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AR226-2927 FOR DUPONT USE ONLY Subchronic Inhalation Toxicity of Haskell Laboratory Report No. 182-85 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: May 8, 1985 Company Sanitized. Does not contain TSCA CBI Subchronic Inhalation Summary Three groups of 20 male Crl:CD(SD)BR rats we davs/week for 2 weeks to 7.6, 58 or 480 mg/m3 o f M f l H ] i n air. A control group was exposed simultaneously to air only. "After the exposure period, rats were observed for up to 12 weeks of recovery. Blood and urine samples were collected for clinical analysis from 10 rats/group at the end of the exposure period and on the 14th and 41st days of recovery, and from 5 rats per group on the 84th day of recovery. Five rats per group were killed for pathologic examination after the 10th exposure and on the 14th, 41st and 84th days of recovery. In addition, at each sacrifice, blood samples were collected from each rat to be analyzed for fluorine concentration. Mean body weights for rats exposed to 480 mg/m of jBBflwere significantly lower than controls from the 2nd exposure through the 17th day' of recovery. No other significant adverse clinical signs were observed in any rats throughout the test. Clinical analyses after 10 exposures revealed several hematologic and clinical chemical changes in rats exposed to 480 mg/m-3 of Hematologic changes included elevated erythrocyte count, hemoglobin concentration and hematocrit, and depressed mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. Clinical chemical changes included elevated alkaline phosphatase activity, urea nitrogen concentration, urine volume and urine pH, and depressed serum cholesterol concentration and urine osmolality. These changes were absent after 14 days of recovery. No adverse clinical chemical or hematologic changes were observed in rats exposed to 7.6 or 58 mg/m3. Pathologic examination showed compound-related changes in the livers and kidneys of rats exposed to 480 mg/m3. The liver effects included elevated liver weights after the 10th exposure and after 14 days of recovery, and minimal to moderate fatty change in the centrilobular hepatocytes at all 4 sacrifices. Microscopic examination of the kidneys showed minimal to mild nephrosis of tubular epithelium of the cortex after 10 exposures. This change was absent after 14. days of recovery. No advers^ gross or microscopic effects were observed in rats exposed to 7.6 or 58 mg/m. Blood fluorine analyses indicated that 99%-100% of the total fluorine in the blood of test rats was present as organic fluorine. Total blood fluorine concentrations in rats killed after the 10th exposure ranged from 10 ppm to 150 ppm. Blood clearance of total fluorine during the recovery period appeared to be biphasic, with a rapid decline in blood fluorine concentra tions over the first 2 weeks of recovery (approximate half-life of 9 days), followed by a gradual decline over the remaining 10 weeks (approximate half-life of 25 days). After 84 days of recovery, blood fluorine - 2- Company Sanitized. Does not contain TSCA CBI concentrations for rats exposed to 7.6 mg/m3 were indistinguishable from controls. However, fluorine concentrations for rats exposed to 58 mg/m3 and rats exposed to 480 mg/m3 were still significantly elevated. No significant adverse effects were observed in rats exposed to 7.6 or 58 mg/m3 of J U K The 58 mg/m3 level is considered the "no-effect" exposure concentrati orameler the conditions this test. Work by: Ihomas A. Kegiiman Technician Robert T. Turner Technician 57a. / < * Supervised by: AO f t Laura A. Kinney 1 Chemist S/ 3 / 2S Study Director: AaJocOv/ C 57 3/5* Nancy T. Chromey, IPh.D. Section Supervisor Acute Investigations Approved by: S'! t ' / g ' //^ ^ ^ D a v Manager, Toxicology Acknowledgements: Bruce A. Burgess also participated in the conduct of this study. LAK:HLR 9.4 - 3Company Sanitized. Does not contain TSCA CBI Haskell Laboratory Report No. 182-85 Sponsor: Polymer Products Department E. I. du Pont de Nemours and Co., Inc. Wilmington, Delaware Material Submitted by: Polymer Products Department E. I. du Pont de Nemours and Co., Inc. Wilmington, Delaware Test Facility: Haskell Laboratory for Toxicology and Industrial Medicine E. I. du Pont de Nemours and Co., Inc. Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Study Initiated/Completed: 7/9/84 - 10/12/84 There are 154 pages in this report. _4 _ Company Sanitized. Does not contain TSCA CBI TABLE OF CONTENTS Page Introduction................................... Materials and Methods .......................................... 6 Results and Discussion .......................................... 9 Conclusion......................... ............................ 13 Figure I - Growth C u r v e ........................................ 14 Figure II - Blood Flourine Elimination ......................... 15 Appendix I - Daily Atmosphere Characterization .............. 16 Appendix II - Mean Body W e i g h t s ............................... 17 Appendix III - Mean Organ W e i g h t s .............................22 Appendix IV - Mean Organ-to-Body Weight Ratios ................ 27 Appendix V - Pathology Report No. 19-85 ....................... 32 Appendix VI - Clinical Pathology Report No. 24-84 ............ 79 Appendix VII - Blood Fluorine AnalyticalReport ................ 136 Appendix VIII - Blood FluorineStatistics ...................... 153 6 - 5Company Sanitized. Does not contain TSCA CBI INTRODUCTION Jhas v e TM low toxicity on an acute g ition -basis. The 4-hour ALC f o r f l M r a s greater than 2100 mg/m The purpose of this study war to detqermine_the toxic effects of repeated inhalation of sublethal concentrations of Wk MATERIALS AND METHODS A. Animals Young adult male Crl :CD(SD)BR rats were received from Charles River Breeding Laboratories, Kingston, New York. Each rat was assigned a unique 6-digit identification number which was recorded on a 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 14" x 8" suspended, steel-mesh cages in rooms maintained at 23-60% relative humidity and 21-26C on a timer-controlled 12 hour/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 Four groups of 20 rats, 8 weeks old and weighing between 210 and 265 grams, were restrained in perforated, stainless steel cylinders with conical nose pieces. Rats were grouped by computer randomization such that the groups' initial mean body weights were similar (p>0.99)-3 Three arouDS were exposed to design concentrations of 5, 50 or 500 mg/nr of ( H f i n air. A control group was exposed to air only. Exposure was *nosc?only, 6 hour/day, 5 days/week for 2 weeks. Five rats per group were randomly selected and killed after the 10th exposure, and after 14, 41 and 84 days of recovery. Rats were weighed and observed daily throughout the exposure period and for 14 days post exposure (weekends excluded), then were weighed and observed weekly and on the morning prior to sacrifice for 17 to 84 days post exposure. C. Test Material Physical Form: Purity: - 6- Company Sanitized. Does not contain TSCA CBI Composition: Synonyms: Stability: The test material was assumed to be stable throughout the exposure phase of the study. The test material is hydroscopic, and readily absorbs water when exposed to moist air. Therefore, the amount of contact of the test material with room air was minimized throughout the test. D. Atmosphere Generation Dust atmospheres of f H J i n air were generated with a 2-stage, vertical glass generato^^^^round flask served as a dust reservoir. A cyclone-shaped flask, inserted above the reservoir, served as an elutriator. A motorized stirring rod with plastic paddles agitated dust in the generator. Air introduced at the reservoir blew dust particles upward to the elutriator. Air introduced at the elutriato^wept dust particles into the exposure chamber. The concentration the atmosphere was controlled by varying the 2 airflows. E. Analytical The atmospheric concentrations o f j J H w e r e determined daily at approximately 30-minute intervals for'each exposure chamber by drawing calibrated volumes of chamber atmosphere through preweighed glass fiber filters. Filters were weighed on a Cahn model 26 Automatic Electrobalance. The atmospheric concentration of particulate was determined from the filter weight differential before and after sampling. Particle size distributions (mass median aerodynamic diameter and percent respirable) were determined with a Sierra model 210 cascade impactor . Particle size samples were collected 2 times per week per exposure chamber. During most exposures, chamber temperatures were monitored with mercury thermometers, relative humidities were measured with a Bendix model 566 psychrometer, and chamber oxygen contents were monitored with a BioMarine model 225 oxygen analyzer. F. Pathology Five rats per group were randomly selected and killed by chloroform asphyxiation after the 10th exposure and on the 14th, 41st and 84th days of recovery for gross and histopathologic examinations. Organs and tissues examined were the heart, lungs, nasal cavities, mesenteric lymph nodes, trachea, liver, pancreas, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, rectum, kidneys, urinary bladder, bone marrow - 7- Company Sanitized. Does not contain TSCA CBI (sternal), spleen, thymus, thyroid, testes, epididymides, adrenal glands, brain and eyes. G. 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 lungs, liver, spleen, kidneys, testes and thymus. Data were statisti cally 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-to-within group variation. Significance was judged at the 0.05 probability level. H. Clinical Pathology Urine samples were collected overnight from 10 rats per group after the 9th exposure and on the 13th and 40th days of recovery, and from 5 rats per group on the 83rd day of recovery. The 10 rats were selected such that the 5 rats per group designated to be killed the next day and the 5 rats per group designated to be killed at the next sacrifice were sampled. Samples were analyzed for volume, osmolality, pH, blood, sugar, protein, bilirubin, urobilinogen 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 10 rats per group (same rats as above) after the 10th exposure and on the 14th and 41st days of recovery, and from 5 rats per group on the 84th day of recovery. Samples were analyzed for erythrocyte count, hemoglobin concentration, mean corpuscular volume, platelet count, leukocyte count, and relative numbers of neutrophils, band neutrophils, lymphocytes, atypical lymphocytes, eosinophils, monocytes and basophils. Hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were calculated from the erythrocyte data. In addition, serum activities of alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase, and serum concentrations of urea nitrogen, creatinine, total protein and cholesterol were also measured. I. Blood Fluorine Analysis At each sacrifice, vena cava blood samples were collected from 5 rats per group in lithium-heparinized tubes. Samples were lyophilized by S. R. Laas, Polymer Products Department, Experimental Section, and were analyzed by E. Kissa, Chemicals and Pigments Department, Jackson Laboratory. Four control samples (1 collected after the 10th exposure and 3 collected after 14 days recovery) and 4 high group samples (3 collected after the 10th exposure and 1 collected after 14 days recovery) - 8- Company Sanitized. Does not contain TSCA CBI were analyzed for both total fluorine and ionic fluorine. Organic fluorine was calculated from the difference between the total and ionic fluorine values. Remaining samples were analyzed for total fluorine only. J. 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 DuPont Hall of Records, E. I. du Pont de Nemours and Co., Wilmington, Delaware. RESULTS AND DISCUSSION A. Exposure Conditions Chamber temperatures ranged between 25-31C, relative humidities ranged from 55-66%, and chamber oxygen contents were maintained at 21%. Particles size analyses indicated that atmospheres ranged between 80-89% respirable with mass median aerodynamic diameters between 4.7-6.3 urn for the design concentration of 5 mg/m, and between 51-72% respirable with mass median aerodynamic diameters of 6.5-9.8 urn for the design concen trations of 50 and 500 mg/m-3. Overall mean atmospheric concentrations are presented in Table I. Daily atmospheric characterization data are presented in Appendix I. Table I Mean Atmospheric Concentrations of Design Concentration 5 mg/m^ 50 mg/mf 500 mg/m13 3 Analyzed Concentration (mg/m ) Mean S. D. Range 7.6 58 480 8.1 38 210 0 - 50 0 - 230 20 - 1200 a Represents mean, standard deviation and range of all samples all exposures. The large variations in atmospheric concentrations, and the relatively low respirability and large mass median aerodynamic diameters, were due to the hydroscopicity of the test material. The test material was "sticky" and tended to agglomerate in the generator and the chamber, - 9Company Sanitized. Does not contain TSCA CBI causing the particles to be large and the atmospheres to be difficult to control. B. Clinical Observations 3 Mean body weights for rats exposed to 7.6 or 58 mg/m were indistinguishable from controls throughout the test. Rats exposed to 480 mg/m3 had significantly depressed body weights compared to controls throughout the exposure period and for the first 17 days of recovery. A growth curve is attached as Figure I. Mean body weights are presented in Appendix II. During exposures, rats in all groups (including controls) exhibited red nasal and ocular discharges, effects common in rats under restraint. During the recovery period, 1 control rat had a red ocular discharge on the 14th day of recovery, and 1 control rat had brown-stained fi^r from the 46th to 59th days of recovery. One rat exposed to 480 mg/m had hair loss from the hip from the 11th to 31st days of recovery. No other adverse clinical signs were observed in any rats throughout the test. C. Pathology No adverse gross or microscopic effects^were-^^ejived at any sacrifice in rats exposed to 7.6 or 58 mg/m of Rats exposed to 480 mg/nr had compound-related changes in the liver and kidneys. Liver changes included elevated liver weights and/or liver-to-body weight ratios after the 10th exposure and after 14 days of recovery, and fatty change in centrilobular hepatocytes which persisted for 84 days of recovery. After 10 exposures, the fatty change was of minimal severity, and affected hepatocytes contained small numbers of fine lipid vacuoles. However, after 14 days of recovery, the fatty change was mild to moderate, and hepatocytes were moderately distended with numerous lipid vacuoles. After 41 and 84 days of recovery, the fatty change was mostly minimal, although affected hepatocytes appeared similar to those at 14 days recovery. Rats exposed to 480 mg/m3 had minimal to mild nephrosis in the kidneys after the 10th exposure. This lesion was characterized by foci of cholesterol-like clefts, regenerative tubular epithelial cells and occasional necrotic epithelial cells in the cortex. This lesion was absent after 14 days recovery. ' In addition to the liver and kidney changes, rats exposed to 480 mg/m3 had depressed spleen weights and spleen-to-body weight ratios, and elevated testis weights after 10 exposures. These changes were absent after 14 days recovery. Several statistically-significant organ weight changes were observed that were not considered compound related. Rats exposed to 7.6 mg/m had - 10 - Company Sanitized. Does not contain TSCA CBI elevated thymus weights on the 14th day of recovery and depressed lung-tosbody weight ratios on the 84th day of recovery. Rats exposed to 58 mg/m and rats exposed to 480 mg/m had elevated spleen-to-body weight ratios on the 84th day of recovery. These changes were believed to be unrelated to treatment. Mean organ weights and organ-to-body weight ratios are presented in Appendices III and IV. The Pathology report is attached as Appendix V. C. Clinical Pathology No treatment-related clinical chemical or hematologic effects were observed in rats exposed to 7.6 or 58 mg/m throughout the test. 3 After the 10th exposure, rats exposed to 480 mg/m had several significantly altered hematologic and clinical chemical parameters. Hematologic changes included elevated red blood cell count, hemoglobin concentration and hematocrit, and depressed mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. Clinical chemical changes included elevated alkaline phosphatase activity, urea nitrogen concentration, urine volume and urine pH, and depressed urine osmolality and serum cholesterol concentration. Several of the clinical changes were consistent with the microscopic pathologic findings. The elevated alkaline phosphatase activity, and the elevated urea nitrogen concentration and urine volume could indicate changes in the liver and the kidneys, respectively. The mild polycythemic effect, indicated by the elevated red blood cell parameters, may have been the result of dehydration. After 14 days of recovery, all of the above changes were absent. No other treatment-related changes were observed at any sacrifice. The Clinical Pathology report is attached as Appendix VI. E. Blood Fluorine Analysis A comparison of total fluorine with ionic fluorine indicated that, for control rats, organic fluorine was greater than 96% of total fluorine, and for rats exposed to 480 mg/m3, organic fluorine was greater than 99.9% of total fluorine. Mean total fluorine concentrations for each sampling interval are presented in Table II. Reported values are averages of 5 samples. - 11 - Company Sanitized. Does not contain TSCA CBI Table II Total Fluorine Concentration (ppm)a Mean (S.D.) Exposure Concentration Controls7.6 mg/m3 58 mg/m:; 480 mg/m3 After 10 After 14 After 41 After 84 Exposures Days Recovery Days Recovery Days Recovery 2.0 (1.5) 10 (1.4) 42 (7.9) 150 (26) 0.92 (0.20) 4.0 (0.58) 13 (2.0) 40 (8.6) 0.86 (0.30) 1.8 (0.29) 7.2 (1.3) 17 (3.2) 0.40 (0.17) 0.61 (0.084) 2.2 (1.2) 4.4 (1.1) a ug total fluorine per g blood Mean total fluorine concentrations after the 10th exposure increased with increasing exposure concentration. However, the increase in fluorine was not directly proportional to exposure concentration: a 10-fold increase in exposure concentration did not result in a 10-fold increase in blood fluorine concentration. Elimination of fluorine from the blood appeared to be biphasic, with a rapid decline in blood fluorine over the first 14 days of recovery, followed by a gradual decline over the remaining 10 weeks. During the first phase of elimination, the average half-life of total fluorine in blood was approximately 9 days. The clearance rate during the first phase appeared to be dose-dependent: the higher the initial blood concentration, the faster the test material was cleared. The half-life for rats exposed ^,4 8 0 mg/m was 7.5 days, while the half-life for rats exposed to 7.6 mg/m was 10.4 days. During the second phase of elimination, the clearance rate appeared to be similar for all exposure concentrations. The average half-life of fluorine in blood during the second clearance phase was approximately 25 days. A statistical comoaj^on of the test groups with controls indicated that rats exposed t o f l M h a d significantly elevated total fluorine concentrations at the'-first 3 sampling intervals. After 84 days of recovery, blood values for rats exposed to 7.6 mg/m were indistinguish able from controls. However, blood fluorine concentrations for rats exposed to 58 or 480 mg/m3 were still significantly elevated. All reported half-lives were determined graphically. A blood fluorine elimination curve is attached as Figure II. Fluorine concentrations for individual rats and mathmatical expressions of the observed fluorine eliminations are presented in Appendix VII. The statistical comparisons of total fluorine concentrations at.each sampling interval are presented in Appendix VIII. - 12 - Company Sanitized. Does not contain TSCA CBI CONCLUSION No significant adverse effects wereoObserved in rats exposed to 7.6 or 58 mg/m3 throughout the test. The 58 mg/m level is considered the "no effect" concentration under the conditions of this test. Rats exposed to 480 mg/m3 o f i ^ ^ a d significant adverse effects in the liver and the kidneys. The liver changes persisted for 84 days of recovery. The kidney changes were absent after 14 days of recovery. Blood fluorine concentrations for rats exposed t o { ( B ^ w e r e dose-depend ent and significantly elevated compared to controls for the first 6 weeks of recovery. Fluorine concentrations returned to normal after 12 weeks of recovery for rats exposed to 7.6 mg/m only. Elimination of blood fluorine was biphasic, with a rapid decline in blood fluorine over the first 2 weeks of recovery followed by a gradual decline over the remaining 10 weeks. 1 Calculation described in Sierra Instuments, Inc., Manual 7-79-210IM, Instruction Manual: Series 210 Cascade Impactors and Ambient Preseparators. - 13 Company Sanitized. Does not contain TSCA CBI Figure I Company Sanitized. Does not contain TSCA CBI ------- CONTROLS 0------0 7.6 MG/CM ------0 5 MG/CM A------ A 480 MG/CM Cm = c u b ic me,ter Figure II Company Sanitized. Does not contain TSCA CBI - CONTROLS & 0 7.8 MG/CM O -0 5fl HG/CM is- A 480 MS/CM cm -- c u b ic m eter APPENDIX I MDAILY ATMOSPHERE CHARACTERIZATION OF Exposure No. Mean S.D. Range Respi rable MMD ( A. Design Concentration of 5 mg/m^ 1 6.9 7.0 2 16 17 3 8.2 7.2 4 8.3 6.5 5 8.1 8.8 6 5.3 4.6 7 5.4 3.7 8 6.5 4.3 9 5.5 2.9 10 5.2 3.0 3 B. Design Concentration of 50 mg/m 2-26 0-50 0-25 0 - 20 0-32 0-13 2-11 2-14 1 - 10 0 -1 0 1 63 27 24 - 120 2 55 46 16 - 180 3 78 57 8 - 230 4 64 34 0 - 120 5 47 21 12 - 100 6 61 54 0 - 150 7 58 25 20 - 110 8 60 35 8 - 120 9 45 10 28 - 62 10 48 43 17 - 170 Design Concentration of 500 mg/m'* 1 520 290 20 - 920 2 400 95 180 - 570 3 420 98 190 - 550 4 430 220 150 - 730 5 450 150 180 - 620 6 470 110 310 - 690 7 480 200 240 - 870 8 400 240 80 - 870 9 580 240 280 - 960 10 650 250 200 - 1200 "_ 80 83 84 89 - 60 - - 55 - 51 - 72 - - 70 64 '61 60 - 6.3 4.7 5.3 4.7 - 8.5 - - 8.9 - 9.8 - 6.5 - 6.9 - 7.8 - 7.9 - 8.0 - a Mass median aerodynamic diameter. - 16 - Company Sanitized. Does not contain TSCA CBI APPENDIX II MEAN BODY WEIGHTS - 17 Company Sanitized. Does not contain TSCA CBI MEAN BODY WEIGHTS (GRAMS) H# 15,388 - EXPOSURE PERIOD GROUP CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM ANOVA(l) T R E N D (2) LSD(3) DUNNETT(4) B A R T L E T T (5) INTERVALS IN TEST DAYS 1. 2. 3. 232.7 234.4 235.4 235.8 237.1 235.4 240.2 229.6+ 0.778 0.316 6.4858 7.8220 0.177 0.028* 0.116 6.9935 8.4344 0.356 242.6 240.1 242.8 231.0# 0.011* 0.012* 7.8406 9.4560 0.277 4. 247.4 245.1 245.6 229.5# 0.001* 0.001* 8.0042 9.6533 0.313 5. 250.8 251.8 252.6 234.3# 0.001* 0.001* 8.4181 10.1525 0.403 GROUP INTERVALS IN TEST DAYS 8. 9. 10. CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM ANOVA(l) T R E N D (2) L S D (3) DUNNETT(4 ) B A R T L E T T (5) 270.1 270.0 269.5 250.5# 0.001* 0.001* 9.4285 11.3711 0.336 277.0 277.6 273.1 249.6# 0.001* 0.001* 9.9104 11.9522 0.543 280.9 279.0 277.5 247.8# 0.001* 0.001* 10.3550 12.4884 0.532 11. 284.9 284.3 282.4 250.3# 0.001* 0.001* 10.6629 12.8598 0.258 12. 289.4 288.1 285.0 246.7# 0.001* 0.001* 11.3864 13.7324 0.125 (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 (alpha=0.05) F RATIO, any two means differing by more than the LSD are significantly different with a false positive (alpha) error rate'of 0.05. ' (4) DUNNETT TEST - any treatment mean differing from the control mean by more than the DUNNETT statisticis significantly different from the control mean with a variable-wise false positive (alpha) error rate of 0.05. (5) BARTLETTS TEST FOR EQUAL VARIANCE P VALUE. + SIGNIFICANTLY DIFFERENT .# SIGNIFICANTLY DIFFERENT cm = c u b ic m eter (P<0.05) from CONTROLGROUP by LSD. (P<0.05) from CONTROL.GROUP by DUNNETT TEST and LSD. 4 A Company Sanitized. Does not contain TSCA CBI ^M EAN BODY WEIGHTS (GRAMS) TO 2 WEEKS POST EXPOSURE GROUP INTERVALS IN TEST DAYS 15. 16. 17. CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM ANOVA(l) T R E N D (2) LSD(3) D U N N E T T (4) B A R T L E T T (5) 309.9 305.8 300.5 263.0# 0.001* 0.001* 14.3258 17.4059 0.533 312.9 309.5 304.3 266.9# 0.001* 0.001* 14.7224 17.8877 0.466 323.0 319.2 312.5 278.3# 0.001* 0.001* 15.0779 18.3197 0.602 18. 325.9 323.3 315.9 284.2# 0.001* 0.001* 15.6897 19.0630 0.536 19. 330.3 326.1 318.3 287.9# 0.001* 0.001* 15.7935 19.1891 0.516 GROUP INTERVALS IN TEST DAYS 22. 23. 24. CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM ANOVA(l) T R E N D (2) LSD(3) DUNNETT(4 ) B A R T L E T T (5) 354.1 349.6 339.0 312.7# 0.001* 0.001* 17.8518 21.6900 0.440 359.3 353.6 343.2 315.5# 0.001* 0.001* 18.0962 21.9869 0.428 364.2 359.4 349.5 322.9# 0.001* 0.001* 19.0094 23.0965 0.440 25. 371.1 365.9 352.7 328.7# 0.001* 0.001* 19.6318 23.8526 0.373 26. 373.8 363.3 356.3 331.6# 0.001* 0.001* 18.8130 22.8578 0.220 (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 (alpha=0.05) F RATIO, any two means differing by more than the LSD are significantly different with a false positive (alpha) error rate, of 0.05. (4) DUNNETT TEST - any treatment mean differing from the control mean by more than the DUNNETT statistic is significantly different from the control mean with a variable-wise false positive (alpha) error rate of 0.05. (5) BARTLETTS 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. cm = c u b ic m eter r\ "i Company Sanitized. Does not contain TSCA CBI H# 15,388 MEAN BODY WEIGHTS (GRAMS) TO 12 WEEKS POST EXPOSURE GROUP INTERVALS IN TEST DAYS 29. 36. 43. CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM ANOVA(l) TREND(2) LSD(3) DUNNETT(4) BARTLETT(5) 389.9 381.0 371.1 347.2# 0.022* 0.003* 27.7810 33.8025 0.606 421.6 415.3 404.2 384.4+ 0.125 0.022* 32.7937 39.9017 0.468 447.4 445.5 432.1 411.8+ 0.161 0.034* 34.9541 42.5303 0.352 50. 472.1 472.4 459.7 438.6 0.258 0.067 38.4790 46.8193 0.352 53. 481.6 475.4 464.8 444.6 0.254 0.054 39.1459 47.6307 0.210 GROUP INTERVALS IN TEST DAYS 58. 64. 71. CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM ANOVA(l) TREND(2) LSD(3) DUNNETT(4 ) BARTLETT(5) 505.4 499.4 488.8 457.2 0.494 0.159 70.4257 87.3718 0.590 521.2 514.4 503.2 477.0 0.642 0.229 77.1268 95.6854 0.389 545.2 538.0 524.2 493.2 0.559 0.183 81.7306 101.3970 0.496 78. 561.8 555.4 543.8 514.2 0.677 0.257 87.9705 109.1384 0.359 85. 572.2 570=. 2 556.8 529.2 0.742 0.314 91.8318 113.9288 0.237 GROUP INTERVALS IN TEST DAYS 92. 96. CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM ANOVA(l) T R E N D (2) LSD(3) DUNNETT(4 ) B A R T L E T T (5) 583.6 582.6 577.0 539.8 0.742 0.355 96.5097 119.7323 0.270 . cm = c u b ic m eter 586.2 575.4 567.6 532.6 0.627 0.228 90.1122 111.7954 0.424 20C, ompany Sanitized. Does not contain TSCA CBI (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 (alpha=0.05) F RATIO, any two means differing by more than the LSD are significantly different with a false positive (alpha) error rate of 0.05. (4) DUNNETT TEST - any treatment mean differing from the control mean by more than the DUNNETT statistic is significantly different from the control mean with a variable-wise false positive (alpha) error rate of 0.05. (5) BARTLETTS 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 cm = cubic meter 0 1Company Sanitized. Does not contain TSCA CBI APPENDIX III MEAN ORGAN WEIGHTS - 22 Company Sanitized. Does not contain TSCA CBI ___ _ MEAN ORGAN WEIGHTS (GRAMS) H# 1 5 , 3 8 8 - RATS SA CRIFICED AFTER 10 EXPOSURES GROUP CONC. FINAL WT. . . LUNGS LIVER CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 2 9 0 . 4( 2 8 9 . 6( 2 8 5 . 4( 2 4 8 . 0( 0.000) 0.936) 0.617) 0.001)# TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.001 0.001 0.369 1.329( 1.260( 1.302( 1.148( 0.000) 0.373) 0.723) 0.029) 0.123 0.051 0.159 10.086( 10.258( 10.801( 11.312( 0.000) 0.770) 0.233) 0.050) 0.178 0.034 0.375 GROUP CONC. SPLEEN KIDNEY TESTIS CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.598( 0.542( 0.541( 0.360( 0.000) 0.335) 0.322) 0.001)# TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.003 0.001 0.767 2.216( 2.329( 2.364( 2.145( 0.000) 0.395) 0.268) 0.587) 0.330 0.666 0.920 2.849( 2.807( 2.727( 2.742( 0.000) 0.731) 0.324) 0.386) 0.720 0.306 0.630 GROUP CONC. THYMUS .. CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.547( 0.638( 0.547( 0.442( 0.000) 0.285) 0.998) 0.221) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.171 0.138 0.636 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 cm = cubic m eter 3 Company Sanitized. Does not contain TSCA CBI _________________ MEAN ORGAN WEIGHTS (GRAMS) H# 15,388 - RATS SACRIFICED AFTER 14 DAYS RECOVERY GROUP CONC. FINAL WT. LUNGS LIVER CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 376.0( 361.0( 350.6( 337.0( 0.000) 0.367) 0.135) 0.028) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.143 0.024 0.267 1.635( 1.566( 1.486( 1.459C 0.000) 0.399) 0.081) 0.042) 0.154 0.028 0.480 13.924( 12.423( 12.917( 18.836( 0.000) 0.464) 0.622) 0.026)+ 0.021 0.028 0.002 GROUP CONC. SPLEEN KIDNEY TESTIS CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.804( 0.718( 0.6 29( 0.698( 0.000) 0.283) 0.038) 0.190) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.200 0.116 0.943 2.808( 2.822( 2.693( 2.660( 0.000) 0.933) 0.494) 0.379) 0.692 0.285 0.351 3.228( 2.918( 3.060( 3.050( 0.000) 0.133) 0.404) 0.376) 0.491 0.534 0.123 GROUP CONC. THYMUS CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.619( 0.761( 0.591( 0.587( 0.000) 0.033)+ 0.648) 0.600) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.034 0.182 0.554 ' 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 cm = cu b ic m eter 24Company Sanitized. Does not contain TSCA CBI __ _______________ _ _ MEAN ORGAN WEIGHTS (GRAMS) H# 1 5 , 3 8 8 - RATS SACRIFICED AFTER 41 DAYS RECOVERY GROUP CONC. FINAL WT. . . LUNGS CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 4 7 0 . 2( 465.0( 4 5 4 . 0( 442.8( 0.000) 0.840) 0.531) 0.295) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0. 712 0. 262 0. 208 1.815( 1.671( 1.684( 1.724( 0.000) 0.193) 0.235) 0.403) 0.537 0.450 0.228 GROUP CONC. SPLEEN KIDNEY CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.773( 0.723( 0.728( 0.743( 0.000) 0.507) 0.551) 0.688) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0. 904 0. 719 0. 234 3.517( 3.344( 3.336( 3.187( 0.000) 0.551) 0.532) 0.261) 0.719 0.282 0.651 LIVER 18.641( 17.815( 17.603( 18 -262( 0.000) 0.694) 0.622) 0.857) 0.958 0.839 0.586 TESTIS 3.246( 3.126( 3.176( 3.191 ( 0.000) 0.514) 0.701) 0.762) 0.928 0.840 0.808 GROUP CONC. THYMUS CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.633( 0.708( 0.579( 0.596( 0.000) 0.280) 0.436) 0.591) Te s t - h o m o g e n e i t y TEST - TREND BARTLETT'S TEST 0.265 0.277 0.108 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 cm = c u b ic m eter 25 Company Sanitized. Does not contain TSCA CBI _ r MEAN ORGAN WEIGHTS (GRAMS) RATS SACRIFICED AFTER 84 DAYS RECOVERY GROUP CONC. FINAL WT. LUNGS LIVER CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 586.2( 575.4( 567.6( 532.6( 0.000) 0.803) 0.668) 0.225) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.627 0.228 0.4 24 2.008( 1.582( 1.953( 1.942( 0.000) 0.031) 0.766) 0.719) 0.112 0.765 0.235 21.936( 21.614( 20.026( 20.215( 0.000) 0.889) 0.415) 0.461) 0.783 0.363 0.4-84 GROUP CONC. SPLEEN CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.749( 0.000) ' 0.802( 0.647) 0.944( 0.106) 0.875( 0.287) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.373 0.170 0.015 KIDNEY 3.952( 3.730( 3.521( 3.690( 0.000) 0.539) 0.241) 0.469) 0.685 0.386 0.491 TESTIS 3.210( 3.454( 3.355( 3.204( 0.000) 0.129) 0.357) 0.970) 0.322 0.812 0.092 GROUP CONC. THYMUS CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.709( 0.681( 0.676( 0.540( 0.000) 0.816) 0.789) 0.181) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.519 0.199 0.927 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 D U NNETT'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 cm = c u b ic m eter 26 Company Sanitized. Does not contain TSCA CBI APPENDIX IV MEAN ORGAN-TO-BODY WEIGHT RATIOS - 27 Company Sanitized. Does not contain TSCA CBI MEAN ORGAN-TO-BODY WEIGHT RATIOS VTS SA CRIFICED AFTER 10 EXPOSURES GROUP CONC. LUNGS CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.458( 0.436( 0.456( 0.464( 0.000) 0.330) 0.925) 0.800) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.620 0.601 0.369 GROUP CONC. KIDNEY CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM . '^ TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.763( 0.80 3( 0.827( 0.868( 0.000) 0.292) 0.097) 0.011) 0.068 0.010 U.b56 LIVER SPLEEN 3.472( 3.534( 3.782( 4.573( 0.000) 0.686) 0.055) 0.000)# 0.000 0.000 0.034 0.206( 0.187( 0.189( 0.144( 0.000) 0.289) 0.327), 0.002)# 0.012 0.003 0.341 TESTIS THYMUS 0.982( 0.9?3( 0.957( I 106( 0.000) 0.851) 0.577) 0.012)# 0.014 0.021 0.482 0.188( 0 -222( 0.190( 0.176( 0.000) 0.249) 0.947) 0.674) 0.435 0.457 0.049 Values in parentheses - P VALUE OF STUDENT T TEST COMPARISON ~ ' l ~ SIGNIFICANTLY DIFFERENT ("p ^Of o 5 F R O l ^ C O N T R O L ^ R O U P ^ B Y "LSD # D U N N ? ^ S YTESTFERENT (P<0*05) FR0M CONTROL GROUP BY LSD AND HOMOGENEITY - P VALUE OF F TEST OF WHETHER GROUP MEANS ARF Fnnar TREND - P VALUE OF F TEST OF WHETHER THERE IS DOSE-RELATED CHANGE IN GROUP MEANS. -A T B D - BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE cm = c u b ic m eter 28 Company Sanitized. Does not contain TSCA CBI MEAN ORGAN-TO-BODY WEIGHT RATIOS H# 1 5 , 3 8 8 - RATS SA CRIFICED AFTER 14 DAYS RECOVERY GROUP CONC. LUNGS CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.435( 0.434( 0.424 ( 0.434( 0.000) 0.941) 0.510) 0.943) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.897 0.800 0.267 GROUP CONC. KIDNEY CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.747( 0.781( 0.768( 0.790( 0.000) 0.301) 0.517) 0.190) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.564 0.259 0.923 LIVER 3.697( 3.437( 3.685( 5.502 ( 0.000) 0.484) 0.975) 0.000)# 0.000 0.000 0.233 TESTIS 0.858( 0.807( 0.8 76( 0.914( 0.000) 0.410) 0.763) 0.357) 0.374 0.225 0.238 : SPLEEN 0.213( 0.199( 0.179( 0.206( 0.000) 0.407) 0.061) 0.667) 0.251 0.444 0.002. THYMUS 0.165( 0.212( 0.168( 0.175( 0.000) 0.015) 0.833) 0.566) 0.055 0.815 0.565 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 cm = c u b ic m eter 7 Company Sanitized. Does not contain TSCA CBI MEAN ORGAN-TO-BODY WEIGHT RA TIO S H# 1 5 , 3 8 8 - RATS SACRIFICED AFTER 41 DAYS RECOVERY GROUP CONC. LUNGS CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.387( 0.360( 0.37K 0.390( 0.000) 0.202) 0.452) 0.870) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.430 0.742 0.208 GROUP CONC. KIDNEY CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0 .749( 0 .720( 0 .735( 0 .7 1 8 ( 0 .000) 0 .5 5 5 ) 0 .784) 0 .517) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.902 0.606 0.759 LIVER 3.9 75( 3.797( 3.858( 4.126( 0.000) 0.601) 0.730) 0.656) 0.770 0.632 0.259 TESTIS 0.692( 0.676( 0.700( 0.722( 0.000) 0.656) 0.829) 0.432) 0.657 0.343 0.719 SPLEEN 0.165( 0.156( 0.159( 0.169( 0.000) 0.576) 0.679) 0.815) 0.840 0.788 0.995 THYMUS 0.134( 0.153( 0.127( 0.135( 0.000) 0.129) 0.516) 0.980) 0.180 0.499 0.274 Values in parentheses - P VALUE OF STUDENT T TEST COMPARISON ~ A 0F 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 D U N N E T T 'S TEST TM ENEITY " P VALUE 0F 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 cm = cu b ic m eter Company Sanitized. Does not contain TSCA CBI mean organ- to - body w eight r a t io s H# 1 5 , 3 8 8 - RATS SA C R IFIC ED AFTER 84 DAYS RECOVERY GROUP CONC. LUNGS CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.344( 0.273( 0.345( 0.368{ 0.000) 0.010)# 0.963) 0.336) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.008 0.079 0.424 GROUP CONC. KIDNEY CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.676( 0. 649( 0. 620( 0. 694( 0 . 000) 0 . 522) 0 . 196) 0 . 687) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.345 0.867 0.003 LIVER 3.7 39( 3.7 55( 3.506( 3.788( 0.000) 0.948) 0.354) 0.843) 0.649 0.897 0.088 TESTIS 0.550( 0.602( 0.595( 0.611( 0.000) 0.124) 0.180) 0.073) 0.266 0.099 0.376 SPLEEN 0 .128( 0 .1 3 9 ( 0 .1 6 5 ( 0.161( 0 .0 0 0 ) 0 .3 4 2 ) 0 .0 0 4 )# 0 .010)# 0.012 0.003 0.152 THYMUS 0 .120( 0 .120( 0 .1 1 8 ( 0 .0 9 9 ( 0 .000) 0 .995) 0 .9 1 6 ) 0 .2 7 1 ) 0.617 0.282 0.438 Values in parentheses - P VALUE OF STUDENT T TEST COMPARISON = , - q t p u TDr m m . F fllEATKBNT MEAN TO CONTROL MEAN. * - DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD # SG" YTED^ FFERENT (P<0'05) FR0M C0NTR0L GROUP BY LSD AND ?TRESND EN-EPiTVVAArL~TUTER OoF LFRET-rE2SeT FOFTEWSHTETHFERWHTEHTEHREER GISR0DUOPSMEE-ARNESLATAERDE EQUAL. CHANGE IN GROUP MEANS. BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE cm = c u b ic m eter ` 31 Company Sanitized. Does not contain TSCA CBI APPENDIX V PATHOLOGY REPORT NO. 18-85 - 32 Company Sanitized. Does not contain TSCA CBI SS*s*f- *EV. 11/82 E5TABU5HED(802 E . I. du P o n t de N e m o u r s & C o m p a n y INCORPORATED Haskell Laboratory for Toxicology and Industrial Medicine I' O. Box 50, Elkton Road N e w a r k , Delaware 19711 central research and development department PATHOLOGY REPORT NO. 19-85 H -15388, POLYMER PRODUCTS DEPARTMENT SDBCHRONIC INHALATION STUDY IN MALE Crl:CD(SD)BR RATS APRIL 4. 1985 % Summary Crl:CD(SD)BR male rats exposed w M * w l0na/r 10 dfyS/ ere examlned g r S ^ l ^ n e l e c ^ d t i r u e r ^ J V 3 weighed and/or examined microscopically. Compound-related lesions consisting of fatty change in centrilobular hepatocytes of the liver and nephrosis of animals. The fatty changefwatshemost severe in animals kociclulrerded14 idfay^sh d o . , following the last exposure. A slight degree of fatty change was still present in the liver of 2 of 5 animals killed after 84 days of recovery. The kidney lesion was only noted in the animals killed on the last day o^ exposure. The no-effect-level for histopathology Was the design concentration of 0.05 mg/L. gn Introduction ' This report will summarize the results Crl:CD(SD)BR rats tof` were as follows: inhalation exposure of male for 10 days. Treatment groups 33 Company Sanitized. Does not contain TSCA CBI - 2- Group I II III IV Design Chamber Concentration of |(mg/L) 0 (Control) 0.005 (Low Dose) 0.05 (Intermediate Dose) 0.5 (High Dose) Animals were exposed "nose only" to the compound 6 hours/day, 5 days/week for -2 weeks. Five animals from each group were killed and examined at each of 4 different time periods - on the last day of exposure and 14 41 and 84 days following the last exposure. Organ weights were determined for lungs, liver, spleen, kidneys, testes and thymus. Selected tissues were processed and examined for histopathology1 . ', Results T&bl6 I contains the gross observations made at necropsy. Tables II III, IV and V summarize the microscopic observations for rats with 0 14 *41 and 84 days recovery respectively. Table VI contains microscopic ' ' observations for individual animals. Compound-related lesions occurred in the liver and kidneys of high dose animals. Fatty change occurred in centrilobular hepatocytes of the liver in A `ratS killed on the laot dQy exposure, 5 of 5 rats killed on days 14 and post-exposure and 2 of 5 rats killed on day 84 post-exposure. Diffuse fatty change of minimal severity occurred in the animals killed on the last day of exposure. Affected hepatocytes contained small numbers of fine lipid vacuoles without being appreciably enlarged. At 14 days recovery, the fatty change was moderate in one animal and mild in the other four. Affected hepatocytes were moderately distended by numerous lipid vacuoles. At 41 days recovery, the lesion was mild in one animal, minimal in three and only present in a few scattered hepatocytes in one animal. Eighty-four days following the last exposure, the lesion was minimal in one animal and only present in a few scattered hepatocytes in one animal. Affected hepatocytes at 41 and 84 days post-exposure were similiar in appearance to those at 14 days post-exposure. Minimal to mild nephrosis occured in the kidneys of all five high dose animals killed on the last day of exposure. The lesion was characterized by foci of cholesterol-like clefts, regenerative tubular epithelial cells and 1 Liver, kidneys, lungs, heart, spleen, thymus, pancreas, adrenal glands, thyroid gland, trachea, esophagus, brain, stomach, duodenum,- jejunum * ileum, cecum, colon, rectum, mesenteric lymph node, testes, epididymides urinary bladder, sternum, bone marrow, eyes, nose and all gross lesions. 3 4 Company Sanitized. Does not contain TSCA CBI - 3- occasional necrotic epithelial cells in the cortex of the kidneys. The lesion was not present after 14 days of recovery. Conclusion Compound-related lesions consisting of fatty change in the liver and nephrosis in the kidneys occurred in animals exposed to a design concentration of 0.5 mg/L o f f l ^ H f o r 10 days. A slight degree of fatty change was still present in theraver of 2 of 5 animals after 84 days of recovery. The kidney lesion was not evident after 14 days of recovery. The no-effect-level for histopathology was the design concentration of 0.05 mg/L. Acknowledgement Pathology supervisory personnel associated with this study'.were Joan A. Wolfe (Histology) and Bobby L. Moore (Necropsy). TWS/WCK/wfd TWS 1.6 Report by: Theodore W. Slone, Jr. D.V.M Diplomate A.C.V.P. Staff Pathologist Approved by: William C. ___ , ___ _M Manager, Pathology Division 35 Company Sanitized. Does not contain TSCA CBI - 4KEY TO TABLES Mode of Death SD = Sacrificed by design Tissue Accounting Code N = No change observed . L = Change observed 0 = No tissue present 1 - Insufficient tissue present for evaluation Lesion Grades P = Change present, severity not graded 1 -Minimal degree of change present 2 = Mild degree of change present 3 -- Moderate degree of change present 4 = Marked degree of change present ~ = Lesion not present 36 Company Sanitized. Does not contain TSCA CBI H-15388. - 5TABLE I Animal Days on Recovery Number Test Days Group I - Control Mode of Death _________________Observation_______ 376825 376839 376840 376870 376873 12 12 12 12 12 376835 376841 26 26 376849 376863 ` 26 26 376872 26 376801 376836 53 53 376837 376847 376878 376807 376829 376834 53 53 53 96 96 96 0 .0 0 0 0 14 ' 14 14 14 14 41 41 41 41 41 84 84 84 SD No abnormalities detected SD No abnormalities detected SD No abnormalities detected SD No abnormalities detected SD Mandibular Lymph Nodes - large, slight SD No abnormalities detected SD Lungs - discoloration, red, gray, patchy areas SD No abnormalities detected SD Urinary Bladder - dilatation, (1.0 cc) SD Mediastinal Lymph Node discoloration, red SD No abnormalities detected . SD Liver - large Lungs - discoloration, white patchy areas SD No abnormalities detected SD No abnormalities detected SD ' No abnormalities detected SD No abnormalities detected SD No abnormalities detected SD No abnormalities detected 37 Company Sanitized. Does not contain TSCA CBI - 6- Animal Days on Recovery Mode of Number Test Days Death Observation 376861 96 84 SD No abnormalities detected 376869 96 84 SD Lungs - discoloration, dark red foci, (< 2 mm in diameter), scattered Group II - Low Dose 376804 12 376806 12 376818 12 376823 12 376844 12 0 0 0 0 0 376810 ' 26 14 376822 376852 376876 26 26 26 14 14 14 376881 376800 376848 376856 26 53 53 53 14 41 41 41 SD No abnormalities detected SD No abnormalities detected SD No abnormalities detected SD Lungs - foci, red, (< 2 mm), several SD Renal Pelvis - dilatation, right, slight SD Lungs - foci, red, (< 2 mm in diameter), few SD Lungs - discoloration, pale SD No abnormalities detected . SD Lungs - focus, brown, (1 mm in diameter) Testes - small, left, (wt. = 0.688 grams) SD No abnormalities detected SD . Thymus - discoloration, red patchy areas, slight SD Lungs - foci, red, few, (< 2 mm in diameter) SD Liver - discoloration, pale 38 Company Sanitized. Does not contain TSCA CBI 7 Animal Number Days on Test Recovery Days Mode of Death Observation 376866 53 41 376871 376827 376831 53 96 96 41 84 84 376862 96 84 376877 96 ' 84 376882 96 84 SD Lungs - foci, dark red, lower right lobe, (< 2 mm in diameter), few Thymus - foci, dark red, (1 mm in diameter), several SD No abnormalities detected SD No abnormalities detected SD Lungs - foci, black, (2 mm in diameter), caudal lobe SD No abnormalities detected . SD No abnormalities detected SD No abnormalities detected Group til - Intermediate Dose 376805 12 0 376821 12 0 376838 12 SD SD SD 376851 376867 12 12 0 SD 0 SD 376812 26 14 SD 376813 26 14 SD 376830 26 14 SD No abnormalities detected No abnormalities detected Renal Pelvis - dilatation, right, moderate No abnormalities detected Periocular - chromodacryorrhea, right, slight Thymus - discoloration, red patchy areas Lungs - focus, dark red, (< 1 mm in diameter), postcaval lobe No abnormalities detected No abnormalities detected 39 Company Sanitized. Does not contain TSCA CBI H-15388 m - 8- TABLE I GROSS PATHOLOGY Part 4 Animal Number Days on Test Recovery Days Mode of ^eath Observai- inn 376857 26 376874 26 376803 - 53 376808 53 376811 53 376843 53 376860 t 376817 376846 376855 376864 376875 53 96 96 96 96 96 14 14 41 41 41 41 41 84 84 84 84 84 SD SD SD SD SD SD SD SD SD SD SD SD Lungs - foci, red, right lower lobe, two, (< 1 mm in diameter) No abnormalities detected No abnormalities detected Liver large Lungs -- foci, red, few, (< 1 mm in diameter) Lungs - foci, dark red, diffuse, 2 mm in diameter) Lungs - focus, dark, (2 mm in diameter), lower right lobe Thymus - discoloration, red patchy areas No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Group IV - High Dose 376820 12 0 376828 12 0 376854 12 0 376859 12 0 SD No abnormalities detected SD No abnormalities detected SD No abnormalities detected SD Lungs - discoloration, white patchy areas, scattered 40 Company Sanitized. Does not contain TSCA CBI - 9- H-15388- (J TABLE I GROSS PATHOLOGY IMALATION SOBCHRONIC - MALE RATS Part 5 Animal Days on Recovery Mode of Number Test Days Death Observation 376879 12 376819 26 376824 26 376833 376858 376880 * 26 26 26 376814 376815 53 53 376832 376850 376853 376816 376826 53 53 53 96 96 0 SD Oral Cavity - discharge, clear Perineum - stain, brown Whole Body - thin 14 SD Liver - discoloration, lobular patterns prominent Lungs - discoloration, pale 14 SD Liver - foci, (< 1 mm in diameter), diffuse, dark Lungs - foci, red, scattered, ( < 1 mm in diameter) Thymus - foci, red, multiple, ( < 2 mm in diameter) 14 SD No abnormalities detected 14 SD No abnormalities detected 14 SD Liver - discoloration, lobular patterns prominent Lungs - foci, red, (< 2 mm in diameter), few 41 SD No abnormalities detected 41 . SD Liver - large Thymus - discoloration, dull red, left lobe 41 SD Lungs - discoloration, dark red foci, (< 2 mm), scattered 41 SD . No abnormalities detected 41 SD No abnormalities detected 84 SD No abnormalities detected 84 SD Lungs - foci, red, brown, (1 mm in diameter), scattered vi Company Sanitized. Does not contain TSCA CBI 10 - Animal Number Days on Test Recovery Days Mode of Death Observation 376842 96 84 SD Lungs -- foci, red, (1 mm in diameter), scattered 376845 96 34 SD Liver - hernia, through diaphragm 376868 - 96 84 SD No abnormalities detected 42 Company Sanitized. Does not contain TSCA CBI o in Company Sanitized. Does not contain TSCA CBI __J I S S U E / L E S IO N : LIVER TABL II SUMMARV TABLE SPECIES, S U B C H R O N I C INI LESION GRADES: (P.1 .2,3,4) males GROUP DESIGNATIONDOSE (MG/L): _____ N U M B E R IN GROUP: =========: C- L E S I O N S (days-on-test from II . 0.005 5' F TMc"i;sei f r ; i s i uL`" 5 to 1 2 ) III 0.05 5 5 NECROSIS.' COAGULATI VEVIA c t f HEpACVTES- CENTRILOBULAR NECROSI S , COAGULATIVE.' s Sb I c t ^ L T I F < ^ CAL KIDNEYS P ' 5 ;?ct C L E F ^ ^ E N E , n ,, E t u s i e .e s /,n ,, , v . C I L ,, E C T O S I S PROTEIN DROPLETS, p t Sf JJ t TUOUL LUNGS O nI HIS?iOc0?oil!UBFOcIf;M FOCAL/MULTIFOCAL i ^ i r S S I - ' TM TM " LT,F0C.L ^ ^ p o l v , ,, ,, p ,, o n u c L e . . . - ' : T R Mu ti:'ssTL ; p S s ; r * ^ ^ S C U L A R 1 (- '.-.-) 2 (-.2,-,-,-) 2 (-.2 _> (- 1. ~ 5 1 (- 1.-.".-) 5 - 5 1 " " v'o o e o e n e r a t .o n . e o c l /m u l t i p o c l . VOC.RO,U pancreas ATROPHY. FOCAL. LOBULE I N F L A M M A T I O N , C H R O N I C I N T E R S T I T ti hit-,- thymus ' pigmented macrophages HEMORRHAGE. ACUTE, MULTIFOCAL SPLEEN ADRENAL g l a n d s degenerative focus Th y r o i d g l a n d CYST ULTIMOBRANCHIAL cyst 5 1 (1 PART IV 0.50 5 5 4 (-.4.-. I ,- , 5 5 (-.2.3, ) Company Sanitized. Does not contain TSCA TABLE II SUMMARY TABLE Ji'CU.tS : COMPOUND SUBCHRONIC I N R A U m O ^ ^ ^ ^ TISSUE/LESION TRACHEA LESION GRADES: ( P , 1,2,3.4) MALES GROUP DESI G N y ION DOSE (MG/L): NUMBER IN GROUP: I 0.00 5 Cdays-on-test from II 0.005 5` ESOPHAGUS brain STOMACH DUODENUM __ 5 _ __ 5_ __ 5_. __ 5_ __ 5 _ __ 5 _ 5 __ 5 _ JEJUNUM __ 5_ __ 5_ ILEUM __ 5_ __ 5_ CECUM COLON nematode, lumen RECTUM ne m a t o d e , lumen mesenteric lymph node urinary bladder testes SS epididymides SPERM GRANULOMA eyes iuSutil; s;tiIS;iL __ 5_ __ 5_ 5 5 __ 5_ __ 5_ __ 5_ 1 (-, 1 5 - __ 5_ 5 5 __ 5_ 5 __ 5_ 5 sternum bone marrow nose i n f l a m m a t i o n , a c u t e , m u c o s a ,s u b m u c o s a . r e s p i r a t o r y e p i t h . __ 5_ __ 5__ __ 5_ __ 5_ __ 5_ 2 2 5 to 12) III 0.05 5 5 5 5 5 5 5 5 5 __ 5_ __ 5_ 3 5 __ 5_ __ 5_ 5 3 3 5 O 00 PART IV 0.50 5 S 5. 5 5 5_ 5 J5 5 5 5 _5 5 5 5 J5_ 5 _5 A HN-153BB ii table i i SUMMARY TABLE SPECIES: RAT1 NCIDENC" L y ^ S T I C SUBCHRONIC UNIONS males ___TISSUE/LESION: s5 = S5 ss s = s a . 5Saa = s ^ ' s . M J ____ dNNnDSUUOnsMMSEBBE^EPR,(DMIGEN/SLI)GG:RNOAUTP:r0N: NOSE (cont'a) === inflammation acutf i n f l a m m a t i o n ,' f o c a l ' s u B A r u T F U B .M U C 0 S A ' v e n t r a l m e a t u s INFLAMMATION, S U B A C U T F M M ^ I f ' MAXILLOTURBINATE S SQUAMOUS METAPLASIA FOCa ^ ocCAL' RESPIRATORV TURBINATFC SOU.MOUS E T .P L .Iii: 3 % ? ^ TM TM ^ ^ ' " " " OTHER -------M A N D I B U L A R L Y M P H NOOE- H Y P E R P i i c j . , PLASIA LYMPHOID NOTES: 0.00 5 (days-on-test from 11 0.005 5' : t-.l. 1 1 (-.-.1.-.-) to 12) III 0.05 5 IV 0.50 5 -te U ~1 l e s io n g r a de s c o r r e s p o n d ^b y ^p o s i t i o n ^w i t h ^t h e ^^ u n d e r l i n e d . with the nu m b e r s in p a r e n t h e s e s , wh i c h indicate how often each grade was observed Company Sanitized. Does not contain TSCA o CD II ft II(IIIIIII1III IIIIIIII )IIIIII1I(IIIIIIIIIIII1II1IIIIIfIII IIIIII Company Sanitized % -te o\ Uoaa>) o3 Oo3r** sr 3* H Co>/> o CD IN-15308, n TABLE I I I SUMMARY TABLE SPECIES: ^ ^ C ' P g N C K ^ N Q N - a E O P L ^ J I C LESIONS S U B C H R O N I C IN* El a t i o n s t u d y TISSUE/LESION: LESION GRADES: (P.I,2,3,4) LIVER .V SSSt: S S S T i S i S ' i a r " MALES GROUP DESIGNATIONDOSE (MG/L): NUMBER IN GROUP: I N F L A M M A T I O N | S U B A C U T E A L M U L T I F O C A L E S 'S C A T T E R E D C E N T R I L O B U L A R "Siil: g5fS5LA?5iVISi^EHE?SS:Sf4 , c S n t R1 ,0 ^ n e c r o s i s , c o a g u l a t i v e : s Sb Ic te m u l t i f o c a l KIDNEYS CYST?S^ C A L CLEFTS/RE^ N E R A T I V E TUBULES/INDIV. CELL NECROSIS GLOMERULONEPHROPATHV, CHRONIC Don?cTEPHRSIS' BILATERAL protein droplets, proximal tubules LUNGS [ 0.00 5 (days-on-test from II K0.00 5 13 to 26) III 0.05 IiIi IIIIII 5 1 (-, 1 . 1 C-. 1 - __ 5_ - 1 ( - . 1 ,-,- .-) 5 - 5 __ 5_ __ 5_ H i s ? i o c C ? o s i f U B ^ T E ' f c a l /m u l t i f o c a l __ 5_ __ 5 _ P O L V M O ftPHONUCLEAR HEART m y o d e g e n e r a t i o n , f o c a l /m u l t i f o c a l . MYOCARDIUM PANCREAS atrophy, focal, lobule INFLAMMATION,CHRONIC,INTERSTITIAL.WITH PIGMENTED MACROPHAGES THYMUS HEMORRHAGE, ACUTE, MULTIFOCAL SPLEEN ADRENAL GLANDS DEGENERATIVE FOCUS THYROID GLAND CYST ULTIMOBRANCHIAL CYST 1 (-.1 1 (-, 1 1 1 c-.i.-,-. -) ,1 -) -) 5 1 ( - . 1 ,-.-, -) 5 - 1 (-.1 5 1 (-.1 5 __ 5_ __ 5_ 5 __ 5_ __ 5_ 5 4 2 (2 .-,-,-,-) 1 ( 1 ,-. PART IV 0.50 5 5 (-.-,4. 11 ((--..--..11,, 2 (-.2.- 2 (-.2 . .-) 5 2 (-.2. 1 (".I.-.1 Cl.-,-.- Company Sanitized. Does not contain TSCA CBI H N - 15368 3 TABL III SUMMARY TABLE SPECIES: Ra t - - - - ^ m ^ V E O P L A S T IC LESIONS SUBCHRONIC INHALATION STUDY TISSUE/LESION TRACHEA ESOPHAGUS BRAIN STOMACH DUODENUM JEJUNUM ILEUM CECUM COLON NEMATODE, LUMEN -te. -"J RE C T U M NEMATODE, LUMEN LESION GRADES: (P.1.2.3,4) MALES GROUP DESIGNATION DOSE (MG/L): NUMBER IN GROUP: (days-on-test from 1 0.00 5 II 0.005 51 -------------------- = = = == 55 5 __ 5_ 5 . 5 55 55 A __ 5_ 55 55 5 __ 5_ 55 MESENTERIC LYMPH NODE URINARY BLADDER TESTES atrophy, ATROPHY, SEMINIFEROUS SEMINIFEROUS TUBULES TUBULESi EPIDIDYMIDES SPERM GRANULOMA BILATERAL UNILATERAL A 3 5 5 EVES STERNUM BONE MARROW NOSE INFLAMMATION. ACUTE, MUCOSA/SUBMUCOSA RESPIRATORY EPITH. _5_ _5 S_ 5 _5 _5 5_ 5 13 to 26) III 0.05 5 5 5 5 5 5 __ 5_ 5 5 5 5 5 5 II II It II II II II II II Il 1 II II II II II II II II II II II II PART: IV 0.50 5 5 5 5 5 A 5 5 5 5 5 5 5 5 _5 _5 A_ 5 I w I S P E C I E S : R A T I N C I D E N C rEL ^ , . . Ng ^ PLA S T IC L E S I O N SUBCHRONIC i N f R u f f l O ^ S S r ___ T S S U E / L E S I O N : LESION GRADES(P.1.2.3.4) MALES GROUP DESIGNATE O N DOSE (MG/L): NOSE (cant'a) INFLAMMATION INFLAMMATION' INFLAMMATION,' ACIITP FOCAI ' c m ? o A/ SU0M U C S A , VENTRAL MFarnc S U B A C U T E BMuiJi ^ n M A X l L L 0 T U R B I N A T E ME S ===; I 0.00 5 (days-on-test from -= = = = = = 11 0.005 5' II M II II II 1 II II II II 5 1 (~ . 1 1 (-. 1 O T H4EPRD MANDIBULAR LVMPH NODE: HYPERPLAST/: -------------------------- - notes; LYMPHOID 1 ____________ ' ( - . 1. 13 to 26) III 0.05 5 PART; IV 0.50 5 :s -Ci OD s sss4rr^..-tama^, each grade was observed. Company Sanitized. Does not contain TSCA CBI c H N - 15388 0 TABLE IV SUMMARY TABLE PART: Company Sanitized. Does not contain TSCA CBI males (days-on-test from 27 to 5 3 ) TISSUE/LESION: LIVER LESION GRADES: ( P . 1,2 .3 .4 ) GROUP DESIGNATIONDOSE (MG/L): NUMBER IN GROUP: 1 0.00 5 II 0.005 5' III C90. 05 IV 0.50 5 F A T T Y CHHAANNGgEI>' FOCAL, M ECDEINATNRILLOOBBEU L A R FATTY CHANGE, INDIVIDUAL HEPATOCVTF; -r-reorr I N F L A M M A T I O N . S U BA CU TE , M U L T I F O C A L ^ 'S C A T T E R E D C E N TM i L O B U L A R s KIDNEYS : 5 1 (-, 1 . __ 5_ - - 1 1, __ 5 _ 2 ( - . 2 ,-,- .-) 5 4 (-.3.1,-.-) 1 1 c-.i ' IUBULES/,HOI. GLOMERULONEPHROPATHY, CHRONIC HYDRONEPHROSIS. UNILATERAL PROTEIN OROPLETS. PROXIMAL TUBULES CELL HECEOS.S LUNGS __ 5_ 2 ( - . 2 ,- __ 5_ __ 5_ 1 (-.1 .-.-.-) __ 5_ - HEMORRHAGE, SUBACUTE, FOCAL/MULTIFOPAI -te. SO HISTIOCYTOSIS. FOCAL^ULTI FOCAL INFLAMMATION, SUBACUTE. FOCAL/MU1 TTcnrsi HEART __ 5_ _ 1 (-.-.1 . 1 ( - . 1 .-. _5 _ 5 i 2 (-.2 .-,-.-) 2 (-.2 .-.-,-) 1 2 1 1 MYODEGENERATION, FOCAL/MULTIFOCAL. MYOCARDIUM PANCREAS ATROPHY, FOCAL, LOBULE INFLAMMATION.CHRONIC.INTERSTITIAL.WITH PIGMENTED MACROPHAGES thymus __ 5_ 5 -- 5 2 (-.2 ,-,-,-) 5 - 1 5 2| 5 HEMORRHAGE, ACUTE, MULTIFOCAL SPLEEN __ 5_ 5 2 (-.2 ,-,-,-) 5 i 5 ADRENAL GLANDS DEGENERATIVE FOCUS THYROID GLAND CYST ULTIMOBRANCHIAL CYST __ 5_ __ 5_ 5 __ 5_ 5 - 5 55 55 4 __ 4_ - - 2( aN N - 153BB SPECIES: TABLE IV TISSUE/LESION trachea LESION GRADES(P.1 ,2,3.4) GROUP DESIGNATIONDOSE (MG/L): NUMBER IN GROUP: esophagus brain STOMACH DUODENUM JEJUNUM ILEUM CECUM COLON (j -j N E M A T O D E , L U M E N C D R ectum NEMATODE. LUMEN MESENTERIC LYMPH NODE urinary bladder testes atrophy, ATROPHY, seminiferous seminiferous epididymides .SPERM GRANULOMA tubules tubules EYES bilateral UNILATERAL STERNUM BONE MARROW NOSE I N F L A M M A T I O N . Aa Co Ui Tt Ec . M U C O S A / S U B M U C O S A RESPIRATORY EPITH. __5 5 5 5 5 5 5 5 5 5 1 (1 5 5 5 5 _5 5 5 5 5 5 5 5 5 5 5 __ 5_ 5 5 5 5 27 to 53) III 0.05 5 5 5 .5 5 5 5 PART : IV 0.50 5 5 _5 5 _5 5 J5 5 5 5 5 _5 5 5 _5 1 _5_ 5 5_ 11 I t-- 00 I Company Sanitized. Does not contain TSCA CBI iHtLIES: RAT table IV SUMMARY TABLE PART: 3 Company Sanitized. Does not contain TSCA CBI IIIIIIIIIIIIIIIIIIII IIII TISSUE/LESION: LESION GRADES: (P.1.2,3,4) GROUP DESIGNATIONDOSE (MG/L): NUMBER IN GROUP: N O S E C c o n t 'd ) nPlS S n : ocIl ! SUBCAcSESUBMAU^,SrATVENTRAL MEATUS Ss Oq Uu Aa Mm Oo Uu Ss "^Mm EeTtAaPpLLl 2a ssS ^aAa U:T f o c a l *"T r e s p i r a t o r ^ ^ ^ ^ ^ R ^ t^u r b i n a t e s OTHER -- . M ^ O I B U L A R L V M P H N O D E : HYPERPLASIA, LYMPHOID (days-on-test from I 0.00 5 11 0.005 5 __ 5_ __ 5_ 2 (-, 2. - , - , - ) 1 2 2.-." .-) 1 (-,-.1 __ 0_ 0 27 to 5 3 ) III 0.05 0 IV 0 .5 0 5 __ 5_ 3 ( - . 1 , 1 , 1 ,-) n 5 1 - (-.1 2 (-.2.-.-.-) NOTES: o THE NUMBER OF o LESION GRADES ?C OnRRRoEpSLPnOMN-DiMBIYNEDP O SFI0TRI OENACWHI TGHROUTHPE IS UNDERLINED. NUMBERS IN PARENTHESES WHICH INDICATE HOW OFTEN EACH GRADE WAS OBSERVED. Ln HN-153BB SUMMARY TABLE SPECIES: RATINCI^N CE S. OF N O N - ^ g g p ^ s T ^ LESI0ns SUB CHRONIC I N H A U m o i ^ T G D Y ^ T I S S U E / L E S ON: LESION GRADES: CC PP.,1.,22 . 3 , 4 ) LIVER S I : flS ^ E S S r iS r "' MALES GROUP DESIGNATIONOOSE (MG/L): NUMBER IN GROUP: I 0.00 5 Cdays-on-test from ** -9 e ___________ __5_ -4 - 54 to 9 6 ) III . oos 5 _JL_ ; S r T I" : su aflc rE AI'MULT:F0CALe S ' SCATTERED-CENTRIL0BU*-AR f c S S : " I I i " v , ; i s HEFps ; ; Lc s E si l EE* 'TM , L0, ,, Ea, . N K . O S I S . COAGULAT IVE, kidneys - l c-.1 .-.-.-) i : 1 c-.i C Y S T ? SioCAL CLEFTS/REGENERATIVE T U B U L E S / I N D I V . CELL NECROSIS __5_ -- L- 5 Ln rvj h y d r o n e p h r O s !?s ^ ^ u n i *l a t e r a l ^ ^ PROTEIN DROPLETS. r S ^ M A L TUBULES LUNGS (-.1 .-.-.-) 1 1 C(-1..i-,, 2 (-.1.1 .-,-) 1 C - . - 5-- __5_ L V M P H O c C c N i N F I L ? R A l * F 0 C * L / M "'-T1FO C A L 3 (-.3 .-.-.-) ^ polymorphonuclear 2 (-.2 ,-.-,-) 1 (-.1. ; ? (-*3 ' . m y o d e g e n e r a t i o n , f o c a l /m u l t i f o c a l . m y o c a r d i u m PANCREAS ATROPHY. FOCAL. LOBULE t h y INF mus L A M M A T I O N . C H R O N I C . I N T E R S T I T I A L l .wW I i T t H h pi rM P U T cn pigmented MACROPHAGES hemorrhage, acute, multifocal SPLEEN 5 1 -L1 5 -- 5 1 (".I.-.-.-) - 1_ :1 ,C-.-.i.-,-) 5 ,i c-. i.- __5 _ -4 - __5_ adrenal glands degenerative focus thyroid gland CYST ULTIMOBRANCHIAL cyst __ 5_ __5_ -- -4 -- 5 _ 5_ PART: IV 0.50 5 5 1 (-. 1,- 1 C-. 1.2 C-.2 ,-) 5 -) -) ' l-.-.l.-.-) 5 ) ) 1 (~. 1 11 1 (-.1 ) ) ) 5 1 ('.I.-.-.-) __ 5_ j1 __5 5_ 5 2 1 (1 1 (1 ) ) Company Sanitized. Does not contain TSCA CBI HN-- 15388 TABLE V SPECIES ID E N C " ^ . . . Ng N^ ^ A S T I C L E S I O N . SUBCHRONIC I N P R H r i o i n S f TISSUE/LESION trachea LESION GRADES: (P.1,2,3,4) MALES ^ P D E S GNAION: DOSE CIWG/L) : number in g r o u p - j ,, 00 (days-on-test from II 0,005 5' ciUPHAGUS brain STOMACH DUODENUM JEJUNUM ILEUM CECUM COLON Ln NEMATODE. LUMEN Osl R E C T U M NEMATODE, LUMEN m e s e n t e r i c LVMPH NODE URINARY BLADDER TESTES s k k h s vst EPIDIDYMIDES SPERM GRANULOMA eyes bilateral unilateral sternum bone marrow NOSE inflammation a c u t e , m u c o s a /s u b m u c o s a respiratory epith. J5 _5_ _5_ 5 5 4 96) III 0.05 5 _5 _5_ 5_ _ 5 PART; IV 0.50 5 .5 5 _5 5 5 5_ _ 5 5 5 5 _3 5 5 1 (-.1,- 5 _5 5_ _ 5 Company Sanitized. Does not contain TSCA CBI TABLE V SUMMARY TABLE SPECIES: RAT INCIDENCES OF NONANEOPLA STIC LESIONS SUBCHRONIC I t i s s u e /l e s i o n LESION GRADES: (P , 1.2 .3,4) -- ^55 GROUP DESIGNATIONDOSE (MG/L): NUMBER IN GROUP: NOSE (cont'd) E i S : S I E : "s S ! ; i eSUBE E r S 5 : i E" * TU5 g L Lr r ; ^ p E i ; "TEc: ^ i" f " ^ Ts ' f i ; ; TM i ITM=->`*Tis SQUAMOUS METAPLASIA, RESPIRATORY EPITHELIUM OTHER ___ M A N D I B U l a R L Y M P H NODE: H Y P E R P L A S I A . L Y M P H O I D 5 0 (days-on-test from II 0.005 5 54 to 96) III 0.05 5 5_ __ 5 '( - . 1 . - 00 NOTES: o THE NUMBER OF ORGANS EXAMINED FOR EACH GROUP I S i m p d . O - S . GRADES CGRRESRORD R O S , IOR ,,,C,, ,,,,,, cn PART: 3 IV 0.50 5 5 0 __ Company Sanitized. Does not contain TSCA CBI Company Sanitized. Does not contain TSCA TABLE VI H N - 15388 N ION ST UDV POLYMER P R O D U C T ^ S S S m S ! ? 1 SPECIES: RAT PART: TI SS U E S / O B S E R V A T IONS LIVER F$TTV CHANCF- pnrFUSE' CENTRILOBULAR FflTxv f A N G E ' F 0 C A L - M E D I A N l o b e SEX: MALE GROUP: ANIMAL NLMBER: MODE OF DEATH: DAYS ON TST: DAYS ON RECOVERY: DOSE: CONTROL 376 625 S12O 0 376 376 376 376 839 840 870 873 SD 12 0 SD 12 0 SD 12 0 SD 12 0 376 835 SD 26 14 376 841 SD 26 14 376 849 SD 26 14 376 863 SD 26 14 376 872 SD 26 14 376 801 SD 53 41 376 836 SD 53 41 376 837 SD 53 41 376 847 SD 53 41 376 878 SD 53 41 LN N N LNNNN IN F L A M M A T I O N S U B A C U T ^ ^ U L T I i o C A L ^ 'S C A T T E R E D CENIrR IL O B U L A R OCD Ln KIDNEYS un " ? T E " o c 2 i C L EF 7S /R EG E,'E B * T 1 "E T O B U L E S / I N D I V . C E L L N E C R O S I S N N N N L N N N N N N _~ " - - - _ PROTEIN DROPLETS. PROXIMAL TUBULES -- 1 --- - - LUNGS "------- - _ H I S ? ? o c 0 ^ l f UBFnrT E ' FOCAL/MULTIFOCAL NNNNNLNNLNNLNL POLYMORPHONUCLEAR HEART MYODEGENERATION. FOCAL/MULTIFOCAL. MYOCARDIUM PANCREAS ATROPHY. FOCAL, LOBULE INFLAMMATION.CHRONIC .INTERSTITIAL.WITH thymus HEMORRHAGE. ACUTE MULTIFOCAL SPLEEN PIGMENTED MACROPHAGES ADRENAL GLANDS DEGENERATIVE FOCUS 1 ------ 1 - 1 N N N N N N N N N N N NN N N N N .N ~ N - N - N - N - L 1 N - NN N NN 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 2 N N N N N Company Sanitized. Does not contain TSCA CBI HN-1538B L? TABLE VI s u b c h r o n i c INHALATION s t u d v PART: 2 TISSUES/OBSERVATIONS THYROID GLAND CYST ULTIMOBRANCHIAL CYST SEX: MALE GROUP: ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST; DAYS ON RECOVERY DOSE: CONTROL 376 625 SD 12 0 376 639 SO 12 0 376 640 SD 12 0 376 870 SD 12 0 376 673 SD 12 0 376 635 SD 26 14 376 841 SD 26 14 376 849 SO 26 14 376 863 SD 26 14 376 872 SD 26 14 376 601 SD 53 41 376 376 376 636 837 047 SD SD SD 53 53 53 41 41 41 376 878 SD 53 41 NNNNNNNNNNNNNN N TRACHEA ESOPHAGUS BRAIN Ln ON STOMACH DUODENUM JEJUNUM ILEUM CECUM COLON NEMATODE, LUMEN RECTUM NEMATODE. LUMEN MESENTERIC LYMPH NODE URINARY BLADDER TESTES ATROPHY. ATROPHY, SEMINIFEROUS SEMINIFEROUS EPIDIDYMIDES SPERM GRANULOMA TUBULES TUBULES,' BILATERAL UNILATERAL EYES NNNNNNN NNNNNNNN NNNNNNNNNNNNNNN NNNNNNNNHNNNNNN N N NNN N N NN N N N N N N NNNNNNNNNN N NN N H NNNNN0N NNN N NN NN N N N N N N N N N N N N N N N NNNNNNNNNN NNNNN N N N N N N N N N N N N N N N NNNNNNNNNNNNLNN -P- - NNNNNN0NNNNNNNN NNNNNN0 N0NNNNNN N N N L N N N N N N N N N N N. "1 --------_:- NNNNNNNNNNNNNNN NNNNNNNNNNNNN NN K -ft- I Ul "-J om JHN" 15388 0 POLVMEr PRODUCTS DEPARTMENT SPECIES: RAT SEX: MALE GROUP: I PAR T; TIs s u e s /o b s e r v a t i o n s STERNUM BONE MARROW NOSE ANIMAL NUMBER: MODE OF DEATH: OAVS ON TEST: OAVS ON RECOVERY- ; S S E : E ? : s ' S s i : ; s s s T s r x S S 1TM - T U R S , _ Tes CDs q u a m o u s m e t a p l a s i a , r e s p i r a t o r y e p ?h e l i C m T H E L I U M OTHER M A N D I B U L A R L Y M P H NODE: nH vVnPtERRPPLLAASSItAa. L,Y M P H O I D 825 f 0 N N L lit S?,2D? 0 N N N BAO S?,2D? 0 N N N tit SS,D2O 0 N N N tit 8SD ,2 0 N N N HI 8SD 26 14 N N N tlf SD 26 14 N N N R76 376 376 226 SD 26 14 8 S! D3 26 14 * 1SD1 26 14 80, SD 53 41 NNNN NNNN LN LN 376 636 SD 53 41 N N 376 837 SD 53 41 N N N 376 847 SD 53 41 N N L 376 878 SD 53 41 N N L 11 11 L 2 .Company Sanitized. Does not contain TSCA J.BL, V I H N - 15388 3 SPECIES: RAT SEX: MALE G R O U P .- DOSE: CONTROL TISSUES/OBSERVATIONS LIVER ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY- 376 807 SO 96 84 376 629 SD 96 84 376 834 SO 96 B4 376 661 SD 96 64 376 869 SD 96 84 FATTY CHANGE, DIFFUSE CENTRILOBULAR K TM S S !K - " T ?c n T a ai I a h . si s N *" N - N - N - _N _" - - _ NECR5siri?cTEUBA^ ^ LM^ ^ L ES'SCATTERED-CENTRIL0BULAR ~ -- - - - _ _ n e c r o s i s ! c o a g u ^a t ?v e VIa c u t e HEf o ?CVTES' CENTRIl o b u l a r NECROSIS. COAGULAT^; S ^ T E ^ ^ r ^ A T ^ -- - _ _- - - - Ln kidneys " - --- Od CYST?SioCAL CLEFTS/REGEnERATIYE TUBULES/INDIV. CELL NECROSIS GLOMERULONEPHROPATHY CHRONir NECROSIS N - N - N - - L - - L prVoDS P^ SIS- u r ilAter2l otein oroplets. proximal tubules -- - --- - 1 lungs ~-2 1 h i S??ocC?olSBBFOclL;Mm ? L/MULTIF0CAL N LLLL ' v m p h o c y ?N n^ ^ e - f o e l /m u l t i f o c a l POLYMORPHONUCLEAR heart -v o oeos,, ,, T10N. P0C4L/,, ULT1FOCA^ m 0 U R D l u m pancreas a t r o p h y , f o c a l . LOBULE T H V MIUNSF L A M M A T I O N , C H R O N I C . I NTMTSE TR SITTIITAI ALI. W uIitTtHu , Pr ,I, G M E N T E D M A C R O P H A G E S HEMORRHAGE. ACUTE. MULTIFOCAL SPLEEN adrenal glands DEGENERATIVE focus NNNNN NNNNN CO o PART: 4 c I Company Sanitized. Does not contain TSCA TABLE VI H N - 15388 POLYMER PRODUCTS DEPARTMENT ^ SPECIES: RAT T I SSUES/OBSERVATIONS THYROID GLAND CYST ULTIMOBRANCHIAL CYST SEX: MALE GROUP: I DOSE: CONTROL ANIMAL NUMBER: 376 376 376 376 376 MOOE OF DEATH: OAVS ON TEST: OAYS ON RECOVERY: 8 ? 96 84 8 S?D? 96 84 834 SD 96 84 fl6 > SO 96 64 669 SD 96 84 0 INN TRACHEA ESOPHAGUS brain en STOMACH NNNNN NNNNN NNNNN DUODENUM NNNNN JEJUNUM NNNNN ' ILEUM NNN NN CECUM NNNNN COLON NEMATODE, LUMEN RECTUM NEMATODE, LUMEN MESENTERIC LYMPH NODE URINARY BLADDER N N N N N N ~ L P N - N - N NNN LN ~P- N N N N- N testes 4Io p h y . SEMINIFEROUS a t r o p h y , SEMINIFEROUS EPIDIDYMIDES SPERM GRANULOMA TUBULES, TUBULES, BILATERAL UNILATERAL EYES NNNN NN NNN ~--N_ N N N N " -- NNNNN OCQ PART: 5 Company Sanitized. Does not contain TSCA H N - 15388 ) SEX: MALE GROUP: I DOSE: CONTROL TISSUES/OBSERVATIONS STERNUM ANIMAL NUMBER: M0DE 0f DEATH: DAYS ON TEST: DAYS ON RECOVERY: 376 376 376 376 376 807 829 834 861 869 SD SO SO SD SO 96 84 96 84 96 84 96 84 96 84 BONE MARROW NNNNN NOSE NNNNN N N NN N ~--- - - - -_ ON O ass OTHER - ---_ "- -- _ -- - -_ -- -- MANDIBULAR LYMPH NODE: HYPERPLASIA. LYMPHOID 0 0 00 0 ** e n d OF GROUP I oCO PART: 6 OC I Company Sanitized. Does not contain TSCA Company Sanitized. Does not contain TCA H N - 15388 J-VUIJC, V PART ; TI S S U E S / O B S E R V A T IONS LIVER E; S I EE1- TM UL,R SEX: MALE GROUP: II ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: d a y s o n r e c o v e r y .- 376 376 804 806 SD SD '2 12 00 NN DOSE: LOW 376 376 818 823 SD SD 12 12 00 376 376 844 810 SD SD 12 26 0 14 376 822 SD 26 14 376 852 SD 26 14 376 876 SD 26 14 376 881 SD 26 14 376 800 SD 53 41 376 848 SD 53 41 376 856 SD 53 41 376 866 SD 53 41 376 871 SD 53 41 NNNLNL N n e c r o s i s T I O N S u b a c u e ? Lm u l t i f o c a l E S 'S C A T T E R E D c e n t r IL O B U L A R n e c r o s i s .' c o a g u l a t i ^v e ^ ^ a c u t e ^ E f o c a *V T ^ S ' c e n T R I L O B U L A R n e c r o s i s , c o a g u l a t i v e ; s Sb Ic t e m u l t i f Jc ! l CAL ON KIDNEYS CvSitSi S CLEFTS,,,EC" E" T1V TUBULES/INDIV. CELL ,,e c EOE.E NN N N M. N L N N N VC PROTEIN d r o p l e t s , p r o x i m a l t u b u l e s . LUNGS 1 B in l fl B am " ma ^^ tio i n ", ,sBuebocaUcIulEt;fmuFlc^nrf^**cMaUlLTIFOCAL LYMPHOCYTIC Tnpti t d a Zc ^CAL/MULTIFOCAL POLYMORPHONUCLEAR I N F ^ T ^ ' F O ^ ^ K s c U L A R HEART 1 LLNLNNN 1 m y o d e g e n e r a t i o n , f o c a l /m u l t i f o c a l . m y o c a r d i u m PANCREAS atrophv. focal, lobule t h yIus M A T I 0 N 'C H R 0 N I C , I N T E R S T I T I A L , W I T H P I G M E n t e d m a c r o p h a g e s N L1 N NN N N NN NN NN NNNN hemorrhage, acute, multifocal SPLEEN adrenal glands degenerative focus N NNNNNNN NNNNNNN NN N L 1 N N LN 1 NN N N NN NN NN N N NN NN Company Sanitized. Does not contain TSCA SPECIES: RAT PART; SEX: MALE GROUP: II ANIMAL NUMBER: DOSE: LOW TISSUES/OBSERVAT!ONS THVRID GLAND CYST ULTIMOBRANCHIAL CVST TRACHEA MODE OF DEATH: DAYS on TEST:' DAYS ON RECOVERY 1 1 I 1 i i -a g i J 376 12 0 12 0 12 0 12 0 %12 0 % 26 14 0 LNNN0 P_ 26 14 L P 26 14 N -- 26 14 26 14 53 41 L -- N _ N P 53 41 N m 871 53 4i 53 4! SD 53 41 NNN esophagus brain o STOMACH rv> DUODENUM JEJUNUM ILEUM CECUM 'C O L O N NEMATODE. LUMEN RECTUM nematode, lumen MESENTERIC LYMPH NODE ffl NN NN NN NN N `N NN NN NN 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 N N N N N _N N N n M N R 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 NN NN NN NN NN NN N .N NN N N N N N N N N N N N N N N ~ N N N urinary bladder testes atrophy, a t r o p h y .' seminiferous seminiferous tubui tubui epididymides sperm granuloma bilateral unilateral N N NNN0 N NN N N N N N '-Ki N N N N N N N - N - N _ N N N -- N " L ~ 3 N -- NNNN NNNN NN NN eves NN NN NN N N NN TC Company Sanitized. Does not contain TSCA H N - 15388 PART : T I S S U E S / O B S E R V A T IONS STERNUM BONE MARROW NOSE SBS Ei; SEX: MALE GROUP: II DOSE:' LOW ANIMAL NUMBER: MODE OF DEATH: DAVS ON TEST: DAVS ON RECOVERY: 376 804 SD 12 0 376 806 SD 12 0 376 B 18 SD 12 0 376 823 SD 12 0 376 844 SD 12 0 376 810 SD 26 14 SO 26 14 SO 26 14 SO 26 14 SO 26 14 SO SD 53 53 41 41 SO 53 41 SO 53 41 SO 53 41 IN IINNNNNN NN N NN IN IIN N NN N N N N N N N NNNNNLNN NNNNN LN ON Os! OTHER MANDIBULAR LYMPH NODE: HYPERPLASIA, LYMPHOID ---"---- 1 000000 2 2 TABLE VI m mM N - 15388 SPECIES: RAT "TIS S U E S / O B S E R V A T IONS LIVER SEX: MALE GROUP; ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST; days on recovery- II DOSE: LOW 376 827 SD 96 84 376 376 83 1 862 SD SD 96 96 84 84 376 877 SD 96 84 SO 96 84 ffiss K ? ;; , 5" s lp svltes tiebedS I ' F "s - - ~ L,S N ~ N L - N 'N e" t ..u u u , - -- NECROSIS.' COAGULATI V E VIAC UT EH E Fo?0 C Y T e S - CENTRILOBULAR NECROSIS. COAGULATIVE.' s S a I c T E CMULTlFcAFLCAL 1 -- - ON KIDNEYS ---- -fs* GLOMERULONEPHROPATHY CHRONir TUBULES/In DIV, HYDRONEPHROSIS, u n i l a t e r a l PROTEIN DROPLETS, P R ^ J ^ TUBULES CELL NECROSIS NECROSIS lungs LN ---- 1_ NN - -_ -_ -- h i 5 ? ? S w ? o s i ! "B T O f ; M i;5A L / " u '-TI FOCAL 'SStti y m p h o c C ? N ^ fSS ^ - f < ^ m u l t i f o c a l ^POLYMORPHONUCLEAR INFITRATe " pS S ^ E ^ S C U L A R MYODEGENERATION, f o c a l ,MULTIFOCAL. MYOCARDCUM pancreas ATROPHY, FOCAL, LOBULE i n f l a m m a t i o n .Ch r o n i c ,i n t e r s t i t i a i u/ t t thymus pigmented MACROPHAGES HEMORRHAGE, ACUTE. MULTIFOCAL SPLEEN _N ~ N - N - L - "- - _- - - _: - 1 NNNN L N. 2 N adrenal glands degenerative focus N NN N N N N N NN oCO PART: Company Sanitized. Does not conttn TSCA TABLE V I H N - 15388 POLYMER PRODUCTS DEPA1UMENT SPECIES: RAT TISSUES/OBSERVATIONS THYROID GLAND CYST ULTIMOBRANCHIAL CYST SEX: MALE GROUP: ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY II DOSE: L O W 376 B27 SD 96 84 376 831 SD 96 84 376 862 SD 96 84 376 877 SD 96 84 376 882 SD 96 84 N0NN0 TRACHEA ESOPHAGUS brain O'' Ln STOMACH DUODENUM JEJUNUM ILEUM CECUM ` COLON NEMATODE, LUMEN RECTUM NEMATODE, LUMEN MESENTERIC LYMPH NODE URINARY BLADDER TESTES ATROPHY ATROPHY SEMINIFEROUS seminiferous EPIDIDYMIDES SPERM GRANULOMA TUBULES tubules! BILATERAL UNILATERAL EYES NN NNN N N N NN N NNNN NNNNN N NNNN N NNNN NN NNN N NNNN N NNNN NN LNN P-- N N NNN N N NN NNNNN N N NNN " ~ -- - NNN N N PART ; Company Sanitized. Does not contain TSCA CBI H N - 15368 & TABLE VI POLYMER P R O D U C r ^ E P A R T M E f ? SPECIES: RAT TISSUES/OBSERVATIONS STERNUM BONE MARROW NOSE ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST:' DAYS ON RECOVERY- DOSE: LOW 376 827 SD 96 84 376 831 SD 96 84 376 862 SD 96 84 376 877 SD 96 84 376 882 SD 96 84 NNNNN NNNNN On KiSSiiS!' K i ; ; ? " "ucosa- at TM w i t h i n f l a m m a t i o n ! i S c I E S S ? ! ; i I u s " i " sf: TM " TM AL . ,, TS `TM - INFLAMMATION, SUBACUTE Mn^TTcnrff LLOTURBI NATE fnMAM0US A P L A S I A , FOCAL RESPIRATnDvPcRATRV TURBINATES N -- L - N - N- N -1- -- O n S Q U A M O U S M E T A P L A S I A . R E S P I ^ i o R Y ^ p i i H E L ' u M 7^ 1-1^ OTHER MANDIBULAR LYMPH NODE: HYPERPLASIA. LYMPHOID *** E N D OF G R O U P II 00000 PART : Company Sanitized. Does not contain TSCA CBI Company Sanitized. Does not contain TSCA CB ,HN-15388 SPECIES: RAT PART ; SEX: MALE GROUP: III ANIMAL NUMBER: DOSE: INTERMEDIATE T I S S U E S / O B S E R V A T IONS LIVER MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY- g " : E"feSS!SiSlT: Ils iT i" i ? " necrosis. coaoulatE: L" :^ " SSilO ^ rS ; e s -SCATTE`,,0 .CENTRILOBULAR f ' i i S i TMCEN"TR'-I LOBULAR f t 12 0 12 0 12 0 12 0 12 3 26 14 26 14 26 14 376 857 SD 26 14 376 874 SD 26 14 376 803 SO 53 4i 376 808 SD 53 41 376 811 SD 53 41 376 843 SD 53 41 376 860 SD 53 41 N NN N O s KIDNEYS "vi S T ? * TM ! ! : " ^ ' R E C E N E R A T I V E T U B U L E S A . N D . V . CE LL N E C R O S I S MaasBs^Trj- PROTEIN DROPLETS. R R ^ S J t TUBULES LUNGS ft N N L. HISTIOCYTOSl|UBForIf; F0Cal/MULTIFOCAL vStSC il'^iN l^I-'^iiuL T .E O C A L H ^ R O L TM o R P ,, o N u c L , R ; ; f i - ' ; s ; ^ s c' : ; r * S R " t :s c ,, L . R v o d e c e n e r a t i o n . e o c .l /n u l t .e o c a l . u v o c a r o i u n pancreas ATROPHY. FOCAL. LOBULE I N F L A M M A T I O N , C H R O NI C, INTERSTITIfli l.,-t THYMUS .INTERSTITIAL.WITH PIGMENTED MACROPHAGES L 1 NLLNLL 1 11 11 NN L NN 2 N NN N NN N HEMORRHAGE, a c u t e , m u l t i f o c a l SPLEEN adrenal glands degenerative focus N NN NN N N N N N N' N N N N N N N N NN N NN NN N N NN NN NN N N TABLE VI H N - 15308 CTn OO t i s s u e s /o b s e r v a t i o n s thvroid gland CYST ULTIMOBRANCHIAL CYST TRACHEA esophagus brain STOMACH DUODENUM JEJUNUM ILEUM CECUM ' COLON NEMATODE, LUMEN RECTUM NEMATODE, LUMEN MESENTERIC LYMPH NODE SEX: MALE GROUP: III ANIMAL NUMBER; MODE OF DEATH; DAYS ON TEST: DAYS ON RECOVERY- i N N N M N N N N N N CH/. PART : oco DOSE: INTERMEDIATE 1 f - B - a s i - l l ' ! - n0 0 ON SD 26 14 SD 26 14 SD 26 ; S2D 26 14 14 26 14 53 4 1. 53 41 53 41 NN LN NN -- P _ 3 7 6 40o<oc-/J) 860 SD SD*q 53 53<l> 41 4i 'c NO - CO 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 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 N N N N N N N N N N N N N N N " c3 N NI o N NO NN NN NN NN N N NN N N NNNNNN NNNN URINARY b l a d d e r testes seminiferous atrophy, seminiferous epididymides SPERM GRANULOMA tubules t u b u l e s ,' BILATERAL UNILATERAL eyes N N N 0. 0 N N N N N N N N N N "N N . N N N N N IM N ~- " N - - N - N _ N MIN N N " " N - - N _- NNNNNNNNNN N N N NNNNNNN NNNN TABLE VI CO O Company Sanitized. Does not contain TSCA H N - 15386 L^^^^^^^^JHAM lTIONSTUDV POLYMER P R O D U C T S D E P A ^ S f f SPECIES: RAT PART : SEX: MALE GROUP: III DOSE: INTERMEDIATE TISSUES/OBSERVATIONS STERNUM ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY: s*-sHi"2K "s SSK isss ss 376 376 376 SD 12 O SD 12 O SD SD 12 12 O SD 12 O SD 26 14 SD 26 14 SD 26 14 SD 26 14 SD 26 14 SD 53 41 811 843 B60 SD SD SD SD 53 53 53 53 41 41 41 41 BONE MARROW 0 N N IN N N NN N N NN N N NOSE 0 N N IN N N NN N N N N N N inrcMraraftiiuN, A C U T E M U C O S A / S U B M U C O S A , R E S P I R A T O R V f d t t u I N F L A M M A T I O N , F O C A L ] SSUUBBAACrUnTiEf,U BMrAUXCI0LSLAOT U^R BnItNrAaTETS e t u s 1T H N M N N N N 'N N N N N N L L L 2 o\ FFfOlCrAL|,L T DR cE S? PIARLA'T ORREVS P IERPAITTOHREYL I UTMU R B I N A T E S -- - - _ --------- _ vD OTHER RESPIRATORV EPITHELIUM -- - ::-------- - 2 32 1 :: H Y P E R P L A S I A , L Y M P H O I D 00000000000000 0 TABLE VI SPECIES: RAT a t i s s u h s /o b s e r v a t i o n s liver SEX: MALE GROUP: III ANIMAL NUMBER: MODE OF DEATHDAVS ON TEST: OAVS ON RECOVERY- DOSE: INTERMEDIA-Tt 376 817 SD 96 84 376 846 SD 96 64 376 855 SD 96 84 376 864 SD 96 84 376 075 SD 96 84 H; S i : S S " T ; , 1 t " TM S TM i r s s" T T ' . c E T I t M U L ,, N r E e CcRrOoSsI.Ss*. ? c S o r ou co ; l a,ti." I;V , S cS ^t ,oH T'Epp?ScTMiC;ViT?rSLj;C;EfN"T RLI LOBULAR NLNNN ~-- - - _- - - _ _** - - - _ "~- - "-- - _ 1- - _ ~''xl kidneys ---- CD c y s t !Sf o c a l CLEFTS/r e g e n e r a t i v e t u b u l e s /i n d i v . c e l l NECROSIS NNNLN otein droplets, proximal tubules LUNGS ---P1 -- ~ - -- . i ^ ; 5 S 5 s S s . i "B: s ; f ; , f f i t a T ,roc* 1 l y m p h o c Oc ^ n f i l r a e ' m u l t i f MULTIF0EAL P O L Y M O R P H O N U C L E A R INFT ^ T iFM uC ^ L i F - - - - RUL A R HEART VM3CULAR L L L. N N - -- _I M Y O D E G E N E R A T I O N , f o c a l ,m u l t i f o c a l . m y o c a r d i u m PANCREAS ATROPHY. FOCAL. LOBULE I N F L A M M A T I O N , C H R O N I C I N TE RS TI TT a , ,,,-r THYMUS INTERSTITIAL.WITH PIGMENTED MACROPHAGES L 1 HEMORRHAGE. ACUTE, MULTIFOCAL SPLEEN N adrenal glands degenerative focus N NN N N N* N N N N PART; Company Sanitized. Does not contain TSCA CBI TABLE VI TISSUES/OBSERVATIONS thyroid gland CYST ULTIMOBRANCHIAL CYST SPECIES: RAT SEX: MALE GROUP: III ANIMAL NUMBER: MODE OF DEATHDAYS ON TEST: DAYS ON RECOVERY: DOSE: INTERMEDIATE 376 817 SD 96 84 376 846 SD 96 84 376 855 SD 96 84 376 864 SD 96 B4 376 875 SD 96 84 N0 I0N TRACHEA ESOPHAGUS N NNNN BRAIN "N i STOMACH N N NNN N N NNN DUODENUM N NNNN JEJUNUM NN NNN ILEUM NNNNN CECUM N N NNN ' COLON NEMATODE, LUMEN RECTUM nematode, lumen m e s e n t e r i c LYMPH n o d e N N- N N N NN NNN "-NNNNN URINARY BLADDER N I N 1_ I TESTES atrophy, atrophy. SEMINIFEROUS SEMINIFEROUS EPIDIDYMIDES SPERM GRANULOMA tubules. tubules. BILATERAL UNILATERAL eyes N NNNN N " N - N - N - N N. R N N N NNNN N PART: 5 Company Sanitized. Does not contain TSCA CBI "'Vi ho V JL H N - 15388 J j ^ ^ N * ^ IN H A L A T IO N STUDV 3 P l vivitK h r o d u c t ^ e p K ? SPECIES: RAT TISSUES/OBSERVATIONS STERNUM BONE MARROW NOSE SEX: MALE GROUP: III ANIMAL NUMBER: MODE OF DEATHDAVS ON TEST: DAVS ON RECOVERY: DOSE: INTERMEDIATE 017 SO 96 84 846 SD 96 64 855 SD 96 04 864 SD 96 04 075 SD 96 84 N NNNN N NNNN n f l S ^ 1 Jf- m u c o I ^ U B M U C O s a - e s p i r a t o r v e p i t h i n f l a m m a t i o n ! f o c I l : s u b a c u e m a x ? m A t v e n t r a l m ^a t u s T H - I N F L A M M A T I O N . S U B A C U T E miii I L L 0 T U R 8 I N A TE SQUAMOUS METAPLASIAUTFOCALLTR P C D t n ' RE SpIRATORV TURBINATES s q u a m o u s T . P L . I ; ; : 5 ! r H . S i v Is ; ? S i L f E i TM = <-i<" OTHER MANDIBULAR LVMP,, NODEj HVPEPL. S ,, . *** END OF GROUP III N NNNN --- _ _ -- _~ - - -- - ---- - 00000 Company Sanitized. Does not contain TSCA PART: CO O t C I Company Sanitized. Does not contain TSCA C TABLE V I CQ H N - 15386 0 TISSUES/OBSERVATIONS LIVER FATTY CHANGE. DIFFUSE, CENTRILOBULAR CHANGE. FOCAL. MEDIAN LOBE ^ ^ ^ H R O N j^ ^ ^ H A L A T IO N STIIDV ^ ^ O ^ M E R ^ R O D O C T ^ T eS SPECIES: RAT 1 PART: SEX: MALE GROUP: IV DOSE: HIGH ANIMAL NUMBER: MODE OF DEATH: DAVS ON TEST: DAVS ON RECOVERY: 376 820 SD 12 0 376 B28 SD 12 0 376 654 SD 12 0 376 859 SD 12 0 376 879 SD 12 0 376 819 SO 26 14 376 824 SD 26 14 376 833 SD 26 14 376 858 SD 26 14 376 880 SD 26 14 376 814 SD 53 41 376 815 SD 53 Ai 376 832 SD 53 41 376 850 SD 53 41 376 853 SD 53 41 L 1 L 1 L 1 L 1 L2 S S I ! ! : ~ ,,t i l su la ri n f l a m m a t i o n ! s u b a c u t e ?Lm u l t i f o c a l E S 'SCATTERED'CENTRIL0b u l a r 0" h cSSi;!SI; SSS.li,I C;tif?!JiISCAL ""J KIDNEYS LH SvS!?S;iSSt " -ERTS/REOENSRATIVE TUBULES/1NDIV. CELL NECROSIS glomerulonephropathy. chronic hydronephrosis, unilateral PROTEIN DROPLETS. PROXIMAL TUBULES LUNGS 2 L 1 L L N N .L 2 H I S ? ? o r S T ^ , i UBACUTE- pOCAL/MULTI FOCAL POLYMORPHONUCLEAR I~R.:T;!;TLl : PSuCi!i,ScSi;r# U !iA'scULR HEART m y o d e g e n e r a t i o n , f o c a l /m u l t i f o c a l . m y o c a r d i u m PANCREAS ATROPHY, FOCAL. LOBULE .NFLAMMATION,CHRONIC.INTERSTITIAL.WITH RICMSNTEO .ACROPMAOes THYMUS HEMORRHAGE. ACUTE. MULTIFOCAL SPLEEN adrenal glands degenerative focus NNNNNN N NNNNN ` - - NNN NN N NN NNNN N' N N N N N L N L N N L 1 L N L 11 1 N N N N N N L ] L N N N N N. N N N N N ---- -- :- L 1 N L 1 N N N N N N N NN N NN NNN N LN 1 N N N N N N Company Sanitized. Does not contain TSCA C MN-15388 TABLE VI PART : t i s s u e s /o b s e r v a t i o n s thvroid gland CVST ULTIMOBRANCHIAL CVST TRACHEA esophagus brain STOMACH DUODENUM JEJUNUM ILEUM CECUM ` COLON NEMATODE. LUMEN RECTUM NEMATODE, LUMEN M E S E N T E R I C LVMPH NODE URINARY BLADDER TESTES ATROPHY. ATROPHY. SEMINIFEROUS SEMINIFEROUS TUBULES TUBULES,' epididymides SP ERM GRANULOMA EYES S E X : MALE GROUP: ANIMAL NUMBER: MODE OF DEATH: DAYS ON T E S T : DAYS ON RECOVERY ; bilatera l UNILATERAL DOSE: HIGH 376 820 SD 12 0 N '- N N N N N N N N N " 376 82B SD 12 0 N - - N N N N N N N N N ~ 376 854 SD 12 0 N - - N N N N N N N N N " 376 859 SD 12 0 376 879 SD 12 0 0I NN NN NN NN NN N.N NN NN NN 376 819 SD 26 14 N " N N N N N N N N N 376 824 SD 26 14 N ~ N N N N N 0 N N N 376 833 SD 26 14 N - N N N N N N N N N 376 858 SD 26 14 L P N N N N N N N N N 376 880 SD 26 14 N - N N N N N N N N N 376 814 SD 53 41 L P N N N N N N N N N 376 815 SD 53 41 N - N N N N N N N N N 376 832 SD 53 41 I N N N N N N N N N 376 850 SD 53 41 N - N N N N N N N N N 376 853 SD 53 41 L P N N N N N N N N N N - N - N NN 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 NN NN -- - N 'N -NN N ' NN -"- NN ~- NN 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 L 1 - N - N' N N - L 2 N N N - - N -* N N N - - N - N Company Sanitized. Does not contain TSCA CBI TABLE VI SEX: MALE SPECIES: RAT GROUP: IV ANIMAL NUMBER: DOSE: HIGH TISSUES/OBSERVATIONS MODE OF DEATH: DAYS ON TEST: STERNUM BONE MARROW NOSE INFLAMMATION ACUTP ""J DAYS ON RECOVERY- N N N 12 0 N N N 12 0 N N N 12 0 N N N 12 0 26 14 26 14 NNN NN I O N' N 26 14 N N N 26 14 N N N 26 14 N N N 53 41 N N N 53 41 53 41 53 41 NNN N NN N LL 53 41 N N L 1 c_n s o S S I SSi;;: M s i T O H ' ? j r ? s s i TM " i""li8I",TES OTHEERR MANDIBULAR l y m p h NODE: nHYrPPEtRKPPLLAASSIIAA, L,YMPHOID 11 00 H N - 15388I 3 polvmer^ odu^ ^ eparH n? SPECIES: RAT TISSUES/OBSERVATIONS LIVER SEX: MALE GROUP: ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY; IV 37 SD 96 84 DOSE: HIGH 376 B26 SD 96 B4 376 842 SD 96 B4 376 645 SD 96 B4 376 866 SD 96 64 K ;S s l : LL NNL -- --- 1 1 -- NECROSIS,' C O A ^ A T I V E ACUTEHEFni?CVTES> CENTRILOBULAR n e c r o s i s , c o a g u l a t i v e ! s S b ! c t e ? Cm u ^ ^ ^ af C a l _- - 1 --- - kidneys " "-- o c t ? % TK c f t s e m m m a t i v , TUSULesiIN0IV L NLN glomerulonephropathy chrontp HYDRONEPHROSIS. UNILTERA? necrosis ~- - -- --" - - PROTEIN DROPLETS. PROXIMAL TUBULES -_ 1~ LUNGS 2--- HI STIOCYTOSI S ^ F O C A L ^ ^ / M U L T I FOCAL IN F L A M M A T O N s C b a c u P U L I ^ 0 C A L LYMPHOC YTI c i NFILTRATE ' m U I F 0 C A L ^POLYMORPHONUCLEAR l L T K S ^ i r a t C J ^ MYODEGENERATION. FOCAL/MULTIFOCAL. MYOCARDIUM PANCREAS ATROPHY, FOCAL. LOBULE INFLAMMATION,CHRONIC INTERSTTXia, THVMUS C.INTERSTITIAL.WITH PIGMENTED MACROPHAGES -L N N N --- 1--1-- ---_ "' -- N L NN 1 N N L. N i hemorrhage, acute, multifocal SPLEEN adrenal glands degenerative focus NNNNN N' N N N N oC PART: A Company Sanitized. Does not contain TSCA TABLE VI HN-153SS HULYMER P R O D U C T S D E P A ^ T O I E r ? SPECIES: RAT SEX: MALE GROUP: IV ANIMAL NUMBER: DOSE: HIGH TISSUES/OBSERVATIONS THYROID GLAND CYST ULTIMOBRANCHIAL cys t MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY 016 Z6 842 845 868 SD SD SD SD SD 96 96 96 96 96 84 84 84 84 84 ^o 0 0l trachea -p -"J esophagus brain STOMACH N N N NN NN NNN N N N NN DUODENUM JEJUNUM ILEUM CECUM ' COLON NEMATODE, LUMEN RECTUM NEMATODE, LUMEN MESENTERIC LYMPH NODE URINARY BLADDER TESTES seminiferous atrophy, seminiferous epididymides SPERM GRANULOMA tubules, tubules. bilateral UNILATERAL EYES NNNNN N N NNN NN N NN NNNNN NNNNN NN --- N - N - N NNNNN -~"- N I N N. I N N N N '' N NNNNL *~ - - - 1 N N N N N NNNNN PART; 5 -LC I Company Sanitized. Does not contain TCA CBI N N - 15,388 SPECIES: RAT TII!S S U E S / O B S E R V A T I O N S STERNUM SEX: MALE GROUP: ANIMAL NUMBER: MODE OF DEATH: DAVS ON TEST: D A VS O N R E C O V E R V: IV DOSE: H I Gt 37 SD 96 84 376 B26 SO 96 64 376 842 SO 96 84 376 845 SO 96 84 376 668 SD 96 84 BONE MARROW IN N N N NOSE NNNNN INFLAMMATION,' ACUTe ' MUCoi/SUBMUC SA * RESPIRATORY EPITH i n f l a m m a t i o n f o c a l ' s u i A r n i f UB.M U C 0 S A A N T R A L M E A T U S INFLAMMATION. SU BAc t I M m irini?A X I L L 0 T U R B I N A TE N N ~ N - N - N _ --- _ ''s i SQUAMOUS M E T A P U S I A FOCAL RESPIRATORV TURBINATES - -_ *- - _ co s q u a m o u s m e t a p l a I aA : r e s p i r a t o r y p ? h e l " m T H E L Iu m -- - OTHER ----- MNr,.a,LR LVP,, n o d e ! hyperpl . . Lnnml0 0000 *** END OF GROUP IV OCO PART: Company Sanitized. Does not contain TSCA 190 V0S1 uibjuoo jou saoQ pazunieg AueduioQ APPENDIX VI CLINICAL PATHOLOGY REPORT NO. 24-84 - 79 - # 180 VOSI uiB^uooioiLsaon pazniuBs ueduioo LO ESTABLISHED 1302 E. I . d u P o n t d e N e m o u r s 51 C o m p a n y IN CO RPO RATED Haskell Laboratory for T oxicology and Industrial Medicine P.O. Box 50, Elkton Road N e w a r k , D elaware 19711 CENTRAL RESEARCH AND DEVELOPMENT DEPARTMENT CLINICAL PATHOLOGY REPORT NO. 24-84 SUBCHRONIC INHALATION TOXICITY 0 MEDICAL RESEARCH PROJECT NO. HASKELL LABORATORY NO. 15388 FEBRUARY 2 8 . 1985 Summary. ^ ^ fIa l^ C r ^ C D (S D )B R r a t s were exposed, by in h a la tio n , to L -- ^ Q a t con cen tration s o f 0 (c o n tr o l), 0 .0 0 7 6 , Q .O S^nd^A S mg/L. Compound-related e ff e c t s observed in high-dose (0 .4 8 mg/L) m ales a t the 0 day recovery period in cluded a lt e r a t io n s in s e v e r a l hem atologic and c m i c a l chem ical p a ra m e te rs. The h em atologic changes in clu d e d an in c r e a s e in red blood c e l l co u n t, hemoglobin and h e m ato crit and a d e c r e a se in mean c o rp u sc u la r hemoglobin and mean c o rp u sc u la r hem oglobin c o n c e n tr a tio n . The c lin ic a l chem ical changes included an in cre ase in a lk a lin e ph osph atase, urea n itr o g e n , u rin e volume and pH and a d e c r e a se in u rin e o s m o la lity and serum c h o le s te r o l. These e f f e c t s were not p resen t a t any o f the subsequent recovery periods. The 0 .0 5 8 mg/L exp osu re c o n c e n tra tio n was in te r p r e te d to be a n o - e ffe c t dose le v e l f o r the h em ato lo gic and c l i n i c a l chem ical p aram eters measured under the con dition s of th is study. Procedure Four groups o f 20 male Crl:CD(SD)BR r a t s were exposed, by in h a la tio n f o r s i x hours p e r day fo r 10 days to Telomer B s u lf o n ic a c id a t con cen tra tio n s o f 0 ( c o n t r o l) , 0 .0 0 7 6 , 0.058 and 0 .4 8 mg/L. A fte r the n in th exp osu re, an overn igh t (app roxim ately 16-hour) urine specim en was c o lle c t e d from ten r a t s p er group to m easure volume (VOL) o s m o la lity (0SM 0L), pH and u ro b ilin o g e n (UR0BL); and to determ ine the ' p resen ce o f b lo o d , su gar (g lu c o s e ) , p r o te in , b ilir u b in and ketone . ( a c e t o a c e t i c a c i d ) . The appearan ce ( c o lo r and tra n sp a re n c y ) was recorded and tne sedim ent from each specim en was m ic r o s c o p ic a lly exam ined. 80 A fter the tenth exposure (0-Day R ec), and a t the 14-day recovery period (14-Day Rec) and 41-day recovery period (41-Day R ec), blood was taken from the t a i l o f ten r a ts per group fo r measurement o f ery th ro cy tes (RBC), hemoglobin (H b), mean c o rp u sc u la r volume (MCV), p l a t e l e t s (PLAT), le u k o c y te s (WBC) and r e l a t i v e numbers o f n e u tro p h ils (N e u t), band n e u tr o p h ils (B an d ), lymphocytes (Lymph), a t y p ic a l lymphocytes (Alym), monocytes (Mono), e o sin o p h ils (E o sin ) and b a so p h ils (B a so ). A bsolute numbers o f v a rio u s types o f leu k ocytes were c a lc u la te d from the le u k o c y tic d a ta . H em atocrit (H t), mean c o rp u sc u la r hemoglobin (MCH) and mean c o rp u sc u la r hem oglobin c o n c e n tra tio n (MCHC) were c a lc u la te d from the e r y th r o c y tic d a t a . Serum a c t i v i t i e s o f a lk a l in e ph osp h atase (ALP), a la n in e a m in o tra n sfe ra se (ALT) and a s p a r ta te am in o tran sfe rase (AST) and c o n ce n tratio n s o f u rea n itro g e n (BUN), c r e a tin in e (CREAT), t o t a l p r o te in (TPROT) and c h o le s t e r o l (CHLOS) were a ls o measured. A fter each sam pling tim e, fiv e r a ts from each group were then k ille d for pathologic evaluation . Follow ing an 84-day recovery period (84-Day R ec), the hem atologic and c l i n i c a l chem ical (serum and u rin e) measurements were rep eated on the fiv e remaining ra ts in each group. S ta tistic s Hem atologic and c l i n i c a l chem ical d a ta were s t a t i s t i c a l l y analyzed u sin g a one-way a n a l y s is o f v a r ia n c e fo r each sam pling tim e. When the F - t e s t was s ig n if ic a n t , le a s t s ig n if ic a n t d iffe re n c e (LSD) and Dunnett t e s t s were used to compare the control" group and the groups exposed to Telomer B su lfo n ic a c id . S ig n ific a n c e was ju d g e d a t the 5% p r o b a b ilit y le v e l u sin g Dunnett c r ite ria . R esults R e su lts o f hem atologic and c l i n i c a l chem ical measurements are summarized in T ab le s I , I I and I I I , s t a t i s t i c a l a n a ly s e s in T ab le s IV and V. Data fo r in d iv id u al anim als are l i s t e d in the computer p rin to u ts attach ed to th is r e p o r t . A le g e n d , p re c e d in g the computer p r in t o u t s , d e fin e s term s and c r it e r ia used fo r u rin a ly se s. At the 0-day reco v ery sam plin g tim e , r a t s in the h ig h -d o se (0 .4 8 mg/L) group had an in c r e a se d e ry th ro c y te co u n t, hemoglobin and h e m a to c r it. Mean c o rp u sc u la r hemoglobin co n c e n tratio n was in c re ase d fo r the in te rm e d iate -d o se (0 .0 5 8 mg/L) r a t s and d e c re a se d fo r the h igh -d ose r a t s . D ecreased mean co rp u scu lar hemoglobin and p l a t e le t count were observed fo r r a t s in the high -dose group. Serum a lk a lin e phosphatase and serum a sp a r t a t e am in o tran sfe rase a c t i v i t i e s and serum u rea n itro g en co n ce n tratio n were in creased fo r the h igh -dose r a t s . R ats in the high-dose group had decreased serum c h o le s te r o l c o n c e n tr a tio n . U rine volume and pH were in c r e a se d f o r r a t s in the high -dose grou p. D ecreased u rin e o sm o la lity was ob served fo r the high-dose r a ts . 81 Company Sanitized. Does not contain TSCA CBI At the 14-day recovery sam pling tim e, r a t s in the high-dose group had d e c re a se d hem oglobin, mean c o rp u scu la r hemoglobin and mean c o rp u sc u la r hem oglobin c o n c e n tr a tio n . Urine pH was d e c re a se d f o r the in te r m e d ia te - and high-dose r a ts . At the 41-day recovery sam pling tim e, r a t s in the high-dose group had a d e c re a se d e ry th ro c y te co u n t. The p l a t e l e t count was in c r e a se d f o r the h ig h -d o se r a t s . D ecreased serum a la n in e a m in o tra n sfe r a se a c t i v i t y was observed fo r r a t s in the low -(0.0076 mg/L) and high-dose groups. At the 84-day recov ery sam pling tim e, r a t s in the in te rm e d ia te - and h igh -dose groups had in c re ase d leukocyte counts and a b so lu te numbers o f lym ph ocytes. The a b so lu te number o f n e u tr o p h ils was in c r e a se d f o r the h igh -dose r a t s . Serum u rea n itrogen co n cen tratio n was d ecreased fo r r a t s in the high-dose group. D iscu ssio n and C onclusions There was a s t a t i s t i c a l l y s ig n if ic a n t in c r e a se in red blood c e l l count, hem oglobin, h e m a to crit, a lk a lin e ph osph atase, u rea n itro g e n , urin e volume and pH in the h ig h -d o se an im als a t the 0-day re c o v e ry sam pling tim e. At t h i s tim e p e r io d , th e re was a l s o a s t a t i s t i c a l l y s i g n i f i c a n t d e c re a se in mean c o rp u sc u la r hem oglobin, mean c o rp u sc u la r hem oglobin c o n c e n tra tio n , u rin e o sm o la lity and serum c h o le ste r o l in the h igh -dose an im als. The o th e r h em ato lo gic and c l i n i c a l ch em ical p aram eters shown to be s t a t i s t i c a l l y s ig n if ic a n t ly changed were w ithin the range o f expected b io lo g ic a l v a r ia tio n and were not re la te d to the ad m in istratio n o f the compound. The 0 .0 5 8 mg/L exp osu re c o n c e n tra tio n was in te r p r e te d to be a n o - e ffe c t dose le v e l fo r the h em ato lo gic and c l i n i c a l ch em ical p aram eters measured under the con dition s o f th is study. DRH:bl CP 3 2/28/85 Report by: Donna R. H olt Technician Approved by: CAjUtAjb C h a r lo tte M. Keenan Acting Coordinator C lin ic a l Pathology Section 8Z Company Sanitized. Does not contain TSCA CBI TABLE I SUMMARY OF HEMATOLOGIC FINDINGS FOR MAI.F. RATS EXPOSED BY INHALATION T o Q g H H H M f l H H M V ' O R 10 DAYS GROUP MEANS AN^STANDAR^DEvIATIONSfSDN O UJ K <01 =r co 0 UJ os <c 0 1 xt U2J: M H0 O UJ 2 OS M >H 2On < Q <1 CO T"" yx yx yx vo on \ o cn ? f - ON fO OOOO W V/ X_U i n y o n 3- h - 3 - OO co t-- co y x yx. / / - \ m 3 f CM CO 3* 3* in 3* oooo >/ w CM V on i n S- t- w ON 0> i n rvj S- S- yx yx yx vo a* m in m 3 c o in oooo Na/ X.-U W ^ (NJ ON CO C-- r* O 3 r* t - r - t>* /-S /*N y x 0 0 v o CO CO 0O O O V / W W V/ 0 i n c o r-- VO i n i n i n T- 1- y x y x /*\ y x a* in 0 00 O w V-/ V-/ N-/ in in in O in in in in r-- r~ y /-S y x i n i n i n VO 000O V/ XU x - / c o ON O CO * i n i n vo 3T T-- T - t-- y y x /-S *-- r a - m >u N^U W y o> on 0 J3- o n 3T xr yx yx yx O J cm m CM W W X_u my y 0 3T 3T yx CM CM 1- on X.U x - ' X-/ x u y O CM 0 XT 3T 3* y x /--X y x y x y CM CM CM w XU XU Xu ON *-- T-- *-3T in i n in yx yx yx CM 1-- CM CM Xu XU XU on ^ St in in in in y x /x /-x y x CM CM t - CM Nu xu XU XU c-- t - v o i n in in in in yx yx yx yx r -- CM y y XU x_u w w O 0 ON ON CM CM r -- -- /--X y x y x y x y y *-- w XU XU XU e0 * T-- *-CM CM CM CM yx yx yx yx CM y 1-- t-- XU XU XU XU * CM CM y y CM CM CM CM O yx yx yx yx yx yx yx yx yx yx yx yx yx yx yx yx yx yx y yx UJ t - ^ C - =t ON i n PS i n i n r r CM on on cm CM. y T-- **-- CM t-- y y y 0 * O OO 00O O 00 00< O XU XU XU XU XU X XU XU x_u X U XU XU XU U XU x u XU Xu xU XU 1 vo in O 3 T CM cm i n VO m in on CM CM ON t*- t-- *-- y CM ON in in in vo 3T 3T =r in in m in CM CM CM T" c*-- D-- CO T-- y y T- UJ yx to j 0s Q bO O VO O 0 O N * 00 0 0 0 in co O O 0 xt oooo O vO O O O sc o 0 O 0 in co O 0 0 xr oooo 0 VO O O 0 t - co 0 0 0 in co 0 0 0 a* oooo 0 VO O O 0 sra o 0 0 in co 0 0 0 =f oooo 0 vO O O 0 so o 0 0 0 in 00 0 O 0 .3T oooo U OT O \ H vO oo O O u 0 y E-i O S X J 0 JO X X t>0 4^ X ** - 83 - > 0 2 : Cm 2 U bO s: a Company Sanitized. Does not contain TSCA CBI TESTS MCHC g/dL PLAT x 1 0 3 /uL 00 1 lAoLc. I t co n tin u e d ) SUMMARY OF HEMATOLOGIC FINDINGS FOR MALE RATS EXPOSED BY INHALATION T o t a B ^ H l | B | [ ^ M A r o R 10 DAYS GROUP MEANS DOSE (m g/L) 0.0000 0.0076 0.0580 0.4800 0.0000 0.0076 0.0580 0.4800 0-DAY REC SAMPLING TIME 14- DAY REC 41- DAY REC 84- DAY REC 3 7 .( 3 7 .( 3 8 .( 3 3 .( 1 .) 2 .) 1 .) 1 .) 3 9 .( 39. ( 3 8 .( 37. ( 2 .) 2 .) 1 .) 2 .) 37. ( 38. ( 38. ( 38. ( 1.) 1 .) 2 .) 1 .) 39. ( 40. ( 37. ( 37. ( 1 .) 3. ) 2 .) 2 .) 9 2 9 . ( 121 .) 843. ( 110.) 821.( 137.) 729.( 111.) 1081.( 1064.( 1069.( 1080.( 163.) 125.) 162.) 9 6 .) 9 5 0 .( 1074.( 1099.( 1166.( 129.) 121 .) 151 .) 159.) 1208.( 1221.( 1141.( 1035.( 108. ) 2 6 7 .) 121. ) 146.) Company Sanitized. Does not contain TSCA ooo Company Sanitized. Does not contain TSCA CBI TESTS WBC x 103/u L Neut 1 WBCx% U0i0 1 Band WBCx% Lymph WBCx% Alym WBCx% TABLE I(continued) SUMMARY OF HEMATOLOGIC FINDINGS FOR MALE RATS EXPOSED BY INHALATION TO H H M B H I H H H H I f o Rj10 DAYS GROUP MEANS AN! DOSE (mg/L) 0.0000 0.0076 0.0580 0.4800 0.0000 0.0076 0.0580 0.4800 0.0000 0.0076 0.0580 0.4800 0.0000 0.0076 0.0580 0.4800 0.0000 0.0076 0.0580 0.4800 0-DAY REC SAMPLING TIME 14-DAY REC 41-1DAY REC 84-:DAY REC 1 2 .5( 1 1 .7( 1 1 .3( 12.4C 3.3) 2 .1 ) 2.4) 3.1) 13.K 13.7( 14.7( 14.9( 1.9) 3.0) 5.5) 2.9) 12.1 ( 14.3( 15.3( 14.8( 1 .6 ) 2.7) 5.6) 4.5) 11 .6 ( 13.0 ( 17.K 2 0 .1 ( 1 .0 ) 1.9) 3.3) 3.3) 2223.( 920.) 2638.( 1108.) 1929.( 583.) 2429.( 579.) 0 .( 13.( o.( o.( 0 .) 42.) 0 .) 0 .) 2578.( 2719.( 2989.( 2873.( 1078.) 1456.) 1428.) 677.) 0 .( 0 .) o.( 0 .) o.( 0 .) 0 .( 0 .) 2091.( 839.) 2921.( 913.) 3137.( 1762.) 3480.( 2311.) 0 .( 0 .( 0 .( 15.( 0 .) 0 .) 0 .) 47.) 1728.( 311.) 2 1 2 0 .( 773.) 2 9 2 2 .( 592.) 5270. ( 1 7 2 2 .) 0 .( 0 .( 43.( o.( 0 .) 0 .) 96.) 0 .) 9492.( 3033.) 8284.( 1637.) 8559.( 1953.) 9173.( 2833.) 10468.( 1744.) 1 0 6 7 2 .( 3099.) 11487.( 4450.) 11803.( 2548.) 9775.( 1128.) 11053.( 2056.) 11557.( 4068.) 10782.( 2058.) 9374.( 1259.) 10417.( 1467.) 13069.( 2127.) 13634.( 2 2 1 0 .) 167.( 240. ( 208. ( 142.( 1 1 2 .) 180.) 139.) 6 8 .) 14.( 45. ( 91.( 104.( 44.) 72.) 91.) 128.) 45. ( 6 8 .( 171.( 141.( 59.) 72.) 228.) 140.) 167.( 188.( 275.( 378. ( 180.) 145.) 452.) 197.) Company Sanitized. Does not contain TSCA CBI TESTS Mono WBCx% Eosin WBCx% 00 I Baso WBCx56 t a b l e It continued) SUMMARY OF HEMATOLOGIC FINDINGS FOR MALE RATS EXPOSED BY INHALATION 10 DAYS GROUP MEANS ANDSTANDAR^DEV^^^ONSCSD) DOSE (mg/L) 0.0000 0.0076 0.0580 0.4800 0.0000 0.0076 0.0580 0.4800 0.0000 0.0076 0.0580 0.4800 0-DAY REC 541.( 170.) 475.( 260.) 554. ( 196.) 656.( 301 .) 48.( 69. ( 50.( 0 .( 67.) 8 6 .) 65.) 0 .) o.< 0 .) 0 .( 0 .) o.( 0 .) 0 .( 0 .) SAMPLING TIME 14-DAY REC 41- DAY REC 84-:DAY REC 16.( 49.) 142.( 155.) 126. ( 118.) 131.( 140.) 90.( 96.) 193.( 216.) 233. ( 246.) 208. ( 209.) 2 1 1 .( 285.) 242. ( 125.) 526. ( 677.) 525. ( 519.) 25. ( 83.( 48. ( 0 .< 54.) 77.) 84.) 0 .) 90.( 81 .) 61.( 80.) 140.( 105.) 174. ( 243.) 160.( 1 2 0 .) 74. ( 69.) 226. ( 209.) 253.( 303.) 0 .( 0 .) 0 .( 0 .) o.( 0 .) o.< 0 .) 0 .( 13.( 2 2 .( 0 .( 0 .) 42.) 70.) 0 .) 0 .( 0 .) 0 .( 0 .) o.< 0 .) 0 .( 0 .) Company Sanitized. Does not contain TSCA CBI TESTS ALP U/L ALT U/L AST U/L BUN mg/dL 1ADLE. J.J. SUMMARY OF CLINICAL CHEMICAL FINDINGS FOR MALE RATS EXPOSED BY INHALATION TO GROUP MEANS A N ^ S T A N D M ^ jIe VIATIONS^D) 10 DAYS DOSE (mg/L) 0.0000 0.0076 0.0580 0.4800 0.0000 0.0076 0.0580 0.4800 0.0000 0.0076 0.0580 0.4800 0.0000 0.0076 0.0580 0.4800 0-DAY REC 191.( 199.( 206. ( 325. ( 62.) 52.) 49.) 48.) 37.( 39.( 44.( 44.( 5.) 7.) 11 .) 8 .) 87.( 83. ( 91 .( 108.( 14.) 1 2 .) 15.) 17.) 16.( 17.( 16.( 29. ( 3.) 2 .) 3.) 4.) SAMPLING TIME 14-]DAY REC 41-1DAY REC 84-1DAY REC 171. ( 179.( 1 9 6 .( 215.( 58.) 56.) 38.) 59.) 131.( 151.( 157.( 152.( 30.) 40.) 42.) 55.) 97. ( 134.( 126.( 1 2 0 .( 37.) 41.) 56.) 73.) 35.( 34. ( 36. ( 36.( 4.) 7.) 5.) 5.) 40.( 32. ( 37. ( 33.( 7.) 4.) 4.) 6 .) 34. ( 29. ( 43.( 35.( 5.) 5.) 25.) 1 1 .) 76.( 75. ( 79. ( 70. ( 11 .) 1 0 .) 15.) 11 .) 76.( 73.( 76.( 77.( 1 2 .) 1 2 .) 14.) 1 1 .) 6 6 .( 60.( 83.C 71.( 1 1 .) 6 .) 35.) 17.) 17.( 17.( 17.( 19.( 3.) 2 .) 3.) 4.) 17.( 17.( 17.( 17.( 2 .) 1 .) 2 .) 2 .) 2 0 .( 19.( 19.C 15.C 4.) 1 .) 3.) 2 .) Company Sanitized. Does not contain TSCA CBI TESTS CHEAT mg/dL TPROT I g/dL 0000 I CHLOS mg/dL TABLE Il(continued) SUMMARY OF CLINICAL CHEMICAL FINDINGS FOR MALE RATS EXPOSED BY INHALATION FOR 10 DAYS GROUP MEANS A N ^ S T ANDAR^D^m^^^^fsn') DOSE (mg/L) 0.0000 0.0076 0.0580 0.4800 0.0000 0.0076 0.0580 0.4800 0.0000 0.0076 0.0580 0.4800 0-DAY REC 0.54( 0.07) 0.59( 0.05) 0.63( 0.06) 0.64( 0.14) 5.9( 6 ,0 ( 6 .K 6 .2 ( 0 .2 ) 0 .3 ) 0.3) 0 .5 ) 57.( 49.( 50.( 19.( 13.) 1 1 .) 5.) 6 .) SAMPLING TIME 14-1DAY REC 41-1DAY REC 84-lDAY REC 0.59( 0.06) 0.59( 0.06) 0.58 ( 0.04) 0.60( 0.07) 0.65( 0.04) 0 .6 8 ( 0.06) 0.67 ( 0.06) 0.65( 0.07) 0.63( 0.05) 0.69 ( 0.06) 0.67( 0.04) 0.64( 0.06) 6 .2 ( 6 .1 ( 6 .1 ( 6 .6 ( 0.7) 0.4) 0 .8 ) 0.5) 6.3( 6.4( 6 .2 ( 6.1 ( 0.5) 0.5) 0 .6 ) 0.4) 6.5( 7.0< 7.1( 6 .9 ( 1 .1 ) 0.4) 0.3) 0.3) 71.( 62. ( 63.( 59. ( 13.) 11 .) 1 1 .) 9.) 67 .( 69. ( 71.( 63.( 13.) 19.) 19.) 1 2 .) 117.( 92. ( 94. ( 75. ( 53.) 17.) 2 0 .) 16.) Company Sanitized. Does not contain TSCA CBI TESTS VOL mL OSMOL 1 mOs OD . VO I pH UROBL mg/dL 1 H D L .il 1 1 1 SUMMARY OF CLINICAL URINE ANALYSIS FINDINGS FOR MALE RATS EXPOSED BY INHALATION FOR 10 DAYS GROUP MEANS AND, STANDAH^DEv Ta TJONS(SDJ DOSE (m g/L) 0-DAY REC SAMPLING TIME 14-DAY REC 41-DAY REC 84-DAY REC 0.0000 0.0076 0.0580 0.4800 7.2( 5.2( 7.5( 1 1 .9( 3.7) 1 .6 ) 3.3) 2.5) 1 3 .2 ( 1 2 .4( 1 2 .5( 1 2 .0 ( 4.3) 4.5) 4.5) 1 .8 ) 13.5( 13.8 ( 13.3( 13.5( 4.9) 5.0) 4.6) 7.0) 13.5( 6.4) 17.4( 13.7) 16.3( 5.4) 1 7 .0 ( 9.0) OOsT 0.0000 0.0076 0.0580 0.4800 1714.( 296.) 1795.( 350.) 1610.( 389.) 850. ( 171.) 1447.( 1316.( 411.) 1566.( 335.) 1538.( 312.) 1895.( 370.) 1633.( 373.) 1821., ( 523.) 1626.( 467.) 1784.( 756.) 1602.( 663.) 1364.( 3 6 1 .) 1446.( 551 .) 0.0000 0.0076 0.0580 0.4800 7 -3( 6 .8 ( 7.0( 8.3( 0.7) 0 .6 ) 0.7) 0.7) 8 .1 ( 7.6( 7.1( 7.2 ( 0.7) 0.5) 0 .6 ) 0.4) 7.2( 7.3( 7.0( 7.0( 0.4) 0.5) 0.5) 0.5) 7.4 ( 7.0 ( 7.4( 7.2( 0.5) 0 .0 ) 0.5) 0.4) 0.0000 0.0076 0.0580 0.4800 0.9( 0.9( 1 .0 ( 0 .6 ( 0.3) 0.3) 0 .0 ) 0.5) 1 .0 ( 0 .8 ( i.o( 1 .0 ( 0 .0 ) 0.4) 0 .0 ) 0 .0 ) 1 .0 ( 1 .0 ( 1 .0 ( 1 .0 ( 0 .0 ) 0 .0 ) 0 .0 ) 0 .0 ) 0 .3 ( 0 .6 ( 0.6 C 0.5( 0.4) 0.5) 0.5) 0.5) TABLE III (continued) SUMMARY OF CLINICAL URINE ANALYSIS FINDINGS FORMALE RATS EXPOSED BY INHALATION TOI FOR 10 DAYS Sampling Time Dose (mg/L) 0 .0076 .058 .48 Measurement Blood Number Positive 1 /1 0 * 3/10 1 / 1 0 0 / 1 0 Sugar (Glucose) Number Positive 2 / 1 0 3/10 1 / 1 0 3/10 Protein Number Abnormal 2 +3 0/10 0/10 0/10 0/10 Bilirubin Number Positive 6 / 1 0 3/10 2 / 1 0 3/10 Ketone Number Positive 9/10 8 / 1 0 1 0 / 1 0 0 / 1 0 Appearance (Color 0 / 1 0 and Transparency) 0/10 0/10 0/10 Microscopic Number Abnormal 4/10 1 / 1 0 1 / 1 0 0 / 1 0 0 .0076 .058 .48 0/10 0/10 1/10 0/10 0/10 1/10 2/10 0/10 1/10 0/10 1/10 0/10 4/10 2 / 1 0 7/10 6 / 1 0 9/10 8 / 1 0 9/10 8 / 1 0 0/10 0/10 0/10 0/10 6 / 1 0 1 / 1 0 4/10 3/10 * Number of abnormal or positive findings/number of individual specimens examined 90 Company Sanitized. Does not contain TSCA CBI TABLE III (continued) SUMMARY OF CLINICAL URINE ANALYSIS FINDINGS FOIL MALE RATS EXPOSED BY I N H A L A T i o T T O l ^ H H H H H H n F O R 10 DAYS Sampling T i m e ___________41-Day Recovery________________84-Day Recovery Dose (mg/L)___________ 0 .0076 .058 .48 0 .0076 .058 .48 Measurement Blood Number Positive 0 / 1 0 1 / 1 0 0 / 1 0 1 / 1 0 3/5 4/5 3/5 5/5 Sugar (Glucose) Number Positive 1 / 1 0 2 / 1 0 1 / 1 0 2 / 1 0 3/5 3/5 3/5 5/5 Protein Number Abnormal >+3 1 / 1 0 1 / 1 0 0 / 1 0 2 / 1 0 2/5 0/5 0/5 0/5 Bilirubin Number Positive 2/10 2/10 6/10 6/10 2/5 2/5 1/5 0/5 Ketuiie Number Positive 1 0 / 1 0 1 0 / 1 0 1 0 / 1 0 9/10 4/5 3/5 3/5 4/5 Appearance (Color 0 / 1 0 and Transparency) 0/10 0/10 0/10 0/5 0/5 0/5 0/5 Microscopic Number Abnormal 1/10 1/10 2/10 0/10 0/5 2/5 0/5 1/5 91 Company Sanitized. Does not contain TSCA CBI TABLE IV SUMMARY OF STATISTICAL ANALYSES OF HEMATOLOGIC AND CLINICAL CHEMICAL FINDINGS FOR MALE RATS EXPOSED BY INHALATION TO Sampling Time Statistic 0-Day Recovery p** Dunnett Measurement Hematology RBC Hb Ht MCV MCH MCHC PLAT WBC Neut Band Lymph Alym Mono Eos in Baso 0.000 0.003 0.000 0.755 0.000 0.000 0.007 0.748 0.280 0.404 0.673 0.358 0.407 0.112 1.000 ** ** ** ** ** ** Clinical Chemistry (Serum) ALP . 0 . 0 0 0 ALT 0.135 AST 0.003 BUN 0 . 0 0 0 CREAT 0.057 TPROT 0.120 CHL0S 0.000 ** ** ** ** Clinical Chemistry (Urine) VOL 0 . 0 0 0 0SML 0.000 pH 0 . 0 0 0 UROBL 0.069 ** ** ** 14-Day Recovery p Dunnett 0.270 0.000 0.353 0.323 0.015 0.021 0.991 0.627 0.880 1.000 0.740 0.106 0.092 0.038 1.000 ** ** ** 0.283 0.903 0.398 0.426 0.891 0.445 0.094 0.911 0.432 0.002 0.099 ** * = Value of p for F-statlstic . ** = Significantly different from controls at 5% level by Dunnett criteria 92 Company Sanitized. Does not contain TSCA CBI TABLE IV (continued) SUMMARY OF STATISTICAL ANALYSES OF HEMATOLOGIC AND CLINICAL CHEMICAL FINDINGS FOR MALE RATS EXPOSED BY INHALATION TO [FOR 10 DAYS Sampling Time Statistic 41-Day Recovery _______ P Dunnett 84-Day Recovery P Dunnett Measurement Hematology RBC 0.045 ** 0.313 Hb 0.170 0.165 Ht 0.053 0.207 MCV 0.789 0.375 MCH 0 . 1 0 0 0.302 MCHC 0.179 0.050 PLAT 0.014 ** 0.335 WBC 0.289 0.000 ** Neut 0.259 0.000 ** Band 0.404 0.418 Lymph 0.472 0.005 ** Alym 0.168 0.611 0 Mono Eosin 0.412 0.316 0.552 0.500 Baso 0.554 1.000 ' Clinical Chemistry (Serum) ALP 0.532 ALT 0.008 AST 0.933 BUN 0.980 CREAT 0.496 TPROT ' 0.511 CHLOS 0.686 ** 0.727 0.487 0.355 0.048 0.299 0.412 0.227 ** Clinical Chemistry (Urine) VOL 0.998 OSMOL 0.425 pH 0.382 R0BL 1.000 0.904 0.704 0.455 0.585 93 Company Sanitized. Does not contain TSCA CBI TABLE V SUMMARY OF STATISTICALLY SIGNIFICANT HEMATOLOGIC AND CLINICAL CHEMICAL FINDINGS FOR MALE RATS EXPOSED BY INHALATION TO] kFOR 10 DAYS Sampling Time 0-Day Rec Measurement Hematology RBC Hb -HfeMCH MCHC PLAT RBC Neut Lymph MV MV -MV MV MU, MV IV Clinical Chemistry (Serum) ALP -MV ALT AST M V BUN 4.IV CHLOS IV Clinical Chemistry (Urine) VOL +IV OSMOL MV pH M V 14-Day Rec MV MV MV M U , IV 41-Day Rec MV MV -MI,IV 84-Day Rec M U , IV -MV Mil,IV MV + = Significantly higher than controls by Dunnett criteria + = Significantly lower than controls by Dunnett criteria Group Designation and Dose Concentration (mg/L) II = Low Dose (0.0076) III = Intermediate Dose (0.058) IV = High Dose (0.48) 94 Company Sanitized. Does not contain TSCA CBI LEGEND TERMS AND CRITERIA USED IN URINALYSES Abbreviations for Descriptive Terms Normally Used for Gross Evaluation of Urine (other Abbreviations and Descriptive Terms may be used if they are more applicable). Y = Yellow LY = Light Yellow DY = Dark Yellow A = Amber DA = Dark Amber ^3 = Green BL = Bloody R = Red C = Clear CL = Cloudy PPT = Precipitate F = Feed FEC = Feces Abbreviations for Descriptive Terms Used for Microscopic Evaluation of Urine Epith = Epithelial Cells hpf = high power field lpf = low power field RBC = Red Blood Cells WBC = White Blood Cells TNTC (99-99) = Too Numerous to Count Definition of "Normal" and "Abnormal" Designations Used for Gross and Microscopic Appearance of Urine Appearance Color Microscopic Red Blood Cells Casts Epithelial Cells White Blood Cells Normal Light to dark yellow or amber Average of 0 to 4 red blood cells per high power field None observed Average of 0 to 9 per high power field Average of 0 to 9 per high power field Abnormal Color other than yellow or amber Average of more than 4 red blood cells per high power field Average of more than 0 per low power field Average of more than 9 per high power field Average of more than 9 per high power field" 95 Company Sanitized. Does not contain TSCA CBI MR: HASKELL NUMBER: 15388 HASKELL C O D E :Q ^ ) COMPOUND: PERIOD SEX: l-DAY REC MALE DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-0CT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 07/20/84 ANIMAL#: 376825 376835 376839 376840 376841 376849 376863 376870 376872 376873 RBC x 106 /u L 7-31 6.73 7.61 7.63 6.41 7.06 7.59 7.73 8.45 7.57 Hb g/dL 15.2 15.1 15.9 15.5 14.0 15.0 15.6 16.1 17.5 15.7 AVG. S. D. S,, E. 7.409 0.570 0.180 15.56 0.90 0.28 Ht % 42. 40. 43. 45. 37. 41. 44. 44. 50. 42. 42.7 3.3 1.0 SPECIES: RAT BIRTH DATE: 05/14/84 MCV MCH MCHC PLAT fL Pg g/dL x103/uL 57. 2 1 . 36. 1 0 6 8 . 58. 23. 38. 952. 56. 2 1 . 37. 984. 58. 2 0 . 35. 716. 58. 2 2 . 38. 1030. 57. 2 1 . 37. 1008. 58. 2 1 . 35. 842. 57. 2 1 . 37. 876. 58. 2 1 . 35. 1044. 55. 2 1 . 37. 774. 57.2 1.0 0.3 21.0 0.7 0.2 36.5 1.1 0.3 929.4 121.2 38.3 GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 07/20/84 BIRTH DATE: 05/14/84 ANIMAL#: 376804 376806 376810 376818 376822 376823 376844 376852 376876 376881 RBC x 106/u L 7.37 7.32 6.75 6.26 6.81 7.35 7.61 7.33 7.90 8.05 Hb g/dL 15.4 16.5 14.8 14.6 15.2 15.5 15.1 15.0 15.4 15.7 AVG. S. D. S. E. 7.275 0.542 0.171 15.32 0.53 0.17 Ht $ 42. 42. 40. 36. 41. 42. 43. 43. 44. 47. 42.0 2.7 0.8 MCV fL 57. 56. 59. 58. 59. 57. 56. 58. 55. 57. 57.2 1.3 0.4 MCH Pg 21. 23. 22. 23. 22. 21. 20. 21. 20. 20. MCHC g/dL 37. 40. 37. 40. 38. 37. 35. 35. 35. 34. PLAT x 103/u L 814. 1032. 758. 802. 984. 936. 728. 876. 776. 720. 21 .1 1.3 0.4 36.6 2.0 0.6 842.6 109.5 34.6 96 Company Sanitized. Does not contain TSCA CBI HASKELL CODEf j ^ POLYMER PRODUCTS 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 07/20/84 BIRTH DATE: 05/14/84 ANIMAL#: 376805 376812 376813 376821 376830 376838 376851 376857 376867 376874 RBC x 106/u L 8.00 7.04 7.27 6.70 7.30 6.95 7.25 7.90 6.60 7.61 Hb g/dL 16.8 15.5 16.2 15.8 16.0 15.3 15.6 16.6 14.5 15.7 Ht % 46. 41. 43. 39. 42. 41. 40. 44. 38. 43. MCV fL 56. 58. 58. 57. 57. 58. 55. 56. 57. 56. MCH MCHC PLAT Pg g/dL x 103/u L 21. 37. 722. 22. 37. 692. 22. 38. 724. 24. 41. 1164. 22. 38. 806. 22. 38. 836. 22. 39. 890. 21. 38. 804. 22. 38. 852. 21. 37. 722. AVG. S. D. S. E. 7.262 15.80 0.468 0.66 0.148 0.21 41.6 2.4 0.7 56.8 1.0 0.3 21.8 0.8 0.3 38.0 1.2 0.4 821.2 137.3 43.4 GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 07/20/84 BIRTH DATE: 05/14/84 ANIMAL#: 376819 376820 376824 376828 376833 376854 376858 376859 376879 376880 RCBC x10/uL 8.67 8.65 8.18 8.90 8.21 8.67 8.58 8.30 8.74 8.63 Hb g/dL 16.6 16.1 16.1 17.4 15.8 17.9 16.6 16.3 17.0 ' 15.6 Ht % 49. 50. 48. 51. 48. 53. 49. 48. 51. 48. MCV fL 56. 57. 58. 57. 58. 61. 57. 58. 57. 55. MCH MCHC PLAT . Pg g/dL x 103/u L 19. 34. 690. 19. 32. 590. 20. 34. 808. 20. 34. 524. 19. 33. 21. 34. 670. 864. 19. 34. 766. 20. 34. 806. 20. 34. 846. 18. 33. 722. AVG. S. D. S. E. 8.553 16.54 0.240 0.72 0.076 0.23 49.4 1.8 0.6 57.4 1.6 0.5 19.4 0.7 0.2 33.5 0.6 0.2 728.6 111.5 35.3 97 Company Sanitized. Does not contain TSCA CBI MR: ___ COMPOUND | HASKELL NUMBER: PERIOD: O-DAY REC SEX: MALE 15388 HASKELL CODe B DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376825 376835 376839 376840 376841 376849 376863 376870 376872 376873 WBC x103/uL 13.6 14.8 8.9 10.5 13.3 16.0 10.5 9.1 18.5 9.5 AVG. S. D. S. E. 12.47 3.28 1.04 Neut WBCxj 2992. 3700. 2136. 1785. 1330. 3520. 2100. 1092. 1295. 2280. Band WBCx$ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 2223.0 919.6 290.8 0.0 0.0 0.0 Lymph WBCx$ 9792. 10508. 6141. 7875. 11172. 11680. 7560. 7735. 16095. 6365. Alym WBCxi 408. 148. 89. 210. 266. 160. 105. 0. 185. 95. Mono WBCx$ 408. 444. 534. 525. 532. 640. 735. 182. 740. 665. Eosin WBCxi 0. 0. 0. 105. 0. 0. 0. 91. 185. 95. Baso WBCx$ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 9492.3 166.6 540.5 3032.7 112.3 169.6 959.0 35.5 53.6 47.6 66.6 21.1 0.0 0.0 0.0 GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 07/20/84 BIRTH DATE: 05/14/84 ANIMAL#: 376804 376806 376810 376818 376822 376823 376844 376852 376876 376881 WBC x 103/u L 9.5 11.1 13.0 13.6 13.2 10.1 13-0 10.4 15.0 8.3 AVG. S. D. S. E. 11.72 2.14 0.68 Neut Band WBCx$ WBCx? 2185. 0. 4107. 0. 2730. 0. 1904. 0. 3300. 132. 1717- 0. 3770. 1456. 0. 0. 4050. 0. 1162. 0. 2638.1 13.2 1107.9 41.7 350.4 ' 13.2 Lymph WBCx? 6270. 6327. 8580. 11288. 9372. 7373. 8710. 8528. 9750. 6640. Alym WBCxi 285. 222. 390. 136. 132. 404. 130. 104. 600. 0. Mono WBCx? 665. 444. 1040. 272. 132. 505. 390. 208. 600. 498. Eos in WBCx 95. 0. 260. 0. 132. 101. 0. 104. 0. 0. Baso WBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 8283.8 240.3 475.4 1636.5 180.1 260.5 517.5 57.0 82.4 69.2 86.4 27.3 0.0 0.0 0.0 98 Company Sanitized. Does not contain TSCA CBI MR: ^ H f c ^ ^ H A S K E L ^ 0 M B E R ^ 1 5 3 8 8 tonHASKELL CODE: COMPOUND: DEPARTMENT: POLYMER PRODUCTS PERIOD: O-DAY REC REPORT DATE: 17-OCT-84 SEX: MALE GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 07/20/84 BIRTH DATE: 05/14/84 ANIMAL#: 376805 376812 376813 376821 376830 376838 376851 376857 376867 376874 WBC x 103/u L 6.6 14.4 14.4 11.7 10.4 9.4 12.7 12.5 11.0 9.9 AVG. S. D. S. E. 11.30 2.39 0.76 Neut WBCxi 1122. 2160. 1872. 2106. 1768. 1598. 3302. 2000. 1980. 1386. Band WBCxi 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 1929.4 583.3 184.5 0.0 0.0 0.0 Lymph WBCxi 4884. 11376. 11.376. 9009. 7280. 7332. 8636. 9500. 8470. 7722. Alym WBCxi 66. 144. 432. 117. 416. 94. 254. 125. 330. 99. Mono WBCxi 528. 720. 576. 468. 832. 376. 381. 750. 220. 693. Eosin WBCxi 0. 0. 144. 0. 104. 0. 127. 125. 0. 0. Baso WBCxi 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 8558.5 1952.8 617.5 207.7 139.3 44.1 554.4 195.6 61.9 50.0 65.2 20.6 0.0 0.0 0.0 GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 07/20/84 BIRTH DATE: 05/14/84 ANIMAL#: 376819 376820 376824 376828 376833 376854 376858 376859 376879 376880 WBC x103/uL 10.9 8.5 16.7 9.8 13.5 11.1 12.7 14.0 9.0 17.8 Neut WBCxi 2180. 1700. 2338. 1862. 2160. 3663. 2667. 2800. 2070. 2848. Band WBCxi 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. Lymph WBCxi 7739. 6545. 13360. 7546. 10800. 6105. 9144. 10220. 6390. 13884. Alym WBCxi 218. 85. 167. 98. 0. 222. 127. 140. 180. 178. Mono WBCxi 763. 170. 835. 294. 540. 1110. 762. 840. 360. 890. Eosin WBCxi 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. Baso WBCxi 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. AVG. S. D. S. E. 12.40 3.14 0.99 2428.8 579.0 183.1 o.'o 0.0 0.0 9173.3 141.5 656.4 0.0 0.0 2833.1 6 7 . 6 301.4 0.0 0.0 895.9 21.4 95.3 0.0 0.0 99 Company Sanitized. Does not contain TSCA CBI MR: COMPOUND PERIOD: SEX: HASKELL NUMBER: 1 5 3 8 8 HASKELL C O D E : f m 5-DAY REC MALE DEPARTMENT: POLYMER PRODUCTS REPORT DATE 17-OCT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376825 376835 376839 376840 376841 376849 376863 376870 376872 376873 AVG. S. D. 5 E ALP U/L 130. 339. 237. 137. 161. 184. 183. 211. 140. 185. 190.7 62.1 19.6 ALT U/L 35. 44. 42. 46. 33. 31. 32. 37. 37. 32. '36.9 5.4 1.7 AST U/L 75. 96. 71. 9T. 73. 68. 93. 98. 95. 109. BUN mg/dL 16. 16. 13. 15. 14. 14. 23. 19. 16. 15. CREAT mg/dL 0.54 0.59 0.53 0.56 0.56 0.55 0.41 0.46 0.56 0.66 TPROT g/dL 5.9 6.0 6.2 6.0 5.6 5.8 5.9 6.0 5.5 5.9 CHLOS mg/dL 62. 60. 64. 60. 62. 81. 40. 54. 40. 45. 86.9 14.0 4.4 16.0 0.542 2.9 0.068 0.9 0.021 5.88 0.20 0.06 56.7 12.8 4.0 GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 07/20/84 BIRTH DATE: 05/14/84 ANIMAL#: 376804 376806 376810 376818 376822 376823 376844 376852 376876 376881 ALP U/L 98. 166. 177. 265. 262. 242. 153. 211. 206. 207. AVG. S. D. S. E. 198.7 52.0 16.4 ALT U/L 35. 46. 43. 41. 41. 54. 33. 28. 35. 37. 39.3 7.4 2.3 AST U/L 69. 90. 72. 82. 77. 106. 70. 92. 93. 77. BUN mg/dL 17. 20. 18. 16. 17. 16. 12. 20. 14. 18. CREAT mg/dL 0.58 0.52 0.59 0.59 0.59 0.65 0.66 0.67 0.54 0.56 TPROT g/dL 6.3 6.0 6.0 6.5 6.0 5.8 6.1 5.8 6.1 5.3 CHLOS mg/dL 62. 47. 53. 69. 52. 50. 45. 34. 41. 34. 82.8 12.1 3.8 16.9 0.595 2.4 0.051 0.7 0.016 5.99 0.32 0.10 48.6 11.0 3.5 f 00 Company Sanitized. Does not contain TSCA CBI MR: _____ COMPOUND PERIOD SEX: HASKELL NUMBER: .15388 HASKELL CODE : 0-DAY REC MALE DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: DOSE: .058 mg/L SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376805 376812 376813 376821 376830 376838 376851 376857 376867 376874 ALP U/L 299. 127. 229. 228. 210. 240. 204. 187. 141. 199. AVG. S. D. S. E. 206.4 49.1 15.5 ALT U/L 71. 43. 43. 40. 35. 40. 50. 46. 39. 33. 44.0 10.7 3.4 AST U/L 116. 72. 83. 78. 102. 105. 96. 99. 79. 76. 90.6 14.9 4.7 BUN mg/dL 15. 13. 15. 16. 19. 14. 14. 24. 12. 17. 15.8 3.4 1.1 CREAT mg/dL 0.67 0.53 0.70 0.-68 0.55 0.72 0.61 0.63 0.61 0.59 0.629 0.063 0.020 TPROT g/dL 6.3 6.1 6.2 6.4 5.9 6.4 6.7 5.8 5.6 6.0 6.14 0.33 0.10 CHLOS mg/dL 47. 61. 53. 50. 48. 49. 50. 42. 49. 52. 49.9 4.8 1.5 GROUP: 4M DOSE: .480 mg/L SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376819 376820 376824 376828 376833 376854 376858 376859 376879 376880 ALP U/L 372. 287. 324. 322. 351. 334. 263. 254. 328. 411. AVG. S. D. S. E. 324.6 48.0 15.2 ALT U/L 47. 45. 41. 62. 50. 50. 38. 35. 38. 37. 44.3 8.3 2.6 AST U/L 124. 123. 93. 137. 91. 94. 99. 94. 101. 124. BUN mg/dL 27. 25. 34. 29. 31. 23. 28. 25. 36. 32. CREAT mg/dL O. 7 0 0.62 0.71 0.29 O. 7 4 0.76 0.71 0.60 0.62 0.68 108.0 17.0 5.4 28.9 0.643 4.2 O. 1 3 5 1.3 0.043 TPROT g/dL 6.1 5.9 6.4 6.1 5.4 6.3 6.2 6.0 7.1 6.9 6.24 O. 4 9 0.15 CHLOS mg/dL 32. 18. 19. 19. 20. 16. 18. 9. 18. 16. 18.6 5.5 1.7 101 Company Sanitized. Does not contain TSCA CBI MR: _ COMPOUND PERIOD: SEX: HASKELL NUMBER O-DAY REC MALE 15388 HASKELL CODE: fj DEPARTMENT: POLYMER PRODUCTS REPORT DATE 17-OCT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376825 376835 376839 376840 376841 376849 376863 376870 376872 376873 AVG. S. D. S. E. VOL mL 5.8 6.1 5.4 5.5 7.9 6.7 3.5 17.0 7.8 6.3 OSMOL mOs 1862. 1641. 2028. 1739. 1552. 1901. 1593. 1002. 1879. 1944. BLOOD - SUGAR PRO- TEIN +1 +2 +1 +1 +1 +1 +2 + +1 +1 7.20 1714.1 3.67 296.2 1.16 93.7 PH BILI UROBL Ke RUBIN mg/dL toi 7.0 1.0 +1 7.0 +1 1.0 +1 7.0 +1 1.0 +1 8.0 - 1.0 + 8.0 - 1.0 + 8.0 +1 1.0 +1 6.0 +1 1.0 + 8.0 - 0.1 7.0 +1 1.0 + 7.0 +1 1.0 + 1 7.30 0.67 0.21 0.91 0.28 0.09 GROUP: 2M DOSE: .0076 mg/L SPECIE SAMPLE DATE!: 07/20/84 BIRTH i ANIMAL#: 376804 376806 376810 376818 376822 376823 376844 376852 376876 376881 AVG. S. D. S. E. VOL mL 4.6 5.1 7.4 4.6 5.0 4.2 7.7 2.2 6.5 4.4 OSMOL mOs 1966. 1607. 1641. 1926. 1666. 2130. 1664. 1868. 1090. 2388. BLOOD SUGAR ---++ -++ -++ --- PRO TEIN +2 +1 +1 +1 +1 +1 +1 +1 +1 +1 5.17 1 7 9 4 . 6 1.64 350.5 0.52 110.8 PH BILI UROBL Ke RUBIN mg/dL tone 6.0 +1 1.0 + 8.0 +1 1.0 + 7.0 - 1.0 +1 7.0 - 1.0 + 7.0 - 1.0 +1 6.0 - 1.0 _ 7.0 +1 1.0 +1 7.0 - 0.1 7.0 - 1.0 + 6.0 - 1.0 +1 6.80 0.63 0.20 0.91 0.28 0.09 02 Company Sanitized. Does not contain TSCA CBI HASKELL C O D E :^ ^ J l POLYMER PRODUCTS 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SAMPLE DATE: 07/20/84 ANIMAL#: 376805 376812 376813 376821 376830 376838 376851 376857 376867 376874 VOL mL 5.0 7.3 6.2 8.3 6.7 5.0 9.0 7.1 4.6 16.0 OSMOL mOs 2062. 1534- 1763. 1398. 1471. 1976. 1322. 1669. 2080. 821. BLOOD _ _ _ __ + - SC _ _ + - AVG. S. D. S. E. 7.52 1609.6 3.31 389.0 1.05 1 2 3 . 0 SPECIES: RAT BIRTH DATE: 05/14/84 PRO TEIN +2 +1 +1 +1 +1 +1 +1 +1 +1 + PH BILI UROBL Ke RUBIN mg/dL tone 7.0 - 1.0 +1 8.0 - 1.0 + 7.0 - 1.0 + 7.0 +1 1.0 + 8.0 - 1.0 + 6.0 - 1.0 +1 7.0 +1 1.0 + 7.0 - 1.0 +1 6.0 - 1.0 + 7.0 - 1.0 + 7.00 O. 6 7 0.21 1.00 0.00 0.00 GROUP: 4M DOSE: .480 mg/L SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376819 376820 376824 376828 376833 376854 376858 376859 376879 376880 AVG. Sa Da S. E. VOL mL 11.0 9.1 12.0 16.0 15.0 11.0 10.0 8.7 14.0 12.0 OSMOL mOs 1039. 955. 944. 886. 730. 1099. 537. 861. 725. 723. BLOOD - SUGAR + + *4* _ - PRO TEIN +1 +1 +1 + +1 +1 + +1 +1 11.88 .849.9 2.45 171.0 0.78 54.1 PH BILI UROBL Ke RUBIN mg/dL tone 8.0 - 0.1 9.0 - 0.1 _ 8.0 +1 1.0 7.0 - 0.1 8.0 - 1.0 _ 9.0 +1 1.0 m, 8.0 - 0.1 9.0 +1 1.0 9.0 - 1.0 8.0 - 1.0 - 8.30 O.6 7 0.21 0.64 0.46 0.15 03 Company Sanitized. Does not contain TSCA CBI MR: (| COMPOUND: PERIOD: O-DAY REC SEX: MALE 5388 HASKELL CODE{ f l DEPARTMENT: POLYMER PRODUCTS REPORT DATE 17-OCT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 RBC ANIMAL#: /hpf 376825 0-0 376835 0-0 376839 0-0 376540" 0-0 376841 0-0 376849 0-0 376863 0-0 376870 0-2 376872 0-0 376873 0-0 WBC /hpf 4-8 5-10 0-2 5-8 8-10 0-4 0-1 10-20 1-3 5-10 Epith /hpf 0-3 0-2 1-2 0-3 2-4 0-2 0-1 1-3 0-1 0-2 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 FEED DY CL PPT FEED Y CL PPT FEED LY CL PPT FEED DY CL PPT FEED DY CL PPT FEED DY C PPT Y CL PPT FEED Y C PPT FEED DY CL PPT FEED GROUP: 2M DOSE: .0076 rng/L SPECIES: RAT SAMPLE DATE: 07/20/84 BIRTH DATE: 05/14/84 ANIMAL#: 376804 376806 376810 376818 376822 376823 376844 376852 376876 376881 RBC /hpf 0-0 0-0 0-0 0-0 0-0 0-2 0-0 0-1 0-0 0-0 WBC /hpf 1-4 1-3 20-30 0-2 2-4 5-8 1-2 0-2 0-1 0-2 Epith Cast /hpf /lpf 0-1 0-0 0-1 0-0 3-6 0-0 0-1 0-0 0-1 0-0 0-2 0-0 0-0 0-0 0-2 0-0 0-0 0-0 0-1 0-0 APPEARANCE DY CL PPT FEED Y CL PPT FEED DY CL PPT FEED DY C PPT LY C PPT Y C PPT Y C PPT FEED DY C PPT LY CL PPT Y C PPT 04 Company Sanitized. Does not contain TSCA CBI MR: HASKELL NUMBER: COMPOUND :1 PERIOD: O-DAY REC SEX: male 15388 HASKELL CODE: ( 0 ^ DEPARTMENT: POLYMER PRODUCTS REPORT DATE 17-OCT-84 GROUP: DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 07/20/84 BIRTH DATE: 05/14/84 ANIMAL#: 376805 376812 376813 376821 376830 376838 376851 376857 376867 376874 RBC /hpf 0-0 0-0 0-1 0-0 0-0 0-0 0-0 0-0 0-3 0-0 WBC /hpf 5-10 3-6 1-3 4-6 1-4 0-3 0-2 0-2 2-4 0-3 Epith /hpf 1-4 0-2 1-2 0-1 0-3 0-1 1-2 0-1 0-2 0-1 Cast /lpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 APPEARANCE Y CL PPT FEED Y CL PPT FEED Y C PPT Y a PPT FEED Y C PPT FEED DY CL PPT FEED Y C PPT FEED Y C PPT FEED DY CL PPT FEED LY CL PPT FEED GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 07/20/84 BIRTH DATE: 05/14/84 ANIMAL#: 376819 376820 376824 376828 376833 376854 376858 376859 376879 376880 RBC /hpf 0-0 0-0 0-0 0-1 0-0 0-0 0-0 0-0 0-0 0-0 WBC /hpf 1-3 0-4 0-1 0-2 1-4 1-3 0-1 2-4 0-2 1-3 Epith /hpf 1-2 0-2 0-1 0-1 1-2 0-2 0-2 2-4 0-1 2-4 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 Y CL PPT FEED Y CL PPT FEED LY CL PPT FEED Y CL PPT FEED DY CL PPT LY CL PPT A CL PPT Y CL PPT LY CL PPT 105 Company Sanitized. Does not contain TSCA CBI MR: COMPOUND:! PERIOD: 14-DAY REC SEX: MALE 5388 HASKELL C O D E : ( j H \ DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/03/84 ANIMAL#: 376801 376835 376836 376837 376841 376847 376849 376863 376872 376878 RBC x 106/u L 6.73 6.49 7.63 7.75 6.39 7.93 7.27 7.28 7 .2 6 6.51 Hb g/dL 15.2 16.4 16.0 16.0 14.8 15.8 1 5 .8 15.9 16.4 16.0 Ht % 39. 39. 4343. 38. 42. 42. 41. 42. 38. AVG. S. D. S , E. 7.124 0 .5 6 1 0.177 15.83 0.49 0.16 40.6 2 .0 0 .6 SPECIES: RAT BIRTH DATE: 05/14/84 MCV MCH MCHC PLAT fL Pg g/dL x 103/u L 57. 23. 39- 940. 59. 25. 43. 1 2 6 2 . 56. 2 1 . 37. 1 1 3 8 . 54. 21 . 38. 944. 59. 23. 39. 1190. 52. 2 0 . 38. 1158. 58. 2 2 . 38. 954. 56. 2 2 . 39. 998. 57. 23. 39. 864. 58. 25. 42. 1360. 56.6 2 .2 0.7 22.4 1.7 0.5 39-2 1 .8 0 .6 1 0 8 0 .8 163.4 51.7 GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 ANIMAL#: 376800 376810 376822 376848 376852 376856 376866 376871 376876 376881 RBC x 1 0 6/u L 7.25 6.68 6.23 6.74 7.49 7.72 7.03 7.43 7.20 7.18 Hb g/dL 16.2 15.0 16.1 15.5 16.4 16.3 16.3 15.8 15.1 16.3 Ht MCV % fL 41. 56. 40. 59. 37. 58. 38. 57. 44. 58. 43. 55. 40. 56. 42. 55. 39. 54. 41. 57. MCH MCHC PLAT Pg g/dL x 103/u L 22. 40. 1118. 23. 38. 888. 26. 44. 1330. 23. 40. 1042. 22. 38. 1078. 21. 38. 936. 23. 41. 1162. 21. 38. 972. 21. 39. 1048. 23. 40. 1066. AVG. S. D. S. E. 7.095 0.441 0.140 15.90 0.52 0.17 40.5 2.1 0.7 56.5 1.6 0.5 22.5 1.4 0.5 39.4 2.0 0.6 1064.0 124.7 39.4 ] 0 6 Company Sanitized. Does not contain TSCA CBI mb;(aiCOMPOUND :|I PERIOD: 14-DAY SEX: MALE HASKELL REC NUMBER: 15388 . J DEPARTMENT: REPORT DATE HASKELL C O D E : p ^ POLYMER PRODUCTS 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 ANIMAL#: 376803 376808 376811 376812 376813 376830 376843 376857 376860 376874 RBC x 106/u L 7.54 7.66 7.99 7.16 7.07 7.57 7.29 7.90 7.05 7.54 Hb g/dL 16.1 16.3 16.2 16.6 15.7 16.2 15.3 16.6 15.3 15.8 AVG. S. D. S. E. 7.477 16.01 0.329 0.47 0.104 0.15 Ht % 41. 42. 44. 42. 41. 43. 40. 44. 40. 42. 41.8 1.5 0.5 MCV fL 54. 55. 54. 58. 57. 57. 54. 55. 56. 55. 55.5 1.4 0.5 MCH Pg .21. 21. 20. 23. 22. 21. 21. 21. 22. 21. MCHC g/dL 39. 39. 37. 40. 39. 38. 38. 38. 38. 38. PLAT x 1 0 3 /u L 1064. 1126. 768. 1300. 878. 1060. 1026. 1134. 1282. 1050. 21 .4 0.8 0.2 38.3 0.8 0.2 1068.8 161.8 51.2 GROUP: 4M DOSE: .480 mg/L SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376814 376815 376819 376824 376832 376833 376850 376853 376858 376880 RBC x 105/u L 7.52 7.32 6.83 6.18 6.76 7.25 7.71 8.01 7.40 6.70 Hb g/dL 15.2 14.7 14.5 14.0 14.9 15.3 15.6 15.4 15.2 13.6 Ht % 41. 40. 38. 35. 37. 44. 43. 43. 43. 37. MCV fL 54. 54. 56. 56. 55. 60. 55. 53. 57. 54. MCH Pg 20. 20. 21 . 23. 22. 21. 20. 19. 21. 20. MCHC g/dL 37. 37. 38. 40. 40. 35. 36. 36. 35. 37. PLAT x 1 0 3 /u L 1052. 1140. 900. 1146. 1078. 1256. 1036. 1120. 1074. 998. AVG. S. D. S. E. 7.168 14.84 0.546 0.64 0.173 0.20 40.0 3.1 1.0 55.4 2.0 0.6 20.8 1.0 0.3 37.2 1.7 0.6 1080.0 95.7 30.3 107 Company Sanitized. Does not contain TSCA CBI MR; (| HASKELL NUMBER: 15388 HASKELL C O D E ^ f l COMPOUND; PERIOD 14-DAY REC DEPARTMENT; POLYMER PRODUCTS REPORT DATE 17-OCT-84 SEX; MALE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376801 376835 376836 376"837 376841 376847 376849 376863 376872 376878 AVG. S. D. S. E. ALP U/L 166. 307. 151. TOT. 168. 201. 207. 128. 139. 139. 170.7 57.7 18.2 ALT U/L 39. 39. 32. 38. 35. 29. 37. 28. 37. 35. 34.9 4.0 1.3 AST U/L 71. 103. 70. 77. 78. 75. 5971. 83. 77. BUN mg/dL 22. 16. 15. 12. 19. 18. 16. 21. 18. 16. CREAT mg/dL 0.63 0.68 0.60 0.55 0.58 0.49 0.64 0.60 0.54 0.56 TPROT g/dL 6.2 6.4 6.5 7.4 7.5 5.4 5.7 5.7 5.8 5.8 CHLOS mg/dL 63. 67. 63. 76. 72. 64. 101. 61. 61. 87. 76.4 11.3 3.6 17.2 0.587 3.0 0.055 1.0 0.017 6.24 0.72 0.23 71.5 13.2 4.2 GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 MAL#: 376800 376810 376822 376848 376852 376856 376866 376871 376876 376881 ALP U/L 219. 127. 261. 87. 137. 145. 176. 180. 242. 219. AVG. S. D. S. E. 179.3 55.8 17.6 ALT U/L 39. 32. 46. 24. 30. 31. 28. 36. 39. 39. 34.4 6.6 2.1 AST BUN U/L mg/dL 72. 16. 70. 15. 70. 20. 98. 17. 81. 15. 76. 16. 59. 17. 67. 16. 79. 19. 75. 15. CREAT mg/dL 0.53 0.60 0.69 0.57 0.59 0.56 0.61 0.61 0.63 0.49 TPROT g/dL 6.0 6.3 6.6 6.1 6.2 6.2 6.8 6.3 5.7 5.2 CHLOS mg/dL 50. 64. 64. 65. 66. 55. 86. 50. 51. 65. 74.7 10.3 3.3 16.6 0.588 1.6 0.055 0.5 0.017 6.14 0.45 0.14 61.7 10.8 3.4 I 08 Company Sanitized. Does not contain TSCA CBI MR: ____ HASKELL NUMBER: 15388 HASKELL CODESw_ COMPOUND:! PERIOD: ------------------14-DAY REC ------ DEPARTMENT: REPORT DATE: POLYMER PRODUCTS 16-OCT-84 SEX: MALE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376801 376835 376836 376837 376841 376847 376849 376863 376872 376878 WBC x 103/u L 9.9 12.4 14.4 13.8 14.1 15.5 14.9 10.6 11.6 13.8 O U S. E. 13.10 1.88 0.60 Neut WBCx/S 1287. 3720. 3168. 4002. 2961. 1860. 3725. 2332. 1624. 1104. Band WBCx$ 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 2578.3 1078.5 341.0 0.0 0.0 0.0 Lymph WBCxi 8514. 8680. 11232. 9798. 11139. 13485. 11026. 8268. 9976. 12558. Alym WBCx$ 0. 0. 0. 0. 0. 0. 0. 0. 0. 138. Mono WBCxi 0. 0. 0. 0. 0. 155. 0. 0. 0. 0. Eosin WBCx? 99. 0. 0. 0. 0. 0. 149. 0. 0. 0. Baso WBCxji 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 10467.6 1743.6 551.4 13.8 43.6 13.8 15.5 49.0 15.5 24.8 53.6 16.9 0.0 0.0 0.0 GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 ANIMAL#: 376800 376810 376822 376848 376852 376856 376866 376871 376876 376881 WBC x 1 0 3 /u L 14.7 13.1 13.8 16.7 10.4 16.4 12.0 18.0 13.2 8.3 AVG. S. D. S. E. 13.66 2.97 0.94 Neut WBCxi 5292. 2882. 3174. 1169. 1560. 2460. 1680. 2160. 5148. 1660. Band WBCx$ 0. 0. 0. 0. 0. 0. 0. 0. . 0. 0. 2718.5 1456.0 460.4 0.0 0.0 0.0 Lymph WBCxi 9261. 9563. 10488. 15030. 8528. 13612. 10320. 15660. 7788. 6474. Alym WBCxi 147. 131. 0. 167. 0. 0. 0. 0. 0. 0. Mono WBCx? 0. 524. 138. 167. 208. 164. 0. 0. 132. 83. Eosin WBCx* 0. 0. 0. 167. 104. 164. 0. 180. 132. 83. Baso WBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. . o. 10672.4 3099.0 980.0 44.5 72.2 22.8 141.6 154.7 48.9 83.0 77.0 24.4 0.0 0.0 0.0 109 Company Sanitized. Does not contain TSCA CBI MR: B W HASKELL NUMBER; 15388 HASKELL C0DE:(j^3 C O M P O U N D D E P A R T M E N T : POLYMER PRODUCTS PERIOD: 14-DAY REC SEX: MALE REPORT DATE: 16-OCT-84 GROUP: DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 ANIMAL#: 376803 376808 376811 376812 376813 376830 376843 376857 376860 376874 WBC x 103/u L 11.3 24.4 10.6 21.2 10.7 12.2 15.2 12.4 21.2 8.2 Urn S. E. 14.74 5.55 1.75 Neut WBCx$ 2260. 4148. 2014. 3392. 1712. 1586. 4104. 3100. 5936. 1640. Band WBCxjS 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 2989.2 1427.8 451.5 0.0 0.0 0.0 Lymph WBCx* 8588. 19764. 8480. 17808. 8881. 10126. 11096. 8804. 14840. 6478. Alym WBCx 113. 0. 106. 0. 107. 122. 0. 248. 212. 0. Mono WBCx$ 226. 244. 0. 0. 0. 244. 0. 248. 212. 82. Eosin WBCx* 113. 244. 0. 0. 0. 122. 0. 0. 0. 0. Baso WBCx 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 11486.5 4450.2 1407.3 90.8 125.6 90.9 118.1 28.7 37.4 47.9 84.5 26.7 0.0 0.0 0.0 GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 ANIMAL#: 376814 376815 376819 376824 376832 376833 376850 376853 376858 376880 WBC x 103/u L 16.7 17.3 11.6 16.7 11.5 12.2 19.0 13.8 12.6 17.7 AVG. S. D. S. E. 14.91 2.85 0.90 Neut WBCx$ 2672. 2422. 2552. 4008. 2300. 2684. 4180. 3036. 2394. 2478. Band WBCx 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 2872.6 676.5 213.9 0.0 0.0 0.0 Lymph WBCx 13861. 14705. 9048. 12358. 9085. 9272. 14440. 10764. 9450. 15045. Alym WBCx 0. 173. 0. 0. 0. 122. 190. 0. 378. 177. Mono WBCx 167. 0. 0. 334. 115. 122. 190. 0. 378. 0. Eosin WBCx 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. Baso WBCx 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 11802.8 104.0 130.6 0.0 0.0 2548.0 127.8 139.8 0.0 0.0 805.7 40.4 44.2 0.0 0.0 110 Company Sanitized. Does not contain TSCA CBI MR: COMP PERIOD: SEX: 14-DAY REC MALE 15388 W HASKELL CODE DEPARTMENT: POLYMER PRODUCTS REPORT DATE : 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 ANIMAL#: 376803 376808 376811 376812 376813 376830 376843 376857 376860 376874 ALP U/L 185. 236. 171. 116. 252. 200. 209. 178. 213. 196. AVG. S. D. S. E. 195.6 37.5 11.9 ALT U/L 40. 36. 36. 42. 37. 27. 36. 43. 31. 32. 36.0 5.0 1.6 AST U/L 104. 72. 81. 69. 74. 79. 56. 107. 73. 79. BUN mg/dL 22. 17. 17. 15. 18. 19. 14. 21. 15. 13. CREAT mg/dL 0.56 0.53 0.66 0.59 0.63 0.57 0.62 0.53 0.57 0.54 TPROT g/dL 6.5 6.9 6.5 6.6 6.3 5.5 4.0 6.3 6.4 6.4 CHLOS mg/dL 52. 84. 68. 70. 54. 48. 56. 57. 71. 67. 79-4 15.5 4.9 17.1 0.580 2.8 0.044 0.9 0.014 6.14 0.83 0.26 62.7 11.2 3.6 GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 ANIMAL#: 376814 376815 376819 376824 376832 376833 376850 376853 376858 376880, ALP U/L 210. 277. 234. 233. 139. 239. 122. 247. 150. 294. ALT U/L 46. 31. 38. 41. 38. 35. 33. 32. 27. 36. AST U/L 64. 61. 88. 68. 90. 65. 60. 63. 77. 65. BUN mg/dL 16. 16. 19. 27. 16. 18. 16. 22. 19. 17. CREAT mg/dL 0.60 0.64 0.49 0.72 0.58 0.69 0.58 0.58 0.62 0.50 TPROT g/dL 6.4 6.8 6.9 7.5 6.5 6.9 6.4 6.3 5.9 5.9 CHLOS mg/dL 73. 63. 63. 58. 55. 65. 44. 46. 66. 60. AVG. S. D. S. E. 214.5 58.7 18.6 35.7 5.4 1.7 70.1 11.0 3.5 18.7 0.600 3.7 0.073 1.2 0.023 6.55 0.49 0.16 59.2 8.8 2.8 1 I Company Sanitized. Does not contain TSCA CBI MR: HASKELL NUMBER: 15388 HASKELL CODE COMPOUND: DEPARTMENT: POLYMER PRODUCTS PERIOD: T M ) A Y REC REPORT DATE: 17-OCT-84 SEX: MALE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376801 376835 376836 376837 376841 376847 376849 376863 376872 376878 VOL mL 5.4 13.8 10.2 17.6 14.3 11.8 18.6 8.9 17.9 13.9 OSMOL mOs 2496. 1371. 1608. 1061. 1300. 1573. 1367. 1344. 1147. 1201. BLOOD - SUGAFI PRO TEIN - +2 - +2 - +2 - +1 - +1 - +3 - +1 - +2 - +1 - +1 pH BILI UROBL Ke- RUBIN mg/dL tone 7.0 +1 1.0 + 8.0 - 1.0 + 8.0 - no - 9.0 - 1.0 + 8.0 - 1.0 + 9.0 +1 1.0 +1 8.0 +1 1.0 + 9.0 +1 1.0 + 7.0 - 1.0 + 8.0 - 1.0 + AVG. S. D. S. E. 13.24 1446.8 4.25 406.4 1.35 128.5 8.10 0.74 0.23 1.00 0.00 0.00 GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 ANIMAL#: 376800 376810 376822 376848 376852 376856 376866 376871 376876 376881 AVG. S. D. S. E. VOL mL 12.9 22.8 11.0 8.1 10.0 8.2 15.4 8.0 13.9 14.0 OSMOL mOs 1603. 642. 1455. 932. 834. 1874. 1151. 1694. 1332. 1640. BLOOD - SUGAR - - + - - - - PRO TEIN +2 +1 +1 +1 + +2 +1 +1 +1 +1 12.43 1315.7 4.54 411.3 1.44 1 3 0 . 1 pH BILI UROBL Ke- RUBIN mg/dL tone 7.0 - 1.0 +1 8.0 - 1.0 + 8.0 - 0.1 + 8.0 - 0.1 - 7.0 - 1.0 + 8.0 - 1.0 +1 8.0 - 1.0 - 7.0 +1 1.0 +1 8.0 - 1.0 + 7.0 +1 1.0 +1 7.60 0.52 0.16 0.82 0.38 0.12 I 2 Company Sanitized. Does not contain TSCA CBI M R :'___ COMPOUND:' PERIOD: SEX: MALE HASKELL NUMBER: 15388 HASKELL CODE:o n DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 ANIMAL#: 376803 376808 376811 376812 376813 376830 376843 376857 376860 376874 AVG. S. D. S. E. VOL mL 7.0 9.9 12.2 19.0 9.0 12.2 11.0 12.8 10.0 21.7 OSMOL mOs 1998. 1894. 1473. 1063. 1707. 1573. 1682. 1532. 1785. 957. BLOOD - - - + - - - - SUGAR - - + -- - - + PROTEIN +1 +1 +3 +2 +2 +2 +2 +2 +1 +2 12.48 1566.4 4.53 334.9 1.43 105.9 PH BILI- UROBL Ke- RUBIN mg/dL tone 7.0 1.0 + 6.0 +1 1.0 +1 8.0 +1 7.0 _ 1.0 + 1.0 - 7.0 +1 1.0 + 7.0 +1 1.0 + 7.0 +1 1.0 + 8.0 +1 1.0 +1 7.0 +1 1.0 +1 7.0 - 1.0 + 7.10 0.57 0.18 1.00 0.00 0.00 GROUP: 4m DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 ANIMAL#: 376814 376815 376819 376824 376832 376833 376850 376853 376858 376880 VOL mL 10.0 10.2 10.5 15.0 14.1 13.0 12.7 10.0 11.9 12.3 OSMOL mOs 1570. 1754. 1775. 13031413. 1272. 1705. 1957. 912. 1722. BLOOD SUGAR ------ -- -- -- -- -- . PRO- TEIN +1 +1 +1 +2 +1 +1 +2 +2 +1 +1 PH BILI- UROBL Ke- RUBIN mg/dL tone 7.0 +1 1.0 + 7.0 +1 1.0 + 7.0 1.0 + 7.0 +1 1.0 + 7.0 8.0 _ 1.0 + 1.0 - 7.0 +1 1.0 + 7.0 +1 1.0 + 8.0 1.0 - 7.0 +1 . 1.0 + AVG. S. D. S. E. 11.97 1538.3 1.78 311.7 0.56 98.6 7.20 0.42 0.13 1.00 0.00 0.00 113 Company Sanitized. Does not contain TSCA CBI M R * HASKELL NUMBER; 15388 mHASKELL CODE: COMPOOND: DEPARTMENT: POLYMER PRODUCTS PERIOD: 14-DAY REC SEX: MALE REPORT DATE 17-0CT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376801 376835 376836 376837 376841 376847 376849 376863 376872 376878 RBC /hpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 WBC /hpf 3-5 10-20 10-15 10-20 10-20 10-20 4-6 4-8 10-20 5-8 Epith /hpf 0-1 0-2 1-2 1-3 2-4 2-4 0-1 4-6 0-2 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 YC Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED DY CL PPT FECES Y CL PPT DA CL PPT FECES Y CL PPT FEED Y CL PPT GROUP: 31 DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 ANIMAL#: 376800 376810 376822 376848 376852 376856 376866 376871 376876 376881 RBC /hpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 WBC /hpf 4-6 3-5 3-6 0-1 0-0 1-5 4-8 0-2 3-6 8-12 Epith /hpf 2-3 0-2 0-3 0-2 0-0 0-0 1-4 0-1 1-2 1-3 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 FEED Y CL PPT FEED DY CL PPT FEED Y CL PPT Y CL DY CL PPT FEED Y CL PPT Y CL Y CL PPT DY CL PPT FECES 14 Company Sanitized. Does not contain TSCA CBI MR: HASKELL NUMBER: 15388 HASKELL C O D E :(0 B ) COMPOUND: i DEPARTMENT: POLYMER PRODUCTS PERIOD: 14-DAY REC REPORT DATE: 17-OCT-84 SEX: male GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 RBC ANIMAL#: /hpf 376803 0-0 376808 0-0 376811 0-0 376812 0-0 376813 0-0 376830 0-1 376843 0-0 376857 0-0 376860. 0-0 376874 0-0 WBC /hpf 10-15 2-4 1-3 3-6 4-6 5-10 4-8 10-15 3-5 5-10 Epith /hpf 0-3 0-2 0-1 0-2 0-2 1-3 0-1 1-2 0-2 2-4 Cast /lpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 APPEARANCE Y CL PPT DY CL PPT FEED DY CL PPT FEED DY CL PPT FEED Y CL PPT DY CL PPT FEED Y CL PPT Y CL PPT FEED Y CL PPT FEED DY CL PPT FEED FECES GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 08/03/84 BIRTH DATE: 05/14/84 ANIMAL#: 376814 376815 376819 376824 376832 376833 376850 376853 376858 376880 RBC /hpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 WBC /hpf 4-8 10-20 3-5 1-3 0-2 4-8 5-10 5-10 0-1 0-3 Epith /hpf 1-3 0-3 0-2 0-1 0-1 0-2 1-2 1-3 0-1 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 Y CL PPT Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED DY CL PPT FEED DY CL PPT FECES Y CL PPT Y CL PPT FEED 1 1 5 Company Sanitized. Does not contain TSCA CBI MR: COM PERIOD SEX: HASKELL NUMBER 41-DAY REC MALE 388 HASKELL C O D E :C 0 l DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 2 7 -F E B -8 5 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/30/84 ANIMAL#: 376801 376807 376829 376834 376836 376837 376847 376861 376869 376878 RBC x 106/ uL 7.55 7.25 8.34 7.50 7.78 8.09 8.70 8.28 7.62 8.06 Hb g/dL 15.4 15.1 16.0 15.1 15.1 15.5 15.8 15.8 15.4 16.1 Ht % 43. 39. 44. 40. 41. 43. 46. 43. 42. 45. AVG. S. D. S. E. 7.917 15.53 0.451 0.38 0.143 0.12 42.5 2.1 0.7 SPECIES: RAT BIRTH DATE: 05/14/84 MCV MCH MCHC PLAT fL Pg g/dL x 1 0 3 / u L 57. 20. 36. 1008. 53. 21. 39. 1020. 52. 19. 37. 694. 53. 20. 38. 1000. 53. 19. 37. 974. 53. 19. 36. 968. 52. 18. 35. 882. 52. 19. 37. 1054. 54. 20. 37. 1122. 55. 20. 36. 782. 53.4 1.6 0.5 19.6 0.8 0.3 36.6 1.1 0.4 950.4 129.3 40.9 GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 08/30/84 BIRTH DATE: 05/14/84 ANIMAL#: 376800 376827 376831 376848 376856 376862 376866 376871 376877 376882 RBC x 1 0 6 /uL 7.36 6.90 7.26 7.14 8.00 7.77 7.68 7.53 7.55 8.44 Hb g/dL 15.4 15.9 15.1 15.3 15.6 15.6 15.6 14.6 15.1 17.2 AVG. S. D. S. E. 7.563 0.443 0.140 15.54 0.69 0.22 Ht % 41. 39. 40. 40. 43. 42. 42. 41. 39. 46. 41.2 2.3 0.7 MCV MCH MCHC PLAT fL Pg g/dL x 1 0 3 / u L 55. 21. 38. 1158. 56. 23. 41. 1236. 54. 21. 38. 1266. 55. 21. 39. 1094. 53. 20. 37. 904. 54. 20. 37. 1086. 54. 20. 37. 994. 53. 19. 36. 1046. 51. 20. 39. 920. 55. 20. 37. 1038. 54.0 .20.6 1.4 i.o 0.4 0.3 37.8 1.3 0.4 1074.2 121.0 38.3 i 16 Company Sanitized. Does not contain TSCA CBI MR: ___ COMPOUND PERIOD: 4` 1-DAY REC SEX: MALE J5388 HASKELL CODE DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 27-FEB-85 GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 08/30/84 BIRTH DATE: 05/14/84 ANIMAL#: 376803 376808 376811 376817 376843 376846 376855 376860 376864 376875 RBC x 1 0 6 /uL 8.45 7.51 7.33 7.96 7.75 7.96 7.83 7.44 6.59 7.10 Hb g/dL 16.4 15.4 15.7 15.3 15.3 16.0 15.8 14.8 15.1 15.5 Ht % 45. 41. 39. 42. 42. 44. 41. 44. 37. 39. MCV fL 53. 53. 53. 52. 53. 55. 52. 59. 56. 55. MCH MCHC PLAT Pg g/dL x 1 0 3 / u L 20. 37. 1142. 21. 38. 1108. 22. 40. 1004. 19. 37. 1244. 20. 37. 1064. 20. 36. 852. 20. 38. 1144. 20. 34. 1398. 23. 41. 1066. 22. 40. 964. AVG. S. D. S. E. 7.592 0.520 0.164 15.53 0.46 0.15 41.4 2.5 0.8 54.1 2.2 0.7 20.5 1.2 0.4 37.7 2.1 0.7 1098.6 150.9 47.7 GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE : 08/30/84 BIRTH DATE: 05/14/84 ANIMAL#: 376814 376815 376816 376826 376832 376842 376845 376850 376853 376868 RBC X106/ uL 7.00 8.06 7.26 7.52 7.47 7.38 6.32 7.07 7.77 7.00 Hb g/dL 15.3 16.1 14.4 15.1 15.1 14.9 13.4 15.8 15.2 15.1 Ht % 39. 43. 38. 41. 40. 41. 36. 39. 41. 39. MCV fL 55. 53. 52. 53. 53. 55. 56. 55. 52. 56. MCH MCHC PLAT Pg g/dL x 1 0 3 / uL 22. 39. 1134. 20. 37. 1544. 20. 38. 1294. 20. 37. 986. 20. 38. 1060. 20. 36. 1080. 21. 38. 1168. 22. 41. 1224. 20. 37. 1088. 21. 38. 1080. AVG. S. D. S. E. 7.285 0.480 0.152 15.04 0.74 0.23 39.6 2.0 0.6 54.0 ' 20.7 1.6 0.9 0.5 0.3 37.9 1.2 0.4 1165.8 159.2 50.4 1 1 7 Company Sanitized. Does not contain TSCA CBI MR: H P ' HASKI COMPOUND : PERIOD: -DY REC SEX: MALE IBER: J5 3 8 8 HASKELL C O D E $ f^ DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 2 7 -F E B -8 5 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376801 376807 376829 376834 376836 376837 376847 376861 376869 376878 WBC x 103/uL 11.8 9.1 12.3 12.9 11.5 13.9 12.2 10.1 13.2 13.9 Neut WBCx 1416. 1274. 1968. 2064. 1380. 3892. 1952. 1414. 2904. 2641. Band WBCx 0. 0. 0. . 0. 0. 0. 0. 0. 0. Lymph WBCx? 10384. . 7462. 10086. 0836. 10005. 10008. 10004. 8080. 9900. 10981. Alym WBCx? 0. 91. 0. . 0. 0. 122. 101. 132. 0. Mono WBCx? 0. 91. 123. . 115. 0. 0. 303. 132. 139. Eosin WBCx? 0. 182. 123. 0. 0. 0. 122. 202. 132. 139. Baso WBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. AVG. S. D. S. E. 12.09 1.56 0.49 2090.5 838.6 265.2 0.0 0.0 0.0 9774.6 1127.7 356.6 44.6 58.6 18.5 90.3 96.4 30.5 90.0 81.4 25.8 0.0 0.0 0.0 GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 08/30/84 BIRTH DATE: 05/14/84 ANIMAL#: 376800 376827 376831 376848 376856 376862 376866 376871 376877 376882 WBC x 1 0 3 /uL 15.7 19.3 13.2 15.4 14.0 13.4 10.0 13.3 11.8 17.0 Neut WBCx 3768. 4632. 2772. 2464. 2800. 3350. 1400. 3458. 2360. 2210. Band WBCx 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. Lymph WBCx? 11618. 14282. 10164. 12782. 10500. 9916. 8500. 9576. 9086. 14110. Alym WBCx? 157. 0. 132. 0. 140. 134. 0. 0. 118. 0. Mono WBCx? 157. 193. 0. 0. 420. 0. 100. 266. 118. 680. Eosin WBCx? 0. 193. 0. 154. 140. 0. 0. 0. 118. 0. Baso WBCx? 0. 0. 132. 0. 0. 0. 0. 0. 0. 0. .AVG. S. D. S. E. 14.31 2.65 0.84 2921.4 912.7 288.6 o.o 11053.4 68.1 193.4 60.5 13.2 0.0 2055.8 72.4 216.4 80.2 41.7 0.0 650.1 22.9 68.4 25.4 13.2 1 18 Company Sanitized. Does not contain TSCA CBI MR: COMPOUND PERIOD: SEX: 41-DAY REC MALE i jJ 5 3 8 8 HASKELL CODE DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 27-FEB -85 GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 08/30/84 BIRTH DATE: 05/14/84 ANIMAL#: 376803 376808 376811 376817 376843 376846 376855 376860 376864 376875 WBC x 1 0 3 /uL 9.4 22.2 7.8 18.9 12.4 9.7 17.8 24.2 15.8 14.4 AVG. S. D. S. E. 15.26 5.56 1.76 Neut WBCx 1316. 4662. 1482. 3402. 4Z1.2. 1552. 2492. . 6776. 2528. 2448. Band WBCx 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 3137.0 1762.2 557.3 0.0 0.0 0.0 Lymph WBCx% 7990. 17094. 6084. 14742. 7440. 7857. 13884. 16940. 12166. 11376. Alym WBCx 0. 0. 78. 378. 0. 0. 712. 242. 158. 144. Mono WBCx 0. 0. 0. 189. 124. 194. 356. 242. 790. 432. Eosin WBCx .94. 222 156. 189. 124. 97. 356. 0. 158. 0. Baso WBCx .0. 222 0. 0. 0. 0. 0. 0. 0. 0. 11557.3 4067.7 1286.3 171.2 227.8 72.0 232.7 245.7 77.7 139.1 105.: 33.: 22.2 70.2 22.2 GROUP: 4M DOSE: .480 mg/L ;SPECIES: RAT TE: 08/30/84 BIRTHI DATE: 05/14/84 ANIMAL#: 376814 376815 376816 376826 376832 376842 376845 376850 376853 376868 WBC x 1 0 3 /uL 11.1 12.5 22.0 15.0 9.5 16.6 20.8 18.4 9.8 12.3 AVG. S. D. S. E. 14.80 4.50 1.42 Neut Band WBCx WBCx . 1776. 0. 1500. 0. 6600. 0. 2700. 150. 1045. 0. 4316. 0. 7280. 0. 5704. 0. 1666. 0. 2214. . 0. 3480.1 2311.2 730.9 15.0 47.4 15.0 Lymph WBCx 9213. 10625. 14740. 11250. 8265. 11786. 12688. 11224. 7938. 10086. Alym WBCx 0. 250. 0. 300. 190. 0. 208. 368. 98. 0. Mono WBCx 111. 125. 0. 450. 0. 332. 416. 552. 98. 0. Eosin WBCx 0. 0. 660. 150. 0. 166. 208. 552. 0. 0. 10781.5 , 2057.9 650.8 141.4 140.2 44.3 208.4 209.2 66.1 173.6 243.2 76.9 Baso iBCx 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.0 0.0 0.0 Il 9 Company Sanitized. Does not contain TSCA CBI MR: f M f t HASKELL NUMBER: 15388 HASKELL CODE COMPOUND DEPARTMENT: POLYMER PRODUCTS PERIOD: '41-DAY R E C ^ ^ ^ ^ ^ ^ " ^ REPORT DATE: 27-FEB-85 SEX: MALE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 ALP ALT AST BUN CREAT TPROT CHLOS ANIMAL#: U/L U/L U/L mg/dL mg/dL g/dL mg/dL 376801 131. 44. 96. 17. 0.68 6.0 53. 376807 121. 36. 67. 20. 0.66 6.6 71. 376829 125. 39. 80. 18. 0.70 6.8 62. 376834 91. 28. 75. 17. 0.65 5.4 63. 376836 166. 37. 81. 15. 0.60 5.6 62. 376837 100. 35. 56. 16. 0.62 6.9 71. 376847 172. 42. 68. 15. 0.65 6.3 58. 376861 173. 43. 78. 16. 0.57 6.5 56. 376869 125. 54. 68. 20. 0.68 6.7 93. 376878 104. 46. 91. 19. 0.67 6.1 85. AVG. 130.8 S. D. 30.1 S. E. 9.5 40.4 7.1 2.2 76.0 11.9 3.8 17.1 0.648 1.9 0.040 0.6 0.013 6.29 0.51 0.16 67.3 12.8 4.0 GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 08/30/84 BIRTH DATE: 05/14/84 ALP ANIMAL#: U/L 376800 197. 376827 134. 376831 174. 376848 99. 376856 102. 376862 219. 376866 156. 376871 139. 376877 120. 376882 . 173. ALT AST BUN CREAT TPROT CHLOS U/L U/L mg/dL mg/dL g/dL mg/dL 36. 101. 16. 0.66 6.0 47. 31. 77. 19. 0.64 6.4 55. 39. 65. 19. 0.61 . 6.6 70. 31. 68. 16. 0.63 6.1 60. 37. 66. 15. 0.64 5.3 52. 28. 78. 17. 0.75 6.9 95. 31. 63. 18. 0.72 7.3 102. 35. 71. 17. 0.69 6.5 58. 28. 61. 19. 0.66 6.3 64. 28. 84. 17. 0.81 6.7 89. AVG. S. D. S. E. 151.3 39.8 12.6 32.4 4.1 1.3 73.4 12.2 3-8 17.3 0.681 1.3 0.062 0.4 0.020 6.41 0.54 0.17 69.2 19.2 6.1 20 Company Sanitized. Does not contain TSCA CBI MR: fl COMPOUND PERIOD: SEX: HASKELL NUMBER: 15388 t mHASKELL CODE DEPARTMENT: POLYMER PRODUCTS 41-DAY REC REPORT DATE: 27-FEB-85 MALE GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 08/30/84 BIRTH DATE: 05/14/84 ANIMAL#: 376803 376808 376811 376817 376843 376846 376855 376860 376864 376875 ALP U/L 117. 224. 138. 127. 182. 147. 155. 144. 230. 106. ALT AST BUN CREAT TPROT CHLOS U/L U/L mg/dL mg/dL g/dL mg/dL 35. 100. 23. 0.78 5.8 41. 40. 87. 18. 0.62 5.8 75. 32. 75. 18. 0.64 5.3 55. 41. 73. 18. 0.59 5.6 64. 38. 65. 17. 0.59 5.8 48. 41. 83. 14. 0.74 6.4 88. 36. 95. 15. 0.69 6.7 88. 30. 60. 15. 0.68 6.5 81. 41. 62. 19. 0.71 7.2 102. 33. 64. 18. 0.67 6.4 70. AVG. S. D. S. E. 157.0 42.4 13.4 36.7 4.1 1.3 76.4 14.3 4.5 17.5 0.671 2.4 0.063 0.8 0.020 6.15 0.58 0.18 71.2 19.3 6.1 GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 08/30/84 BIRTH DATE: 05/14/84 ANIMAL#: 376814 376815 376816 376826 376832 376842 376845 376850 376853 376868 ALP U/L 171. 227. 216. 120. 74. 187. 113. 90. 201. 125. AVG. S. D. S. E. 152.4 54.7 17.3 ALT AST BUN CREAT TPROT CHLOS U/L U/L mg/dL mg/dL g/dL mg/dL 38. 76. 20. 0.71 5.9 69. 22. 71. 16. 0.54 6.0 56. 43. 73. 14. 0.55 6.0 46. 32. 76. 17. 0.66 5.6 53. 26. 80. 17. 0.66 5.4 68. 37. 102. 23. 0.67 6.1 50. 38. 87. 16. 0.63 6.4 87. 31. 65. 15. 0.67 6.4 57. 30. 65. 19. 0.59 6.4 71. 31. 71. 17. 0.78 6.7 70. 32.8 6.3 2.0 76.6 11.1 3.5 17.5 0 .,646 2.5 0.073 0.8 0.023 6.09 0.40 0.13 62.7 12.4 3.9 I2 1 Company Sanitized. Does not contain TSCA CBI MR: ____ HASKELL NUMBER: 15388 HASKELL CODE m COMPOUND: DEPARTMENT: POLYMER PRODUCTS PERIOD: 41-DAY REC REPORT DATE: 27-FEB-85 SEX: MALE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376801 376807 376829 376834 376836 376837 376847 376861 376869 .76878 VOL mL 10.0 7.8 15.0 8.0 13.0 24.0 12.4 17.0 16.5 11.5 OSMOL raOs 1961. 2420. 2280. 1967. 1877. 1164. 2170. 1537. 1915. 1655. BLOOD - SUGAR -- + -- -- -- -- -- -- - PRO TEIN +1 +3 +2 +1 +2 +1 +2 +2 +2 +2 AVG. S. D. S. E. 13.52 1894.6 4.88 369.7 1.54 116.9 pH BILI UROBL Ke RUBIN mg/dL tone 7.0 +1 7.0 +1 1.0 +1 1.0 +1 7.0 1.0 +1 7.0 1.0 + 7.0 -- 1.0 + 8.0 _ 1.0 + 7.0 -- 1.0 + 1 8.0 1.0 + 7.0 _ 1.0 + 7.0 - 1.0 + 7.20 0.42 0.13 1.00 0.00 0.00 GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 08/30/84 BIRTH DATE : 05/14/84 ANIMAL#: 376800 376827 376831 376848 376856 376862 376866 376871 376877 376882 VOL mL 16.0 15.0 10.5 9.0 11.0 9.0 22.5 11.5 11.5 22.0 OSMOL mOs 1608. 1365. 1889. 2126. 1761. 2064. 1389. 1536. 1726. 865. BLOOD SUGAR --- --+ ---- ---- --- +3 -- -+ --- - -- -- PROTEIN +2 +2 +2 +2 +1 +3 +2 +1 +2 +1 PH BILI UROBL Ke RUBIN mg/dL tone 7.0 _ 1.0 +1 7.0 _ 1.0 + 7.0 + 1 1.0 + 7.0 1.0 + 7.0 1.0 +1 7.0 + 1 1.0 + 8.0 . . 1.0 + 7.0 1.0 +1 8.0 _ 1.0 +1 8.0 - 1.0 + AVG. S. D. S. E. 13.80 1632.9 5.00 372.8 1.58 117.9 7.30 0.48 0.15 1.00 0.00 0.00 122 Company Sanitized. Does not contain TSCA CBI MR COM] PERIOD: SEX: male HASKELL NUMBER: -15388 HASKELL C O D E : _ DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 27-FEB-85 GROUP: 3M DOSE .058 mg/L SPECIES: RAT SAMPLE DATE: 08/30/84 BIRTH DATE: 05/14/84 ANIMAL#: 376803 376808 376811 376817 376843 376846 376855 376860 376864 376875 AVG. S. D. S. E. VOL mL 6.5 11.0 12.0 17.0 10.0 18.5 19.5 18.0 12.0 8.5 OSMOL mOs 2420. 2362. 1939. 1534. 2338. 1258. 981. 1344. 1773. 2260. BLOOD -- - -- -- - - -- -- -- -- SUGAR + - - -- PRO TEIN +2 +2 +2 +1 +2 +1 +1 +1 +2 +2 13.30 1820.9 4.60 522.8 1.45 165.3 pH 7.0 7.0 7.0 7.0 6.0 ' 8.0 7.0 7.0 7.0 7.0 BILI RUBIN +1 +1 +1 -- +1 -- -- -- +1 +1 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 + +1 + + + +2 7.00 0.47 0.15 1.00 0.00 0.00 GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 08/30/84 BIRTH DATE: 05/14/84 ANIMAL#: 376814 376815 376816 376826 376832 376842 376845 376850 376853 .76868 VOL mL 12.0 11.5 15.0 15.0 16.0 4.6 30.5 12.5 6.8 11.0 OSMOL mOs 1646. 1808. 1105. 1555. 1232. 2292. 956. 1883. 2336. 1446. BLOOD -- -- + -- -- -- -- SUGAR + + - - - - PRO TEIN +2 +2 +3 +2 +1 +2 +1 +1 +3 +1 AVG. S. D. S. E. 13.49 1625.9 6.97 466.7 2.20 147.6 pH BILI UROBL Ke RUBIN mg/dL tone 7.0 + 1 1.0 + 1 7.0 +1 1.0 +1 8.0 +2 1.0 +1 7.0 -- 1.0 +1 7.0 -- 1.0 + 6.0 + 1 1.0 + 7.0 -- 1.0 + 7.0 + 1 1.0 + 1 7.0 + 1 1.0 -- 7.0 1.0 +1 7.00 0.47 0.15 1.00 0.00 0.00 123 Company Sanitized. Does not contain TSCA CBI MR: _____ COMPOUND: PERIOD: SEX: MALE 388 HASKELL C O D E : * DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 27-FEB-85 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 RBC ANIMAL#: /hpf 376801 0-0. 376807 0-0 376829 0-0 37-6834 0-0 376836 0-0 376837 0-0 376847 0-0 376861 0-0 376869 0-0 376878 0-0 WBC /hpf 3-5 10-15 2-4 0-2 3-5 4-6 0-4 4-8 0-3 0-3 Epith /hpf 1-3 0-3 0-2 0-1 1-3 1-2 0-2 0-3 0-2 2-3 Cast /lpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 APPEARANCE Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED DY CL PPT FEED Y CL PPT FEED Y CL PPT GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 08/30/84 BIRTH DATE: 05/14/84 RBC ANIMAL// : /hpf 376800 0-0 376827 0-0 376831 0-0 376848 0-0 376856 0-0 376862 7-10 376866 0-0 376871 0-0 376877 0-0 376882 0-0 WBC /hpf 0-0 0-3 1-2 0-2 0-2 2-4 1-2 1-3 2-3 0-1 Epith /hpf 4-6 3-5 4-6 6-8 5-7 7-9 2-4 1-3 1-2 2-4 Cast /lpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 APPEARANCE Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED DY CL PPT FEED Y CL PPT FEED Y C PPT FEED Y CL PPT FEED YCL PPT FEED 24 Company Sanitized. Does not contain TSCA CBI compou PERIOD: SEX: MALE HASKELL NUMBER; 1 5 388 HASKELL C O D E :( J ( J n d d e p a r t m e n t : polymer products REPORT DATE: 27-FEB-85 GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 08/30/84 BIRTH DATE: 05/14/84 RBC ANIMAL#: /hpf 376803 0-3 376808 0-0 376811 0-0 37-6817 0-0 376843 0-0 376846 0-0 376855 0-0 376860 0-0 376864 0-0 376875 0-0 WBC /hpf 4-6 1-2 3-5 1-2 0-2 5-10 2-4 10-20 5-8 0-4 Epith Cast /hpf /lpf 0-2 0-0 0-2 0-0 1-2 0-0 0-1 0-0 0-1 0-0 0-3 0-0 0-2 0-0 1-4 0-0 0-3 0-0 0-3 0-0 APPEARANCE Y CL PPT FEED Y C PPT FEED Y CL PPT FEED Y CL PPT FEED Y C PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y C PPT GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 08/30/84 BIRTH DATE: 05/14/84 RBC ANIMAL#: /hpf 376814 0-0 376815 0-0 376816 0-1 376826 0-0 376832 0-1 376842 0-0 376845 0-0 376850 0-0 376853 0-0 376868 0-0 WBC /hpf 1-2 0-2 1-2 1-2 0-0 0-1 1-2 0-1 1-2 0-1 Epith /hpf 4-6 1-2 1-3 3-5 0-1 0-2 1-3 1-2 3-5 1-3 Cast /lpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 APPEARANCE Y CL PPT FEED Y CL PPT FEED DY CL PPT FEED FECES Y CL PPT FEED Y C PPT Y C PPT LY CL PPT FEED Y CL PPT FEED Y C PPT Y C PPT I 25 Company Sanitized. Does not contain TSCA CBI MR: COMPOUND: HASKELL NUMBER: _______ PERIOD: 84-DAY REC SEX: MALE L5388 HASKELL C O D E ^ ^ DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 10/12/84 ANIMAL#: 376807 376829 376834 376861 376869 RBC x 105/u L 7.80 8.60 8.31 8.51 7.54 Hb g/dL 16.1 16.1 15.7 16.5 15.8 AVG. S. D S. E* 8.152 16.04 0.462 0.31 0.206 0.14 Ht % 40. 42. 41. 41. 39. 40.7 1.2 0.5 SPECIES: RAT BIRTH DATE: 05/14/84 MCV MCH MCHC PLAT fL Pg g/dL x 1o 3/u L 50. .21. 40. 1120. 48. 19. 39. 1288. 49. 19. 38. 1154. 48. T9. 40. 1120. 51. 21. 41. 1356. 49.2 1.3 0.6 19.7 1.0 0.4 39.4 1.1 0.5 1207.6 108.1 48.3 GROUP: 2M DOSE: 0076 mg/L SPECIES: RAT SAMPLE DATE: 10/12/84 BIRTH DATE: 05/14/84 JIMAL#: 376827 376831 376862 376877 376882 AVG. S. D. S. E. RBC x 106/u L 7.08 7.54 6.91 8.21 8.81 7.710 0.795 0.355 Hb g/dL 15.4 16.2 14.8 15.2 16.0 15.52 0.58 0.26 Ht % 38. 40. 35. 39. 45. 39.5 3.6 1.6 MCV fL 53. 53. 51. 47. 51. 51.0 2.4 1.1 MCH Pg 22. 22. 22. 19. 18. 20.3 1.8 0.8 MCHC g/dL 41. 41. 42. 39. 36. PLAT x 103/u L 1434. 1324. 1446. 1074. 826. 39.6 2.5 1.1 1220.8 266.6 119.2 j 26 Company Sanitized. Does not contain TSCA CBI MR: [j COMPOI PERIOD: SEX: MALE HASKELL NUMBER: _15388 HASKELL CODE: DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 10/12/84 BIRTH DATE: 05/14/84 ANIMAL#: 376817 376846 376855 376864 376875 RBC x 106/ uL 9.52 8.42 9.26 7.12 8.12 Hb g/dL 15.9 16.5 16.5 14.6 15.6 Ht MCV % fL 47. 49. 43. 51. 46. 49. 38. 52. 43. 53. MCH MCHC PLAT Pg g/dL x 1 0 3 / u L 17. 34. 1022. 20. 38. 1162. 18. 36. 1180. 21. 39. 1312. 19. 36. 1028. AVG. S. D. S. E. 8.488 15.82 0.958 0.79 0.429 0.35 43.5 3.7 1.6 50.8 1.8 0.8 18.7 1.5 0.7 36.5 2.0 0.9 1140.8 120.6 53-9 GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 10/12/84 BIRTH DATE: 05/14/84 RBC Hb Ht MCV MCH MCHC PLAT ANIMAL#: x 1 0 6 / u L g/dL ? fL Pg g/dL x 1 0 3 / u L 376816 7.53 14.9 37. 49. 20. 40. 1208. 376826 7.90 14.7 39. 49. 19. 37. 1174. 376842 8.13 15.6 43. 52. 19. 37. 894. 376845 7.47 14.1 40. 53. 19. 36. 972. 376868 8.18 16.2 43. 53. 20. 38. 926. AVG. S. D. S. E. 7.842 15.10 0.330 0.82 0.148 0.36 40.5 2.5 1.1 51.2 2.0 0.9 19.3 0.5 0.2 37.4 1.7 0.7 1034.8 145.8 65.2 127 Company Sanitized. Does not contain TSCA CBI MR: ____ HASKELL NUMBER: 15388 HASKELL C O D E : 1 _ COMPOUND: PERIOD: 84-DAY REC SEX: MALE DEPARTMENT: POLYMER PRODUCT? REPORT DATE: 17-OCT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 10/12/84. SPECIES: RAT BIRTH DATE: 05/14/84 IIMAL#: 376807 376829 376834 376861 376869 WBC x 103/u L 11.9 10.9 13.0 10.4 12.0 AVG. S. D. S. E. 11.64 1.02 0.45 Neut WBCxi 2142. 1744. 1560. 1872. 1320. Band mcx% 0. 0. 0. 0. 0. 1727.6 311.1 139.1 0.0 0.0 0.0 Lymph WBCxi 8449. 8938. 11050. 8112. 10320. Alym WBCx$ 476. 109. 130. 0. 120. Mono WBCx* 714. 109. 130. 104. 0. Eosin WBCx 119. 0. 130. 312. 240. Baso WBCx$ 0. 0. 0. 0. 0. 9373.8 1259.2 563.1 167.0 180.5 80.7 211.4 285.5 127.7 160.2 120.1 53.7 0.0 0.0 0.0 GROUP: 2M DOSE: .0076 mg/L SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376827 376831 376862 376877 376882 WBC x 103/u L 13.3 13.5 15.5 10.1 12.8 AVG. S. D. S. E. 13.04 1.94 0.87 Neut WBCxi 2926. 2700. 2325. 1111. 1536. Band WBCx$ 0. 0. 0. 0. 0. 2119.6 772.5 345.5 0.0 0.0 0.0 Lymph WBCx 9709. 10125. 12710. 8787. 10752. Alym WBCx* 133. 270. 155. 0. 384. Mono WBCx* 399. 270. 310. 101. 128. Eosin WBCx* 133. 135. 0. 101. 0. Baso WBCx$ 0. 0000.... 10416.6 188.4 241.6 1467.4 145.4 125.4 656.3 65.0 56.1 73.8 68.7 30.7 0.0 0.0 0.0 28 Company Sanitized. Does not contain TSCA CBI MR: j B r t ^ ^ H A S K E L L N W B E R ^ 5 3 8 8 HASKELL CODE: COMPOUND: PERIOD: 84-DAY REC SEX: MALE DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 10/12/84 BIRTH DATE: 05/14/84 ANIMAL#: 376817 376846 376855 375864 376875 WBC xIO^/uL 17.1 18.1 16.5 12.2 21.4 AVG. S. D. S* E* 17.06 3.31 1.48 Neut WBCx 3420. 3620. 2805. 2196. 2568. Band WBCx 0. 0. 0. 0. 214. 2921.8 591.9 264.7 42.8 95.7 42.8 Lymph WBCx$ 12996. 13937. 13365. 9638. 15408. Alym WBCx$ 0. 181. 0. 122. 1070. Mono WBCx? 342. 0. 330. 244. 1712. Eosin WBCxf 342. 362. 0. 0. 428. Baso WBCx 0. 0. 0. 0. 0. 13068.8 2126.6 951.0 274.6 451.5 201.9 525.6 677.3 302.9 226.4 209.1 93.5 0.0 0.0 0.0 GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 10/12/84 BIRTH DATE: 05/14/84 ANIMAL#: 376816 376826 376842 376845 376868 WBoC xIO-VuL 24.2 17.9 23.1 18.0 17.1 AVG. S. D.. S. E. 20.06 3.32 1.48 Neut WBCxJ 7260. 3938. 5775. 6300. 3078. Band WBCx? 0. 0. 0. 0. 0. 5270.2 1721.6 769.9 0.0 0.0 0.0 Lymph WBCx 15972. 12351. 15708. 10800. 13338. Alym WBCx$ 242. 716. 231. 360. 342. Mono WBCx? 0. 537. 1386. 360. 342. Eosin WBCx 726. 358. 0. 180. 0. Baso WBCx 0. 0. 0. 0. 0. 13633.8 378.2 525.0 252.8 2209.8 197.5 519.1 303.4 988.3 88.3 232.1 135.7 0.0 0.0 0.0 1 2 9 Company Sanitized. Does not contain TSCA CBI MR: COMP PERIOD: SEX: MALE JASKELL NUMBER: 15388 HASKELL C O D E : DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376807 376829 376834 376861 376869 AVG. Sa D S E. ALP U/L 84. 78. 66. 161. 96. 97.0 37.4 16.7 ALT U/L 35. 40. 29. 37. 27. 33.6 5.5 2.4 AST BUN U/L mg/dL 65. 21. 81. 16. 69. 1 7 . 64. 21. 49. 24. CREAT mg/dL 0.61 0.59 0.64 0.59 0.71 TPROT g/dL 4.6 7.4 6.4 6.9 7.0 CHLOS mg/dL 119. 198. 75. 64. 132. 65.6 11.5 5.1 1 9 . 7 0.628 3.5 0.050 1.6 0.022 6.46 1.10 O.4 9 117.5 53.3 23.8 GROUP: 2M SAMPLE DATE: DOSE: 10/12/84 .0076 mg/L SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376827 376831 376862 376877 376882 ALP U/L 110. 136. 190. 83. 150. AVG. S. D. S. E. 133.8 40.5 18.1 ALT U/L 30. 35. 32. 26. 23. 29.2 4.8 2.1 AST U/L 60. 68. 65. 53. 56. 60.4 6.2 2.8 BUN g/dL 21. 19. 19. 20. 18. CREAT mg/dL O. 6 5 0.64 0.74 0.65 0.77 TPROT g/dL 6.4 7.2 7.3 7.1 7.2 CHLOS mg/dL 73. 94. 118. 83. 94. 1 9 . 5 O.6 9 O 1.0 0.060 0.4 0.027 7.04 0.36 0.16 92.3 16.9 7.5 30 Company Sanitized. Does not contain TSCA CBI M R :(^ B g^ _ H A S K E L L COMPOUND PERIOD: SEX: MALE NUMBER: 5 3 8 8 HASKELL C 0 D E : J H DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 10/12/84 BIRTH DATE: 05/14/84 ANIMAL#: 376817 376846 376855 376864 376875 AVG. S. D. S. E. ALP U/L 84. 156. 92. 211. 89. 126.4 55.7 24.9 ALT U/L 33. 87. 26. 40. 30. 43.2 25.0 11.2 AST U/L 70. 145. 70. 66. 65. BUN mg/dL 23. 16. 19. 19. 18. CREAT mg/dL 0.67 0.62 0.74 0.65 0.67 TPROT g/dL 6.9 6.8 7.3 7.4 6.9 CHLOS mg/dL 71. 96. 99. 124. 81. 83.2 34.6 15.5 1 9 . 2 0.670 2.7 0.044 1.2 0.020 7.06 0.27 0.12 94.4 20.1 9.0 GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 10/12/84 BIRTH DATE: 05/14/84 ALP ALT AST BUN CREAT TPROT CHLOS ANIMAL#: U/L U/L U/L mg/dL mg/dL g/dL mg/dL 376816 171. 49. 71. 14. 0.55 7.3 79. 376826 64. 25. 61. 16. 0.65 7.0 77. 376842 376845 376868 224. 70. 72. 43. 36. 23. 97. 74. 53. 19. 0.71 15. O. 6 3 14. O. 6 7 6.4 6.7 7.0 49. 93. 78. AVG. S. D. S. E. 120.2 73.1 32.7 35.2 11.2 5.0 71.2 16.6 7.4 15.4 0.642 2.1 0.059 0.9 0.027 6.88 0.34 0.15 75.0 16.1 7.2 131 Company Sanitized. Does not contain TSCA CBI MR: _____ HASKELI^UMBER^ 15388 HASKELL C O D E : COMPOUND:: W K ^ APARTMENT: POLYMER PRODUCTS PERIOD: 84-DAY REC REPORT DATE: 17-OCT-84 SEX: MALE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376807 376829 376834 376861 376869 AVG. S. D. S. E. VOL mL 6.4 10.5 19.5 21.0 10.0 OSMOL mOs 2636. 2348. 763. 1337. 1836. BLOOD + + + SUGAR + + + - PROTEIN +3 +2 + +2 +3 13.48 1784.0 6.40 756.5 2.86 338.3 PH BILI- UROBL Ke- RUBIN mg/dL tone 7.0 +1 1.0 +1 7.0 +1 8.0 -- 0.1 +1 . 0.1 8.0 0.1 + 7.0 - 0.1 + 7.40 0.55 0.24 0.28 0.40 0.18 GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 10/12/84 BIRTH DATE: 05/14/84 ANIMAL#: 376827 376831 376862 376877 376882 VOL mL 41.0 ' 8.4 10.2 9.4 18.0 OSMOL mOs 721. 2070. 1849. 2212. 1100. BLOOD + +1 +1 + SUGAR +1 +1 + PROTEIN +1 +2 +2 +2 +1 PH BILI- UROBL Ke- RUBIN mg/dL tone 7.0 0.1 7.0 +1 1.0 + 7.0 +1 1.0 + 7.0 1.0 +1 7.0 - 0.1 AVG. S. D. S. E. 17.40 1602.4 13.73 662.8 6.14 296.4 7.00 0.00 0.00 0.64 O.4 9 0.22 I 32 Company Sanitized. Does not contain TSCA CBI MRs l B H ^ ^ ^ H A S K E L ^ i r o i B r a ! l 5388 HASKELL CODE:( COMPOUND: DEPARTMENT: POLYMER PRODUCTS PERIOD: 84-DAY REC SEX: MALE REPORT DATE: 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 10/12/84 BIRTH DATE: 05/14/84 ANIMAL#: 376817 376846 376855 376864 376875 AVG. S. D. S. E. VOL mL 13.0 14.0 25.0 18.0 11.5 OSMOL mOs 1448. 1398. 778. 1421. 1773. BLOOD SUGAR -++ ++ ++ -- PRO- TEIN +2 +1 +1 +1 +2 16.30 1363.6 5.43 361.3 2.43 161.6 PH BILI UROBL Ke RUBIN mg/dL tone 8.0 1.0 +1 7.0 0.1 7.0 0.1 7.0 1.0 8.0 +1 1.0 +1 7.40 0.55 0.24 0.64 O. 4 9 0.22 GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 10/12/84 BIRTH DATE: 05/14/84 ANIMAL#: 376816 376826 376842 376845 376868 AVG. S. D. S. E. VOL OSMOL mL mOs 18.5 1292. 18.5 1372. 5.7 2348. 30.0 839. 12.5 '1381. BLOOD + + + +1 + SUGAR + + +1 + + PROTEIN +1 +2 +2 +1 +1 17.04 1446.4 8 . 9 6 551.2 4.01 246.5 pH BILI- UROBL Ke- RUBIN mg/dL tone 8.0 - 0.1 + 7.0 - 1.0 +1 7.0 - 1.0 + 7.0 - 0.1 7.0 - 0.1 + 7.20 0.45 0.20 0.46 O. 4 9 0.22 133 Company Sanitized. Does not contain TSCA CBI MR: f l H | ^ ^ ^ I i A S K E L y i U M B E R ^ 1 5 3 8 8 HASKELL CODE C O M P O U N D T f l p | ^ ^ g j j ^ B | B P \ DEPARTMENT: POLYMER PRODUCTS PERIOD: 04-DAY REC ^ REPORT DATE: 17-OCT-84 SEX: MALE GROUP: 1GM DOSE: CONTROL SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL#: 376807 376829 376834 376861 376869 RBC /hpf 0-0 0-1 0-1 0-0 0-1 WBC /hpf 4-6 1-3 3-6 5-8 1-2 Epith /hpf 1-3 0-2 0-1 1-2 0-3 Cast /lpf 0-0 0-0 0-0 0-0 0-0 APPEARANCE Y CL PPT Y CL PPT LY CL PPT Y CL PPT FEED Y CL PPT GROUP: 2M DOSE: .0076 mg/L SPECIES: RAT SAMPLE DATE: 10/12/84 BIRTH DATE: 05/1 ANIMAL#: 376827 376831 376862 376877 376882 RBC /hpf 0-2 0-1 0-2 0-3 0-1 WBC /hpf 5-10 4-8 3-5 10-20 0-2 Epith /hpf 3-5 0-2 1-2 4-8 0-1 Cast /lpf 0-0 0-0 0-0 0-0 0-0 APPEARANCE LY CL PPT FEED DY CL PPT FEED DY CL PPT FEED Y CL PPT FEED Y CL PPT FEED 3 4 Company Sanitized. Does not contain TSCA CBI MR: ____ COMPOUND PERIOD: SEX: HASKELL NUMBER: 4-DAY REC MALE 15388 HASKELL C O D E ^ f O DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-0CT-84 GROUP: 3M DOSE: .058 mg/L SPECIES: RAT SAMPLE DATE: 10/12/84 BIRTH DATE: 05/14/84 ANIMAL#: 376817 376846 376855 376864 376875 RBC /hpf 0-0 0-1 0-2 0-0 0-0 WBC /hpf 0-3 5-8 3-4 2-4 1-3 Epith /hpf 0-2 3-5 0-2 3-6 1-2 Cast /lpf 0-0 0-0 0-0 0-0 0-0 APPEARANCE Y CL PPT' FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT Y CL PPT GROUP: 4M DOSE: .480 mg/L SPECIES: RAT SAMPLE DATE: 10/12/84 BIRTH DATE: 05/14/84 ANIMAL#: 376816 376826 376842 376845 376868 RBC /hpf 1-2 0-3 0-1 0-3 0-2 WBC /hpf 0-3 4-8 0-3 10-15 2-4 Epith /hpf 1-3 1-4 0-2 3-6 1-2 Cast /lpf 0-0 0-0 0-0 0-0 0-0 APPEARANCE Y CL PPT Y CL PPT FEED Y CL PPT Y CL PPT FEED FECES Y CL PPT 135 Company Sanitized. Does not contain TSCA CBI APPENDIX VII BLOOD FLUORINE ANALYTICAL REPORTS - 136 Company Sanitized. Does not contain TSCA CBI Ep ESTABLISHED 1802 E . I. d u P o n t d e N e m o u r s S C o m p a n y .IN C O R PO R A TED W il m in g t o n , D e l a w a r e 19898 CHEMICALS AND PIGMENTS DEPARTMENT JACKSON LABORATORY October 18, 1984 FROM: L. A. Kinney CR&D, Haskell Lab. E. Rissa sCutsK* C&P, Jackson Lab. c* - FLUORINE IN BLOOD Wf ^ave analyzed j:at blood samples of the inhalation subchronic study fluorine. Sixty rat blood samples were analyzed ror total fluorine by the oxyhydrogen torch method and four samples for ionic (inorganic) fluorine by our analyte addition method. The difference between total fluorine and ionic (inorganic) fluorine is organic fluorine. The ionic fluorine values were found to be so low that the difference between total and organic fluorine is insignificant in this study. The amount of organic fluorine in exponentially with the increasing (Fig. 1), expressed as: cb k can C|j, was found to increase oncentration in air, ca The values of the coefficient, k, and to a lesser extent. the values (Tab5,le eIx).Pnent decreased with the increasing recovery time. % 137 Company Sanitized. Does not contain TSCA CBI Page 2. October 18. 1984 I. A. Kinne BLOOD TABLE I ORGANIC FLUORINE IN RAT RT.nnn Exposure Co |(mq/m3 ) Initial 2-Weeks Recovery 6-Weeks . Recovery 0 7.6 58.0 480.0 2.0 10.2 42.0 147.0 0.9 4.0 13.0 40.5 0.9 1.8 7.2 16.6 Average values for blood samples of five rats. k 2.87 1.31 0.67 n 0.64 0.56 0.54 recovefy Period the logarithm of organic fluorine content of blood decreased with the square root of the recovery time fFio process?681103 that 1UClne ls * a dUfusIonconUoiled log (ct/c0 ) = kct*5 is tile organic fluorine concentratio initial organic fluorine concentration, and k coefficient. at time t. c0 the the recovery TABLE II DESORPTION RATE OF FLUORINE FROM RT.non tonsure Cone, (m\ Wqa //mm3*N)\ in Air 0 7.6 58 480 -- -0.31 -0.32 -0.39 Recovery time (weeks) Needed for the Fluorine Values to Return to Normal (1 ppm or lessl Values 11 26 31 ptlbabxie ? L t!'Lfe^ rPti0?.Coetficlent "t or human blot") differs similar^ od- but the desorption mechanism may be The inorganic (ionic) perhaps significantly, If the slight increase to normal values in a fluorine in rat blood increased slightly, but as a result of exposure toHtfR(Table Hi), was significant, the ionic^^uorine returned relatively short time. - ] 38 - Company Sanitized. Does not contain TSCA CBI b V U C i . JL U # L 7 0 * * L. A. Kinney FLUORI N BLOOD ExD^ur e ll^Qconc. in Air (mg./m3 ) 0 0 0 0 480 480 480 480 TABLE III INORGANIC (IONIC) FLUORINE IN RAT BLOOD Recovery Time (Weeks) 0 2 2 2 0 0 0 2 Organic Fluorine (ppm) 1.4 0.7 1.1 0.7 140.0 112.0 168.0 41.2 Inorganic Fluorine (ppm) 0.016 0.025 0.019 0.007 0.055 0.034 0.063 0.020 Rat No. 376 840 376 849 376 835 376 841 376 854 376 828 376 879 376 858 The remaining 56 blood samples will be analyzed for ionic fluorine. _ if the significance of the apparent ionic fluorine elevation byflHpQ exposure has to be established. The total fluorine values of the sixty blood samples analyzed are given in Table IV. EKissa/jve 0524J 39 Company Sanitized. Does not contain TSCA CBI uccoDer b , 1984 L. A. Kinney____ FLUORINE IN BLOOD 1 TABLE IV iUTAL FLUORINE IN RAT BLOOD OF THE INHALATION SUBCHRONIC STUDY ON ________ TOTAL FLUORINE (PPM) roup Cone. in Air Initial Rat Number ppm F I - Control 0 mg/m3 376839 376870 376840 376873 376825 1.5 1.7 Avg. 1.4 2.0 4.6 1.0 II - Low 7.6 mg/m3 376804 376844 376806 376823 376818 10.8 7.6 10.5 10.8 11.1 Avg. 10.2 Cl - Inter. 58 mg/m3 376805 376838 376851 376821 376867 44.3 46.0 44.4 47.4 28.0 Avg. 42.0 V - High 480 mg/m3 376854 376879 376828 376820 376859 140.0 168.0 112.0 176.0 138.0 Avg. 147 2-Weeks Recovery Rat Number 376872 376849 376835 376841 376863 1.0 0.7 1.1 0.7 1.1 Avg. 0.9 376810 376876 376852 376822 376881 3.4 4.4 3.4 4.0 4.7 Avg. 4.0 376874 376812 376813 376857 376830 15.1 12.9 10.3 11.8 14.9 Avg. 13.0 376858 376824 376880 376833 376819 41.2 34.7 33.6 37.9 55.0 Avg. 40.5 6-Weeks Recovery Rat Number ppm F 376801 376836 376837 376878 376847 0.8 1.3 Avg. 0.5 0.9 0.7 1.0 376871 376800 376848 376866 376856 1.6 1.4 Avg. 2.0 1.8 2.1 1.7 376808 376811 376803 376843 376860 8.2 8.6 5.3 6.9 7.0 Avg. 7.2 376815 376814 376853 376850 376832 16.8 11..1 17.7 18.7 18.8 Avg. 16.6 :j v e 24J 140 Company Sanitized. Does not contain TSCA CBI Company Sanitized. Does not contain TSCA CBI i_rw-A #POE> ESTA9U5HCO IB02 E. I. du P o n t d e N e m o u r s & C o m p a n y IN C O R P O R A T E D W il m in g t o n , D e l a w a r e 19898 CHEM ICALS AND PIGMENTS DEPARTMENT JACKSON LABORATORY December 19. 1984 TO: FROM: L. A. Kinney CR&D. Haskell Lab. E Kissa C&P. Jackson Lab. * FLUORINE IN BLOOD The rat blood samples of the twelve-weeks recovery period have been analyzed for fluorine (Table I). This completes ^^^fluorine data of the inhalation subchronic study on To compare the recovery rate of ft^firelated fluorine in blood to that of perfluorooctanoic acid the data have to be fitted to a kinetic expression that permits the calculation of rate constants or rate coefficients. This is. however, not straightforward, because the elimination of fluorine from blood does hot obey simple kinetics. The decrease of the organic fluorine concentration in blood during the recovery period of the recent inhalation subchronic study on TBSA can be represented as a reasonable approximation with the equation log (ct/c0 ) = kr tO-5. {1) . where is the organic fluorine concentration in blood at time t, cQ the initial organic fluorine concentration in blood, and kr th recovery coefficient. (Fig. 2 in Kissa to Kinney. October 18 1984 ) I 43 Company Sanitized. Does not contain TSCA CBI December 19, 1984 L. A. Kinney - FLUORINE IN BLOOD The average fluorine values of the 12-weeks recovery period are slightly lower than these calculated by this equation from the recovery data of the first six weeks. Initial Fluorine Cone, in Blood ____ RE!________ Fluorine Cone. after 12-weeks Recovery Predicted P P m ________________ _ Found 10.2 42.0 147.0 0.90 3.2 6.6 0.40 2.2 4.4 The recovery coefficients are slightly higher for the 0 to 12 weeks r e c Y | r y period than those calculated for the 0 to 6-weeks recovery period, but the correlation with equation (1) is still reasonable: Exposure Cone. o f H i n Air (m g , / m *) 7.6 58 480 Linear Correlation Coefficient (for log c vs. t05i lbr.iLweeks 0-12 weeks 0.9991 0.995 0.9998 0.993 0.992 0.995 Recovery Coefficient ic. 0-6 weeks 0-12 weeks -0.31 -0.32 -0.39 -0.35 -0.36 -0.43 _ in that the decay of fluorine during recovery period of a perfluorooctanoic acid feeding study approximates first-order kinetics. log ct/cc * krt ( 2) The log c vs. time plot (Fig. 1) shows considerable curvature indicating that the removal of fluorine from blood is more rapid at the beginning of the recovery time than predicted by equation (2). The first-order plot of |^HKjdata also shows curvature (Fig. 2). Conceivably the rate at which a fluorocompound is eliminated from oiood is not the same for differentfMBSjtelomers. Their diffusion rates are likely to vary with their chain length. It is also possible that the adsorptive bond of the fluorochemical in blood may vary. The less strongly bonded molecules may be eliminated at a faster rate and leave the more strongly held fluorochemical molecules back. Since perfluorooctanoic acid is homogeneous, this f . chanism is needed to explain its decreasing coefficient elimination rate. Perhaps perf luorooctanoic acid dissolved in blood is eliminated from blood at a fast rate, but perfluorooctanoie acid bound to protein in blood at. a slower rate perhaps together with the protein on which it is adsorbed. Whatever tne true mechanism, the expected result is a decrease of the recovery rate (fluorine elimination rate) coefficient with increasing time. i 44 Company Sanitized. Does not contain TSCA CBI l / e t o n l L i i i , 1S4 I j . A. K i n n e v 5- FLUORINE IN BLOOD The average fluorine removal rate coefficient kt during a time interval At can be calculated from the eguation Ac At " ktca* (3) where Ac is the average fluorine concentration decrease and tne average fluorine concentration during time interval At. follows that It log (Ac) = log kt + z log C; At (4) ^ J ^ ? tKfJ j P W rfcoverlr data according to the equation (4) yields straight lines with the average z value of one. However, the loa kt. and consequently, the kt, values are not constant, but decrease with the increasing recovery time (Table II), in accord with my explanation of curvature in first order plots (Fig. 3 and 4). Hence log (ct/c0 ) = ktt (5) where kt is the time dependent rate coefficient at time t. The question remains, why does the t H B d a t a fit equation (5) and also, as a reasonable approximation, equation (1). since the left fHunZcrtit oLn ' oZf ti?muea.tioT"hi.sisi.sthethesamcea,se twhheenright side has to be the same kt = kr/ty. where y is an exponent. If y = 0.5 *t = k r / t ` S > and the equation (5) becomes equation (1) log (ct/cD ) = _ j ^ 5 = krt0 *5. (7) (8 ) intervals of(jBBrecovery data are not suited for redefining the time dependence o f t h e rate coefficients, the kt (laoie tII?I?)?. t0 vary approximately with the square root of time: 145 Company Sanitized. Does not contain TSCA CBI uecemoer i , a s b L. A. Kinney_____ - FLUORINE IN BLOOD In summary, the elimination of organic fluorine from blood can be described by a time dependent rate coefficient k* and an exponent z. that is approximately equal to one. A logarithmic plot log (Ac/At) = log kt + z log ca (9 ) or regression analysis using a pocket calculator, yields kt . A comparison ofRBRand perfluorooctanoic acid decay in blood suggests that kt values of anionic fluorosurfactants in blood may not be largely different. H o w e v e r . Q B Q i s much less volatile than perfluorooctanoic acid and poses therefore a lesser environmental problem. EK:jve Attach. 0564J 146 Company Sanitized. Does not contain TSCA CBI TABLE I FLUORINE IN BLOOD AFTER A 12-WEEK RECOVERY PRRtnn Exposure Control: (0 mg/m3) Low: (7.6 mg/m3) Intermediate: (58 mg/m3) High: (480 mg/m3) Rat Number 376869 834 829 807 861 376877 862 882 831 827 376875 864 817 855 846 376826 845 868 816 842 Fluorine DDm 0.54 0.54 0.17 0.49 0.26 0.53 0.72 0.64 0.64 0.52 1.37 1.91 1.18 2.13 4.23 5.89 3.22 4.12 5.21 3.47 Average Fluorine ___ P P m 0.40 0.61 2.16 4.38 147 Company Sanitized. Does not contain TSCA CBI TABLE TT KINETICS OF FLUORINE ELIMINATION FROM RAT BLOOD Recovery Period (weeks)_____ 0-2 2-6 6-12 0-2 2-6 Fluorochemical (i n H R ^ o n ) Perfluorooctanoic Acid (feeding) Rate Coefficient --- t------ 0.36 0.17 0.16 Average 0.73 0.33 Average Exponent z l.io 1.03 1.07 1.07 0.92 1.03 o.98 TABLE III Recovery Period (weeks) 0-2 2-6 6-12 RATE COEFFICIENTS AS A FUNCTION OF TIME Average Recovery Time (weeks) Square Root of Average Recovery Time_______ Found Rate Coefficient Calc. Perfluorooctanoic ______ Acid_______ Found Calc. 1 4 9 1 2 3 0.36 0.17 0.16 0.18 0.12 0.73 0.33 0.37 Calculated by the equation (7). EK:jve Attach. 0564J 148 Company Sanitized. Does not contain TSCA CBI liiiiniiiuimiinHiwiiiiiiiii / Sr Compan/Sanitized. Does not contain TSCA CBI # d S0S 151 Company Sanitized. Does not contain TSCA CBI /ofr /*/ & 0 / 2 / s / f <? ? / * ^ / ? <? z > 3 , t o ?4 5 6 7 9 0 y 152 Company Sanitized. Does not contain TSCA CBI APPENDIX Vili BLOOD FLUORINE STATISTICS - 153 Company Sanitized. Does not contain TSCA CBI _ _ _ ^ MEAN BLOOD FLOURINE CONCENTRATIONS T u e s l n Loq(ppm) + 1) ~ H# 14,930 , GROUP 0 DAYS POST EXPOSURE 14 DAYS POST EXPOSURE 41 DAYS POST EXPOSURE CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 1.2431( 2.0028( 2.6159( 3,161-2 ( 0.000) 0.000)# 0.000)# 0.000)# 0.9546( 1.5961( 2.1095( 2.6001( 0.000) 0.000)# 0.000)# 0.000)# 0.9122( 1.2408( 1.8513( 2.212 9( 0.000) 0.000)# 0.000)# 0.000)# TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.000 0.000 0.034 0.000 0.000 0.818 0.000 0.000 0.425 GROUP 84 DAYS POST EXPOSURE CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.5601( 0.7820( 1.2889( 1.6300( 0.000) 0.054) 0.000)# 0.000)# TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.000 0.000 0.088 Values in parentheses - P VALUE OF STUDENT'S 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 54 Company Sanitized. Does not contain TSCA CBI