisnotahazard[29CFR1910.134].The
exceptionisthatfiltering-facepiecerespirators(forexample,any95or100seriesfilter)canbeusedwithoutarespiratorprotectionprogramwhentheyareusedvoluntarily.
Forinformationandassistanceinestablishingarespiratoryprotectionprogramandselectingappropriate respirators, see the OSHA Respi-ratoryProtectionAdvisoron theOSHAWebsite at http://www.osha.gov.Additional infor-mation is available from the NIOSH Respira-tor Selection Logic[NIOSH2004]documentathttp://www.cdc.gov/niosh/docs/2005–100 andthe NIOSH Guide to the Selection and Use of Particulate Respirators Certified under 42 CFR 84[NIOSH1996].
9.3 Exposure Monitoring9.3.1 Workplace Exposure Monitoring
Program
The workplace exposure monitoring programforworksiteswhereRCFsorRCFproductsaremanufactured,handled,orusedshouldincluderoutine environmental and personal monitor-ingofairbornefiberconcentrations.Themoni-toring strategy should be designed to assesstheeffectivenessofengineeringcontrols,workpractices, PPE, training, and other factors incontrolling airborne fiber concentrations. Themonitoring program should also be used toidentifyareasor tasks that areassociatedwithhigherexposurestoRCFsandthatthereforere-quireadditionaleffortstoreducethem.
The goal of an RCF exposure monitoringprogramistoensureamorehealthfulworkenvironment where worker exposure (mea-suredbyfull-shiftsamples)doesnotexceedtheREL.BecauseadverserespiratoryhealtheffectscanoccurattheRELforRCFs,achiev-ing lowerconcentrations isdesirablewhen-ever possible. For work involving potential
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Table 9–1 . Respiratory protection for exposure to RCFs*
Airborne concentration of RCFs or conditions of use Minimum respiratory protection options
5.0f/cm3(10×REL) Anyair-purifying,elastomerichalf-maskrespiratorequippedwitha100series(NH,R,orP)filterI
Anynegativepressure(demand),suppled-airrespiratorequippedwithahalfmask
12.5f/cm3(25×REL) Anypowered,air-purifyingrespiratorequippedwithahoodorhel-metandahigh-efficiencyparticulateairfilter(HEPAfilter)
Anycontinuous-flow,supplied-airrespiratorequippedwithahoodorhelmet
25f/cm3(50×REL) Anyair-purifying,full-facepiecerespiratorequippedwitha100series(NH,R,orP)filterI
Anypowered,air-purifyingrespiratorequippedwithatight-fittingfacepiece(halforfullfacepiece)andaHEPAfilter
Anynegativepressure(demand),supplied-airrespiratorequippedwithafullfacepiece
Anycontinuousflow,supplied-airrespiratorequippedwithatight-fittingfacepiece(halforfullfacepiece)
Anynegativepressure(demand),self-containedrespiratorequippedwithafullfacepiece
500f/cm3(1,000×REL) Anypressuredemand,supplied-airrespiratorequippedwithahalf-mask
*Abbreviations:APFs=assignedprotectionfactors;HEPA=high-efficiencyparticulateair;NIOSH=NationalInstitueforOccupationalSafetyandHealth;RCFs=refractoryceramicfibers.
HN-100seriesparticulatefiltersshouldnotbeusedinenvironmentswherethereispotentialforexposuretooilmists.IAssignedprotectionfactors(APFs)forotherhalf-maskandfull-facepieceparticulaterespiratorscertifiedunder42CFRPart84are
beingstudiedbyNIOSH.RecommendedAPFsfortheserespiratorswillberevisedaccordingly.
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exposuretoairborneRCFs,performtheexpo-suresamplingsurveyasfollows:
■ Collect representative personal samplesfor the entire work shift using NIOSHMethod 7400 (B rules) [NIOSH 1977a,1998].
■ Perform periodic sampling at least an-nually and whenever any major processchangetakesplaceoranotherreasonex-ists to suspect that exposure concentra-tionsmayhavechanged.
■ Collect all routine personal samples inthebreathingzonesoftheworkers.
■ For workers exposed to concentrationsabove the REL, perform more frequentexposure monitoring until at least twoconsecutive samples indicate that theworker’sexposuresnolongerexceedtheREL.
■ Notifyallworkersaboutmonitoringre-sults and any actions taken to reducetheirexposures.
■ Make sure that any sampling strategyconsiders variations in work and pro-ductionschedulesaswellastheinherentexposurevariability inmost workplaces[NIOSH1995a].
9.3.2 Action Level
NIOSH has recommended an action level(AL) of 0.25 f/cm3for determining when ad-ditional controls areneededorwhenadmin-istrative actions should be taken to reduceRCF exposures. The purpose of the AL is toindicatewhenworkerexposurestoRCFsmaybeapproachingtheREL.Measurementofex-posureconcentrationsatorabove theAL in-dicate that there is ahighdegreeof certaintythatRCFconcentrationsexceedtheREL.TheALisastatisticallyderivedconceptpermitting
theemployertohaveconfidence(forexample,95%)thatifthemeasuredexposureconcentra-tionisbelowtheAL,onlyasmallprobabilityexiststhattheexposureconcentrationisabovethe REL. NIOSH has concluded that the useof anAL permits employers to monitor RCFexposures in the workplace without devot-ingunnecessaryresourcestoconductingdailyexposure measurements. TheAL concept hasservedasthebasisfordefiningtheelementsofan occupational standard in NIOSH criteriadocuments and in comprehensive standardspromulgated by OSHA and MSHA. Employ-ersshoulddeterminewhethertheuseofanALof0.25f/cm3providesadequateassurancethatworkerexposuresarebeingmaintainedbelowtheREL.Insomeworkenvironments,thehighdegree of exposure variability for certain jobtasksmayrequirealowerALtoassurethatex-posuresarebeingmaintainedbelowtheREL.Similar exposure monitoring strategies havebeenespousedbytheAmericanIndustrialHy-gieneAssociation, which recommends that ifmeasuredexposuresare less than10%of thedesignated exposure limit (for example, RELorPEL),thereisahighdegreeofcertaintythattheexposurelimitwillnotbeexceeded.
9.3.3 Sampling Strategies
Whensamplingtodeterminewhetherwork-er exposures are below the REL, a focusedsampling strategy may be more practicalthanrandomsampling.Afocusedsamplingstrategy targets workers perceived to havethehighestexposureconcentrations[LeidelandBusch1994].AfocusedstrategyismostefficientforidentifyingexposuresabovetheRELifmaximum-riskworkersandtimepe-riodsareaccuratelyidentified.Focusedsam-plingmayhelpidentifyshort-durationtasksinvolvinghighairbornefiberconcentrationsthatcouldresultinelevatedexposuresoverafullworkshift.
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Sampling strategies such as those used byCorn and Esmen [1979], Rice et al. [1997],andMaximetal.[1997]havebeenderivedandusedinRCFmanufacturingfacilitiestomoni-torairbornefiberconcentrationsby selectingrepresentativeworkersforsampling.Therep-resentative workers are grouped according todustzones,uniformjobtitles,orfunctionaljobcategories. These approaches are intended toreducethenumberofrequiredsampleswhileincreasingtheconfidenceofidentifyingwork-ersatsimilarrisk.
Areasamplingmayalsobeusefulinexposuremonitoring for determining sources of air-borneRCFexposuresandassessingtheeffec-tivenessofengineeringcontrols.
9.4 Medical MonitoringNIOSHrecommendsperiodicmedicalevalu-ation,ormedicalmonitoring,ofRCF-exposedworkerstoidentifypotentialhealtheffectsandsymptomsthatmayberelatedtocontactwithairbornefibers.ThefollowingsectionsdescribetheobjectivesofmedicalmonitoringandtheelementsofamedicalmonitoringprogramforworkersexposedtoRCFs.
The primary goals of a workplace medicalmonitoring program are (1) early identifi-cation of adverse health effects that may berelatedtoexposuresatworkand(2)possiblehealthtrendswithingroupsofexposedwork-ers.Thesegoalsarebasedonthepremisethatearly detection, subsequent treatment, andworkplace interventions will ensure the con-tinuedhealthoftheaffectedworkforce.
9.4.1 Objectives of Medical Monitoring
Medical monitoring and resulting interven-tions represent secondary prevention andshouldnotreplaceprimarypreventioneffortstominimizeworkerexposurestoRCFs.Inthe
caseofRCFs,medicalmonitoringisespeciallyimportantbecauseachievingcompliancewiththe REL of 0.5 f/cm3 does not assure that allworkerswillbefreefromtheriskofrespiratoryirritationorchronicrespiratorydiseasecausedbyoccupationalexposure.Earlyidentificationof respiratory system changes and symptomsassociated with RCF exposures (such as de-creased pulmonary function, irritation, dys-pnea, chronic cough, wheezing, and pleuralplaques)maysignaltheneedformoreinten-sivemedicalmonitoringandtheassessmentofexistingcontrolstominimizetheriskoflong-termadversehealtheffects.Anongoingmedi-calmonitoringprogramalsoservestoinformworkersofpotentialhealthrisksandpromotesanunderstandingoftheneedforandsupportofexposurecontrolactivities.
Amedicalmonitoringprogramservesasanef-fective secondary prevention method on twolevels—screening and surveillance. Medicalscreeningintheworkplacefocusesontheearlydetection of health outcomes for individualworkersandmayinvolveanoccupationalhis-tory,medicalexamination,andapplicationofspecificmedicalteststodetectthepresenceoftoxicants or early pathologic changes beforethe worker would normally seek clinical careforsymptomaticdisease.Bycontrast,medicalsurveillance(describedinSection9.5)involvestheongoingevaluationofthehealthstatusofagroupofworkersthroughthecollectionandaggregate analysis of health data for the pur-poseofpreventingdiseaseandevaluatingtheeffectivenessofinterventionprograms.
9.4.2 Criteria for Medical Screening
Todeterminewhether testsorprocedures formedicalscreeningareappropriateandrelevanttoagivenhazard(inthiscase,exposuretoair-borneRCFs), the following factors shouldbeconsidered:
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9 ■Guidelines for Protecting Worker Health
■ Prevalence of an associated disease orsymptomsinthepopulation
■ Riskof toxicity associatedwith theex-posure
■ Consequencesoffalsepositivetestresults
■ Sensitivity,specificity,andpredictiveval-ueofthescreeningtest(s)tobeused
■ Reliability and validity of the screeningtest(s)
■ Abilityofthescreeningtest(s)toidentifydisease early so that effective treatmentor intervention may be used to impedediseaseprogression
■ Availability,accessibility,andacceptabil-ity of followup, further diagnostic tests,andeffectivemanagementofthedisease
■ Benefitsof thescreeningprogramcom-paredwiththecosts[Wagner1996].
On the basis of these criteria, NIOSH rec-ommends a medical screening program forRCF-exposedworkers that require initial andperiodicmedical examinations.Theelementsof theprogramshould includeaphysical ex-amination, occupational history, respiratorysymptom questionnaire, spirometric test-ing,andchestradiographwhenwarranted.Ifa particular medical screening test indicatesthe presence of exposure-related disease orthe increasedprobability thatdiseasewillde-velop, further evaluation and diagnostic test-ingmaybeneeded.Recommendedguidelinesandschedulesforspecificmedicaltestsarede-scribed in Section 9.4.5 (Recommended Pro-gramElements).
9.4.3 Worker Participation
All workers potentially exposed to RCFs, inboth manufacturing and end-use industries,
may benefit by being included in an occupa-tional medical monitoring program.Workersshould be provided with information aboutthepurposesofmedicalmonitoring,thehealthbenefits of the program, and the proceduresinvolved. The following hierarchy describesworkerswhoshouldbeincludedinamedicalmonitoring program and who could receivethegreatestbenefitfrommedicalscreening:
■ Workers exposed to elevated fiber con-centrations(forexample,allworkersex-posedtoairborneRCFsatconcentrationsabovetheALof0.25f/cm3[describedinSection9.3])
■ Workers in areas or in jobs and activi-tiesinwhich,regardlessofairbornefiberconcentration,oneormoreworkershaverecentlydevelopedsymptomsorrespira-tory changes apparently related to RCFexposure
■ Workerswhomayhavebeenpreviouslyexposedtoasbestosorotherrespiratoryhazards thatplace thematan increasedriskofrespiratorydisease
■ Workers with potential exposure to air-borneRCFswhoalsosmokecigarettesorothertobaccoproducts(seeSection9.6,SmokingCessation).
9.4.4 Medical Monitoring Program Director
Oversight of the medical monitoring pro-gramshouldbeassignedbytheemployer toaqualifiedphysicianorotherqualifiedhealthcare provider (as determined by appropriateState laws and regulations) who is informedandknowledgeableaboutthefollowing:
■ Theadministrationandmanagementofamedicalmonitoringprogramforoccu-pationalhazards
124 Refractory Ceramic Fibers
9 ■Guidelines for Protecting Worker Health
■ Theestablishmentofarespiratoryprotec-tionprogrambasedonanunderstandingoftherequirementsoftheOSHArespi-ratoryprotection standardand typesofrespiratory protection devices availableattheworkplace
■ The identification and management ofwork-relatedrespiratoryeffectsorillnesses
■ The identification and management ofwork-relatedskindiseases
9.4.5 Recommended Program Elements
Recommended elements of a medical moni-toringprogram forworkers exposed toRCFsinclude provisions for an initial medical ex-aminationandperiodicmedicalexaminationsatregularlyscheduledintervals.Dependingonthe findings from these examinations, morefrequent and detailed medical examinationsmay be necessary. Worker education shouldalsobeincludedasacomponentofthemedi-calmonitoringprogram.SpecificelementsoftheexaminationsandschedulingaredescribedbelowandillustratedintheflowchartdiagraminFigure9–1.
9.4.5.1 Initial medical examination
An initial (baseline) examination should beperformedasnearaspossibletothedateofbe-ginningemployment(within3months).Theinitialmedicalexaminationshouldincludethefollowing:
■ A physical examination of all systems,withemphasisontherespiratorysystemandtheskin
■ Aspirometrictest(Anyoneadministeringspirometric testingaspartof themedi-cal monitoring program should havecompleted a NIOSH-approved training
courseinspirometryorotherequivalenttraining.)
■ AchestX-ray(AllchestX-rayfilmsshouldbe interpreted by a NIOSH-certified Breader using the standard InternationalClassification of Radiographs of Pneu-moconioses[ILO2000orthemostrecentequivalent].)
■ Othermedicaltestsasdeemedappropri-ate by the attending health care profes-sional
■ Astandardizedrespiratorysymptomques-tionnairesuchastheAmericanThoracicSocietyRespiratoryQuestionnaire[Ferris1978orthemostrecentequivalent]withadditionalquestionstoaddresssymptomsofpleuriticchestpainandpleurisy
■ Astandardizedoccupationalhistoryques-tionnaire that gathers (1) informationaboutallpastjobs(withspecialemphasisonthosewithpotentialexposuretodust),(2)adescriptionofalldutiesandpoten-tialexposuresforeachjob,and(3)ade-scriptionofallprotectiveequipment theworkerhasused
9.4.5.2 Periodic medical examinations
Periodic examinations (including a physicalexaminationoftherespiratorysystemandtheskin,spirometrictesting,arespiratorysymptomupdate questionnaire, and an occupationalhistory update questionnaire) should be ad-ministeredat regular intervalsdeterminedbythemedicalmonitoringprogramdirector.Thefrequency of the periodic medical examina-tions should be determined according to thefollowingguidelines:
■ For workers with fewer than 10 yearssincefirstexposuretoRCFs,periodicex-aminationsshouldbeconductedatleastonceevery5years.
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9 ■Guidelines for Protecting Worker Health
I. Worker participation?
WorkinvolvespotentialforexposuretoRCFs,especial-lyforworkerswhoare
■ exposedtoelevatedfiberconcentrations(forexample,aboveadesignatedAL),
■ inworkareaswhereoneormoreworkershaverecentlydevelopedrespiratorysymptomsorchanges,
■ previouslyexposedtoasbestosorotherrespira-toryhazards
YES
II. Initial medical examination
(within3monthsofbeginningemployment)
■ Examinationofrespiratorysystemandskin
■ Spirometrictest
■ ChestX-ray
■ Standardizedrespiratorysymptomquestion-naire
■ Standardizedoccupationalhistoryquestion-naire
III. Adverse symptoms/health outcomes?
■ Respiratorysymptoms(forexample,chroniccough,difficultybreathing,shortnessofbreath,wheezing)
■ Recurrentorchronicdermatitis
■ Medicallysignificantreasonforadditionalas-sessment
YES
IV. More frequent or detailed medical examination and treatment
(asdeterminedbyprogramdirector)
NO Maynotrequiremedicalmonitoring
NO
V. Periodic medical examination
■ Examinationofrespiratorysystemandskin
■ Spirometrictest
■ Standardizedrespiratorysymptomupdatequestionnaire
■ Standardizedoccupationalhistoryupdatequestionnaire
YESVI. Adverse symptoms/health outcomes?
(describedinIII.)
VII. Continue with guidance and schedule in V.
Figure 9–1 .FlowchartofmedicalmonitoringguidelinesforworkersexposedtoRCFs.Thisflowchartisintendedasasimplifiedrepresentationoftheminimumrequirementsoftherecommendedmedicalmonitoringprogramguide-lines.Administrationandmanagementoftheprogramshouldultimatelyrelyonthejudgmentofthemedicalmoni-toringprogramdirector.Frequencyofperiodicmedicalexaminationsareasfollows:
■ IftimesincefirstRCFexposureis<10years,examinationsshouldbeconductedatleastevery5years.
■ IftimesincefirstRCFexposureis≥10years,thenexaminationsshouldbeconductedatleastevery2years.
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9 ■Guidelines for Protecting Worker Health
■ Forworkerswith10ormoreyearssincefirstexposuretoRCFs,periodicexamina-tions shouldbeconductedat leastonceevery2years.
AchestX-rayandspirometrictestingareim-portantuponinitialexaminationandmayalsobeappropriatemedicalscreeningtestsduringperiodic examinations for detecting respira-tory system changes—especially in workerswith more than 10 years since first exposureto RCFs. The value of periodic chest X-raysin a medical monitoring program should beevaluatedbyaqualifiedhealthcareproviderinconsultationwiththeworkertoassesswhetherthe benefits of testing warrant the additionalexposure to radiation. As with the frequencyof periodic examinations, the utility of thechestX-rayasamedical testbecomesgreaterforworkerswithmorethan10yearssincefirstexposuretoRCFs(basedonthelatencyperiodbetweenfirstexposureandappearanceofno-ticeable respiratory system changes). Becausepersons with advanced fiber-related pleuralchanges experience difficulty in breathing asthe parietal and visceral surfaces become ad-herentandloseflexibility,itmayprovebenefi-cialtodetectfibroticchangesintheearlystagessostepsmaybetakentopreventfurtherlungdamage.Similar recommendationshavebeenmadeforasbestos-exposedworkersdiagnosedwithpleuralfibrosisorpleuralplaquestopre-ventmoreserioustypesofrespiratorydisease[Balmes1990].
9.4.5.3 More frequent medical examinations
Anyworkershouldundergomorefrequentanddetailedmedicalevaluationifheorshehasanyofthefollowingindications:
■ Neworworseningrespiratorysymptomsorfindings(forexample,chroniccough,difficulty breathing, wheezing, reduced
lung function,or radiographicevidenceofpleuralplaquesorfibrosis)
■ Historyofexposuretootherrespiratoryhazards(forexample,asbestos)
■ Recurrentorchronicdermatitis
■ Othermedicallysignificantreason(s)formoredetailedassessment
9.4.5.4 Worker education
Workers should be provided with sufficienttraining to recognize symptoms associatedwith RCF exposures (such as chronic cough,difficulty breathing, wheezing, and skin irri-tation).Workers should also be instructed toreport these symptoms to designated safetyandhealthpersonnelandaphysicianorotherqualifiedhealthcareprovider forappropriatediagnosisandtreatment.
9.4.6 Written Reports to the Worker
Followinginitialandperiodicmedicalexami-nations,thephysicianorotherqualifiedhealthcareprovidershouldprovideeachworkerwithawrittenreportcontainingthefollowing:
■ Results of any medical tests performedontheworker
■ Medicalopinioninplainlanguageaboutany medical condition that would in-crease the worker=s risk of impairmentfromexposuretoairborneRCFs
■ Recommendations for limiting theworker=s exposure to RCFs, which mayinclude the use of appropriate PPE, aswarranted
■ Recommendationsforfurtherevaluationandtreatmentofmedicalconditionsde-tected
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9.4.7 Written Reports to the Employer
Followinginitialandperiodicmedicalexami-nations,thephysicianorotherqualifiedhealthcareprovidershouldprovideawrittenreporttotheemployercontainingthefollowing:
■ Occupationally pertinent results of themedicalevaluation
■ A medical opinion about any medi-cal condition that would increase theworker=sriskofimpairmentfromexpo-suretoairborneRCFs
■ Recommendations for limiting theworker=s exposure to RCFs (or otheragentsintheworkplace),whichmayin-cludetheuseofappropriatePPEorreas-signmenttoanotherjob,aswarranted
■ Astatement to indicate that theworkerhas been informed about results of themedicalexaminationandaboutthemed-icalcondition(s)thatshouldhavefurtherevaluationortreatment
Findings,testresults,ordiagnosesthathavenobearing on the worker=s ability to work withRCFsshouldnotbeincludedinthereporttothe employer. Safeguards to protect the con-fidentiality of the worker=s medical recordsshouldbeenforcedinaccordancewithallap-plicableregulationsandguidelines.
9.4.8 Employer Actions
Theemployershouldassurethatthequalifiedhealth care provider=s recommended restric-tionsofaworker=sexposuretoRCFsortooth-erworkplacehazardsarefollowedandthattheRELforRCFsisnotexceededwithoutrequir-ingtheuseofPPE.Effortstoencourageworkerparticipation in the medical monitoringpro-gramandtoreportsymptomspromptlytotheprogramdirectorareessentialfortheprogram=ssuccess.Medicalevaluationsperformedaspart
of the medical monitoring program shouldbeprovidedbytheemployeratnocosttotheparticipatingworkers.Iftherecommendedre-strictionsdeterminedbythemedicalprogramdirector include job reassignment, such reas-signmentshouldbeimplementedwiththeas-suranceofeconomicprotectionfortheworker.Whenmedicalremovalorjobreassignmentisindicated,theaffectedworkershouldnotsuf-ferlossofwages,benefits,orseniority.
Theemployershouldensurethatthemedicalmonitoring program director communicatesregularlywiththeemployer=ssafetyandhealthpersonnel(suchas industrialhygienists),em-ployee representatives, and safety and healthcommitteestoidentifyworkareasthatmayre-quireevaluationandimplementationofcon-trolmeasurestominimizetheriskfromexpo-suretohazards.
9.5 Surveillance of Health Outcomes
Standardized medical screening data shouldbeperiodicallyaggregatedandevaluatedbyanepidemiologistorotherknowledgeablepersontoidentifypatternsofworkerhealththatmaybelinkedtoworkactivitiesandpracticesthatrequireadditionalprimarypreventionefforts.Routine aggregate assessments of medicalscreeningdatashouldbeusedincombinationwithevaluationsofexposuremonitoringdatatoidentifychangesneededinworkareasorex-posureconditions.
Oneexampleof surveillanceusinganalysesofmedical screening data is the ongoing epide-miologicstudyofRCFworkersdescribedintheRCFCproduct stewardshipplanreferred toasPSP2000[RCFC2001].Elementsof thisplanmaybeadaptedandmodifiedbyotheremploy-erstodevelopmedicalsurveillanceprogramsforworkerswhoarepotentiallyexposedtoRCFs.
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9.6 Smoking Cessation
NIOSHrecognizesasynergisticeffectbetweenexposure toRCFsandcigarette smoking thatincreasestheriskofadverserespiratoryhealtheffects.Thecombinedeffectsofsmokinganddust exposures have been recognized as con-tributing to the increased risk of respiratorydiseases,includingchronicbronchitis,emphy-sema,andlungcancer.NIOSHurgesemploy-ers to establish smoking cessation programsthat (1) inform workers about the increasedhazardsofcigarettesmokingandexposuretoRCFs and (2) provide assistance and encour-agementforworkerswhowanttoquitsmok-ing. NIOSH recommends that all workerswhoarepotentially exposed toairborneRCFfibersandwhoalsosmokeshouldparticipateinasmokingcessationprogram.Withregard
tosmoking intheworkplace,NIOSHrecom-mendsthatemployersdothefollowing:
■ Prohibit workers from smoking in theworkplace.
■ Disseminate information about healthpromotion and the harmful effects ofsmoking.
■ Offersmokingcessationprogramstowork-ersatnocosttoparticipants.
■ Collectdetailedsmokinghistoriesaspartofthemedicalmonitoringprogram.
■ Use training, employee assistance pro-grams,orhealtheducationcampaignstoencourage activities promoting physicalfitness and other healthy lifestyle prac-tices that affect respiratory and cardio-vascularhealth.
Refractory Ceramic Fibers 129
10 Research Needs
NIOSH[1993]hasdevelopedafiberresearchstrategythatproposesthefollowing:
■ Research into the mechanisms for hu-manfiberdisease
■ Epidemiologic studies of fiber-exposedworkers for whom limited or no healthdataexist
■ Toxicologic experiments with fibers forwhichhealtheffectshavenotbeenestab-lished
Theresearchstrategyalsoconsiderstheuseful-nessofintegratingfiberdatafromvarioussci-entific disciplines (toxicology, epidemiology,industrialhygiene,occupationalmedicine) toelucidatethecharacteristicsoffibers.
Inaddition,NIOSHrecommendsthatthefollow-ingstepsbetakenwithregardtoRCFresearch:
1. Conductbasicscientificinvestigations,including in vitro and in vivo animalstudies,todelineatethemechanismofactionforRCFtoxicity.
2. Conduct comparable studies for oth-erSVFsandnaturalfibers so that themechanisticdatacanbecompared.Forinstance,Coffinetal.[1992]examinedthe ability of different synthetic andnaturalfiberstoinducemesotheliomas.Theysuggestedthatinadditiontofiberlengthandwidth,currentlyundefinedintrinsic surface characteristics of thefibersaredirectlyrelatedtotheirmeso-theliomainductionpotency.
3. Conductaseriesofinvitroandinvivoanimalstudiestoensurethatfibertox-icity studies share a consistent, stan-dardized approach. Such studies willensure comparability of results in avarietyofexperimentsthatallusewell-characterized, known concentrationsof synthetic or natural fibers.A seriesofcontrolled,systematicinvitrostud-iesofthefactorsbelievedtobeinvolvedin RCF pathogenicity should producevaluable data on their mechanism ofaction. Invitrostudiesprovideanex-cellentopportunitytoinvestigatefibertoxicity factors such as dose, dimen-sion, surface area, and physicochemi-cal composition. This information isanimportantsupplementtodatafromchronicinhalationstudies.
4. Assure thatan independentagencyortestinglaboratoryassemblesandkeepsasetofreferencesamplesofRCFs(sim-ilartotheUnionInternationaleContrele Cancer [UICC] asbestos samples).Well-characterizedRCFmaterialrepre-sentativeofthatfoundinoccupationalexposurescouldserveasanimportantcomponent of future animal toxicol-ogy research into the mechanisms offiber-induced disease. Additional SVFsuchasfibrousglass,mineralwool,andotherceramicfibersshouldalsoberep-resentedinthisrepository.
5. Initiate and continue occupationalhealth surveillance for industries that
130 Refractory Ceramic Fibers
10 ■Research Needs
manufacture,process,install,orremovenew fibrous materials. Understandingofthisemergingindustryisimperativeso that exposures to synthetic fibrousmaterialscanbeavoidedandindustry-specificcontrolscanbedeveloped.
6. ContinueandexpandsurveillanceofRCF exposure in U.S. manufactur-ing facilities. Continue monitoringofairbornefiberandtotalparticulate
concentrations and analyze them to-getherwith thehealthdatausingepi-demiologic research methods. Extendsurveillance efforts to include assess-mentsofworkerexposureinsecondaryfacilities.
7. Assesstheeffectsofvariableworksched-ules(suchasshiftslongerthan8hr)onRCFexposureconcentrationsandhealtheffects.
Refractory Ceramic Fibers 131
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Refractory Ceramic Fibers 147
APPENDIX A
Air Sampling Methods*
*ReprintedfromNIOSHManual of Analytical Methods (NMAM),FourthEdition,8/15/94.
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Appendix BFunctional Job Categories
for RCF Workers
Table B–1 . Functional job categories for RCF workers
Functional category Definition General examples Additional comments
Fibermanufac-turing
Theproductionormanu-factureofRCFbulkorblanket,exceptinasupervisorycapacity.Includesalljobfunc-tionsontheproductionline,frommixingtherawingredientstopackagingthefinishedproduct(bulkorblanket)attheendoftheline.
Rawmaterials,furnaceman,furnaceoperator,orassistantfurnaceoperator
Productionworkerorrelief
Blanketline
Workingleader
Needler
Slit/cut/pack
Lineutility
Utilityoperator
Chopperoperator
Endofline,baggingofbulkRCF
Endoflinetrimming,rolling,andpackagingofRCFblanket
Nonetodate
Finishing CuttingormachiningRCFmaterialsafterfibermanufacture.Handorpowertoolsmaybeusedinfinishingoperations.
OperatingdiestamponRCFblanketorpaperexceptforautomotiveapplications
Sawing,slotting,trimming,orfilingcastingtipsorrisersleeves
Cuttingblanketforductwrap
WorkinginanareawherefinishingistakingplacebutnotpersonallyworkingwithRCFsunlessinasupervisorycapacityorinotherauxiliary operations.
(Continued)
AdaptedfromMaximetal.1997.
180 Refractory Ceramic Fibers
Appendix B ■Functional Job Categories for RCF Workers
Table B–1 (Continued) . Functional job categories for RCF workers
Functional category Definition General examples Additional comments
Finishing(Continued)
CuttingortrimmingRCFboardorothervacuum-formedRCFmaterialcapacity
SandingRCFboardorothervacuum-formedRCFmaterial
Loadingsander
Off-linecuttingandtandemrerollingand/orrepackagingofRCFblanket
CuttingortrimmingRCFmod-ulesforuseinappliances
MillingorroutingRCFboardorothervacuum-formedRCFmaterial
Off-sitecuttingofbattenstripsfromRCFblanket
EXAMPLE:Unloadingdryformsfromthedryingovenandtakingthemtothefinishingareaforfinalshaping,orpackagingshapesimmediatelyafterfinishingwouldbeconsideredfinish-ing.However,unloadingdryformsfromanovenandtak-ingthemtobepackaged,orpackagingshapesthatcomedirectlyfromthedryingovenwouldbeconsideredauxiliary operations.
Installation Buildingormanufactur-ingindustrialfurnacesorboilers,refineryorpetro-chemicalplantequip-ment,kilns,foundries,electricpowergenerators,andindustrialincinera-torsatenduserlocations.Includesfurnacemainte-nance.Doesnotincludefactorymanufactureofindustrialfurnacecompo-nents.
Installinghardwareormodules
On-sitecutting(trimming)modulestofit
Caulkingandfillinggaps
WrappingmoldswithRCF
SprayingorpumpingRCFcast-ablematerialinsidefurnace
Cuttingandinstallinglaid-inblanket
Workinginsidefurnacedur-ingtheinstallationofRCFmaterials,eventhoughnotworkingdirectlywiththatmaterial(e.g.,aplumberorelectricianworkinginsideafurnaceduringaninstalla-tion)
Removal Removalofafter-serviceRCFmaterialfromanin-dustrialfurnace,etc.,thathascompleteditseco-nomiclife.IncludestheremovalofRCFmaterialduringfurnacemainte-nance.
Unwrappingandknockingoutmolds
Furnacedisassembly
Furnacemaintenance
Cleanupanddisposalofre-movedmaterial
Workinginsidefurnacedur-ingtheremovalofRCFmaterials,eventhoughnotworkingdirectlywiththatmaterial(e.g.,aplumberorelectricianworkinginsideafurnaceduringaremoval)
Assemblyoperations
CombiningorassemblingRCFmaterialwithothermaterial(RCForother),exceptautomotiveappli-cations.Includesfactoryassemblyofindustrialfurnacecomponents.
Laminating
Cuttingmaterialformodules
EncapsulatingRCFblanket
Unpackingblanketandloadingintomodulefolder
(Continued)
Refractory Ceramic Fibers 181
Appendix B ■Functional Job Categories for RCF Workers
Table B–1 (Continued) . Functional job categories for RCF workers
Functional category Definition General examples Additional comments
Assemblyoperations(Continued)
Installingbandsaroundmodules
Packagingmodulesatendofline
Trimmingmodulesandinstall-inghardware
Assemblingappliances
Off-siteassemblyofindustrialfurnacecomponents(originalequipmentmanufacture)
ChangingRCFgaskets,etc.inappliances
Cuttingandassemblingmaterialforsound-proofingexhaustducts
SewingRCFmaterial
StaplingRCFmaterial
BallmillingorgrindingRCFmaterial
MixingRCFputties,compounds,orcastables
Mixing/form-ing
Wetendproductionofvacuum-castshapes,board,andfelt
FormingRCFboardorshapes
Weighing,batching,ormixingmaterialstobeformed
Placingwetpartsonconveyor
Operatingmixingmachine
Felting
Premixingdrymaterialsbeforeaddingtomixtank
Auxiliaryop-erations
JobsinwhichworkersarepassivelyexposedtoRCFswhileperformingtheirnormaldutiesandwhoseexposures are not likely to parallel those of workers working directly with RCF materials.IncludescertainjobsinwhichRCFsmaybehandledbutwithsmallprobabilityofsignificantexposures(e.g.,ware-houseworkerorpersonunloadingcompletedpartsforpackaging).
MovingRCF-wrappedmoldsintoandoutoffurnace
Warehouseduties,includingdockwork,loadingtrucks,movingmaterials
Supervising
Drivingforklift
MakingcartonstopackageRCFsatendofline
Qualitycontrolinspection
Packagingdryparts
Maintainingorrepairingequip-mentexceptfurnaces
(Continued)
182 Refractory Ceramic Fibers
Appendix B ■Functional Job Categories for RCF Workers
Table B–1 (Continued) . Functional job categories for RCF workers
Functional category Definition General examples Additional comments
Auxiliaryoperations(Continued)
CleaningfurnacesorplantareaswhereRCFsareused
Removingvacuum-formedpartsfromovenand/orpackagingthem(nofinishing)
Other(notelsewhereclassisfied)
AlldutiesperformedintheproductionofRCFpaper,textiles,andautomotivecomponentsorotherin-dustrysectorsnotcoveredinanyoftheforegoingcategories.Also,expo-suresthatcannotreason-ablybeincludedinthecategorieslistedabove(i.e.,notelsewhereclassi-fied).Industrialhygienistpersonnelshouldexplaintasksandindustrysectorsasfullyaspossibleforob-servationsinthiscategory.
Diecuttingpartsforautomotiveairbagfilters,gaskets,mufflers,orcatalyticconverters
Wrappingsubstrateforcatalyticconverter
Operatingformertomakerov-ing
Operatingtapeloom
Operatingcardingmachine
Papermaking
WrappingRCFblanketaroundahotweldsotheweldmaycoolwithoutstressbetweenthehotseamorjointandthecoolersurroundingmetal(notelsewhereclassified)
Refractory Ceramic Fibers 183
Appendix C
Cellular and Molecular Effects of RCFs (In Vitro Studies)
human pulmonary cells. The human alveolarmacrophagehasavolumeseveral timesgreaterthanthatoftheratalveolarmacrophage[Krom-backetal.1997].Macrophagesizeandvolumemayaffect(1)thesizerangeoffibersthatcanbe phagocytized, dissolved, and cleared by thelungsand(2)theresultingpathogenicityofthefiber.Eventheuseofahumanlungcelllinedoesnotguaranteethatinvitroresultswillbedirectlyapplicable to the intact human response. Theinvivointegrationofstimulifromthenervous,hormonal,andcardiovascularsystemscannotbereproducedinvitro.
Anotherpointtoconsiderwhenreviewingthesedataisthenumberanddefinitionsofvariablesusedindifferentstudies.Variablesincludedif-ferences infibertype,fiber length,fiberdose,celltype,andlengthofexposuretested,amongothers.Disparateresultsbetweenstudiesmakestrongconclusionsfrominvitrostudiesdiffi-cult.Atthesametime,thesestudiesmaypro-videimportantdataregardingthemechanismofactionofRCFsthatwouldnotbeobtainableinothertestingvenues.
RCFsmayexerttheireffectsonpulmonarytar-getcellsviadirectorindirectmechanisms.Di-rectmechanismsaretheresultanteffectswhenfiberscomeindirectphysicalcontactwithcells.DirectcytotoxiceffectsofRCFsinclude effectsoncellviability,responses,andproliferation.
The cellular and molecular effects of RCF ex-posures have been studied with two differentobjectives.Onepurposeoftheseinvitrostud-ies is to provide a quicker, less expensive, andmore controlled alternative to animal toxic-ity testing. These experiments, which strive toact as screening tests or alternatives to animalstudies,arebestinterpretedbycomparingtheirresultswith thoseof invivoexperiments.ThesecondobjectiveofinvitrostudiesistoprovidedatathatmayhelptoexplainthepathogenesisandmechanismsofactionofRCFsat thecel-lular and molecular levels. These cytotoxicityand genotoxicity studies are best interpretedbycomparingtheeffectsofRCFswiththoseofotherSVFsandasbestosfibers.Invitrostudiesserve as an important complement to animalstudiesandprovideimportanttoolsforstudy-ingthemolecularmechanismsoffibers.ItisnotyetpossibletousethesedatainthederivationofanREL.
Drawingstrongconclusions relevant tohumanhealthbasedontheseinvitrostudiesisimpossi-ble.Onepointtoconsiderwhenreviewingthesedata is the relevance of the cell types studied.ManystudiestodatehaveexaminedtheeffectsofRCFsonrodentcelllines.ThecytotoxiceffectsofRCFsmayvarywithcellsize,volume,andlineage.Effects observed in the cells from organs otherthanthelungoreffectsinspeciesotherthanthehumanmaynotbesimilartothoseelicitedwith
184 Refractory Ceramic Fibers
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
IndirectcellulareffectsofRCFsinvolvethein-teractionoffiberswithinflammatorycellsthatmay be activated to produce inflammatorymediators. These mediators may affect targetcellsdirectlyormayattractothercellsthatactontargetcells.AninflammatorycelltypeoftenusedinRCFinvitrostudiesisthepulmonarymacrophage.Pulmonarymacrophagesarethefirst line of defense against inhaled materialthatdeposits in thealveoli, andamong func-tions,theyattempttophagocytizeparticlesde-positedinthelung.EffectsofRCFexposureonmacrophagesandotherinflammatorycellsareassessedbythemeasurementofinflammatorymediatorreleaseinvitro.
Threeimportantgroupsofinflammatoryme-diators are cytokines, ROS, and lipid media-tors (prostaglandins and leukotrienes). Someof thecytokines thathavebeen implicated intheinflammatoryprocessincludeTNFandin-terleukins(ILs).TNFandmanyILsstimulatethedepositionoffibroblastcollagen,aninitialstep infibrosis, andprostaglandins (PG)s in-hibittheseeffects.ROSincludehydroxylradi-cals,hydrogenperoxide,andsuperoxideanionradicals.OxidativestressoccurswhentheROSlevelinacellexceedsitsantioxidantlevel.Oxi-dativestressmayresultindamagetodeoxyribonucelicacid(DNA),lipids,andproteins.
Either direct or indirect effects of RCFs mayresultingenotoxiceffectsonpulmonarytargetcells.Changes in thegeneticmaterialmaybeimportant in tumor development [Solomonetal.1991].Genotoxiceffectsmaybeassessedthrough theanalysisofchromosomechangesoralterationsingeneexpressionfollowingex-posuretoRCFs.
ThefollowingsummaryofRCFinvitrostud-iesexaminestheirdirecteffectsoncellprolif-eration and viability and indirect effects viareleaseofTNF,ROS,andotherinflammatorymediators. The genotoxic effects of RCFs are
alsoexaminedandsummarized.TableC–1de-scribesRCFcytotoxicitystudiesinvolvingtheirdirecteffectsoncells.TableC–2describesRCFcytotoxicity studies involving the release ofmediators.TableC–3summarizesRCFgeno-toxicstudies.
C.1 Direct Cytotoxic Effects of RCFs
RCFsmayhaveadirectcytotoxiceffectontar-getcells.Measurementsofcellviabilityandcellproliferationarebothindicationsofcytotoxiceffects. Cell viability can be assessed throughthe detection of enzymes released by cells ordyestakenupbycellsthatindicatealteredcellmembraneintegrityorpermeability.Measure-mentofcytoplasmicLDHandtrypanblueex-clusionaretwomethodsusedtoassesscellvia-bility.LDHisacytoplasmicenzyme;itsreleaseindicates plasma membrane damage. Trypanblueisadyethatcanonlypenetratedamagedcellmembranes.β-glucuronidaseisalysosom-al enzyme, it assesses lysosomal permeabilityandmembraneviability.Itmayalsobereleasedwhen alveolar macrophages are activated byfrustrated phagocytosis. The cytotoxic effectsofRCFsonratpleuralmesothelialcells,por-cine aortic endothelial cells, human-hamsterhybrid(A
L)cells,humanmacrophages,macro-
phage-like P388D1 cells, and human alveolarepithelial cells are summarized in Table C–1andC–2andinthetextbelow.
Luoto et al. [1997] evaluated the effects ofRCFs, quartz, and several MMVFs on LDHlevels inratalveolarmacrophagesandhemo-lysisinsheeperythrocytes.RCF1,RCF2,RCF3,andRCF4at1.0mg/mlinducedalowerreleaseof LDH (less than 20% of control) from ratalveolar macrophages compared with quartz(approximately 40% of control) [Luoto et al.1997].RCF1stimulatedthelowestamountof
Refractory Ceramic Fibers 185
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
LDHrelease(lessthan10%ofcontrol),lowereven than TiO
2 (approximately 15% of con-
trol). RCF1, RCF2, RCF3, RCF4, MMVF10,MMVF11, MMVF21, and MMVF22 at 0.5,2.5, and 5.0 mg/ml induced a dose-depen-dent increase in sheeperythrocytehemolysis.RCF1andRCF3inducedslightlymorehemo-lysisthanotherMMVFs.Thehemolyticactiv-ityofMMVFswassimilartothatofTiO
2,and
muchlessthanthatofquartz.
At doses of 100, 300, and 1,000 µg/ml RCFs(unspecifiedtype),anincreasedreleaseofLDHwas induced from rat macrophages [Leikaufetal.1995].Atequivalentgravimetricdosesof1,000µg/ml,theeffectsofRCFsweremuchlessthanthoseofsilica.Ceramicfibers(unspecifiedtype)at50µg/mlinducednodifferenceinLDHlevelscomparedwithnegativecontrolsinratal-veolarmacrophages[Fujinoetal.1995].Chrys-otile,crocidolite,amosite,andanthophylliteas-bestosallinducedsignificantincreasesinLDHandβ-glucuronidaselevels.Ceramicfibersalsoinduced a significant increase in β-glucuroni-dasebutmuchlessthanthatinducedbyeachoftheasbestosfibertypes.
In the permanent macrophage-like cell lineP388D1,anelutriatedceramicfiber(unspeci-fiedtype)at10or50µg/mlafter24or48hrhad no significant effect on cell viability asmeasuredbythetrypanblueassay[Wrightetal.1986].Theelutriationprocessusedforthisexperimentprovidedmainlyrespirablefibers.All other fibers examined, excluding short-fiberamosite, reducedviability.Although thespecificdataontheeffectofexposuretofiberson enzyme release was not presented, an as-sociationbetweendecreasingcellviabilityandincreasinglossofintracellularglucosaminidaseandLDHwasreportedundermostconditionsinvestigated. Cytotoxicity was correlated withfiberlengthsgreaterthan8µmwhenallfibertypeswerecombined.
Theeffectof severalfiberson theviabilityofrat pleural mesothelial cells was investigated[Yegles et al. 1995]. On a per weight basis,the rank order of cytotoxicity was NationalInstitute for Environmental Health Sciences(NIEHS) chrysotile, RCF3, MMVF10 andRCF1,Calidriachrysotile,RCF4,andallothers.Basedonthetotalnumberoffibers,therankorder of cytotoxicity was RCF3, MMVF10,RCF1, RCF4, MMVF11, NIEHS chrysotile,amosite, and all others. Cytotoxicity was de-pendent on fiber dimensions as the longest(RCF3,MMVF10,RCF1,MMVF11)orthick-est(RCF4,RCF1,MMVF11,RCF3)fiberswerethemostcytotoxic.
RCF1,RCF2,RCF3,andRCF4werefoundtoinhibit theproliferationandcolony-formingefficiency of Chinese hamster ovary cells invitro [Hart et al. 1992]. The inhibition wasconcentration-dependent. RCF4 was leastcytotoxic,RCF2wasintermediate,andRCF1andRCF3werethemostcytotoxic.Acorrela-tionexistedbetweenaveragefiberlengthandtoxicity, with the shortest fibers being leastcytotoxic.LC
50s for theRCFranged from10
to30µg/cm2.Ineachassay,theRCFswerelesscytotoxic than those of the positive controlsofcrocidolite(LC
50=5µg/cm2)andchrysotile
(LC50
=1µg/cm2)asbestos.
At0to80µg/cm2RCF1,tremolite,anderion-ite were significantly less cytotoxic to human-hamster hybrid A
L cells than chrysotile as de-
terminedby the surviving fractionofcoloniesafterfiberexposure[Okayasuetal.1999].RCF1,crocidoliteasbestos,andMMVF10at25µg/cm2induced focalnecrosis in ratpleuralmesothe-lialcellsafter24hrthatbecameamoreobviousnecrosisby72hr[Janssenetal.1994].At72hr,thequalitativeeffectsof25µg/cm2RCF1werecomparabletothoseof5µg/cm2crocidoliteas-bestos. In contrast,minimalnecrosiswas seenat 25 µg/cm2 crocidolite asbestos, RCF2, and
186 Refractory Ceramic Fibers
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
MMVF10fibersinhamstertrachealepithelialcellsat24hr;nonecrosiswaspresentat72hr.
RCF1, RCF2, RCF3, and RCF4 as well as as-bestosandotherfibershadadose-dependenteffectoncytotoxicity,asmeasuredbycellde-tachment,inthehumanalveolarepithelialcelllineA549[Cullenetal.1997].Celldetachmentisassociatedwithepithelialdamage,animpor-tant step in the inflammatory process. Thesecells are a primary target of inhaled fibers.Whenequivalentdoses(10,25,50,and100µg/ml) were tested with various fibers, all RCFshadalesssignificanteffectthanbothcrocido-liteandamositeasbestos.Whenthedosedatawereadjustedforthenumberoffibers,RCF1,RCF2, and RCF3 were more cytotoxic thanRCF4andcrocidolite.
Inanassaydeterminingtheabilityoffiberstoinducean increase inthediameterofhumanA549cells,anelutriatedceramicfiber(unspec-ified type) had a midrange of activity whencompared with 12 other fibers [Brown et al.1986].Itwasmoreactivethanmostvarietiesofamositetested(butnotUICCamosite)butlessactivethanthechrysotilefibers.Anassociationwasfoundbetweenincreasinglengthandassayactivity.When these same fiber samples weretestedforcolony inhibition inV79/4Chinesehamsterlungfibroblasts,theceramicfiberhadevenlesseffectthantheTiO
2control.Analysis
ofallfibersupheldtheassociationbetweenin-creasinglengthandincreasedactivity.Inbothassays,fiberdiameterwasnotrelatedtoactiv-ityinmostcases.
Chrysotileasbestosat10µg/cm2andcrocido-lite asbestos at 5 µg/cm2 altered porcine aor-ticendothelialcellmorphologyandincreasedneutrophil adherence [Treadwell et al. 1996].RCF1fibersat10µg/cm2didnotchangecellmorphologyorincreaseneutrophilbinding.
ThesestudiessuggestthatRCFsmayhavesomesimilardirectcytotoxiceffectstoasbestos.Theyarecapableofinducingenzymereleaseandcellhemolysis.Theymaydecreasecellviabilityandinhibit proliferation. In most studies, the ef-fectsofRCFsaremuchlesspronouncedthanthe effects of asbestos at similar gravimetricconcentrations.Fiberlengthwasdemonstratedtobean important factor indetermining thecellresponsesinmanystudies.
C.2 Indirect Effects of RCFs: Effects on Inflammatory Cells
In addition to direct effects on target cells,RCFsmayhaveindirectmechanismsofactionbyactingoninflammatorycells.Inflammatorycells,suchaspulmonarymacrophages,mayre-spondtofiberexposurebyreleasinginflamma-torymediatorsthatinitiatetheprocessofpul-monaryinflammationandfibrosis.CytokinesandROSareamongtheinflammatorymedia-torsreleased.Manystudies,summarizedbelowand in Table C–2, have investigated this linkbetween fiber exposure and mediator releasetotrytoelucidatethemechanismofactionofRCFs.Cytokinesareaclassofproteinsthatareinvolvedinregulatingprocessessuchascellse-cretion,proliferation,anddifferentiation.Oneof thecytokinesmost commonlyanalyzed inRCFcytotoxicitystudiesisTNF.TNFhasbeenimplicatedinsilica-andasbestos-inducedpul-monary fibrosis [Piguet et al. 1990; LemaireandOuellet1996].TNFandmanyILsareas-sociated with collagen deposition (an initialstageoffibrosis),andPGsinhibittheseeffects.ExperimentsontheeffectsofRCFexposureonTNFproductioninvariouscelltypeshavehaddifferingresults.
TNFsecretionhasbeenassociatedwithex-posuretoasbestosbothinvitroandinvivo
Refractory Ceramic Fibers 187
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
[Perkins etal. 1993]. In vitro incubation ofhuman alveolar macrophages from normalvolunteers with 25µg/ml chrysotile asbestosresulted in increased levels of TNF secretion.Alveolarmacrophagesfrom6humansubjectsoccupationally exposed to asbestos for morethan 10 years secreted increased amounts ofthe cytokines TNF, IL–6, PGE
2, and IL–1ß in
vitro.Fivehumansubjectsoccupationallyex-posedfor lessthan10yearsdidnotshowin-creases in these cytokines. The two exposuregroupswerematchedforage,smokinghistory,and diagnosis. The increased TNF secretioninbothinvitroandchronicinvivoasbestos-exposedconditionssuggestsitsimportanceintheresponseofthelungtofiberexposure,al-thoughthesmallexposuregroupsizeswarrantcautionindrawingstrongconclusions.
When equal numbers (8.2 106) of variousfibertypes,includingRCF1,RCF2,RCF3,andRCF4, were incubated separately with rat al-veolar macrophages, silicon carbide whiskers,amosite, and crocidolite asbestos stimulatedthe highest TNF release [Cullen et al. 1997].RCF1,RCF2,RCF3,andRCF4showednosig-nificantincreaseinTNFreleasecomparedwithcontrol.
Incontrast,ceramicfibers(unspecifiedtype)at50 µg/ml (1.72 105 f) significantly increasedTNFreleasecomparedwithcontrolsinratal-veolar macrophages [Fujino et al. 1995]. Po-tassium octatitanate whisker, chrysotile, andcrocidoliteasbestos inducedthegreatestTNFrelease. Alveolar macrophages exposed to ei-ther300or1,000µg/mlRCFsor1,000µg/mlasbestosshowedasignificantincreaseinTNFproduction[Leikaufetal.1995].At300µg/mlRCFs,a significantelevationoccurred in leu-kotriene B
4.At 1,000 µg/ml RCFs, significant
elevationsoccurredinleukotrieneB4andpros-
taglandin E2. Levels induced at lower doses
werenotdifferentfromcontrols.Atequivalent
doses,theeffectonthelevelsofallmediatorsmeasured was greater after asbestos exposurethanafterRCFexposure.
ChrysotileA,chrysotileB,crocidolite,MMVF21,RCF1,andsiliconcarbideat100µg/mlcausedasignificantlyincreasedsynthesisofTNFmRNAafter90minutesof incubationwithratalveo-larmacrophages[Ljungmanetal.1994].After4hrofincubation,chrysotileAstillhadasignifi-cantly increased TNF mRNA production, andallotherfiberswereatbaselineconcentrations.None of the fibers studied increased TNF re-leaseat90minutes.However,anincreasedTNFbioactivity occurred after 4 hr of incubationwith chrysotile A, chrysotile B, crocidolite, orMMVF21.RCF1at100µg/mldidnotincreaseTNFproductionundertheseconditions.
Chrysotile asbestos and alumina silicate ce-ramicfibersincreasedinvitroalveolarmacro-phageTNFproductioninratsexposedtociga-rette smoke invivoand in ratsunexposed tosmoke[Morimotoetal.1993].Asbestosat50and100µg/mlinducedasignificantlygreaterTNFreleaseinratsexposedtocigarettesmokeversus unexposed rats. No significant differ-enceswerefoundbetweengroupsatalldosesof RCF fibers tested (25, 50 and 100 µg/ml).RCF exposure, in contrast to chrysotile, didnot have a significant synergistic effect withcigarettesmokeexposure.
InadditiontothecytokinessuchasTNF,an-other group of inflammatory mediators thathas been studied in vitro are the ROS. Thesemediators, also referred to as reactive oxygenmetabolites (ROMs) are normally producedduringtheprocessofcellularaerobicmetabo-lismandinphagocyticcellsinresponsetopar-ticleexposure.Onemoleculareffectofasbestosexposurehasbeendemonstratedtobethein-ductionofROS[Kampetal.1992].OxidativestressoccurswhentheROSlevel inacellex-ceedstheantioxidantlevel.ROSmayresultin
188 Refractory Ceramic Fibers
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
damagetoDNA,lipidsandproteinsandhavebeenimplicatedinhavingaroleincarcinogen-esis[Klaunigetal.1998;Vallyathanetal.1998].Thisresearchhassuggestedthatfreeradicalac-tivitymaybe involved in thepathogenesisoffiber-inducedlungdisease.
TheabilityofRCFstoinducethereleaseoffreeradicals has been studied in rodent alveolarmacrophages.RF1andRF2(Japaneseceramicfibers)at200µg/mlinducedasignificantpro-ductionofsuperoxideanionandasignificantincreaseinintracellularfreecalciuminguineapig alveolar macrophages [Wang et al. 1999].Both superoxide anion and increased intra-cellular calcium are associated with oxidativestress.Superoxideanionsmaygeneratehydro-gen peroxide and hydroxyl radical, classifiedasROSorfreeradicals.RF2exposureresultedinasignificantdepletionofglutathione.Glu-tathioneisacellularantioxidantthatprotectscellsagainstoxidativestress;depletionofglu-tathioneisassociatedwithoxidativestress.TheRFsdidnotaffecthydrogenperoxideproduc-tion.Ineachtest,theeffectsofchrysotileweresignificantlygreaterthanthoseoftheRFs.
RCF1,MMVF10,andamositeasbestosat8.24×106f/mlinducedasignificantdepletionofintra-cellularglutathioneinratalveolarmacrophages[Gilmouretal.1997].RCF1hadsimilareffectstoamositeasbestos,whereasMMVF10causedthegreatestdepletionofglutathione.
RCF1, RCF2, and RCF3 induced a greaterproductionofROMsinhumanpolymorpho-nuclearcellculturesthanRCF4andchrysotile[Luotoetal.1997].Adose-dependentproduc-tionofROMswasseeninallRCFsandotherMMVFstestedfrom25to500µg/ml.QuartzhadagreatereffectonROMproductionthanallfiberstested.
RCF1hadahighbindingcapacityforratim-munoglobulin (IgG), a normal component
oflungliningfluid[Hilletal.1996].Atdoses>100µgRCF1,fiberscoatedwithIgGinduceda significantly increased superoxideanionre-lease.Thissupportsthepremisethatlunglin-ing fluid and other substances that fibers areexposed to invivomay significantly alter theeffectoffibersoncells. IgG-coated longfiberamosite asbestos, in spite of a poor bindingaffinityforIgG,inducedacomparablesuper-oxideanionreleaseresponsetothatofcoatedRCF1.
Brown et al. [1999] investigated the abil-ityofRCF1,amositeasbestos,siliconcarbide,MMVF10,Cole100/475glassfiber,andRCF4tocausetranslocationofthetranscriptionfac-torNF-κBtothenucleusinA549lungepithe-lial cells. RCF1, amosite asbestos, and siliconcarbideproducedasignificantdose-dependenttranslocationofNF-κBtothenucleus;theoth-er fibers tested did not. Equal fiber numbersweretested.
These cytotoxicity studies indicate that RCFsmaysharesomeaspectsoftheirmechanismofactionwithasbestos.Theybothaffectthepro-ductionofTNFandROSaswellascellviabil-ityandproliferation.TheeffectsofRCFshaveusuallybeenlesspronouncedthanthoseofas-bestos.Resultsofinvitrostudiesaredifficulttocompare,evenwithinstudiesofdifferentfibertypes, because of different study designs, dif-ferentfiberconcentrationsandcharacteristics,anddifferentendpoints.
C.3 Genotoxic Effects of RCFs
Inaddition to researchassessing thecytotox-icity of RCFs, studies have also assessed thegenotoxicityofRCFs.Mostgenotoxicityassaysassesschanges inordamage togeneticmate-rial.Methodsthathavebeenusedtoinvestigatethegenotoxicityoffibersincludecell-freeorin
Refractory Ceramic Fibers 189
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
vitro cell systems investigating DNA damage,studiesofaneuploidyorpolyploidy,studiesofchromosome damage or mutation, gene mu-tationassays,andinvestigationsofcellgrowthregulation[Jaurand1997].Severalstudies,de-scribed below and in Table C–3, have exam-inedtheabilityofRCFstoproducegenotoxicchangesincomparisonwithasbestos.
Severalfibers,includingRCF1andRCF4,wereassayedforfreeradicalgeneratingactivityus-ingaDNAassayandasalicylateassay[Brownet al.1998]. The DNA plasmid assay showedonlyamositeasbestostohavefreeradicalactiv-ity.ThesalicylateassayshowedamositeaswellasRCF1 tohave free radical activity.Coatingthefiberswithlungsurfactantdecreasedtheirhydroxyl radical generation. Differences inRCF1resultsinthetwoassayswereproposedto be a result of increased iron release fromRCF1 in the salicylateassay.An ironchelatorinhibited theRCFhydroxylationof salicylate.RCF4showednofreeradicalactivity.
When equal fiber numbers were compared,RCF1, RCF2, RCF3, and RCF4 had minimalfree- radical-generating activity on plasmidDNA compared with crocidolite and amositeasbestos [Gilmour et al. 1995]. RCFs andotherMMVFproduceda smallbut insignifi-cant amount of DNA damage. This damagewas mediated by hydroxyl radicals. No cor-relationwas foundbetween ironcontentandfreeradicalgeneration.At9.3×105fibersperassay,amositeproducedsubstantial freeradi-cal damage to plasmid DNA [Gilmour et al.1997]. Amosite significantly upregulated thetranscription factors AP–1 and NFkB; RCF1hadamuchsmallereffectonAP–1upregula-tiononly.
SVFs, including ceramic fibers (unspecified),werereportedtoformhydroxylradicalsbasedon the formation of the DNA adduct 8-hy-droxydeoxyguanosine(8-OH-dG)from2-de-
oxyguanosine (dG) in calf thymus DNA andsolution [Leanderson et al. 1989; LeandersonandTagesson1989].Ceramicandglasswoolfi-bershadpoorhydroxylatingcapabilitiesrelativetorockwoolandslagwoolfibers[Leandersonetal.1989].Hydroxylradicalscavengers,suchas dimethyl sulfoxide, decreased the hydrox-ylation. Compounds that increase hydroxylradicalformation,suchashydrogenperoxide,increasedhydroxylation.Rockwool incombi-nationwithcigarettesmokecondensatecausedasynergistic increasein8-OH-dGformation;ceramicandglasswoolfibersdidnothavesyn-ergisticeffectswithcigarettesmoke[Leander-sonandTagesson1989].
RCF1,RCF2,RCF3,andRCF4inducednucle-ar abnormalities, including micronuclei andpolynuclei, in Chinese hamster ovary cells[Hartetal.1992].Micronucleimayformwhenchromosomes or fragments of chromosomesare separated during mitosis. Polynuclei mayarisewhencytokinesis fails aftermitosis.Theincidenceofmicronucleiandpolynucleiafterexposureto20µg/cm2RCFwasfrom22%to33%. At 5 µg/cm2, chrysotile and crocidoliteinduced nuclear abnormalities of 49% and28%,respectively.
Amosite, chrysotile, and crocidolite asbestos,andceramicfiberscausedasignificantincreaseinmicronuclei inhumanamnioticfluid cells[Dopp et al. 1997]. The response was dose-dependent with asbestos fiber exposure butnot with ceramic fiber exposure. Significantincreases in chromosomal breakage and hy-perdiploidcellswerenotedafterasbestosandceramicfiberexposure.
RCF1, RCF3, and RCF4 did not induce ana-phase aberrations in rat pleural mesothelialcells [Yegles et al. 1995]. Of all fibers tested,UICCchrysotilewasthemostgenotoxiconthebasisofweight,numberoffiberswithalength>4 µm and number of fibers corresponding
190 Refractory Ceramic Fibers
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
toStanton=sandPott=scriteria[Stantonetal. 1981;Pott etal. 1987].
TheeffectoffibersonthemRNAlevelsofc-fosandc-junproto-oncogenesandornithinedecarboxylase(ODC)inhamstertrachealepi-thelial (HTE) cells and rodent pleural meso-thelial(RPM)cellswereexamined[Janssenetal.1994].ODCisarate-limitingenzymeinthesynthesisofcompoundsinvolvedincellprolif-erationandtumorpromotion,thepolyamines.InHTEcells,crocidoliteinducedasignificantdose-dependentincreaseinlevelsofc-junandODC mRNA but not c-fos mRNA. RCF1 in-ducedonlysmallnondose-dependentincreasesinODCmRNAlevels.InRPMcells,crocidolitefibersat2.5µg/cm2significantlyelevated lev-elsofc-fosandc-junmRNA.RCF1increasedproto-oncogeneexpressionat cytotoxic levelsof25µg/cm2;nosignificanteffectwasseenatconcentrations≤5µg/cm2.
RCF1 fibers were nonmutagenic in the hu-man-hamsterhybridcelllineA
L[Okayasuetal.
1999].Chrysotilewasasignificant inducerofmutationsinthesamesystem.
These studies demonstrate that RCFs maysharesomesimilargenotoxicmechanismswithasbestos including induction of free radicals,micronuclei,polynuclei, chromosomalbreak-age,andhyperdiploidcells.Otherstudieshavedemonstratedthat,usingcertainmethodsanddoses,RCFsdidnot induceanaphaseaberra-tionsandinducedproto-oncogeneexpressiononly at cytotoxic concentrations. RCFs werenonmutagenicinhuman-hamsterhybridcells.
C.4 Discussion of In Vitro Studies
Thetoxicityoffibershasbeenattributabletotheirdose,dimensions,anddurability.Anytestsystemthatisdesignedtoassessthepotential
toxicity of fibers must address these factors.Durability is difficult to assess using in vitrostudies because of their acute time course.However,invitrostudiesprovideanopportu-nity tostudy theeffectsofvaryingdosesanddimensionsoffibersinaquicker,moreefficientmethod than animal testing. Although theyprovideimportantinformationaboutmecha-nismofaction,theydonotcurrentlyprovidedatathatcanbeextrapolatedtooccupationalriskassessment.
Theassociationbetweenfiberdimensionandtoxicity has been documented and reviewed[Stantonetal.1977,1981;Pottetal.1987;War-heit 1994]. Fiber length has been correlatedwiththecytotoxicityofglassfibers[Blakeetal.1998].Manvillecode100(JM–100)fibersam-plesofaveragelengthsof3,4,7,17,and33µmwere assessed for their effects on LDH activ-ityandratalveolarmacrophagefunction.Thegreatestcytotoxicitywasreportedinthe17µmand 33 µm samples, indicating that length isanimportantfactorinthetoxicityofthisfiber.Multiplemacrophageswereobservedattachedalongthelengthoflongfibers.Relativelyshortfibers, <20µm long, were usually phagocy-tized by one rat alveolar macrophage [Luotoet al. 1994]. Longer fibers were phagocytizedby twoormoremacrophages. Incomplete,orfrustrated,phagocytosismayplayaroleintheincreasedtoxicityoflongerfibers.Longfibers(17 µm average length) were a more potentinducer of TNF production and transcrip-tionfactoractivationthanshorterfibers(7µmaveragelength)[Yeetal.1999].Thesestudiesdemonstrate the important role of length infibertoxicityandsuggestthatthecapacityformacrophagephagocytosismaybeacriticalfac-tor in determining fiber toxicity. The toxicityof individualfibersofthesametypeofRCFsmaydifferaccordingtotheirsizeinrelationtoalveolarmacrophages.
Refractory Ceramic Fibers 191
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
Several RCF in vitro studies reported a di-rectassociationbetweena longerfiber lengthandgreatercytotoxicity.Hartetal.[1992]re-portedtheshortestfiberstobetheleastcyto-toxic.Brownetal.[1986]reportedanassocia-tionbetweenlengthandcytotoxicactivitybutnot between diameter and activity.Wright etal. [1986] reported that cytotoxicity was cor-relatedwithfibers>8µmlength.Yeglesetal.[1995] reported that the longest and thickestfiberswerethemostcytotoxic.ThefourmostcytotoxicfibershadGMlengths≥13µmandGMdiameters>0.5µm.Theproductionofab-normalanaphasesandtelophaseswasassociat-edwithStantonfiberswithalength>8µmanddiameter≤0.25µm.Hartetal.[1994]reportedthatcytotoxicityincreasedwithfiberlengthupto20µm.Allofthesestudiesdemonstratetheimportanceoffiberdimensionsoncytotoxicity.Otherstudieshavenotreportedthelengthdis-tributionoffibersamplesused.WhenstudiesaredonewithRCFsforwhichspecificlengthsareassessedforcytotoxicity(suchashasbeendonewithglassfibers)[Blakeetal.1998],itwillbepossibletodeterminethestrengthoftheas-sociationbetweenRCFfiberlengthandtoxic-ityanddeterminewhetherathresholdlengthexistsabovewhichtoxicityincreasessteeply.
Inadditiontoprovidingdataonthecorrelationbetweenfiberlengthandtoxicity,invitrostud-ieshaveprovideddataontherelativetoxicityofRCFscomparedwithasbestos.Uncertaintiesex-istintheinterpretationofthesestudiesbecauseof differences in fiber doses, dimensions, anddurabilities.RCFsdoappeartosharesomesim-ilar mechanisms of action with asbestos. (SeereferencesinTablesC–1,C–2,andC–3.)Theyhavesimilardirectandindirecteffectsoncellsand alter gene function in similar ways. Theyare capable of inducing enzyme release andcellhemolysis.Theymaydecreasecellviabilityand inhibit proliferation. They both affect theproductionoftumornecrosisfactorandROS,andaffectcellviabilityandproliferation.They
inducenecrosisinratpleuralmesothelialcells.Theyalsomayinducefreeradicals,micronuclei,polynuclei,chromosomalbreakage,andhyper-diploidcellsinvitro.
Invitrostudiesalsoprovideanexcellentoppor-tunityforinvestigatingthepathogenesisofRCF.However,comparisonsaredifficulttomakebe-tweeninvitrostudiesbecauseofdifferencesinfiberdoses,dimensions,preparations,andcom-positions.Importantinformation,suchasfiberlength distribution, is not always determined.Even when comparable fibers are studied, thecelllineorconditionsunderwhichtheyaretest-edmayvary.Muchoftheresearchtodatehasbeendoneinrodentcelllinesandincellsthatarenotrelatedtotheprimarytargetorgan.Invitrostudiesusinghumanpulmonarycelllinesshouldprovidepathogenesisdatamostrelevanttohumanhealthriskassessment.
Short-term in vitro studies cannot take intoaccounttheinfluenceoffiberdissolutionandfiber compositional changes that may occurover time. In an in vivo exposure, fibers arecontinually modified physically, chemically,andstructurallybycomponentsofthelungen-vironment. This complex set of conditions isdifficulttorecreateinvitro.Justasitisunlikelythatonlyonefactorwillbeanaccuratepredic-toroffiber toxicity, it ismuchmoreunlikelythatanyoneinvitrotestwillbeabletopredictfibertoxicity.Bestresultsareobtainedbytox-icityassessmentinseveralinvitrotestsandincomparisonwithinvivoresults.Invitrostud-iesprovideanexcellentopportunitytoinves-tigate factors important tofiber toxicity suchasdose,dimension,surfacearea,andphysico-chemicalcomposition.Theyprovidetheabil-itytoobtaininformationthatisanimportantsupplement to thedataof chronic inhalationstudies.Theydonot currentlyprovide infor-mationthatcanbedirectlyappliedtohumanhealthriskassessmentandthedevelopmentofoccupationalexposurelimits.
192 Refractory Ceramic Fibers
Appendix C ■ Cellular and Molecular Effects of RCFs (In Vitro Studies)
Tabl
e C
–1 .
In v
itro
cyt
otox
icit
y of
RC
Fs:* d
irec
t eff
ects
on
cel
ls
Ref
eren
ceC
ell l
ine
and
en
dp
oin
tsFi
ber
typ
eLe
ngt
h (
µm
)D
iam
eter
(µ
m)
Dos
eR
esu
lts
Bro
wn
et
al.
[198
6]A
549
cells
Cel
ldia
met
er
V79
/4C
hin
ese
ham
ster
lun
gfi
brob
last
s C
olon
yin
hib
itio
n
Elu
tria
ted
(E)
cera
mic
(u
nsp
ecifi
ed)
Tit
aniu
md
ioxi
de
Qu
artz
Sh
ort
fibe
ram
osit
eU
ICC
cro
cido
lite
Efa
ctor
yam
osit
eE
UIC
Cc
roci
dolit
eE
bru
cite
U
ICC
am
osit
eSu
per
fin
ech
ryso
tile
E
UIC
Ca
nth
ophy
llite
U
ICC
ch
ryso
tile
A
Et
rem
olit
eE
lon
gfi
ber
amos
ite
EU
ICC
ch
ryso
tile
A
Not
rep
orte
dN
otr
epor
ted
A54
9ce
lls:
25o
r50
µg/
ml
V79
/4c
ells
:0,
5,1
0,2
5,7
5,
or1
00µ
g/m
l
A54
9as
say:
C
hry
soti
lee
ffec
t>
cera
mic
eff
ect>
m
ost
amos
ites
(n
otU
ICC
am
osit
e).
V79
/4a
ssay
:C
eram
icfi
ber
had
no
effe
ct.
Cer
amic
fibe
rh
add
iffe
ren
tre
sult
sin
th
etw
oas
says
.
Ass
ocia
tion
fou
nd
betw
een
incr
eas-
ing
fibe
rle
ngt
h(
allt
ypes
)an
dac
tivi
tyin
bot
ha
ssay
s.
Cu
llen
et
al.
[1
997]
Hu
man
alv
eola
r
epit
hel
ialc
ells
C
elld
etac
hm
ent
RC
F1
RC
F2
RC
F3
RC
F4
Lon
gam
osit
eC
roci
dolit
eC
100/
475
glas
s10
4Eg
lass
Si
licon
car
bide
1
Silic
onc
arbi
de2
M
MV
F10
MM
VF1
1M
MV
F21
MM
VF2
2
Geo
met
ric
mea
n:
10
.42
±2
.66
12
.43
±2
.66
14
.99
±2
.64
6
.82
±2
.00
3
.03
±2
.86
4
.96
±2
.57
2
.88
±2
.62
3
.50
±2
.17
8
.73
±2
.25
N
otd
one
23
.91
±2
.39
14
.21
±2
.64
15
.66
±2
.76
13
.67
±2
.34
Geo
met
ric
mea
n:
0.
79±
2.0
7
0.84
±2
.01
0.
71±
2.1
2
0.94
±1
.71
0.26
±1
.75
0.
15±
1.5
3
0.22
±1.
85
0.
25±
1.6
0.47
±1
.39
N
otd
one
1.
13±
1.9
0
0.57
±2
.01
0.
81±
1.7
6
0.89
±1
.78
10,2
5,5
0,o
r
100
µg/m
lA
teq
uiv
alen
tdo
ses,
all
RC
Fsh
adle
ss
effe
ctt
han
cro
cido
lite
and
amos
ite
asbe
stos
.
Wh
ena
dju
sted
for
equ
ival
ent
fibe
rn
um
bers
,cro
cido
lite,
RC
F4,
MV
F11,
an
dam
osit
ew
ere
leas
tcy
toto
xic;
RC
F1,R
CF2
,an
dR
CF3
w
ere
mor
ecy
toto
xic
than
cro
cido
-lit
ean
dam
osit
e.
See
foot
not
eat
en
dof
tab
le.
(Con
tin
ued
)
Refractory Ceramic Fibers 193
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
Tabl
e C
–1 (
Con
tin
ued
) . I
n v
itro
cyt
otox
icit
y of
RC
Fs:* d
irec
t eff
ects
on
cel
ls
Ref
eren
ceC
ell l
ine
and
en
dp
oin
tsFi
ber
typ
eLe
ngt
h (
µm
)D
iam
eter
(µ
m)
Dos
eR
esu
lts
Fujin
oet
al.
[199
5]R
ata
lveo
lar
mac
roph
ages
LD
H
β
-glu
curo
nid
ase
Cer
amic
Gla
ssPo
tass
ium
oct
atit
anat
eM
agn
esiu
ms
ulf
ate
(lon
g)M
agn
esiu
ms
ulf
ate
(sh
ort)
Ch
ryso
tile
asb
esto
sC
roci
dolit
eas
best
osA
mos
ite
An
thop
hylli
teE
rion
ite
Geo
met
ric
mea
n:
29
.5±
3.1
12
.8±
3.0
2
.8±
2.0
12
.0±
2.3
4
.9±
2.1
0
.7±
1.9
1
.3±
2.3
2
.7±
2.5
2
.5±
3.5
1
.4±
2.0
Geo
met
ric
mea
n:
1.
92±
2.9
0.
54±
2.2
0.
41±
1.5
0.
44±
1.6
0.
31±
1.5
0.0
85±
1.4
0.
20±
1.5
0.
32±
1.8
0.
36±
2.3
0.
21±
1.6
50µ
g/m
lLD
H:
Cer
amic
fibe
r,m
agn
esiu
ms
ulf
ate
wh
iske
rs,a
nd
erio
nit
ew
ere
not
di
ffer
ent
from
con
trol
;all
oth
ers
sign
ifica
ntl
yin
crea
sed
leve
ls.
β-gl
ucu
ron
idas
e:A
llfi
bers
cau
sed
asi
gnifi
can
tin
crea
sec
ompa
red
wit
hc
ontr
ol;
chry
soti
lec
ause
dth
eh
igh
est
rele
ase.
Har
tet
al.
[1
992]
Ch
ines
eh
amst
er
ovar
yce
lls
Cel
lpro
lifer
atio
n
Col
ony
form
atio
n
RC
F1R
CF2
RC
F3R
CF4
UIC
CC
roci
dolit
eU
ICC
Ch
ryso
tile
Geo
met
ric
mea
n:
21
.5±
16.
12
16.7
±1
5.03
24
.3±
18.
82
9.2
±7
.08
1
.8±
1.9
4
1.65
±1
.83
Geo
met
ric
mea
n:
1.
03±
0.7
3
1.11
±0
.82
1.
22±
0.9
8
1.43
±0
.79
0.
21±
0.1
2
0.12
±0
.07
RC
F1–4
:0,
5,1
0,o
r
20µ
g/m
l
Cro
cido
lite:
0
or5
µg/
ml
Ch
ryso
tile
:0,
1,2
,or
5
µg/m
l
RC
Fsin
duce
da
con
cen
trat
ion
-de
pen
den
tde
crea
sein
col
ony
form
atio
na
nd
cell
prol
ifer
atio
n.
LC50
:R
CFs
10–3
0µg
/cm
2
Cro
cido
lite
5µg
/cm
2
Ch
ryso
tile
1
µg/c
m2
RC
Fcy
toto
xici
ty:R
CF1
an
dR
CF3
are
mos
tcy
toto
xic;
RC
F2
isin
term
edia
te;R
CF4
isle
ast
cyto
toxi
c.
Leik
auf
eta
l.
[199
5]R
ata
lveo
lar
mac
roph
ages
LD
H
RC
FC
roci
dolit
eas
best
osSi
lica
Tit
aniu
md
ioxi
de
Med
ian
:
4.9
2.
5
Not
ava
ilabl
e
Not
ava
ilabl
e
Med
ian
:
0.59
0.
28
0.88
0.
18
100,
300
,1,
000
µg/m
l
RC
Fsin
duce
dm
oder
ate
incr
ease
sin
LD
Hle
vels
.%o
fco
ntr
ol:
RC
Fs
100
µg/
ml—
158%
R
CFs
3
00µ
g/m
l—17
4%
RC
Fs1
,000
µg/
ml—
295%
Si
lica
1,0
00µ
g/m
l—89
6%
See
foot
not
eat
en
dof
tab
le.
(Con
tin
ued
)
194 Refractory Ceramic Fibers
Appendix C ■ Cellular and Molecular Effects of RCFs (In Vitro Studies)
Tabl
e C
–1 (
Con
tin
ued
) . I
n v
itro
cyt
otox
icit
y of
RC
Fs:* d
irec
t eff
ects
on
cel
ls
Ref
eren
ceC
ell l
ine
and
en
dp
oin
tsFi
ber
typ
eLe
ngt
h (
µm
)D
iam
eter
(µ
m)
Dos
eR
esu
lts
Luot
oet
al.
[199
7] Sh
eep
eryt
hro
cyte
s
H
emol
ysis
Rat
alv
eola
r
m
acro
phag
es
LD
H
RC
F1
RC
F2
RC
F3
RC
F4
MM
VF1
0M
MV
F11
MM
VF2
1M
MV
F22
Mea
n:
21.2
9±
17.
42
20.1
8±
19.
63
25.6
6±
25.
74
10.3
4±
11.
59
23.2
1±
15.
57
15.6
5±
13.
31
26.0
2±
23.
10
20.7
5±
20.
52
Mea
n:
1.30
±0
.72
1.39
±0
.98
1.37
±0
.87
1.33
±1
.02
1.42
±0
.78
1.12
±0
.88
1.18
±0
.64
0.88
±0
.45
Hem
olys
is:
0.5,
2.5
,or
5.
0m
g/m
l
LDH
:1.
0m
g/m
l
Hem
olys
is:
Dos
e-de
pen
den
tin
crea
sein
he-
mol
ysis
indu
ced
bya
llfi
bers
an
ddu
sts.
RC
F1a
nd
RC
F3w
ere
slig
htl
ym
ore
hem
olyt
ict
han
all
oth
erfi
bers
bu
tm
uch
less
th
anq
uar
tz.
LDH
:R
CF1
indu
ced
the
leas
tLD
H
rele
ase;
MM
VF
22h
adt
he
grea
test
fi
ber-
indu
ced
LDH
rel
ease
;qu
artz
in
duce
dth
egr
eate
stL
DH
rel
ease
ov
eral
l.
Oka
yasu
et
al.
[1
999]
Hu
man
-ham
ster
hy
brid
ALc
ells
Su
rviv
ing
co
lon
ies
UIC
Cc
hry
soti
le
Trem
olit
eE
rion
ite
RC
F1
Geo
met
ric
mea
n:
1.78
±2
.3
1.41
±2
.7
1.31
±2
.9
13.5
±2
.7
Geo
met
ric
mea
n:
0.12
±0
.08
0.13
±3
.43
0.23
±2
.74
0.95
±2
.6
0–40
0µg
/ml
0–80
µg/
cm2
Ch
ryso
tile
was
mor
ecy
toto
xic
th
ano
ther
fibe
rs.
Mea
nle
thal
dos
es:
Ch
ryso
tile
~
4µg
/cm
2 R
CF1
35µ
g/cm
2 Tr
emol
ite
4
0µg
/cm
2 E
rion
ite
42
µg/c
m2
Wri
ght
eta
l.
[198
6] P
388D
1
Tr
ypan
blu
eas
say
L
DH
co
nce
ntr
atio
ns
G
luco
sam
inid
ase
co
nce
ntr
atio
ns
UIC
Cc
roci
dolit
eU
ICC
am
osit
eU
ICC
ch
ryso
tile
A
EU
ICC
cro
cido
lite
EU
ICC
am
osit
eE
UIC
Cc
hry
soti
leA
E
UIC
Ca
nth
ophy
llite
E
cer
amic
fibe
rE
lon
gfi
ber
amos
ite
Shor
tfi
ber
amos
ite
Et
rem
olit
e
Cu
mu
lati
vefi
ber
len
gth
dis
trib
u-
tion
sre
port
ed
Alm
ost
allfi
bers
m
easu
red
had
di
amet
ers
less
th
an3
µm
;de
tails
not
re
port
ed
Fibe
rn
um
ber
in
10
-10 g
±S
D:
112
±1
0
76±
6
185
±1
8
1
09±
10
112
±1
4
1
44±
20
169
±1
5
15±
0.4
19±
1
Tryp
anb
lue
assa
y:
Cer
amic
fibe
rsa
tbot
hdo
ses
had
the
low
estd
egre
eof
cyt
otox
icit
y;a
llot
her
fiber
s,ex
clud
ing
shor
t-fib
er
amos
ite,r
educ
edv
iabi
lity.
Fibe
rs>
8µm
wer
eus
ually
mos
tef-
fect
ive
ind
ecre
asin
gvi
abili
tya
nd
incr
easi
ngL
DH
and
glu
cosa
min
i-da
sec
once
ntra
tion
s;in
divi
dual
fibe
ref
fect
sw
ere
notr
epor
ted.
See
foot
not
eat
en
dof
tab
le.
(Con
tin
ued
)
Refractory Ceramic Fibers 195
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
Tabl
e C
–1 (
Con
tin
ued
) . I
n v
itro
cyt
otox
icit
y of
RC
Fs:* d
irec
t eff
ects
on
cel
ls
Ref
eren
ceC
ell l
ine
and
en
dp
oin
tsFi
ber
typ
eLe
ngt
h (
µm
)D
iam
eter
(µ
m)
Dos
eR
esu
lts
Wri
ght
eta
l.
[1
986]
(Con
tin
ued
)
Eb
ruci
te
SFA
ch
ryso
tile
T
itan
ium
dio
xide
Q
uar
tz
44±
2.7
22
±1
.6
152
±1
47.
4±
0.5
Fibe
rdo
se:
10o
r50
µg/
ml
80µ
g/m
l20
µg/
ml
Yegl
ese
tal
.
[199
5]R
atp
leu
ral
m
esot
hel
ialc
ells
C
ellv
iabi
lity:
Mit
och
ondr
ial
in
tegr
ity
RC
F1
RC
F3
RC
F4
MM
VF1
0M
MV
F11
Ch
ryso
tile
(ch
rys)
,UIC
C
Ch
rys
445
(Can
adia
n)
Ch
rys
443
(C
anad
ian
)C
hry
s,s
hor
tC
anad
ian
C
hry
s,s
up
erfi
ne
Can
adia
n
Ch
rys,
ph
osph
oryl
ated
Can
adia
n
Ch
rys,
ph
osph
oryl
ated
,
mill
edC
anad
ian
U
ICC
ch
rys,
leac
hed
wit
h
ox
alic
aci
d
Ch
rys,
Cal
idri
aC
hry
s,N
IEH
SA
mos
ite
Cro
cido
lite
Att
apu
lgit
e
Mea
n:
19
.2±
15.
0
31.8
±3
6.0
8
.9±
7.2
21.5
±1
6.8
16
.7±
12.
9
1.7
±2
.2
2
.3±
2.3
1.9
±1
.9
1
.6±
1.4
2.4
±3
.1
4
.7±
5.2
4.7
±5
.9
2
.3±
1.8
2.8
±3
.0
4
.2±
1.2
2.4
±1
.8
2
.1±
3.6
0.8
±0
.5
Mea
n:
1.
30±
0.8
0
0.74
±0
.50
1.
30±
0.6
0
0.55
±0
.50
1.
10±
0.9
0
0.05
±0
.04
0.
04±
0.0
3
0.04
±0
.04
0.
06±
0.0
8
0.04
±0
.03
0.
04±
0.0
3
0.07
±0
.09
0.
17±
0.1
1
0.05
±0
.04
0.
05±
0.0
5
0.31
±0
.20
0.
19±
0.1
2
0.04
±0
.03
12.5
,25,
50,
75,
or
100
µg/
cm2
Cyt
otox
icit
yp
erw
eigh
tba
sis:
Ch
rys
NIE
HS
>R
CF3
>
MM
VF1
0=R
CF1
>C
hry
s,c
alid
ria
>R
CF4
>a
llot
her
s
Cyt
otox
icit
yp
erto
taln
um
ber
of
fi
bers
:
RC
F3>
MM
VF1
0>
RC
F1>
RC
F4>
MM
VF1
1>
Ch
rys,
N
IEH
S>am
osit
e>
allo
ther
s
Fibe
rle
ngt
ha
nd
diam
eter
cor
rela
ted
w
ith
cyt
otox
icit
y:lo
nge
sta
nd
thic
kest
fibe
rsw
ere
mos
tcy
toto
xic.
*Abb
revi
atio
ns:
E=
elu
tria
ted;
LD
H=
lact
ate
dehy
drog
enas
e;M
MV
F=m
an-m
ade
vitr
eou
sfi
ber;
NIE
HS=
Nat
ion
alI
nst
itu
teo
fE
nvir
onm
enta
lHea
lth
Sci
ence
s;R
CFs
=re
frac
tory
ce
ram
icfi
bers
;SD
=st
anda
rdd
evia
tion
;UIC
C=
Un
ion
In
tern
atio
nal
eC
ontr
ele
Can
cer.
196 Refractory Ceramic Fibers
Appendix C ■ Cellular and Molecular Effects of RCFs (In Vitro Studies)
Tabl
e C
–2 .
In v
itro
cyt
otox
icit
y of
RC
Fs:* e
ffec
ts o
n m
edia
tor
rele
ase
Ref
eren
ceC
ell l
ine
and
en
dp
oin
ts
F
iber
typ
eLe
ngt
h (
µm
)D
iam
eter
(µ
m)
Dos
eR
esu
lts
Cu
llen
et
al.
[1
997]
Hu
man
alv
eola
r
ep
ith
elia
lcel
ls
T
NF
RC
F1
RC
F2
RC
F3
RC
F4
Lon
gam
osit
eC
roci
dolit
eC
100/
475
glas
s10
4Eg
lass
Si
C1
SiC
2M
MV
F10
MM
VF1
1M
MV
F21
MM
VF2
2
Geo
met
ric
mea
n:
10
.42
±2
.66
12
.43
±2
.66
14
.99
±2
.64
6
.82
±2
.00
3
.03
±2
.86
4
.96
±2
.57
2
.88
±2
.62
3
.50
±2
.17
8
.73
±2
.25
Not
don
e
23.9
1±
2.3
9
14.2
1±
2.6
4
15.6
6±
2.7
6
13.6
7±
2.3
4
Geo
met
ric
mea
n:
0.
79±
2.0
7
0.84
±2
.01
0.
71±
2.1
2
0.94
±1
.71
0.26
±1
.75
0.
15±
1.5
3
0.22
±1.
85
0.
25±
1.6
0.47
±1
.39
N
otd
one
1.
13±
1.9
0
0.57
±2
.01
0.
81±
1.7
6
0.89
±1
.78
8.2×
106 fi
bers
(>
5µm
lon
g)Si
C1,
SiC
2,c
roci
dolit
e,a
nd
lon
gam
osit
est
imu
late
dth
eh
igh
est
TN
Fpr
odu
ctio
n.
RC
F1–R
CF4
did
not
sh
ow
mor
eT
NF
acti
vity
th
anin
co
ntr
olc
ult
ure
s.
Fujin
oet
al.
[199
5]
Rat
alv
eola
r
mac
roph
ages
T
NF
Cer
amic
G
lass
Po
tass
ium
oct
atit
anat
eM
agn
esiu
ms
ulf
ate
(lon
g)
Mag
nes
ium
su
lfat
e(s
hor
t)
Ch
ryso
tile
asb
esto
sC
roci
dolit
eas
best
os
Am
osit
eA
nth
ophy
lite
Eri
onit
e
Geo
met
ric
mea
n:
29
.5±
3.1
12.8
±3
.0
2
.8±
2.0
12.0
±2
.3
4
.9±
2.1
0.7
±1
.9
1
.3±
2.3
2.7
±2
.5
2
.5±
3.5
1.4
±2
.0
Geo
met
ric
mea
n:
1.
92±
2.9
0.54
±2
.2
0.
41±
1.5
0.44
±1
.6
0.
31±
1.5
0
.085
±1
.4
0.
20±
1.5
0.32
±1
.8
0.
36±
2.3
0.21
±1
.6
50µ
g/m
lA
llfi
bers
sig
nifi
can
tly
in-
crea
sed
TN
Fpr
odu
ctio
n
abov
en
o-fi
ber
con
trol
s;p
o-ta
ssiu
mo
ctat
itan
ate
cau
sed
the
hig
hes
tT
NF
prod
uct
ion
.
See
foot
not
eat
en
dof
tab
le(C
onti
nu
ed)
Refractory Ceramic Fibers 197
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
Tabl
e C
–2 (
Con
tin
ued
) .
In v
itro
cyt
otox
icit
y of
RC
Fs:*
eff
ects
on
med
iato
r re
leas
e
R
efer
ence
Cel
l lin
e an
d
end
poi
nts
Fib
er t
ype
Len
gth
(µ
m)
Dia
met
er (
µm
)
D
ose
Res
ult
s
Gilm
our
eta
l.
[1
997]
Rat
alv
eola
rm
acro
phag
es
G
luta
thio
ne
RC
F1
Am
osit
eas
best
os
MM
VF1
0
Not
rep
orte
dN
otr
epor
ted
8.24
×10
6 /ml
All
fibe
rss
ign
ifica
ntl
ylo
wer
ed
intr
acel
lula
rgl
uta
thio
ne.
MM
VF1
0ca
use
dth
egr
eate
st
decr
ease
.
RC
F1a
nd
amos
ite
had
sim
ilar
ef
fect
s.
Hill
et
al.
[1
996]
Rat
alv
eola
r
mac
roph
ages
Sup
erox
ide
anio
n
rele
ase
afte
rco
atin
gw
ith
rat
im
mu
nog
lobu
lin
(IgG
),a
nor
mal
co
mpo
nen
tof
lu
ng
linin
gfl
uid
.
MM
VF2
1R
CF1
L
FAa
sbes
tos
SiC
Jo
hn
sM
anvi
lleC
ode
10
0/47
5(g
lass
)
WH
Of/
µg
5,4
62
9,0
15
16
4,70
5
70,
550
2
1,74
2
Perc
enta
gele
ngt
h
di
stri
buti
ona
lso
repo
rted
.
Not
rep
orte
dR
CF1
,M
MV
F21:
125
µg–
20
mg/
ml
Cod
e10
0/47
5,
Si
C:1
25µ
g–
1
mg/
ml
LFA
asb
esto
s:
15
.6µ
g–
5
mg/
ml
IgG
-coa
ted
RC
F1fi
bers
and
Ig
G-c
oate
dLF
Aa
sbes
tosfi
bers
in
duce
da
sign
ifica
ntly
incr
ease
dsu
pero
xide
ani
onre
leas
e.
Coa
ting
ofR
CF1
fibe
rsa
tdos
es
>10
0µg
gre
atly
incr
ease
dth
eir
su
pero
xide
pro
duct
ion.
RC
F1fi
bers
had
ah
igh
bind
ing
affin
ityfo
rIgG
;LFA
asb
esto
sdid
no
t.
Leik
auf
eta
l.
[1
995]
Rat
mac
roph
ages
T
NF
LT
B4
P
GE
2
RC
F(u
nsp
ecifi
ed)
Cro
cido
lite
asbe
stos
Si
lica
TiO
2
Med
ian
:4.
92.
5N
A
NA
Med
ian
:0.
59
0.28
0.
88
0.18
100,
300
,1,
000
µg/m
lT
NF
prod
ucti
onw
asin
crea
sed
afte
rex
posu
reto
300
an
d1,
000
µg/m
lRC
Fs.
LTB
4leve
lsw
ere
elev
ated
aft
er
expo
sure
to3
00o
r1,
000
µg/m
lR
CFs
;PG
E 2con
cent
ratio
ns
wer
eel
evat
eda
fter
exp
osur
eto
1,0
00µ
g/m
lRC
Fs;e
ffect
sat
low
erd
oses
wer
eno
tsig
nific
ant.
Ate
quiv
alen
tdos
es,a
sbes
tos
in-
duce
da
grea
ter
resp
onse
than
R
CFs
inT
NF,
LT
B4,o
rP
GE
2co
nce
ntr
atio
ns.
See
foot
not
eat
en
dof
tab
le(C
onti
nu
ed)
198 Refractory Ceramic Fibers
Appendix C ■ Cellular and Molecular Effects of RCFs (In Vitro Studies)
Tabl
e C
–2 (
Con
tin
ued
) . I
n v
itro
cyt
otox
icit
y of
RC
Fs:* e
ffec
ts o
n m
edia
tor
rele
ase
Ref
eren
ceC
ell l
ine
and
en
dp
oin
tsFi
ber
typ
eLe
ngt
h (
µm
)D
iam
eter
(µ
m)
Dos
eR
esu
lts
Lju
ngm
ane
tal
.
[1
994]
Rat
alv
eola
r
m
acro
phag
es
T
NF
Cro
cido
lite
Ch
ryso
tile
A
Ch
ryso
tile
B
MM
VF2
1
MM
VF2
2R
CF1
Si
Cw
h
Mea
n:
9
.9±
7.8
Not
rep
orte
d
Not
rep
orte
d
24.6
±1
9.9
21
.4±
17.
6
22.4
±1
9.0
N
otr
epor
ted
Mea
n:
0.
3±
0.2
Not
rep
orte
d
Not
rep
orte
d
1.3
±0
.8
1.
2±
0.7
1.1
±0
.8
N
otr
epor
ted
100
µg/m
lC
hry
soti
leA
,ch
ryso
tile
B,
croc
idol
ite,
MM
VF2
1,
RC
F1,a
nd
SiC
wh
incr
ease
dT
NF
mR
NA
con
cen
trat
ion
saf
ter
90m
inu
tes;
con
cen
-tr
atio
ns
had
ret
urn
edto
ba
selin
eaf
ter
4h
ours
ina
llbu
tch
ryso
tile
A.
Ch
ryso
tile
A,c
hry
soti
leB
,cr
ocid
olit
e,a
nd
MM
VF2
1in
duce
dan
incr
ease
inT
NF
bioa
ctiv
ity
afte
r4
hou
rs
ofin
cuba
tion
;RC
F1d
id
not
indu
cea
sig
nifi
can
tin
crea
se.
Luot
oet
al.
[199
7]R
ata
lveo
lar
mac
roph
ages
RO
M
RC
F1
RC
F2
RC
F3
RC
F4
MM
VF1
0M
MV
F11
MM
VF2
1M
MV
F22
Mea
n:
21
.29
±1
7.42
20.1
8±
19.
63
25
.66
±2
5.74
10.3
4±
11.
59
23
.21
±1
5.57
15.6
5±
13.
31
26
.02
±2
3.10
20.7
5±
20.
52
Mea
n:
1.
30±
0.7
2
1.39
±0
.98
1.
37±
0.8
7
1.33
±1
.02
1.
42±
0.7
8
1.12
±0
.88
1.
18±
0.6
4
0.88
±0
.45
25,5
0,1
00,
200,
400
,or
500
µg/m
l
All
fibe
rss
how
eda
dos
e-
dep
ende
nt
resp
onse
to
RO
Mp
rodu
ctio
n.
RC
F1,R
CF2
,or
RC
F3e
x-p
osu
rer
esu
lted
inh
igh
er
RO
Mp
rodu
ctio
nt
han
R
CF4
or
chry
soti
lee
xpo-
sure
.
Qu
artz
had
th
egr
eate
ste
ffec
ton
RO
Mp
rodu
ctio
n.
See
foot
not
eat
en
dof
tab
le.
(Con
tin
ued
)
Refractory Ceramic Fibers 199
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
Tabl
e C
–2 (
Con
tin
ued
) . I
n v
itro
cyt
otox
icit
y of
RC
Fs:* e
ffec
ts o
n m
edia
tor
rele
ase
Ref
eren
ceC
ell l
ine
and
en
dp
oin
tsFi
ber
typ
eLe
ngt
h (
µm
)D
iam
eter
(µ
m)
Dos
eR
esu
lts
Mor
imot
oet
al.
[199
3]
Rat
alv
eola
r
m
acro
phag
es
T
NF
Can
adia
nc
hry
soti
le
Alu
min
asi
licat
ece
ram
ic
(J
apan
)
Not
rep
orte
dM
ass
med
ian
ae
rody
nam
icd
i-am
eter
=3
.1µ
m
25,5
0,o
r
100
µg/m
lB
oth
fiber
sstim
ulat
eda
dos
e-de
pend
entT
NF
prod
uctio
nby
al
veol
arm
acro
phag
es.
Chr
ysot
ilest
imul
ated
gre
ater
T
NF
prod
uctio
nth
anc
eram
ic
fiber
sin
cells
from
rat
sex
pose
dto
cig
aret
tesm
oke
and
cells
fr
omr
atsn
ote
xpos
edto
smok
e.
Chr
ysot
ilein
duce
dhi
gher
TN
Fpr
oduc
tion
insm
oke-
expo
sed
rats
than
inc
ontr
ols;
cera
mic
fib
ere
xpos
ure
resu
lted
inn
osi
gnifi
cant
diff
eren
ceb
etw
een
T
NF
prod
uctio
nin
smok
e-
expo
sed
rats
and
con
trol
s.
Wan
get
al.
[199
9]G
uin
eap
iga
lveo
lar
mac
roph
ages
Sup
erox
ide
anio
n
Hyd
roge
np
erox
ide
GSH
Intr
acel
lula
rfr
ee
calc
ium
Japa
nfi
brou
sm
ater
ial:
G
W1
=g
lass
woo
lR
W1
=r
ock
woo
lM
G1
=m
icro
gla
ss
RF1
=r
efra
ctor
yce
ram
ic
RF2
=r
efra
ctor
yce
ram
ic
RF3
=r
efra
ctor
ym
ulli
te
PT
1=
pot
assi
um
tit
anat
eSC
1=
sili
con
car
bide
T
O1
=t
itan
ium
oxi
de
WO
1=
wol
last
onit
eC
hry
soti
le
20.2
±2
.58
16.5
±2
.51
3.0
±2
.22
12.0
±2
.36
11.0
±1
.96
11.0
±1
.75
6.
0±
2.0
46
.4±
2.4
52
.1±
2.0
010
.5±
2.0
3N
otr
epor
ted
0.88
±3
.10
1.80
±2
.32
0.24
±2
.35
0.77
±2
.53
1.10
±2
.00
2.40
±1
.37
0.35
±1
.51
0.30
±1
.58
0.14
±1
.53
1.00
±1
.72
Not
rep
orte
d
20
0µg
/ml
Chr
ysot
ilea
nda
llfib
erso
ther
th
anW
O1
sign
ifica
ntly
in
crea
sed
supe
roxi
dea
nion
pr
oduc
tion.
Chr
ysot
ilesi
gnifi
cant
lyin
crea
sed
hydr
ogen
per
oxid
epr
oduc
tion;
R
Fdi
dno
t.
Chr
ysot
ile,R
F2,P
T1,
TO
1,S
C1,
W
O1,
and
MG
1si
gnifi
cant
ly
decr
ease
dG
SHc
once
ntra
tion.
Chr
ysot
ile,R
F1,R
F2,S
C1,
TO
1,
PT1,
MG
1,a
ndR
W1
sign
ifi-
cant
lyin
crea
sed
intr
acel
lula
rfr
eec
alci
um.
Ina
llte
sts,
chry
sotil
eha
dgr
eate
ref
fect
stha
nth
ose
ofth
eR
CFs
.
* Abb
revi
atio
ns:
GSH
=gl
uta
thio
ne;
GW
1=gl
ass
woo
l;Ig
G=
imm
un
oglo
bulin
;LFA
=lo
ng
fibe
ram
osit
e;L
TB
4=le
uko
trie
ne
B4;
MG
1=m
icro
gla
ss;M
MV
F=m
an-m
ade
vitr
eou
sfi
ber;
P
GE
2=pr
osta
glan
din
E2;P
T1=
pota
ssiu
mt
itan
ate;
RC
Fs=
refr
acto
ryc
eram
icfi
bers
;RF1
=re
frac
tory
cer
amic
;RF2
=re
frac
tory
cer
amic
;RF3
=re
frac
tory
mu
llite
;RO
M=
reac
tive
ox
ygen
met
abol
ites
;RW
1=ro
ckw
ool;
SC1=
silic
onc
arbi
dein
Wan
get
al.
[199
9];S
iC=
silic
onc
arbi
de;T
NF=
tum
orn
ecro
sis
fact
or;T
iO2=
tita
niu
md
ioxi
de;T
O1=
tita
niu
mo
xide
in
Wan
get
al.
[199
9];w
h=
wh
iske
rs;W
O1=
wol
last
onit
e.
200 Refractory Ceramic Fibers
Appendix C ■ Cellular and Molecular Effects of RCFs (In Vitro Studies)
Tabl
e C
–3 .
In v
itro
gen
otox
ic e
ffec
ts o
f R
CFs
*
Ref
eren
ceTe
st s
yste
m a
nd
en
dp
oin
tsFi
ber
typ
eLe
ngt
h (
µm
)D
iam
eter
(µ
m)
Dos
eR
esu
lts
Bro
wn
et
al.
[199
8]P
lasm
ido
X17
4RF1
D
NA
D
NA
sci
ssio
n
Salic
ylat
eas
say
H
ydro
xylr
adic
al
gen
erat
ion
Lon
gfi
ber
amos
ite
asbe
stos
Si
C
RC
F1
RC
F4
MM
VF1
0C
ode
100/
475
glas
s
Siz
edi
stri
buti
on
>10
>
20
64
.75
35.
25
60
.86
27.
6
77.3
64
5.27
59.3
51
7.96
85.2
46
7.17
50.0
01
9.32
Not
rep
orte
dP
lasm
ida
ssay
:9.
249×
105 f/
20µ
l
Salic
ylat
eas
say:
8.
24×
107 f/
ml
Pla
smid
ass
ay:
On
lya
mos
ite
had
free
rad
ical
ac
tivi
ty.
Salic
ylat
eas
say:
A
mos
ite
and
RC
F1h
adfr
ee
radi
cala
ctiv
ity.
Coa
tin
gth
efi
bers
wit
hlu
ng
surf
acta
nt
decr
ease
dhy
drox
yl
radi
cala
ctiv
ity.
An
iron
ch
elat
orin
hib
ited
hy-
drox
ylat
ion
by
RC
F1.
Dop
pet
al.
[199
7]H
um
ana
mn
ioti
c
fl
uid
cel
ls
M
icro
nu
clei
H
yper
dipl
oidy
Ch
rom
osom
al
brea
kage
Am
osit
eas
best
os
Cro
cido
lite
asbe
stos
-R
hod
esia
nc
hry
soti
le
as
best
os
Cer
amic
(u
nsp
ecifi
ed)
Gyp
sum
Ave
rage
:2.
05
1.71
2.
24
12.0
3
Ave
rage
:0.
24
0.25
0.
10
0.90
0.5,
1.0
,5.0
,or
10.0
µg/
cm2
All
fibe
rsc
ause
da
sign
ifica
nt
incr
ease
inm
icro
nu
clei
.
Dos
e-de
pen
den
tre
spon
sew
as
seen
wit
ha
sbes
tos
but
not
wit
h
cera
mic
fibe
rex
pos
ure
.
Asb
esto
san
dce
ram
icfi
bers
in-
duce
dch
rom
osom
alb
reak
age
and
hyp
erdi
ploi
dce
lls.
Gilm
our
eta
l.
[1
995]
Pla
smid
oX
174R
F1
DN
A
D
eple
tion
of
su
perc
oile
dD
NA
Shor
tfi
ber
amos
ite
Lon
gfi
ber
amos
ite
Cro
cido
lite
asbe
stos
RC
F1R
CF2
RC
F3R
CF4
MM
VF1
0M
MV
F11
MM
VF2
1M
MV
F22
Not
rep
orte
dN
otr
epor
ted
Test
eda
teq
ual
fi
ber
nu
mbe
rs:
6.16
6×10
5 or
9.24
9×10
5 or
1.23
32×
106
RC
F1,R
CF2
,RC
F3,a
nd
RC
F4
had
am
inim
alfr
eer
adic
al
effe
ctc
ompa
red
wit
ha
sbes
tos
fibe
rs.
RC
FD
NA
dam
age
was
med
i-at
edb
yhy
drox
ylr
adic
als
but
was
not
ass
ocia
ted
wit
hir
on
con
ten
t.
See
foot
not
eat
en
dof
tab
le.
(Con
tin
ued
)
Refractory Ceramic Fibers 201
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
Tabl
e C
–3 (
Con
tin
ued
) . I
n v
itro
gen
otox
ic e
ffec
ts o
f R
CFs
*
Ref
eren
ceTe
st s
yste
m a
nd
en
dp
oin
tsFi
ber
typ
eLe
ngt
h (
µm
)D
iam
eter
(µ
m)
Dos
eR
esu
lts
Gilm
our
eta
l.
[199
7]
Pla
smid
oX
174R
F1
DN
A
D
eple
tion
of
s
up
erco
iled
DN
A
R
ata
lveo
lar
mac
roph
ages
A
ctiv
atio
no
ftr
an-
s
crip
tion
fact
ors
Am
osit
eas
best
os
MM
VF1
0R
CF1
Not
rep
orte
dN
otr
epor
ted
Equ
alfi
ber
nu
mbe
rsp
er
assa
y.
DN
Aa
ssay
:9.
3×10
5
Iron
ass
ay:
8.24
×10
7 /ml
RC
F1a
nd
MM
VF1
0in
duce
dsi
g-n
ifica
ntl
yle
ssD
NA
free
rad
ical
da
mag
eth
ana
mos
ite
asbe
stos
.
Am
osit
esi
gnifi
can
tly
upr
egu
-la
ted
tran
scri
ptio
nfa
ctor
sA
P–1
an
dN
FkB
;RC
F1h
ada
mu
ch
smal
ler
effe
cto
nA
P–1
on
ly.
Har
tet
al.
[199
2]C
hin
ese
ham
ster
ov
ary
cells
M
icro
nu
clei
in
duct
ion
Po
lyn
ucl
ei
indu
ctio
n
RC
F1
RC
F2
RC
F3
RC
F4
UIC
CC
roci
dolit
eU
ICC
Ch
ryso
tile
Mea
n:
21.5
±1
6.12
16
.7±
15.
03
24.3
±1
8.82
9
.2±
7.0
81
.8±
1.9
41.
65±
1.8
3
Mea
n:
1.03
±0
.73
1.11
±0
.82
1.22
±0
.98
1.43
±0
.79
0.21
±0
.12
0.12
±0
.07
RC
Fs1
–4:
0,5
,10,
or
20
µg/
ml
Cro
cido
lite:
0
or5
µg/
ml
Ch
ryso
tile
:0,
1,2
,or
5
µg/m
l
Nu
clea
rab
nor
mal
ity
inci
den
ce:
At2
0µg
/cm
2 ,RC
Fw
as2
0%to
33%
.
At5
µg/
cm2 ,c
roci
dolit
ew
as2
8%.
At5
µg/
cm2 ,c
hrys
otile
was
49%
.
Jan
ssen
et
al.
[199
4]H
amst
ert
rach
eal
e
pith
elia
l(H
TE
)
cel
ls
mR
NA
con
cen
tra-
tion
so
fc-
fos,
c-
jun
,an
dO
DC
RP
Mc
ells
mR
NA
con
cen
tra-
tion
sof
c-f
os,
c-ju
n,a
nd
OD
C
Cro
cido
lite
Ch
ryso
tile
M
MV
F10
RC
F1
Poly
styr
ene
bead
sR
iebe
ckit
eE
rion
ite
Mea
n:
11.4
1
.1
19.8
24
.0
—
—
6.0
Mea
n:
0.27
0.
08
1.36
1.
07
1.05
0.
80.
8
Asb
esto
s:
≤5µ
g/cm
2
All
oth
erfi
bers
:1.
25–2
5µg
/cm
2
HT
Ec
ells
:C
roci
dolit
ein
duce
dsi
gnifi
cant
do
se-d
epen
dent
con
cent
rati
ons
ofc
-jun
and
OD
Cm
RN
A.
RC
F1in
duce
dsm
alln
on-d
ose-
depe
nden
tinc
reas
esin
OD
C
mR
NA
con
cent
rati
ons
only
.
RP
Mc
ells
:C
roci
dolit
eat
2.5
µg/
cm2 in
duce
del
evat
edc
-fos
and
c-j
unm
RN
A
conc
entr
atio
ns.
RC
F1a
t25
µg/c
m2 in
crea
sed
c-
fos
and
c-ju
nm
RN
A
conc
entr
atio
ns.
See
foot
not
eat
en
dof
tab
le.
(Con
tin
ued
)
202 Refractory Ceramic Fibers
Appendix C ■ Cellular and Molecular Effects of RCFs (In Vitro Studies)
Tabl
e C
–3 (
Con
tin
ued
) . I
n v
itro
gen
otox
ic e
ffec
ts o
f R
CFs
*
Ref
eren
ceTe
st s
yste
m a
nd
en
dp
oin
tsFi
ber
typ
eLe
ngt
h (
µm
)D
iam
eter
(µ
m)
Dos
eR
esu
lts
Lean
ders
one
t
al
.[19
89]
Cal
fth
ymu
sD
NA
Hyd
roxy
lati
on
of
2-dG
to
8–O
H–d
G
dGs
olu
tion
Hyd
roxy
lati
ono
f
dG
to8
–OH
–dG
Eu
rop
ean
sou
rce:
Fi
ber
1=
cer
amic
Fi
ber
2=
gla
ssw
ool
Fibe
r3
=c
eram
ic
Fibe
r4
=r
ock
woo
lFi
ber
5=
roc
kw
ool
Fibe
r6
=r
ock
woo
lFi
ber
7=
roc
kw
ool
Fibe
r8
=r
ock
woo
lFi
ber
9=
roc
kw
ool
Fibe
r10
=r
ock
woo
lFi
ber
11=
roc
kw
ool
Fibe
r12
=s
lag
woo
l Fi
ber
13=
roc
kw
ool
Fibe
r14
=r
ock
woo
lFi
ber
15=
sla
gw
ool
Fibe
r16
=r
ock
woo
l
Surf
ace
area
(m
2 /g):
0.
95
0.91
1.
10
1.30
0.
36
0.60
0.
73
1.01
1.
28
1.16
1.
18
1.14
1.
30
1.06
0.
90
0.62
Not
rep
orte
d10
mg
fibe
ran
d1.
0m
lPB
Sw
ith
0.5
mg
DN
Ao
r
0.5
mM
dG
All
fibe
rsc
ause
dsi
gnifi
can
thy
drox
ylat
ion
of
dG.
Gla
ssw
oola
nd
cera
mic
fibe
rs
had
poo
rhy
drox
ylat
ing
capa
c-it
yre
lati
veto
roc
kw
ools
an
dsl
agw
ools
.
Lean
ders
one
t
al
.[19
89]
Cal
fth
ymu
sD
NA
Hyd
roxy
lati
ono
f
dG
to8
–OH
–dG
Eu
rop
ean
sou
rce:
R
ock
woo
lG
lass
woo
lC
eram
ic
Not
rep
orte
dN
otr
epor
ted
10m
gfi
ber
and/
or3
00µ
lsm
oke-
PB
Sor
10
0µM
H2O
2in
1.0
mlP
BS
wit
h0
.5m
gD
NA
Cer
amic
an
dgl
ass
woo
lfibe
rs
cau
sed
less
DN
Ah
ydro
xyla
tion
th
anr
ock
woo
l.
Roc
kw
oola
nd
ciga
rett
esm
oke
con
den
sate
had
as
yner
gist
ic
effe
cto
nh
ydro
xyla
tion
.
Cer
amic
or
glas
sw
oolfi
bers
an
dci
gare
tte
smok
eco
nde
nsa
ted
id
not
hav
ea
syn
ergi
stic
eff
ecto
n
hydr
oxyl
atio
n.
Oka
yasu
et
al.
[1
999]
Hu
man
-ham
ster
h
ybri
dA
Lcel
ls
M
uta
tion
ass
ay
UIC
Cc
hry
soti
le
Trem
olit
eE
rion
ite
RC
F1
Geo
met
ric
mea
n:
1.78
±2
.3
1.41
±2
.7
1.31
±2
.9
13.5
±2
.7
Geo
met
ric
mea
n:
0.12
±0
.08
0.13
±3
.43
0.23
±2
.74
0.95
±2
.6
0–80
µg/
cm2
RC
F1w
asd
eter
min
edto
be
non
mu
tage
nic
.
Ch
ryso
tile
was
th
em
ost
mu
ta-
gen
ico
ffi
bers
exa
min
edb
ased
on
fibe
rco
nce
ntr
atio
n.
See
foot
not
eat
en
dof
tab
le.
(Con
tin
ued
)
Refractory Ceramic Fibers 203
Appendix C ■Cellular and Molecular Effects of RCFs (In Vitro Studies)
Tabl
e C
–3 (
Con
tin
ued
) . I
n v
itro
gen
otox
ic e
ffec
ts o
f R
CFs
*
Ref
eren
ceTe
st s
yste
m a
nd
en
dp
oin
tsFi
ber
typ
eLe
ngt
h (
µm
)D
iam
eter
(µ
m)
Dos
eR
esu
lts
Yegl
ese
tal
.
[1
995]
Rat
ple
ura
lmes
o-th
elia
lcel
ls
An
aph
ase/
telo
phas
eab
erra
tion
s
RC
F1
RC
F3
RC
F4
MM
VF1
0M
MV
F11
UIC
Cc
hry
soti
le
Ch
rys
445
(Can
adia
n)
Ch
rys
443
(Can
adia
n)
Ch
rys,
sh
ort
Can
adia
n
Ch
rys,
su
per
fin
e
C
anad
ian
C
hry
s,p
hos
phor
ylat
ed
C
anad
ian
C
hry
s,ph
osph
oryl
ated
mill
edC
anad
ian
UIC
Cc
hry
s,le
ach
ed
w
ith
oxa
lica
cid
C
hry
s,C
alid
ria
Ch
rys,
NIE
HS
Am
osit
eC
roci
dolit
eA
ttap
ulg
ite
19.2
±1
5.0
31.8
±3
6.0
8.9
±7
.2
21.5
±1
6.8
16.7
±1
2.9
1.7
±2
.2
2.3
±2
.3
1.9
±1
.9
1.6
±1
.4
2.4
±3
.1
4.7
±5
.2
4.7
±5
.9
2.3
±1
.8
2.8
±3
.0
4.2
±1
.2
2.4
±1
.8
2.1
±3
.6
0.8
±0
.5
1.30
±0
.80
0.74
±0
.50
1.30
±0
.60
0.55
±0
.50
1.10
±0
.90
0.05
±0
.04
0.04
±0
.03
0.04
±0
.04
0.06
±0
.08
0.04
±0
.03
0.04
±0
.03
0.07
±0
.09
0.17
±0
.11
0.05
±0
.04
0.05
±0
.05
0.31
±0
.20
0.19
±0
.12
0.04
±0
.03
12.5
,25,
50,
75,
or
100
µg/
cm2
UIC
Cc
hry
soti
lew
ast
he
mos
tge
not
oxic
on
th
eba
sis
of
wei
ght,
nu
mbe
rof
fibe
rs>
4µm
lon
g,a
nd
nu
mbe
rof
fibe
rs
corr
esp
ondi
ng
toS
tan
ton’
san
dPo
tt’s
cri
teri
a.
Cer
amic
an
dgl
ass
fibe
rsd
idn
ot
indu
cea
nap
has
eab
erra
tion
s.
*Abb
revi
atio
ns:d
G=
deox
ygua
nosi
ne;f
=fib
ers;
HT
E=
ham
ster
trac
heal
epi
thel
ial;
OH
–dG
=hy
drox
ydeo
xy-g
uano
sine
;mR
NA
=m
esse
nger
RN
A;M
MV
F=m
an-m
ade
vitr
eous
fibe
r;
NIE
HS=
Nat
iona
lIns
titu
tefo
rE
nvir
onm
enta
lHea
lthS
cien
ces;
OD
C=
orni
thin
ede
carb
oxyl
ase;
PB
S=ph
osph
ate-
buff
ered
sal
ine;
RC
Fs=
refr
acto
ryc
eram
icfi
bers
;RP
M=
ratp
leur
alm
eso -
thel
ial;
UIC
C=
Uni
onIn
tern
atio
nale
Con
tre
leC
ance
r.
Recommended