UNCLASSIFIED AD NUMBER - DTIC Login · a number of oxides of phosphorus: P401PzO'PzO3 (or P4 0 6), P0 2 (or P?0 4), PZO5 (or P4 0 1 0), and P2 0 6; but only three of these species

UNCLASSIFIED

AD NUMBER

ADB058048

NEW LIMITATION CHANGE

TOApproved for public release, distributionunlimited

FROMDistribution authorized to U.S. Gov't.agencies only; Test and Evaluation; MAY1981. Other requests shall be referred toCommander/Director, Chemical SystemsLaboratory, Attn: DRDAR-CLJ-R, AberdeenProving Ground, MD 21010.

AUTHORITY

CRDEC ltr, 29 Mar 1990

THIS PAGE IS UNCLASSIFIED

The findinqs in this report ar, riot to be construed as an official

Department of the Army flosition. unless so desiqnated by otherauthori/ed documents.

OISPOSITION INSTRUCTIONS

Destroy this report when it is no longer neededDo not return 1i to the origintor,

UJNCLASSIFED11111[c V CLASSIFICATION OF Tw$$ PAGE £e'b.. ON* Bawfomi

REPORT DOCUMENTATION PAGEIt"NSRcuREOR NMS OVT ACCESSION moo 8. MEIZZ61111VI6 CATA&06 semailla

- ARCSL-TR-800)68 -rt-ýS

O THE SUBCHRONIC EFFECTS OF REPEATED EXPOSURE Technical Re"ortC) TO WHITE PHOSPHORUS/FELT SCREENINJG SMOKES IN July 1978-May 1980coRATS effuo0.nvn suai

1. AUTHOR(e) rtichard L. Farr"w0, CONTVRACT ON GPIAMT NUMISE P4*j

fl ernard J. Brown William C. StarkeGarnett. E. AfrIeck Joh T. Weiner2) Edwind G. Cwuulmngti Nipie~ S. QCiwan, SP5

9.l PERFORMING ORGANIZATION NAME AND ADDRES, 10, PROGRAM ELEMEM1,00111AECT. TASKco Commander/Director, Chemical Systems Laboratory ARoEct WR UI NM1 01822 55

tt ATTN: DRDAR-CLB-T PoetI122A5

-& Aberdeen Proving Ground, Maryland 21010 Technical Area 4-5A~< 11. CONTROLLtmNEI OVicE NAME AND ADDRESS 12. REPORT DATE

Commander/Director, Chemical Systems Laboratory May 1981ATTN: DRDt.R-CLJ-R 13. NUMBER OF PAGES

Aberdeen Proving Ground, Maryland 21010 12914. MONITOO41NG AGENCY NAME & AOONESS(11 dittleomtbhef Coustroind 0111cC) IS. SECURITY CLASS. (of Old sopeff

UNCLASSIFIED0S. DECLASSIFICATIONIDOWNGRADONIG

SCH EDULE N

ti. DISTRIBUTION STATEPIENT (of Wel Report)

Distribution limited to US Government agencies only because of test and evaluation; May198 1. Other requests for this document must be referred to Commander/Director, ChemicalSystems Laboratory, ATTN: DRDAR-CLJ-R, Aberdeen Proving Ground, Maryland 21010.

17. DISTRIBUTION STATEMENT (of thse abetted ientered In Stock"2. it differenfrml Pooe.flf)

IS. SUPPLEMENTARY NOTES

19. KEY WORDS (Continue. on reverse sid. It n.ecessary and Identihfy by block raimS.)

Smoke Subchronic toxicityWhite phosphorus RatsFelt White phosphorus/fletScreening smoke

Z&. AVTU AC? (Centhow . reesem.1 *hoIt "Wm...m md fdowitr by blockh number)Toxicity studies were conducted to determine the subchronic effects of repeated expo-sure to three concentration levels of a white phosphorus screening smoke. When whitephosphorus burns, it forms a number of oxides of phosphorus which are rapidly convertedby .moisture to phosphorus fjnd phosphonic acids. It would appe4 that the chance of

ijry is high at 1161 mg/rn and low at 193 mg/rn3 . At 589 mg/rn , one-half of the ratsshowed some exposure effects. The rats apparently developed a tolerance to repeated

exposures, particularly at the lowest level.

DO F 0 1473 EDITION OF MOV GSi IS 0SOLETE UCASFE

SIECURITY CLASSIFICATIONI OF TIMIS PAGE (111bs Dole aM.0091

"p'Best Available Copy

PREFACE

The work described in this report was authorized under ProjectlMI626-!ZASS4, Chemical Munitions and Chemical Combat Support; Technical Area 4-5,

nioke Toxicology. The work was started in July 1978 and completed in May 1980. Theexperimental data are contained in notebook 9839.

In conducting the research described in this report, the investigators adheredto the "Guide for the Care and Use of Laboratory Animals" as promulgated by the Com-mittee on Revision of the Guide for Laboratory Animals Facilities and Care of the Insti-tute of Laboratory Animal Resources, National Research Council.

The use of trade names in thia r,,n-rt does not constitute an official endorse-ment or approva! of the uzte of such commercial hardware or software. This report maynot be cited for purposes of advertisement.

Reproduction of this document in whole or in part is prohibited except withpermission of the Commander/Director, Chemical Systems Laboratory, ATTN: DRDAR-CLJ-R, Aberdeen Proving Ground, Maryland 21010. However, the Defense TechnicalInformation Center is authorized to reproduce the document for United States Govern-ment purposes.

This report has not been approved for release to the public.

Acknowledgment

The authors wish to acknowledge the following:

Clarence E. Hopkins for the performance of gross necropies and body-organ

weight data.

John F. Miller and Franklin Tittle for preparation of blood samples for chemi-

cal analysis and statistical analyses of the results.

Malcom N. Allison, CPT, V.C., for histopathology. These data are included

verbatim as appendixes.

William Lane for his technical assistance.

Acee.ion For

N T TS 8?--.1DTIC W;

DTICELECTE Dtruttn

JUL 3 981Distiz1hntion/_JUL 1 3 1981 Avati.bility Codes

"Avai. And/orB - Dist !peta 1

m 3/

CONTENTSPage

I INTRODUCTION .......................................... 7

EXPEI IMFN1'A|. I'VOCEDURES ............................... 7

2.1 Chamber Operation and Sample Collection ...................... 72.2 Animals Used ........................................ 82.3 Animal Exposures and Observations ........................ 9Z.4 Blood Studies ........................................ 82.5 Pathology .......................................... 8z.6 Physiological and Behavioral Studies ....................... 9

3 RESULTS ................................................ 9

3.1 Exposure Conditions ................................... 93.2 Trxic Signs ......................................... 93.3 Body-Organ Weights ................................... 93.4 Hematology and Blood Chemistry ......................... 9

. Pathzlogy .......................................... 103.6 Reproduction Studies .................................. 103.7 Physiological Studies .................................. 113.8 Behavioral Studies . .................................... 13

4 DISCUSSION ............................................. 13

5 CONCLUSIONS ........................................... 14

LITERATURE CITED ....................................... 15

APPENDIXES ............................................. 17

A. Chemical Analysis of White Phosphorus Smoke .............. 17

B. Details of Toxicological Evaluation ....................... 19

C. Pathology Report - Spontaneous Deaths ................... 39

D. Pathology Report - 6-Week Exposure ..................... 55

E. Pathology Report - 13-Week Exposure .................... 79

F. Pathology Report - 13-Week Exposure and4-Week Recovery Period ........................... 103

DISTRIBUTION LIST ........................................ 17

)++' ...

THE SUBCHRONIC EFFECTS OF REPEATED EXPOSURE TOWHITE PHOSPHORUS/FELT SCREENING SMOKES IN RATS

I. [NTRODUCTION

Toxicity studies were conducted to determine the subchronlc effects ofrepeated exposure to three concentration levels of a white phosphorus screening smoke.This smoke, one of the candidate screening smokes, was generated by burning pieces ofwhite phosphorus-impregnated felt.

The following studies were performed to obtain a subchronic toxicity profileon rats: inhalation toxicity of multiple exposures, including pathology, hematology, andblood chemistry, and effects of exposures on reproduction, behavior, and physiology.

Z. EXPERIMENTAL PROCEDURES

2.1 Chamber operation and sample collection.

Animals for the inhalation studies were placed in compartmented stainless-steel wire-mesh cages. The cages were put on racks in a 20-cubic-meter exposure cham-ber.

Military grade white phosphorus, which had been forced under pressure intothick pieces of wool felt, was cut into cubes having specific weights. For each exposure,one of these cubes on an aluminum foil pan of a known weight was placed on an electrichotplate within the chamber. The hotplate was a fast-heating unit capable of tempera-tures in excess of 7000 F.

The chamber door was closed and sealed, and the chamber exhaust systemwas shut down. The hotplate was plugged in and the white phosphorus/felt ignited,usually in less than 2 minutes, producing a dense white smoke. This smoke is made up ofa number of oxides of phosphorus: P 4 01PzO'PzO3 (or P4 0 6 ), P0 2 (or P?0 4 ), PZO5 (orP 4 0 1 0 ), and P2 0 6 ; but only three of these species - P O0, PO, and P7 O5 - are wellestablished. All three of these oxides are deliquescent and they could, therefore, con-tribute various aqueous droplets to the smoke. The reaction of P 0 5 with atmosphericmoisture has already been described; the corresponding reaction ior P 2 0 3 produces o-phosphorus acid. The tetraoxide, Pz0 4 , feacts with water to produce equimolar solutionsof o-phosphorous and o-phosphoric acid. The white phosphorus/felt burning time rangedfrom less than 1 minute for some of the small cubes to over 9 minutes for one of thelarge cubes. The smoke was contained within the chamber for 15 minutes before beingremoved by the exhaust system.

Smoke sampling started after 7 minutes of exposure. The samples werecollected on Gelman Type-A glass fiber filter pads. Twelve liters of chamber air, at therate of 3 liters per minute, were drawn through the filter pads contained in the air sam-pler probe. The filter pads were placed in Erlenmeyer flasks. Particulate material wasextracted with distilled water, boiled for 10 minutes, and titrated for phosphoric acidcontent (see appendix A).

7

Air samples were also collected in a modified Rochester cascade impactorand analyzed for phosphoric acid content, and the mass median diameter of the airborneparticles was derived.

Z.Z Animals used.

Four groups of Sprague-Dawley rats were used, one for each dose level plusthe controls. Thirty-six male and 36 female rats were used for the high- and intermedi-ate-exposure levels with 18 rats of each sex acting as controls for each level. Only 18males and a like number of females were-exposed to the low-dose level. Nine animals ofeach sex acted as controls for this exposure.

Additional groups of rats were exposed and the rats were ,-ated on differentschedules to determine the effects of repeated exposures on mammalian germ cells andreproductive performance. Procedures used are discussed in a previous report.*

Z.3 Animal eposures and observations.

Animals were exposed for 15 minutes daily, 5 days a week for 13 weeks. The

rats were observed for toxic signs before and after each exposure. At regular intervalsduring the 13-week exposure and 4-week postexposure periods, all animals were weighed.

After 6 weeks, one-third of the animals were withdrawn from exposure. Halfof these animals were bled and submitted to pathology. The other half were examined tosee if any physiological or behavioral changes occurred. When the 13 weeks of exposureended, the remaining animals were separated into two groups. One group was divided aswere the 6-week animals with half going to pathology and half for physiological andbehavioral studies. The remaining animals were held for a 4-week postexposure period toobserve any recovery that might occur. Then they were bled and submiLted for patholog-ical evaluation.

Z.4 Blood studies.

Blood samples in rats were analyzed for triglycerides, cholesterol, glucose,urea nitrogen, creatinine, uric acid, sodium, potassium, chloride, carbon dioxide, alkalinephosphatase, albumin, globulin, calcium, phosphorus, serum glutamic pyruvic transami-nase, serum glutamic oxalacetic transaminase, red blood cell count, white blood cellcount, differential white blood cell count, hematocrit, and hemoglobin.

2.5 Pathology.

Gross and microscopic pathological examinations of the following body organs

were performed for all animals submitted: heart, lung, liver, spleen, kidney, brain, eve,trachea, nasal turbinate, adrenal, stomach, urinary bladder, pancreas, thyroid, esophagus,duodenum, colon, lymph node, thymus, testis, epididymus, ovary, uterus, bone marrow,and skin. In addition to those animals sacrificed at 6, 13, and 17 weeks, animals that diedduring the experiments were submitted for necropies. The number sacrificed at eachtime interval was adjusted according to the number of animals that died during thatinterval.

*Starke, W. C., and Pellerin, R. J. Technical Memorandum. The Effects of CS-Z onReproduction in Rats (in preparation). 1980.

g'

z.6 Physiolotical and behavioral studies.

Animals were submitted for physiolpgical and behavioral evaluations using theprocedures described in a previous publication.

3. RESULTS

3.1 Exposure conditions.

Target concentrations were 1000, 500, and 200 mg/m 3 . Target and actualconcentrations are used interchangeably in the appendixes. Concentrations are alsoreferred to as high, intermediate, and low, respectively. To obtain desired concentra-tions, 20-, 10-, or 3-gram cubes of the white pbosphorus-impregnated felt were used.When ignited, a. dense white smoke-like mist was produced. The droplets of this mist hada mass median diameter of 0.5 micron. A charred residue weighing approximately 27%of the original weight remained after burning.

Appendix B, table B-1, shows the mean exposure doses produced by each cuberecorded.

3.2 Toxic signs.

Animals were not visible for observation until the smoke cloud was evacuatedfrom the chamber. Visible toxic signs were not observed during the first 3 days of expos-ure to the high dose. One hour after the fourth exposure one female rat died. Two otherrats wheezed for about 2 hours. Of the 72 rats starting this high-dose study, 23 diedduring the first 6 weeks of exposure. Four more died during the remaining 7 weeks.Transitory dyspnea and wheezing were observed in many rats, with recovery within 2hours of each exposure. The cumulative exposures at which deaths occurred are shown inappendix B, table B-Z.

Rats exposed to the intermediate and low doses showed no visible toxicsigns. None of these animals died.

3.3 Body-organ weights.

There were no consistent changes in total body weights or in weights of theorgans regardless of dose or time. Means and standard errors for body and organ weightsof control and exposed rats are shown in tables B-3 and B-4, appendix B. Significantdifferences, where they did occur, are indicated.

3.4 Hematology and blood chemistry.

No agent-related changes were observed in the blood chemistry and hema-tology analyses. "T" test evaluations indicated there were no significant agent-relateddifferences between control and exposed values. No sex-related changes wereobserved. Means and standard errors of all blood constituents analyzed are shown intables B-5 through B-10, appendix B.

9

3.5 Pathology.

3.5.1 Spontaneous deaths.

A high mortaJity rate (about 40%) occurred in the group of colony rats ex-posed to the 1161 mg/mr dose level. The deaths appear to be agent and dose related.None of the rats exposed to the intermediate- or low-dose levels died. A completedescription of pathological findings is presented in appendix C.

3.5.2 Six-week exposure.

Although laryngitis or tracheitis was not observed In any of the control ani-mals, all laryngeal and tracheal specimens from rats exposed to the high-dose leveldisplayed a moderate-to-severe laryngitis/tracheitis. Fifty percent of the rats receivingthe intermediate-dose level displayed a minimal-to-mild tracheitis while one-third had amild laryngitis. Only one rat receiving the low dose displayed tracheitis. Four of sixhigh-dose rats had a minimal-to-severe interstitial pneumonia. Two of the 18 controlrats displayed a minimal interstitial pneumonia. A complete description of these patho-logical findings is presented in appendix D.

3.5.3 Thirteen-week exposure.

Although none of the control rats displayed laryngitis or tracheitis, all of themale rats receiving the high-dosage level of white phosphorus/felt exhibited moderatelaryngitis. Of the female rats receiving the same dosage level (1161 mg/m ) of whitephosphorus/felt, one of two larynges examined displayed a moderate laryngitis; whereastwo out of three tracheae displayed mild-to-moderate tracheitis. Three out of six fe-male rats receiving the medium-dosage level of white phosphorus/ felt displayed a mod-erate tracheitis; whereas three out of five male rats receiving the same level exposuredisplayed slight-to-moderate tracheitis. None of the low-dosage-level animals displayedlaryngitis or tracheitis. A complete description of these pathological fitdings is present-ed in appcnri.i E.

3.5.4 Thirteen-week exposure with four-week recovery period.

Significant findings were limited to the respiratory tracts of the rats exposedto the high- and intermediate-dose levels. Lesions were noted in the larynx or trachea of15 of 16 high-dose rats and 20 of 24 intermediate-dose rats. Pulmonary lesions werenoted in 11 of 16 high-dose and 6 of 24 tnto.r.ieite-dose rats. None of the control orlow-dose animals exhibited significant lesions. A complete description of these patholog-ical findings is presented in appendix F.

3.6 Reproduction studies.

To assess the effects of white phosphorus/felt smoke on reproduction pro-cesses in rats, three studies were conducted: teratology, dominant lethal mutation, andreproduction in a single generation. Each of these studies was conducted at both thehigh- and intermediate-exposure levels and in the control (smoke-free) atmosphere.

At the high-dose level of each study, several of the animals died. Five of the24 high-dose teratology females died before their scheduled necropsy date. Twelve ofthe 20 males for the single-generation study died prior to their time for mating. Nine ofthe 20 males for the dominant lethal mutation study died before they could be mated.

10

3.6. 1 Teratolo.y.

Pregnant females were exposed to test and control atmospheres from days 6to 15 of Restation. There were no major abnormalities found among the control or testfetuses. The pregnancy rates for control, intermediate-dose and high-dose smoke were100%, 100%, and 9004, respectively. Data on the number and condition of implants, themean body weights of the fetuses, and the averaged data on implants appear in appendixB, table B-i. Statistical analysis of these data showed no differences between controland treatment groups.

3.6.2 Dominant lethal mutation.

In the dominant lethal mutation study, analysis by the chi-square methodshowed that, for the first mating, significantly more of the dams mated to intermediate-dose males had one or more resorptions as compared to the dams mated to control males,appendix B, table B-12. This difference was not observed at the high dose, indicatingthat the difference observed with the intermediate-dose group was probably not attribut-able to the effects of white phosphorus/felt smoke.

3.6.3 Single-generation reproduction.

The single-generation reproduction study results are more difficult to ana-lyze. Although there were no significant differences in the body weights of the pups atbirth, survivability of the exposed pups was significantly lower than that of the controlpups, appendix B, table B-13. Exposures continued for the pups and dams through this Zi-day period. Weight gain in the surviving exposed pups was less than that of the controlpups, appendix B, tahb1 B-14. The difficulty arises from the inability to discern whetherthe deficiency in weight gain was (1) the result of the exposed dams not caring for theirpups, (2) a decrease in mammary gland secretion, (3) the inability of the pups to nursebecause of irritated and congested tracheas, or (4) exposure effects.

3.7 Physiological studies.

Physiological measurements were made on days 3 and 4 after the animalswere removed from the exposure. The number of animals (sample size) used in the testsare shown in appendix B, tables B-15 and B-16.

An analysis of variance (ANOVA) was made on the data to determine theeffect of dose (exposure level), sex difference, and the effect of dose within sexes.Following this, a T-test was I-crformed to locate any significant differences.

The logic for determining a physiological effect from the white phosphor-us/felt smoke required that the following conditions apply: (1) a significant difference ata P _< 0.05 level be evidenced by the analysis of variance and Student T test, (2) the dif-ferences must be dose related and directional so that significant differences occurring ina low-dose group that were not reinforced by similar effects in the high-dose groupswould be considered a chance occurrence, and (3) the difference should be time relatedunless an adaptive response for increased tolerance has developed. With a bioaccumu-lated material, it would be expected that effects shown after a 6-week exposure wouldbe repeated after a 13-week exposure. With white phosphorus smoke, it is interesting tonote from pathology (page 10) that upper airway irritation, i.e., tracheitis and laryngitis,

1M

decreased after a 6-weeks' exposure. Assuming that phosphorous pentoxide unites withwater lining the respiratory tract to form a phosphoric acid, the response to this irritantmay be decreasing with time of exposure and consequently the application of presentstatistical judgments takes the possibility of increased tolerance into effect.

The results are shown in appendix B, tables B-15 through B-17. At both 6-and 13-weeks' exposure, significant sex differences were shown which appear to berelated to the greater size of the male rats. These included breathing volumes and theincreased inhaled volume responses to 6% CO In addition, blood pressures from malerats were slightly higher than those of female rats. This has been observed in othertests.

Some differences appeared to be the effect of dose and these are indicated intables B-1 5 and B-16. However, none of these effects satisfied the logic described abovefor determining a physiological effect. The same applies for the sex-related doses. It isnoted that the sample size in the high-dose exposures was reduced because of deathsduring the procedure. It is possible that, if the sample size were larger for high-dosegroups, a statistical significance would have been noted. It appears that some effect wasdeveloping in the group toward a reduction in tidal volume and an increase in breathingfrequency with dose in the 13-week exposed animals. Ther'. is also indication that therewas less growth in the male rats of this group.

Table B-17 contains the qualitative or nonparametric observations made onrats in the exposure groups. Three of tht- 13-week high-exposure groups had loud bubblyrales 3 days after exposure which were absent on the fifth post-exposure day.

Although no statistical validation for a functional effect exists, the presenceof rales and the tendency for a reduction in tidal volume and an increase in breathingfrequency in the high-dose animals indicate that a careful examination of the lung path-ology data and the pulmonary resistance data be made.

The evaluation of the pulmonary function as a result of exposure to whitephosphorus/felt smoke was carried out on rats that had been exposed for a period of 13weeks. The method for estimating the pulmonary resistance in these animals was basedon a comparison of the plethysmographic pressure during a respiratory cycle and the peakrespiratory flow. The rationale for using this method is based on the principle that thechanges in pressure in a body plethysmograph during a respiratory cycle are proportionalto the alveolar pressure during post cycle. (Pulmonary resistance is determined by theratio of alveolar pressure to the flow rate during a respiratory cycle; therefore, anestimate of the resistance can be determined by substituting the plethysmographicpressure for the alveolar pressure.)

The results of the pulmonary tests in the unanesthetized rat following 13-weeks exposure to white phosphorus/felt smoke are presented in appendix B, table B-18.There were no significant differences from control values in the respiratory rate or peakinspiratory flow rates in either males or females exposed to smoke. There was-no signifi-cant difference in the estimated pulmonary resistance of the female rats followingexposure. The estimated pulmonary resistance of exposed male rats had a tendency toincrease slightly over that of the controls. This increase was significantly different inthe low-dose rats but rot in the high-dose animals; however, the indication is that somepulmonary damage may be present in the male rats exposed to white phosphorus/feltsmoke. No rats were tested at 6 weeks postexposure.

3.8 Behavioral studies.

The behavioral responses of rats exposed to white phosphorus smoke foe 6 or13 weeks was measured using spontaneous activity and passive avoidance tests. In aUinstances, values are compared statistically to a group of unexposed control rats of equalage and weight.

3.8.1 Spontaneous activity.

The results of these tests are presented in appendix B, table B-19. whichshows the gross and fine activity of the rats and the ratio between these two types ofactivity. Both male and female animals exposed for 6 weeks appeared to exhibit a dif-ference in activity; however, the mean values presented were influenced by one or twoanimals from each group including controls. If the ratio is calculated from these means,the values become more uniform, indicating that spontaneous activity was not altered asa result of exposure.

3.8.11 Passive avoidance.

Passive avoidance test results are presented in appendix B, table B-ZO. Theexposed female rats, at 1161- and 589-mg/m3 dose levels and 6-week/13-week exposuretime periods, were no different from control animals. This indicated that the animals'ability to passively avoid shocks was not adversely affected by exposure to white phos-phorus smoke. Male rats exposed to the high dose received more shocks than the con-trol rats but statistically the values were not significantly different. The number ofpassive avoidance responses were no different. One of the 13-week high-dose male ratsreceived an unusually large number of shocks with no attempted avoidance, raising themean value for this group of animals. This animal had either a higher pain threshold thanthe other animals or a delay in determining how to avoid the shock. The lower-dose malerats showed no differences from the control animals.

4. DISCUSSION

When white phosphorus burns, it forms a number of oxides of ph•sphoruswhich are rapidly converted by moisture to phosphorus and phospronic acids. ' Al-though at ordinary expected field concentrations (100-Z00 mg/mr ), t~is may not bphazardous, some irritation to the eyes, nose, and throat may occur. Cullumbine'exposid a total of 108 men to white phosphorus smoke at concentrations from 87 to 1770mg/m . Throat irritation was produced at all concentrations. From these data, it hasbeen estimated that the minimum harassing concentration (requiring a respirator) isabout 700 mg/m 3 . In the documentation lor threshold limit values (TLV), it has beenrepojted that concentraýions of 100 mg/m were unendurable except to hardened work-ers. A TLV of I mg/mi was established as the level to which nearly all workers may berepeatedly exposed without adverse effect. A Iran exposed to 100 mg/mr would probablymask or remove himself from the smoke cloud.

In the study just completed, the 1000 mg/m 3 dose, with 40% spontaneousdeaths and injury to all other animals, was obviously a hazardous concentration. None ofthe animals exposed at +he 500- or Z00-mg/rn dose levels died. The intermediate dosedid, however, produce tracheitis in 50% of the rats. Only one of the low-dose animalsshowed any signs of irritation.

13

S. CONCLUSIONS

It would appeaj that the chance of injury is high at 1161 mg/m3 and low at193 mg/mr. At 589 mg/rn, one-half of the rats showed aome exposure effects.

The rats apparently developed a tolerance to repeated exposatses, particularlyat the lowest exposure level.

14

LITERATURE CITED

I. Milham, M. E., Anderson, D. H., Frickel, R. H., and Tarnove, T. L.ARCSL-TR 77067. New Findings on the Nature of WP/RP Smokes. July 1977.

Z. Cummings, E. G., Armstrong, R., Farrand, R. L., and McNamara, B. P.ARCSL-TR-79015. Physiological and Behavioral Methodology for Evaluating ChemicalEffects on Unanesthetized Rats. March 1979.

3. Van Wazer, J. R. Phosphorus and Its Compounds. Volume I: Chemistry.pp. 267-279. Interscience Publishers, Inc., New York, New York. 1958.

4. Technical Manual TM 8-Z85. Treatment of Chemical Agent Casualties. p.79. Department of the Army, the Navy, and the Air Force. January 1968.

5. Cullumbine, H. Porton Report 2604. The Burning Power and HarassingEffects of White Phosphorus. March 17, 1944.

6. Documentation of the Threshold Limit Values for Substances in WorkroomAir. American Conference of Governmental Industrial Hygienists. 3rd editioA.. 1971.

7. Weimer, J. T., Affleck, G., Preston, J., Lucey, J., Manthei, J., and Lee,F. ARCSL-TR-77052. The Acute Effects of Single Exposures to United Kingdom RedPhosphorus Screening Smoke in Rats, Guinea Pigs, Rabbits, and Dogs. August 1977.

15/16

APPENDIX A

CIITE.C°IrAL ANALYSIS OF WHITE PHOSPH4ORTIS SMOKE*

"xposure chamner air samples received were diluted with distilled water,shaken, then boiled 10 minuties to convert the phosphorus acids to orthophosphoric acid,then cooled to room temperature. Sample volume was measured after hoiling. Using aplT meter as an indicator, the acid content was determined hv titration against 0.10043 Nsodium hydroxide to a p74 of P.6. After measuring the amount of 0.10043 N sodiumhydroxide required to adjust the sample pF to 9.6, the following formula was used todetermine normality of the orthophosphoric acid:

1. Nsample x Vsample = NNaOH x VNaO]T

N Normalitv

V = Volume of sample in milliliters

The normalitv of the acid is multiplied by 3Z.66 (milliprams per milligram-equivalents of orthophosphoric acid).

. milligram equivalents 32.66 milligrams milligrams

milliliters milligram equivalents rmilliliters of(normalitv of sample) orthophosphoric acid

3. millir-,rams

milliliters X milliliters = milligrams of orthophosphoric acid in sample

B. P. Pearce. Porton Technical Paper 154. The Stability of Red PhosphorusCompositions. June 1974. UNCLASSIFIED Paper.

17/19

APPENDIX B

DETAILS OF TOXICOLOGICAL EVALUATION

Table B-I. Inhalation Exposure Doses Produced by Burning Cubes of White

Phosphorus/Felt

Cube Average exposure Total cumulativeCube Avrage eposure 15-minuteepouet

weight concentration exposure CCt

gm mg/M 3 mg min/m 3 mg min/m 3

zo 1161 1-7,415 1,097,151 (63 days)

10 589 8,833 556,480 (63 days)

3 19Z.5 Z,887 179,991 (62 days)

19

. . . ......

Table B-2. Spontaneous Deaths in Rats Exposed to the High-Dose Concentration ofWhite Phosphorus Smoke

Deaths

Exposure day Male Female Cumulative exposure Ct,:.

ing minim 3 -

4 1 54,2Z55 1 69,2259 ! 143,975

10 1 158,820-11 2 176,34012 1 3 194,79013 1 1 210,960,-"14 2 1 225,12016 1 251,9Z523 z 376,Z6024 1 397,65025 1 420,330Z6 1 441,30027 1 460,545z9 1 499,56034 1 588,04547 1 813,02154 1 936,8Z057 1 995,426

Appendix B

20

00 0o00 000 00.4 000 000

%n- It- N:$ 9. ,140 N * ar~ fn1 a-)2

C;fv 6 • 0I C; C ti ( C; Cm; CM5 all f; C; C; C

0 ell

oo

-n v ' - t. 0 %nkPC I -: -: It) e It I (1ý li Cý N •I - 1: 4 fl "

o 'Q 00 C) > A Q Q . 00 0 00

4)

00, 0Q 00A 0 tOCpmO 0 00

SO,,< ~ ~~~~ 1 11•••• •.,:_.en N. en mm en f"v " N m-1

441

4) -'U, 0 O• • c 0 . Lu• m we

I0

it'0e r - '0 t- '0 'D m

' r U 0 00 00 00 00 00 ix0

Append ix B :

4.

M~) o'm e~JM 0r.~ LI~O. f),?

P A t00 10 0 000 0004 c

It r!f + '1', 0,0 00 0 000 Q 0 C00 0;00

.- m.4 0

c;~ coo 000 00 0

(14 C '-4 t (4 f4W. CA CA 1i 4

93

.4.. ~ ~ ~ ~ ~ ~ i 4) u LO *~ ~~** o0:

* ~ ~ ~ ~ , .o~0 0

jenm 0' Qf)0 *f4 f"

-0 Cf -a i,

Appendix

-04

Or

C, C,

R 00r

-wD C,

Lo o a0~

6 rii

0 o 0,C -2 0

.1 5

Z fe

1Z3

AA€ 6A• 'r '-

Iz

. __ ___-- -- -- -

~~~~~a , 40o•)• ..

-- -

"• .v tý r-a!

r- S; a.-

S" .

rno , .. e.- Zv

-ro

.14

e me g 4 -Z0•ts....

0

.. 4) _ _ ____

IAC

U0U

Appendix B Z4

6) 5 o-i-

I)C C, C I

o'4 to -4w -.0

7W ~ 0~

.00.

0.0

0 "

CC

4L C5

Z ------ eýi

OOD 0

0~ '4v0, u -v

- 0- 0

Appendix B

~0e00 25

I~~---- C4-.----

mo b j 00 0

IX~ m m -4j . hOJC .Z

lo -A t, .1~~o --

41

~~~~!. !2 q~~-

- ... 4

4* ~ .O4O..O-. -

-- ZN N f

4,G -c- . .V~ ..- ~OR 'R A.~C . A4

0O~CC C~ ~ 5'. C~ 0000 .41

±.~~ ~ - -~ -CC~ C -O -- -. -. . -

tE

. . - C;. _ c

-Z . ," "-- p- e.- . . u ,. .

-_ .... *:' -' ....-----

N A I.

- r- '

.5 s

" .:E E. . . . . - -o:,

Q0 0 c

s. C - ,..C - .,; . . . . .

- -- ,- -

0~~ E 4,

----- " :L , - " - "". ~-

--*4E.. ... ... .. ; ... ... *

S E ., . .. . . . .

E ---- - - --

.A 0 a oZ

Cm V. W. -,I

0c 0 o :1*

-. 6 5n.J. O -W se. -sj -

OOCCC -A OO4. 00 4

z ~ Z7

C.__=__=__ ___

U2 fie-

Ap en i B.. 27.

- 5

-~~C aC,- - a 0

____Z_ ~ I TO- .eooo.

-aa

0 E4 0 1

-; 0 0

cý a. oZc :7, oc

000000~ ~ a : ~ 4 -

EL1 a ]a- z 9

Apeni B 4' ~ #

75 POO 0cI. -t -k%o in, o.' 0000N •, +I+I+I +1 +1 +I

- tJ *O " ,, i

4J

'C

'U OL""A44. I

cb I=..

X O• 4 k )Q a% G ;

r 4 ,-N en +1+1+1 +11,co C" 1- % o CDP

S0

(C--

LL. -4

0 enOO LIN M1 +

0 0 0

.~0

a... I C.

41 "6 41

Z4). 'a 41.

Appendix B

Al

E -4 "4 4

4' - r- ýo

IA.

UJ N N

ho r- -4 - 4 "

* ~ ~ ~ o '-Lon -L -urN N 00 O44L

WE 494 N.5"4 ~

"0 * '-" -0

(~~ C ~ -r4, -0a, L '0 -r

4.9 ~ ~ o O- co" co~~9- -yq ~-

.4 -. ~ N M -. -N r4

0 0 9Lr- 0- 0' 10 A

Appeniix0 0 0 30 ~11

0

en

00

0. 0 9-

0' 00 0oj 0 i f

PC

004)4

.00

0~ ~ 0~.

UJC

4j CL

:i3u

Appendix B 31

1 0 inl N in

00 + -+ +

ri co fn i~+ i+

""4 N4 -

a UiU) 10 0 L4) 01 10

.4-"'1-

- - en-

0 -,0o

oA - .-- -

00 -. 1' '0

N -00 1 ' en N

o 0 '0 &A LA0'A +1 +1 + Nt

I' qt - ..10 O 0el ~

0' n 0' r- r '

'0 4 %0 N M

U) u)

co, a,

-4 . - U)%

m -4 10 a, Ln- 0

t .4. 10 m0nW

A LA '. L

Apeni 0B 321

IIc

I E

I I I

Appendix ft

331.,11

IsI

I L -- - -

Bu

-L-

is Apenix

34

B *22

Table B-17. Oualitative Observations on Rats Exposed to White Phosphorous/Felt Smoke

Number responding

Exposure period

Observation

6 Weeks 13 Weeks

_......__ Control Low dose High dose Control Low dose High dose

Vasomotor reflex 12/12 12/12 6/6 12/12 12/1Z 7/7

Light reflex 12/12 12/12 6/6 12/12 12/12 7/7

-.espiratory response 12/12 12/12 6/6 12/12 12/12 7/7to CO

Sniffing response 9/12 12/l 6/6 ll/1Z 12/12 7/7

Moist rales 0/1Z 0/12 0/6 0/12 0/12 3/12

Appendix B

35

Table B- 18. Pulmonary Responses of Rats Exposed to White Phosphorus/Felt

Smoke for 13 Weeks

Response (mean and SE)Number '-'-

Condition Sex of Estimated Respiratory Peakanimals pulmonary rate inspiratory

resistance flow

cmHZO/1/sec resp/min ml/sec

Control Male 5 1.03 +_0.06 179 + 14.3 24.8 + 0.92

High dose Male 4 1.29 + 0.18 171 + 2.74 24.7 +0.70

Low dose Male 5 1.75 + 0.27 14Z + 5.07 24.1 + 0.55

Control Female 6 1.58 + 0.88 120 + 3.3 22.6+0.90

High dose Female 3 1.75 + 0.27 145 + Z6.6 24.2 + 0.59

Low dose Female 6 1.33 + 0.13 134 + 5.8 Z3.3 + 0.7Z

Appendix B

36

TATIhe B-10. T'he Spontaneos Activity Pesponses of Pats Exposed to White Phosphortis/Felt SmokeI i

Number Response IGross activit ratiosCondition sex of (mean and SE) fine activityanimals Gross activity Fine activity from individual data from mean

6-Week exposure

Control Female 6 457 + 143 1680 + 512 5.12 + 1.39 3.68High dose Female 3 502 + 21 1739 +140 3.49 + 0.37 3.46Low dose Female 6 574 -; 134 1874 7353 6.32 + 3.40 3.Z0

Control Male 6 278 + IZZ 1093 + 3Z7 5.10 + 0.53 3.93High dose Male 3 336 + 65 723 +319 1.97 -0.37 Z.15Low dose Male 6 760 +109 g 2253 +306 3.07 + 0.34 Z.96

13-Week exposure

Control Female 6 608 + 133 160 + 300 2.82 + 0.46 2.65High dose Female 3 46Z +- 38 1548 +149 3.4Z+0.53 3.35Low dose Femal 6 575 T 177 1652 "4z1 3.44 +0.46 2.87

Control Male 6 601 + 138 1287 + 176 2.40 + 0.29 2.14High dose Male 4 420 + 48 1368 T+308 2.86 " 0.54 2.91Low dose Male 6 450 + 123 1651 +191 3.25 + 0.23 3.67

Appendix B 37

444

fJn,- N;$iV t-le m V- n M

ccc 00 0-40r a - IL

0

+ 1+1+1 4+1+I+ +1+1+1 +1~+I+0 9oa - 0 -NO m'N LU)

0 C), C) 0I t- Ln

en~-,~ R 'ng ri~r C! - Rco m mU- "ieni- en I-

mn- %D enr- ou) 10

00IIAA.A

InI 0 r-0r- U0 .4 u

oAppendixen'

03

APPENDIX C JPATHOLOGY REPORT - SPONTANEOUS DEATHS

PATHOLOGY REPORTPROJECT SMOKE I1, WHITE PHOSPHORUS/FELT

INHALATION STUDY - SPONTANEOUS DEATHS"COLONY" RATS

I. INTRODUCTION.

Six and thirteen week studies designed to assess potential local and systemictoxic effects of inhalation exposure of the agent White Phosphorus/Felt wereperformed on Edgewood Area Colony Rats. Three dosage levels of the agent weretested. High (1000 mg/mni) dosage level studies began on 31 July 1978. Medium-(500 mg/m 3 ) dosage level studies began on 7 August 1978. Low (200 mg/m 3 ) dosagelevel studies began on 11 September 1978. All rats were approximately six weeksof age at the beginning of the studies and were housed in Bldg E3266.

Of forty-three rats (19 male, 24 female) receiving the high (1000 mg/m3)dosage level exposure to White Phosphorus/Felt, twenty-nine (15 male, 14 female)died spontaneously during the studies while one control animal and none of themedium or low dose group animals died.

Following necropsy. tissues were imbedded in paraffin and subsequentlyprocessed for staining with hematoxylin and eosin. The following tissues wereevaluated microscopically: nasal turbinate, larynx, trachea, lungs, heart,esophagus, stomach, small intestine, pancreas, large intestine, liver, adrenal,thyroid, thymus, kidney, bladder, ovary/teste, uterus, mammary gland, prostate,bone marrow, spleen, brain, eye and pituitary.

Histologic findings are tabulated in Tables 1-3. Since one or more tissuesfrom various animals were lost at necropsy or during processing, one mustcalculate the incidence of lesions based upon the number of tissues examinedrather than on the number of animals necropsied.

Two previous reports have been submitted regarding the histopathologicalfindings in the colony rats that completed the six and thirteen week studies.This report deals only with the histopathological findings in those animalsthat died spontaneously before completing the studies.

11. RESULTS.

The microscopic observations are presented in the Histopathology IncidenceTables.

a. Table 1 tabulates incidence of lesions by organ observed in male andfemale rats dying spontaneously.

b. Table 2 tabulates incidence and severity Vf lesions by organ observed in malerats dying spontaneously from the high (1000 mg/mr) dosage level exposure group.

39

c. Table 3 tabulates incidence and severity of lesions by organ observedin female rats dying spontaneously from the high (loon mng/m 3 ) dosage levelexposure group.

llt. DISCUSSION.

Numerous sporadically occurring lesions were noted in the high (1000 mg/m3)dosage level rats that died prior to completion of the White Phosphorus/Feltsmoke inhalation studies. Moderate to severe laryngitis was observed in allof nine male rats examined and in five out of six female rats examined.Moderate to severe tracheitis was observed in five out of seven male rats andin all of nine female rats examined. Laryngeal and tracheal lesions often in-cluded varying degrees of vessiculation (blistering) and ulceration of themucosal surfaces. Death of many of these animals probably resulted from as-phyxiation produced by mechanical blockage of the larynx/trachea from swelling orfrom laryngospasm resulting from irritation of the larynx by the smoke.Moderate to severe congestion (hyperemia) was observed in twenty-five out oftwenty-nine lungs examined. Irritation produced by the inhaled smoke may beresponsible for this finding. A minimal to mild multifocal to diffuse inter-stitial pneumonia was observed in sixteen out of twenty-nine lungs examined.Peribronchiolar lymphoid aggregates were noted in the lungs of eighteen oftwenty-nine animals examined.. The interstitial pneumonia and peribronchiolarlymphoid aggregates have been observed historically in colony rats held inthis and adjacent animal research facilities. The death of one control ratis attributed to a generalized Phycomycosis (non-contageous fungal agent) in-volving the gastrointestinal tract, liver and brain.

IV. CONCLUSION.

A high mortality rate was noted in the high (1000 mg/mr) dosage levelexposure group of colony rats being exposed to White Phosphorus/Felt smokevia inhalation exposure. The death of these animals appears to be agent anddose related. A moderate to severe laryngitis/tracheitis accompanied byvarying degrees of vessiculation (blistering) and ulceration was observed inmost of the animals. Death in these animals probably resulted from asphyxiationproduced by mechanical blockagie of the larynx/trachea from tissue swelling orfrom laryngospasm resulting from irritation of the larynx by the smoke. Moderateto severe pulmonary congestion was observed in many of the animals and isprobably agent related.

MALC N. ALLISON, CPT, VCComparative Pathology BranchVeterinary Medicine Division &

Resources Support DivisionUS Amy Biomedical Laboratory

Appewt Lx C 40

L:

Project Smoke II

White Phosphorus/Fel t

Inhalation Study - Spontaneous Deaths

"Colony" Rats

S~~Key to--Microscopic Findings :i

Table I

Number of Animals: Represents total number of animals in each group necropsied.

Numbers following tissues represent the number of tissues from each groupactually examined. --

Numbers following lesions indicate the number of tissues examined showingthe particular lesion.

Tables 2-3

- - tissue present

+ = tissue not available for microscopic evaluation

Numbers following organ: Number of specimens examined

Severity of Response j1 Minimal

2 = Slight

3 = Moderate

4 = Severe

P = Present

,' ni ix C 41

- L

'A in ci.4 snL M a

I-- Ln -1

CL

-LJ

e.J ton - , uLAJ - )u JU- LU-

=A 4-S 41 " 4J

L'0 UMC 4

J C LUj 0 4u 0 C

o ca 4) ý 0s- uC - AL

m .'0 0v 0 0 4

cz IA 4) Li 4) @A c a) 4C> 0- 4-' meU ~ E

ck ..J +j Z Cn In w 0). & C~

Lol "' U' E W..0 .0 4(#Lm. m - .1j M:u- =C

Appendix C *42

IAItA u1

Ne2

&A I ri- --

I (CA~I1co JCD- - - - - - -- - - - - - -

0

C-)~

IL m. n en *A

.-i -= .

(-. -o -1 0U)J L. 0 4

I.- ;E~ -0 &A -

0 -

U- do -j 1 -j -b "-

Vi V

Li so #- -u 4 5

C) cc o o 0IA - - 5 4 aCL - - - :m--

;. DL U c? C * L.LI6LA- JS U)0

Apeni C4

LLIV)ILAI

> .LL 3C

co ID0u

LL -

I U -j CL V)U 4

cc -j -u - - -

-wmc( s. - C

IA'A

o r= 10 0 m . 0 0 n - 9= -

C6 -j -.(A LU -C 9c

0peci C 4

L-- -- . -: -- en - - - -

ILA ON LA

= -7

r -- 4

LA -.- v----t- _

co1

-- A$-CD CDaiL

(ILI

4.,LA- LA4A -

C-~.9 ua.-0 t

15. C.U 0 A t)-C>. 'A .9- 0 tI- C - ..- 1_ c

-. LA, Ml'9 ~ - L O C I L-. C-U

-- ol kmIf 0>< 'U LA 0 . Ca- .

Ut w4 vd CC.c ~LJ >1

(A U. App.ndi45

Th7L.7

-.-L.~-

- - -. - - - - -,.+

66L8OL + CV')- 4 ~ 9 %

SOL-91

IOL-st + E~

o ..J 00" -SL * 4. * 1. -

_ - -- -- - -

(Aj 0i-S + + cC

00-S C__

999-OL I M-- - - - -

-4 -S

0in8 +1 a 41

Cý Ix>.C)CDC-4=~ -S 1= Q

0- Ld C

_.) _i V) C

0 an- U.

:lc 0U 0U as

_0 as~jE . 0 0 )

0A Wr cc rz 0 S

Apperndix C 46

IM-8

0M -8

Cl I

VEL-8L 'S - - --

609-8t

LO m

_9a =2 . +.

U- _ _

[t9L , .-

4.. uj ~ IA

U..

00Ln C3

o W-

Apeni 0 47 #

.0 s- w i ~ 1 I4

- .-I-.Lz

Lii 66L-SL +4 IU4 - 44 4i+IL9L-8L8L~aaa* *

S1L-BL+

wtn S0L-OL + aaa+ a

o UJI ~SOIL + ..

CL IOOL-RL +

z [~~~~~LP-9L + - - . -' 4.

1E9-8L. + _ - -.. ~ .019-SL + - - - + a* +

609-OL + a+F

+ 4 .----o

La- Lo4U)U

nz 41

0u 4x.)C

44

14 "% .. A L

44 1

c~~ U~-U4-1 0 ..

.. V) L" aJ 4A Co 2 0.-j0C 4

Appendix C *.48

L6.

w n6 L 9LSd,8

9- -

-. GE48

USIL-OL

oI LAS I

A-) OiOL-9L c,,

AM-9

I-JI

C-j

C.) 0

-=- LACD

In du 0

C)J 404

0 ~ ~ F .-. t

Append. 4j 4

-- -d III- ..- _,%

-> .------ i.,-, I

Q.L

Lii

U,7

(AW 629-OL .en~-29-9L

m OL9-SL *~, * n

-. 5

SL I 9-

- D U- -BL

0- -j - -.

£BS8L -j r-4

.4 " 0 0 V -t

4! 4) )

m LAJ UU Ue4 I

Apeni C 50

161-81 - - aaa

COL-OL 7.L- - - - - 2.~

Ce999-8L 1.1.......LS

L.) L61 '9-8L

a I. t9-8LI a i

*Z9-8La

Ot 9,8L a {a - a - s - - - +

co tp19-8L

S-3 aa, $A to

U- w

w tea L. D

C> ~ ~ ~ ~ 9 w9- - L4w cm >. CDf :cL~a La v n .d~ 41

EUv-i~i C'

uI

4A

60-S

T9o -8 -

CLh

Z6L-9L 1 04

* t'L1Jt M ~+9.a

o 6OL9 t a

CBS a'

X S98L&-------------------------------------

zo q 0 a * aa

u n 4. n2L N

0 -

O b98 Wl :I CA-- N -

CA aa

CL-8 a^ N a= a 0 -X FS . a a

0U) 0)L C i

%C w gi .i

Appendix c 52

F' - - ~ .V)

on w

L6L-9L + + m*2

t -J S9984 + cu II

ig OZ0-8L + + +a'

O9 LU £9-8L o . 429~ + + + a.o~~~~~L t~-9-.---------- - -Oz -. +

039-OL + ~ 4

90'19-81 + +

Vv5( 199L +

09 -9 .7 7

I.)IA

lU

.ý 4. 0L

-' -L -u f lAA G LL

0) 10 41i

App'ni. CA 0

to4Kt

APPENDIX D

PATHOLOGY REPORT - 6-WEEK EXPOSURE

Project Smoke II

Inhalation Study Six Weeks

"Colony" Rats

1. Introduction,

The present study was designed to assess potential local and toxic effects

following inhalation exposure to White Phosphorus/Felt for a period of fifteen

minutes per day, five days a week, for six weeks.

A group of six female rats were exposed by the inhalation route to bhite

Phosphorus/Felt at a high dose level (1000 mg/mr) and two groups of twelve rats,

equally divided as to sex. received intermediate (500 mg/mr3 ) and low (200 mg/m3)

dosage levels for the prescribed period of time followed by euthanasia. A fourth

group of eighteen'rats, equally divided as to sex, that were exposed to air only

and maintained under similar conditions, served as controls.

At termination and necropsy. tissues were imbedded in paraffin and subsequently

processed for staining with henatoxylin and eosin. The following tissues were

evaluated microscopically: nasal turbinate, larynx., trachea, lungs, heart,

esophagus, stomach, small intestine, pancreas, large intestine, liver, adrenal.

thyroid, thymus, kidney, bladder, ovary/teste, uterus, mammary gland, prostate..

bone marrow, spleen, brain, eye and pituitary.

2. Results.

The microscopic observations are presented in the Histopathology Incidence

Tables.

a. Tables 1-4 tabulate incidence of lesions (by organ) observed in the four

groups of male and female colony rats. A

5,.5

b. Tables 5-8 tabulate incidence and severity of lesions (by organ) observed

in male and female control rats.

c. Tables 9-12 tabulate incidence of lesions (by organ) observed in each

female rat receiving the high dose level exposure to White Phosphorus/Felt. 7

d. Tables 13-16 tabulate incidence of lesions (by organ) observed in each

male and female rat receiving the intermediate dose level exposure to White

Phosphorus/ Fel t.

3. Discussion.

A number of spontaneous lesions were noted in the liver, kidney, thyroid, and

pituitary; the lesions occurring with equal severity and frequency in control and

Wnite Phosphorus/Felt exposed rats. While none of the control animals displayed

laryngitis or tracheitis, all of the laryngeal and tracheal specimens examined

from the rats receiving the high dosage level of White Phosphorus/Felt displayed

a moderate to severe laryngitis/tracheitis. Fifty percent of the rats receiving

intermediate dose levels of White Phosphorus/Felt displayed a minimal to mild

tracheitis while one out of three rats had a mild laryngitis. Only one rat

receiving the low dose level of White Phosphorus/Felt displayed tracheitis. Four

out of six female rats receiving the nigh dose level of White Phosphorus/Felt

displayed minimal to severe interstitial pneumonia while one control rat of each

sex displayed a minimal interstitial pneumonia.

4. Conclusion.

The agent, White Phosphorus/Felt, at the dosage levels tested and in the

manner tested show a dose related laryngitis and tracheitis. It is suggestive

Appendix D 56

that high dosage levels of White Phosphorus/Felt may produce interstitial

pneumonia in some animals.

MALCO N. ALLISON, CPT, VCComparative Pathology & Surgery Group-Veterinary--Medicine Division.

US Amy Biomedical Laboratory4 September 1979

-A

Appendix D 57

j:-~~ ~ ~~~ - -- - - -

Project Smoke I IWhite Phosphorus Felt

Inhalation Study Six Weeks"Colony" Rats

Key to Microscopic Findings

Tables 1.4

Number of Animals: Represents total number of animals in each group utilizedin the study.

Numbers following tissues represent the number of tissues from each group actuallyexamined. acua

Nu•lbcrs following lesion indicate the number of tissues examined showing the i-particular lesion.

Tables 5-16

tissue present* tissue not available for microscopic evaluation

SeveriL ypfResponse

I = minimal2 = slight3 moderate '14 severeP present

Al~pendi 1) 58

LL. Lt7- e--1--O

V )~

LOn

~ J

Ljj C0

It)~ J--------

---

O

VII

vi I

~~In

09,z

V ) - J L

ca in

U-

-

__44

tnt

M~ L

'-I

eo0

InuCLii '0U5

oI

IIn.ý

=ý

IIto

V6 0 c aI

- V)- CL

0-

Apeni a. D . wC

U- t

CL

0* 4,

00LJi

-. fa

L-4

L)

OL ( U m41J

a. Lu O64'0i O

V) T-LiWU

LjJ LLo)

0U - L "

-a - --------- - -~

ko 2!

e- ln I Lfl to 0 0

* aI

90 - -- -- -- -..- 4D--.

LA.~~L C" .LlU

uw V

I.-.

WUJ W- M 00 r

0.L

L))

j CI-

W C

'AppenI.. C

__ ._ %a- - - -

0 Lan

-JL

U- %. CD -o C~ 0o 0v .t q

LA-

(/,zUo 4D

0 Ln- D~

2; LA O~~f _

0 CD

C) :F

4)

C> LAJLw Uk

U- o u,

Ci 0o 4) V

C, to 0 C

t:. UJJ 4)0 U

ccJ CLi U'. -- 0l. 0 ~ E=D EU 'A ' 0 06I. )

0v CD >- fo.

I- U-

Appendix D 62

LL.: *1

0. I S C%

C-)-)e"

U,

0.0 L

o Li 4

f-) m S I

I-j

cc

6M fa

M 4J

LL-V

I..In

LAJ a) 4j #A 4. IA 4JU- Uj -: 1-C

Ln c e,0 w = ~~II.. CR - = S u 3 Im 4-

cl: M~ u. U5i >. 446, cm 4).< *O .- CA to ' 0 Ch

5.41O C>/I ACL .. JOL

InK0OJ >--In

Appenidix D 63

__d

_ _I I

V) ca it~a

w V) aaI

umlV) ~

0 I I- X

-u- - - - - - - - - - -

a- le a ia i0L~ u I

- & C3 1a 1

__ o _ I-.I

,-J

ut =LR0

0 u1.. 0 = I-

C, ~ i.LA WA 2 u 111~.r LU. LLa..

U- -. u.,3

oa X :. - . - 4nJ ~ ,~aL" -anw V) CD ~

2t~- a- .0f. 1.4au an) an ar. W- o -J4

Appendix D 64

9-

zui

.~LAJ

06:K1 1

I.. __ __ _

L-)

f) -f LAJ.o0 W 0e

o o 41a

0 0) 0

ul 0 LLI i

ac 00 Cuf

Appendc x r 65

4.!.

..- F-..-'

V)

on.

a SI

cm w

z- -.-

-J _______a. Er

o au -- -- *o

-j it Cc 1

(AJ

IIV

00 0L- a:. 0 1IwC

mO . C.LA-

w aA : P -L I -

jo !;-c--P

i m n a - 6U .

Appendx D 6

4k

LLii

C.%- -

CA

I o

o 0to

L A . L A

to

C)UL U 0d 0 c

IA UPC 0-~ 40 Uc

w . ID 2C- c0. CL 41

I.- - -ci

LA - M .- ý -A n U*

C) :b OL) 4J 0

-Lo CL'~~0 ~ -C1

w~ E W. 0'

L' Ln IAm i I

C im )0~

Appendix D.

- a --- - - - - - .- - - - -- -- - - -

LACD0

ceIA I-

- . - - - - - -- - - - - . -

to-

A

IA

-. 00 -0

CD -IV) (A_

LL . - -L

0 ) 3 ULL A4uj 0 j W)L wl ;t-Couo431J j S.+ 2

on Co P z

Appendix D 68

wI- - .- - -. ..: .. 1

co - -

0 ___ ____ I , II-cc

F

L.

.~LL

IA0

IL3J

V) M~ 00 0Lj I. u 4J%

LAA C Q 4. 0 *- 1- 4j

Ly.CL..L Cj .C 4) 4.

c~). ** 0 0 0 ) -ClI I A. 0 N' C-)-

CA U . ., ; L. S.I.. .C 4) 4j r . - CU

u4C>LJV 3 ) r- Mi M. Uh fG E

CL_.%0. 4) U .1 > XV, CD: 0- (. :_w UIS - -&

It- V A = 7 U Q 0 Q I.- 0 .GI . Q I

Appendix D) 69

I. -- - - ~7- -V--i -A

co

cJD CE S S

o l co S

n LJ - _i o-4

4-' SA V)I .J'

Lv w

IAJ -X 4U -A LD Q. -- *--* - - - -

-J CL Ln c

Appndi D 0

Ln

41T

44-

uu1

C%) LA

I.4A

coo 0 ; (I L

L4JLU-j tn 0:U 0 .) 0Lc. L

C-) .4.) U

Ln:cC) Z' <

Apeni D 71

V11

Co

oY Ill0-g

O;X

LA... *

VA 4. g 1E

LU _ . ,, - .- - - - --.

1: L/S

(AWa

00 ua (I I*

A- 0 +1 m.--.-.. -

U u W LA 0 u S.

A-A

In 1-0ta c

0 0 U 0 4Vol il 16, < ! t11j IC a)6 i

=7

___5_ Li ---- I I

I-

0. U. *LA J

U-)

U. -o

a fa- . - -I

z 0

- I-

CD C

CL. Sl 4N Ie

0o 4-- -f--- - 4

C w . = 4j) I

nA -J L4

-VL J w0I

; " 10 L 0 m . ý c : 4

Appendix1)7

77 77 7777- `- -. - - - - -1 ''

0 .o&

0 m

co - -5I

IA g g g.C6 W-_ a-~- m

I- .L.LII .

-~~~4 - -- - - - - - - -

IA:, o

ui 0 1

c0o__ _ _

~o. ,--.CA

IA~ - _ _ - -

CJ 4J

I Iy

ZI5 !I-) I - --

(n 411=' -Z-- - - - - - - - - -

IL I I

----------------------- I 4L4J 0 Uz C. _j 0. 4J X

I-i 0.

Appendix D 74

ul a

a CD

o: L^ -- -

U- I S ~ I

z -A

~L&

aA 0to- m -.. a

4a ad cc

In a 0

0 0 u -

4.)oo to =

to 0 U- 0)cn~~~" 4jt EC

0-. 0 4-'(A I. 0 x 0 +0 S.. n 0

a,' -1 U .I. Z, W

. a. j a. 0o

0- 0...JQ

ct Lu >-- 4) (.>

I- U IC CLUo

Apppendix D 7

- - - - - - - - . . . . . . . . . ..

V) c1V)

_VF

u= Z- - - - - . ' - - - - - -

be C3

ca I sa

co

cc I I * *U.. _ _CD

V) 3I0 Ik I I I U,

w~ CL. -j u-(A.

=D l< 4

LA &. ___ .i2ItoT LhiILai%- S - I1 I I I -

u U ) -j

Mu _j CA aq^ ~ ** C IUI3, *0 ta Wd -0 0 1.4W

C.) )..D U) 4J LJ

Appe~ndix D 76

-.- 7.- Y7--- ...

7;

-ii - ---- \4- L

IRS

- *--- c - ----.

LU)

0 .3 L .J 3 ..

U.U

0

o o 10 10.-

0, 47

AppendixA

-7-

c-0 La

4-41

LL..S

Sn =D S

V) ~~ -*

- -*'-..I~lE

cc LA

00 ____Lai

CL&J

_ _ _ _ _ . .. .. .. ~ a-

-j-w V 5

00

5- .4CDj * - '

I- -u

CD -1 X-j

LL IML *1 - us 3cQ 0 CVCiJ 0 4' 4 . J 4

L0 CD 4- 4.) #A

UJ.4 1^ W k a ItujO~ .. V'U -D L cj 4 _

Appendix D 78

APPENDIX E

PATHOLOGY REPORT - 13-WEEK EXPOSURE

PATHOLOGY REPORTPROJECT SMOKE 11, WHITE "PHOSPHORUS/FELT

INHALATION STUDY - THIRTEEN WEEKS"COLONY"RATS

I. INTRODUCTION.

The study was designed to assess potential local and systemic toxic effectson Edgewood Area Colony rats following inhalation exposure in a chamber to WhitePhosphorus/Felt for a period of fifteen minutes per day, five days a week, forthirteen weeks. Three separate dosage levels were studied with each dosage levelbeginning on a different date and having a separate set of control animals re-ceiving sham treatment and housing under similar conditions. All animals wereapproximately six weeks of age at the beginning of each study. The exposuresand animal holding were performed in Bldg E3266.

3Exposure of the high dose (1000 mg/m ) group began on 31 July and endedon 31 October 1978. The exposed group consisted of eight animals, four of eachsex. A separate group of three male ind three female controls were utilized.Exposure of the medium dose (500 mg/m ) group began on 7 August 1978 and endedon 7 November of that year. Twelve rats, six of each sex, were exposed to theagent. Three male and three femal• control rats were utilized in this study.Exposure of the low dose (200 mg/m ) began on 11 September 1978 and ended on12 December of the same year. A group of twelve animals, six of each sex, wereexposed to the agent. Three male and three female controls were utilized inthe study.

In addition to the above animals, a total of four rats, two of each sex, thathad been exposed with the high dose group and utilized in physiology studiesfor eight days were necropsied. No controls were submitted with this group ofanimals. These animals were included separately in Tables 17-20, but are notconsidered part of the study in interpreting pathology findings.

Following necropsy, tissues were imbedded in paraffin and subsequently pro-cessed for staining with hematoxylin and eosin. The following tissues wereevaluated microscopically: nasal turbinate, larynx, trachea, lungs, heart,esophagus, stomach, small intestine, pancreas, large intestine, liver, adrenal,thyroid, thymus, kidney, bladder, ovary/teste, uterus, mammary gland, prostate,bone marrow, spleen, brain, eye and pituitary,

Histologic findings are tabulated in Tables 1-20. Since one or more tissuesfrom various animals were lost at necropsy or during processing, one must cal-culate the incidence of lesions based upon the number of tissues examined ratherthan on the number of animals necropsied.

79

II. RESULTS.

The microscopic observations are presented in the Histopathology IncidenceTables.

a. Tables 1-4 tabulate incidence of lesions (by organ) observed in thesix groups of male and female colony rats utilized in the three studies.

b. Tables 5-8 tabulate incidence and severity of lesions (by organ)observed in male and female control rats.

c. Tables 9-12 tabulate incidence of lesions (by orga-) observed in-each male and female rat receiving the high dose (1000 mg/mr) level exposureto White Phosphorus/Felt.

d. Tables 13-16 tabulate incidence of lesions (by orgaa) observed ineach male and female rat r'eceiving the medium dose (500 mg/mr) level exposure.

e. Table 17-20 tabulate incidence of lesions (by organ) observed ineach male and female rat receiving the low dose (200 mg/mr) level exposure.

III. DISCUSSION.

A number of spontaneous lesions were noted in the liver, kidney, thyroid,spleen, heart, uterus, bladder, mammary glands and large intestine. The lesionsoccurred either sporadically or with equal frequency and severity in both controland White Phosphorus/Felt exposed rats. While none of the control rats displayedlaryngitis or tracheitis, all of the male rats receiving the high dosage levelof White Phosphorus/Felt exhibited a moderate laryngitis. Of the female ratsreceiving the same dosage level (1000 mg/m 3 ) of White Phosphorus/Felt, one of twolarynOes examined displayed a moderate laryngitis while two out of three trac'leaedisplayed mild to moderate tracheitis. Three out of six female rats receivingthe medium dosage level of White Phosphorus/Felt displayed a moderate tracheitiswhile three out of five male rats receiving the same level exposure displayedslight to moderate tracheitis. None of the low dosage level animals displayedlaryngitis or tracheltis.

IV. CONCLUSION.

Though the small number of tissues examined prevents a definitive con-clusion, it appears that the agent, White Phosphorus/Felt produces a doserelated laryngitis and tracheitis when rats are exposed in the manner tested.

"/iMiCO ALLI ON, CPTVCorr ative Pathology GroupVeterinary Medicine DivisionUS Army Biomedical Laboratory

Appendix E 80

Project Smoke II

White Phosphorus/Felt

Inhalation Study - Thirteen Weeks

"ColonY Rats

Key to Microscopic Findings

Tables 1-4

Number of Animals: Represents total number of animals in each group utilizedin the study. m

Numbers following tissues represent the number of tissues from each groupactually examined.

Numbers following lesions indicate the number of tissues examined showing

the particular lesion.

Tables 5-20

- = tissue present

+ = tissue not available for microscopic evaluation

Numbers Following Organs: First number is number of tissues from malesexamined, second number is number of tissuesfrom females.

Severity of Response

1 Minimal

2 = Slight

3 = Moderate

4 = Severe

P = Present

Appendix E 81

cr.

* AM

*Lin

(A 04

cz~l

f-.)

S,, F 'C) 4..

Ifr

o fooj 00

L) U

a. -~a

0 uj Is- C~~t2

0 C IA

4.-) 4. C uU) wJ.C

cceni u 0

%0) %D LO %D to0

-AJ

CAU.

In - - ILI I

z w

w LA

zww

LAJ LL. ~ c., v~ cn evn m~ en~cc------------------- - - - - - - - - -

U_

L.) A A~

a. 0 A

W - - . - - - ' - .

C) ..a :a 2 -a- .- - - -- -0 e x~ V 4.1 .64r

=:; US AS- .

C- ) tn w LUL

3-, .,J LaiIA. * )0u) ccI La V C

U) IA IA E .3

-L ,--..

o gJ CL Ir)V l) %

xU C3 -j

>a -C.IU 4" m O' Cdi (%J%- m'8I ,-

40 bu n n nWN n0 .

0 L

o au

0

in 0

aja to, A ' z in

0 L 0 t) C). .*CL 4 - -- - -

w J L. L

LL. L.U

C -l

Appendix0E 84

- -- -- .-- --

*L W-~ 0

vi MD %0.... ---- *~

fn~ en

w) L .

- -~U to- o .

-' -L7:1

VI)

LU C .C4 C.J

C..4C'm

C)~~4- I-. 0J1.i

73 7.- . *- - -- - -

C) I --. .-.. .-.-

W. 4

3 0 I

4A u0V

oe w 21 j

cd 0-c

~~ &a

u I1

La 4 a I

o - , . 1! o

U.1.

W- a• 4 a

Va

:7) 03 1 , -

V)

>! LJE.., •,i .. .:S + I a I

LLO .j a

U . c. oC)a

-. 1 Co- I

ot a o

LU JI

S• • ac"-a 41o.a-,r, i.' • ,,

V

EdO •0 " UI m1

4)f 4.4 VI

U. WL 41 4

OkýLa (U u vC~US.z I.- A-'ll~ >- L ~ a..~ 3 C IN .

CL CALJA : Ed n ~ -3 7 = c C), do (A3 .

w ~ J vi. I - V) 4:1 GIx CL L) 4..

Ajppendaix Ai

La fm t I--

i

*i CO

I

o ýi4. !L* i+

00 - x

C MIL-CC,

-j - -

'-3a-enI

I

o o~~--

-- .CC)-

cc C

cs- - - . - --

-n -j.- - . . :E cc- -

u P.

C..a .00..

u .a L A'U -~

I I*- -

Appndix F S"

I I~II! - -. -

* I a In4i

C, I CY I I Ni co I + I - --

(, ,c~ I I - I

x it-__ - - - .: - - ----

C- -cc + + a -

L..J + Pl I I f.

LAJ

u--r

i+I- 0_- -,

L GI c I m + + +

< +e-ON

u--- 0.O'I (O

L), (3 I +

+. +

tnI + +

+ + +

LA -c + +

i+

I.o rn~ I g+ +

< rn + + + +

C 410

0 'A c .- CL 4

L C45. I. I- I

<~ CL

0A 10 CL

Su0.App.r'ddx F cc

LnLj lCDtio a m J 30L e 0

CDC%ko CO 1 3 + + II CY

(C, 6. 4. 4..

'-5 c + + ~LU.+

L). + + +.S£ ~ II 4

0 cc c 4 . .II C

-6 7

-~c

++.

L.J.

c? c

__ cco4

5-) 0? cc) +

cc m.<-+

s- 06-J 0-u

= ;tao0 j

m L

NA 'i +j 0.

>.-

1^ !7c 1: . -. =

o a lo M L ýL r I

Appendix E F

1f4CI + C JJ- ,

aa+ C-

- -.-

o ~ ~ ,.j C.) I-

ul.

Ii'c -9 -o -I --01 -)Ci

0oLc

---u------- -

0 ao.+a -4

co I ++- - --- -- - - :1.

a '.

en. U- - .,1

-0 . Au L :3 to

Q, 0 0 4-' - +j 4 '

-0. X04 0 V 0 41 C

(P.C 10 0 4-' to 4

xI, -c.f #)- C . A IfS

4A 0 AO 4J -ALA0 ,Lf ýo W 41' U0 4.) to~-~- C 4.

-~~~ .£0 k" Mr 4' 0oUJ~ -al U 4;'U, .~

CD-;3 L CL 41 1. 'C 1. C~~a I- CI.m-~

0~~~c 1-

c *-J IM 4-4 ,oS- -J C

Appendix F 90

+1

-j w

-- - - - -- - - - - -- - - - -

0 I

V)

l.-

C:)

5/))

(-j

C)l

41 @AEsl~ 0

00 LL LJLu

30 0 LA- mX 0n InuL

CL0 04, 0& to_j)0 =n -03 .0 A. LJJ #A - VL--

LL La Mn - u. w.0 A o14:I- toj 06 CX ) .)'i r_4- = I- 4j - 4

-A1 E = C Lai ea v f-w '-o041 nJ Q. *r

OLJ~~~ qm.+ 4j 4- ~ ~ -

a.. ILI LI- 41 LL -4 0' j

X cD a ~ -j-C

Appenldix E 91

I +UIA

+ +

z) u

w. -O I

s- s

(4, -) -ý'

o to

0

= .- :3 4 -4

3t 0 Ij I- 4

4-0

d)~~~~ 40Q L A 0 Z=

CL

LA.a

a-4A WC' 11-0 0- :o wC5U 0 IL. +

4.' * C 44 EU

Apeni r.-, 9. . z IA .

a+ +

S+ + -+a+

z~ +

LJJ

(AJ

CC +

cc c(A

_,

C ) 0- - - K r -c -d - - -0C

re) 41 0 I I - III C JE . - - - -

c CD S-

-)L

0- C- X J

u --. CA 4- 0---- .4-

CL A 0

di a=-6., 0 4A 0 Lx C 0 2

4)~t 4II** CL 1 1

VaIli E 93r 341 LJ0 CD c u

-(A- -- - - - -

L6 , . - - - - - , -_

LUJ I - * S

0 LLoc

Lr)

Z LLUohe

LL. ++a ja-

wA + ._ _ + I . - .%..

0i a. +a

Cl Co

4-.Q0 0 1

0

#a. #a 0 0

E I. 4b

CDWE-3. .0 to Q. cm( V)

1=4 r,

.

uL,

'

cn w ixm : 0 0~ 0 P

IL 0 -1 I L tan 4.- .- . .c n a

Appndi F_9

4 1

0 a LI a

LIO

S:

4) A=

-0A

e . In. I +

4-- -- K

m 4J

V) -& VI -n m -- -4 - **j *

Apici.-

zJ ,L% - m

IAA

U,6oL co Icl

3 m +

V)oV) - - -

a-)iL.JN4

L2

UJJ "i +

to to+ zC n L

000

to tOU~ t Nto

0 U9.-0& 4 ..-

In -r 'a 0 z U.-

4) .C4) .

.D La L" 1.5 -a L L cOCie, 3u'. C to - ' - , C9

= U) 4.) 0 . ID 'a ý CVI. I s-C 4J C3

C) Lki X ix ImC M 0.0 C = 9CL (A 0) 41 C '

Appendix E 96

I A

F-o

o~k *Ln~-, ,

-- - a -

LLI.

U0 LA 0

01

w - - --- § -+10w.--3.

n aA 21 LA 0 oIIG d

199

-~~~ - - -. -. -- -- - -----

- - -_ _. - .- ... _

C-.3- - -

o~~a c ~

L -% = - N

I +a Iý m j g-P

(ar 1- - .. j.. ..V- t_._ _ - A3f

ki "C - .

I•LI

G9w --. CL L0 F

+ _ g

All•.lx I-. I ) .

*1 -.

LI --

'I,ý

-00

0

LA. aa 3 u a a

Ln - - A

m ' L.-L CI

>~~0 L------a: 0. . < DL W a _- ut- c, a , LDIA.l I- :! -C 7- A JC-.n LLJ -3 < U I A

Appendi E 9

0,-5

- . - - - - - -

C). cc

L)

ry- LA, - - - -

0* ,

L0 0 0 U

00 4.jn

5di 4)a41; LL4 C LA, .1 -

.0 0 'a4

>- A L"0 I

CD CIS 4= k)

hec

100 C C 4.~

-- -

U.++

IL~ CIOI.

a a

CC

cl

0

__j .1 1

coS0 W r

-I-, k 4

~~2 D

Appenix E

APPENDIX F

PATHOLOGY REPORT - 13-WEEK EXPOSURE AND 4-WEEK RECOVERY PERIOD

PATHOLOGY REPORTPROJECT SMOKE II, WHITE PHOSPHORUS/FELT

INHALATION STUDY PERFORMED FOR THIRTEEN WEEKS INEDGEWOOD COLONY RATSPROTOCOL NO. PEM 78-7

1. INTRODUCTION.

Male and female Edgewoqd area colony rats approximately six weeks old wereexposed to high (1000 mg/m ), medium (500 mg/mr) and low (200 mg/mr) dose levelsof thae agent White Phosphorus/Felt in the form of smoke. The above doses wereadministered 15 minutes a day, 5 days a week for a period of thirteen weeks.Thirty days following final exposure, the rats were killed by intraperitonealinjection of sodium pentobarbital and necropsied. Since each dose group was.exposed on different calender dates, separate control groups were at-wiiiW'itheach exposure group. Controls were placed in the exposure chamber for the samelength of time each day as the exposed animals. Controls were necropsied con-currently with the exposed groups. All animals were housed in Building E3266in standard laboratory animal facilities during non-exposure periods. Followingnecropsy, tissues were fixed in ten percent buffered formalin. The preservedtissues were submitted to the American HistoLab, for imbedding in paraffin, pro-cessing, and staining with hematoxylin and eosin. The following tissues from thehigh dose group and controls were processed for microscopic examination: nasal 'turbinate, larynx/trachea, lungs, heart, esophagus, salivary gland, stomach,simall intestine, pancreas, large intestine, liver, adrenal, thyroid, thymus,kidney, bladder, ovary/testis, uterus, mammary gland, skin, muscle, prostate,bone marrow, bone, spleen, nerve, eye, brain, and pituitary. Turbinates wereremoved at necropsy for processing. The trachea was sampled from the proximalportion and lungs were sectioned randomly. The respiratory tracts only (targetorgan) consisting of nasal turbinates, trachea, larynx, and lungs were examinedin medium and low dose groups.

2. RESULTS.

Significant findings were limited to the respiratory tract. These dataare presented in Tables 1-3. Microscopic diagnoses from all tissues of highdose and control rats are presented in Tables 4-7. Respiratory tract lesionsare presented from al' other animals in Tablei 8-13. Lesions were noted in the 'larynx or trachea of 15 of 16 high (1000 mg/m ) dose level rats, 20 of 24medium dose (500 mg/mi) level rats and in none of the controls. Pulmonarylesions were noted inll of 16 high dose rats, 6 of 24 medium dose rats andnone of the controls for these two groups. Although none of the low doseanimals exhibited significant lesions, one control (79-0176) for this groupdid display the same pulmonary lesion as the high and medium dose exposed animals.Lesions were most extensive and severe in the larynx and trachea. They con-sisted mainly of thickening of the lamina propria and submucosa by collagen,endothelial cell proliferation, and macrophage infiltration. Areas of collagenwere tinctorially different and characterized by an amphophilic to basophilicappearance. Epithelioid macrophages with giant cell formation surrounded someof the altered collagen. Overlying epithelium often lacked cilia and was attimes thickened and metaplastic. Occassionally, Inflammatory cells were seen

103

I1

in thE epithelium. Similar but much less extensive lesions were seen in bronchiand bronchioles. These lesions were characterized by focal areas of alteredcollagen within the lamina propria. These foci were amphophtlic to basophilicin appearance and occassionally surrounded by macrophages and epithellotd giantcells. Small granulomas were noted within respiratory bronchioles. Thesegranulomas often extended into the adjacent lung parenchyma. The granulomaswere characterized by swirling configurations of histiocytes and epithelloidmacrophages with giant cell formation.

3. DISCUSSION.

A number of incidental lesions were observed in various organs of the high(1000 mg/m 3 ) dose group. These lesions either occurred sporadically or withequal frequency in both exposed and control animals. Smoke-related lesionswere limited to the upper airways and to a lesser extent, the smaller airwaysof the lung and the parenchyma adjacent to the terminal bronchioles. Sinceonly the respiratory system was involved in the high dose animals, examinationwas confined to this system in the medium and low dose groups. All lesionsattributable to the smoke were of a chronic inflammatory nature, characterizedby collagen degeneration, and thickening of the lamina propria and submucosaof airways by fibrovascular proliferations.

Nasal lesions consisting of focal squamous metaplasia and a slight inflam-matory cell infiltrate were seen in one high dose animal, accession number78-910F. It is felt that lesions may have been present in other exposed animalsas well; however, the sampling technique precluded our observing this. In lightof this, it is recommended that a more systematic approach to studying the upperrespiratory tract lesions be followed in subsequent studies.

4. CONCLUSION.

Rats exposed to the agent, White Phosphorus/Felt at the 1000 ,g/mg3 and500 mg/m 3 dosage levels developed a dosage related response characterized bychronic inflammation of the airways; lesions were most severe in the larynxand trachea but also involved the lower areas to a slight degree.

~REVIEWED BY:

'I 1(1

MALCOM N. ALLISON, CPT, VC WIL.IAM C. HALL, MAJ, VCComparative Pathology Branch U.S. ArmyVeterinary Medicine & Laboratory USAMRIIDResources Support Division

US Army Biomedical Laboratory30 May 1980

Appendix F 104

:I

LA g: 0L U

L) Ch

I--.

Lo C

LA~

0 00

C0 I 1-.C- ) 0L LL

LA-,UI C) CL C

C) _-; U- 0.W iC3 a

C 0 l I h kCl C3

X: >< uL

- Z-U c

(a

W-4:

(no Ln 0

ui Li 40

w CI w ~ C)0n ca

Apedx 0

C)

0 S 0 0)

C: co-

LLI Ch.. L

mV)OOC.

V)0 CD 0-C. (

* LLJ-

Ol~ -0 (

-):. a

0)LLiJCOf L.I m

Li ...

U- __- I

C). CD (LD

tn -)LL-1

0 -c 0 j

0A C>

C-A(/5 Lf

LiO)

u a4: r C

-14.') 4-C-. r- r-

(A *- 0- im

C) X ) L. . 0o ow~ ~ ~ ~ . *,-DL. )r 1 -$

V)@ .jco oc

Appendix F 0

o o

1 C '140 0 CD

-LJU-

LL.~ 0.X 0

UlI- 0 )m-I (^C t

Q- LL )C

cr 0) >-

-I-- c

>< LU.J

IX LL -I-

0 CD

> 0C> w

1tL) Of

Of L- D I t

-4-

0. 0

~L1-* 0 VI W.

C; ~ Q* 04

L) I

Lnn

Appndi F10

Lo.

CD u

to >b .4

EU4J toEUE

CS CL O.

C -I 103 -

Li) -; C; 41.

., 5- CL L. W 4vC ~ 4 , a ~ E .U ~ nC, . 4 ~ * 4 ;EU C C S U 0 EU ~ E .9-G

VI a fa U 0) ( . UC)* V) 4J vi M o

=- 4v%-4~~~~~~ EUr~~g ~ -..En 0 EU- to EU ."E +. 1.- '1

En~~ a W CO0rC 0 - 03 0,-ic0 IA 0 0 tm aCZ 0 L. 0 05 EL.~LAU 4' to #A EU toE . - U O ~ -WE 4' 4' MC Vr C 4 4-b 4' Q C . 4'C¾En u 4 4 41 L. o -t- #A En -P- L. '9- n.. .-

CD 0 LO ei L * L. 0 C 4 C C SEn D.C 0 0~C C S-

-LJ

LL-

7LLJ-P Lai LA..CD 6 C' C %J CJ CJ C'.j J

a a V~)**OE0S

C) V~L) I IoLUI CIO. CID co- co. -

"5.-a- u,

C-) -3 AJW

0) (D-I

1= Lu< X. L) 0,Cl- V'S Lu -j ... 0

Appendix F 108

4.)eu

CD 1

IL) "0 4-.4.) 4

C ev

C' 4.)4I+- o 4 4.) #A 4) 4+) >~~-

I t-- f- Iu - A> u 0

CD ~ k A 0 A F A . A 4

0L u >-) r_ ) U' 4)c 4 ) Q rCr- *- Im ,-E tm to f- 1-

- 4J U 4.) A j 40 0. w) 4 0 fa EuO

,- 5

r.4 0 E- m 0 Z7A

kA CL cI m E CLAE - 0 -

IAA ~ U .

LA L2 0 2 OU -.- '- 0

4.A- LL ca - 0 u a a .

LM A.- LA

==J LA =3 ) ~J I - (

U- C

C)

cmw )

LU C

I-109

Apenix FL -

Co

uil 4JLlL m

en )0)

o CU...Id C-0 F~9 i

LULL

(F) 0 4 0

b.1 0 0 tA

C.3.

VIU

--

I- U I U

00 CD -C000CA- *9 . 4-

LLJ4~ C.) C) C

CDtAS CL..)

-j U

C3 ( I-- I

0- Cn LW 0

Apeni F11

4.1

IA-

4.1 4a

Z! 4.j 0.

S2 j- c 'a

1; E, u to E0) 'a

fo to t a *- to 0 >

C) 46 4A

Ma 'a EU 'a2a, 02 .- *. to . a

d) S- %C 'a e

.) I" %-- U E (A

S-. -. 0)L - -

L U- 4 .' ' a &.J u1.4 1 4 1'

Ca) Lý % * 01 , a 'LO* ; 'aT- - m7- u .- f

IK *0. - U -E E to .- 'aueD n 2 'a j 2 '

!4l -! -; a- = a AJ , a, - e.C:) Ln. 'a LA 'a e 4j ~ 4' '

LnJ. = 2u a-' 4- . 2Un 4- 2t- E~ . e -

i 4- - ' 4- 4- to (V * e

CA C) -a *- *- **, . .4.1

U , U LA U IA cu 4.1 ja

- .~ en . .. U *- -u 0 U e

0 ,4 0 4. 0 0 4.1 'a ' 4-0. 4- L. . . 0 C~ 4-S- I+- .C *- en . -- a e -

C) U V U . en ..

. 0a o -en en a e 0a eLA -

..- 4) .4 4+ - 4.' 'a to' 4.1 0

LU 4.1~4 .0- 4.1 j . 4.1J P 4.1- -3

.4. 4. .. 4J '- - 41 -0 - r- 4.14.1

'a 40 f a o" a 0 'a a 04.CJ. 0 . a- CL. 0

L)L

C)

L.I

Ln

C)

2-ý

p-.A

CL) rJ CD CD

V. () CD

ICAI co I I

ro C) )LU 1 r- r-

)< ac

LU n0-- C)

C) 0lI-ý-) -- CJ

-X< l LJ 0Z

C) X AI2W

Ln "( CC) LU a-

Appendix F11

4j,Cl 4.0

U) L

'U MU -- L.aC) > LL c . n ' 1 '

.4L.

2 2 a EC a r= 4.j -~

E E E L *.- a. 4A E 'a Ao~~ 4.) = 0 . .

V V EJ - -- 4- 4--

CE E C.U. - 2 4a 2 4n 2- u a0-u0r U)C) - U -4 - CO 4

Ca a aj c 4- 41a 0 a.J4. a 0C) 0 0 .- W 0 4- 04.E 000j

tf - 4- 'a '- 4J . I- 4J CA E-4-

:heCM 4-J 4. 4' C30 V U (M- 0 E2 = 4- a M'V/)) CD~. -4j to a 'a 'aE 4- s

-n Y: : .0* (A .) = Ca.- -u- ) ca, E EU :3 E 0. - 4' L. "a 0 a

'a CA 'a 0 Ma* S_ A 4'.j

000 0 am. )' 0 U) 0 02S.-.-. 9- U)- U - 4-- L. . 0 a

?21 0 00 U 4- 4' 4' 4' 4-) 0.0 70 = -doC)~ 4- LC . a4 ) .~ ca 0

u 000 V to CA 'a 6- 0 4-I-. 0 am 0 a ..- a (m

U) U 4U - OC U) aJ 4A ) ) a. . e 4j 0 .- 'aM 4' 0 * - 4' .- 'a m0

UJ 4J 4J 4' U).A .p 4' 4' .. - 4' 0 -- 4j fa1.- .- . - '0. 4' JC. 4' 4' -. 4' . CCLI W~0 ICM 4' LU) IAf A ) t

C) - ~C C O ) U- to U 0) 0_ a C 4.) c

'ao 0- 0 C mw 0300 a to 0 0 L )0iL a L . S_ c CL. L. 0 L. L. $_ Co c a

I-- -1 _j cc ix .(_3 0. co 0X. C. I- CO CL .. j 0.LC)

C:)

C)ý.eC

C)CDC

-I/

VI

IC3)C~C)

U.D ex ><

L) * 0 - .- . -L

C3 V tr->C" II

ce w ) X CO u) CDCL -1 w~ < . C L .-

Appendix

c-

C)

01 4- 4

4-. U C C L

of U, 4- a4- E

(¶) C- r= 4

tyl ~ ~ C) a 0 6- 0 14J -U 4-

0 4- 4a*- t -

- a - 4- 4 a

(A ~ 4- 4j a .)

0~~ a 9 9

LI CD Ll 4.) E .

w) 0 0 EC2

f-)) 0.4

U- L-AJ

0I I; C),fl

a--VC) 4.) 4.. aCD j) a.- *.- C

CD. -< 0 0

.. .c 4.) 4.D

1.. CD1 0 0 C

C) V .

LrI > DL C

L/ W < -jC

Apedx 1

i 4J

L3 4A

A 4J~4J

0 r-

0C E .

o ) 0 0 -V 4- 4

I. LJ =9 C -

o A~~~4 0U C 4- . C

- 4J 4.r- %A 00) 4 .)

CD~~ ~ 4.. 55L0 An~9

((C) 44? 40 )E *0 C 0

I-~ 00 00 4b ý5 LA n_i 0v 4.)0 5

IA4 M -r-. MA 4 14) ~ In0 (CL 49- A Q 4j +

Q 9 06C C 0 C4LI

A) A- A L4- T I ~ 0 * - A

in ~ ~ ~ ~ ~ ~ ~ t Q3C I. AI *0- AC

C) 0~ 4 9

L" U 3U5 0 C

C))(-II

LA . C

((I 0 .ee

cl a_(l

CD. ý1 CC

.- JAiLLJ 00.M)

(-> .=~

o fl r. UJ /cr "I' x (., L"i C>

Appendix F 114

(U 4)

1~C S- =L5J c j0Jr

5-UJ V) U C VS.

LL 4. EU . E - '

4- E 3~ 4- m. -u 4I 0

E C0.. 5-~ E.- -C 5-m' :l CE 4fa ro - E W 41 't

V) Co uCo o9 E 0

4- E

(Al 4- u 4.1 EU .Ln4b .= c. to 0 .0 = = .g- A E

fOL~ 4 E. 4 - @3 1- - '.- to A- 4- wIa 5

~~~~~~ EU a U 0 I.E U(A 'A 00 UC 'a 0 0

4 44- t

4)4-)W LI EU EL 0~. U W e4J LIý M 40 -O fV 4jtoLI ~ ~ ~ ~ I I-CC EU 0 C *'- .

E C 4-0 04-4 UE 4- 4- Un

co a) U)0 EU in - £0 a EU 00 m 4 ) VI 0(D~ 4J tm a M 4- tM C ) U t~

(A 0a 0 C LI EU M CE @ OLfo IV0 d. . N - 0 ).-

LA- ui u U- 0 - .

9.-. -. >- V). I- .J L Z - L L

M C

CL k

I-I-

-J LjLJ C)a

- u- ) Z , -

>< CX. W Z-' f/l

Cl~f IJ > ý.lLOLCCl f L.J i)I.J0 LI

Apedx 1

44.

- I-

-- I 06w

A9 4-%

=:) be Ar IA V

CA C>. 1 1

C -X: CD G - -- -

4- ~ f L4. A- r.I-~a. = 4- 0* ' 0

4- 0

-(A~( W ~ 0 *U

-, w *ý 0

C) L 0)%-0I. 0 O

41_je- 0

0l-

L'I

LAJ

0)

* .fl

CDLAJU Q-L L L C ).

U- CV)

LLI LiC)a.u =) = Li

CDf ii0LCD m uo "Le0- X(D C

0 o16Apeni FLJ- i

r-'

I-

C)a.

EUJ 4-)

06 1

L UCL

C) E

LAL

0.0

L/) urI V) 0 r

V) 4-.

S.. 4-e E U EU

-~L a41 i A

C 4--Ca

4- C t- Q)U ~ C

41 ifý C1 4- 44J'CC 4U (U to- c 4

oi 0 - E 0 U 40Ln - - U

4- .) C4o

CDP~~I ) 5- 0 i

C))

C> P

C-)i

C3L

w m-. r- ->C) e.,, OL cLLJ~

LI) aA a aC) t.~ I

C-. In C)L' a.. -< -. .. pV)-

CD >< CL) Lii 0 C-

W _L > LI) Ca- (/ ),<.-ia

Appenix F11

4-? 4- 1L

c. 4.j

.22.4 J C

L4- 4-14.

L.. L. 4j 44? 5

X .0 rm 4j

o 0 %_ u- 40A a)~ S_ 0. P

o~t 4J~

LLI 0 2 . 4.? 5.

o~~4 (AA~ Ej- 1 4

cu 0 L^ 0

0 4- 4- +-" ft U

u. C 4-

wn V 4-- C~*

tol 4- to 0 0 A'-

4J 0 V 3 4- 41 43? 4j

I-CC cr et*C

00 - 0)40J0A 4

.4V) f f 4. .- A > l

co4 1 - ~ - 4?.

0.0 - - 4- 4.?4?0 0 - '4

ONU40 - 0 0~

"LAAp 4? .- s. e

_e *.J U? L l A G F U . U

00 7-C . U C CO4 C

Ln. 0 0 .1 LJ

(A0

LIA

0LLI

-JJ

'Co

00

0) C'L LAJ V)? '

or- L ~ LA X C!) LAJ 0

C) ~ULA LtJO a.

Appndi F0C.'

4-4-

1-4-) 1.- 1.

63 4-)E UUU to4-

< to

W 0) EU44-

4-) . 0 E

cLLU C-4

0c 0 4j 0

La~ *F 4- 4- -

w) 4J V.) *. -

(AU.) +- .- f. f- U u *

I-jC +) 4-) U U*

4- U - 4,- 4

0 y

'-4j

LA Il .

CDhJ

U- L"0 to IQ ' 0 A) C) ON

Ln <o co LJ 0

f-I)Lii OV- L 0~

Ap=ni F: 119

cm 44.)

V- 41 E1. : 44)4.

AL I. U E U IU 1 0 1. X .4u- 4j*UEU E -

4.) 0U 4j EUwEUP @

EU) 4A 0.

40- *f rI-

4j MV) 0- *

Ul E U C"r - +) r- a ~

.. i- C 0 0 a 4.) 4- 4) 4J 4-% 4- 4

tj C 4) C)4j in fa 0 0

I- Wc 4 Loco EUu n g.

ad4 U EU E .

V) ~ Cca.

a . Ua a

inC* n f n in i n i

CL inJ co EU S. . to EU E

0m0

C' < 0 OD i Go .OD D co 00 c

2: C

CD a- CA-

_j ./ LO W~ CL0

Appndi OC 1

CC Xw 43 1C

LUU

N4 u

LU a1>1.~

17

4-) ,-t7)Ii U

C) u

C)

'-4 N4 >-I- M C .- C

ca 5

= ~ ~ I -- ' :zL CD

V*)0 eLJ>cC i(

CLA i j0

Appni-

4-)

LU

uj

4n VV 4A

Nd& fa vo "

4A L a

L II 4-1 440 4 I- 2

4-).

UVo

4n~ CL0$4.A

LL 4L) (6) 4)

Lnl

Lii

N-)

U-UCA O0 ^04 0

CLi

-J u

0 CL0

LLIW

CA Lii -tI

Appendix F U

LL)

LjJIf A DIA s IA

VP vo M I

41 E 4.) 4jE, J

tA 4L J

0- th U U U(ALLJ ~ ~ om 4-. . 4 4 4

b-4 C a ta c**~' - .,- *I.- I.. *f

CL

Cl>

0 L)I

C-)

L-)

CuJ0I

C-)

LA- u

21 c JJ L-If n f n O L

=M

--. h cn Ch) m a L

ca, 06 u ~ u ~ u ~ u

-V) L C c0 ce m

C> = =)

L U CL LU 0LAL JJ~.J =-

App endi FL 123

CD1

ocLc0

ccc

0. 10 c

CCC

C~4-k

e e t t P 0430 0

ww4

0-4 m- a~C

V)4

_j Ne CO U DC0.-' 0.

4 A M, en U I Ialco S (A r- 9-

9- LAL 0 1-

C)Lw ýU L

0; L)ý,.w C

-J I

0 '

-4Z

Apedi

4-A

41,

oo

C; "2

LA.4j c

LAJ 4. ';C.0 CU C; u

cU F- fa u.4-.

0c

Co 4- f

P- r- 4j 0 00

( 4-

LA-J

IA C L - i '- I

c4 4-)4 4 - 4

'p. 4- 0.

L/) C 4) U~- 4

OCK f.c 44-'~ Q

C.)l

0ý0

C-)

LJ '4 L)J

V)

C) LW.

L-) ~.LLJC3 tI.- 0 5 a

cl-t w -t r.. a-

Appendix F US5

(A

6 6C)

Ln 4.)

w 0-.

C)C

(A~

CA 0 U_n I-

ui~' CD )0I.- I CA

Z7 C)C) W- Q0LA

w~t C-)-.

(A ..- -_ L .

C 0)

a- ;R 0)M~~ ~ ~ LlI> U -

a.L - Ja

Apedx A

DISTRIBUTION LIST h

Names Copies Names Copies

CHEMICAL SYSTEM. LABORATORYFederal Emeoyoncy Management Agency

ATTN: DRDAR-Ci.r I Office of Mitigation anJ ResearchATTIN: DHR)AR-CLC-n I ATIN: 0avid W. lensenATTN: IDRDAR-CLC-C I Washington. DC 20472ATTN: URDAR-CLC-E IATTN: DHtAR-CLJ,-R 3 US Army Reoearch and StandardiZatIonATIN: DRDAR-CLJ-L 3 Group (Europe)ATTN; DROAR-CLT I ATTN: DRXSN-E-SCATIN: DRDAR-CLT-E I Box 65, FPO Now York 09510ATTN- ORDAR-CLT-PAITN: I)RI)AR-CLN I CommanderATTN- DRDAII-CLW-C 1 14Q 7th Medical CofmendATTN. DRI)AR-Cl.13-C I ATTN: AEWPMATTN. OHi)AR-C.3-1P 1 APO New York 09403ATTN: DRDAR-CLLB-PA IAT I N: DROAR-C1.1-PO 1 CommanderAT IN: DRDAR-CLB-R I USAOTEAATTN: DRDAR-CLR-TE 1 ATTN: CSTE-ZXAiTN: DODAR-CIY-A 1 5600 Columbia PikeAlTN: ORDAR-CLY-R 1 Fa I Is Ch orchh, VA 22041

AU1ThOR$S COII1S: Rosearch Division 0 OFFICE OF 1111. SUHU-CON GENERAL

FPIARTMENT OF DEFENSE CommanderUS Army Medical IfloenginaerIng Research

D,,ton,--i Tochnc-il Information Centerr ano five iopmehl Latoratory

Al IN: I) T I C-t)DA-2 2 ATTN: SGHI)-U)D-AL.CLamoro, Station. Dui ding 5 Fort DetrIck, Bldg 568Alexandria, VA 22314 Frederick, MI) 21701

UI rector US ARMY HEALTH SERVICE COMMANDD)efohso Intelligence AgencyAI)N: 01-40G I Super I ntendentWashIngton, 0)C 20301 Academy of Health Sciences

U1S Army

Special kgont In Charge AI TN: -'SA-CI)HARO. 902d Military Intel I ligonce GP AiiN: HSA-IPM IAITN: IAGPA-A-AN I fort Sam lHoi,,ton, TX 78234

Abordtien Provintl (round, MV 21005

US ARMY MATERIrEL. DEVELOPMENT ANDCommander READINESS COMMANDSFO), HiQ, INSCOMATTN: IRFM-SED: (Mr. Joutert) 1 Commander

Fort Meade, MD 20755 US Army Materiel Develooment andReadiness Command

DL.PARTMi.NT OF THE ARMY ATTN; DRCLOC IATTN: DRCSF-P

HODA (DAMO-NCC) 1 5001I Esenhower AveWASH 0G, 20310 Alexandria, VA 22333

127

US ARMY ARMAMENT MATERIEL READINESS

Commander COMMAND

Us Army Foreign Science & TechnologyCommander

Center U A.M

ATTN: DRXST-MT3 US Army Armadnet MatrCm lad

220 seventh Ste, WECharlottesvllie, VA 22901 ATTN: DRSAR-IRCATTN% ORSAR-ISE

Director ATTN: DRSAR- LEP-L

us Army Materiel Systems Analysis ATTN: DRSAR-SF

Activity -Rock Island, IL 61299

ATTN: DRXSY-MP Comne

ATTN: DRXSY-T (Mr. Metz) 2 Commander

Aberdeen Proving Ground, MD 21005 USA ARTCOI4ATTt4: SARTE

Commander Aberdeen Proving Ground, MD 21010

Coommand 1!

US Army MissI le Command CommanderRedstone Scientific informationComne

cientir US Army Ougway Proving GroundATTN t ORSMI-RPR (Documents) ATTN% Technical Library (Docu Sect)ATT N: e DIM- P D c m n s

Redstone Arsenal, AL 35809 Ougway, UT 84022

US ARMY TRAINING & DOCTRINE COMMAND

01irector

DARCOM Field Safety Activity

ATTN: DRXOS-C Comia•edant

Charlestown, IN 47111 USAMP&CS/TC&FMATTN: ATZN.CM-CDM

Comirander Fort McClellan, AL 36205

US Army Nat ick Research andDevelopment Commander

ATTN: DRDHA-VR I US Army Infantry Center

AT'I : DRDNA-VI 1 ATTN: ATSH-CD-MS-C

Natick, MA 01760 Fort Banning, GA 31905

US ARMY ARMAMENT RESEARC1H AND Commander

DEVELOPMENT COMMAND USA Combined Arms Center and

Fort Leavenworth

Commander A1TN: ATZL-CA-COG

US Army Armament Research and Fort Leavenworth, KS 66027

Dave Iopnent Command

ATTN: DRDAR-LCE j DEPARTMENT OF THE NAVY

AT1N. ORDAAP Lv-C C

ATTN: DRDAR-LC-SA 1 Commander

ATTN: DRDAR-PMA (G.R. Sacco) I Naval Weapons Center

ATTN: DRDAR-SCM 1 ATTN: Technical Library (Code 343)

ATTN: DRDAR-SCA-W I Chine Lake, CA 93555

ATTN: ORDAR-TSS 2

ATTN: DRCPIA-CAWS-AM I Commander Of ficer

Naval Weapons Suport Center

ATTN; Code 5042 (Dr. B.E. Douda)

Crane, IN 47522

128

,.AMl

DEPARTMENT OF THE AIR FORCE

HQ Foreign Technology Division (AFSC)

ATTN: TQTR I

Wright-Patterson AFB, OH 45433

CommanderAeronautical Systems Division

ATTN; ASD/AELD 1

ATTN: ASD/AESD 1

WrIght-Patterson AFB, OH 45433

OUTSIDE AGENCIES

Battelle, Columbus Laboratories

ATTN: TACTEC

505 King Avenue 1-Columbus. OH 43201

Toxicology Information Center, WG 1008

National Research Council 1

2101 Constitution Ave., NW

Washington, DC 20418

US Public Health Service

Center for Disease Control

ATTN: Lewis Webb. Jr.

Building 4. Room 232

Atlanta, GA 30333

129