Document 82qpBGR1yxDm4VQzYk7NB5mkB

FOR DU FONT USE ONLY AR226-2792 Subchrontc Inhalation Toxicjty of Haskel! Laboratory Report No. 273-85 MR No Haskell E. I. du Pont de Nemours and Co., Inc. Laboratory for Toxicology and Industrial P. 0. Box 50, Elkton Road Newark, Delaware 19714 Medicine Date Issued: July 16, 1985 Company SanSized. Does not contain TSCA CBI Subchronic Inhalation Toxiclty of HtR 273-85 SUMMARY of|^fin Three groups of 10 male Crl:CD*(SD)BR rats eact^ey exposed 6 hours/day, 5 days/week for 2 weeks to 3.1, 10; or 30 mg/L air. A control group was exposed simultaneously to air only. At me end of the exposure period, blood and urine samples were collected for clinical analyses, and 5 rats per group were killed for pathologic examinations. Remaining rats were observed for 13 days post exposure, and then subjected to the same clinical and pathologic evaluations. Na&al_rc1tat1on was histploglcally observed In 2 of 5 rats exposed to 30 mg/L olMHwapor and sacrificed Immediately after the 10th exposure. Thirteenaays later, nasal Irritation was found In 1 of 5 rats from the same group. When compared to controls, rats In the 30 mg/L group had elevated serum aspartate aminotransferase activity and decreased cholesterol concen trations Immediately after the 10th exposure. Thirteen days later, these values were similar to those of the control rats. During the exposure and recovery periods, mean body weights and clinical signs for all rats were similar for control andfl^Kfcxposed rats. There were no biologically significant effects seen in rats exposed for 2 weeks to 3.1 or 10 nig/I, of PFBI vapor. 2 - ^"'""""""'-"------"oWnTSCACB, HLR 273-85 Work by: / ^ ^ ^ ^ ^ ^ir Clarence M. Hutt. Technician 6 ISIPS- JW^^ ^''^ L^ Robert T. Turner Technician ^MUS< Supervised by; ura A. KinnejT Chemist Report by; ^^fM^ -^^ ^ David P.jkellar ^/</7S <'i^' Study Director: A^ ^ ^ ^ y ^ HNa&nMcyMZgC^.hCrUommfefym.p^igb. Section Supervisor, Acute Investigations (e/ep/^r Approved by: /J^/. /^^\ r Dtvitf F. Krahn. Ph.D. Manager, Toxicology 7lrtl^ Acknowledgements: Thomas A. Kegelman and Bruce A. Burgess also participated in the conduct of this study. DPK:tak:smk:HLR9.5 - 3 - Company Sanitized. Doss not contain TSCA.CBS Haskell Laboratory Report No. 273-85 j Haskell No. 14.808 Material Tested: Sponsor: Material Submitted By: Test Facility: Study Initiated-Completed; Chemicals and Pigments Department E, I. du Pont de Nemours and Company Hilmington, Delaware Chemicals and Pigments Department Jackson Laboratory E. I. du Font de neniours and Company E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine P.O. Box 50, Elkton Road Newark, Delaware 19714. 4/25/83 - 5/19/83 There are 74 pages in this report. Distribution: - 4 - Company SanHSzed. Doss no? corstais TSCA C3I TABLE OF CONTENTS HLR 273-85 Summary General In.fo.rm.a.tio.n........................ 2 Introduction ....................... 4 Materials and .M.eth.od.s....................... 6 Results ...................... 6 Conclusion.s............................. 9 Figure I - Gr .ow.th.... Curve. ..................... 10 ..................... 11 oljUBT Appendix I - Daily Atmospheric Concentrations . 13 . Appendix II Mean Body Weights. ................. Appendix III - Mean Organ Heights. . . . . . . , - . . . . Appendix IV - Mean Organ-to-Body Weight Ratios e = c . . . . . . . . . . Appendix V - Clinical Pathology Report No/HBlJ. ................... Appendix VI - Pathology Report NoJfHB( 15 . 19 23 27 59 5- ^"----------------------.^ INTRODUCTION HLR 273-85 jJiBlJr85 very low toxicity on an acute inhalation basis. Th ^ryjjjjr approximate lethal concentration for this material was 160 mg/Ll__ ' The purpose of this study was to detennineJhgJLoxic effects oifTreppeeaatied Inhalation of sublethal concentrations Except as documented In the ofjfff study records, this study was conducted according to the applicable Good Laboratory Practice Regulations. MATERIALS AND METHODS A. Animals Young adult male CN:CD*(SD)BR rats were obtained from Charles River Breeding Laboratories, Kingston, New York. Each rat was assigned a unique 6-dlglt 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 peri ode During the test, rats were housed In pairs in 8" x 14" 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 gram^jrape exposed whole-body to vapor concentrations of 3.1, 10, or 30 mg/L^UQn air. A control group with rats weighing between 219 and 244 grams war 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; Company SanIGzea. Composition: HLR 273-85 Synonyms: CAS Registry No.;^ Stability: The test material was assumed to be stable throughout the exposure phase of the study. 0. Atmosphere Generation Gas atmospheres ofJUyMere generated by pumping the liquid into a round bottom flask which was at ambient temperature for the 3.1 mg/L concentration but was heated to about 50-60C to generate the 10 and 30 mg/L concentrations. The resulting vapors were carried by houseline air to the 17 liter glass exposure chambers. E. Analytical iffftras The atmospheric concentration of^^----P^asdetermined at approximately 30-minute intervals by drawing samlpileess of the test atmosphere from each exposure chamber with a glass syringe. Samples were analyzed with a Hewlett-Packard 5790A gas chromatograph equipped with a flame ionization detector and a 6' X 1/4" 0.0. glass column packed with 101 SE 30 on Supelcoporf. Concentrations were determined by comparison with standard curves, which were-DrfiDared daily. Gas standards were prepared by evaporating 1iquio|^Hnn 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 225 Oxygen Analyzer. F. Clinical Measurements Urine samples were collected overnight from 10 rats per group after the 9th exposure, and from 5 rats per group on the 12th day of recovery. Samples were analyzed for volume, osmolBitty, pH, blood, sugar, protein, Company SanffFzed. Doss not conla'n TSCACBg HLR 273-85 blllrubin, uroblllnogen and ketone. Each specimen was noted for color and transparency, and the sediment from each sample was examined microscopically. Blood samples were collected from the tails of all rats after the 10th exposure, and from 5 rats per group on the 13th day of recovery, Samples were analyzed for erythrocyte count, hemoglobin concentration, mean corpuscular volume, platelet count, leukocyte count, and relative numbers of neutrophlls, band neutrophlls, lymphocytes, atypical lymphocytes, eoslnophlls, monocytes and basophlls. Hematocrit, mean, corpuscular hemoglobin and mean corpuscular hemoglobin concentration were calculated from the erythrocyte data. In addition, serum activities of alkaline phosphatase, alanlne aminotransferase and aspartate annnotransferase, and serum concentrations of urea nitrogen, creatlnlne, total protein and cholesterol were also measured. G. Pathology Five rats per group were killed after the 10th exposure, and the remaining 5 rats per group were killed on the 13th day of recovery for gross and histopathologic examinations. Rats were killed by chloroform asphyxlatlon. Organs and tissues examined were the heart, lungs, nasal cavitlfcles, mesenteric and thoracic lymph nodes, trachea, liver, pancreas, esophagus, stomach, duodenum, jejunum, lleum, cecum, colon, kidneys, urinary bladder, bone marrow (sternal), spleen, thymus. thyroid, testes, epidldymldes, adrenal glands, brain and eyes. H. Organ and Body Weight Analyses Mean body weights for test rats were compared to controls during the exposure and recovery periods. In addition, at each sacrifice, mean organ weights and organ-to-body weight ratios were calculated for the heart, lungs, liver.. spleen, kidneys, testes, and thymus. Data were statistically analyzed by a one-way analysis of variance-. Test rats were compared with controls by least significant difference and Dunnett's tests when the ratio of variance (F) indicated a significant among-towithin group variation. Significance was judged at the 0.05 probability level. Steel, R.G.D. and Torrle, J.H. Principles and Procedures of Statistics. 2nd.edition. MeGraw-Hlll Book Company. Inc., 1980. 8 " Company Sanreised. Doss not contasn TSCA CB( HLR 273-85 I. Records Retention All raw data (Including tissue slides and paraffin blocks) and final reports will be stored in the archives of Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware, or in the OuPont Hall of Records, E. I. du Pont de Nemours and Co., Milmington, Delaware, RESULTS A. Exposure Conditions Chamber tempe-atures ranged between 22-36C, relative humidities ranged from 36-591, and chamber oxygen concentrations were 211. Overall mean atmospheric concentrations and standard deviations are presented below. Daily atmospheric concentration data are presented in Appendix I. Atmospheric Concentrations (mg/L) of During Ten Exposures Design Concentration Analyzed Concentration (mg/L) Mean S.D. Range 3 3.1 0.4 2.2-4.7 10 10 0.8 6.2-12 30 30 '2.0 21-35 Mean, S.D. and Range represent all samples from all exposures. 8. Clinical Observations tyfywere Mean body weights for rats exposed indistinguishable from those of the controls during both the exposure and the recovery periods. During the exposure period and the recovery period, clinical signs for all rats exposed tu----kere also indistinguishable from the control group. Mean body weignts^re presented in Appendix II. A growth curve is attached as Figure I. C. Organ Weight Analyses When compared to the concurrent control group, the mean kidney/body weight ratio in the 10 mg/L exposure group was elevated at the end of the - 9 Company Sanresd. Does not contain TSCA CBB HLR 273-85 recovery period but was"not absence of a dose-response elevated after the final exposure. In the findings, the kidney w e i g h t r ela inc t r ions ease hip wa s or n o s t upportive patholo considefied^abe g i c a l biologically significant. were indistinguishable Organ weights in all other||fpxposed rats and organ-to-body weighftrormatitohsoseareofptrheesenctoendtraoslsA. ppNenedaincdersgaInII waenidghItVs , D. Clinical Pathology IncrreeA.a.fs.te.e.rin1.0see^rxuupmaousu.cre:s,,, rrdattss exposed to 30 mg/L offV|fUe^xihxibbib1itteedd an serujmm c o n c e n t r a t i o a n spa of rtate aniino chhonlleosctefwroiil t ransferas c---om-p-a--re-d' e a ^to- c t i v i t y - and a decrease in ences between control and test rats were not controls. These differ evident at the end of the erxepcoosveedrytope3r.i1odo. r N1o0.0clmingi/cL aalltyesitihgenrifiscaacnrtificchean. gesTheweCrelinoibcsaelrved in rats report is attached as Appendix V. Pathology E. Pathology offend Two of 5 rats exposed to 30 mg/L the 10th killed immediately exposure showed nasal degeneration/regeneration with irritatioh characterized by mild after focal nasal turbinates. Thirteen squamous days later. metaplasia 1 of the 5 in the mucosa remaining of the wgreoreupcoshnoswideedresdimuinlarer lantaesdal toirrthiteattieosnt . All other rats in this pathological findings attached as Appendix VI. treatment. The Pathology report is CONCLUSIONS NasaUnntation was observed mg/L off----lvapor and sacrificed hi stologically in 2 of 5 rats exposed to 30 Thirteen aays group. later, nasal immediately after the irritation was found in 1 of tenth exposure. 5 rats from the Increased serum aspartate cholesterol concentration ami notransferase activity and same decreased 10th exposure. Thirteen were observed in the 30 days later these values mg/L group following the control changes rats. 'me serum aspartate are suggestive of a m i n o t r a n s f e r a we se r e a s ct i i mila vity r a to nd those of the cholesterol of supportive histological a minimal findings, hepatic effect; the biological however, in the absence clinical changes is unknown. significance of the There were weeks to 3.1 or no biologTcaUv^ignifleant 10 mg/L offlfivapor. effects in rats exposed for two 10 Company SanSlzed. Does not contain TSCACBi n--Bawnn. ----OUM DAYS ON TEST nuEBinuTE HTf 12 - Company Sanitized. Does not contain TSCA CBI .1 ^ HLR 273-85 APPENDIX I DAILY ATMOSPHERIC CONCENTRATIONS 01 N ^ Company Sanitized. Dess not confasn TSCA CBi APPENDIX I DAILY ATMOSPHERICCONCENTRATIONOSpt HLR 273-85 A. Desf 1 2 3 4 5 6 7 8 9 10 Overall 3.5 3.2 3.1 3.1 3.1 2.8 3.4 2.9 2.8 3.0 XT 0.6 0.3 0.2 0.2 0.4 0.5 0.2 0.2 0.2 0.4 0-.-7 8. Design Concentration of 10 mg/L 1 2 3 4 5 6 7 8 9 10 Overall 9.97 Q 7 / 10.1 10.1 10.1 10.1 10.3 10.2 10.0 10.0 ToTo 0.6 1.2 0.5 0.7 1.1 0.6 0.7 0.7 1.3 0.6 '078 C. Design Concentration of 30 mg/L 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 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 5 6 7 8 9 10 Overall 29.5 28.4 30.3 29.4 30.4 29.7 30.7 29.7 29.6 29.5 2977 2.0 3.1 0.7 2.3 2.7 2.3 1.4 1.4 0.8 1.3 ~ro 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 21.2-34.9 CompanySanitized. Does no! contain TSCA CB! 14 HLR 273-85 APPENDIX II MEAN BODY WEIGHTS - 15 - CompanySanfEizsd DDoae^3 n0^. contain TSCA CB? [ -- J H - I1H-14808 _ -- SSuumnamnaarny' TTaable HLR 273-85 GROUP Control Low Intermediate High ANOVA(l) TREND(2) LSD(3) DUNNETT(41 BARTLETT(5) TEST DAYS 1. 2. 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.?876 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. 10. 11. 12. Control Low Intermediate High ANOVA(l) 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 14.9W4 0.009 299.3 297.7 294.8 291..0 0.548 0.157 12.3571 15.0355 0.025 308.4 309.2 305.3 300.6 0.589 0.216 13.9009 16.9139 0.076 310.5 309.5 304.9 303.4 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 SIGNIFICANT" DIFFERENCE - given a significant (a1pha=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 iiore 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 CONTROL GROUP by LSD. # SIGNIFICANTLY DIFFERENT (P<0.05) from CONTROL GROUP by DUNNETT TEST AND LSD. Company Sam-f^ ,, Doesoofc0^^^ GRCUP CONTROL LOW INTERNED:IATE HIGH ANOVA(l) TREND(2) LSD{3) DUNNETT(4) BARTLETT(5) 14808 ^^Summa^r TTiable 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 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 UKLIW TEST DAYS 22. 23. 24. 25. COHi^iji LOW INTERMEC IATE 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 f ^ e ANOVA(l) TREND(2) 0.740 0.715 0.772 0.908 LSD(3) 0.517 30.7882 0.368 30.8363 0.504 0.539 DUNNETT(4) BARTLETT(5) 38.1966 38.2563 32.1534 39.8903 3355.4150 4433.9367 0.165 0.129 0.111 0.097 (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. (3) (* LEAST indicates P value less than 0.05) SIGNIFICANT DIFFERENCE - any two given a significant (alpna=0.05) F RATIO, with a means differing by more positive (alpha) than the LSD are significantly different (4) DUNNETT', ^ST than the DUNNETT any error treatment mean rate of 0.05. differing from the control by with a statistic variable-wise false is significantly positive (alpha) different from the mean control more mean (5) BARTLETT'S TEST FOR EQUAL VARIANCE error rate of 0.05. + SIGNIFICANTLY DIFFERENT (P<0.05) P.VALUE. from CONTROL b;^OUP SIGNIFICANTLY DIFFERENT (P<0.05) from CONTROL GROUP bbyy DLUSONN. ETT TEST and LSD Company Sanitized. Does not contain TSCA CBB 17 - 81 ISO VOS1 isjBluoo iou SSOQ pszHsues Auedmoo HLR 273-85 APPENDIX III MEAN ORGAN WEIGHTS ^s, ^ ^r ^pany Sanded n ^^an.TSCAcs, - 19 - H-14808 MeaannAossooTTSSlie Weight Table 0 Days Rec. HLR 273-85 GROUP CONC. BODY WT. 0 mg/L 3.1 mg/L 10 mg/L 30 mg/L 307.8( 310.8( 307.2( 302.8( 0.000) 0.731) 0.945) 0.568) TEST TEST - HOMOGENEITY TREND BARTLETT'S TEST 0.828 0.503 0.640 HEART 1.030( l.l08( 1.014( 1.050( 0.000) 0.049) 0.667) 0.592) 0.094 0.772 0.526 LUNGS 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( 11.194( 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) 0.499 0.856 0.530 KIDNEY 2.550( 2.724( 2.658( 2.836( 0.000) 0.294) 0.510) 0.094) 0.372 0.138 0.771 GROUP CONC. TESTIS THYMUS 0 mg/L 3.1 mg/L 10 mg/L 30 mg/L 2.952( 2.752( 2.844( 2.868( 0.000) 0.374) 0.628) 0.706) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.837 0.820 0.855 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 OF TREATMENT MEAN TO CONTROL MEAN. + - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD # - SIGNDUIFNICNAETNTT'SLY DTEIFSFTERENT (P<0.05) FROM CONTROL GROUP BY LSD AND HOMOGENEITY - P VALUE OF F TEST OF WHETHER TREND - P VALUE OF F TEST OF WHETHER THERE CHANGE IN GROUP MEANS. GROUP MEANS ARE IS DOSE-RELATED EQUAL. BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE p0 _ Company Sanitized. Does not contain TSCA CBj GROUP (-- ^14808 Mean Absolute Weiight Table 13 Days Recovery BODY WT. HEART HLR 273-85 LUNGS CONTROL LOW INTERMEDIATE HIGH 386.8( 388.4( 379.2( 378.8( 0.000) 0.925) 0.655) 0.639) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.908 0.539 0.097 GROUP LIVER 1.186( 1.260( 1.236( 1.286( 0.000) 0.348) 0.523) 0.210) 0.614 0.271 0.070 SPLEEN 1.740( 1.804( 1.642( 1.666( 0.000) 0.518) 0.327) 0.456) 0.357 0.228 0.740 KIDNEY 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 0.700( 0.734( 0.724( 0.690( 0.000) 0.499) 0.632) 0.842) 0.793 0.800 0.058 THYMUS 2.932( 3.096( 3.198( 3.050( 0.000) 0.415) 0.193) 0.555) 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 Q.346 0.217 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. RARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE 21 Company San^erf. Does not contain TSCA CBf HLR 273-85 Company Sa^ed. Does notcontafn TSCACBg 22 - HLR 273-85 APPENDIX IV MEAN ORGAN-TO-BODY WEIGHT RATIOS - 23 CompanySanitized. Does not contain TSCA CBI I------W-14808 MearT Relative Height Table 0 Days Recovery HLR 273-85 GROUP CONC. HEART LUNGS LIVER 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 BARTLE.T'S TEST 0.164 0.786 0.640 GROUP CONC. SPLEEN 0.474( G.485( 0.491( 0.478( 0.000) 0.674) 0.508) 0.871) 0.910 0.817 0,858 KIDNEY 3.612( 3.820( 3.643( 4.021( 0.000) 0.198) 0.844) 0.018) 0.064 0.048 0.065 TESTIS |te"1^!^I'-mg/L I'O mg/L 30 mg/L 0.196( 0.225( 0.211( 0.208( 0.000) 0.141) 0.441) 0.530) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.507 0.717 0.436 GROUP CONC. THYMUS 0.828( 0.876( 0.864( 0.936( 0.000) 0.259) 0.388) 0.018) 0.105 0.028 0.460 0.961( 0.882( 0.929( 0.947( 0.000) 0.265) 0.646) 0.842) 0.682 0.980 0.152 0 mg/L 3.1 mg/L 10 mg/L 30 mg/L 0.203( 0.211( 0.232( 0.204( 0.000) 0.598) 0.078) 0.928) TEST TEST - HOMOGENEITY 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 Sanitized. Does nolconlainTSCACBS GROUP flAn-14808 Mean Relative Weight Table 13 Days Recovery HEART LUNGS HLR 273-85 LIVER CONTROL LOW INTERMEDIATE HIGH 0.307( 0.325( 0.327( 0.340( 0.000) 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 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 ft - 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 CHANGE IN GROUP MEANS. BARTLETT'S TEST - P VALUE OF TEST OF THERE IS DOSE-RELATED HOMOGENEITY OF VARIANCE 25 Company San'daed. Does not contain TSCA. CBj HLR 273-85 CompanySan'rtized. Does nol contain TSCACBj 26 - , HLR 273-85 APPENDIX V CLINICAL PATHOLOGY REPORT NO. The Clinical Pathology Report is signed by C. C. Matarese and R. M. Everett. Ms. Matarese prepared the report. Or. Everett interpreted the data. The design concentrations cited in the report are accurate to 2 significant figures. Company Sanitized. Does not contain TSCA CBj eo-iwi (gffPB) ESTUUUCOIWl E. 1. OU PONT DE NEMOURS & COMPANY INCORPORATED HASKELL LABORATORY FOR TOXICOLOGY AND INDUSTRIAL MEDICINE ELK70N ROAD, NEWARK, DELAWARE 19711 CENTRAL RESEARCH AND DEVELOPMENT DEPARTMENT JLIKICAL PATHOLOGY REPORT NO. SubacuCe Inhalation Toxicity o Medical Research Project No' Haskell Labora;ory No. 14808 . August 23, 1983 Suni.-nary .^lale CD rats were exposed by innalation ccfU^Hat concentrations [ ^ of 0.0 (concrol), 3.1, 10.0 and 30.0 mg/L. - 3 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 ag/L exposure concentration was considered to be a no-effect dose for the hematologic and clinical chemical parameters measured under the conditions of this study. Procedure Four groups of ten male CD^^rat^were exposed, by inhalation, for six of 0.0 (control), 3.1, 10.0 an'd30.^ig/L^^^^^^^^^^ After the ninth exposure, an overnight (16 hour) urine specimen was collected from each rat to measure volume (VOL), osmolality (OSMOL) and pH; and Co determine the presence of blood, sugar (glucose), protein, bilirubin, urobilinogen (UROBL) and ketone. The appearance (color and transparency) of each specimen was recorded and the sediment from each was microscopically examined. Company SanTRzeS. Does naS eanfam TSCA CBI - 2 - After the tenth exposure (End-of-Exposure, 0-Day Recovery), blood was taken from the tail 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 laukocytes were calculated from the leukccytic 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 (GREAT), 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) and_)unnett tests were made between the control rats and the rats exposed toyH^B| Significance was judged at the 5% probability level using the Dunnett criteria. Results The results for the hematologic and clinical chemical measurements are summarized in Table I - parts 1 co 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-oucs attached to this report. tcgU^t Statistical analysis of the daca.mdieateJ chat male C3 rats exposed for six hours per day for ten days thtt highest concentration (30.0 mg/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. l w " Following a recovery period' of 13 days, the low-dosed rats (3.1 mg/L) excreted uriinngewjwiitth a higher solute concentration. Urine urobilinogen levels in alJH^K'fcexposedgroups were higher than the controls. ^^y^iv^ooe3^ contain TSCACB& '} Discussion and Conclusions The statistically significant increase in the serum activity of AST/GOT and decrease in the serum concentration of cholesterol observed for rats exposed to the high dose (30.0 mg/L) oa^ffwere interpreted as evidence of a treatment-related hepatic effecc^^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. M3 The 10.0 mg/L exposure concentration o<|IHiJaas interpreted to be a no-effect dose for the hematologic and clini ical cneamical parameters under the conditions of this study. CCM/RME/wfd Report by: t s ^ ^ ^ C . C , a t L. her ^ in L e ^L C. A- M A at ^arJ^es-0e^ Technician ^:g=1<^^J^^ Approved by;'=1StfR*aa1yyfmKmo^onnddM'(^M..I'kEEv^v<e^r-e-t_t,_D_._V._M_..__Ph_.D_. Coordinator, Clinical Pathology Company Sanitized. Does not contain TSCA CBI j U TESTS RBC MM/mo Hb B/dL Ht % MCV CL MCH pg MCHC g/dL PLAT M/mm .IABLEJ pa ^ SUMMARY OF HEMATOLOGIC FINDINGS IN MALE RATS EXPOSED TflljBJFOR TEN DAYS^- GROUP MEANS AND STANDARD DEVIATIONS (SD^ 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 7.0()( 7.21r( 6.9<)( 6.9^<( 0.44) 0.45) 0.17) 0.26) 15.( 16.()( 15.(>( 15.'.5( 0.6) 0.8) 0.5) 0.5) 43 .( 2.) 43 .( 3.) 42 .( 1.) 41 .( 2.) 60. ( 2.) 58 .( 1.) 59 .( 1.) 59 .( 1.) 22 .( 1.) 22 .( 1.) 22 .( 1.) 22 .( 0.) 37 .( 1.) 37 .( 1.) 38 .( 1.) 38. ( 1.) 1046 .( 1028 .( 1059 .( 933 .( 126.) 172.) 105.) 129.) TIhE ON TEST RECOVERY 7.08( 7.15< 7.00( 6.90( 0.46) 0.37) 0.25) 0.37) 16.0( 0.8) 16.0( 0.7) 15.8( 0.7) 15.8( 0.6) 42.( 2.) 41.( 2.) 40. ( 2.) 40.( 2.) 59. ( 3.) 58. ( 1.) 57.( 2.) 57. ( 1.) 23.( 1.) 22.( 1.) 23.( 1.) 23.( 1.) 38. ( 1.) 39. ( 1.) 39. ( 1.) 40.( 1.) 978. ( 900. ( 980. ( 972. ( 129.) 45.) 50.) 131.) 1'ABI.l; 1 ^Con_^inut-_c0 Y OF HEMATULOG;C FINDINGS IN MALE RATS EXPOSED O^ TEN DAY.S - ^OU^.MEAN8 M^^ANDARl) DEVIATIONS (SD) TESTS WBC M/mm Nuuc WBCx% Band WBCx{ Lymph WBCx% Alym WBCx DOSE 10 DAY TIME ON TEST RECOVERY CONTROL 3.1 rtG/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 MO/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 3/L 13.6( Z.t) 12.0( 2.3) 12.5( 1.5) 12.3( 2.5) 1306.( 1023.( 1301.( 1332.( 636.) 248.) 518.) 287.) 13.K 1.5) 11.4( 1.8) 10.2( 2.3) 11.0( 2.t) 1766.( 1060.( 1U91.( 2200.( 602.) 455.) '70.) 585.) o.( o.) 0.( 0.) 0.( 0.) 0.( 0.) 24.( 55.) 0.( 0.) 0.( 0.) 0.( 0.) 11237.(2068.) 10012.(2295.) 10073.(1555.) 9916.(2083.) 10547.(1731.) 9780.(2072.) 7694.(2018.) 10554.(2062.) 207.( 189.( 212.( 218.( 129.) 142.) 102.) 135.) 256.( 118.) 161.( 108.) 312.( 218.) 395.( 200.) TESTS Eosin WBCxf Mono WBCx? Baso WBCx TAUI.K I .(Co'll. ijnjei)) N ^UNMAKY OF HEMATOl.OC 1C FOR TKM DAYS - CROUP FINDINCS IN MALE RATS EXPOSED MKANS AND STANDARD DEVIATIONS (SD) DOSE CONTROL 3.1 MG/L 10.0 HG/L 30.0 HG/L CONTROL 3.1 rtG/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L 10 DAY 14.( 44.) 75.( 88.) 49.( 65.) 52. ( 69.) 846. ( 391.) 700. ( 210.) 895. ( 324.) 752. ( 402.) o.( 0.) o.( 0.) o.( 0.) 0.( 0.) TIME ON TEST RECOVERY 51.( 70.) 23.( 52.) 48.( 66.) 25.( 55.) 496. ( 357. ( 655. ( 787. ( 462.) 177.) 193.) 433.) o.( 0.) o.( 0.) o.( 0.) o.( 0.) TESTS AP IU ALT IU AST IU 0 0 1 fl) 3 a 0) 13 ;3. i' n) p. ra 0 <B V) 3 s. 0 0 3 af9l a 5? 8 > 0 CO BUN n{ CHEAT met TPROT &% CHLOS net TA 111,1:: II SUMMARY OK CI.IN1CAI. Cl.l'-MlCAl. FINDINGS IN -1ALE KATS EXPOSED TO I'OR I'l^N DAYS - CKOUl' Mj'-ANS^.A^.-.^TA^A'lP^g.yjATIONS (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 MQ/L 10 DAY 20).( 180.( 198. ( 192.( 35.) 23.) 5L.) 36.) 30. ( 3.) 27. ( 4.) 29. ( 4.) 31.( 3.) 63.( 7.) 6'<.( 7.) 73.( 12.) 76. ( 10.) 16.9( 19.2( 16.7( 14.4( 2.5) 3.0) 3.2) 2.9) 0.6( 0.1) 0.7( 0.1) 0.7( 0.1) 0.7( 0.1) 5.*( 0.2) 5.f( 0.3) 5.3( 0.2) 5.'4( 0.2) 65. ( 7.) 65. ( 14.) 57. ( 10.) 47. ( 9.) TIME ON TEST F^COVERY 224. ( 181.( 172.( 226. ( 41.) 46.) 34.) 46.) 35.( 4.) 37.( 4.) 30.( 3.) 34.( 4.) 66. ( 11.) 67.( 7.) 66.( 10.) 68. ( 10.) 20.K 1.3) 22.0( 3.6) 18.4( 0.5) 18.7( 0.5) 0.6( 0.0) 0.7( 0.1) 0.6( 0.0) 0.6{ 0.0) 5.9( 0.3) 5.6( 0.2) 5.8( 0.2) 5.9( 0.1) 70. ( 15.) 58. ( 12.) 59. ( 9.) 59. ( 6.) H-14808 TABLE III ^ SOUUMl-lMTUAlRIMY O' F Cl.iNICAL URINE ANALYSIS IN MALE RATS EXPOSED TllflApOR3_R_TEN DAYS - GROUP MEANS AND STANDARD DEVIATIONS (SD) TESTS VOL L OSMOL mOa PH 'i UROBL og/dL V ig ',, w w 3 W R' io o 1 o 4 S DOSE CONTROL 3.1 HO/L 10.0 MG/L 30.0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L COhTROL 3.1 MG/L 10.0 MO/L 30*0 MG/L CONTROL 3.1 MG/L 10.0 MG/L 30.0 MG/L 10 DAY TIME ON TEST RECOVERY 8.( 2.) 7.( 2.) 7.( 2.) 9.( 4.) 1677.( 392.) 1909.( 248.) 1732. ( 503.) 1443.( 354.) 13.( 5.) 9.( 3.) 9.( 2.) 11.( 1.) 153-.( 285.) 2100.( 344.) 1653.( 220.) 1675.( 319.) 7.4( 0.5) 7.2( 0.4) 7.4( 0.5) 7.3( 0.5) 7.01 0.0) 7.0( 0.0) 7.2( 0.4) 7.6( 0.5) 0.5( 0.5) 1.0( 0.0) 0.8( 0.4) 0.8( 0.4) 0.6( 0.5) 1.0( 0.0) 1.0( 0.0) 1.0( 0.0) ^ H-14808 ^ TABLE I II (Continued) SUMMARY OF CLINICAL URINE; ANALYSIS IN MALE RATS EXPOSED TMHFOR TEN1 DAYS Sampling Time: Dose mg/L: End-of-Eiposure, 0-Day Rec;overy 1.3-Day R 0.0 3.1 10.0 30.0 0.0 3.1 Measurement Blood 5/10* 1/10 0/10 P/10 1/4 0/5 Sugar (glucose") ProLein Bilirubin ^ Ketone 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 1/10 0/4 0/5 0/10 0/10 0/4 0/5 0/10 0/10 0/4 0/5 0/10 0/10 0/4 0/5 Appearance (color and transparency) Microscopic 0/10 6/10 0/10 0/10 0/10 0/10 0/4 0/5 0/10 0/10 1/4 1/5 O a 3, * Number of abnormal or positive findings/Number of individual urine specimens examined 0) S. 0 B5 . w ^ 0 St TABLE IV H-14 808 SUMMARY OF STATISTICAL ANALYSES OF HEMATOU nCAND CLINICAL CHEMICAL FINDINGS FOR MALE RATS EXPOSED TO^H^1^'O^ R TEN DAYS Sampling Time: End-of-Exposure, 0-Day Recovery 13-Day R Statistic; p* Dunnect+t P Measurement HemaCology RBC Hb Ht MCV MCH MCHC Platelets WBC Neut 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 Clinical Chemistry AP ALT/GPT AST/GOT BUN GREAT TPROT CHLOS (Serum) 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 VOL OSMOL PH UROBL Chemistry (Urine)- 0.246 0.075 0.762 0.014 0.392 0.244 0.049 0.070 0.029 * Value of p for F-test for among group differences ++ Dunnett (shown when significantly different from controls at 5Z level) Q -- j H-14808 TABLE V SUMMARY OF STATISTICALLY SIGNIFIICCAANT CLINJICC,AL CHEMICAL FINDINGS FOR MALE RATS EXPOSEDD--_Tlr^d^--^--sB~aIR TEN DAYS Sampling Time: Measurement Clinical Chemistry (Serum) AST/GOT CHLOS End-of-Exposure, 0-Day Recovery -t IV + IV 13-Day Reco Clinical Chemistry (Urine) OSMOL UROBL t II + Significantly higher than controls by Dunnett criteria + Significantly lower than controls by Dunnett criteria + II + II, I Group Designations and Exp _____Concentrations___ II a Low Dose - 3.1 mg/L Intermediate Dose - IIIIV High Dose - 30.0 mg/L MR:< COMPHD<_ PERIOD: 10 DAT TOXICOLOGIST; KINNEI HASKELLf: 14808 HASKELL CODE*: DPRTOMT: CHEMICALS & PIWESTS REPOBT DATE: 17-MAY-83 CLINICAL LAB: MATARESE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 6-MAI-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAB-83 RBC Hb Hfc MCV ANIMAL*: MH/OB g/dL % fL 348420 7.13 15.9 42. 59. 348432 6.78 15.5 40. 58. 348400 7.68 16.8 47. 60. 348430 6.68 15.2 40. 60. 348437 7.40 16.3 44. 59. 348421 7.02 15.7 .42. 60. 348433 6.30 15.8 41. 64. 348409 7.64 16.7 45. 59. 348422 6.88 14.8 41. 59. 348425 7.35 15.4 45. 60. HCH HCHC PLAT pe g/dL M/mB 22. 38. 856. 23. 39. 1010. 22. 36. 990. 23. 38. 944. 22. 37. 1162. 22. 37. 1192. 25. 39. 1018. 22. 37. 1152. 22. 37. 1220. 21. 34. 920. AVG. S. D. S. E. 7.086 0.441 0.140 15.81 0.64 0.20 42.7 2.3 0.7 59.8 1.6 0.5 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 SPECIES; RAT BIRTH DATE: 3-MAR-83 ANIMALS: 348410 348411 348380 348426 348391 348381 348384 348387 348418 348413 RBC MH/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 MCV % fL 40. 57. 42. 57. 42. 58. 40. 59. 39. 59. 44. 59. 46. 59. 45. 59. 43. 58. 48. 59. MCH MCHC PLAT PS g/dL M/nnn 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 0.446 0.141 16.00 0.81 0.26 42.9 2.8 0.9 53.4 0.8 0.3 22.1 0.8 0.2 37.4 1028.4 1.2 172.0 0.4 5't.4 Company SanSizsd. Does not contain TSCACBj j ^ ^^B^^WP HR:fl--------]^HASKBLL*: COHPND(fl/ PERIOD: 10 DAT TOXICOLOGIST: KZNNE? ^ c r 3 14808 HASKELL CGDEfx DPRTMST: CHEMICALS & P:IGMENTS REPORT DATE; 17-HAI-83 CLINICAL LAB: MATARESE GROUP: 3M DOSE: 10.0 MG/L SAMPLE DATE: 6-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 RBC Hb Hfc MCV MCH MCHC PLAT ANIMAL*: MH/oa g/dL ( fL P8 g/dL M/Bffl 348392 7.05 16.4 41. 58. 23. 40. 1216. 348398 7.07 16.1 43. 61. 23. 37. 1160. 348399 7.37 16.1 44. 59. 22. 37. 1002. 348404 6.94 15.6 40. 58. 23. 39. 918. 348405 6.72 15.2 40. 59. 23. 38. 1030. 348388 6.98 15.2 42. 60. 22. 36. 1094. 348389 6.92 15.2 40. 57. 22. 38. 1196. 348393 7.00 16.1 41. 58. 23. 39. 938. 348416 6.90 15.2 43. 61. 22. 36. 982. 348427 6.92 15.3 42. 60. 22. 37. 1056. AVG. S. D. S. E. 6.987 0.166 0.052 15.64 0.48 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 33.2 GROUP: 4M DOSE: SAMPLE DATE: 6-MAY-83 30.0 MG/L SEX: MALE SPECIES; RAT BIRTH DATE: 3-MAR-83 ANIMAL)?: 348397 348429 348412 348417 348436 348396 348428 348434 348385 348407 RBC m/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 Ht MCV % fL 39. 58. 40. 58. 39. 59. 43. 58. 41. 57. 42. 58. 42. 59. 44. 60. 43. 62. 40. 60. MCH MCHC PLAT PB g/dL M/nnB 23. 39. 864. 23. 39. 730. 23. 38. 1014. 22. 38. 1022. 22. 38. 914. 22. 38. 786. 22. 37. 874. 23. 38. 1132. 23. 37. 1084. 22. 37. 906. AVG. S. D. S. E. 6.935 0.256 0.081 15.54 0.54 0.17 41.2 1.8 0.6 58.9 1.4 0.5 22.4 0.5 0.2 37.7 0.7 0.2 932.6 128.7 40.7 40 Company BaniSaed. Doss not contain TSCA CB8 MR:| ODMPND^_ PERICD: 10 DA? TOXICOLOfflST: KINHET HASKELL*: 14808 HftSEELL CODBf: _ DPRTHIT: CHEMICALS & PIGMENTS REPORT DATE: 2-JON-83 CLINICAL LAB: MATARESE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 6-MAT-83 ANIMAL*: 34B420 348432 348400 348430 348437 348421 348433 348409 348422 348425 AVG. 3. D. S. E. WBC H/nn 9.5 11.7 14.0 12.7 15.5 12.2 13.4 18.3 14.5 14.3 13.61 2.37 0.75 Neufc MBCx{ 570. 1170. 560. 889. 1550. 1952. 1742. 732. 2465. 1430. Band WBCx 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 1306.0 C.O 636.5 0.0 201.3 0.0 SEX: HALE SPECIES: RAT BIRTH DATE: 3-KAR-83 Lymph UBCx{ 8455. 9945. 12040. 11049. 13020. 9394. 10854. 15738. 10150. 11726. Alyo WBCxf 190. 117. 140. 0. 155. 244. 134. 366. 435. 286. Mono NBCxf 285. 468. 1120. 762. 775. 610. 670. 1464. 1450. 858. Eosin mcf.% 0. 0. 140. 0. 0. 0. 0. 0. 0. 0. Baso MBCxf 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 11237.1 206.7 846.2 14.0 0.0 2068.0 128.5 391.3 44.3 0.0 654.0 40.6 123.8 14.0 0.0 GROUP: 2M DOSE : 3.1 MG/L SAMPLE DATE: 6-MAY-83 ANIMALS: 348410 348411 348380 348426 348391 348381 348384 348387 348418 3143413 AVG. S. D. S. E. WBC M/nm 12.3 13.4 12.8 9.2 15.2 13.7 13.5 7.9 9.9 12.1 12.00 2.29 0.72 Neut VBCx% 615. 1340. 1024. 1196. 1216. 822. 675. 1185. 1188. 968. Band WBCX? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 1022.9 0.0 247.7 0.0 78.3 0.0 SEX: MALE SPECIES: RAT BIRTH DATE; 3-MAR-83 Lymph WBCx? 11070. 10988. 11136. 7084. 12768. 11782. 11745. 6004. 7623. 9922. Alyu WBCxjl 0. 134. 128. 92. 456. 274. 135. 158. 396. 121. Mono WBCxK 369. 938. 512. 736. 760. 822. 810. 395. 693. 968. Eosin WBCxf 246. 0. 0. 92. 0. 0. 135. 158. 0. 121. Baso WBCxf 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 10012.2 189.4 700.3 75.2 0.0 2295.4 142.1 210.4 88.1 0.0 725.9 44.9 66.5 27.9 0.0 Company Sanitized. Does noS contain TSCA CBI W^sis ^^pyljw111-1 MR: OOMPt PERIODTTO DAT TOXIOOLOGI3T: KINNEI HASKELLf: 14808 HASKELL CODE*: {JMlj DPRTWT: CHEMICALS & PIOCHTS REPORT DATE: 2-JOH-83 CLINICAL LAB: MATARESE GROUP: 3M DOSE: 10.0 MG/L SAMPLE DATE: 6-MAY-83 ANIHALf: 348392 348398 348399 348404 348405 348388 348389 348393 348416 348427 WBC M/fflB 12.5 14.9 14.9 11.3 12.7 10.4 13.1 11.1 12.1 12.3 Neufc MBCx? 1000. 1192. 596. 904. 2032. 1456. 2096. 555. 1452. 1722. Band UBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. AVG. S. D. S. E. 12.53 1 .49 0.47 1300.5 0.0 548.1 0.0 173.3 0.0 SEX: HALE SPECIES: RAT BIRTH DATE: 3-MAR-83 Lymph MBCxf 10250. 12069. 13559. 96135. 9017. 8528. 9694. 9102. 9559. 9348. Alym MBCxf 250. 298. 149. 113. 381. 104. 131. 333. 242. 123. Mono NBCxf 1000. 1192. 596. 565. 1270. 312. 1179. 999. 726. 1107. Eoain NBCxf 0. 149. 0. 113. 0. 0. 0. 111. 121. 0. Baso WBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 10073.1 212.4 894.6 49.4 0.0 1555.1 101.6 323.7 64.6 0.0 491.8 32.1 102.4 20.4 0.0 GROUP: 4M DOSE: 30.0 tT./L SAMPLE DATE: 6-MAY-83 ANIMALS: 348397 348429 348412 348417 348436 348396 348428 348434 348385 348407 WBC M/nn 15.7 12.0 10.7 12.0 9.7 8.7 16.0 14.0 13-3 10.7 Neu t WBCx % 1570 , 1200 1391 , 1440 , 776 , 1044 1760 , 1260. 1596 . 1284 Band V BCx? 0. 0. 0. C. 0. 0. 0. 0. 0. 0. AVG. S. D. S. E. 12.28 2.45 0.78 1332.1 0.0 287.1 0.0 90 .8 0.0 SEX; MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 Lymph WBCx? 13031. 10560. 8346. 9480. 8148. 6786. 13280. 10780. 9975. 8774. Alym WBCx? 314. 120. 428. 240. 194. 174. 160. 420. 133. 0. Mono WBCx? 785. 120. 535. 840. 582. 609. 640. 1400. 1463. 642. Eosin WBCx? 0. 0. 0. 0. 0. 87. 160. 140. 133. 0. Baso V BCx? 0. 0. 0. 0. 0. 0. 0. . 0. 0. 0. 9916.0 218.3 761.6 52.0 0.0 2083.4 135.3 401.9 69.5 0.0 658.8 42.8 127.1 22.0 0.0 Company Sanitized. Does not contain TSCA CBj /. . -t ^ PEBIODTiO DAT' TOIICOLOGIST: RHINE? HASEBLL*: 14808 HASKELL CODE*: 'IWS^^^ DPflTMIT: CHEMICALS & P HEPORT DATE: 17-MAT-83 CLINICAL LAB; MATARESE GROUP: 1CM DOSS: CONTROL SAMPLE DATE: 6-MAY-83 ANIMAL*: 348420 348432 3^8400 348430 348437 348421 348433 348409 348422 348425 AVG. S. D. S. E. AP IU 173. 224. 200. 246. 157. 161. 243. 236. 177. 226. 204.3 34.9 11.0 ALT ID 29. 32. 33. 33. 32. 27. 31. 29. 31. 24. 30.1 2.9 0.9 AST 10 56. 72. 69. 54. 59. 67. 61. 71. 68. 52. 62.9 7.4 2.3 BUN 08% 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 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAH-83 GREAT 08% 0.7 0.7 0.7 0.6 0.6 0.6 0.6 0.6 0.6 0.7 0.64 0.05 0.02 CHLOS 08% 70. 68. 61. 61. 72. 61. 67. 50. 68. 72. 65.0 6.9 2.2 TPROT &% 5.5 5.8 5.6 5.4 5.5 5.4 5.1 5.1 5.3 5.3 5.40 0.22 0.07 GROUP: 2M SAMPLE DATE: DOSE: 6-MAY -83 K^'IMALff: b484l0 3'.8411 ^48 380 J48426 348391 348381 348384 348387 3^8418 348413 AP IU 201. 191. 161. 159. 185. 164. 203. 163. 156. 219. ALT IU 28. 34. 32. 27. 27. 22. 21. 27. 26. 30. AVG. S. D. S Cfr 180.2 22.5 7.1 27.4 4.0 1.3 3.1 MG/L AST IU 60. 78. 67. 61. 55. 69. 66. 66. 52. 68. 64.2 7.5 2.4 BUN as% 21.8 21.4 19.6 19.9 17.8 14.8 24.6 17.2 15.2 19.1* 19.17 3.03 0.96 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 CREAT ffigX 0.7 1.0 0.7 0.9 0.8 0.6 0.6 0.7 0.6 0.6 0.73 0.13 0.04 CHLOS Digit 91. 64. 76. 71. 76. 67. 54. 46. 55. 48. 64.8 14.1 4.5 TPROT g; 5.6 5.8 5.8 5.5 5.5 5.2 5.3 4.9 5.3 5.2 5.41 0.28 0.09 company Sanitized. Does not contain TSCA CBl -; / - -' ^ k MR:1 CO)MMPlPi ND{.iBJ PERIOD: 10 DA? TOXICOLOGIST: KDtMEY HASKELL*: 14808 HASKELL CODE*: (jBR DPRTHNT: CHEMICALS & PIGMENTS REPORT DATE! 17-MAY-83 CLINICAL LAB: MAURESB GROUP: 3M DOSE: SAMPLE DATE: 6-HAY-83 10.0 MG/L SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL*: 348392 348398 348399 348404 348405 3483. 348389 348393 348416 348427 AP IU 278. 245. 233. 177. 178. 163. 256. 150. 146. 155. ALT AST BUN CREAT CHLOS TPROT IU IU m&% 08% Bg{ 8$ 31. 82. 18.') 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 12.1 3.8 16.70 3.18 1.00 0.65 0.06 0.02 56.5 10.5 3.3 5.34 0.21 0.07 GROUP: 4M DOSE: SAMPLE DATE: 6-MAX-83 30.0 M(;/L SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL)?: 348?97 348429 348412 348417 348436 348396 348428 348434 348385 348407 AVG. S. D. S. E. AP IU 205. 223. 130. 230. 170. 225. 136. 207. 188. 202. 191.7 35.8 11.3 ALT IU 29. 34. 28. 36. 35. 28. 30. 31. 30. 30. 31.1 2.9 0.9 AST IU 70. 72. 77. 70. 34. 68. 91. 69. 64. 94. 75.9 10.3 3.3 BUN m&% 13.0 19.7 13.9 12.3 11.2 15.4 17.0 17.4 13.3 10.9 CREAT a&% 0.7 0.7 0.8 0.7 0.8 0.7 0.7 0.7 0.6 0.5 CHLOS mgK 46. 53. 66. 54. 37. 47. 48. 36. 41. 41. TPROT &% 5.8 5.5 5.5 5.7 5.6 5.6 5.2 5.3 5.1 5.2 -14.41 2.89 0.91 0.67 0.08 0.03 47.0 9.1 2.9 5.45 0.24 0.07 ^"^"y Sanded. Does, HB.Of___ COHPND(^1^ PERIOD: 10 DAY TOXICOLOGIST: KINNEY HASKELL*: 14808 HASKELL CODE*: DPRTKHT: CHEMICALS i PIGME|NJTMS REPORT DATE: 17-MAY-83 CLINICAL LAB: MATARESE GROUP: 1CM SAMPLE DATE: DOSE; 6-MAY-83 CONTROL 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 mL 7. 7. 6. 5. 10. 9. 11. 6. 6. 10. OSMOL m0s 1698. 1749. 2016. 2218. 974. 1589. 1180. 1494. 1756. 2100. BLOOD +1 +1 + + +1 SUGAR - PRO TEIN +2 +1 +2 +2 +1 +1 -.-1 +1 +2 +1 7.7 1677.4 2.2210JJ11 71 0.7 123.9 ?H BILI- RUBIN 7.0 +1 8.0 +1 8.0 7.0 8.0 7.0 7n u 8.0 +1 7.0 +1 7.0 7.40 0.52 0.16 UROBL ng/dL 1.0 ^.0 0.1 0.1 0.1 0.1 0.1 0.1 1.0 1.0 Retone + + 4+ + - +1 + + 0.46 0.46 0.15 GROUP: 2M DOSE: 3.1 MC /L SAMPLE DATE: 6-MAY-83 SEX: r1ALE ;SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMALff: 348410 348411 348380 348426 348391 348381 34838') 348387 348418 348413 AVG. S. D. S. E. VOL mL OSMOL mOs BLOOD SUGAfl PRO TEIN 7. 1985. +2 5. 1910. 1 7. 1945. + - +2 8. 1706. +1 7. 1732. -- +1 9. 1571. - +1 4. 2480. +2 7. 2000. 6. 1991. ~ +2 +1 7. 1771. +2 6.6 1909.1 1.5 248.1 0.5 78.5 PH n f 1 V 7.0 8.0 8.0 7.0 7.0 7.0 7.C 7.0 7.0 BILI- RUBIN " +1 - 4.1 7.20 0.42 0.13 UROBL mg/dL 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 Ketone + + + + + 1 + - + + + 1.00 0.00 0.00 Trace Company Sanitized. Does not contain TSCA CBi mCOl:MM\Pd pi!QU7 PERIOD: 10 DAY TOXICOLOGIST: EINNE? HASKELLt: f | 14808 HASKELL CODBft DPRTHHT: C;HHEaMCICCAALLS & PPIGI MENT; REPORT DATE: 17-MAY-83 CLINICAL LAB: HATARESE GROUP: 3M DOSE: 10.0 MG/L SAMPLE DATE: 6-MAI-33 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 oL m0s TEIN 6. 1887. +1 12. 1067. +1 7. 1619. +1 7. 2930. +2 7. 1624. - +2 7. 1827. - +1 5. 1425. +1 9. 1259. +1 6. 1821. +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 7.0 8.0 7.0 8.0 7.0 7.0 7.0 - 7.40 0.52 0.16 OROBL Bg/dL 1.0 0.1 1.0 1.0 1.0 1.0 1.0 C ii 1.0 1.0 Ka- tonf* + + + + +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 ^48385 348407 /OL mL 9. 5. 8. 15. 6. 8. 17. 6. 7. 9. OSMOL m0s 1465. 1312. 1635. 1013. 1563. 1217. 711. 1774. 1618. 1617. BLOOD ^ - SUGAR + . - PRO TEIN +.1 +2 4-2 +1 +2 +1 + +2 4-? +1 PH 7.0 7.0 8.0 7.0 7.0 8.0 8.0 7.0 71 nu 7.0 BILI- RUBIN +1 - - UROBL mg/dL 1.0 1.0 1.0 0.1 1.0 1.0 0.1 1.0 1.0 1.0 Retone + +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 Comoanv Sani^^ea.Ooesnot contain TSCACBf ^C--L^ aawaff^fiJ BERIODriO DAT TOXICOLOGIST: EINNEY HASKELL*: 14808 HASKELL CODE: DPROfflT: CHEMICALS & PI REPORT DATE: 13-JUN-83 CLINICAL LAB: MATARESE GROUP: 1CH DOSE: CONTROL SIMPLE DATE: 6-MAY-83 WOULf: 348420 348432 348400 348430 348437 348421 348433 348409 348422 348425 RBC /hpf 1-2 2-5 0-0 0-0 0-1 0-2 0-0 0-1 2-4 0-0 WBC /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 &-.3 0-? 1-2 5-8 8-10 3-6 1-3 0-2 Cast /Ipf 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: HALE SPECIES: RAT BIRTH DATE: 3-HAR-83 APPEARANCE DY CL PPT F DY CL PPT F Y CL PPT Y CL Y CL-PCT Y CL PPT P Y CL PPT Y CL PPT DY CL PPT F Y CL PPT FEC PEC FEC GROUP: 2M DOSE- 3.1 MG/L SAMPLE DATE: 6-MAY-83 WIMALi?: 3*8410 348411 348380 348426 348391 348381 348384 348387 34841.8 348413 RBC /hpf 0-0 0-0 0-1, 0-0 0-0 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 ^.Q-^5 5-8 2-3 4-6 0-2 2-4 3-6 4-6 Cast /Ipf 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 BIR'"H DATE: 3-MAR-83 APPEARANCE Y CL PPT LY CL PPT Y CL PPT F Y CL PPT Y CL PPT LY CL PPT Y C PPT Y CL PPT F Y CL PPT Y CL PPT F FEC FBI" Company SanWzed. Does not contain TSCA CBJ HR:C--------Ll ODHPNDfJ PERIODF 10 DAI TDXICOLOGIST: KIMNEY HASEELL*- w \ 14808 HASKELL CODUt DPRIMHTt CHBKICALS & PIICHBFSS REPORT DATE: 13-JUH-83 CUBICAL LAB: MATARE3E GROUP: 3M DOSE: 10.0 MG/L SAMPLE DATE; 6-MA3f-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 /Ipf 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: HALE SPECIES: RAT BIRTH DATE: 3-MAB-83 APPEARANCE Y CL PPT LY 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 ANIMALft: 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 Epifch /hpf 4-8 2-4 4-6 3-5 0-4 2-5 0-2 2-4 5-10 0-3 Cast /Ipf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 A.VG. 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 LY CL PPT F Y CL PPT LY CL PPT LY CL PPT Y CL PPT Y CL PPT F Y CL PPT F FEC Company Sanitized. Does no! contain TSCA CBf i f&> MR: COMPNDf) PERIOD :-^ECOVERX TOXICOLOGiIST: KitINE? HASKELLO : ( ^ | 148138 A!SKELL CODE: DPRTMI<T: CHE(CCALS & PIGMENTS REPOWF DATE: 1-JUM-83 CLINK;AL LABi; MATARESE GROUP: SAMPLE 10M DATR: DOSE: 19-^1AY-83 CONTROL SEX: W ILE SPECIES: RAT BIRTH I)ATE: 3-MAR-83 ANIMALS: 348420 348432 348400 348430 348437 348421 348433 348409 348422 348425 AVG. S. D. S. E. RBC MM/lPBl 6.90 6.53 7.80 7.02 7.14 7.078 0.464 0.207 Mb g/dL 15.8 15.7 17.3 15.5 15.5 15.96 0.76 0.34 Ht < 41 . 41. 45. 40. 41. 41 .6 1.8 0.8 MCV fL 58. 63. 57. 57. 58. 58.6 2.5 1.1 MCH Pg MCHC g/dL PLAT M/nsn 23. 24. 22. 22. 22. 22.6 0.9 0.4 39. 1080. 38. 886. 39. 878. 39. 1154. 38. 894. 38.4 0.6 0.3 978.4 129.3 57.8 GROUP: 2M DOSE: 3.1 MG/L SAMPLE DATE: 19-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMALff: 348410 348411 348380 348426 3483cn 348381 348384 348387 348418 348413 AVG. S. D. S. E. RBC MM/mn 6.63 7.58 7.34 7.24 6.94 7.146 0.369 0.165 Hb <?/dL 15.9 16.8 16.3 16.1 15.0 16.02 0.66 0.30 Ht % 40. 43. 43. 41 . 40. 41 .U '..6 0.7 MCV fL 51. 57. 58. 57. 57. 57.6 0.9 0.4 MCH P<? MCHC g/dL PLAT M/mm 24. 22. 22. 22. 22. 22.4 0.9 0.4 40. 938. 39. 900. 38. 922. 39. 824. 37. 916. 38.7 900.0 1.1 44.6 0.5 19.9 Company Sanitized. Dses nsS contain TSCACBI i / ^(------Bl COHPNDi(fJ PERIOD: RECOVER? TOXICOLOGIST: RINNEY HASKELLD: ^ f | 14808 HASKELL CODEf: DPRTWT: CHEMICALS & PIGMENTS REPORT DATE: 1-JIM-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 ANIMALS: 348392 348398 348399 348404 348405 348388 348389 348393 348416 348427 RBC t tl/mn 7.37 6.93 7.04 6.99 6.67 Hb g/dL 16.6 15.1 15.9 16.4 15.0 Ht MCV % fL 43. 58. 38. 54. 41. 57. 41. 58. 39. 58. MCH Pg MCHC 6/dL PLAT M/mm 23. 39. 1020. 22. 40. 1014. 23. 39. 940. 23. 40. 912. 22. 39. 1014. AVG. 7.000 15.80 40.2 57.0 22.5 39.3 980.0 S. D. 0.251 0.73 1.0 1.7 0.6 0.6 50.? S. E. 0.112 0.33 0.8 0.8 0.3 0.3 22.5 GROUP: 4M DOSE: 30.0 MG/L SEX: MALE SPECIES: RAT SAMPLE DATE : 19-MAY-83 3IRTH DATE: 3-MAR-83 ANIMAL: 348397 34842Q 348412 348417 34B436 343396 348428 3464^4 3483S5 345407 AVG. S. D. S. E. RBC MM/mm 7.15 6.81 7.39 6.44 5.71 6.900 0.374 0.167 Hb R/dL 15.7 15.^ 16.5 16.1 15.0 15.82 0.55 0.25 Ht 1. 41 . 3?. U3 "(C. 38. 40.0 2.1 O.c MCV fL 5.1. 57. t:a. '^. '^. ^7.2 1.3 1.6 MCH PE MCHC ?>/dL PLAT M/nm 22. 2?. 22. 25. 22. 22.9 1.2 0'.6 39. BqO. 40. 1202. 38. 940. 42. 'W. 40. 8^0. 39.5 1.4 0.6 971.6 131.0 Sfi.P ~J U con1^^^^ "otcoMamTSCACBl ID MR:mH COMPNDU PERIOD: RE(3OTER? TOXICOLOGKTi KINHET HASEELL#: ' I S 3 14808 HASKEILL OODE1 DPRTMBT: CHEHICJ1LS & P;[GffiNTS REPORT D1&TE: 2.-JON-83 CLINICAL LAB: W ITARESB GROUP: 1CM DOSEit CONTROL SAMPLE DATEi: 19-MAY-8;$ ANIH&Lf: 348420 348432 348400 34W30 348437 348421 348433 348409 348422 348425 MBC Warn 13.3 11.7 15.5 12.2 13.0 Neufc WBCx Band VBCx% 1463. 2457. 1550. 2318. 1040. 0. 0. 0. 122. 0. AVG. S. D. S. E. 13.14 1.46 0.65 1765.6 601 .6 269.0 24.4 54.6 24.4 SEX: HALE SPEC;IES: Rfl^ BIRTH DAT1S: 3-MA11-83 Lymph Alym Mono Eoain Baso WBCxf WBCxX WB'xf UBCxf WBCxl 10241. 399. 1064. 133. 0. 8658. 351. 234. 0. 0. 12865. 155. ^30. 0. 0. 9272. 244. 122. 122. 0. 11700. 130. 130. 0. 0. 10547.2 255.8 496.0 51.0 0.0 1731.3 118.0 461.9 69.9 0.0 774.3 52.8 206.6 31.3 0.0 GROUP: 2M DOSE : 3.1 r1G/L SAMPLE DATE : 19-MAY-83 ANIMAL 0: 348410 348411 348380 348426 348391 348381 348384 348387 348418 348413 AVG. S. D. S. E. WBC M/mn 14.0 11 .1 9.0 11.1 11.7 11.38 1.79 0.80 Neut WBCxt Band WBCx? 840. 0. 555. 0. 1530. 0. 1554. 0. 819. 0. 1059.6 0.0 454.5 0.0 203.3 0.0 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 Lymph WBCxK Alym WBCxK Mono WBCx{ Eosin WBCxf Baso WBCxil 12740. 140. 280. 0. 0. 10101. 111. 333. 0. 0. 7110. 8769. 90. 111. 270. 666. 0. . 0. 0. 0. 10179. 351. 234. 117. 0. 9779.8 160.6 356.6 23.4 0.0 2072.1 107.9 176.6 52.3 0.0 ' 926.7 48.3 79.0 23.4 0.0 Company Sanitized. Does not contain TSCACBj PERIOD: RECOVERY TOXICOLOGIST: KINNEY HASKELL*: 14808 HASKBLL OGOEf: DPRTrtIT: CHEMICALS & PlOffiHTS REPORT DATE; 2-JOM-83 CLINICAL LAB: HA TARES GROUP: 3M DOSE: 10.0 MG/L SAMPLE DATE: 19-MAY-83 ANIMAL*: 348392 348398 348399 348404 348405 348388 348389 348393 3484.16 348427 AVG. S. D. S. E. WBC M/mn 10.2 10.7 9.1 13.b 7.4 10.20 2.28 1.02 Neufc Band WBCxX WBCxX 1938. 0. 2033. 0. 1274. 0. 952. 0. 1258. 0. 1491.0 0.0 470.5 0.0 210.4 0.0 SEX: HALE SPECIES: RAT BIRTH U-e: 3-MAR-83 Lymph WBCxf Alyn WBCxf Mono Eosin WBCxK WBCxf B&30 WBCxf 7446. 204. 510. 102. 0. 7811. 107. 749. 0. 0. 7007. 273. 546. 0. 0. 10880. 680. 952. 136. 0. 5328. 296. 518. 0. 0. 7694.4 312.0 655.0 47.6 0.0 2018.4 218.5 192.8 66.3 0.0 902.7 97.7 86.2 29.6 0.0 GROUP: 4M DOSE: 30.0 MG/L SAMPLE DATE : 19-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMALS: 348397 348429 348412 348417 348436 348396 348428 348434 348385 348407 AVG. S. D. S. E. WBC M/nm 12.3 17.7 14.9 12.9 12.0 13.96 2.38 1 .06 Neut WBCx? Band WBCxH Lymph WBCx? Alyn) WBCxjl Mono WBCx? Eosin WBCxf Baso WBCxf 1353. 2301. 2533. 1935. 2880. 2200.4 585.5 251.8 0. 0. 0. 0. 0. 0.0 . 0.0 0.0 9471. 369. 984. 123. 0. 13275. 708. 1416. 0. 0. 11920. 10062. 149. 387. 298. 516. 0. . 0. 0. 0. 8040. 360. 720. 0. 0. 10553.6 394.6 786.8 24.6 0.0 2061.9 200.3 433.4 55.0 0.0 922.1 39.6 193.8 24.6 0.0 Company San,% t-^. Does not con(a;nTSCACB? V} KR:[-------- coMpNDC^ PERIOD: RECXWERY TOXIOOLOGISiT: KIN NEY HASKELL ft: ( j f ^ \ 148118 HA:3KELL CODE#: DPRTH(T: CHEICCALS & PIGMENTS REPOR1F DATE: 1-JUN-83 CLINK:AL LAB : MATARESE GROUP: 101 DOSE: CONTROL SAMPLE DATE;: 19-MAY-83 SEX: W ILE SPECIES; RAT BIRTH 1)ATE: 3--MAR-83 ANIMALS: 348420 348432 348400 348430 348437 348421 348433 348409 348422 348425 AP IU 177. 265. 245. 182. 249. ALT AST BUN CREAT CHLOS TPROT IU IU ing 56 mg< ms% 8% 32. 78. 19.6 0.7 60. 5.6 36. 58. 22.2 0.6 88. 6.1 41. 76. 20.4 0.6 51. 5.5 34. 64. 10.0 0.6 77. 6.1 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 10.7 4.3 20.06 1.32 0.59 0.65 69.9 5.88 0.03 14.7 0.30 0.01 6.6 0.14 , GROUP: 2M DOSE: 3.1 MG/L SAMPL!-: DATE : 1Q-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE; 3-MAR-83 ANIMALS: 348410 348411 348380 348U26 348301 348331 348384 348387 3148418 348413 AVG. S. D. S. E. AP rj 176. 232. 166. nf.. 216. 181.2 US.6 r'0.4 ALT ID 33. 42. 41 . 35. 36. 37.4 3.9 i .7 AST IU BUN mK% CREAT ingt CHLOS ng5 TPROT S% 66. 74. 70. 70. 55. 67.0 7.3 ?.3 10.9 21.7 25.1 25.3 17.3 22.02 3.63 1.62 0.6 0.8 0.8 0.7 0.7 0.71 0.07 0..03 77. 52. 46. 64. 54. 58.2 12.1 5.4 5.8 5.5 5.5 5.8 5.6 5.64 0.15 0.07 Company Sa^sd. Does not contain TSCACBg - ( I COMPND^j--------J PERICD: RECOVERY TOXICOLOGIST: KIMHET GROUP: 3M DOSE: SAMPLE DATE: 19-MAY-83 HASKELLf: 10.0 MG/L (jB^ 14808 HASKELL CODEf: DPRTMMT: CHEMICALS & PIGMENTS REPORT DATE: 1-JUM-83 CLINICAL LAB: MATARESE SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL?: 348392 348398 348399 348404 348405 348388 348389 348393 348416 348427 AP IU 153. 231. 160. 145. 171. ALT AST BUN CREAT CHLOS TPROT IU IU mg% ngt mg( 81 30. 77. 18.6 0.6 55. 5.5 27. 56. 18.5 0.6 56. 5.8 28. 64. 18.0 0.7 62. 5.8 30. 59. 19.1 0.6 50. 5.9 35. 76. 17.9 0.6 73. 5.8 AVG. S. D. S. E. 172.0 34.3 15.4 30.0 3.1 1 .4 66.4 9.7 4.3 18.42 0.49 0.22 0.63 0.04 0.02 59.2 8.8 3.9 5.76 0.15 0.07 GROUP: 4M DOSE: ?0.0 MG/L SAMPLE DATE: 19-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMALS: 348:i97 348429 348412 348417 348436 348396 348428 348434 3483S5 348407 AVG. S. D. S. E. AP IU 278. 158. 246. 203. 244. 225.8 46.3 20.7 ALT IU 38. 37. 36. 28. 32. 34.2 4.1 1.9 AST IU BUN i'ig'6 CHEAT mg? CHLOS mg% TPROT g? 82. 74. 62. 59. 62. 67.8 9.8 4.4 18.8 19.2 18.4 18.1 19.1 18.72 0.47 0.21 0.6 0.6 0.6 0.6 0.6 0.62 0.03 0.01 62. 68. 55. 52. 56. 58.7 6.3 2.8 5.8 6.0 5.7 6.0 5.0 5.88 0.13 0.06 Company Sari'ffeed. Does not contain TSCA CBl M>.(--------1 COMPND(fl J PERIOD: HBCWEHI roxicoLOGrsT; KINNET HASKELLf: 14808 HASXELL CODE*: {11 DPRTHIT; CHEMICALS & PIGMENTS REPORT DATE: 2-JDH-83 CLINICAL LAB: MATARESB (SHOWS 1CM DOSE: CONTROL SAMPLE DATE: 19-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL*: 343420 348432 348400 -34A430 348437 348421 348433 348409 348422 348425 VOL imnL OSMDL fnflOOaa BLOOD SUGAR PROTEIN 20. 1200. - + 10. 1431. +1 +1 9. 1864. - +1 13. 1643. - +1 pH BILI- UROBL Ke- RUBIN og/dL tone 7.0 0.1 + 7.0 0.1 +1 7.0 1.0 +1 7.0 1.0 +1 AVG. S. D. S. E. 13.0 1534.5 5.0 284.6 2.5 142.3 7.00 0.00 0.00 0.55 0.52 0.26 GROUP; 2M DOSE: 3.1 MG/L SAMPLE DATE: 19-MAY-83 SEX: MALE SPECIES: RAT BIRTH DATE: 3-MAR-83 ANIMAL : 348410 348411 348380 3H8426 348391 348381 348384 348387 348418 348413 4VG. S. D. C* >-? C* Ci VOL mL OSMOL mOs BLOOD SUGAR PROTEIN 14. 1740. +1 8. 1978. +1 6. 2228. +2 6. 2630. +2 11 . 1925. +1 9.1 2100.2 3.4 343.7 1.5 153.7 "H BILI- UROBL Ke- RUBIN mg/dL tone 7.0 7.0 +1 7.0 7.0 7.0 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 Coma;any SanFf?. "^Ooesnofcor b ! B M T 1 A* w> ^CO S IS (7M 5 1iaft | B g s &s d i f- 0 8 1-1 a m K ^ ft 1(n ? W u (3 S as x (aK a < "5 Sj ^j Sty 0 B ^a rig a S I g aQs M u & K ^ + + - CM + * + 00000 ,-.-.-,-.- ooooo f- CO ^ [^ t-- '^ '? "^ '^ '^ ^ce < w ,, o 8 o ^ '" <o i i i i+ i i ii+ it0 ^i>.1< 3 S fnQ ^"MJ "ftsit, m QO) XQ (WMN(M>to\|fCi;O.=Or 8COB fr-inioo>=r ryo0coco (0MWoo0o'0^m0 c<otoo'tC^T> t^Of(M^.jOmOOcOnCmOC.sOrOgOmOOrCrOifOiOsCf.OsC.OjHE'v^s'wtsmrsf^rsi'^fsrtnsmr^msm-smT 000000 ^.00 0 IA 0 rkt-ffu t--OO 10 (M in D<OCO "'fUCT' O(M ^r i>-1- o\ - o U Q M > 4; ff: w K s w Cd >-t U u ft ft CO OS ^ m u P ^g sc SB - t1 W 03 1 0 bd H >J ffl ^ S 3 M 5 ri m B: % , z M Cd & (- ++++ + OOOOO i-- ------- 000000 -0o +1111 ooooo CO 00 CO t-- t~ o in sr >ainr\j t- 0 0. (\i + +- ^ + ,+- -- + j "^ M o 0 la pn o"? ? Q !M <T> U s5 ^ Q S s 0 +11+1 s Q,,) B looowcyico m-'c.o^wino0*(3y"> ^ ^ .- CM - ^^ 0(\|(\j0-- <fct'c-cr>T(t\r)^-f.--vror>ifciho(o\i.r-nricno^og.jcponc.oac-.oscro^<ao-cao-mooac-ogcco-cl.6t SMam-smraro-.mg-ns"rma-'.ya>-am-smrar^- oo .- t~a-<y(M t---aoro^ ^ o o at -- - 0 . . . C3Q(d > MM < MRs QOfNDt PEHZCD: ERZ TOCECOLOGC9T: KIRHBT HASKELL^i 14808 HASKELL CQDE: DPRTWTt CHEMICALS & __ PIGMBHTS REPORT DATE; 2-JOH-83 CLIHIQU. LAB: MAMBSE GHOOP: 1CM DOSE: CONTROL SJUPLE DATE: 19-^'AY-83 ANDftLf: 348420 348432 348400 348430 348437 348421 348433 348409 348422 348425 RBC /hpf 0-0 0-2 0-0 0-0 AVG. S. D. S. E. WBC /hpf 2-4 5-7 0-0 0-2 Epitti Cast /hp! /Ipf 5-8 o-o 3-5 0-0 2-4 0-0 1-3 0-0 SEX: MALE SPECIES: RftT ;,IRTH DATE: 3-MAR-83 A1PB&MNCE L1t a - PPT Y CL PPT F Y CL PPT F Y CL PPT FEC GROUP: 2H DOSE: 3.1 hu/L SAWLE DATE: 19-MAY-83 ANIMAL*: 38410 348411 348380 348426 348391 348381 348384 '48387 348418 348413 RBC /hpf 0-0 0-0 0-1 0-0 0-0 WBC /hpf Epith Cast /hpf /Ipf 1-3 10-12 0-0 4-6 2-4 0-0 0-0 1-3 0-0 15-20 12-15 0-0 12-15 8-10 0-0 AVG. S. D. S. E. SEX: HALE SPECIES: RAT BIRTH DATE: 3-MAR-83 APPEARANCE Y CL PPT F Y CL PPT Y CL PPT F FEC Y CL PPT F Y CL PPT F Company Sanitized. Does not contain TSCA CBf 57 wUl^^Hml MR: OOPKNPDN^D^^^^B^B^ ^ PERIODS RBOOVEBT TOKIOOLOGESTt KjJiHfiT HASKELL#: 14808 HASKELL CODEft DPRTWTt CHEMICALS & PIGMENTS REPORT DATE: 2-JW-83 CLINICAL LABi K&URBSB GROUP; 3H DOSE: 10.0 MG/L SAHLE DATE: 19-MAI-83 KNIMU-: 348392 348398 348399 348404 348405 348388 348389 348393 3484Ki 348427 RBC /hpf 0-1 0-0 0-0 0-0 2-3 VBC /hpf Epifch Cast /hpf /Ipf 1-3 7-io 0-0 3-5 5-8 0-0 25-30 15-20 0-0 10-12 4-6 0-0 25-30 15-20 0-0 AVG. S. D. S. B. SEIs HUE SPECIES: RAT BIRTH OATBt 3-MAR-83 APPEARANCE Y CL PPT T CL PPT Y CL PPT I CL PPT Y CL PPT FEC FBC GROUP: 4H DOSE: 30.0 MG/L SAMPLE DATE: 19-MAI-83 ANIM6LS 348397 34'i429 348'12 348417 348436 348396 348428 348434 348385 348407 RBC /hpf 0-2 0-0 0-0 1-3 0-0 WBC /hpf Epifch Cast /hpf /Ipf 0-2 0-2 0-0 5-8 0-1 0-0 15-20 3-6 0-0 4-8 0-3 0-0 8-10 4-6 0-0 AVQ. S. C. So E. SEX: HALE SPECIES: RAT BIRTH DATE: 3-MAR-83 APPEARANCE DY CL PPT F Y CL PPT P Y CL PPT F Y CL PPT F Y CL PPT F FEC ^^^"^AD^nof contain TSCA eg? 58 HLR 273-85 APPENDIX VI PATHOLOGY REPORT NO -- ~ 3'? ~ Company Sanitized. Does not contain TSCA CB8 E. 1. DU PONT DE NEMOURS 5 COMPANY HASKELL LABORATORY FOR TOXICOLOOY AND INDUSTRIAL MEDICINE P.O. BOX SO. ELKTON ROAD NEWARK. DELAWARE \y'i i CENTRAL RESEARCH AND DEVELOPMENT DEPARTMENT REVISED 4/4/85 PATHOLOGY REPORT NO. SUBCHROMIC INHALATION TOXICITY "TODY IN RATS MARCH 28. 1985 Summary to|fHlH|mBB|H Hale Crl:CD*(SD)BR rats were exposed by Inhalation at concentrations of 3.1, 10 or jOrngTL, 6 hours/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 fflg/L exposure levels following the 2 weeks exposure or following a 2-eeek post-exposure recovery period. Introduction II III Groups of 10 young adult male Crl:CD(SD)BR rats each were exposed by inhalation to the test compound at concentrations of 0 og/L (Group I - Control), 3.1 mg/L (Group - Low), 10 mg/L (Group - 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*, thyaus*, lymph nodes (thoracic and nesenteric), adrenal glands, thyroid-trachea-esophagus, pancreas, urinary bladder, stomach, duodenum, jejunum, ileuo, cecuffl, colon, bra-in, testes*, epididynides, sternebrae with bone marrow, eyes, nose and any other tissues with grossly observed changes were removed for histologic evaluation. (*0rgans weighed) O'J Qownany Sanitized. Does not contain TSCA CB8 Results and Discussion III The gross and histoiaorphologic observations for Individual rata are listed In Tables I and II, respectively. Table lists the Incidences of microscopic findings per group of rats. Compound-related effects were detected In the high-exposure group (30 mg/L) rats. 2/5 rats had lesions In the nose (focal degeneration and regeneratlon/squamous metaplasia of the respiratory mucosa In the nasal turblnates) 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 inlcroscoplcall^. All of thejhis-tologl-c -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 Co the test compound. HHCC/WCK/wfd CHEN 1.30 ^Port by: X^. 6^*^ ^W^ Bans H. C. Chen, D.V.M. Senior Research Pathologist Approved by; /^- // AU,/^/KlAM^ (/- . /W>gz^flA^_____ William C. Rrauss, D.V.M. Manager, Pathology Division ^PQfiySanttsees n/, b i ^^^nTSCACBl - 3 - KEY TO TABLES Mode of Death SD Sacrificed by design Tissue Accounting N - Normal L - Altered 0 - Tissue not present/insufficient for evaluatiou U 3 Only one tissue present of paired organs/tissues Lesion Grading - = No lesion 1 = Mild lesion 2 = Moderate lesion P = Lesion present; severity not graded ^moarwsan^ Daeswco^r^m Jc A - REVISED fi H-14808 ^^---- ^ 4/4/85 TABLE I EXP GORSOEDSS TOOB3Sg B E m o a y N B A r s ^ Aniaal Number Test Days Recovery Days Mode of Death Group I - Cont:rol - 0 mg/L 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 SO 348425 25 13 SD 348433 25 13 SD Group II - Low Level - 348380 12 0 3.1 mR/L SD 348391 12 0 SD 348410 12 0 SD 348411 12 0 SD 348426 12 0 SD 348381 25 13 SD 348384 25 13 SD 348387 25 13 SD 348413 25 13 SD 348418 25 13 SD Observations 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 No abnormalities detected Lungs - left lobe, white mottling No abnormalities detected No abnormalities detected No abnormalities detected Thymus - left lobe, pink with dark red mottling No abnormalities detected No abnormalities detected Kidneys - slight hydronephrosis, bilateral No abnormalities detected Company Sanitized. Does not contain TSCACBI - 5 ^mp^ TABLE I GROSS OBSERVATIONS IN RATS EXPOSED TOl Part 2 Animal Number Test Days Recovery Days Mode of Death Observations Group III - Inc ennedtate Level - 348392 12 0 SD 348398 12 0 SD 10 mg/L No abnoraallties detected Brain - cut at necropsy Lungs - mottled white throughout 348399 12 0 SD No abnormalities detected 348404 12 0 SD Kidneys - right, hydronephrosis 348405 12 0 SO No abnormalities detected 348388 25 13 SO No abnormalities detected 348389 25 13 SD No abnormalities detected 348393 25 13 SO No abnormalities detected 348416 25 13 SD Kidneys - right, hydronephrosis 348427 25 13 SD No abnormalities detected Group IV - High Level - 30 mg/L 348397 12 0 SD No abnormalities detected 348412 12 0 SD No abnormalities detected 348417 12 0 SD Kidneys - hydronephrosis, bilateral 348429 12 0 SD No abnormalities detected 348436 12 0 SD No abnormalities detected 348385 25 13 SD No abnormalities detected 348396 25 13 SD No abnormalities detected 348407 25 13 348428 25 13 SD Lungs - red foci scattered throughout left lobe, 1.0 mm in diameter Testis - left, small and soft SD No abnormalities detected 348434 25 13 SD No abnormalities detected ^f,44 company Sanitized. Does not contain TSCA CBi REVISED ^A/85 0 TISSUES/OBSERVATIONS ^ iBLE II: INDIVIDUAL SUBCI-IRONIC INHALA ANIMAiL MI TION TOXI CROS>COP1iC DOiTA cm' sn)DV ^-^SPECIE S; f (AT SEX: MALE L.WUUP: I 00;>E: 0 MC1/L AN1MA1 NUMBER: MODE OF DEATH: OAVS ON TEST: DAYS ON RECOVERY; 348 348 348 34S 348 348 348 348 318 3 400 420 430 432 437 409 421 422 425 4 SD SO SO SO SO SD SD SO SO 12 12 12 12 12 25 25 25 25 0 0 0 0 0 13 13 13 13 LIVER EXTRAMED. HEMATOP01ESIS. MARKED/NUMEROUS. uMli MmI ji ri tc- KIDNEYS DEGENERATION, HYALINE DROPLET, CORTICAL. HVDRONEPMROSIS MVDRONEPHROSIS. UNILATERAL If NEPHRITIS. INTERSTITIAL. CHRONIC. MNECOnUIDNIfT( I1CA . IJMNTICFDn^&TIJITIIIA&IL, PLMnBnfU^tnJ 1 i , FOCAL prun^f*AAL1 ,, DIFFUSE UNlLAlfc CnJHAL| . LUNGS PNEUMONIA, INTERSTITIAL. SUBACUTE, FOCAL HEART SPLEEN THVMUS HEMORRHAGE. FOCAL, ARTIFACT LVMPH NODES, THORAC1C ADRENALS TMVBOID CYST. ULT1MOBRANCMIAL OUCT. UNILATERAL TRACHEA a ESOPHAGUS N N N N N N N N N N N N N N N N N N - N N N N N N N N N ---------- N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N 0 0 N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N. N N PANCREAS PANCREATITIS. SUBACUTE. FOCAL URINARY BLADDER PROTEINACEOUS PLUG I BRAIN f s N N N H N N N N N --------- N N N N N N N N N N N N N N N N N N REVISED 4/4/85 C r t HN-_14BOB ),, TISSUES/OBSERVATIONS TABlf: I 1 : 1N01V1D UAiL Ar.1-1MIL MI CRO;>COPI C DJTA SUBC HMONIC INIH LA Tl ON TOXI 1 STU DV EC;IE S: FIAT SEX: MALI: (jNUUP: I DU!>E: 01 MG /L ANIMAL NUMBER: MODE OF DEATH: DAVS ON TEST: DAYS ON RECOVERY : 346 346 340 348 348 348 348 348 340 3 400 420 430 432 437 409 421 422 425 4 SD SO SD SO SO SO SD SO SO 12 12 12 12 12 ZS 25 26 25 0 0 0 0 0 13 13 13 13 STOMACH N N N N N N N N N DUODENUM H N N N N N N N N JEJUNUM N N N N N N N N N ILEUM CECUM N N N N N N N N N N N N N N N N N N COLON N N N N N N N N N LVMPH NODES. MESENTERIC N N N 0 N N 0 N N TESTES ATROPHY ATROPHY, UNILATERAL N N N N N N N N N EPIDIOVMIDES GRANULOMA. SPERMATIC. UNILATERAL OLICOSPERMIA, BILATERAL OLIGOSPERMIA. UNILATERAL N N N N N N L N N P STERNAL MARROW N N N N N N N N N STERNEBRAE N N M N N N N N N EVES N N N N N N N N N NOSE j OEGEN. ft REGEN.tSQ. METAP.). RESP. IfArA CIIQAf en^Al MISCELLANEOUS END OF GROUP 1 N N N N N H N N N 0 0 0 0 0000 ?" s REVISED 4/4/85 ----------^ TABLE INDIVIDUAL ANIMiL Ml:CRO!iCOPI C OfITA n, cm SUBCHRONIC 1NHALA TION TOX1 ' STIIDV ^ SPECIE S: RIAT TISSUES/OBSERVATIONS SEX; MALE GROUP; II ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY; DO!>E: !1.1 Iti/L 348 348 348 348 348 348 348 348 34B 380 391 410 411 426 301 384 387 413 SO SO SD SO SO SO SO SD SO 1.! 12 12 12 12 25 25 25 26 0 0 0 0 0 13 13 13 13 LIVER N N N N N N N N N EXTRAMEO. MEMATOPOIESIS. MARKED/NUMEROUS MINUTb RE CELL FOCI KIDNEYS DEGENERATION, HYALINE DROPLET. CORriCAL. HVDRONEPHROSIS HVORONE'PHROSIS. UNlLArEhAL NEPHRITIS, INTERSTITIAL. CHHONIC. FOCAL NEPHRITIS. INTERSTITIAL, CHRONIC, FOCAL. DIFFUSt UN1LATEHAL LUNGS PNEUMONIA, INTERSTITIAL. SUBACUTE. FOCAL HEART ( 0 SPLEEN ^ THVMU3 n> HEMORRHAGE. FOCAL. ARTIFACT 01 LYMPH NODES. TMURAC1C s w ADRENALS THYROID CYST. ULT1MUBHANCHIAL OUCT, UNIIATCRAL TRACHEA N N N N N N N N L 1 N L N N L N N N N 1 1 N N N N N N N N N N N N N N N N N N N N N N N L N N N P N N N 0 N N N N N N N N N N N N N N H N N N N 0 N N N H N N N N N N N N ESOPHAGUS H N N N N N N N N PANCREAS PANCREATITIS. SUBACUTE. FOCAL URINARY BLADDER PROTEINACEOUS PLUG N N N N N N N N N L N N L L L N L h P - - P P P - P - BRAIN N N N N N cCc w w 2 ..-< N (0 0. 01 0 3" CO 0 > Q REVISED 4/4/85 T1SSUES/08SERVA 11UNS I I : T A B L E INDIVIDUAL ANIMAL MICROSCOPIC DATA SUBO U)MIC INHALATION TOXICITV STUOV ^ SPECIES:: KIAT ,9 SEA; MALE tiROUP: 11 DO!>E: ;1. 1 kIG/L ANIMAL NUMBER: MOOE OF DEATH; DAYS ON TEST: DAYS ON RECOVfcRV: 348 348 348 348 348 348 348 348 348 38U 391 410 41 1 426 381 384 387 413 SD SO SO 10 SD SO SD SD SO 12 12 12 12 12 25 25 25 26 0 0 0 0 0 13 13 13 13 STOMACH OU OENUM JEJUNUM lLElM CECUM COLON LVMPH NODES. MEStNTERIC TESTES A~'?3PMV ATl'OPHV, UNILATERAL EPIDIDVMIDES GRANULOMA. SPERMATIC. UNILATERAL OLIGOSPERMIA, BILAIERAL OLIGOSPERMIA. UNILATERAL STERNAL MARROW STERNEBRAE EVES NOSE DEGEN. & REGEN.(SQ. METAP.'), Kbi-P. MULUSiA. SUBAC., FOCAL MISCELLANEOUS END OF GROUP .11 N N N N N N N H N N N N N N N N N N N N N N N N N N N N N N N N 0 N N N . N N N N N N N N N N N N N N N N N N N 0 N N N N N N N N N 1. N H N N N N N N L N N N N N - - - 1 N N N M N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N 000000 0 0 9 REVISED 4/4/85 oMriMri-- 1i JIDlRUnOfl TISSUES/OBSERVATIONS cm TOiBLE 11: INDIVIDUAL AllIMfiL MI CRO!>COP]1C OfITA SUBCHIROJ1IC INHALAA TION TOXI t STIJOY - SPECIE Si FIAT MALE GROUP: III ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: OAVS ON RECOVERY: DOSI:: 113 MGj'L 348 34U 348 348 348 348 348 348 348 34 392 3U8 399 404 405 388 380 383 4)6 42 SO SO SD SO SO SO SD SD SO S 1^ 12 12 12 12 25 25 25 25 2 0 0 0 0 0 13 13 13 13 1 LIVER N N L N N N N N N N EXTRAMEO. KCMAIOP01E&lS. MARKED/NUMEROUS MINUTE RE CELL FOLl P KIUNEVS llEGENEMAflUN. HYALINE DROPLET. CURIILAL, rtVOHUNtPMf<U^>l :> MVORONEPHROSIS. UNILATERAL NEPHRITIS. INTERSTITIAL, CHRONIC. FOCAL NEPHRITIS, INTERSTITIAL, CHRONIC. FOCAL, DIFFUSE UNILATERAL 1 UNGS PNEUMONIA, INTERSTITIAL. SUBACUTE. FOCAL N N N 1 N N N N L N - . - 1 - - - - 1 ---... - - - - 1 - - - - 1 - N N N N N N N N N N HEART N N N N N N N N N N SPLEEN N N N N N N N N N N THVMUS HEMORRHAGE, FOCAL. ARTIFACT LYMPH NUDES. TMURALIL ADRENALS N N N N N N N N N N N N 0 N N 0 N N N N N N N N N N N N N N THYROID CVST, ULTIMUBRANCHIAL DUCT. UNlLAFtRAL TRACHEA N N L N N N N N N N P - - - - - - N N N N N N N N N N ESOPHAGUS N N N N N N N N N N PANCREAS PANCREATITIS. SUBACUTE. FOCAL URINARY BLADDER PROTEINACEOUS PLUG N N N N N N N N N N N L N L N L N L N r - P - P - P - P - - BRAIN N N N M -^; c; a s < M n N" <D P, 0 0 a a 2 0 03 REVISED 4/4/85 TABLE 11: INDIVIDUAL ANIMAL MICROSCOPIC DATA SuBCHRUNIC 1NHALAAT10N TOX1CITY STUDY -- -- -- <SiPPECIE<Si:- BRAT ^ TISSUES/OBSERVATIONS SEX: MALE GROUP: III ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: OAVS ON HECOUEWV: DOSE: 10 MG/L 348 348 348 348 348 348 348 348 346 392 390 399 4U4 4U5 388 389 383 416 SO SD SD SD SD SO SO SD SO 12 12 12 12 12 28 25 25 26 0 0 0 0 0 13 13 13 13 STOMACH N N N H N N N N N DUODENUM JEJUNUM ILEUM CECUM N N N N N N N N N N N N N N N N N N N N N N N N N N N H N N N N N N N N COLON LYMPH NODES. MESENTlERIC TESTES ATROPHY ATROPHY, UNILATERAL EPIOIOYMIOES GRANULOMA, SPERMATIC. UNILATERAL OLIGOSPERMIA, BILATERAL OLIGOSPERMIA, UNILATERAL STERNAL MARROW STERNEBRAE EYES H N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N tn N N N N N N N N .. N N N N N N N N N N N N N N N NOSE OEGEN. & REGEN.(SQ. METAP.'), RESP. MUCOSA. SUBAC.. FOCAL MISCELLANEOUS . END OF GROUP III N N N N N N N. N N 000000 0 -'s' ? o a 1(0 ?? s. b 0 (0 01 3 a 5? 5 -1 V 0 ca 1.^ HN-148Qa REVI SED A/4/85 TABLE 11: INDIVIDU AL ANIMA L MI CROS COP I C DAiTA suBCHRpNic INMIALATION TOXI CITV STUIDV bEX: MALE '' SPC CIcS: GROUP: 1 V R AT DOSE : 301 MG/ L TISSUES/OBSERVATKaNS ANIMAL NUMBER: MUUE OF D&ATIl: OAVS ON TFSI: DAJ ON RECOVERY: 348 348 348 348 348 348 348 348 348 3 397 412 417 429 436 385 396 407 428 4 SO SO SO SD SO SD SO SO SO 12 12 12 12 12 25 25 26 25 0 0 0 0 0 13 13 13 13 LIVER N N N N N N N N N EXTRAMED. HEMA TOPOIESIS. MARKED/NUMtKUUb M1NUII Ht (; E 1. L f-L1C I KIDNEYS DEGENERATION. 1MVAL1NE DKOPLET. CDRIILAL, MVDRONEPMROSIS MVORONEPHROSIS , UNILATERAL NEPHRITIS, I NT ERST1TIAL. CHRON1L, FOCAl UN cCmDUnD1 f1T1ICA i I1 hNi T1 ERSTIT1AL. CHRONIC. FOCAL. Ull-FUbE UN1LAIERAL LUNGS PNEUMONIA. INF ERST1TIAL, SUBACUTE, FOCAL N N L N L N N N N P 1 1 1 N N N N N N N L N 1 HEART N N N N N N N N N SPLEEN N N N N N N N N N TH/MUS HEMORRHAGE, FO CAL. ARTIFACT LVMPH NODES, THORACIC ADRENALS N N N N N N N N N 0 N N N N N N N N N N N N N N N N N THVR01D CVST. TRACHEA Ul.TlMUBHarn.ni <L uui. l , unil-x i CKML N N N H N N N N N - - - - - - N N N N N N N N N ESOPHAGUS N N N k* N N N N N PANCREAS PANCREATITIS. SUBACUTE, FOCAL URINARY BLADDER or-nHfUtTI cCAl MmA>fEpunUi i3^. BRAIN PLUG N N N N N N N N N --------- N L N N N N. L N N P P N N N N N N N N N ff - ---'"^ ^^^hg^^ 13 - g^KIOI-ZZZZZIZZIlZll ZZZlll.llIll ? ZZZZZZZZII a u$ -i3i-osoiaiMo S "^ lfl>^1 g5">0.- a a in n Z Z Z Z Z Z 0 aoioino Z Z Z Zl 0 Z Z Z Z I 0 -I- go>gr<Oflmn- Z Z Z Z Z Z Z -I.e. -11 IN Z Z Z 0 g<o<go foXu"x-i Z Z Z Z Z Z Z Z. . Z Z Z Z. 0 amou) n SS"""" -. o>. 10 a N o * z z z z z z o ?"l/'- z. zi -i- 0 Z. ,, Z Z Z Z . 0 i . . z z z o ..S?1'" Uj ZZZZZZOZI,Z...ZZZZIO 3>- - 5S 3?;'7'" 1/1 is r- 0 r< o ZZZZZZZZI. ZZZZ. S X -> S < a 3) CM a N 0 ?;'"" 2ZZ2ZZOZI. ZZZ-,-0 2 z S2 .. < >- in zzzzzzoz.i rzzzi < UJ ^S""' B r* a IM o Zi>. 0 Z..- zi.i o -J -I -- u > a z S1 "" >; S -? ~ in .. a ^ - " a3 . o.c. r.. > y< 0 oZ^Z-/'zoam<Li-ni-^oj -^ a^ i .3 z uj uj uj ^ o^c. u" ui..-i-0>> =S ='00 ^.; " " u- Z 2 ; " uj 2 uj 1.1 i/i 5 3 '-I < Z 3 << l/l ai z <c x a a S S t S ^^ -3- g Q 5 S > Ed oi ^^ ^| r a ^U % ^< UJ 2 a! ^ ' . ? ^ L . ; . < (E oc<i-<-jae ui -> u ui >- " *J -^ ^ < LU z a: !- S< 5-i S-. ; i Ul s S o - 2 "^ j'- S ^ g 1j11,, i ji IIP n i j r /'a-i-uu-ii-r' a; - UJ , j> S . yi in z ^5 a3 n < tU "2S j a, . . z a 3 -,<S5 g ujxujuj 030.0. ac < u z uS s io 3 .JJ n40S u. r00 2 s --Q uj mulujz 51 /Z Company Sanitized. Does not contain TSCA CBI  REVISED 4A/85 c" Ills TABLE INCIDENCES OF NON-NEOPLASTIC LESIONS SUBCHRONIC INHALATI:ONtUTTOI X1C1TY STUDY SPECIES; RAT COMPOUNDS ->.' L.^. 0 0 <-i 01 3 < w (1> a i (!) P. ra 0 I j 5" (^ s Tr 0 S! MALES TISSUE/LESIONi LESION GRADES; (P.I,2.3.4) GROUP DESIGNATION: DOSE (MG/L): NUMBER IN GROUP; LiVER EXTRAMEO. MEMATOP01ESIS, MARKED/NUMEROUS MINUTE RE CELL FOCI KIDNEYS DEGENERATION. HYALINE DROPLET. CORTICAL, HVORONEPHROS1S HYDRONEPHROSIS, UNILATERAL NEPHRITIS, INTERSTITIAL, CHRONIC, 1-ULAL NEPHRITIS, INTERSTITIAL. CHRONIC. FOCAL, DIFFUSE UN1LAIEWAL LUNGS PNEUMONIA, INTERSTITIAL. SUBACurfe. FOCAI. HEART SPLEEN I 0 10 10 - 10 - 10 ' -J.- 10 II 3. 1 10 III 10 10 sssscsosmmas 10 10 - 1 (l. - 10 -'-. - - 1 ( - 1 - , , - , .-) 2 (-.2 2 ( ,2 10 10 ' 2 (-.2.-.- .-) 10 -10- 10 10 THVMUS 10 HEMORRHAGE. FOCAL. ARTIFACT TMOBAC1C8 LYMPH NODES. ADRENALS 10 THYROID 10 CYST, ULTIMOBHANCH1AL DUCT. UNILATERAL ' - ' TRACHEA 10 ESOPHAGUS 10 PANCREAS 10 PANCREATITIS. SUBACUTE. FOCAL 1 URINARY BLADDER 10 PROTEINACEOUS PLUG BRAIN 10 STOMACH 10 IU 1 (1.-.-.- .-) 9 -10. 9 ''";- 10 10 (-. 1 .-.-.- )-^ 10 5 (5.-.-.- .-) 10 -LO- 10 -JB. 10 10 ----T~( 1 .- -'fl-lfl -ia- 10 --i-(4, -JO-IfiL  REVISED A/4/85- TABLE III: INCIDENCE!) OF NUN-NEOPLA SUBCMRON1C INHALATIUN^.TOXltl TV i>T I C LESIONS STUPV ;^ MALES TISSUE/LESION: ass DUODENUM JEJUNUM ILEUt CECUM COLON LES ION W. ADES: (P .1,2.3 .4) GHODP Ufcb IQNAtI UN: I DO&E IMC>/ L) : 0 NL'MBEK IN GHUUP: 10 10 10 10 10 10 (I 3. 1 10 10 10 9 10 10 III 10 10 -IS- -10 -!-ia- 10 LVMPM NUDES, MESENTEHK: e y 10 TESTES ATROPHY ATROPHY, UNlLftTtHAL EP101DVM10ES GRANULOMA. S>PER"1H: . UNIL Althfit OLIGOSPERMIA, BI..ATE HAL OLIGOSPERMIA. UN.ILAT ERAL 10 10 1 (1. -.-.-.-, 10 10 i (-.1.-.-.-) 10 -Ifl- ' (-.1.-.-.- STERNAL MARKOW 10 10 10 ! STERNEBRAE 10 EVES 10 NOSE 10 OEGEN. & REGEN.(SO. METAP. J . Rl:i>P. Mill.USA, M 111AC. . FOCAL ^ w f MISCELLANEOUS 0 {NOTES: 1. o , o THE NUMBER OF ORGANS EXAMINED FOR EACH UKOUP IS UNUERL1NEO. LESION GRADES CORRESPOND BV POSITION WITH TMfc NUMBERS IN PARENTHESES. WHICH 10 10 0 INDICATE HOW OFTEN 10 10 0 EACH GRA a .% 0 0 3 O?