The Evaluation and Hazard Classification of Toxicological Information for Workplace Hazardous Materials Information System Material Safety Data Sheets

REGULATORY TOXICOLOGY AND PHARMACOLOGY 27, 61–74 (1998)ARTICLE NO. RT971179

The Evaluation and Hazard Classification of Toxicological Informationfor Workplace Hazardous Materials Information System

Material Safety Data Sheets

Rosanne Cote, Hugh Davis, Colleen Dimock, Mary Korpan, Ken Loewen, and Lawrence M. Segal1

Workplace Hazardous Materials Information System Evaluation Section, Product Safety Bureau,Health Protection Branch, Health Canada, Ottawa, Ontario, Canada K1A OL2

Received July 28, 1997

produced over 80 policy issue sheets (PIS) which pro-vide consistent interpretations of WHMIS legislation.Hazardous materials used occupationally in Can-The WHMIS regulators caucus, the Intergovernmentalada are subject to the legislated requirements of the

Workplace Hazardous Materials Information System WHMIS Coordinating Committee (IWCC), has also(WHMIS). This paper describes the administrative produced a number of guidelines and policy papers toframework of WHMIS and how toxicological data are facilitate a common understanding of WHMIS require-evaluated to determine if a substance triggers WHMIS ments.classification for the toxicological endpoints of acute WHMIS establishes uniform national requirementstoxicity, skin irritation, eye irritation, corrosion, der- to ensure that information regarding the health haz-mal sensitization, respiratory sensitization, chronic ards, safe use, storage, and handling of hazardoustoxicity, mutagenicity, teratogenicity/embryotoxicity, workplace substances is provided to employers andand carcinogenicity. Problems encountered with the workers (Anonymous, 1989a). Products are covered byinformation on material safety data sheets are also dis- WHMIS if they fall within the criteria specified in thecussed for each of the toxicological endpoints. q 1998 Controlled Products Regulations (CPR) and are knownAcademic Press as WHMIS ‘‘controlled products’’ (Anonymous, 1988a).

The sections of the CPR applicable to toxicological haz-ards are summarized in Table 1. Controlled products

INTRODUCTION used occupationally in Canada must be classified andlabeled according to the provisions of the CPR. Comple-

The goal of the Workplace Hazardous Materials In- mentary WHMIS OSH legislation requires that theformation System (WHMIS) is to reduce the incidence prescribed hazard information disclosed on MSDSs andof illnesses and injuries resulting from the use of haz- product labels be conveyed to employers and workers.ardous materials in the workplace. The legislative re- Each product, whether a pure substance or a mixture,quirements for WHMIS were adopted in 1987 through must be evaluated against the criteria specified in theamendments to the Hazardous Products Act (HPA) and CPR. The CPR establishes six classes into whichprovincial, territorial and federal occupational safety WHMIS controlled products may fall: Class A, com-and health (OSH) legislation including the Canada La- pressed gas; B, flammable and combustible material;bour Code (CLC), and the enactment of the Hazardous C, oxidizing material; D, poisonous and infectious ma-Materials Information Review Act (HMIRA). WHMIS terial; E, corrosive material; and F, dangerously reac-legislation was the result of a consensus proposal devel- tive material.oped through extensive consultation between labor, in- In some instances an employer, supplier, importer,dustry, and federal and provincial governments. The or manufacturer may not wish to disclose the identityongoing development and interpretation of WHMIS or concentration of an ingredient in a controlled prod-requirements are managed through the tripartite uct, in which case a trade secret claim may be filedWHMIS Current Issues Committee (CIC). The CIC has with the Hazardous Materials Information Review

Commission (HMIRC) for exemption from the full dis-closure requirements of WHMIS. Hazard information1 To whom correspondence should be addressed at Workplace Haz- for a controlled product cannot be claimed as confiden-ardous Materials Information System Evaluation Section, Producttial. A review of all health and safety information onSafety Bureau, HPB, Health Canada, Locator 0302G1, Tunney’s Pas-

ture, Ottawa, Ontario, Canada K1A 0L2. MSDSs that are the subject of trade secret claims is

61 0273-2300/98 $25.00Copyright q 1998 by Academic Press

All rights of reproduction in any form reserved.

AID RTP 1179 / 6e18$$$$21 04-27-98 20:25:01 rtpa AP: RTP

62 COTE ET AL.

TABLE 1 WHMIS controlled products. It is an example of thescientific basis for regulatory decisions.Sections of the CPR Applicable

to Toxicological EndpointsPRELIMINARY CONSIDERATIONS IN THE

CPR section content CPR section No.aEVALUATION OF HEALTH HAZARDS FOR WHMIS

Acute toxicityWHMIS Classification versus Hazard DisclosureClassification 46–51

Formula for 4-h equivalent LC50 44 on the MSDSFormula for LD50/LC50 of mixture 45

Skin irritation 60(a) A WHMIS controlled product is any product, mate-Eye irritation 60(b) rial, or substance which falls within the hazard criteriaCorrosion 65 specified in Part IV of the CPR. A controlled productSkin sensitization 61

may be a ‘‘pure’’ substance, a tested mixture, or anRespiratory tract sensitization 56untested mixture. The HPA requires that suppliers ofChronic toxicity 52, 59

Mutagenicity 57, 62 controlled products intended for use in a workplace inReproductive toxicity 55 Canada provide precautionary labeling and MSDSs asTeratogenicity/embryotoxicity 53 a condition of sale and importation. The CPR specifiesCarcinogenicity 54

what information the MSDS and label must discloseas well as what symbol(s) must be depicted on the label.a In addition, CPR Section 33 applies to all toxicological endpoints.The symbols correlate to the WHMIS hazard classesinto which the product falls. WHMIS Class D includesthe following three divisions which correspond to a dif-required to ensure full compliance with the HPA andferent hazard symbol: Division 1, ‘‘materials causingCPR. HMIRC screening officers have the authority toimmediate and serious toxic effects’’; Division 2, ‘‘mate-issue an order to a claimant to modify his MSDS torials causing other toxic effects’’; and Division 3, ‘‘bio-comply with the requirements of the HPA and CPR.hazardous infectious material.’’ The label for a productHealth Canada is responsible for providing the HMIRCwhich falls within the criteria for both Divisions 1 andwith advice regarding the accuracy and completeness2 need only depict the hazard symbol corresponding toof the health and safety information on such MSDSs,Division 1 (Anon., 1996d).and has evaluated approximately 1000 MSDSs over the

The criteria which determine a product’s classifica-past several years.tion are different and narrower in scope from the infor-Problems with MSDSs have been described in a num-mation which must be disclosed on a MSDS. The infor-ber of recent reports, and indicate that a high propor-mation which must be disclosed on a MSDS is thattion of MSDSs are incomplete or inaccurate in disclos-which is ‘‘available to the supplier and applicable toing available toxicological hazard information. In a re-the controlled product.’’ The CPR does not limit MSDScent study of 28 randomly selected WHMIS MSDSs,disclosure to the criteria which determine a product’snone were found to comply with all requirements ofclassification. Although the classification criteria speci-WHMIS legislation, and on 18 of the 28 MSDSs, thefied in Part IV of the CPR may provide a useful guide-health hazard information was incomplete, too general,line for certain MSDS information, it is Section 12 anduninformative, or out of date (Karpinski, 1994). Of 196Schedule I of the CPR which set out what informationMSDSs adjudicated by HMIRC in 1 year, noncompli-must be disclosed on a MSDS; paragraph 13(a) of theance with WHMIS requirements was most frequentlyHPA sets out what ingredients are subject to disclosurenoted in the toxicological properties section of theon the MSDS; Section 4 of the CPR specifies the concen-MSDSs, accounting for almost one-third (609/1977) oftration above which those ingredients must be dis-all violations (Anonymous, 1996b). Studies conductedclosed.in the United States also suggest that a high proportion

The CPR and HPA do not specify a requirement forof the MSDSs available in that country are noncompli-the WHMIS classification or the corresponding picto-ant with the OSHA Hazard Communication Standard.gram to appear on the MSDS. However, if a supplierAn OSHA-sponsored study revealed that health effectschooses to include the classification on the MSDS, itinformation was inaccurately disclosed on 63% of 134must be complete and accurate.randomly selected MSDSs (Kolp et al., 1995). Of 678

MSDSs for lead- or ethylene glycol ether-containing Applicable Routes of Exposureproducts evaluated in another study (Paul and Kurtz,1994), 62% contained no information on reproductive As indicated in subitem 7(1) of CPR Schedule I, the

toxicological hazards associated with exposure via thetoxicity hazards, and were thus judged incomplete andinaccurate. inhalation, dermal, ocular, and oral routes are those

that are applicable for a WHMIS health hazard evalua-This paper summarizes issues and problems relatedto toxicological hazard evaluation and classification for tion (Anonymous, 1989a, 1996d, 1997d). In certain


63INFORMATION FOR WHMIS MATERIAL SAFETY DATA SHEETS

cases, data from in vitro studies may be used for MSDS must disclose all the applicable toxicological informa-tion for these ingredients (Anonymous, 1996d, 1997d).disclosure purposes (i.e., mutagenicity), although such

data are not generally applicable for WHMIS hazardPolicy on Weight of Evidenceclassification. Toxicity data obtained from studies con-

ducted via routes of exposure not relevant to normal WHMIS classification does not involve a weight-of-occupational exposure, such as intraperitoneal, intra- evidence approach. It is Health Canada’s policy thatvenous, subcutaneous, or intramuscular, are not nor- a single positive, well-conducted study is consideredmally considered applicable for WHMIS classification sufficient as the basis for including a product innor MSDS disclosure. WHMIS Class D, except where specified otherwise in

the CPR. Section 33 of the CPR places an obligation onHazard versus Risk the supplier to establish whether a product, material,or substance meets WHMIS classification criteria. De-WHMIS classifications and MSDS disclosures arecisions should be made by an individual who is knowl-based upon the hazards of workplace chemicals (Anon-edgeable in the appropriate science necessary to evalu-ymous, 1989a, 1988a, 1996d, 1997d). With regard toate the product, material, or substance. Decision mak-the Toxicological Properties section of the MSDS, riskers have an obligation to consider sufficient evidenceto worker health is applicable neither to MSDS disclo-to make a reasonable and responsible decision. Weightsure nor to the determination of the WHMIS classifica-of evidence does not refer to the quantity of evidence.tion. Toxicological hazards are intrinsic properties andRather, the credibility of each study considered mustconsequently it is not appropriate for toxicological databe evaluated and all relevant, credible evidence is thento be qualified or limited, based on the anticipated risksweighed or balanced.resulting from intended use of the product. It is the

Well-conducted studies could point to different con-responsibility of users of controlled products to evalu-clusions regarding whether the product, material, orate the risks associated with their use in each work-substance is a controlled product. The supplier mustplace setting, based on the exposure conditions re-assess the impact of deciding whether the product is asulting from each use. Consequently, it is very im-controlled product. In the final analysis the supplier’sportant that suppliers, manufacturers, and importersdecision should be both reasonable in light of the scien-of WHMIS controlled products ensure that thoroughtific evidence, and responsible considering that the sup-and accurate toxicological hazard information is trans-plier is selling or importing a potentially hazardousmitted to users via the MSDS.material for use in the workplace. Similar considera-

Tested versus Untested Mixtures tions are required when deciding what informationshould be disclosed on an MSDS (Anonymous, 1996d).

Toxicological testing of WHMIS controlled products For example, if a well-conducted and reported teratol-is not required. However, if products have been tested, ogy study in one species and route indicates adverseit is these data that are used for classification and effects on fetal development, it is not appropriate toMSDS disclosure (Anonymous, 1989a, 1996d, 1997d). use a weight-of-evidence approach in the classificationOur experience has shown that most WHMIS con- of this substance, even if the same test conducted introlled products that are mixtures are untested with another species or by other route(s) does not elicit arespect to toxicological properties. Controlled products similar response. In this example, the studies do notthat are untested mixtures with respect to one or more constitute ‘‘replicates’’ (i.e., same species and route),applicable toxicological endpoints specified in the CPR and CPR 53(1)(a) specifies ‘‘an assay’’ (one study).are evaluated on the basis of the hazards associated Therefore, the supplier must consider the substance aswith each ingredient present at a reportable concentra- falling within the WHMIS classification criteria (Anon-tion in the mixture. Reportable concentrations are 0.1% ymous, 1996d).w/w or more for substances which meet the classifica-tion criteria for teratogenicity, embryotoxicity, carcino-

EVALUATION OF TOXICOLOGICAL HAZARDS FORgenicity, reproductive toxicity, germ cell mutagenicity,WHMIS CLASSIFICATION AND MSDS DISCLOSUREor respiratory tract sensitization. The concentration

cutoff is 1% w/w for all other toxicological criteria in Acute ToxicityWHMIS (i.e., acute and chronic toxicity, somatic cellmutagenicity, skin and eye irritation, and dermal sen- Adverse health effects resulting from acute exposure

to a controlled product must be disclosed on the MSDS,sitization). It is Health Canada’s policy that in the caseof a controlled product that is an untested mixture, as specified in CPR Schedule I, Item 7(2). An acute

exposure is generally considered to be a single expo-the mixture is generally considered to have the sametoxicological hazards as the ingredients subject to dis- sure, or multiple exposures within 24 h (Anonymous,

1996d). Effects may be immediate and/or delayedclose present at or above the cutoff concentrations.Therefore, the MSDS for a product that is untested (Anonymous, 1997d). All adverse effects are subject to


64 COTE ET AL.

TABLE 2WHMIS Dose Criteria for Acute Toxicity Classification

Route of exposure Dose criterion for Class D1A acute toxicity Dose criterion of Class D1B acute toxicity

Oral LD50 ° 50 mg/kg LD50 ú 50 mg/kg but °500 mg/kgDermal LD50 ° 200 mg/kg LD50 ú 200 but °1000 mg/kgInhalation (4-h) LC50 ° 2500 ppm No criterion

GasInhalation (4-h) LC50 ° 1500 ppm and a saturated vapor concentration LC50 ú 1500 but °2500 ppm and a saturated

Vapor at normal atmospheric pressure at 207C of more vapor concentration at normal atmosphericthan 2 times the LC50 pressure at 207C of more than 0.4 times

the LC50

Inhalation (4-h) LC50 ° 500 mg/m3 LC50 ú 500 but °2500 mg/m3

Dust, mist, or fume

WHMIS disclosure, whether they occur in animals sur- value used in the calculation should have been deter-mined using the same animal species, sex, and route/viving or not surviving the exposure. Acute toxicity

tests must be carried out in accordance with OECD duration of exposure (Anonymous, 1997d). The mixtureis then considered to be tested and is not subject to theTest Guidelines 401 or 420 for oral toxicity, and 402

and 403 for dermal and inhalation toxicities, or by untested mixture criteria in CPR Sections 48 and 51(Anonymous, 1988c), and consequently, the calculatedother means specified in Section 33 of the CPR (Anony-

mous, 1989a, 1995b). LD50/LC50 value may be disclosed on the MSDS in placeof the LD50/LC50 values of the ingredients (Anonymous,LD50/LC50 values, defined as a single dose or concen-

tration which is expected to cause death in 50% of test 1988a).LD50/LC50 value(s) determined by testing the mixtureanimals (Anonymous, 1989a), are determined using

these tests. These values must be disclosed on the must be disclosed on the MSDS in place of the LD50/LC50 values of the ingredients, as specified in CPR Sec-MSDS, as specified in CPR Schedule I, Items 1(3) and

1(4), and they may trigger WHMIS D1 classification, tion 12(10). Occasionally, LD50/LC50 values are re-ported for both the mixture and the ingredients, al-as specified in CPR Sections 46, 48, 49, and 51. The

specific LD50/LC50 values meeting WHMIS Class D1 though this is not required.If more than one LD50/LC50 value is available for acriteria are summarized in Table 2. Inclusion in Cana-

dian Transportation of Dangerous Goods (TDG) classi- tested mixture or an ingredient, it is recommended thatthe supplier disclose: (i) the value established in accor-fications 2.3 or 6.1 (packing group I and II) is also a

criterion for inclusion in WHMIS Class D1 criteria. dance with OECD guidelines (if available) or the valueestablished using other protocols carried out in accor-LD50 values must indicate the route of exposure, the

species used in the test, and the unit of measurement. dance with generally accepted standards of good scien-tific practice at the time the test was carried out (inLC50 values must indicate the species used, the unit of

measurement (e.g., ppm or mg/m3 for gases and vapors, accordance with CPR Section 33(3)(b)(v)); (ii) the lowestvalue in the rat, and (iii) the value for another speciesand mg/m3 or mg/L for dusts, mists, and fumes), and

the exposure duration (Anonymous, 1997d). For if lower than the rat value (Anonymous, 1997d).Acute toxicity ‘‘limit tests’’ do not provide preciseWHMIS classification, LC50 values are based on 4-h

exposure periods, as specified in CPR Sections 46(c)– LD50/LC50 values. Rather, they specify a single dose orconcentration above which the LD50/LC50 lies (i.e., LD50/(e) and 49(c)–(d). LC50 values determined from other

exposure periods may be converted to a 4-h equivalent LC50 ú ‘‘X’’). Where such information is available, it isconsidered to be applicable for MSDS disclosure, al-value by applying the appropriate formula outlined in

CPR Section 44. though it is not a basis for WHMIS classification inClass D1. If a specific LD50/LC50 value is not available,For untested mixtures, available LD50/LC50 values

must be disclosed for ingredients subject to disclosure ‘‘greater than’’ values may be disclosed on the MSDS.If applicable and available, ‘‘less than’’ values may alsounder Section 13 of the HPA. If LD50/LC50 values are

not available for one or more ingredients of a mixture, be disclosed. The percentage mortality observed at thelimit dose tested is optional information for MSDS dis-CPR Section 45(2) specifies that the LD50/LC50 value of

the mixture is considered to be that of the most acutely closure (Anonymous, 1996d).lethal ingredient present in the mixture at ¢1%w/w. If LD50/LC50 values are known for each ingredient Skin Irritationpresent in the mixture at ¢1% w/w, the product LD50/LC50 may be calculated using the formula specified in Many definitions and scales of classification exist for

skin irritants. CPR Sections 60(a) and 33(3)(b)(ii) spec-CPR Section 45(1)(a). In such instances, each LD50/LC50



TABLE 3ify the tests applicable to WHMIS, which includeOECD Test Guideline 404 (Anonymous, 1992a) and the Numerical Equivalents for Descriptive Phrases:

Skin IrritationDraize skin irritation test (Draize, 1944). CPR Section33(3)(b)(v) indicates that other test methods conducted

Assigned primaryin accordance with good scientific practice may also be irritation index WHMISconsidered. Examples of skin irritation test protocols Descriptive phrase (range of values) classificationthat are considered applicable for WHMIS evaluation

Nonirritating 0 Noneinclude the EC Test Method B4: Acute toxicity—SkinMinimally irritating 0.1–0.5 Noneirritation (Anonymous, 1990) and several protocols de-Slightly irritating 0.6–1.5 Noneveloped by U.S. federal government agencies such as Mildly irritating 1.6–3.0 None

the EPA, DOT, FDA, and CPSC. For the most part, Moderately irritating 3.1–5.0 D2BSeverely irritating 5.1–6.5 D2Bthese tests vary only in the manner in which the resultsExtremely irritatinga 6.6–8.0 D2Bare scored and interpreted, and do not differ signifi-

cantly in the way in which the bioassay is conducted. a Materials achieving this score could be corrosive. The MSDSIn vitro tests for dermal irritancy assessment are not writer should look for signs of reversibility of effects in the study. Ifnormally considered applicable for hazard evaluation no reversibility of effects is seen by the end of the observation period,

the material should be considered a WHMIS Class E corrosive.(Anonymous, 1990).Classification as a skin irritant in WHMIS is depen-

dent on the numerical scores achieved when a materialis tested in accordance with the above noted methods.

Peripheral to the issue of scoring is that of the obser-As specified in CPR Section 60, dermal irritants testedvation period during which the scores are determined.in accordance with OECD guideline 404 must have aFor the OECD method, irritation is graded beginningmean score of ¢2 (out of 4) for the formation of ery-at 4 h after application of the test material and contin-thema (inflammatory redness) and/or edema (swell-ues until 72 h, with the highest irritation score ob-ing), at any of the observation times specified in theserved during this period used for classification (Anon-test (Anonymous, 1992a). Difficulties in the applicationymous, 1992a). In contrast, in the Draize method, irri-of data derived from other test methods to the assess-tation is graded 24 h after application of the testment of dermal irritancy in WHMIS sometimes occursubstance (Draize, 1944). It should be noted that thebecause the scoring systems and contact times varyexposure period used in the Draize method is signifi-from one method to another. Another problem commoncantly longer (24 h) than the corresponding exposureto all of these tests is that the descriptive phrase (i.e.,specified in the OECD method (4 h). The difference insevere, moderate, mild, slight) assigned to a materialthe exposure duration between the two methods mayas the result of a dermal irritation score varies withresult in greater dermal penetration and greater irrita-each method. In many studies, the score reported is thetion when a substance is tested in accordance with the‘‘primary irritation index’’ (PII) (Draize, 1944), whichDraize method.is determined by combining the erythema and edema

scores. The descriptive phrase that corresponds to the Eye IrritationPII is based upon the original system proposed byDraize (1944). For example, a material that produces CPR Sections 60(b) and 33(3)(b)(ii) specify the tests

for eye irritation applicable to WHMIS, which in-a PII of°2 is considered to be (at most) ‘‘mildly irritat-ing,’’ a PII of 2–5 is ‘‘moderately irritating,’’ and a PII clude OECD Test Guideline 405 (Anonymous, 1987b)

and the Draize eye irritation test (Draize, 1944). CPRof ¢6 is ‘‘severely irritating.’’ Published data do notalways include the individual animal or summary test Section 33(3)(b)(v) indicates that other test methods

conducted in accordance with good scientific practicescores, and may provide only a qualitative descriptionof the severity of the irritation produced. In other stud- may also be considered. Classification as an eye irri-

tant in WHMIS is dependent on the numerical scoresies, the descriptive phrase assigned to a test substancemay not be consistent with the test score reported. Al- achieved when a material is tested in accordance

with the above-noted methods. Eye irritants tested inthough the studies themselves may be applicable forWHMIS hazard assessment, they are deficient in not accordance with OECD guideline 405 must produce

mean scores for corneal, iris, or conjunctival effectsproviding the numerical score or the corresponding de-scriptive phrase, resulting in errors in the application as noted in Table 4, when measured at any of the

observation times specified in the test. Other accept-of the WHMIS criteria for classification as a skin irri-tant. To aid in the classification of dermal irritants able test methods for eye irritation commonly found

in the scientific literature include the modifiedwhere studies conducted in accordance with OECDguidelines are unavailable, a conversion scale was de- Draize method (Kay and Calandra, 1962) and the

French Association for Standards method (Associa-veloped, as shown in Table 3, to assist MSDS preparers(Johnston, 1988). tion FrancJ aise de Normalisation; AFNOR), which in-


66 COTE ET AL.

TABLE 4Numerical Equivalents for Descriptive Phrases: Eye Irritation

Irritation score Irritation scorea WHMISDescriptive phrase (Draize, 1944) (OECD, 1987) classification

Nonirritating 0 Cornea: õ2.0 NoneMinimally irritating 0.5–2.5 Iris: õ1.0 NoneSlightly irritating 2.5–15.0 Conjunctiva: õ2.5 NoneMildly irritating 16.0–25.0 NoneModerately irritating 26.0–50.0 Cornea: ¢2.0 D2BSeverely irritating 51.0–80.0 Iris: ¢1.0 D2BExtremely irritating or corrosive 80.0–110.0 Conjunctiva: ¢2.5 D2B

a Mean score achieved at completion of testing; descriptive phrase assigned if any of the 3 endpoints meet or surpass specified score.

volves a modification of the Kay and Calandra scoring involves the assessment of abrasive and particulatematerials. Insoluble particulate matter can cause eyemethod (Guillott, 1982). In vitro tests for ocular irri-

tancy assessment are not currently considered appli- (or skin) irritation through the physical mechanism ofabrasion, so care should be taken to not classify thesecable for WHMIS hazard evaluation.

The evaluation of eye irritancy can be problematic materials as WHMIS eye (or skin) irritants (Anony-mous, 1988b).because the assessment of data derived from methods

other than OECD test guideline 405 are based upondifferent scoring systems, dosing volumes, and/or con- Corrosiontact times. There are two major ocular irritancy scoringmethods which are commonly encountered when re- Section 65 of the CPR specifies the classification cri-

teria for a corrosive material in WHMIS (Anonymous,viewing the toxicological literature. Protocols based onthe Draize (1944) method use a maximum score of 110, 1988a). Of the six criteria listed in this section of the

regulations, two specify biologically based endpoints.in which the total score is weighted toward cornealdamage (maximum of 80/110 points). The assumption These are Section 65(b) (corrosive to skin in OECD

test 404) and Section 65(e) (causes visible necrosis ofunderlying this scoring method is that the cornea isthe most critical target tissue. The Draize irritancy human skin). The other criteria deal with physical or

chemical properties and the TDG classification of thescale also takes into account the persistence of the irri-tation and/or damage to the eye. Studies based on the product. Materials that fall within the criteria for skin

corrosivity will also meet the criteria for skin and eyeOECD protocol include separate scales for corneal, iris,and conjunctival effects. The scores for these effects are irritation (Anonymous, 1996d). Classification of these

materials into both Classes E and D2B is redundant,not weighted, and a positive response in any one couldtrigger designation as a WHMIS eye irritant. There is and could result in confusion on the part of MSDS us-

ers. Consequently, it was agreed that materials meet-considerable latitude in the interpretation of both theDraize and OECD scoring methods. Some investigators ing the biological classification criteria for skin corro-

sion (CPR 65(b),(d), or (e)) need not be classified inscore irritancy on a ‘‘pass/fail’’ basis, such that the testis considered positive if a specified score is attained Class D2B for skin or eye irritancy (Anonymous, 1989b,

1993a, 1996d). It is important to note that the exemp-at any time during a 21-day postexposure observationperiod. In other studies, the persistence of the effect(s) tion from including a product in Class D2B which al-

ready falls within Class E applies only to the skin oris considered when determining the irritation score andassigning a descriptive phrase. As a general rule, when eye irritancy of a substance and does not apply to other

Class D2B hazard criteria. Materials may be includedno eye irritation scores have been provided in a well-conducted study, the WHMIS classification is based on in Class D2B based on any of several other toxicity

endpoints (i.e., skin sensitization, mutagenicity, orthe descriptive phrase (i.e., slight, mild, moderate, se-vere). The ocular irritancy disclosed on the MSDS chronic toxicity). For such products, the appropriate

classification includes both E and D2B.should be qualified with the appropriate descriptor(i.e., mild, moderate, severe) (Anonymous, 1997d). When considering the irritancy versus corrosivity of

products that are untested mixtures, it is possible forSuch information is often missing on WHMIS MSDSs,and should be included to convey the seriousness of the a substance to exhibit both irritant and corrosive prop-

erties, depending on the concentration of the substancehazard to the user. Table 4 provides a cross-referencefor the interpretation and application of the two most in a mixture, and the duration of exposure to the sub-

stance in the test for dermal irritancy/corrosion. Forcommon ocular irritancy scoring methods to WHMIS.Another problem in the evaluation of ocular irritancy corrosive materials present in untested mixtures, data



TABLE 5WHMIS Classification of Corrosive Materials

WHMISCriterion Available test information classification

pH Material is a pure substance or mixture with a pH less than 2, or greater than 11.5. Class ESkin irritant/ Material is an untested mixture with an ingredient, present at ú1%, that has been tested in accordance Class E

corrosive with OECD test 404 (acute skin irritation/corrosion), or similar acceptable test, and score indicates acorrosive.

Material is a mixture containing a known corrosive, present at ú1%, tested in accordance with OECD Class D2Btest 404 (acute skin irritation/corrosion), or similar acceptable test, and score indicates an irritant.

Material is a mixture containing a known corrosive, present at ú1%, and the known corrosive has beentested in a diluted concentration equal to, or greater than, its concentration in the material inquestion, and score indicates an irritant. The diluted corrosive must have been tested in accordancewith OECD test 404 (acute skin irritation/corrosion), or similar acceptable test.

Eye irritant/ Material is an untested mixture with an ingredient, present at ú1%, that has been tested in accordance Class D2Bcorrosive with OECD test 405 (acute eye irritation/corrosion), or similar acceptable test, and score indicates a

corrosive.Material is a mixture containing a known corrosive, present at ú1%, tested in accordance with OECD

test 405 (acute eye irritation/corrosion), or similar acceptable test, and score indicates an irritant.Material is a mixture containing a known corrosive, present at ú1%, and the known corrosive has been

tested in a diluted concentration equal to, or greater than, its concentration in the material inquestion, and score indicates an irritant. The diluted corrosive must have been tested in accordancewith OECD test 405 (acute eye irritation/corrosion), or similar acceptable test.

Skin necrosis There is evidence that the material causes visible necrosis of human skin tissue. Class EEye necrosis There is evidence that the material causes visible necrosis of human eye tissue. Class D2B

may be available to show that the substance is corro- sons following exposure in the workplace (Anonymous,sive at high concentration, but is an irritant, or pro- 1988a). Respiratory tract sensitization as defined induces no effect, when diluted to a concentration similar Section 32 of the CPR means the development of severeto its concentration in the mixture. If such data are asthma-like symptoms such as sneezing, runny noseavailable, it is Health Canada’s practice to use the test (rhinitis), lung congestion, labored breathing, and/orinformation for the dilute material as the ‘‘applicable’’ asthma in a person who is not atopic (Anonymous,information for the purposes of WHMIS classification 1988a, 1997d). No test method for the evaluation ofand MSDS disclosure. Table 5 provides guidance for respiratory sensitization is specified in the CPR. Conse-the classification of materials in Class E. quently, medical case reports are the most common

Corrosive properties often depend on the pH of a source of information available for assessment of respi-material. OECD Test Guideline 404 states that ratory sensitization.‘‘strongly acidic or alkaline [materials] with a demon- A material is a WHMIS skin sensitizer if it causesstrated pH of 2 or less, or 11.5 or greater, need not dermal sensitization reactions in persons following ex-be tested for primary dermal irritation, owing to their posure in the workplace, or if it produces a positivepredictable corrosive properties’’ (Anonymous, 1992a). response in an animal assay carried out in accordanceTherefore, products with a pH °2 or ¢11.5 are consid- with OECD Test Guideline 406 (skin sensitization)ered to meet the criteria for WHMIS Class E, unless (Anonymous, 1981a). In the updated version of theskin test data demonstrate this is not the case (Anony- OECD protocol (Anonymous, 1992b), the guinea pigmous, 1989b, 1996d). maximization test (GPMT) of Magnusson and Kligman

(which involves use of an adjuvant) and the BuehlerRespiratory or Skin Sensitization test (no adjuvant) are given preference over other test

methods (e.g., Draize test, split adjuvant technique,Sections 56 and 61 of the CPR list the criteria foropen epicutaneous test, and the Mauer optimisationclassification of a material as a respiratory or skin sen-test). The mouse ear swelling test (MEST) and the localsitizer, respectively (Anonymous, 1988a). Sensitizationlymph node assay (LLNA) are specified as screeningis an immune system response to repeated exposure toassays that may be used as the first stage in the assess-a material, in contrast to irritation, which is a localment of skin sensitization. If a positive result is seenor topical phenomenon. The identity of the sensitizingin either assay, the substance may be considered a skinagent(s) should be disclosed on the MSDS (Anonymous,sensitizer, and it may not be necessary to conduct fur-1997d).ther tests. However, a GPMT or Buehler test must beIn WHMIS, a respiratory tract sensitizer is a mate-

rial that causes respiratory tract sensitization in per- performed to confirm a negative result in either the


68 COTE ET AL.

TABLE 6MEST or LLNA tests. In order to be classified as aWHMIS skin sensitizer based on animal data, a sub- WHMIS Dose Criteria for Chronic

Toxicity Classificationstance must produce a response in ¢30% of the testanimals if a test employing an adjuvant is used, or

Dose criterion¢15% of the test animals, if one of the techniques not for class D2A Dose criterion for classincorporating use of an adjuvant is used (Anonymous, Route of exposure chronic toxicity D2B chronic toxicity1988a).

Oral °10 mg/kg/day ú10 but °100 mg/kg/dayIn humans, skin sensitization (allergic contact der-Dermal °20 mg/kg/day ú20 but °200 mg/kg/daymatitis) may be characterized by pruritis, erythema,Inhalation °25 ppm by ú25 but °250 ppm byedema, papules, vesiculae, bullae, or a combination of Gas or vapor volume volume

these. In other species the reactions may differ and Inhalation °10 mg/m3 ú10 but °100 mg/m3

dust, mist, or fumeonly erythema and edema may be seen (Anonymous,1992b). CPR 32 specifies that these reactions shouldbe observed in nonatopic persons or animals if theyare to be used for WHMIS classification (Anonymous,1988a). Atopy is a Type I allergic reaction, specifically 59, and 33 specify classification criteria based on ani-

mal assays for subchronic and chronic toxicity. Whenone with strong familial tendencies, caused by variousallergens and associated with the production of IgE a substance is tested in a long-term assay and causes

effects of sufficient severity to threaten life or causeantibodies (Stedman, 1990). For example, individualsdescribed as having hay fever, asthma, a history of serious permanent impairment that is statistically sig-

nificant, it meets WHMIS Class D chronic toxicity crite-eczema, or a family history of any of these symptomswould be considered to be atopic for the purposes of a ria when the dose administered does not exceed those

listed in Table 6 (Anonymous, 1988a).WHMIS hazard evaluation.The wording of CPR Sections 56 and 61(b) requires The CPR specifies that chronic toxicological testing

be carried out in accordance with various guidelinesthat human data used for classification based on respi-ratory or dermal sensitization must be derived from such as those developed by OECD, FDA, and EPA. If

the toxicological information was derived from testingreports in which exposures occurred in occupationalsettings. For classification purposes, evidence of sensi- carried out prior to the establishment of these guide-

lines and the testing was performed in accordance withtization in ¢2 nonatopic persons is required. Thesecases can be from the same, or different, studies (Anon- generally accepted standards of scientific practice at

the time, the information can also be used (Anonymous,ymous, 1988a). If a study or case report does not specifywhether a subject displaying sensitization reactions as 1996d). In the absence of data on chronic or subchronic

exposure, the results of studies of shorter durationthe result of occupational exposure to a material isatopic, it is assumed for the purposes of the WHMIS (‘‘subacute or short-term’’ studies) are evaluated for

MSDS disclosure or classification (Anonymous, 1997d).classification assessment that (s)he is not. There is norequirement to determine whether a person described A material for which there is valid documented evi-

dence (epidemiological studies and case reports) basedin a case report (or other human data) is nonatopic inorder to render such information applicable for WHMIS on established scientific principles, indicating an ad-

verse effect in humans following chronic occupationalclassification (Headrick, 1995).The route of exposure to humans/animals in studies exposure, is also sufficient to include that material

within Class D. In this context, adverse effects meansto be used for the evaluation of skin or respiratory sen-sitization must be dermal and inhalation, respectively. injury to humans resulting from occupational expo-

sure, including any reversible or irreversible impair-Studies reporting sensitization reactions following ex-posures by other routes (i.e., oral) are not considered ment to health or irreversible diminished functional

capacity (Anonymous, 1996d). However, when evaluat-normally applicable for WHMIS hazard evaluation.ing these types of studies, one must be aware of com-mon confounding factors, such as a concurrent expo-Chronic Toxicitysure to other chemicals which may have contributed tothe effects observed.The CPR defines a chronic toxic effect as an adverse

health effect that can develop over time following a The omission of chronic toxicity information and/orits use for Class D classification is a problem encoun-single exposure to a toxic substance, or more commonly

from prolonged or repeated exposure to a toxic sub- tered frequently on WHMIS MSDSs. Although a prod-uct may meet WHMIS classification criteria for an en-stance under conditions that do not produce that effect

from a single exposure (Anonymous, 1988a). The CPR tirely different reason, such as flammability (Class B)or skin irritation (Class D2B), disclosure of the applica-requires the disclosure of chronic toxic effects on the

MSDS, even if the effects are not life-threatening or ble chronic toxic effects in animals and/or humans isalso required. In the case of ethylene glycol, whichserious (Anonymous, 1988a, 1997d). CPR Sections 52,



meets WHMIS Class D criteria for teratogenicity and of WHMIS controlled products. Generally acceptedassays for the detection of DNA damage include un-reproductive effects, the MSDS must also disclose all

other adverse effects associated with chronic exposure scheduled DNA synthesis (UDS), the investigation ofsister chromatid exchange (SCE), and DNA adduct for-to ethylene glycol. For example, ethylene glycol pro-

duced nephrotoxicity in rats when administered orally mation in cultured mammalian cells. When theseassays are conducted in vivo, they can provide evidenceat a dose of 1000 mg/kg/day for 12 months (DePass,

1986). of interaction with DNA and are thus indicators of mu-tagenic potential (Anonymous, 1986, 1987a).Another example of information often absent from

MSDSs is the tumorigenic effects observed in chronic The CPR classification criteria specify in vivo assaysand human evidence. A material is included in Classanimal studies of materials that have not been classi-

fied as carcinogens by the International Agency for Re- D based upon mutagenic effects if there is: (1) epidemio-logical evidence that shows a causal connection be-search on Cancer (IARC) or the American Conference

of Governmental Industrial Hygienists (ACGIH). Al- tween exposure of two or more persons to the materialand heritable genetic effects, (2) evidence of mutagenic-though these effects do not fall within the criteria for

carcinogenicity specified in Section 54 of the CPR, tu- ity in mammalian germ cells in vivo as shown by posi-tive results in a study that measures mutations trans-morigenic effects observed at doses less than or equal to

the cutoff concentrations listed in Table 6 meet WHMIS mitted to offspring, (3) a positive result in an in vivostudy showing chemical interaction with the geneticcriteria for Class D chronic toxic effects. For example,

respirable nonasbestiform talc has been shown to be material of mammalian germ cells and positive resultsin an in vivo study assessing either gene mutation orcarcinogenic and tumorigenic in rats following chronic

inhalation exposure at 6 or 18 mg/m3 (Anonymous, chromosomal aberration in somatic cells, or (4) evi-dence of mutagenicity in mammalian somatic cells in1993b). Evidence of carcinogenic activity in rats was

based on an increased incidence of benign or malignant vivo obtained in a test to assess either gene mutationor chromosomal aberration.adrenal tumors and adenomas and carcinomas of the

lung at the highest dose in female rats. Nonasbestiform The omission of mutagenicity information and/or itsuse for classification in Class D is a problem encoun-talc is not currently classified as a carcinogen by IARC

or ACGIH. However, one positive well-conducted study tered commonly on WHMIS MSDSs. The CPR requiresMSDS disclosure of mutagenic effects seen in animalsis sufficient for WHMIS classification and this study

meets Class D criteria for chronic toxic effects, i.e., seri- and/or humans of all WHMIS controlled products, evenif they meet WHMIS classification criteria for an en-ous impairment at a respirable dose of less than 100

mg/m3. This hazard must be disclosed on the MSDS. tirely different reason such as skin irritation (Anony-mous, 1988a). Results of tests on bacteria (e.g., AmesSalmonella mutation test), insects (e.g., Drosophila),Mutagenicityor cultured cells, while not relevant to WHMIS classi-fication for mutagenicity, should also be disclosed onNumerous mutagenicity tests are available for use in

hazard evaluation. These tests detect the two different the MSDS (Anonymous, 1997d). Acrylamide is a goodexample of a chemical causing in vivo mutagenic effectscategories of mutations, gene mutation, and chromo-

somal damage, as well as indications of DNA damage. in mammalian germ cells (Gutierrez-Espeleta, 1992)and somatic cells (Shiraishi, 1978), and therefore meetsTests to assess these endpoints can be carried out both

in vitro (with and without mammalian activation en- WHMIS criteria for Class D mutagenic effects. It isalso mutagenic in bacteria (Zeiger, 1987) and mamma-zymes (S9)) and in vivo. Generally, in vitro assays are

used for mutagen screening while in vivo assays are lian cells (Moore, 1987; Dearfield, 1988). All of the invivo and in vitro information should be disclosed on theused to confirm in vitro activity. In general, in vivo

tests are considered to have greater predictive weight MSDS. It should also be noted that a chemical shouldbe administered by an occupationally relevant route ofthan in vitro tests, tests with eukaryotic cells may have

greater weight than tests with prokaryotic cells, and exposure (oral, dermal, or inhalation) in in vivo muta-genicity assays evaluated for WHMIS.tests using mammalian species have greater weight

than tests using nonmammalian species. A chemicalmay selectively produce gene and/or chromosomal mu- Reproductive Toxicitytations, and since separate tests are required to investi-gate these endpoints, a minimum of two assays should Section 55 of the CPR specifies the WHMIS classifi-

cation criteria for reproductive toxicity based on effectsbe considered if available (Anonymous, 1986, 1987a,1993c). in humans and experimental animals. Examples of ad-

verse effects on male or female reproduction includeThe CPR references certain guidelines for obtainingevidence of mutagenic activity (Anonymous, 1978, disruption of gonadal function, estrous cycle, mating

behavior, conception, implantation, parturition, lacta-1986, 1987a). Table 7 lists some of the available muta-genicity assays recommended for hazard evaluation tion, or weaning (Anonymous, 1996d). Adverse effects


70 COTE ET AL.

TABLE 7Mutagenicity Assays Recommended for WHMIS Hazard Evaluation

Gene Chromosome In In CPR criterion for CPR criterion forAssay mutation aberrations vitro vivo somatic effects germ cell effects

Salmonella typhimurium reversemutation (Ames) x x

Gene mutation in yeast ormammalian cells x x

Mouse spot test x x xCytogenetic assay in cultured

cells x xMicronucleus test x x xCytogenetic assay in animals x x xDominant lethal assay x x xMammalian germ cell cytogenetic x x xHeritable translocation x x xUnscheduled DNA synthesis in

animals x xDNA adduct formation in animals x xSister chromatid exchange in

animals x x

on embryo–fetal development and/or fetotoxicity are substances for which little or no existing reproductivetoxicity information is available. In the absence ofdealt with in Section 53 of the CPR (refer to the Terato-

genicity and Embryotoxicity section). data from other more definitive reproductive toxicitytests, positive effects observed in studies of this typeThe criteria based on human reproductive toxicity

are specified in Section 55(a), which states that a sub- are useful for initial hazard assessment. However,due to the relatively small numbers of animals testedstance is considered a reproductive toxin if there is

‘‘evidence that shows it causes sterility or an adverse and short duration of the tests, negative findings instudies of this type cannot provide definitive evidenceeffect on reproductive capability in persons following

exposure to it in the workplace’’ (Anonymous, 1988a). of a lack of adverse effects on reproduction.Determining whether adverse effects should be con-Therefore, human data, such as case reports or epide-

miological studies, that are used for classification of sidered reproductive toxicity or teratology/embryo-toxicity can sometimes pose a problem. In some cases,reproductive toxicity must be derived from reports in

which exposures occurred in occupational settings. For adverse effects observed in multigeneration or contin-uous breeding studies may overlap between bothclassification purposes, evidence of reproductive toxic-

ity in at least two persons is required. These cases can parts of the WHMIS criteria. Studies in which expo-sure is limited to the pregnant female during all orbe from the same, or different, studies (Anonymous,

1996d). part of gestation are considered applicable for the as-sessment of developmental and embryotoxic effects.Section 55(b) lists the criteria for classification

based on reproductive toxicity in animal tests. OECD Studies in which animals are exposed during gameto-genesis, mating, after parturition, and during gesta-Test Guidelines 415 (one-generation reproduction

toxicity) and 416 (two-generation reproductive toxic- tion are potentially applicable to both the reproduc-tive and developmental toxicity criteria. Professionality) are listed in this section of the regulations (Anon-

ymous, 1983a,b). In addition, CPR Section 33(3)(b)(v) judgment is required to determine the applicable sec-tion of the CPR.permits consideration of other test methods con-

ducted in accordance with good scientific practice Effects such as testicular atrophy or degenerationof the seminiferous tubules observed in a chronic or(Anonymous, 1988a). Examples of other test protocols

that may be considered for the evaluation of reproduc- subchronic toxicity study may affect the reproductivecapability of the animal. However, this type of infor-tive toxicity include the reproductive assessment by

continuous breeding (RACB) method (Morrissey et al., mation by itself cannot be used to classify a substanceas a WHMIS reproductive toxin, since there is no1989), OECD Test Guidelines 421 and 422 (Anony-

mous, 1994b, 1995a). Since these other methods can evaluation of the breeding success or reproductiveperformance. However, the data may be applicable toprovide initial information on all aspects of reproduc-

tion, they may be of particular benefit in screening chronic toxicity classification, provided that the dose



falls within a range specified in those sections of the Many developmental toxicants fall outside theWHMIS classification criteria for this endpoint becausecriteria. Such information should be disclosed on the

MSDS, regardless of the class(es) into which the prod- fetal effects occur only at doses that elicit some formof maternal toxicity. Nonetheless, the MSDS must dis-uct falls.close this information for ingredients which are them-selves controlled products, and which have producedTeratogenicity and Embryotoxicityteratogenic or embryotoxic effects in the presence ofmild maternal toxicity (Anonymous, 1997d). The ratio-CPR Sections 53 and 33(3)(b)(iii) establish the

WHMIS classification criteria for teratogenicity or em- nale for this requirement is that the handling, storage,or use of these WHMIS controlled products may occa-bryotoxicity. Examples of the kinds of adverse effects

on fetal development applicable to WHMIS hazard sionally produce exposures resulting in mild maternaltoxicity, thereby resulting in potential developmentalevaluation include malformation, death, permanent

metabolic or physiological dysfunction, growth retarda- toxicity hazards. The assessment of mild maternal tox-icity is somewhat subjective and requires the applica-tion, psychological or behavioral alteration that occurs

during pregnancy, at birth, or in the postnatal period tion of professional judgment. However, studies inwhich fetal effects were observed in the presence of(Anonymous, 1988a). The classification criteria specify

that these effects should be observed in a statistically ¢10% maternal mortality are not considered applica-ble for hazard disclosure in WHMIS.significant proportion of the test population.

CPR Sections 53(a), (b), and (c) reference OECD TestGuidelines 414 (teratogenicity), 415 (one-generation re- Carcinogenicityproduction study), and 416 (two-generation reproduc-tion study) (Anonymous, 1981b, 1983a,b). The WHO Section 54 of the CPR specifies that, in order to be

classified as a carcinogen, a substance or a tested mix-guideline Principles for the Testing of Drugs for Terato-genicity is listed in CPR Section 33(3)(b)(iii) (Anony- ture must be listed in Section A1a, A1b, or A2 of Appen-

dix A of the Threshold Limit Values for Chemical Sub-mous, 1967). In addition to these specific test methods,CPR 33(3)(b)(v) allows for consideration of other test stances and Physical Agents in the Work Environment,

published by ACGIH or must be included in Group 1methods conducted in accordance with good scientificpractice (Anonymous, 1988a). Examples of such tests or 2 in the IARC Monographs on the Evaluation of

Carcinogenic Risk of Chemicals to Humans (Anony-include the Chernoff/Kavlock assay, OECD Test Guide-lines 421 and 422. The Chernoff/Kavlock assay has mous, 1988a). However, ACGIH has recently adopted

a revised classification system and substances now des-been extensively validated and accepted by the U.S.EPA as providing preliminary evidence of develop- ignated as A1, A2, or A3 should be classified as carcino-

gens under WHMIS (Anonymous, 1996c). There are nomental toxicity (Wickramaratne, 1987; Seidenberg andBecker, 1987; Siedenberg et al., 1986; Hardin et al., test methods for carcinogenicity specified in the CPR.

In this respect, the WHMIS classification criteria for1987; Schardein, 1993). Since the Chernoff/Kavlockassay generally provides an accurate prediction of the carcinogenicity is significantly different than all other

toxicological criteria.in vivo response that one would expect from conven-tional teratology tests, it is considered applicable for It should be noted that if carcinogenic effects are

observed in chronic toxicity tests with materials thatthe evaluation of developmental toxicity hazard inWHMIS. are not listed by either IARC or ACGIH, these effects

may trigger chronic toxicity classification under CPRA major factor that must always be considered whendetermining the WHMIS classification of a material as 52 or 59.

WHMIS classification criteria for carcinogens do nota teratogen or embryotoxin is maternal toxicity. CPRSection 53(1) specifies that effects on the fetus must apply to industrial processes. This has sometimes cre-

ated some confusion for MSDS preparers. For example,occur ‘‘at a concentration that has no adverse effecton the pregnant female.’’ Although the assessment of IARC and ACGIH recently assigned Group 1 and A2

designations, respectively, to occupational exposures tomaternal toxicity is critical in determining if a sub-stance is to be classified as a teratogen or fetotoxin, strong-inorganic-acid mists containing sulfuric acid.

IARC groupings include chemicals, classes of chemi-maternal toxicity is not defined in the CPR. To clarifythis issue, the federal and provincial regulatory agen- cals, industrial processes, and occupational exposures

that are carcinogenic to humans and/or experimentalcies prepared a policy paper on this subject (Anony-mous, 1997c). This document provides guidance for the animals. The IARC classification in this case refers to

an occupational exposure, which does not imply thatinterpretation of observed changes in maternal factorssuch as mortality, body weight, body weight gain, organ sulfuric acid, or solutions thereof, is carcinogenic. Con-

sequently, sulfuric acid present in WHMIS controlledweights, food and water consumption, and clinical ob-servations of toxicity in the context of WHMIS classifi- products does not trigger a WHMIS carcinogenicity

classification. However, the MSDS for controlled prod-cation requirements.


72 COTE ET AL.

TABLE 8Information Sources

Item Source

HPA and CPR Available for purchase from the Canadian Government Publishing Centre, Ottawa,Ontario, Canada K1A 0S9. (819) 956-4802

WHMIS Core Material Available for purchase from the Workers’ Compensation Board of British Columbia,P.O. Box 5350, Vancouver, BC, Canada, V6B 5L5. (604) 276-3137

Reference Manual for the WHMIS Requirements Product Safety Bureau, Health Canada, Ottawa, Ontario, Canada K1A 0L2. (613)of the HPA and CPR 957-4467

WHMIS Information Bulletins and Policy IssueSheets

ucts from which a mist containing sulfuric acid could refer to airborne concentrations of specific substances,and represent conditions under which various organi-be generated should indicate that occupational expo-

sure to strong-inorganic-acid mist containing sulfuric zations have concluded that nearly all workers maybe repeatedly exposed without adverse health effectsacid is carcinogenic to humans (Anonymous, 1997a).(Anonymous, 1994a, 1996a, 1997b). They are recom-

Toxicological Synergisms mended by bodies such as the ACGIH and the U.S.National Institute for Occupational Safety and HealthToxicologically synergistic products must be dis-(NIOSH), or are legislated by provincial health andclosed on the MSDS, as specified in CPR Schedule I,safety regulatory agencies in Canada. ACGIH specifiesItem 7(11). These are defined as ‘‘any substances, mate-three categories of exposure limits, termed thresholdrials, or products which interact with the controlledlimit values (TLVs): Time-weighted average (TWA),product,’’ including its ingredients (Anonymous,short-term exposure limit (STEL), and ceiling (C)1997d), ‘‘to produce a toxic effect greater than the sum(Anonymous, 1996a). Exposure limits specified byof their separate effects’’ (Anonymous, 1996d). How-NIOSH (recommended exposure limits or RELs) andever, this subitem was intended to incorporate differentthe U.S. Occupational Safety and Health Administra-kinds of toxicological interactions, of which there aretion (OSHA) (permissible exposure limit or PELs) arefour general types: synergism, additivity, antagonismTWAs unless noted otherwise (ST or C) (Anonymous,(i.e., inhibition), and potentiation (Anonymous, 1997d).1994a). For substances for which neither a TLV norThus, information concerning additivity, antagonism,PEL or a REL has been developed, the American Indus-and potentiation should also be disclosed on the MSDStrial Hygiene Association (AIHA) sets guidelines for(Anonymous, 1997d).workplace environmental exposure levels (WEELs), ex-Toxicological interactions are rarely disclosed onpressed as TWAs, short-term TWAs, or ceiling valuesMSDSs. Considering the widespread occurrence of(Anonymous, 1997b). Exposure limits may also be rec-multiple chemical exposures in the workplace, the needommended by the supplier. A skin notation accompa-to anticipate possible toxicological interactions is es-nying an exposure limit indicates potential significantsential for WHMIS MSDS disclosure. For example, si-toxicity from skin absorption (Anonymous, 1994a,multaneous exposure to toluene and acetylsalicylic acid1996a, 1997b), and should be included on the MSDS.results in auditory impairment significantly greaterExposure limits set by agencies other than those listedthan the sum of the effect induced by each substance above are not normally required for WHMIS MSDSindividually (synergism) (Johnson, 1993). The fetotoxi- disclosure, unless a limit set by a North American bodycity produced by sodium salicylate is significantly is unavailable.greater with concurrent exposure to ammonium chlo- Since all exposure limits may be applicable underride, which itself is not fetotoxic (potentiation) (Khera, various working conditions, all appropriate values for1991). the substance should be disclosed on the MSDS (Anon-Unfortunately, guidelines for assessing which toxico- ymous, 1997d). The MSDS should also disclose values

logical interactions are applicable within the WHMIS for ingredients if this info is applicable to the mixture.framework are currently not available. As a general To be useful, the values should be current and fullyrule, HC considers only those interactions in which ex- detailed. Omission of a C/ceiling, ST/STEL, or a skinposure to the controlled product, or its ingredients, oc- notation, which occurs occasionally, may compromisecurs via an occupational route of exposure. worker health and safety. ACGIH’s ‘‘Notice of Intended

Changes’’ may be consulted for substances for whichExposure LimitsTLVs are under review.

Exposure limits must be disclosed on the MSDS, as It is anticipated that the CPR will be amended torequire that the exposure limit(s) be qualified on thespecified in CPR Schedule I, Item 7(4). Exposure limits



Directorate, Health Canada, Environmental Health Centre, Tun-MSDS by indicating the source, and adding a state-ney’s Pasture, Ottawa, K1A 0L2.ment to the effect ‘‘consult local authorities for accept-

Anonymous (1987a). Introduction to the OECD Guidelines on Ge-able provincial values’’ (Anonymous, 1996d, 1997d).netic Toxicology Testing and Guidance on the Selection and Appli-The MSDS should indicate the source of all exposure cation of Assays. OECD Guidelines for the Testing of Chemicals.

limits disclosed on it (Anonymous, 1997d). For sub- Environmental Health and Safety Division, Organization for Eco-nomic Cooperation and Development, 2, rue Andre-Pascal 75775stances without currently established exposure limits,Paris Cedex 16, France.but which fit into a general category of substances for

Anonymous (1987b). OECD Test Guideline No. 405: Acute Eye Irrita-which exposure limits have been established (e.g., nui-tion/Corrosion. OECD Guidelines for the Testing of Chemicals. En-sance particulates or mineral oil mists), a supplier willvironmental Health and Safety Division, Organization for Eco-occasionally disclose exposure limits for the general nomic Cooperation and Development, 2 rue Andre-Pascal 75775

category of substances. This is acceptable, provided the Paris Cedex 16, France.values are fully qualified. Anonymous (1988a). Controlled Products Regulations (CPR). Can-

Where it is known that the use of the product could ada Gazette, II 122(2), 551–589.give rise to lethal conditions, a NIOSH immediately Anonymous (1988b). Policy Issue Sheet No. 40: CPR s. 60—Skin

and Eye Irritation. WHMIS Policy Section, Product Safety Bureau,dangerous to life and health (IDLH) limit, where avail-Health Canada. 1000 Wing, Statistics Canada Main Bldg., Tun-able, may be disclosed as applicable information on theney’s Pasture, Ottawa, Ontario K1A 0L2.MSDS (Anonymous, 1997d).

Anonymous (1988c). Policy Issue Sheet No. 29: Classification of Con-There are many useful sources of guidance avail-trolled Products for Acute Lethality using the LD50 Summation

able to WHMIS MSDS and label preparers. These Formula (Sections 45, 46, 48, 49 and 51 of CPR). WHMIS Policyhave been outlined for convenience in Table 8. Sev- Section, Product Safety Bureau, Health Canada. 1000 Wing, Sta-

tistics Canada Main Bldg., Tunney’s Pasture, Ottawa, Ontarioeral of these documents are also available on the In-K1A 0L2.ternet at the following addresses: http://www.hwc.

Anonymous (1989a). WHMIS Core Material: A Resource Manual forca/datahpb/dataehd/English/psb/psb.htm (English);the Application and Implementation of WHMIS. Worker’s Compen-http: / /www.hwc.ca /datahpb/dataehd/Francais /bsp/sation Board of British Columbia, 6951 Westminster Highway,

bsp.htm (French). Richmond, British Columbia, V7C 1C6.Anonymous (1989b). Policy Issue Sheet No. 60: CPR 65(b)—Criteria

for inclusion in Class E—Corrosive Material. WHMIS Policy Sec-REFERENCEStion, Product Safety Bureau, Health Canada. 1000 Wing, StatisticsCanada Main Bldg., Tunney’s Pasture, Ottawa, Ontario K1A 0L2.Anonymous (1967). Principles for the Testing of Drugs for Teratoge-

Anonymous (1990). ECETOC Monograph No. 15: Skin Irritation.nicity. WHO Technical Report No. 364, World Health Organiza-European Centre for Ecotoxicology and Toxicology of Chemicals.tion, Geneva.

Anonymous (1992a). OECD Test Guideline No. 404: Acute DermalAnonymous (1978). Proposed guidelines for registering pesticides inIrritation/Corrosion. OECD Guidelines for the Testing of Chemi-the U.S.: Hazard evaluation: Human and domestic animals. Fed.cals. Environment Directorate, Organization for Economic Cooper-Regist. No. 163. 43 (37), 336–337 and 403.ation and Development, 2, rue Andre-Pascal 75775 Paris CedexAnonymous (1981a). OECD Test Guideline No. 406—Skin Sensitiza-16, France.tion. OECD Guidelines for the Testing of Chemicals. Environment

Anonymous (1992b). OECD Test Guideline No. 406—Skin Sensitiza-Directorate, Organization for Economic Cooperation and Develop-tion (Adopted 17 July 1992). OECD Guidelines for the Testing ofment, 2, rue Andre-Pascal 75775 Paris Cedex 16, France.Chemicals. Environment Directorate, Organization for EconomicAnonymous (1981b). OECD Test Guideline No. 414—Teratogenicity.Cooperation and Development, 2, rue Andre-Pascal 75775 ParisOECD Guidelines for the Testing of Chemicals. Environment Direc-Cedex 16, France.torate, Organization for Economic Cooperation and Development,

Anonymous (1993a). Policy Issue Sheet No. 78: Precedence of Class2, rue Andre-Pascal 75775 Paris Cedex 16, France.E (‘‘Corrosive’’) Over Class D2B (‘‘Skin and Eye Irritation’’) in theAnonymous (1983a). OECD Test Guideline No. 416: Two-GenerationClassification of Products. WHMIS Policy Section, Product SafetyReproductive Toxicity. OECD Guidelines for the Testing of Chemi-Bureau, Health Canada, 1000 Wing, Statistics Canada Main Bldg.,cals. Environment Directorate, Organization for Economic Cooper-Tunney’s Pasture, Ottawa, Ontario K1A 0L2.ation and Development, 2, rue Andre-Pascal 75775 Paris Cedex

Anonymous (1993b). Technical Report on the Toxicology and Carcino-16, France.genesis Studies of Talc in F334/N rats and B6C3F1 Mice. (Inhala-Anonymous (1983b). OECD Test Guideline No. 415: One-Generationtion Studies) National Toxicology Program Research. NTP TR 421.Reproductive Toxicity. OECD Guidelines for the Testing of Chemi-NIH Publ. 93-3152. National Toxicology Program, P.O. Box 12233,cals. Environment Directorate, Organization for Economic Cooper-Research Triangle Park, NC 27709.ation and Development, 2, rue Andre-Pascal 75775 Paris Cedex

Anonymous (1993c). The Assessment of Mutagenicity: Health Protec-16, France.tion Branch Mutagenicity Guidelines. Publication No. 93-EHD-Anonymous (1984). Commission Directive of 25th April, 1984 adapt-168, Environmental Health Directorate, Health Canada, Environ-ing to technical progress for the sixth time Council directive 67/mental Health Centre, Tunney’s Pasture, Ottawa, K1A 0L2.548/EEC on the Approximation of Laws, Regulations and Adminis-

Anonymous (1994a). NIOSH Pocket Guide to Chemical Hazards.trative Provisions relating to the classification Packaging and La-DHHS (NIOSH) Publication No. 94-116. U.S. Department ofbeling of Dangerous Substances. Annex V, Part B: Method for theHealth and Human Services, National Institute for OccupationalDetermination of Toxicity (84/449/EEC). Off. J. Eur. CommunitiesSafety and Health.L251, pg. 106.

Anonymous (1986). Guidelines on the Use of Mutagenicity Tests in Anonymous (1994b). OECD Test Guideline No. 422: Combined re-peated dose toxicity study with the reproduction/developmentalthe Toxicological Evaluation of Chemicals. Environmental Health


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The Evaluation and Hazard Classification of Toxicological Information for Workplace Hazardous Materials Information System Material Safety Data Sheets