Document rBj8wmqaZGJ5eZKqBMyqNx8BG

FOR DU PONT USE ONLY AR226-2792 Subchronic Inhalation Toxicity of iln Rats Haskell Laboratory Report No. 273-85 MR No E. I. du Pont de Nemours and Co., Inc. Haskell Laboratory for Toxicology and Industrial Medicine P. 0. Box 50, Elkton Road Newark, Delaware 19714 Date Issued: July 16, 1985 ! ii .! Company Sanitized. Does not contain TSC CBI % HLR 273-85 Subchronic Inhalation Toxicity of SUMMARY 5d r a r , ,y t T i v ei: w s ;k m x " ss-",sra s ' ? . B sirjs^ sra 5 obseriS k111f d for Pathologic examinations. Remaining rats were andepathoiog1c3evaiuattons?XPSlire' " * *hB" SUbJeCted t0 ths sTM WNa mg/L o Thirteen d3y tation was histologically observed in 2 of 5 rats exposed to 30 apor and sacrificed Immediately after the 10th exposure, later, nasal Irritation was found in 1 of 5 rats from the same cl?.TM* WlS? t0 controls, rats In the 30 mg/L group'had'eTevated serum aspartate aminotransferase activity and decreased cholesterol concen trationS ,,cedlately after the 10th exposure. Thirteen days later S e M values were similar to those of the control rats. 2n,Ti s effects seen rats * i 2C o m O s n V S a^ e d . D0es not contain TSCA CB| % HLR 273-85 Work by: Clarence k. Hutt, iTF Technician S /r/*r R f / '-uf f. 1 Robert T. Turner Technician (=>le>` / ^ < Supervised by: Laura A. Ki nnejk Chemi st Llil Report by: David P. Toxicoroamf Study Director: b l & H C M <t.<Uwrrt**4 Nancy C(T Chromey, P<LB. Section Supervisor, Acute Investigations (eU N I T S ' Approved by: r Davia F. Krahn, Ph.D. Manager, Toxicology 7 irti#S Acknowledgements: Thomas A. Kegelman and Bruce A. Burgess also participated in the conduct of this study. DPK:tak:smk:HLR9.5 - 3Company Sanitized. Does not contain T S C A C B I Sponsor: Material Submitted By: Test Facility: Study Initiated-Completed: Chemicals and Pigments Department 5 * 1; d" Pon de Nemours and Company Wilmington, Delaware c Chemicals and Pigments Department Jackson Laboratory E. . du Pont de Nemours and Company u* *,du.P?nt de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine P.0. Box 50, Clkton Road Newark, Delaware 19714 4/25/83 - 5/19/83 There are 74 pages In this report. Distribution: - 4Company Sanitized. Does not contain TSCA C B ! I ii TABLE OF CONTENTS 5 u m m a r y ........... .............. General Information ................... Introduction ............. ......... Materials and Methods ................. ( Results ................. . . . . . . Conclusions............................ Figure I - Growth Curve. . . ............. Appendix I - Daily Atmospheric Concentrati Appendix II ~ Mean Body Weights........... Appendix III - Mean Organ Weights......... 9eeee Appendix IV - Mean Organ-to-Body Weight Ratios . . , Appendix V - Clinical Pathology Report Appendix VI - Pathology Report N o ^ H ^ ......... HLR 273-85 2 4 6 9 10 11 13 15 19 23 27 59 -5- ComP aftySaniaSBij Q Q 2 2 ""WWnrscACBl INTRODUCTION HLR 273 -8 5 T m t m l as very low toxicity on an acute Inhalation basis. Th approximate lethal concentration for this material was 160 mg/Ll The purpose of this study was to determlnt^h^bpxlc effect 1 inhalation of sublethal concentrations o f J H J Except as documented in the study records, this study was conducted according to the applicable Good Laboratory Practice Regulations. MATERIALS AND METHODS A. Animals Young adult male Crl:CD(SD)BR rats were obtained from Charles River Breeding Laboratories, Kingston, New York. Each rat was assigned a unique 6-digit identification number which corresponded to a numbered card affixed to the cage. Rats were quarantined for one week prior to testing, and were weighed and observed twice during the quarantine period. During the test, rats were housed in pairs in 8" x id" x 8 " suspended, stainless steel, wire-mesh cages in rooms maintained on a timer-controlled 12 hour light/dark cycle. The rat assigned the lower number in each cage was identified by a slash in the right ear. Rats' tails and cage cards were color-coded with water-insoluble markers so that individual rats could be identified after exposure. Except during exposure, Purina Certified Rodent Chow #5002 and water were available ad libitum. B. Exposure Protocol Three groups of 10 rats, 7-8 weeks old and weighing between 220 and 242 g r M ^ j j g r e exposed whole-body to vapor concentrations of 3.1, 10, or MHn air. A control group with rats weighing between 219 and 244 grams was^exposed simultaneously to air only. Exposures were 6 hours/day, 5 days/week for two weeks. Rats were assigned to groups so that the group initial mean body weights were similar. Five rats per group were killed after the 10th exposure, and five rats per group were allowed to recover for 13 days post exposure. Rats were weighed and observed daily throughout the exposure and recovery periods, weekends excluded. C. Test Material Physical Form: - .0ompa,w s i a . D W S ,, oi contain T S C A C fil Composition: HLR 273-85 Synonyms : CAS Registry N o . : ^ | Stability: The test material was assumed to be stable throughout the exposure phase of the study. 0* Atmosphere Generation Gas atmospheres oii B 8 * e r e _generated by pu_mping the liquid into a round bottom flask whiilcch was at a--mbient te-m-p-erature f*or t-he i-.I^mg/L1 I?" J-* was i??ated tp about 5-60c t0 generate the 10 and 30 to the ?177 Sliitertlg0l?aSs*s eTxhpeosruerseulcthlanm9be^rPso.r s were carried by houseline air E. Analytical in m IhV tT!pher?c concentration o f f a H ^ a s determined at aporoximatelv 30-minute intervals by drawing samples of the test atmosphere from each 3 9lafs syringe* Samples were analyzed with a ddeettleccttorr and ia f6i? ?X f1//24SnOC.SDr.0mg?lta0s9sracpo?luemqnuippapcekdedwiwtihtha 1f0l*amSeE i3o0nioznation f?rI^0p S Concentrations were determined by comparison with standard curves, which w e r ^ ^ ^ M r e d daily. Gas standards were prepared by evaporating l i q u i < 0 | B i n calibrated glass bottles. * _ Chamber temperatures were measured with mercury thermometers, relative humidities were measured with a Bendix Model 566 Psychrometer and chamber oxygen concentrations were measured with a BioMarine Model cco uxygen Analyzer. E. Clinical Measurements .. samples were collected overnight from 10 rats per group after ?th exp0Surei and from 5 rafcs Per> Group on the 12th day of recovery. Samples were analyzed for volume, osmolality, pH, blood, sugar, protein, - 7Company Sanitized. Does no! contain TS C A C B f HLR 273-85 i i r r Ubln* urobllino?en and ketone. Each specimen was noted for color microscopical"^' * th* sed1ment fPOm each samP1e ** examined m f K Bl00d samP1esJwfre collected from the tails of all rats after the 10th exposure, and from 5 rats per group on the 13th day of recovery "ere ?na1y2fd for erythrocyte count, hemoglobin concert rat i w mean corpuscular volume, platelet count, leukocyte count, and r e l a t l w numbers of neutrophils, band neutrophils, lymphocytes, atypical lymphocytes, eosinophils, monocytes and basophils. Hematocrit mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were ca culated from the erythrocyte data. In addition, serum actiilties " firal2nea P!l0SpbataSe' a^ar,ine ^ n o t r a n s f e r a s e and ferase, and serum concentrations of urea nitrogen, aspartate creatinine amtiontoatlrans protein and cholesterol were also measured. creatinine, total 6 . Pathology r n a i i ^ rctS ? er 9roup were killed after the 10th exposure, and the o S c I nInrt h-rftS Pr.9roup were killed on the 13th day of recoveryfor gross and histopathologic examinations. Rats were killed bv c h l o r a l TM asphj-xiM.on. organs and tissues examined w r e t h e hea" 'u5-s and thoracic lymph nodes. trachea, l i ? ' "S'' pancreas, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon kidneys, urinary bladder, bone marrow (sternal), spleen, thymus thyroid testes, epididymides, adrenal glands, brain and eyes. *^ * H. Organ and Body Weight Analyses >v,,!?ean b2y weights for test fats were compared to controls during the exposure and recovery periods. In addition, at each sacrifice mean hpfr? w? lghts ??d or9an-to-body weight ratios were calculated for the llvfr *Pjeen. kidneys, testes, and thymus. Data were statistically analyzed by a one-way analysis of variance^ Test rate t.IessttssCSwhen rtthheeW iraatiiioo oSf rva1rSiibanyce (F) isnidginciaftiecdanta dsiifgfneirfeicnacnet aanmd oDnunn-tSnetfs level? 9r0UP variation* Sl`9ni^cance was judged at the 0.05 probability 1 Steel, R.G.O. and Torrie, J.H. Principles and Procedures 2nd.edition, McGraw-Hill Book Company, Inc., 1980. of Statistics. -8Company Sanitized. Does not contain TSCACBli * Records Retention reports ... o, HLR 273-85 bJ ocks) and fin*' Kre_ RESULTS A. Exposure Conditions ranged fr'om S*"" ^*veSSSU 22"36C ' humidities mean atmospheric concentrations ions were 21* ` Overall 6e.ow. Daily atoospberic S L S S t i S T S S S ' j S M r S S i , , Atmospheric Concentrations fmq/i) o f ^ H ^ I During Ten Exposures Design Concentration 3 10 30 Analyzed neon Concentration S.D. (mg/L) Ranae 3.1 0.4 2.2-4.7 10 0.8 6.2-12 30 "2.0 21-35 Mean, s.D, and Range represent all samples from all exposures clinical Observations f r o m ^ h L f o f " l5chTM t i S i s rd i r t n S S f i * ^ re i^istfngaishable periods. D u r i S signs for all rats exDosed t,,e recover d re5?very Period, clinical control group. Mean body ici(i%ifPnrfeSOi-1!id -Stin9ufshable from the curve is attached as Figure j9 are Presented in Appendix II. A growth Organ Weight Analyses . -9- not contain T S C A C B f HLR 273-85 in m e findings, the kidnev Sidht ?n?il?2fhip or fuPPortive pathological biolog?cali;esigi??icS i T l 2 * 2 and organ-to-body weight ratios are p r e l e K g . u. C l i n i c a l P a th o lo g y . 1 n c 4 e ri J S S S S J ! 30 "S/L an serum concentration of cholesterol r n m w r i e er #Ctlv* ^ TM * decrease in c lin ic a lly f*iL?S^eences between control and test rats S o ni*t0 ?ntrols* These differ- recovery period. No v1dent at the end of the exposed to 3.1 or iS.SmS/i f ^ ^ erVed report is attached as Appendix V. " sacTM f i c e . The Clinical Pathology E. Pathology the 10thExposure degeneration/regeneretion^Hith killed i * d , e l y nfter `rasterized by mild f a l nasal turbinate;. Thi T 1" `(. ` s a of the group showed similar nasal irritation * A l l ^ E i A S i n TM 9 I*ats in th1s were considered unrelated to the t t * t r i a m S f ?2th21?2 1fal En d i n g s attached as Appendix VI St treatment- The Pathology report is CONCLUSIONS ju group. Increased serum aspartate anrinnt-rancf!!!L1n * ?f ? rats from the same cholesterol c o n c e n t r a t i o ^ ^ i e o b s S v e S in t h r ^ 6 a? ,v^ and C r e a s e d 10th exposure. Thi r t e e n d a v s l a t e r i h i U i 30 m,/L gro uP fo11 owing the control rats. S m r t S S J f f i Z r X l X L ? TM f!m ?]ar t0 thosa of the changes are suggestive of a minimal8hl!!i!KanSi?rase activity and cholesterol of supportive histological findings the bioloairai h?We^ s in th absence clinical changes is unknown. 9 ' blological significance of the There were weeks to 3.1 or no 10 biologiiiccaall.lv mg/L o Iw s.significant apor. effects in rats exposed for two - 10 Company Sanitized. Does not contain TSCA C B I lO ID MM HLR 273-85 GROUP MEAN BODY WEIGHT IN GRAMS oo r0^3)> 3* CO 8 Oa I 11 I Il i ; .5 1 |P - 12 Company Sanitized. Dees not contain TSCOBI . /I HLR 273-85 APPENDIX I DAILY ATMOSPHERIC CONCENTRATIONS 0 Company Sanitized. D ess not contain TSCA CBi - 13 - HLR 273-85 appendix I DAILY ATMOSPHFPTr CONCENTRATION ncj B ' ^ l S n Concentration of ? n ^z, ,, Overall 21 3 4 5 6 7 8 9 10 3.5 3.2 3.1 3.1 3.1 2.8 3.4 2.9 2.8 3.0 3.1 0.6 0.3 0.2 0.2 0.4 0.5 0.2 0.2 0.2 0.4 07? 8` ^ l a r U goncentration nf in my, 2.8- 4.7 2.8- 3.7 2.9- 3.4 2.7- 3.5 2.7-4.0 2.2-3.7 3.1- 3.8 2.5- 3.0 2.6-3.0 2.4-3.6 2.2- 4.7 Overal1 1 2 3 4 5 6 7 8 109 Design Concentratin' Overal1 1 2 3 4 5 6 7 8 9 10 9.9 9.7 10.1 10.1 10.1 10.1 10.3 10.2 10.0 10.0 To.o 0.6 1.2 0.5 0.7 1.1 0.6 0.7 0.7 1.3 0.6 0.8 of 30 ma/l. 29.5 28.4 30.3 29.4 30.4 29.7 30.7 29.7 29.6 29.5 29.7 2.0 3.1 0.7 2.3 2.7 2.3 1.4 1.4 0.8 1.3 2.0 8.7- 10.6 8.4-12.2 9.2-10.9 8. 8- 11.1 7.6- 11.3 9.1- 11.0 9.2- 11.5 8.7- 10.7 6.2-10.9 9.4-11.3 6. 2- 12.2 26.9-34.6 21.2- 31.5 29.5- 30.9 26.8- 34.9 25.9- 34.9 25.3- 32.7 28.6- 32.9 26.3- 31.5 27.9- 32.0 26.9- 32.0 2T.2-34.9 - 14 - ^wnpany Sanitized. Does not contain TSCA CBI HLR 273-85 APPENDIX II MEAN BODY WEIGHTS - 15 Company Sanitized. Coes nof confain TSCA CBf H-14808 Surnma^ Table HLR 273-85 GROUP TEST DAYS 1. 2. Control Low Intermediate High ANOVA(l) TREND(2) LSD(3) DUNNETT(41 BARTLETT(5) 231.6 228.9 231.1 229.7 0.721 0.677 5.3416 6.4994 0.144 239.7 238.8 240.1 237.3 0.846 0.584 6.8519 8.3370 0.071 3. 248.3 248.4 248.3 247.9 0.996 0.815 7.6331 9.2876 0.244 4. 258.0 258.5 257.3 255.6 0.902 0.521 8.3219 10.1257 0.031 5. 266.6 265.9 262.8 262.3 0.729 0.283 9.4212 11.4633 0.032 GROUP TEST DAYS 8. 9. Control Low Intermediate High AN0VA(1) TREND(2) LSD(3) DUNNETT(4) BARTLETT(5) 289.9 290.3 287.5 286.2 0.850 0.419 10.9058 13.2696 0.063 295.3 295.2 291.8 289.6 0.739 0.291 12.2789 14.9404 0.009 10. 299.3 297.7 294.8 291.0 0.548 0.157 12.3571 15.0355 0.025 11. 308.4 309.2 305.3 300.6 0.589 0.216 13.9009 16.9139 0.076 12. 310.5 309.5 304.9 303.4 0.640 0.215 13.1701 16.0247 0.080 (1) P VALUE of F-TEST from ONE-FACTOR ANALYSIS OF VARIANCE. (* indicates P value less than 0.05) (2) P VALUE OF TEST FOR LINEAR TREND OVER GROUPS. (* indicates P value less than 0.05) (3) LEAST SIGNIFICAN12345DIFFERENCE - given a significant (alpha=0.05) F RATIO, any two meens differing by more than the LSD are significantly different with a false positive (alpha) error rate of 0.05. (4) DUNNETT'S TEST - any treatment mean differing from the control mean by .iore than the DUNNETT statistic is significantly different from the control mean with a variable-wise false positive (alpha) error rate of 0.05. (5) BARTLETT'S TEST FOR EQUAL VARIANCE P VALUE. + SIGNIFICANTLY DIFFERENT (P<0.05) from CONFROL GROUP by LSD. # SIGNIFICANTLY DIFFERENT (P<0.05) from CONTROL GROUP by DUNNETT TEST AND LSD. - 16 nofconfab TSCA CBl GROUP CONTROL LOW INTERMEDIATE HIGH ANOVA(1) TREND(2) LSDf3) DUNNETT(4) BARTLETT(5) GROUP fr-14608 ^ Suronar/ Table TEST DAYS 15. 16. 17. 333.8 335.2 327.6 324.2 0.786 0.363 26.0834 32.3597 0.157 339.0 ~ 338.4 330.6 330.0 0.824 0.392 26.5250 32.9076 0.247 344.8 345.6 338.4 337.2 0.866 0.455 26.2859 32.6109 0.177 TEST DAYS 22. 23. 24. HLR 273-85 18. 349.2 352.6 348.8 341.2 0.842 0.507 27.4476 34.0522 0.107 19. 354.8 360.6 348.6 345.6 0.687 0.362 28.2838 35.0896 0.136 25. CONiROL LOW INTERMEDIATE HIGH 370.0 3:9.4 3o/.0 364.0 377.4 382.8 373.8 366.2 381.6 389.8 380.4 373.8 386.8 388.4 379.2 378.8 AN0VA(1) TREND(2) LSD(3) DUNNETT(4) BARTLETT(5) 0.740 0.517 30.7882 38.1966 0.165 0.715 0.368 30.8363 38.2563 0.129 0*772 0.504 32.1534 39.8903 0.111 0.908 0.539 35.4150 43.9367 0.097 (1) ( 2) VA(f*EiinnHdfi-cFa'tIeEsSTPnfrvoa,lnue0NlEe-sTMsctthoarnAnNALnsYlSIS OF VARIANCE (3) P ^ ( * ^ 1ndicates FpRya1 ueA?ess^than^0^05) any^twoImeansCd?ffeMngRbyEmore^than*the1LSDflCant'^a! ^ a=C*05) F RATIO, (4) ^ E ? T ^ ;I ?IsS!it1Ve i f o!o5. S' 9" ' ,Ca" t,y than the DUNNETT statistic^rsTgnificIntirdiffp"1 tJe.contro1 fl'ean by more (5) with a variable-wise false positive lalnhaT a erent from the control mean + ? I ^ TEST TM e o w l error rate f -05- # sis!{f S ; SIfT eK Zm "TM.L^ by LSD. KtNT (P<0-05) fr"> CONTROL GROUP by DUNNETT TEST and LSD 17 Company Sanitized. Does not contain TSCA CBS is P t il Company Sanitized. Does not contain TSCA CBS 18 - HLR 273-85 APPENDIX III MEAN ORGAN WEIGHTS " " '''" H ' S . M b w L 0o8s"<WcoMahTSCAce! 19 - Meaatnn iAnbsoltotieH-W1e4i8g0h8t Table 0 Days Rec. HLR 273-85 GROUP CONC. BODY WT. ? ">g/L 3.1 mg/L m9/L 30 m9/L 307.8( 310.8( 307.2( 302.8( 0.000) 0.731) 0.945) 0.568) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.828 0 503 0.640 HEART 1.030( 1.108( 1.014( 1.050( 0.000) 0.049) 0.667) 0.592) 0.094 0.772 0.526 1.460( 1.508( 1.510( 1.448( 0.000) 0.601) 0.586) 0.896) 0.857 0.906 0.248 GROUP CONC. LIVER 0 mg/L 3.1 mg/L 10 mg/L 30 mg/L 11.148( 11.876( 11194( 12.174( 0.000) 0.271) 0.943) 0.128) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.320 0.253 0.485 SPLEEN 0.602( 0.702( 0.650( 0.632( 0.000) 0.146) 0.473) 0.652) 0.495 0.856 0.530 KIDNEY 2.5 50( 2-724( 2.658( 2.836( 0.000) 0.294) 0.510) 0.094) 0.372 0.138 0.771 GROUP CONC. 0 mg/L 3.1 mg/L 10 mg/L 30 mg/L TESTIS 2.952( 2.752( 2844( 2.868( 0.000) 0.374) 0.628) 0.706) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.837 0.820 0.855 THYMUS 0.626( 0.656( 0.714( 0.618( 0.000) 0.593) 0.130) 0.886) 0.325 0.848 0.915 Values in parentheses - P VALUE OF STUDENT T TEST COMPARISON ~ BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE - 20 - Company Sanitized. Does not contain TSCA CBf Mean LHHtosoIufe 1 W 4 i 808 ght Tab] 13 Days Recovery HLR 273-85 GROUP B O M WT. HEART LUNGS CONTROL LOW INTERMEDIATE HIGH 386.8( 388.4( 379.2( 378.8( O.OOO) 0.925) 0.655) 0.639) TEST - HOMOGENEITY test - Trend BARTLETT'S TEST 0.908 0.539 0.097 GROUP LIVER CONTROL LOW INTERMEDIATE HIGH 16.110( 15.440( 15.160( 15.358( 0.000) 0.564) 0.416) 0.518) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.851 0.491 0.321 GROUP TESTIS 1 .186( 1 .2 6 0 ( 1 .2 3 6 ( 1 .2 8 6 ( 0 .0 0 0 ) 0 .3 4 8 ) 0 .5 2 3 ) 0 .2 1 0 ) 0 .6 1 4 0 .2 7 1 0 .0 7 0 SPLEEN 0.700( 0.734( 0.724( 0.690( 0.000) 0.499) 0.632) 0.842) 0.793 0.800 0.058 THYMUS 1 .7 4 0 ( 1 .8 0 4 ( 1 .6 4 2 ( 1 .6 6 6 ( 0 .0 0 0 ) 0 .5 1 8 ) 0 .3 2 7 ) 0 .4 5 6 ) 0 .3 5 7 0 .2 2 8 0.740 KIDNEY 2.932( 3.096( 3.198( 3.050( 0.000) 0 .4 1 5 ) 0 .1 9 3 ) 0 .5 5 5 ) 0.603 0.472 0.183 CONTROL LOW INTERMEDIATE HIGH 2.954( 3.058( 3.268( 2.994( 0.000) 0.501) 0.054) 0.795) 0.696( 0.802( 0.602( 0.696( 0.000) 0.123) 0.168) 1.000) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.205 0.500 0.256 0.054 0.346 0.217 Values in parentheses - P VALUE OF STUDENT T TEST COMPARISON 9F TREATMENT MEAN TO CONTROL MEAN, t " 0IFFEKtNT (P<0.05) FROM CONTROL GROUP BY LSD # ~ SIGDUNNETT^SV DIFFETEST iP<*5) FR0M C0NTR0L GR0UP BY LSD AND ?TRESNDE-NEPiTLV,A'L,,UcE IOFiLFUETE0SFTFOFTEWSHTET0HFERWITTHHEERRE GISRODUOPSEM-ERAENLSATAERDE EQUAL. CHANGE IN GROUP MEANS. U BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE " - 21 - Com pany S a " sf'*ed. D oes not contain T S C A C B f I HLR 273-85 C o m p aq S an itto *. D oss nolcon(ain t s c a HLR 273-85 APPENDIX IV MEAN ORGAN-TO-BODY WEIGHT RATIOS CompanySanitized. Does no,contain TSCACBI 23 r f l H H l H - 14808 MearrRelative Weight Table 0 Days Recovery HLR 273-85 GROUP CONC. HEART 0 mg/L 3.1 mg/L 10 mg/L 30 mg/L 0.335( 0.357( 0.331( 0.347( 0.000) 0.085) 0.746) 0.327) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST GROUP CONC. 0.164 0.786 0.640 SPLEEN -Ovmg/L pal mg/L 16 mg/L 30 mg/L 0.1961 0.2251 0.2111 0.2081 0.000) 0.141) 0.441) 0.530) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.507 0.717 0.436 LUNGS 0.4741 0.4851 0.4911 0.4781 0.000) 0.674) 0.508) 0.871) 0.910 0.817 0.858 KIDNEY 0.8281 0.8761 0.8641 0.9361 0.000) 0.259) 0.388) 0.018) 0.105 0.028 0.460 LIVER 3.6121 3.8201 3.6431 4.0211 0.000) 0.198) 0.844) 0.018) 0.064 0.048 0.065 TESTIS 0.9611 0.8821 0.9291 0.9471 0.00) 0.265) 0.646) 0.842) 0.682 0.980 0.152 GROUP CONC. 0 mg/L 3.1 mg/L 10 mg/L 30 mg/L THYMUS 0.203( 0.211( 0.2321 0.204( 0.000) 0.598) 0.078) 0.928) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.251 0.616 0.967 __ _ _ _________ Values in parentheses - ? VALUE OF STUDENT T TEST COMPARISON OF TREATMENT MEAN TO CONTROL MEAN. + - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD # - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD AND DUNNETT'S TEST HOMOGENEITY - P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL. TREND - P VALUE OF F TEST OF WHETHER THERE IS DOSE-RELATED CHANGE IN GROUP MEANS. ' BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE - 24 - Company SanWzefl. Does not contain TSCACB1 [ A h -14808 Mean Relative Weight Table 13 Days Recovery HLR 273-85 GROUP HEART LUNGS LIVER CONTROL LOW INTERMEDIATE HIGH 0.307( 0.325( 0.327( 0.340( O.OOO) 0.356) 0.310) 0.099) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.404 0.110 0.097 GROUP SPLEEN 0.452( 0.465( 0.433( 0.440( 0.000) 0.563) 0.408) 0.596) 0.511 0.347 0.055 KIDNEY 4.145( 3.972( 3.999( 4.049( 0.000) 0.350) 0.429) 0.603) 0.783 0.655 0.038 TESTIS CONTROL LOW INTERMEDIATE HIGH 0.181( 0.190( 0.191( 0.182( 0.000) 0.503) 0.417) 0.955) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.780 0.920 0.417 GROUP THYMUS 0.756( 0.795( 0.843( 0.805( 0.000) 0.127) 0.003)# 0.063) 0.022 0.023 0.418 0.768( 0.790( 0.863( 0.792( 0.000) 0.645) 0.057) 0.609) 0.232 0.334 0.140 CONTROL LOW INTERMEDIATE HIGH 0.180( 0.206( 0.159( 0.184( 0.000) 0.094) 0.186) 0.789) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.045 0.470 0.381 =i==sss:s5---- ------- ------- ------- IIIIIII11I1IIIIf1IIIIIII11I1II1IIl1 Values in parentheses - P VALUE OF STUDENT T TEST COMPARISON OF TREATMENT MEAN TO CONTROL MEAN + - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD # - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD AND DUNNETT'S TEST HOMOGENEITY - P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL. TREND - P VALUE OF F TEST OF WHETHER THERE IS DOSE-RELATED CHANGE IN GROUP MEANS. BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE IIiIIIiIHIIIIIIIIliiIIIiIIIIlIIiIII - 25 - Company Sartfeed. Does not contain TSC CBf HLR 273-85 Company Sanitized. Does not contain TSCA CBf - 26 - HLR 273-85 APPENDIX V CLINICAL PATHOLOGY REPORT The Clinical Pathology Report is signed by C. C. Matarese and R. M. Everett. Ms. Matarese prepared the report, Dr. Everett interpreted the data. The design concentrations cited in the report are accurate to 2 significant figures. Company Sanitized. Does not contain TSC A C B f es*W2 E. 1. ou Pont NESTAtU&MCOWOZ de emours & Company INCORPORATED Ha s k e u . L aboratory for Toxico lo gy a n d In d u s t r ia l Me d ic in e E lk t o n R o a d , Ne w a r k , De l a w a r e 19711 central research and development department JL1KICAL PATHOLOGY REPORT NO. Subacute Inhalation Toxicity o Medical Research Project No1 Haskell Labora*ory No. 14808 August 23, 1983 Summary Male CD'S) rats were exposed by innalation of 0.0 (control), 3.1, 10.0 and 30.0 mg/L. concentrations Rats exposed to the 30.0 mg/L concentration had increased serum AST/GOT activity and decreased serum concentrations of cholesterol. These changes were interpreted to be evidence of a minimal treatment-related hepatic effect. This hepatic effect was absent after a 13-day recovery period. The 10.0 mg/L exposure concentration was considered to be a no-effect dose tor the hematologic and clinical chemical parameters measured under the conditions of this studv. Procedure Four groups of ten male Pt^-L^tj-jjere_ej{posed, by inhalation; for six hours per day for ten days to 3 1ot 0.0 (control), . , 10.0 and 30.0 mg/L. at concentrations After the ninth exposure, an overnight (16 hour) urine specimen was collected from each rat to measure volume (VOL), osmolality (OSMOL) and pH; and to determine the presence of blood, sugar (glucose), protein, bilirubin, uroDilinogen (UROBL) and ketone. The appearance (color and transparency) ot each specimen was recorded and the sediment from each was microscopically examined. J j Company SanfizeS. Does noi contain TSCA CB I After the tenth exposure (End-of-Exposure, 0-Day Recovery), blood was taken from the tall of each rat for measurement of erythrocytes, (RBC), hemoglobin (Hb), mean corpuscular volume (MCV), platelets (PLAT), leukocytes (WBC) and relative numbers of neutrophils (Neut), band neutrophils (Band), lymphocytes (Lymph), atypical lymphocytes (Alym), eosinophils (Eosin), monocyt. s (Mono) and basophils (Baso). Absolute numbers of various types of leukocytes were calculated from the leukocytic data. Hematocrit (Ht), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were calculated from the erythrocytic data. Serum activities or con centrations of alkaline phosphatase (AP), alanine aminotransferase (ALT/GPT), aspartate aminotransferase (AST/GOT), urea nitrogen (BUN), creatinine (CREAT), total protein (TPROT) and cholesterol (CHLOS) were also measured. Five rats from each group were then sacrificed for pathologic evaluation. Following a 13-day recovery period (Recovery), the hematologic and clinical chemical (serum and urine) measurements were repeated on the five surviving rats in each group. Statistics The hematologic and clinical chemical data were statistically analyzed by a one-way analysis of variance at each time point. When the F-test was significant, least significant difference (LSD) am^^wroett tests were made between the control rats and the rats exposed t o U ^ ^ H Significance was judged at the 5% probability level using the Dunnet^criteria. Results The results for the hematologic and clinical chemical measurements are summarized in Table I - parts 1 to 3, Table II and Table III parts 1 and 2; statistical analyses in Tables IV and V. Data on individual animals are listed in the computer print-outs attached to this report. Statistical analysis of the dat^^nd^^teJ that male CD rats exposed for six hours per day for ten days t c f l U B ^ t the highest concentration (30.0 rag/L) had increased AST/GOT activities and decreased serum cholesterol concentrations. The low-dose group (3.1 mg/L) excreted more urobilinogen in the urine. nWg w ith aFollowing a recovery period' of 13 days, the low-dosed rats (3.1 mg/L) excreted uri jwith a higher solute concentration. Urine urobilinogen levels in al exposed groups were higher than the controls. C o mpanjrsa, 1 ^""oma/nTsCAce, - 3- Discussion and Conclusions The statistically significant increase in the serum activity of AST/GOT and decrease in the serum concentration ofcholesterol observed for rats exposed to the high dose (30.0 mg/L) o i U H H l r e r e interpreted as evidence of a treatment-related hepatic effec^^^Evidence for the hepatic effect was reversible during the 13-day recovery period. The other clinical chemical parameters shown to be statistically significantly changed (urine osmolality and urobilinogen) in Table V, were within the range of expected biological variation and were therefore not interpreted to be biologically significant or related to compound administration. The 10.0 mg/L exposure concentration o f ^ m ^ / a s interpreted to be a no-effect dose for the hematologic and clinical clfemical parameters under the conditions of this study. Report by: bdtlojuu* , (2. Catherine C. Matarese Technician Approved by: x4=^ Rhymond'tf. TEverett, D.V.M., Ph.D. Coordinator, Clinical Pathology CCM/RME/wfd Company Sanitized. Does not contain TSC CBI J Company Sanitized. Does not contain TSCACBf L'AliLE I . SUMMARY OF HEMATOLOGIC FINDINGS IN MALE RATS EXPOSED Tff T EN DAYS - GROUP MEANS AND STANDARD DEVIATIONS (SD) TESTS RBC MM/nun Hb g/dL Ht 1 MCV fL MCH PB MCHC g/dL PLAT M/nun DOSE CONTROL 3.1 KG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L 10 DAY TIME ON TEST RECOVERY 7.09( 0.44) 7.27( 0.45) 6.99( 0.17) 6.94( 0.26) 7.08( 0.46) 7.15( 0.37) 7.00( 0.25) 6.90( 0.37) 15.8( 16.0( 15.6( 15.5( 0.6) 0.8) 0.5) 0.5) 16.0( 16.0( 15.8( 15.8( 0.8) 0.7) 0.7) 0.6) H3 -c *3.( 42.( m.( 2.) 3.) 1.) 2.) 42.( 41.( 40. ( 40.( 2.) 2.) 2.) 2.) 60. ( 58. ( 59. ( 59. ( 2.) 1.) 1.) 1.) 59. ( 58.( 57. ( 57. ( 3.) 1 .) 2.) 1.) 22. ( 22.( 22.( 22. ( 1.) 1.) 1.) 0.) 23.( 22.( 23.( 23-( 1 .) 1.) 1.) 1.) 37. ( 37. ( 38.( 38. ( 1.) 1.) 1.) 1.) 1046.( 126.) 1028.( 172.) 1059.( 105.) 933. ( 129.) 38. ( 39. ( 39. ( 40. ( 1.) 1.) 1.) 1.) 978. ( 129.) 900. ( 45.) 980. ( 50.) 972. ( 131.) Part 1 of 3 Company Sanitised. Does not contain TSCACBt ,, 1ABI.1:. 1 (Cont inut-d) SUMMI, ARY OF HEMATOLOGIC FINDINGS IN MALE RATS EXPOSED ' P i OR TEN DAYS - GROUP MEANS AND STANDARD DEVIATIONS (SD) TESTS WBC M/mm None WBCx% Band WBCxJ Lymph WBCx.% Alym WBCx* DOSE 10 DAY TIME ON RECOVERY CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L 1 3 .6 ( 12.0( 12.5( 12.3( 2.H) 2.3) 1.5) 2.5) 13.H 11.4( 10.2( 14.0( 1.5) 1.8) 2.3) 2.4) CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L 1306.( 636.1 1023.( 28.) 1301.( 548.) 1332.( 287.) 1766.( 602.) 1060.( 455.) 1491.( 470.) 2200.( 585.) CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L 0.( 0.) 0.( 0.) 0.( 0.) 0.( 0.) 24.( 0.( 0.( 0.( 55.) 0.) 0.) 0.) CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L 11237.(2068.) 10547.(1731.) 10012.(2295.) 9780.(2072.) 10073.(1555.) 7694.(2018.) 9916.(2083.) 10554.(2062.) CONTROL 3.1 MG/L 10.0 MG/L 30.0 G/L 207. ( 129.) 189-( 142.) 212.( 102.) 218.( 135.) 256.( 118.) 161.( 108.) 312.( 218.) 395.( 200.) # Parr 2 of 3 SmSted. Does noi containTSCA CBt H - 14808 t a b l e (Coni inucci) C _ i Ul!MFMOARKYTENOK HEMAT01.0C IC DAYS - CROUP KIND INOS IN MALE RATS EXPOSED MEANS AND STANDARD DEVIATIONS (SD) TESTS Eosin WBCxJ Mono WBCxJ Baso WBCxf DOSE CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 3.0 MG/L 10 DAY TIME ON TEST RECOVERY 14.( 75.( 49 -( 52. ( 44. ) 86.) 65.) 69.) 51.( 23.( 48.( 25.( 70.) 52.) 66.) 55.) 646. ( 391.) 700. ( 210.) 895. ( 324.) 72. ( 402.) 496. ( 462.) 357. ( 177.) 655. ( 193.) 787. ( 433.) o.( 0.) o.( 0.) 0.( 0.) 0.( 0.) 0.( o.( o.( 0. ( 0.) 0.) 0.) 0.) I B3<a> Part 3 of 3 Sized. Doss noiconfala TSCACBf TESTS AP IU ALT IU AST IU BUN mg} 4s CREAT S? mg} TPROg}T CHLOS mg} .urtri/vix i b'OK TEN DAYS t a b u : 11 rmuiNUb --- 1. ^ UOC.U 1U JU^J^TAJNDAltoJDEVIATIONS (SD) DOSE CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L 10 DAY TIME ON TEST FTCOVERY 20M -( 180.( 198. ( 192.( 35.) 23.) 5L. > 36.) 229. ( 181. ( 172.( 226. ( 91.) 96.) 39.) 96.) 30. ( 27. ( 29. ( 31.( 3.) 9.) 9.) 3.) 35.( 37. ( 30.( 39.( 9.) 9.) 3.) 9.) 63.( 69. ( 73.( 76. ( 7.) 7.) 12.) 10.) 66. ( 67.( 66.( 68. ( 11.) 7.) 10.) 10.) 16.9( 19.2( 16.7( 19.9( 2.5) 3.0) 3.2) 2.9) 20.1 ( 22.0( 18.9( 18.7( 1.3) 3.6) 0.5) 0.5) 0.6 ( 0.7( 0.7 ( 0.7 ( 0.1) 0.1) 0.1 ) 0.1) 0.6( 0.7 ( 0.6( 0.6( 0.0) 0.1) 0.0) 0.0) 5.9( 5.9( 5.3 ( 5.9( 0.2) 0.3) 0.2) 0.2) 5.9( 5.6( 5.8 ( 5 -9( 0.3) 0.2) 0.2) 0.1) 65. ( 65. ( 57. ( 97. ( 7.) 19.) 10.) 9.) 70. ( 58. ( 59. ( 59. ( 15.) 12.) 9.) 6.) II H-14808 SUMMARY OF CLiNICAL URINE ANALYSIS IN MALE RATS EXPOSED iFOR TEN DAYS - GROUP MEANS AND STANDARD DEVIATIONS (SD) TESTS DOSE 10 DAY TIME ON TEST RECOVERY CONTROL 8.( 2.) 13.( 5.) VOL 3.1 MG/L 7.( 2.) 9.( 3.) L 10.0 MO/L 7.( 2.) 9.< 2.) 30.0 MQ/L 9 ( 4.) 11.( 1.) OSMOL mOs CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L 1677.( 392.) 1909.C 248.) 1732. ( 503.) 1443.( 354.) 1535.( 285.) 2100.( 344.) 1653.C 220.) 1675.( 319.) CONTROL 7.4( 0.5) 7.0( 0.0) PH 3.1 MG/L 7.2 ( 0.4) 7.0( 0.0) 10.0 MG/L 7.4( 0.5) 7.2( 0.4) C '. 30.0 MG/L 7.3( 0.5) 7.6( 0.5) UROBL ng/dL CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L 0.5( 1.0< 0.8( 0.8( 0.5) 0.0) 0.4) 0.4) 0.6( 1.0( 1.0( 1.0( 0.5) 0.0) 0.0) 0.0) Pa.-t 1 of 2 Compar},; Sanaze. Does not contata TSCACB| Ai mi TABLE III (Continued) SUMMARY OF CLINICAL URINE ANALYSIS IN MALE RATS EXPOSED T 'OR TEN DAYS Part 2 of 2 Sampling Time: Dose mn/L: End-of -Exposure, 0-Day Recovery 13-Day Recovery 0.0 3.1 mn 30.0 0.0 3.1 10.0 30.0 Measurement Blood 5/10* 1/10 0/10 0/10 1/4 0/5 1/5 2/5 c-C"' 01 v8s Wa)- Sugar (glucose) ProLe in Bilirubin Ketone Appearance (color and transparency) Microscopic 0/10 0/10 0/10 0/10 0/10 6/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 1/10 0/10 0/10 0/10 0/10 0/10 0/4 0/4 0/4 0/4 0/4 1/4 0/5 0/5 0/5 0/5 0/5 1/5 * Number of abnormal or positive findings/Number of individual urine specimens examined 1/5 0/5 0/5 1/5 0/5 2/5 0/5 0/5 0/5 0/5 0/5 2/5 0 1 8 contain TSCA O i.Does no! contain TSCACBf )H-14808 TABLE IV SUMMARY OF STATISTICAL ANALYSES OF HEMATOLOGIC AND CLINICAL CHEMICAL FINDINGS . ______ FOR MALE RATS EXPOf17" 'r^ M B 1 l l | l Mil I.I __________________ Sampling Time: Statistic : End-of-fexposure, 0-Day Recovery p* Dunnecttt 13-Day Recovery P Dunnett Measurement Hematolofty RBC Hb Ht MCV MCH MCHC Platelets WBC Neut L'-' Band Lymph Atlym Eosin Mono 0.163 0.394 0.243 0.157 0.685 0.620 0.164 0. 387 0.404 1.000 0.428 0.962 0.271 0.590 0.752 0.945 0.425 0.482 0.850 0.292 0.526 0.038 0.026 0.418 0.113 0.206 0.834 0.254 O Clinical Chemistry (Serum) 3 AP 13 <3S<t ALT/GPT AST/GOT wCO BUN oIN3=Dr... CREAT TPROT CHLOS 0.515 0.120 0.009 0.009 0.133 0.781 0.001 10.533 11.583 0.125 0.044 0.991 0.040 0.027 0.206 0.302 Clinical Chemistry (Urine)VOL OSMOL PH UROBL 0.246 0.075 0.762 0.014 0.392 0.244 0.049 0.070 0.029 508.628 0.399 f t* Value of p for F-test for among group differences Dunnett (shown when significantly different from controls at 5% level) i H 1 1 CompanySanded. Doesno!containTSCACB| m TABLE V SUMMARY OF STATISTICALLY SIGNIFICANT CLINII!CAL CHEMICAL FINDINGS FOR MALE RATS EXPOSED Ti OR TEN DAYS Sampling Time: Measurement Clinical Chemistry (Serum) AST/GOT CHLOS L*: OC Clinical Chemistry (Urine) OSMOL UROBL End-of-Exposure, 0-Day Recovery i IV + IV t II + Significantly higher than controls by Dunnett criteria i Significantly lower than controls by Dunnett criteria 13-Day Recovery + II + II, III, IV Group Designations and Exposure ________ Concentrations_________ II = Low Dose - 3.1 mg/L III > Intermediate Dose - 10.0 mg/L IV = High Dose - 30.0 mg/L j i i i l J  B MR: COMPRO PERIOD: 10 DAT TOXICOLOGIST: KINHEY HASKELL#: 14808 HASKELL CODE#: M DPRTMHT: CHEMICALS & PIGM^TS REPORT DATE: 17-MAY-83 CLINICAL LAB: MATARESE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 6-MA-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348420 348432 348400 348430 348437 348421 348433 348409 348422 348425 RBC M/mm 7.13 6.78 7.68 6.68 7.40 7.02 6.30 7.64 6.88 7.35 Hb g/dL 15.9 15.5 16.8 15.2 16.3 15.7 15.8 16.7 14.8 15.4 Ht t 42. 40. 4740. 44. .42. 41. 45. 41. 45. AVG. S. D. S. E. 7.086 0.441 0.140 15.81 0.64 0.20 42.7 2.3 0.7 MCV fL 5958. 60. 60. 5960. 64. 59. 5960. 59.8 1.6 0.5 MCH MCHC PLAT PS g/dL M/mm 22. 38. 856. 23. 39. 1010. 22. 36. 990. 23- 38. 944. 22. 37. 1162. 22. 37. 1192. 25. 39. 1 0 1 8 . 22. 37- 1152. 22. 37. 1220. 21. 34. 920. 22.4 1.1 0.4 37.1 1046.4 1.3 126.4 0.4 40.0 GROUP: 2M DOSE: 3.1 MG/L SAMPLE DATE: 6-MAY-83 SEX: MALE BIRTH DATE: 3-MAR-83 ANIMAL#: 348410 348411 348380 348426 348391 348381 348384 348387 348418 348413 RBC M/mm 6.90 7.42 7.20 6.67 6.58 7.39 7.74 7.62 7.27 7.93 Hb g/dL 15.2 16.0 15.4 15-8 14.7 16.5 17.2 15.9 16.1 17.2 Ht $ 40. 42. 42. 40. 3944. 46. 45. 43. 48. MCV fL 5757. 58. 59. 5959595958. 59- MCH MCHC PLAT PS g/dL M/mm 22. 38. 1042. 22. 38. 944. 21. 36. 1064. 24. 40. 1100. 22. 38. 904. 22. 38. 1258. 22. 37. 1330. 21. 35. 828. 22. 38. 1016. 22. 36. 798. AVG. S. D. S. E. 7.272 16.00 0.446 0.81 0.141 0.26 42.9 2.8 0.9 58.4 0.8 0.3 22.1 0.8 0.2 37.4 1028.4 1.2 172.0 0.4 54.4 RAT Company Sanitized. D oss not contain TSC A C B f Yi HR: mI g L > COMPhIdTO(^ P I H W PERICO: 10 OAT TOXICOLOGIST: KINHET HASKELL#: 14808 HASKELL CODE#: ____ DPRTMNT: CHEMICALS A PIGMNTS REPORT DATE: 17-HAI-83 CLINICAL LAB: MATARESE GROUP: 3M DOSE: 10.0 MG/L SAMPLE DATE: 6-HAT-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348392 348398 348399 348404 348405 348388 348389 348393 348416 348427 RBC Mt/om 7.05 7.07 7.37 6.94 6.72 6.98 6.92 7.00 6.90 6.92 Hb g/dL 16.4 16.1 16.1 15.6 15.2 15.2 15.2 16.1 15.2 15.3 Ht t 41. 43. 44. 40. 40. 42. 40. 41. 43. 42. MCV fL 58. 61. 59. 58. 5960. 57. 58. 61. 60. MCH PE 23. 2232.. .23. 2232. ..22. 2232. 22 MCHC g/dL 40. 37. 37. 39. 38. 36. 38. 39. 36. 37. PLAT M/mn 1216. 1160. 1002. 91H. 1030. 1094. 1196. 938. 982. 1056. AVG. S. D. S. E. 6.987 15.64 0.166 0.48 0.052 0.15 41.6 1.4 0.4 59.1 1.4 0.4 22.4 0.5 0.2 37.7 1059-2 1.3 105.1 0.4 3 3 . 2 # GROUP: 4M DOSE: 30.0 MG/L SEX: MALE SPECIES: RAT SAMPLE DATE: 6-MAY-83 BIRTH DATE: 3-MAR-83 ANIMAL#: 348397 348429 348412 348417 348436 348396 348428 348434 348385 348407 RBC tti/nm 6.64 6.77 6.63 7.32 6.99 7.18 7.02 7.23 6.91 6.66 Hb g/dL 15.2 15.4 15.0 16.0 15.2 15.8 15.6 16.5 16.0 14,7 AVG. S. D. S. E. 6-935 0.256 0.081 15.54 0.54 0.17 Ht % 39. 40. 39. 43. 41. 42. 42. 44. 43. 40. 41.2 1.8 0.6 MCV fL 58. 58. 59. 58. 57. 58. 59. 60. 62. 60. 58.9 1.4 0.5 MCH Pg 23. 23 23 ..22. 22. 22 22 23. 23. 22. MCHC g/dL 39. 39. 38. 38. 38. 38. 37. 38. 37. 37. PLAT M/mm 864. 730. 1014. 1022. 914. 786. 874. 1132. 1084. 906. 22.4 0.5 0.2 37.7 932.6 0.7 128.7 0.2 40.7 Company Sanitized. Doss not contain TSCA CBI 40 cdhphd( ^ B ^ J PERICO: 10 SAY TOXICOLOGIST: KINNEY HASKELL#: 14808 OmiHASKELL CODE#: DPRYOT: CHEMICALS & PIGMENTS REPORT DATE: 2-J0N-83 CLINICAL LAB: MATARESE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 6-MAY-83 ANIMAL#: 348420 348432 348400 348430 348437 348421 348433 348409 348422 348425 WBC M/nm 9.5 11.7 14.0 12.7 15.5 12.2 13.4 18.3 14.5 14.3 Neut HBCxf 570. 1170. 560. 889. 1550. 1952. 1742. 732. 2465. 1430. Band HBCxf 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. AVG. 3. D. S. E. 13-61 2.37 0.75 1306.0 636.5 201.3 0.0 0.0 0.0 SEX: MALE SPECIES: RAT BIRTH DATE: 3-KAR-83 Lymph HBCxf 8455. 9945. 12040. 11049. 13020. 9394. 10854. 15738. 10150. 11726. Alym HBCxf 190. 117. 140. 0. 155. 244. 134. 366. 435. 286. Mono HBCxf 285. 468. 1120. 762. 775. 610. 670. 1464. 1450. 858. Eosin HBCxf 0. 0. 140. 0. 0. 0. 0. 0. 0. 0. Baao HBCxf 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 11237.1 206.7 846.2 2068.0 128.5 391.3 654.0 40.6 123.8 14.0 44.3 14.0 0.0 0.0 0.0 GROUP: 2M DOSE: 3.1 MG/L SAMPLE DATE: 6 -MAY- 8 3 ANIMAL#: 348410 348411 348380 348426 348391 348381 348384 348387 348418 34.3413 WBC M/mn 12.3 13.4 12.8 9-2 15.2 13.7 13-5 7.9 9.9 12.1 Neut HBCxf 615. 1340. 1024. 1196. 1216. 822. 6751185. 1188. 968. Band HBCxf 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. AVG. S. D. S. E. 12.00 2.29 0.72 1022.9 247.7 78.3 0.0 0.0 0.0 SEX: MALE S>ECIES: RAT BIRTH DATE: 3-MAR-83 Lymph HBCxf 11070. 10988. 11136. 7084. 12768. 11782. 11745. 6004. 7623. 9922. Alyu HBCxf 0. 134. 128. 92. 456. 274. 135. 158. 396. 121. Mono HBCxf 369. 938. 512. 736. 760. 822. 810. 395. 693. 968. Eosin HBCxf 246. 0. 0. 92. 0. 0. 135. 158. 0. 121. Baso HBCxf 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 10012.2 1 8 9 . 4 7 0 0 . 3 2295.4 142.1 210.4 '725.9 44.9 66.5 75.2 88.4 27.9 0.0 0.0 0.0 Company Sanitized. Does no! contain TSCA CB t.  < - H IL, ODMPNlMH PERICO: 10 DAT TQXIOOLOGE3T: SINNET HASKELL#: 14808 HASKELL CODE#: J j H K j DPRTMiT: CHEMICALS & PIGMENTS REPORT DATE: 2-JUN-83 CLINICAL LAB: MATARESE GROUP: 3M DOSE: 10.0 MG/L SAMPLE DATE: 6-MAT-83 ANIMAL#: 348392 348398 348399 348404 348405 348388 348389 348393 348416 348427 AVG. S. D. S. E. WBC M/an 12.5 14.9 14.9 11.3 12.7 10.4 13.1 11.1 12.1 12.3 12.53 1 .49 0.47 Neut WBCxf 1000. 1192. 596. 904. 2032. 1456. 2096. 555. 1452. 1722. Band WBCxJ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 1300.5 548.1 173.3 0.0 0.0 0.0 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 Lymph WBCx* 10250. 12069. 13559. 96135. 9017. 8528. 9694. 9102. 9559. 9348. Alym WBCxf 250. 298. 149. 113. 381. 104. 131. 333. 242. 123. Mono WBCxf 1000. 1192. 596. 565. 1270. 312. 1179. 999. 726. 1107. Eosin NBCxff 0. 149. 0. 113. 0. 0. 0. 111. 121. 0. Baso HBCxf 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 10073.1 212.4 894.6 1555.1 101.6 323.7 491.8 32.1 102.4 49.4 64.6 20.4 0.0 0.0 0.0 GROUP: 4M DOSE: 30.0 MG/L SAMPuE DATE: 6-MAY-83 ANIMAL#: 348397 348429 348412 348417 348436 348396 348428 348434 346385 348407 WBC M/mn 15.7 12.0 10.7 12.0 9-7 8.7 16.0 14.0 13-3 10.7 Neut WBCx? 1570. 1200. 1391. 1440. 776. 1044. 1760. 1260. 1596. 1284. Band WBCx? 0. 0. 0. C. 0. 0. 0. 0. 0. 0. AVG. S. D. S. E. 12.28 2.45 0.78 1332.1 287.1 90.8 0.0 0.0 0.0 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 Lymph WBCx? 13031. 10560. 8346. 9480. 8148. 6786. 13280. 10780. 99758774. Alym WBCx* 314. 120. 428. 240. 194. 174. 160. 420. 133. 0. Mono WBCxjC 785. 120. 535. 840. 582. 609. 640. 1400. 1463. 642. Eosin Baso WBCx* WBCx* 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 87. 0. 160. 0. 140. - 0. 133. 0. 0. 0. 9916.0 2 18.3 761.6 2083.4 135.3 401.9 658.8 42.8 127.1 52.0 69.5 22.0 0.0 0.0 0.0 Company Sanitized. Does noi contain TSCA CB I /. -t L wn "mmmmtnnKtgi m m m CQHPraMH PERIOD" 10 DAT TOXICOLOGIST: KINNEY HASKBLL#: 11,808 HASKELL CODE#: DPRTHNT: CHEMICALS & P l f f l ^ ^ * REPORT DATE: 17-MA-83 CLINICAL LAB: MA1ARESE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 6-MAY- 8 3 OE X : MALE SPECIES: RAT BIRTH DATE: 3-MAR- 8 3 ANIMAL#: 348420 348432 348400 348430 348437 348421 348433 348409 348422 348425 AP IU 173. 224. 200. 246. 157. 16 1. 243. 236. 177. 226. AVG. S. D. S. E. 204.3 34.9 11.0 ALT IU 29. 32. 33. 33. 32. 27. 31. 29. 31. 24. 30.1 2.9 0.9 AST IU 56. 72. 69. 54. 59. 67. 61. 71. 68. 52. 62.9 7.4 2.3 BUN ogf 19.4 19 .7 17.1 15.6 12.7 19 .3 17.2 13.3 16.1 18.3 16.87 2.47 0.78 CREAT mg? 0.7 0.7 0.7 0.6 0.6 0.6 0.6 0.6 0.6 0.7 CHLOS mg* 70. 68. 61. 61. 72. 6 1. 67. 50. 68. 72. TPROT si 5.5 5.8 5.6 5.4 5.5 5.4 5.1 5.1 5.3 5.3 0.64 0.05 0.02 65.0 6.9 2.2 5.40 0.22 0.07 GROUP: 2M DOSE: 3.1 MG/L SAMPLE DATE: 6-MAY- 8 3 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 a n i m a i .#: 348410 3-8411 ->48380 348426 348391 348381 348384 348387 348418 348413 AP IU 201. 191. 161. 159. 185. 164. 203. 163. 156. 219. AVG. S. D. S. E. 180.2 22.5 7.1 ALT IU 28. 34. 32. 27. 27. 22. 21. 27. 26. 30. 27.4 4.0 1.3 AST IU 60. 78. 67. 61. 55. 69. 66. 66. 52. 68. BUN mgt 21.8 21.4 19.6 19.9 17.8 14.8 24.6 17.2 15.2 19.4 CREAT mg? 0.7 1.0 0.7 0.9 0.8 0.6 0.6 0.7 0.6 0.6 CHLOS mg? 91. 64. 76. 71. 76. 67. 54. 46. 55. 48. TPROT S 5.6 5.8 5.8 5.5 5.5 5.2 5.3 4.9 5.3 5.2 64.2 7.5 2.4 19.17 3.03 0.96 0.73 O.13 0.04 64.8 14.1 4.5 5.41 0.28 0.09 ompahv Sanitized. Does not contain TSCA BI "7 U7 ... i,j .^ jm rn w 9 W m m m m HRil___ COMPND^I PERIOD: 10 DAT TOXICOLOGIST: KINNEY HASKELL#: 14808 HASKELL CODE#: l l H DPRTMNT: CHEMICALS & PIOtBHTS REPORT DATE: 17-MAY-83 CLINICAL LAB: M A U R E SE GROUP: 3M DOSE: 10.0 MG/L SAMPLE DATE: 6-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348392 348398 348399 348404 348405 3483. 348389 348393 348416 348427 AP IU 278. 245. 233177. 178. 163256. 150. 146. 155. ALT AST BUN CREAT CHLOS TPROT IU IU mg* mg* mg* S 31. 82. 18.0 0.6 59. 5.3 31. 72. 21.2 0.7 68. 5.8 35. 72. 15.7 0.6 63. 5.5 32. 91. 19.6 0.7 63. 5.4 28. 78. 16. : 0.8 71. 5.4 29. 73- 13.9 0.6 53. 5.1 28. 62. 14.4 0.6 44. 5.4 27. 86. 10.5 0.5 42. 5.2 20. 53. 18.9 0.7 44. 5.2 29. 59. 18.4 0.7 58. 5.1 AVG. S. D. S. E. 198.1 49.6 15.7 29.0 3-9 1.2 72.8 16.70 12.1 3.18 3.8 1.00 0.65 0.06 0.02 56.5 10.5 3-3 5.34 0.21 0.07 GROUP: 4M DOSE: 30.0 MG/L SAMPLE DATE: 6-MAY-83 SEX: MALE BIRTH DATE: 3-MAR-83 ANIMAL#: 348397 348429 348412 348417 348436 348396 348428 348434 348385 348407 AVG. S. D. S. E. AP IU 205. 223130. 230. 170. 225. 136. 207. 188. 202. 191.7 35.8 11.3 ALT IU 2934. 28. 36. 35. 28. 30. 31. 30. 30. 31.1 2.9 0.9 AST BUN CREAT CHLOS TPROT IU mg* mg* mg91 6% 70. 1 3 . 0 0.7 46. 5.8 72. 1 9 . 7 0.7 53- 5.5 77. 1 3 . 9 0.8 66. 5.5 70. 12.3 0.7 54. 5.7 84. 11.2 0.8 37. 5.6 68. 15.4 0.7 47. 5.6 91. 17.0 0.7 48. 5.2 69. 17.4 0.7 36. 5-3 64. I3 . 3 0.6 41. 5.1 94. 10.9 0.5 41. 5.2 75-9 10.3 3.3 14.41 2.89 O .91 0.67 0.08 0.03 4 7 .O 9.1 2.9 5.45 0.24 0.07 4 '+ fe P ^ S a M d .DoesTO! contain TSCA C1F uiM iniifipn COMPNDM 5 PERIOD: TODAY TOXICOLOGISTS KINNEY HASKELL#: 14808 HASKELL CODE#: DPRTHNT: CHEMICALS & PIGMSTS REPORT DATE: 17-MAY-83 CLINICAL LAB: MATARESE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 6-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348420 348432 348400 348430 348437 348421 348433 348409 348422 348425 AVG. S. D. S. E. VOL OSMOL BLOOD SUGAR PRO mL mOs TEIN 7. 1698. + 1 7. 1749. + 1 6. 2016. _i _ +12 +2 5. 2218. +2 10. 974. +1 9. 1589. + +1 11. 1180. +1 6. 1494. + +1 6. 1756. + 1 10. 2100. - - ++21 7.7 1677.4 2.2 391.7 0.7 1 2 3 . 9 PH 7.0 8.0 8.0 87..00 7.0 7.0 8.0 7.0 7.0 BILI RUBIN +1 +1 4-1 +1 UROBL mg/dL 1.0 '.0 0.1 0.1 0.1 0.1 00..11 11..00 Ke tone +1 7.40 0.52 0.16 C.46 0.46 0.15 GROUP: 2M DOSE: 3.1 MG/L SAMPLE DATE:: 6 -MAY- 8 3 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348410 348411 348380 348426 348391 348381 348384 348387 348418 348413 AVG. S. D. S. E. VOL OSMOL mL mOs 7. 1985. 5. 1910. .7. 1945. 8 1706. 7. 1732. 9. 1571. .4. 7. 22408000. 6 . 1991. 7. 1771. BLOOD SUGAR PRO TEIN +2 +1 +2 + + 11 +1 +2 +2 +1 +2 6.6 1 9 0 9 . 1 1.5 248.1 0.5 78.5 PH BILI RUBIN 7.0 7.0 - 8.0 + 1 8.0 7.0 7.0 7.0 7.C I 7.0 7.0 - UROBL Kemg/dL t 1.0 + 1.0 + 1.0 + 1.0 + 1.0 + 1 1.0 1.0 1.0 + 1.0 + 1.0 + 7.20 0.42 0.13 1.00 0.00 0.00 + = Trace Company Sanitized. Does not contain TSCA CBI. mCrO:HuPnmth^Lg)J PERIOD : 10 DAY TOXICOLOGIST: KINNEY HASKELL#: 10808 HASKELL CODE#: DPRTMNT: CHEMICALS & PIGMENTS REPORT DATE: 17-MAI-83 CLINICAL LAB: MATARESE GROUP: 3M DOSE: 10.0 MG/L SAMPLE DATE: 6-MAI-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348392 348398 348399 348404 348405 348388 348389 348393 348416 348427 AVG. S. D. S. E. VOL OSMOL BLOOD SUGAR PRO- mL mOs TEOi 6. 1887. +1 12. 1067. _ +1 7. 1619. 7. 2930. 7. 1624. +1 ++22 7. 1827. 5. 1425. _ ++11 9. 1259. 6. 1821. 1 +2 5. 1857. - +2 7.1 1731.6 1.9 502.9 0.6 159.0 pH BILI- ROBIN 7.0 8.0 - 8.0 87..00 - - - 78..00 - - 7.0 - 7.0 - 7.0 - UROBL mg/dL 1.0 0.1 1.0 . 1.0 11..00 C.1 1.0 1.0 Keton* - - + + + ++1 + + + 0.82 0.38 0.12 GROUP: 4M DOSE: 30.0 MG/L SAMPLE DATE : 6-MAY-83 SEX: MALE SPECIES : RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348397 348429 348412 348417 348436 348396 348428 348434 348385 348407 JOL mL 9. 5. 8. 15. 6. 8. 17. 6. 7. 9. OSMOL BLOOD mOs 1465.1912. 1635. 1013. 1563. 1217. 711. 1774. 1618. - 1617. - SUGAR + _ _ ,, - PRO TEIN +1 +2 +2 +1 +2 +1 + +2 +2 +1 PH BILI RUBIN 7.0 7.0 8.0 + 1 7.0 7.0 8.0 - 8.0 7.0 7.0 . 7.0 - UROBL mg/dL 1.0 1.0 1.0 0.1 1.0 1.0 0.1 1.0 1.0 1.0 Ke tone + +1 + * + -- AVG. S. D. S. E. 8.8 1442.5 3.9 354.4 1 .2 112.1 7.30 0.48 0.15 0.82 0.38 0.12 + = Trace no! contain TSCA CBF Mi\ GOMFHDl PERIOD: 10 DAI TOXICOLOGIST: KINNEY HASKELL#: 14808 HAsra.:. CODE#: DPRTMNT: CHBdCALS & PIGMalTS REPORT DATE: 13-JON-83 CLINICAL LAB: MATARESE 3 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 6-MAI-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348420 348432 348400 348430 348437 348421 348433 348409 348422 348425 RBC /hpf 1-2 2-5 0-0 0-0 0-1 -2 0-0 0-1 2-4 0-0 VBC /hpf 3-6 8-12 5-10 1-3 4-6 15-20 20-30 5-10 3-5 2-5 Epith /hpf 2-3 4-6 0-3 0-2 1-2 5-8 8-10 3-6 1-3 0-2 Cast /lpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 APPEARANCE DY CL PPT P PEC DY CL PPT F PEC Y CL PPT Y CL Y CL-PPT Y CL PPT F Y CL PPT Y CL PPT DY CL PPT F PEC Y CL PPT AVG. S. D. S. E. GROUP: 2M DOSE: 3.1 MG/L SAMPLE DATE: 6-MA-83 SEX: MALE SPECIES: RAT BIR'rH DATE: 3-MAR-83 1IMAL#: 3*8410 348411 348380 348426 348391 348381 348384 348387 348418 348413 RBC /hpf 0-0 0-0 O-o 0-0 0-C 0-0 0-0 0-0 0-0 0-0 WBC /hpf 10-15 5-8 30-40 10-20 5-10 10-20 2-3 8-10 8-12 10-15 Epith /hpf 4-8 . 2-4 10-15 5-8 2-3 4-6 0-2 2-4 3-6 4-6 Cast /lpf 0-0 0- 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 APPEARANCE Y CL PPT LY CL PPT Y CL PPT F PEC Y CL PPT Y CL PPT LY CL PPT Y C PPT Y CL PPT F FEC Y CL PPT Y CL PPT F . AVG. S. D. S. E. Company Sanitized. Does not contain TSCA CB1 ta g L . ODMPHDI PERIOD: 10 DAI TOXICOLOGIST: KINNEY HASKELL#* 14808 B.qria.i. CODE#: T M \ DPRTMHT: CHBdCALS & P I G M H ^ " REPORT DATE: 13-JUN-83 CLINICAL LAB: MATARESE GROUP: 3M DOSE: 10.0 MG/L SAMPLE DATE: 6-MA-83 ANIMAL#: 348392 348398 348399 348404 348405 348388 348389 348393 348416 348427 RBC /hpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 WBC /hpf 10-20 5-10 4-8 20-30 10-15 4-8 5-10 8-12 20-30 40-50 Epith /hpf 3-5 0-3 2-4 5-10 5-10 4-6 5-8 5-10 8-10 10-15 Cast /lpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 AVG. S. D. S. E. SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 APPEARANCE T CL PPT L CL PPT Y CL PPT Y CL PPT F Y CL PPT LY CL PPT LY CL PPT LY CL PPT F Y CL PPT LY CL PPT GROUP: 4M DOSE: 30.0 MG/L SAMPLE DATE: 6-MAY-83 ANIMAL#: 348397 348429 348412 348417 348436 348396 348428 348434 348385 348407 RBC /hpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 WBC /hpf 10-15 4-10 10-20 10-15 3-6 2-5 2-4 10-20 10-15 4-8 Epith /hpf 4-8 2-4 4-6 3-5 0-4 2-5 0-2 2-4 5-10 0-3 Cast /lpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 AVG. S. D. S. E. SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 APPEARANCE Y CL PPT F Y CL PPT DY CL PPT F FEC LY CL PPT F Y CL PPT LY CL PPT LY CL PPT Y CL PPT Y CL PPT F Y CL PPT F . Company Sanitized. Does not contain TSC CBf PERICO ^RECOVERY TOXICOLOGIST: KINNEY HASKELL#: 14808 HASKELL CODE#: DPRTMNT: CHEMICALS 4 P I G MENT^^ REPORT DATE: 1-JUN-83 CLINICAL LAB: MATARESE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 19-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 RBC ANIMAL#: MM/mo 348420 Hb g/dL Ht MCV MCH MCHC PLAT J fL Pg g/dL M/mm 348432 348400 348430 348437 348421 6.90 15.8 41 . 58. 23. 39. 1080. 348433 6.53 15.7 41 . 63. 24. 38. 886. 348409 7.80 17.3 45. 57. 22. 39. 878. 348422 7.02 15.5 40. 57. 22. 39. 1154. 348425 7.14 15.5 41. 58. 22. 38. 894. AVG. S. D. S. E. 7.078 0.464 0.207 15.96 0.76 0.34 41 .6 1.8 0.8 58.6 2.5 1.1 22.6 0.9 0.4 38.4 978.4 0.6 129.3 0.3 57.8 GROUP: 2M DOSE: 3 . 1 MG/L SAMPLE DATE: 19-MAY-83 SEX: MALE SPECIES: BIRTH DATE: 3-MAR-83 RBC Hb Ht MCV MCH MCHC PLAT ANIMAL//: MM/mm g/dL 348410 % fL Pg g/dL M/mm 348411 348380 348426 348341 3 ^83 81 6.63 15.9 40. 54. 24. 40. 938. 348384 7.58 16.3 4 3. 57. 22. 39. 900. 348387 7.34 16.3 4 3. 58. 22. 38. 922. 348418 7.24 16.1 41 . 57. 22. 39. 824. 348413 6. 94 15.0 40. 57. 22. 37. 916. AVG. S. D. S. E. 7.146 16.02 0.369 0.66 0.165 O.3 0 41.4 1.6 0.7 57.6 0.9 0.4 22.4 0.9 0..4 38.7 900.0 1.1 44.6 0.5 1 9 . 9 Company Sanitized. Does not contain T SC C B I *t / <T^3 :s p ' COMPD^HHJ PERICO: RECOVERY TOXICOLOGIST: KINNEY HASKELL#: 14808 HASKELL CODE#: ( , J | Q DPRTtWT: CHEMICALS & PIGMENTS REPORT DATE: 1-JUN-83 CLINICAL LAB: MATARESE GROUP: 3M DOSE: 10.0 MG/L SAMPLE DATE: 19-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348392 348398 RBC m/tm Hb g/dL Ht MCV MCH MCHC PLAT X fL Pg g/dL M/mm 348399 348404 34845 348388 7.37 16.6 4 3. 58. 23. 39. 1020. 348389 6.93 15-1 38. 54. 22. 40. 1014. 348393 7.04 15.9 41 . 57. 23. 39. 940. 348416 6.99 16.4 41 . 58. 23. 40. 912. 348427 6.67 15.0 39. 58. 22. 39. 1014. AVG. S. D. S. E. 7.000 0.251 0.112 15.80 0.73 0.33 40.2 1.9 0.8 57.0 1.7 0.8 22.5 0.6 0.3 39.3 980.0 0.6 50.3 0.3 22.5 GROUP: 4M DOSE: 30.0 MG/L SAMPLE DATE: 19-MAY-83 SEX: 1MALE BIRTH DATE: 3-MAR- 8 3 RBC Hb Ht MCV MCH MCHC PLAT ANIMAL#: MM/mm g/dL % fL PE g/dL M/nm 348397 348429 348412 348417 348436 34 3396 7.15 15.7 41 . 56. 2 2 . 39. 890 348428 6 . 8 1 15.3 3?. 57. 23. 40. 1 202 3484 34 7.39 16.5 4 3. c8. 2 2 . 38. Q40 348385 6.44 16.1 3C. ''i. 25. 42. 035 345407 6.71 15.0 38. c6 . 2 2 . 40. 630 AVG. S. D. S. E. 6.900 O.374 0.167 15.32 0.55 0.25 40.0 2.1 0. c 57.2 1.3 1.6 22.9 1.2 O'.6 39.5 971.6 1.4 131.0 0.6 58.6 Gorrn j u TMvs^fT*ed.Does notWain TSCACBI rnmft OOMPNd Cj^ B v PERICO: RECOVERY TOXICOLOGIST: KINNEY HASKELL#: 14808 HASKELL CODE#: DPRTMT: CHEMICALS & PIQBHTS REPORT DATE: 2-JON-83 CLINICAL LAB: MATARESE GROOP: 1CM DOSE: CONTROL SAtffLE DATE: 19-MA-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348420 348432 348400 345430 348437 348421 348433 348409 348422 348425 WBC M/an 13.3 11.7 15.5 12.2 13.0 Neut Band WBCxf UBCxf Lymph Alym Mono Eoain Baso WBCx* WBCx* WB'xf UBCxf WBCx 1463. 2457. 1550. 2318. 1040. 0. 0. 0. 122. 0. 10241 . 8658. 12865. 9272. 11700. 399351. 155. 244. 130. 1064. 234. 30. 122. 130. 133. 0. 0. 122. 0. 0. 0. 0. 0. 0. AVG. S. D. S. E. 13-14 1 .46 0.65 1765.6 601 .6 269.0 24.4 54.6 24.4 10547.2 255.8 496.0 1731.3 1 1 8 . 0 461.9 774.3 52.8 206.6 5 1.0 69-9 31.3 0.0 0.0 0.0 GROUP: 2M DOSE: 3 . 1 MG/L SAMPLE DATE: 19-MAY-83 ANIMAL#: 343410 348411 348380 348426 348391 348381 348384 348387 34841 8 348413 WBC M/nm 14.0 11 .1 9.0 11 .1 11 .7 Neut Band WBCx* WBCx 840. 555. 1530. 1554. 819. 0. 0. 0. 0. 0. AVG. S. D. S. E. 11.38 1 .79 0.80 1059.6 454.5 203.3 0.0 0.0 0.0 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 Lymph Alym Mono Eosln Baso WBCx* WBCx/t WBCx* WBCx WBCx* 12740. 10101. 7110. 8769. 10179. 140. 111. 90. 111. 351. 280. 333270. 666. 234. 0. 0. 0. . 0. 117- 0. 0. 0. 0. 0. 9779-8 2072.1 ' 926.7 160.6 107.9 48.3 356.6 176.6 79.0 23-4 52.3 23.4 0.0. 0.0 0.0 Company Sanitized. Does not contain TS C A C B I siiti i PERIOD: RECOVERY TOXICOLOGIST: KINNEY HASKELL#: 14808 HASKELL CODE#: f i H V l DPHTWT: CHEMICALS & PIOffiHTJi ^ REPORT DATE: 2-JON-83 CLINICAL LAB: MA TARES 00P: 3M DOSE: 10.0 MG/L SAMPLE DATE: 19-MAY-83 ANIMAL#: 348392 348398 348399 348404 348405 348388 348389 348393 348416 348427 WBC M/mn 10.2 10.7 9.1 13.6 7.4 Neut Band WBCxf WBCxff 1938. 20331274. 952. 1258. 0. 0. 0. 0. 0. AVG. S. D. S. E. 10.20 2.28 1.02 1491.0 470.5 210.4 0.0 0.0 0.0 SEX: MALE SECIES: RAT BIRTH DA'S: 3-MAR-83 Lymph Alym Mono Eoaln Baso WBCxf WBCxf WBCx* WBCx* UBCx* 7446. 7811. 7007. 10880. 5328. 204. 107. 273. 680. 296. 510. 749. 546. 952. 518. 102. 0. 0. 136. 0. 7694.4 3 1 2 . 0 6 55.0 2018.4 218.5 192.8 902.7 97.7 86.2 47.6 66.3 29.6 0. 0. 0. 0. 0. 0.0 0.0 0.0 GROUP: 4M DOSE: 30.0 MG/L SAMPLE DATEI: 19-MAY-83 SEX: MALE SECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348397 348429 348412 348417 348436 348396 348428 343434 348385 348407 WBC M/mn 12.3 17.7 14.9 12.9 12.0 Neut Band WBCx? WBCxJ Lymph Alym Mono Eosln Baso WBCx? WBCx* WBCxjt WBCx* WBCxJt 1353. 2301 . 2533. 1935. 2880. 0. 0. 0. 0. 0. 9471 . I3 2 7 5 . 11920. 10062. 80 40. 369. 708. 149. 387. 360. 984. 1416. 298. 516. 720. 123. 0. 0. . 0. 0. 0. 0. 0. 0. 0. AVG. S. D. S. E. 13.96 2.38 1 .06 2200.4 5 85.5 251.8 0.0 . 0.0 0.0 10553.6 394.6 786.8 2061 .9 2 0 0 . 3 4 33.4 922.1 39.6 1 9 3 . 8 24.6 55.0 24.6 0.0 0.0 0.0 notCompany Sanife* * Does contain tsca CBI  PERICO: RECOVERY TOXICOLOGIST: KIRNET HASKELL#: 14808 HASKELL CODE#: DPRTMiT: CHEMICALS & PK2OENTS REPORT DATE: 1-JUN-83 CLINICAL LAB: MATARESE ' GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 19-MAY-83 SEX: MALE SPECIES BIRTH DATE: 3-MAR-83 ANIMAL#: 348420 AP IU ALT AST BUN CREAT CHLOS TPROT IU IU mg% mgt mg? g* 348432 348400 348430 348437 348421 177. 32. 78. 19.6 0.7 60. 5.6 348433 265. 36. 58. 22.2 0.6 88. 6.1 348409 245. 41 . 76. 20.4 0.6 51. 5.5 348422 1 8 2 . 34. 64. 14.0 0. 6 77. 6.1 348425 249. 32. 54. 19.1 0.6 74. 6.1 AVG. S. D. S. E. 223.6 41 .0 18. 3 35.0 3.7 1.7 66.0 20.06 10.7 1.32 4.3 0.59 0.65 0.03 0.01 69.9 14.7 6.6 5.88 0.30 0.14 , GROUP: 2M DOSE : 3.1 MG/L SAMPLE DATE:: 1Q-!MAY-83 SEX: MALE SPECIES BIRTH DATE: 3-MAR-83 ANIMAL#: 348410 34841 1 348380 348426 348391 348331 348384 348387 348418 348413 AP IU 176. 232. 166. 116. 216. ALT AST BUN CREAT CHLOS TP ROT I IU mg? mg? mg? gi 33. 66. 19.9 0.6 77. 5.8 42. 74. 21.7 0.8 52. 5.5 41 . 70. 25.9 0.8 46. 5.5 35. 70. 25.3 0.7 64. 5.8 36. 55- 17.3 0.7 54. 5.6 AVG. S. D. S. E. 181.2 45.6 20.4 37.4 3.9 1 .7 67.0 22.02 7.3 3.63 3-3 1.62 0.71 0.07 0-03 58.2 12.1 5.4 5.64 0.15 0.07 Company SaxlUzeS. Does noi contain TSCA CBf h ( M ) 2com pnd( ] B B P PERICO: RECOVE TOXICOLOGIST: KINNEY HASKELL#: 14808 HASKELL CODE#: H V 3 DPRTMNT: CHEMICALS & PIOOENTS REPORT DATE: 1-JUN-83 CLINICAL LAB: MATARESE GROUP: 3M DOSE: 10.0 MG/L SAMPLE DATE: 19-MAY-83 SEX: MALE SPECIES: RAT EIRTH DATE: 3-MAR-83 ANIMAL#: 348392 348398 348399 348404 348405 348388 348389 348393 348416 348427 AVG. S. D. S. E. AP IU 153. 231. 160. 145. 171. 172.0 34.3 15.4 ALT IU 30. 27. 28. 30. 35. 30.0 3.1 1 .4 AST BUN CREAT CHLQS TPROT IU mg* mgt mg* K 77. 1 8 . 6 56. 18.5 64. 18.0 59. 19.1 76. 17.9 66.4 18.42 9.7 0.49 4.3 0.22 0.6 0.6 0.7 0.6 0.6 0.63 0.04 0.02 55. 56. 62. 50. 73. 59.2 8.8 3.9 5.5 5.8 5.8 5.9 5.8 5.76 0.15 0.07 GROUP: 4M DOSE: 30.0 MG/L. SAMPLE DATE: 19-KAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348397 348429 34 8412 348417 34 8436 348396 348428 3484 34 348385 348407 AP IU 278. 158. 246. 203. 244. ALT AST BUN CREAT CHLQS TP ROT IU IU mg? mg% mg? e% 38. 82. 18.8 0.6 62. 5.8 37. 74. 19.2 0.6 68. 6.0 36. 62. 18.4 0.6 55. 5.7 28. 59. 18.1 0.6 52. 6.0 32. 62. 19.1 0.6 56. 5.4 AVG. S. D. S. E. 225.8 46.3 20.7 34.2 4.1 1.9 67.8 18.72 9.8 0.47 4 . 4 0.21 0.62 0.03 0.01 58.7 6.3 2.8 5.88 0.13 0.06 Company Sani f*zed. Does not contain TSCA CB " fl ,, ooMP( r o t t e l i PERIOD: RECOVERT TOXICOLOGIST: KINNEY HASKELL#: 14808 HASKELL CODE#: ( DPRTMJT: CHEMICALS & PI O C NTS REPORT DATE: 2-J0N-83 CLINICAL LAB: MATARESE OOP: 1CM DOSE: CONTROL SAMPLE DATE: 19-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 343420 348432 348400 348430 348437 348421 348433 348409 348422 348425 AVG. S. D. S. E. VCX. OSMOL BLOOD SUGAR PRO- dL dC s TEIN .20. 10 1431. 9. 13. -- +1 -- 13.0 1534.5 5.0 284.6 2.5 142.3 - + +i +1 +1 pH BILI- UROBL Ke RUBIN ng/dL tone 7.0 7.0 7.0 7.0 - 7.00 0.00 0.00 0.1 0.1 +1 1.0 +1 1.0 +1 0.55 0.52 0.26 GROUP: 2M 3.1 MG/L SAMPLE DATE: 19-MAY-83 SEX: MALE SPECIES : RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348410 348411 348380 348426 348391 348381 348384 348337 348418 348413 AVG. S. D. S. E. BLOOD SUGAR PRO mL mOs TEIN 814. 1740. . 1978. - .66. 2228. 2630. - 11 . 1925. -- 9.1 2 100.2 3.4 343.7 1.5 153-7 - -- +1 +1 +2 +2 +1 "H BILI UROBL Ke RUBIN mg/dL tone 7.0 7.0 7.0 7.0 7.0 +1 - - 7.00 0.00 0.00 1.0 + 1.0 + 1.0 +1. 1.0 + 1 1.0 + 1 .00 0.00 0.00 + = Trace Corna,sn V Sanfff-gjj Does nof cnfainTSCAC8F 00MPNd I 8 B V J PERIOD: RECOTERI TOXICOLOGIST: KINNEI HASKELL#: 14808 HASKELL CODE#* M 0 DPRTWT: CHEMICALS & PIOhjSMTS REPORT DATE: 2-J0N-83 CLINICAL LAB: MATARESE i GROUP: 3M DOSE: 10.0 MG/L SAMPLE DATE : 19-MAI-83 SEX: MALE SPECIES : RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348392 348398 348399 348404 348405 348388 348389 348393 348416 348427 VOL OSMOL BLOOD SUGAR PRO ml. mOs TEIN 12. 1729. 9. 1522. 10. 1626. 8. 1582. 8. 1404. _ +1 - +1 . + 1 _ +1 + +1 PH BILI UROBL Ke RUBIN mg/dL tone 7.0 8.0 7.0 7.0 7.0 - 1.0 +1 1.0 +1 1.0 + 1.0 4-2 1.0 4- AVG. S. D. S. E. 9.4 1652.6 1 .7 220.2 0.7 98.5 7.20 0.45 0.20 1.CO 0.00 0.00 GROUP: 4m DOSE: 30.0 MG/L SAMPLE DATE: 19-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348397 348429 348412 348417 348436 348396 348428 348434 348385 348407 VOL OSMOL BLOOD SUGAR PRO- raL mOs TEIN 10. 1516. + 1 12. 1268. 1 2 . 1593. 10. 2009. + 1 11. 1988. - _ _ - - +2 4-1 +1 4-1 + I pH BILI UROBL Ke RUBIN mg/dL tone 8.0 4-1 8.0 8.0 7.0 7.0 - 1.0 41.0 4-1 1.0 41.0 4-1 1.0 4-1 AVG. S. D. S. E. 11.0 1674.8 1.0 319.1 0.4 142.7 7.60 0.55 0.24 1.00 0.00 0.00 + = Trace fySaRf{f2ed. Does noi contain TSC A C Sf j >n,(agv, qow PERICO: ISCOVER? TOIICOLOGI3TS KINNE? HASKELL#: 14808 HASKELL CODB#t C f l V ) DPRnHTi CHEMICALS & PIQCHTS REPORT OAR: 2-J0H-83 CLINICAL LAB: MATARES OP* 1CM DOSE: CONTROL SALE DAR: 19-KAI-83 SZ : MALE SPECIES: RAT LIRTH DAR: 3-MAR-83 RBC ANDftL#: /hpf 348420 346432 348400 348430 348437 348421 348433 0-0 348409 0-2 348422 0-0 348425 0-0 NBC /hpf 2-4 5-7 0-0 0-2 Epifch Cast /hpf /lpf 5-8 0-0 3-5 0-0 2-4 0-0 1-3 0-0 APPEARANCE LI CL PPT I CL PPT F FEC Y CL PPT P I CL PPT AVG. S. D. S. E. GROUP: 2M DOSE: 3.1 ta/L SAWLE DAR: 19-MAY-83 SEX: MALE ; BIRTH DAR: 3-MR-83 ANIMAL#: 318410 348411 348380 348426 348391 348381 348384 '48387 348418 348413 RBC /hpf 0-0 0-0 0-1 0-0 0-0 WBC Epith Cast /hpf /hpf /lpf 1-3 4-6 0-0 15-20 12-15 10-12 2-4 1-3 12-15 8-10 0-0 0-0 0-0 0-0 0-0 APPEARANCE Y a PPT F Y CL PPT Y CL PPT F FEC Y a PPT F Y CL PPT F AVG. S. D. S. E. RAT Company Sanitized. Does not contain T S C A C B i GROUP: 3M DOSE: 10.0 MG/L SAHLE DATE: 19-MAT-83 SEX: MALE S!PECIES: RAT BIRTH DATE: 3-MAR-83 RBC ANIMAL#: /hpf 3*8392 348398 348399 348404 348405 348388 0-1 348389 0-0 348393 0-0 348416 0-0 348427 2-3 WBC Epith Cast /hpf /hpf /lpf 1-3 3-5 25-30 10-12 25-30 7-10 5-8 15-20 4-6 15-20 0-0 0-0 0-0 0-0 0-0 APPEARANCE Y CL PPT F Y a PPT F Y a PPT F Y a PPT F FEC Y CL PPT F FEC AVG. S. D. S. B. GROUP: 4M DOSE: 30.0 MG/L SAMPLE DATE: 19-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL#: 348397 348429 348'12 348417 348436 348396 348428 348434 348385 348407 RBC /hpf 0-2 0-0 0-0 1-3 0-0 /lp fWBC Epith Cast /hpf /hpf 0-2 5-8 15-20 4-8 8-10 0-2 0-1 3-6 0-3 4-6 0-0 0-0 0-0 0-0 0-0 APPEARANCE DY a PPT F FEC Y CL PPT F Y a PPT F Y a PPT F Y CL PPT F AVG. S. D. S . Ee &om "o,ar>vS3nftbe<f Ones notcontain TSCAGBit J tj HLR 273-85 APPENDIX VI PATHOLOGY REPORT NO n - 59 - Company Sanitized. Does not contain TSCA CBS / BM fS TV M 2 E. I. d u P o n t d e N e m o u r s & C o m p a n y INCOR RO * TTD Ha s k eu . Laboratory for Toxicology and Industrial Medicin e P.O . Box so . E lkton Road New ark. Delaw are 19711 central research and development department REVISED 4/4/35 SUBCHRONIC INHALATION TOXICITY TUDY IN RATS MARCH 28, 1985 Summary Male Crl:CD*(SD)BR rats were exposed by Inhalation at concentrations of 3.1, 10 or J^mg/LTfthours/day, days/week for 2 weeks. A compound-related effect was detected in the rats exposed to a concentration of 30 mg/L. No compound-related effects were noted in rats at the 3.1 or 10 mg/L exposure levels following the 2 weeks exposure or following a 2-week post-exposure recovery period. Introduction Groups of 10 young adult male Crl:CD(SD)BR rats each were exposed by inhalation to the test compound at concentrations of 0 mg/L (Group I Control), 3.1 mg/L (Group II - Low), 10 mg/L (Group III - Mid), or 30 mg/L (Group IV - High), 6 hours/day, 5 days/week for 2 weeks. Following the 10th exposure, 5 rats in each group were sacrificed and the remaining 5 were allowed to survive for 2 weeks and then sacrificed. At necropsy, represent ative tissue from liver*, kidneys*, lungs* heart*, spleen*, thymus*, lymph nodes (thoracic and mesenteric), adrenal glands, thyroid-trachea-esophagus, pancreas, urinary bladder, stomach, duodenum, jejunum, ileum, cecum, colon, brain, testes*, epididymides, sternebrae with bone marrow, eyes, nose and any other tissues with grossly observed changes were removed for histologic evaluation. (*0rgans weighed) ( j Q emnany Sanitized. Does not contain TSC CBI 2- - Results and Discussion The gross and histooorphologlc observations for Individual rats are listed In Tables I and II, respectively. Table III lists the Incidences of microscopic findings per group of rats. Compound-related effects were detected In the hlgh-exposure group (30 mg/L) rats. 2/5 rats had lesions In the nose (focal degeneration and regeneration/squamous metaplasia of the respiratory mucosa In the turbinates) following the 10th exposure and 1/5 had a similar lesion following the recovery period. No other compound-related effects were detected In the rats grossly or mlcroscogically. All of th^ histologic .findings as they are listed in Table II were believed to be incidental, spontaneous or the result of Intercurrent disease, and were not considered to be the result of exposure to the test compound. HHCC/WCK/wfd CHEN 1.30 Report w . Xg. Hans H. C. Chen, D.V.M. Senior Research Pathologist Approved by: William C. Kraus8, D.V.M. Manager, Pathology Division - 3- KEY TO TAM.Bfi Mode of Death SD Sacrificed by design Tissue Accounting N " Normal L =* Altered 0 - Tissue not present/insuffldent for evaluation 0 - Only one tissue present of paired organs/tissues Lesion Grading ~ = No lesion 1 = Mild lesion ' 2 = Moderate lesion P = Lesion present; severity not graded e <WnDarivSan?fi?ed Doeg nf confain TSCA cgp uc REVISED 4/4/85 - 4TABLE I gross o: EXPOSED TO AniBai Number Test Days Recovery Days Mode of Death Group I - Control - 0 ma/L Observations 348400 12 0 SD 348420 12 0 SD 348430 12 0 SD 348432 12 0 SD 348437 12 0 SD 348409 25 13 SD 348421 25 13 SD 348422 25 13 SD 348425 25 13 SD 348433 25 13 SD Group II - Low Level - 3.1 mg/L No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 348380 348391 348410 348411 348426 348381 12 12 12 12 12 25 348384 348387 348413 25 25 25 348418 25 0 0 0 0 0 13 13 13 13 13 SD No abnormalities detected SD Lungs - left lobe, white mottling SD No abnormalities detected SD No abnormalities detected . SD No abnormalities detected SD Thymus - left lobe, pink with dark red mottling SD No abnormalities detected SD No abnormalities detected SD Kidneys - slight hydronephrosis, bilateral SD No abnormalities detected Company Sanitized. Does not contain TSCA CBI - 5- Animal Number Test Days Recovery Days Node of Death . Group III - Intermediate Level - 10 mg/L Observations 348392 12 0 SD 348398 12 0 SD 348399 12 0 SD 348404 12 0 SD 348405 12 0 SD 348388 25 13 SD 348389 25 13 SD 348393 25 13 SD 348416 25 13 SD 348427 25 13 SD Group IV - High Level - 30 mg/L No abnormalities detected Brain - cut at necropsy Lungs - mottled white throughout No abnormalities detected Kidneys - right, hydronephrosis No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Kidneys - right, hydronephrosis No abnormalities detected 348397 12 0 SD No abnormalities detected 348412 348417 348429 348436 348385 348396 348407 12 12 12 12 25 25 25 0 0 0 0 13 13 13 348428 348434 25 25 13 13 SD No abnormalities detected SD Kidneys - hydronephrosis, bilateral SD No abnormalities detected SD No abnormalities detected SD No abnormalities detected SD No abnormalities detected SD Lungs - red foci scattered throughout left lobe, 1.0 mm in diameter Testis - left, small and soft SD No abnormalities detected SD No abnormalities detected i> 4 Company Sanitized. Does not contain TSCA CB! Company Sanitized. Does not contain TSCACBI REVISED 4/4/85 u n Ia SEX: MALE GROUP: ANIMAI NUMBER: DOSE: 0 MG/L TISSUES/OBSERVAT IONS kivcn MODE OF DEATH: OAVS ON TEST: davs on recoverv SD 12 0 SO 12 0 SD 12 0 SD '2 0 SD SD 12 25 0 ,3 SD 25 ,3 SD SO T 25 25 3 5 ! ] EXTRAMED. HEMATOPOIESIS, MARKED/NUMEROU kidnevs mi nu te he ceil foci NN N 12 N N N N NN HYDRSNERpH^sisHVAUNE DRPLET- "CAL d i f f u s e UNILATERAL NN NNN N N NN N c. =!!: KKSKiKt: SSSii; SSi. unilateral LUNGS * -- -- -- - -- PNEUMONIA. INTERSTITIAL. SUBACUTE. FOCAl HEART NN NNNNNNNN " -- SPLEEN THYMUS HEMORRHAGE. FOCAL. ARTIFACT LYMPH NODES. THORACIC NNNNNN NNN N NN NN N N N NN N NN NN NN NN NN " - - ADRENALS thyroid CYST. ULTIMOBRANCHIAL OUCT, UNILATERAL TRACHEA NN NN N0 0 NN M NN NNN N N N N N H N NNNNN NN N esophagus PANCREAS PANCREATITIS. SUBACUTE. FOCAL URINARY BLADDER PROTEINACEOUS PLUG BRAIN NH NNNNN N N N N H N N N N N. N N N NNNNNH NNN L -1 N N NNN N N N NN NN NNNN N NNN PARTi I I  6 Company Sarffized. des notcontain TSCCB1 REVISED 4/4/85 SUBCHRONIC STUDY SEX: MALE GROUP: TISSUES/08SERVAT10NS STOMACH DUODENUM JEJUNUM ILEUM CECUM COLON ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY : LYMPH NODES, MESENTERIC TESTES ATROPHY ATROPHY, UNILATERAL EPIDIDYMIDES GRANULOMA. SPERMATIC, UNILATERAL OLIGOSPERMIA, BILATERAL OLIGOSPERMIA. UNILATERAL STERNAL MARROW STERNEBRAE EVES NOSE DEGEN, A REGEN.(SO. MISCELLANEOUS METAp!). RESP. MUCOSA, SUBAC.,, FOCAL END OF GROUP 1 DUSE: 0 MG/L 348 400 SD L2 0 N 346 420 SD 0 N 348 430 SD 12 0 N 348 432 SD 12 0 N 348 437 SD 12 0 N 348 348 409 421 SD SD 25 25 13 13 NN 348 422 348 425 348 433 SD SD SD 25 25 2 5 13 13 13 NNN NN N NNN N NN N NN NNNNNNNN NNN NNN NNN N NN N NN NNNN N N N N NNN NNN N N N N 0 N N 0N N N NN N NN HN NN N N N N NN N L NN N -- p "-"-- NN N NNN NNN N N NN NNN NNN N N NN NNN NNN N NNNNNNNNN N 0 0 0 o O 0 0 0 00 PART: 2 confain TSCA REVISED 4/4/85 cr a a 3 Tff3i -3 OT 30 N3 s, o W ANIMAL NUMBER: t i s s u e s /o b s e r v a t i o n s LIVER MODE OF DEATH: DAVS ON TEST: DAVS ON RECOVEHV: EXTRAMEO. HEMATOPOIESIS. MARKEO/NUMEROUS MINUTE RE CELL FOC. KIDNEYS S RiTMSSisMV'L,Nt UHOf>LEr- t0BriC*`- 0FEUSt HYDRONEPHROSIS. UNILATERAL NEPHRITis' T N i i ! i IAL' CMH0N,C- TOC AL NEPHRITIS. INTERSTITIAL. CHRONIC. FOCAL. UNILATERAL LUNGS PNEUMONIA. INTERSTITIAL. SUBACUTE. FOCAL HEART SPLEEN thymus HEMORRHAGE. FOCAL. ARTIFACT L Y M P H NODES, TFIORACIC ADRENALS thyroid CYST. ULTIMOBRANCHIAL DUCT. UNILATCRAL trachea esophagus pancreas pancreatitis, subacute, focal urinary bladder proteinaceous plug brain D O S E : 3. 1 1M / L 348 3BO SO 1 0 N 348 391 SO 12 0 N 348 410 SD 12 0 N 348 411 SD 12 0 N " 348 426 SO 12 0 N - 346 361 SO 25 13 34B 384 SO 25 13 N 348 387 SD 25 13 N 348 413 SO 25 13 N 348 418 SD 26 13 N NN N NN NN LN N h N NN N N N N N NN N NN N N N N N N N NNN LNN NN P -- NNN0 NN NN N N NN NNN N NN N N N N N N N-- 0 N - N- N N N N N NN N N N N N N N NNN NNN NN N N N N" N" N- N- N- N N pL N N pL L P L P N - L P N N N N N HN N N N N N PART Somsany S a^zed. Doss no! contain TSCACBS REVISED 4/4/85 subchi TISSUES/OBSERVATIONS STOMACH DU OENUM JEJUNUM ILEUM CECUM cce COLON LVMPH n o d e s , m e s e n t e r i c TESTES A70PHV ATIOPHV. U N I L A T E R A L EPIDIDYMIDES OLIGOSPERMIA, UHILATERA1 STERNAL MARROW SEA: MALE C R O U P : II ANIMAL NUMBER: MOOE OF DEATH; OAVS ON TEST: DAVS ON RECOVERY- OSE: 3.1 MG/L 348 380 SO 1? 0 N N N N i N N N 348 391 SO )2 0 N N N N N N N N 348 410 SO 12 0 N N N N N N 0 N 348 411 SO 12 0 N N N N N N N L 1 348 426 SO 12 0 N N N N N ti N N 348 381 SO 25 13 N N N 0 N N N N 348 384 SD 25 13 N N N N N N N N 348 387 SO 25 13 N N N N N N H N 348 413 SO 25 13 N N N N N N N N 348 418 SO 25 13 N N N N N N N N NN NLNNNNNN -- - 1 __ - -- - - STERNEBRAE EVES NOSE D E G E N . & R E G E N . (SQ. M E T A P . ', miscellaneous Re s p . m u c o s a , subac E N D O F C R O U P .II focal NN NH NNNHNN NN NNN N NNN N NN NNN NN NN N NN NNNNNN N N oo 0O " OOOOO PART: 2 I vO I j Company Sanitized. Does not contain TSC CBF c si.- REVISED 4/4/85 HN-I 4808 T A B L E II: I N D I V I D U A L A N I M A L M I C R O S C O P I C D A T A SUBCHROjjlC INHALAATION TOXICITY STUDY SPECIES: RAT SEX: MALE G R O U P : III D O S E : IO M G / L ANIMAL NUMBER: TISSUES/OBSERVAT IONS MODE OF DEATH: DAVS ON TEST: days on reco ver y: LIVER EXTRAMED. HEMAIOROIESIS. MARKED/NUMEROUS MINUTE RE CELL FOCI KIDNEYS DHEVGOEHNOENREAPTHIROONS.I S H Y A L I N E D R O P L E T . C O R I I L A L . HYDRONEPHROSIS. UNILATERAL NEPHRITIS, INTERSTITIAL, CHRONIC. FOCAL NEPHRITIS, INTERSTITIAL, CHRONIC. FOCAL. DIFFUSE UNILATERAL IUNGS PNEUMONIA, INTERSTITIAL, SUBACUTE. FOCAL HEART SPLEEN THYMUS HEMORRHAGE, FOCAL, ARTIFACT 348 392 5D 12 N N _ - N N N N 348 398 SO 12 0 N N - N N N N 348 399 SD 12 0 L P N N N N N 348 404 SO 12 0 348 405 SO 12 0 NN tN - -- 1- 1 NN " NN NN N .N 348 3B8 SO 25 13 N - N - - N " N N N 348 389 SD 25 13 N - N - - N " N N N 348 393 SD 25 13 N - N _ - - N - N N N 348 416 SO 25 13 N L _ 1 - i N - N N N 348 427 SD 26 13 N N _ N N N N LYMPH NUDES. THORACIC ADRENALS THVROID C Y S T , l)L T I M O B R A N C H 1 A L D U C T . U N I L A T E R A L TRACHEA ESOPHAGUS pancreas PANCREATITIS. SUBACUTE. FOCAL N N0 NN0 NN N N N N NNNN NN N N N N LNNNNN N N "P ' -- -- - - N N N NN N N N N N N N NNN N NN NN N N NN N N N N N N URINARY BLADDER PROTEINACEOUS PLUG brain -N L N L N L N L N N -- p p P -P - " NNNNN N NNN N PART : I I 0 1 Company Sanitized. Does HN- I4BOH REVISED 4/4/85 iuacHRONIc SEX: MALE GROU P : III ANIMAL NUMBER: D O S E : IO M G / L T ISSUES/OBSERVAT IONS STOMACH DUODENUM JEJUNUM ILEUM CECUM cv C O L O N LYMPH NODES. MESENTERIC TESTES ATROPHY ATROPHY, UNILATERAL EPIOIOVMIDES MODE OF DEATH: DAVS ON TEST: DAVS ON RECOVERY 3BB 4U4 405 3AA n o I,,r SD SD SD SD SD SD *12 4,6 427 ?! " '2 12 12 i1"2 ?? 5? S? SD SD 0 0 0 ' 0I 13 ' 3 2135 13 2135 NN N NNN NNNN N N N NNN N NNN NN N NNN NNN N N NN NN N NNN N MN H NN NNNH N H N NNNH N NH N NN NNN H N naj N KN1 N N N N N N H N N ~- - --- _ " OLIGOSPERMIA, UNILATERAL STERNAL m a r r o w NN N NN N NNN N - - _I --- ~ - -- -- --- sternebrae eves NOSE D E G E N . & R E G E N . ( S O . M E T A P . , . R E S p. M U C O S A . 5 u b a c MISCELLANEOUS , focal NN NNN NN N N N N N i< N N ti N H N N NNNNNNNH NN N N N ti N N N N N "-- E N D O F G R O U P III 00 00000 000 PART '.a " l" W i g P | i Company Sanitized. Does not contain TSCACBi REVISED 4/4/85 SUBCHfi SPECIeS: SEX : MALE GROUP: IV DOSE: 30 MG7L ANIMAL NUMBER: TISSUES/OBSERVATIONS LIVER MOOE OF DEATH: BAYS ON TEST : DAJ ON RECOVERY: e x t r a m e o . h e m a t o p o i e s i s , m a r k e d /n u m e r u u s MINUIt Nt CELL KIDNEVS D E G E N E R A T I O N . H Y A L I N E D R O P L E T c o r t u -ai hydronephrosis l o r i i l a l . DIFFUSE hydronephrosis, unilateral ! I ^ H 2., T , S - i n t e r s t i t i a l . C H R O N I L F O L A I NEPHRITIS, i n t e r s t i t i a l , c h r o n i c ] FOCAL. LUNGS unilaieral pneumonia, interstitial, subacute, focal FOCI HEART SPLEEN t h /m u s HEMORRHAGE, FOCAL, ARTIFACT LVMPH n o d e s , t h o r a c i c ADRENALS thyroid CYST. ULTIMOBHANCHIAL DUCT. UNILATERAL trachea ESOPHAGUS pancreas p a n c r e a t i t i s . SUBACUTE. FOCAL urinary bladder proteinaceous plug brain 348 348 397 so 412 SO 12 '2 00 NN 34B 417 SD 12 0 N 34B 429 SD 12 0 N 348 348 436 so 385 SO 12 25 0 13 NN 348 396 SO 26 13 N - 34B 407 SO 26 13 N - 348 428 SO 25 13 N - 348 434 SD 26 13 N - N N L N L p N N N N N -1 "- -- 1 - - -- 1 "* - N N NNNN NLN N " 1- - NN N NN N NN N N NN NNNNNNN N NN NNNNNNN N ~- - - 0N NNNNNNNN NN NNNN NNN U N N NN N N NN NN " -- N N NN N N NN N N NN N N N NNN N N N N N N NNNNN " -- - N L P N - N - N N. L P N NN NN NNN NNNH N PART.- i I to I Company Sanitized. Does not contain TSCACBf H H - 14 B 0 8 REVISED 4/4/85 : SUBCH|PNI C INHALATION TISSUES/OBSERVATIONS STOMACH SEX: MALE G H O U P : IV ANIMAL NUMBER : MODE OF DEATH: DAVS ON TEST : DAVS ON RECOVERY : duodenum jejunum ILEUM cecum COLON LVMPH NOOES. MESENTERIC TESTES ATROPHV atrophv, unilateral epididvmides g r a n u l o m a . SPERMATIC. UNILATERAL OLIGOSPERMIA. BILATERAL OLIGOSPERMIA. UNILATERAL STERNAL MARROW STERNEBRAE EVES NOSE DEGEN. & R E GEN. (SO. ME TAP.') , MISCELLANEOUS WESP. M U C O S A , S U B A C .,, F O C A L END OF G R O U P IV RAT DOSE: 30 MG/L 34b 397 SO !2 o 348 412 SO 12 Q 348 417 SO 12 nVI 348 429 SO \2 0 348 436 SO 12 0 348 385 SO 25 13 348 396 SO 25 13 348 407 SO 25 13 34B 42B SO 25 13 34B 434 SD 25 13 NN N NN N N NNN NN N NNN N NNN NN N NNN N NNN NN N NNN NNNN NN N NN N NNN N N N N N N N NN NN 0 0 N 00N NNN0 N NN NNN NLNN " -- - -2- - NN NNNNNLNN - - - - - -_ I: ~" - 2 - - NN N NNN NNN N NN N NNN NNN N NN N NNN NN NN N L 1 N N L N N L N N 1 * 1~ - 00 0000O0 0 0 PART TM H/H/OD pe^iusAu s u io q C.N, OCI <p 3 a O O 3 S' 3* USSUE/LESION: =o= = aao = = = c<lasae. LIVER LESION CRADES: CROUP DESIGNATION- d o s e (MG/L): ==i2;?;f;is=SB=ssai=_NNUUMMBBEERR lINN GG RRO0UUPP;. kioneT " 6 0 ' HEMATOPO,BSIS- m i n u t e r e CELL f o c V NV0R0NEPMR0sisHVAL,NE 0R0PLET- CORTICAL. DIFFUSE E 2 E ? ? * 0 ?*?; U N il a t e r a l N E P H R I T I S . ' I N T E R ST I T 1 A L ' irH f , 0 N , t - I'U L A L LUNGS CHRONIC. FOCAL. UNI LAIERAL 1 0 10 10 10 P n e u m o n i a , i n t e r s t i t i a l , s u b a c u t e , f o l -a . heart SPLEEN thvmus hemorrhage, f o c a l , artifact lvmph nodes, thoracic AORENALS thvroid CVST. ULTIMOBRANCHIAL DUCT. UNILATERAL trachea esophagus pancreas Pa n c r e a t i t i s , Su b a c u t e . FOCAL URINARV BLADDER PROTEINACEOUS PLUG BRAIN stomach 10 10 10 10 __ B _ 10 10 10 10 10 1 ( - . 1I . - . - . - ) 10 " 10 >0 11 3. 10 III 10 10 " "ttios-jj, 10 10 1 (1, 10 10 ( -. I.-.-.- > 2 IV 30 (0 B S C B b b S 8 B S 8 >seeane: 10 10 1 (I.-,- 1 cI 120 2 < .2.-.- -) 1 (-. I (-.1.- 10 10 1 (-.1 10 10 10 10 10 10 10 I 10 10 _9_ 10 9 _B_ 10 10 9 10 10 10 10 10 -- =- 10 - ifi_ 10 10 10 10 10 5 (S . 10 10 to > (4 .- . 10 10 10 " TT( 10 - L 2 roa MN- 14808 REVISED 4/4/85" JAULE: III; I N C I D E N C E S O F N O N - N E O P L A S T I C L E S I O N S SUBCHRONIC INHALATION TOXICITY STUDY S E C I E S : RAT C O M P O U N D : A ---- V PART: TISSUE/LESION: LESION GRADES: (P.1,2,3,4) MALES G R O U P D E S I G N A II ON; DOSE (MG/L): NUMBER IN GROUP: I 0 10 DUODENUM JEJUNUM ILEUI CECUM COLON LVMPH NODES. MESENTERIC TESTES atrophy ATROPHY. UNILATERAL epididymides GRANULOMA. SPEN'-AIIC, U N U A I t R A t OLIGOSPERMIA, B ' l ATERAL OLIGOSPERMIA. UNILATERAL STERNAL MARROW STERNEBRAE o o 3 EVES NOSE O)I D E G E N . R E G E N . (SO. Q) M I S C E L L A N E O U S ar-3 gNOTES ME T A P .J , RESP. MIILOSA. SUBAC .. FOCAL a aa an _10 10 10 10 10 a 10 _ 10 1 ( 1.- 10 10 10 10 0 11 3. 1 10 III 10 10 SBSSSSassSBSBtBBBBaSK 10 10 10 10 __ 9 _ 10 10 10 10 10 __ 9__ 10 10 1 ( -. 1 10 - * 10 10 1 (-,.1. 10 " 10 10 10 10 10 10 10 0 IV 30 10 >B833B3esSB8 10 10 10 10 10 5 10 11 10 _ 11 10 10 10 10 S" ( 0 Ui 9 0FTN _ _ ,.s 5? 2 >$