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AR226-2927 FOR DUPONT USE ONLY Subchronic Inhalation Toxicity of Haskell Laboratory Report No. 182-85 I MR No, Haskell E. I. du Pont de Nemours and Co., Inc. Laboratory for Toxicology and Industrial P. 0. Box 50, Elkton Road Newark, Delaware 19714 Medicine Date Issued: May 8, 1985 Company Sanitized. Does not contain TSCA CBI Subchronic Inhalation Toxicit Summary Three groups of 20 male Cri:CD(SD)BR rats wefi_xposed 6 houj days/week lU^in ^{iH^UIB--^ Wter the Blood and for 2 weeks to 7.6, 58 or 480 mg/m air. A control group was exposed simuTtaneousiytoair only. exposure period, rats were observed for up to 12 weeks of recovery. 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 significantly lower than controls from the of recovery. No other significant adverse any rats throughout the test. 480 mg/m of||^BRwere 2nd exposure through the 17th day" clinical signs were observed in ofpU^ Clinical analyses after 10 exposures revealed several, hematologic and clinical chemical changes in rats exposed to 480 mg/m 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/m . Pathologic examination showed compound-related changes in the livers and kidneys of rats exposed to 480 mg/m . 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 a11 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 adverse 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 Company Sanitized. Does not contain TSCA CBI concentrations for rats exposed to 7.6 mg/m3were indistinguishable from controls. However, fluorine concentrations for rats exposed to 58 mg/m and rats exposed to 480 mg/m- were still significantly elevated. JU^ No significant adverse effects were observed in rats exposed to 7.6 or 58 mg/m of The 58 mg/m level is considered the "no-effect" exposure concent rat ionunoer the conditions of this test. Work by: -/^v^^ / ^ ^ ^ TrUnomas A.Keqge-iman Technician ^1 3 I ^ ^t^k T.. LlAQ^lyL-V^YY^-A^. Robert T. Turner Technician ^/s. /<&< Supervised by: 1 OLJL^/N^ 0 . r0^-'i^-r__ Laura A. Kinneyr Chemist S/ 3 / 8S Study Director: fJo^JLCC^L^^L 5"/ S /8S' Nancy T. Chromey, (Ph.D. Section Supervisor Acute Investigations Approved by: /.S Manager, Toxicology Acknowledgements: study. LAK:HLR 9.4 Bruce A. Burgess also participated in the conduct of this - 3 - Company Sanitized. Does not contain TSCA CBI Haskell Laboratory Report No. 182-85 Haskell No. 15,388 Material Tested: 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 Industrial Medicine E. I. du Pont de Nemours and Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Co., and Inc. Study Initiated/Completed: 7/9/84 - 10/12/84 There are 154 pages in this report. Distribution: 4 Company Sanitized. Does not contain TSCA CBI TABLE OF CONTENTS Page Introduction 6 .......................... Materials and Methods 6 ..................... Results and Discussion 9 . . . . . . . . . . . . . . . . . . . . . Conclusion 13 ........................... Figure I - Growth Curve 14 .................... Figure II - Blood Flourine Elimination 15 . . . . . . . . . . . . . Appendix I - Daily Atmosphere Characterization 16 . . . . . . . . Appendix II - Mean Body Weights 17 ................ Appendix III - Mean Organ Weights 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 Analytical Report 136 ................... Appendix VIII - Blood Fluorine Statistics 153 5 Company Sanitized. Does not contain TSCA CBI INTRODUCTION 4-hour ALC for^_J_^_Rlroasw gtroeaxtiecritythaonn an acute -, 2100 mg/m I The purpose of this study was" to determTnethe toxic effects of lalation of sublethal concentrations ofJ----ftF MATERIALS AND METHODS A. Animals Young adult male Cri: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 s that the groups' initial mean body weights were similar (p>0.99). Three were exposed to design concentrations of 5, 50 or 500 mg/m of in air. A control group was exposed to air only. Exposure was nose-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: 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 of|B|in Dust atmospheres air were generated with a 2-stage, vertical glass generator^/\ 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 elutriatorsweDt dust particles into the exposure chamber. The concentration ^JIBB10 the atmosphere was controlled by varying the 2 airflows. E. Analytical The atmospheric concentrations ofB)lwere determined daily at approximately 30-minute intervals for eacn 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 impactor1. 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 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. cally analyzed by a one-way analysis of variance. Data were statisti Test rats were compared with controls by least significant difference and Dunneft'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 "h'thium-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) 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 A11 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 Pout 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 . Overall mean atmospheric concentrations are presented in Table I. presented in Appendix I. Daily atmospheric characterization data are Table I Mean Atmospheric Concentrations of Design Concentration 5 mg/m' 50 mg/m, 500 mg/m- Q Analyzed Concentration (mg/m ) Mean S. D. Range 7.6 58 480 8.1 38 210 0-50 0 - 230 20 - 1200 8 Represents mean, standard deviation and range of all samples from 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, Company Sanitized. Does not contain TSCA CBI causing the particles to be large and the atmospheres to be difficult to control. B. Clinical Observations i 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/m 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 disclfarges, 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 fur from the 46th to 59th days of recovery. One rat exposed to 480 mg/m had hair loss from the hip from the llth 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,-wera-obsenved at any sacrifice in rats exposed to 7.6 or 58 mg/m of [jfly'J 3 Rats exposed to 480 mg/m 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. i Rats exposed to 480 mg/m 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/m 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 1ung-tosbody weight ratios on the 84th day 58 mg/m and rats exposed to 480 mg/m had ratios on the 84th day of recovery. These unrelated to treatment. recovery and depressed of recovery. Rats exposed to elevated spleen-to-body weight changes were believed to be 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/m0, 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)8 Mean (S.D.) Exposure Concentration Controls7.6 mg/m- 58 mg/m" 480 mg/m" After 10 Exposures After 14 Days Recovery After 41 Days Recovery After 84 Days Recovery 2.0 (1.5) 10 (1.4) 42 (7.9) 150 (26) 0.92 4.0 13 40 (0.20) (0.58) (2.0) (8.6) 0.86 1.8 7.2 17 (0.30) (0.29) (1.3) (3.2) 0.40 0.61 2.2 4.4 (0.17) (0.084) (1.2) (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 to480 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 coniDan^on of the test groups with controls indicated that rats exposed tofflRhad 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/m 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 wereiObserved in rats exposed to 7.6 or 58 mg/m 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/m of^B^yiad significant adverse effects in the liver and the kidneys. The liver cnanges persisted for 84 days of recovery. The kidney changes were absent after 14 days of recovery. Blood fluorine concentrations for rats exposed toJd^were 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 rat's exposed to 7.6 mg/m only. 'EThm' nation 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. 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 ^ S 220.00 ^ 0.00 00 -------- CONTROLS B------B 7.6 MB/CM DAYS -0 58 MG/CM -A 480 MB/CM ON TEST cm = cubic me.ter 0.00 CONTROLS 7.8 H6/CM 20.00 40.00 80.00 DAYS 0------0 58 H6/CM A------A 480 MG/CM POST EXPOSURE cm = cubic meter 80.00 Exposure No. APPENDIX I DAILY ATMOSPHERE CHARACTERIZATION OF' Concentration Mean S.D. 0 (mg/m ) Range % Respirable 3 A. Design Concentration of 5 mg/m 1 6.9 7.0 2-26 2 16 17 0-50 3 8.2 7.2 0-25 80 4 8.3 6.5 0 - 20 5 8.1 8.8 0-32 83 6 5.3 4.6 0-13 7 5.4 3.7 2-11 84 8 6.5 4.3 2-14 9 5.5 2.9 1 - 10 89 10 5.2 3.0 0-10 B. Design Concentration of 50 mg/m 1 63 27 24 - 120 60 2 55 46 16 - 180 3 78 57 8 - 230 4 64 34 0 - 120 55 5 47 21 12 - 100 6 61 54 0 - 150 51 7 58 25 20 - 110 8 60 35 8 - 120 72 9 45 10 28 - 62 10 48 43 17 - 170 0 C. Design Concentration of 500 mg/m 1 520 290 20 - 920 70 2 400 95 180 - 570 3 420 98 190 - 550 4 430 220 150 - 730 64 5 450 150 180 - 620 6 470 110 310 - 690 61 7 480 200 '240 - 870 8 400 240 80 - 870 60 9 580 240 280 - 960 10 650 250 200 - 1200 MMD (urn) 6.3 4.7 5.3 4.7 8.5 8.9 9.8 6.5 6.9 7.8 7.9 8.0 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! i,388 - EXPOSURE PERIOD GROUP CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM ANOVA(l) TREND(2) L8D(3) DUNNETT(4) BARTLETT(5) INTERVALS IN TEST DAYS 1. 2. 3. 232 .7 234 .4 235 .4 235 .8 0.778 0.316 6.4858 7.8220 0.177 237.1 235.4 240.2 229.6+ 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 CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM ANOVA(l) TREND(2) LSD(3) DUNNETT(4 ) BARTLETT( 5) INTERVALS IN TEST DAYS 8. 9. 10. 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* 11.3664 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 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. a SIGNIFICANTLY DIFFERENT (P<0.05) from CONTROL. GROUP by DUNNETT TEST and LSD. cm = cubic meter Company Sanitized. Does not contain TSCA CBI -JMEAN BODY WEIGHTS (GRAMS) 0 TO 2 WEEKS POST EXPOSURE GROUP CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM ANOVA(l) TREND(2) LSD(3) DUNNETT(4) BARTLETT(5) INTERVALS IN TEST DAYS 15. 16. 17. 309 .9 305 .8 300 .5 263 Oft 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, 325.9 323.3 315.9 284.2ft 0.0(31* 0.001* 15.6897 19.0630 0.536 19. 330.3 326.1 318.3 287.9ft 0.001* 0.001* 15.7935 19.1891 0.516 GROUP CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM ANOVA(l) TREND(2) LSD(3) DUNNETT(4) BARTLETT(5) INTERVALS IN TEST DAYS 22. 23. 24. 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 0.428 364.2 359.4 349.5 322.9ft 0.001* 0.001* 19.0094 23.0965 0.440 25. 371.1 365.9 352.7 328.7ft 0.001* 0.001* 19.6318 23.8526 0.373 26. 373.8 363.3 356.3 331.6ft 0.001* 0.001* 18.8130 22.8-578 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-vise 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 19 Company Sanitized. Does not contain TSCA CBI MEAN BODY WEIGHTS (GRAMS) "TO 12 WEEKS POST EXPOSURE GROUP CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM ANOVA(l) TREND(2) LSD(3) DUNNETT(4) BARTLETT(5) INTERVALS IN TEST DAYS 29. 36. 43. 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 CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM ANOVA(l) TREND(2) LSD(3) DUNNETT(4) BARTLETT(5) INTERVALS IN TEST DAYS 58. 64. 71. 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 570s. 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) TREND(2) LSD(3) DUNNETT(4) BARTLETT(5) cm = cubic meter 583.6 582.6 577.0 539.8 0.742 0.355 96.5097 119.7323 0.270 586.2 575.4 567.6 532.6 0.627 0.228 90.1122 111.7954 0.424 2Q Company 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 f) -f Company Sanitized. Does not contain TSCA CBI APPENDIX III MEAN ORGAN WEIGHTS - 22 Company Sanitized. Does not contain TSCA CBI MEAN ORGAN WEIGHTS (GRAMS) RATS SACRIFICED AFTER 10 EXPOSURES GROUP CONC. FINAL WT. LUNGS LIVER CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 290.4( 289.6( 285.4( 248.0( 0.000) 0.936) 0.617) 0.001)# TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.001 0.001 0.369 GROUP CONC. SPLEEN 1.329( 1.260( 1.302( 1.148( 0.000) 0.373) 0.723) 0.029) 0.123 0.051 0.159 KIDNEY 10.086( 10.258( 10.80K 11.312( 0.000) 0.770) 0.233) 0.050) 0.178 0.034 0.375 TEST IS 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 GROUP CONC. THYMUS 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 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 DUNNETT'S TEST AND 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 meter ''"'i 7 ^ _) Company Sanitized. Does not contain TSCA CBI MEAN ORGAN WEIGHTS (GRAMS) 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 GROUP CONC. SPLEEN 1.635( 1.566( 1.486( 1.459C 0.000) 0.399) 0.081) 0.042) 0. 154 0. 028 0. 480 KIDNEY 13 .924( 12 .423( 12 917( 18 .836( 0.000) 0.464) 0.622) 0.026)+ 0. 021 0. 028 0. 002 TEST IS CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.804( 0.718( 0.629( 0.698( 0.000) 0.283) 0.038) 0.190) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0. 200 0. 116 0. 943 GROUP CONC. THYMUS 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 CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.619( 0.76K 0.59K 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 DUNNETT'S TEST AND 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 meter 24c ompany Sanitized. Does not contain TSCA CBI MEAN ORGAN WEIGHTS (GRAMS) RATS SACRIFICED AFTER 41 DAYS RECOVERY GROUP CONC. FINAL WT. LUNGS LIVER CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 470 .2( 465 0( 454 .0( 442 .8( 0 .000) 0 .840) 0 .531) 0 .295) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.712 0.262 0.208 GROUP CONC. SPLEEN 1 .815( 1 -67K 1 .684( 1 724( 0.000) 0.193) 0.235) 0.403) 0.537 0.450 0.228 KIDNEY 18 .64K 17 .815( 17 .603( 18 .262( 0.000) 0.694) 0.622) 0.857) 0.958 0.839 0.586 TESTIS 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 3 .246( 3 .126( 3 .176( 3 .19K 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 (180 MG/CM 0.633( 0.708( 0.579( 0.596( 0.000) 0.280) 0.436) 0.591 ) TEST - HOMOGENEITY 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 DUNNETT'S TEST AND HOMOGENEITY-- P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL. TREND - P VALUE OP F TEST OP WHETHER THERE IS DOSE-RELATED CHANGE IN GROUP MEANS. BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE cm = cubic meter 25 Company Sanitized. Does not contain TSCA CBI - MEAN ORGAN WEIGHTS (GRAMS) S 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. 424 GROUP CONC. SPLEEN 2.008( 1.582( 1.953( 1.942( 0.000) 0.031) 0.766) 0.719) 0.112 0.765 0.235 KIDNEY 21.936( 21.614( 20.026( 20.215( 0.000) 0.889) 0.415) 0.461) 0.783 0.363 0.4-84 TEST IS CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.749( 0.802( 0.944( 0.875( 0.000) 0.647) 0.106) 0.287) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0. 373 0. 170 0. 015 GROUP CONC. THYMUS 3.952( 3.730( 3.52K 3.690( 0.000) 0.539) 0.241) 0.469) 0. 685 0. 386 0. 491 3.210( 3.454( 3.355( 3.204( 0.000) 0.129) 0.357) 0.970) 0. 322 0. 812 0. 092 CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0.709( 0.68K 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 DUNNETT'S TEST AND HOMOGENEITY - P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL. TREND - P VALUE OF P TEST OF WHETHER THERE IS DOSE-RELATED CHANGE IN GROUP MEANS. BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE cm = cubic meter 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 TS SACRIFICED 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 0.763( 0.803( 0.827( 0.868( 0.000) 0.292) 0.097) 0.011) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.068 0.010 O.b56 LIVER 3. 472( 3. 534( 3. 782( 4. 573( 0.000) 0.686) 0.055) 0.000)# 0.000 0.000 0.034 TESTIS 0.982( 0.973( 0.957( 1.106( 0.000) 0.851) 0.577) 0.012)# 0.014 0.021 0.482 SPLEEN 0.206( 0.187( 0.189( 0.144( 0 .000) 0 .289) 0 .327). 0 .002)# 0. 012 0. 003 0. 341 THYMUS 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 OP TREATMENT MEAN TO CONTROL MEAN. + - SIGNIFICANTLY DIFFERENT (P<0.05) PROM CONTROL GROUP BY LSD ff - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD DUNNETT'S TEST AND HOMOGENEITY - P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL. TREND - P VALUE OF F TEST OP WHETHER THERE IS DOSE-RELATED CHANGE IN GROUP MEANS. BARTLETT'S TEST - P VALUE OF TEST OP HOMOGENEITY OF VARIANCE cm = cubic meter 28 Company Sanitized. Does not contain TSCA CBI MEAN ORGAN-TO-BODY WEIGHT FIAT I OS RATS SACRIFICED 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 TEST IS 0.858( 0.807( 0.876( 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) 9. 251 0. 444 0. 002, THYMUS 0. l65( 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 DUNNETT'S TEST AND 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 meter 2r~7 Company Sanitized. Does not contain TSCA CBI MEAN ORGAN-TO-BODY WEIGHT RATIOS 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 .371( 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( 0 718( 0.000) 0.555) 0.784) 0.517) TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.902 0.606 0.759 LIVER 3.975( 3.797( 3.858( 4.126( 0.000) 0.601) 0.730) 0.656) 0.770 0.632 0.259 TEST IS 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 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 DUNNETT'S TEST AND 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 meter J (J Company Sanitized. Does not contain TSCA CBI MEAN ORGAN-TO-BODY WEIGHT RATIOS RATS SACRIFICED 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 3.739( 3.755( 3.506( 3.788( 0 .000) 0 .948) 0 .354) 0 .843) 0.649 0.8 97 0.088 TESTIS 0.550( 0.602( 0.595( 0.61K 0.000) 0.124) 0.180) 0.073) 0.266 0.099 0.376 SPLEEN 0.128( 0.139( 0.165( o'.mc 0.000) 0.342) 0.004)# 0.010)# 0.012 0. 663 0.152 THYMUS 0.120( 0.120( 0.118( 0.099( 0.000) 0.995) 0.916) 0.271) 0.617 0.282 0.438 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 DUNNETT'S TEST AND 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 meter 51 Company Sanitized. Does not contain TSCA CBI APPENDIX V PATHOLOGY REPORT NO. 18-85 32 Company Sanitized. Does not contain TSCA CBI ss^ffT' EV. iiiBZ E5TJBUSHEDIB02 E. 1. DU PONT DE NEMOURS & COMPANY INCORPORATED HASKELL LABORATORY FOR TOXICOLOGY AND INDUSTRIAL MEDICINE t'.O. BOX 50, ELKTON ROAD NEWARK, DELAWARE 19711 CENTRAL RESEARCH AND DEVELOPMENT DEPARTMENT PATHOLOGY REPORT NO. 19-85 SUBCHRONIC INHALATION STUDY IN MALE Crl;CD(SD)BR RATS APRIL 4, 1985 Summary inhalation for 10 days were examined grossly and selected tissues were weighed and/or examined microscopically. Compound-related lesions consisting of fatty change in centrilobular hepatocytes of the liver and nephrosis of tubular epithelial cells of the cortex of the kidneys occurred in high dose animals. The fatty change was most severe in animals killed 14 days 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 of exposure. The no-effect-level for histopathology was the design concentration of 0.05 mg/L. Introduction This report will^summarize the results of inhalation exposure of male Crl:CD(SD)BR rats tof----^------ll------Jfor 10 days. Treatment groups were as follows; 35 Company Sanitized. Does not contain TSCA CBI Design Chamber Concentration of I 0 (Control) II 0.005 (Low Dose) III 0.05 (Intermediate Dose) IV 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 histopathology . Results Table I contains the gross observations made at necropsy. Tables II, IV and V summarize the microscopic observations for rats with 0, 14, 41 III, 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 centrilbbular hepatocytes of the liver in 4 of '1 ,raCs killed on-the loot day of exposure, 5 of 5 rats killed on days 14 and 41 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 simlliar 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 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, epidldymldes, urinary bladder, sternum, bone marrow, eyes, nose and all gross lesions. ^5 4 Company Sanitized. Does not contain TSCA CBI 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 offlj^^Hfor 10 days. A slight degree of fatty change was still present in the^Rver 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: ^W^CP^. \^. VJ^CP^^TI Theodore W. Slone, Jr. D.V.M. Diplomate A.C.V.P. Staff Pathologist Approved by; UL^/A^L/ C '/ffffJt/My IffTiliam C. Krauss, D.V.M. Manager, Pathology Division 35 Company Sanitized. Does not contain TSCA CBI - 4 - KEY TO TABLES Mode of Death SD = Sacrificed by design Tissue Accounting Code N = No change observed L = Change observed 0 = No tissue present I = 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 56 Company Sanitized. Does not contain TSCA CBI - 5 C J1 H-153| * TABLE I GROSS ]?/. riON SUBC1HIIONIC - MALE RATS Animal Number Days on Test Recovery Days Group I - Control 376825 12 0 376839 12 .0 376840 12 0 376870 12 0 376873 12 0 376835 26 376841 26 14 ' 14 376849 26 14 376863 l 26 14 376872 26 14 376801 53 41 376836 53 41 376837 53 ^1 376847 53 41 376878 53 41 376807 96 84 376829 96 84 376834 96 84 Mode of Death Observation SD No abnormalities detected SD No abnormalities detected SD No abnormalities de&eeted 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 Medias final 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 - Mg-15388, * TABLE I GROSS P LTHOLOGY^^^^^ IRHALA'riON SUBCHI IONIC - MALE RATS Part 2 Animal Number Days on Test Recovery Days Mode of 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 0 376806 12 0 376818 12 0 376823 12 0 376844 12 0 * 376810 26 14 376822 26 14 376852 26 14 376876 26 14 376881 26 14 376800 53 41 376848 53 41 376856 53 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 58 Company Sanitized. Does not contain TSCA CBI - 7 r jH-15388 * TABLE I -- -- ^ 1 ^ GROSS P/ LTHOLOGY ^ INHAL AT][ON SuBCH IONIC - MALE RATS Part 3 Animal Number Days on Test Recovery Days Mode of Death Observation 376866 53 41 SD Lungs - foci, dark red, lower right lobe, 2 mm in diameter), few Thymus - foci, dark red, (1 mm in diameter), several 376871 53 41 SD No abnormalities detected 376827 96 84 SD No abnormalities detected 376831 96 84 SD Lungs - foci, black, (2 mm in diameter), caudal lobe 376862 96 84 SD No abnormalities detected 376877 96 84 SD No abnormalities detected 376882 96 84 SD No abnormalities detected Group III - Intermediate Dose 376805 12 0 SD 376821 12 0 SD 376838 12 6 SD 376851 12 376867 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 Perlocular - chromodacryorrhea, right, slight Thymus - discoloration, red patchy areas Lungs - focus, dark red, 1 mm in diameter), postcaval lobe No abnormalities detected No abnormalities detected 59 Company Sanitized. Does not contain TSCA CBI - 8 - m 1 H-15388 TAIiL E I GROSS I'ATHOLOCT nc)N SUBClIRom^^ws^Svs Part 4 Animal Number Days o a Test Recovery Days Mode of Death Observation 376857 26 14 SD Lungs - foci, red, right lower lobe, two, 1 mm in diameter) 376874 26 14 SD No abnormalities detected 376803 53 41 SD No abnormalities detected 376808 53 41 SD Liver - large Lungs - foci, red, few, 1 mm In diameter) 376811 53 41 SD Lungs - foci, dark red, diffuse, . 2 mm In diameter) 376843 53 41 SD Lungs - focus, dark, (2 mm In diameter), lower right lobe 376860 53 41 SD Thynus - discoloration, red patchy * areas 376817 96 84 SD No abnormalities detected 376846 96 84 SD No abnormalities detected 376855 96 84 SD No abnormalities detected 376864 96 84 SD No abnormalities detected 376875 96 84 SD No abnormalities detected Group IV - High Dose 376820 12 0 376828 12 0 376854 12 0 376859 12 0 SD SD SD SD No abnormalities detected No abnormalities detected No abnormalities detected Lunge - discoloration, white patchy areas, scattered 40 Company Sanitized. Does not contain TSCA CBI 9 - EJ H-15388, TABLE I ^ GROSS PATHOLOGY a Part 5 Animal Number Days on Test Recovery Days Mode of Death Observation 376879 12 376819 26 376824 26 376833 26 376858 26 * 376880 26 376814 53 376815 53 376832 53 376850 53 376853 53 376816 96 376826 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 nun in diameter) Thymus - foci, red, multiple, ( < 2 nun in diameter) 14 SD No abnormalities detected 14 SD No abnormalities detected 14 SD 41 SD 41 . SD : 41 SD Liver - discoloration, lobular patterns prominent Lungs - foci, red, 2 mm in diameter), few No abnormalities detected Liver - large Thyfflus - discoloration, dull red, left lobe 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 Company Sanitized. Does not contain TSCA CBI W J H-15388. - 10 - TABLE I GROSS PATHOLOGY Part 6 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 84 SD Liver - hernia, through diaphragm 3768&8 . 96 84 SD No abnormalities detected 42 Company Sanitized. Does not contain TSCA CBI ^. ^ 1Q: < Q. Uj 1-15 1--1 1- fT^--^ ^^H ^^BH "^^" ^^^l ^H ^B ^^B 0^1 SB -^^J "^k r^^^B^ '^^^L ^i oRi ^^K i-3 a; ^^!il/l ^"z zz" u-o^ 0 &Z S 0 1/100: UJ U Z u u Z 0} uj 3 a ui M u . Z M . 1- < . Q: 1/1 UJ M u UJ a i/i 1Hf "B 11 ii ^.^ 11 1 1 1 /-t n t ini 1 1 1 * 1 ii 1 1 ii PI 1" ii q- -- N n ^ 0 II U) 11 > o ~< 11 in ii 11 1 1 in T i i i -- i i 1 ^> in m n un ^> n " n 1 -..-. t 1 n i -- i u?i mil mi fs ^-^/-- 1 1 i " N - 0 * -- E " ? 4- i/i vfr* c j? ii u n ii 11 in 11 0 11 -- 11 M o 1-1 in n n 11 ii ' ii ii ii ii ii " in i" 0 11 .0" 11 . ^ (-i o in ii ;;11 ' " 11 'i * N in i i i n i i i i"> ^-^ i i i i i i N -- 1 1 ^ ^ in 1 1 1 CM 1 -- 1 ^ ^ ' 1 1 r* 1 \ | <--' in i i i -- 1 i i i i N M 1 | 1^ IkC (0 1 N CM ) i f--*^-\ r 1 1 i . 1 1 " " -'-" ^ ^ * 1 1 1 i^if ^^ s,r U1 1 1 1 ( in 1 - -- 1 - "1 ' 1.' in* t 1 1 ^" " I "' in - mil in i i in i in l D 11 " 1 1 -. ' 11 11 1 -- 0 11 1 1 0 11 1 11 ii--1--i 1111 o -i in il ll ii in i in i 1 -- 1 1 U) 1 in i in i l in i ii 1/> ll nil a< (/> < >- s Z II -1 3 U1 M0 Q. 1II1 0Hi 0a ! 3 11 U < 0 11 UJ -10: Z 0: 1111 0-<: -<1 z U1 UJ t3 < a 0: 0 < as -l 13/^(3 11 1-3 i-i-l 1/~.Z 11 UJ 11 t3l-i u as ii "a; a u 11 3 UJ 03 11 OUIS ZU i- 11 -i 0: 0 3 11 t- Z 11 00 11 11 1-0 '- -l -i 11 11 n 00. ? l 3. u n -i 11 -)0< 11 "11 00<. o (3-U-II- U1 11 t- UJ " 11 if a f n -3 < 11 t- cc n n 0-11 0-1-1 (M 11 -) 2 11 0l--l1-l1l -i o:s '- --1 1/1 0. 11 < -l t- UJ >- 11 3-1 -1 11 -i 11 U.U I- ll -10 -! 11 -i 11 t-00 .^ 11 11 -3UO - M "11 Z 11 U100 -1-1 0 11 0 0 ii <(-.. oro i- ();y 1/1 11 . -10. t- UJ 11 ^EMI-II-I < S h-U.. -1 11 >t000 00 ^11 --10:0:0: IS 1-1-1- UJ 11 I- -U.UUU uiii-; (r 3 11 a: t0-l U) 11 U1 -<ZZZ uZU)XU>(-- l- 1/1 11 > -1-10. -1 11 -I t- II - 11 11 \ - 11 Z 10 UJ 0 U -1 Q 0. -1 UJ 1- < . UJ UJ 0 -J U U. <t 1- -< <J < a < 3 CD UJ o a -1C -1 cc. Z z < UJ -- U Q U1 u 00 t/1 uj 1> < u u 0 U- < -1 Q. 1UJ -J r 3 S < ui uUJ 3 .-. 1- S 1> ~ -1 u -i 3 S 1- U UJ u. hUJX UJ U -11- < < 3 0 3U 3 a < M E UJ 1/1 - U. 4 - 0 0 U. 3 UJ > 0 1- >- UJ UJ >-> 3 0 > > > (-) Z >i >-i -1 Q <t (D -' 1< 1< Z 3 -1 U1 UJ 3 3 < < UJ UJ UJ Z 0 (3 13 L3 0 < U U Z Z .Z >- < r r j : < M I/I 1/1 U (- (. > > > a ui vi ui 1- h > < < 4CZUJUJUJ U. U. U. 0 ^ ^ -1 u -1 < UJ (-) s U U1 Q: < a < > UJ > 0 Z -< w UJ -J -J -< 3 0. S U UJ UJ ui a t-t < Q '' > a: ,-- i-< i < L < u. < u -1 U UJ (J E < 0 m u 0 u. u. Z r -< 3 1/1 M *-* '.; 1- UJ u. 1^ -J < -1 -1 J UJ -1 1- 3 3 < <at > -1 J E 0 S u 0 3 <t ^ - 4 M l-> 3 S 1 U- 0 1- 1- " - < z t. -J -< } <t t- UJ U- 1-1 l-<< -1 Q: -J U. U -1 1- 1- 1- t M U UJ a: < < <" 0 3 < U 1- U. E Q: -1 3 Q: 0 z r UJ U UJ 0 -1 1- UJ . u- 1- 13 -. 1- X U. 3 S UJ 01 Z 1- UJ 0 Q: > M -1 UJ -- ^ 1- U- < -1 -1 Q: . r a. .UJ -1 3 < Z 1- < U a U 3 3 U 1/1 Z 1- < 3 - 3 (J < 1- o m -< u- 0 Z U. & If) U 0 01 -1 Q: < 3 < U1 UJ 0 - U. >- 03 U1 U. UJ z h- U-1 dr C </1 UJ m3 Z -1 0 -1 U 3 U Q. (/) 1-i ui U i-t Z 3 U) 0 U Z -1 < < 1- <-> Z < 0 < z cc a uj 0 -1 M 0 (C >-1- 0 1- I U- " uj UJ 0 UJ < > < > a 13 3 UJ Z M na: z r u E U IX z UJ > S - UJ >uU 0 UJ 0: 0 S Q: x < r s 13 a 5 h 0 1/1C3 Q 0 1- -i a. > QUJ U) 0. < IX 0 0 J > S 1/1 1J1L S -1 U) UJ ;Z > 0 UJ Q: U. ui S z 3 r aa . >o r r - 0 1- > a S a. z 3 UJ UJ z < L> < >-' S Z ui ' 3 Z UJ > -J l-) < I T n r a a. 1/1 in in i m in i in ID i in T 1 U1 3 U 0 u. UJ U) > 5a -i Z 1- < a: L3 i,11 z -1 Uu < (3. Z UU UJ C3 IX o < 0 Z < -i 13 i- a 1-1 U) 0 > (X U > r - p- <r U) 1 >U) > U -1 < -< X u Z < [X a) 0 s i- 1-1 3 43 Company Sanitized. Does not contain TSCA CBI 12 i/ y > Q - M i/ Z UJ < 0 1 M < ..me M 1- M3 > a 3 < 3< s c < u J 1 rf I z z oz a2 i- ~1 3 M U. 0 >-< 0 Q. Z S 0 </) 0 Q: uj u r U (J 2 ffl UJ 3 Q l/) M U Z M t- < Q: l/l UJ t-4 '-' UJ n. 1/1 ^B <^r^^^^ (0 i Ul ^^^^^^B1 i '~^^^^1 ^J^^^l X^^^H 0 11 in 11 > o in ii in in in in in in in in in 1 10 i *-i 11 ii in in in l i in i in in in T ii ii ii ii ii ii ii N in n - 0 11 >-' o -< in ii 11 in in in in in in mm in i in i n in in i i in i in 0 n in 0 11 " ll ll - ll ll E l" 0 ll i- in n - 0 11 11 0. * ii 0 -< o in n in in in in in in inin a - 11 ** n T- in i m i in in in i i in i in r^ ^ in C I'l ^ 0 11 i i ii iff i) f >> ii . a 11 i O 11 '"". ii 0 11 i 0 11 ii ininininininininin o in 11 >- 11 ii i in i in Ul in i - in i in in in in ii i/i n UJ 11 -j n < " ii S Z 11 0 11 m"u r-i Q- 11 ^ hi, 3 II o n i Z " 0. 11 u n -1/i1 ^-j Z 11 11 ; a UJ U M 11 c Q S 11 * ^-0: 11 < Q- UJ 11 a 3 UJ 0 11 0 1/1 E 11 a Ct 0 3 11 13 0 2 11 11 11 11 11 11 11 . 11 11 11 11 1/1 11 UJ ^ || Q <r ii u 1 -i <t u Q < a a. uJ Ul 1- 0 1- t t/ i -i C -J -1 L i-i z ID 3 e , t/1 1/1 f7 UJ UJ <>, < 11 0-11 a. n n N 11 Z - 11 0-11 -< 11 U1 Q. 11 UJ 11 -1 11 11 -1 -1 3 3 (/ ID 01 C 3 3 ^ t- t- i 1/1 (/l 3 3 0 0 UJ UJ a. a. t- a UJ UJ 11 0 u- u. L 2 Z Z -- M <t <{ uj uj z z z 30. Z 0 w 11 1/1 11 UJ 11 I/) QaU-l>>QU -J 11 3 '~ll<0 1-0: oo uj 11 uj < 3 11 S Z 3 u z l/l 11 u r:C2<USOJZSSZUJ3UJZ l/i 11 0. - i-'ll Q: 1/1 0. 1- 3 <0<001UJU-1 ^11 (- UJ1D t/1 Q 11 UU 11 s s r 3 a: -1 -1 S UJ > Q i 0 ULJ UJ < " -< S S UJ UJ t/1 I/I - o -1 3 Z I/I t UJ Q: Z 0 >-< 1- 3 < 0 s S 3 3 3 U"l J--fJ-i 0 1- < s 3 0 Z 11)0 0 >- a r r CL s '- Q. Q. S S CC < <t UJ > > a. S < i- a s a i/i a: cc. a uj S u. i- < uj t- >-i a. z z h- Z UJ z t- < "< Q 1/1 M n: UJ UJ l-. U i/i i-<* 1/1 i^ UJ UJ Z V) UJ UJ a: UJ a > 1- 0 0 0: S 3 t- UJ UJ i/i CO Z 11 44 Company Sanitized. Does not contain TSCA CBI 11 11 11 11 >- 11 0: 11 d 11 0. 1111 0 11 0 U) 11 UJ 11 > "> o in ini ^r i i i i 1 0 1 UQJ: . ii 10 ii 10 n 0 ii ii 10 ii < ii s ii ii UJ ii 0 '-'(M-' ii in n < a 0 11 0 " ii -' 1111 1-1 o in 11 in 11 0 11 H 11 r 1 0 1 u <t UJ ii -- ii z ii UJ 1 ii 1- ' ii U. E ii 0 11 0 11 2 i- in ll 0 4- 00. 11 11 r V 11 UJ O-i 11111 B) 1-1 o in n in 11 * 11 0 1 <>u I/) Z 01 1111 UJ oinn -1 0 *,!' ? H tf M > >-5 r ^1j z^z n 3U 0-11 V) . - !/) UuJJ > -J Q 3 t-1 (- i-i 1/1 - in z < 0 a. ^ 0 < UJ -1 2 -tf 11 I: 0 Z Q Z -i U. 0 " 0 Q. Z SO 1/1 0 0: O'-'O m <-> r U (J Z 0) t - 3 UJ 3 Q V) M U z OI/ISII QiZI-t- 1-1 0:03 2l-0'-10<:i0-S3 t- < tr i/) UJ M L) UJ Q. 1/1 2a-n11 '^<Z-1l.../Z-1.l.ZU5"3-ll3-03S-0-1.031S-.-I mco|j ^1"111 r---- ---- '--3 ^^" C r 11 0 11 11 i} 11 "f>fH*l" - i1')l D '-- i'l' ll 0 11 0 11 11 -- ii ii V) ll UJ ii -J ii < 11 S Z 11 >.; t* Q- 11 3 11 < 0 11 Z Q: 11 11 i-i -J 11 VI ^ Z 11 aUJ (s3 -i 1111 '-' 0. 11 0. UJ 11 3UJH111 -^ ^ - 1 1 ..- .- -- in i -- --. i -- 10 UJ 1- . < Z VI 3 0i-) 1- 0: < 3 S UJ S uj > -' -J t- (E U-Ji t < 0 Z 11 L3QZII 11 11 11 11 11 11 11 11 11 11 I/) 11 UJ'->11 0 T 11 < 11 11 u i] N11 0--11 1-1 I1I1 100.11 UJ-^11 -1 11 ii 11 11 11 11 11 U> J3iZa-lUJi-i -1 1- 1/1 > UJ 0 UJ 0: I < -1 Q: 0 h- 1/1-1 0 i-i - i-i < Q. U X -1 Q: UJ 3 < < - S S U 0. > (0 0 (/) Q: 3 U. UJ 0 I/) UJ t-i Q; h- ^. - 1- <C 3 I -1 O: o < S <l a U CO U (/) 3 3 UJ g i/i iu u- a: 1-- UJ -1 U < < 1- < <t 1-1 -- 3 u m vi </) (-1 0 3 < < < U- 1/1 -1 -J 0. 0. - - <C < "11 Z 11 0 0 0 0 UJ UJ 0 11 f 1- h- 1- 1 -il/l ll C < < 0( (/) 1/1 0S 5 S UJ ll uSS S -1 11 ^ < < < ES ^11 t < -1-1-1 uj n 3 II u. u- u. 3 3 1/1 11 Z Z Z CTOr Q: UJ (/) 11 I/) M 1-1 1- VI C/l UJ 11 0 -'F 11 Z 11 0 11 "t( -- '1 - 1 1 -- ---- Q ^-1 0 0. g > -1 < (/) < -J 0. u: UJ Q. > . I UJ 0 0 Z r a 2 -J 0. < -1 3 O Q-i Z < s . " 10 UJ 10 Z 5 z I u s 1/1 UJ V) U1 z UJ a o2 UJ z z ) n; i/) UJ Z Q UJ Z CQ 3 g n z >-( UJ a. r 3 1- 0 a I 0 1- -1 r 3 u < z UJ 0 a P 0 i-i U. 10 oS UJ z > - 0) < 0 X Z UJ 0 1/1 0. W Z UJ Ou < 0: 0 cr a: o u. (/) 0 UJ Q CC, < UJ ir CO 13 S 3 Z Z 0 k^ UJ 10 r UJ t- -1 0 I0. 45 Company Sanitized. Does not contain TSCA CBI 14 -- i- 0: < 0. 1 i UJ i"y,a-<l l-lhia>- 10: 32oas2< ^301 VI Z 0 M 1/1 UJ ^ -) Q3 U (-1 fl 1- 1/1 r < 0 -I ^ Q. o < i** UJ -1 z Bf|c4 Z Z oZaZ>-i U- 3OuM 00s. oZ I/IOCE UJ U I U (J z ffl UJ 3 Q I/) (-1 U z t-t < Q: I/I 111 w (J UJ a. 1/1 a a r tf i 2 11 ii ii n ii ii ii ii n ii 0 11 in 11 > 0 M U) 11 ii 1 1 1 1 <~S /-*< i-"- i^-t -- 1 1 1 R ^r ^ ^ i - 1 1 1 N ^^ t 11 ^ in in i i i i - -- ^ f -w in i i CM i i '^ 1 1 - i CM 1 ^ in i i i CM i in i in 11 /-^ 1 1 1 CM - t '--' in N in --> 1 1 1 -- - 1 '--' in -- '-t 1 1 t | V-- ^-' in i - ft ii ii ^\ '--^ ^-\ ii 1 1 1 n ii 1 1 1 -' n - ii 1 1 1 ii k r ii - ~ t miiiii m.iiii---'-' /^- n (0 U) 11 <N| e? 11 1-1 11 1111111 -i0 i- in ii 11 in 0 11 k 1 t in - in i i . in i . . in in i r- ^ in 1 I-- t^ +' 11 11 r^, ^i ^-\<i-^ 1--\ m 11 1 1 1 ii III ii I ii 1 1 I I I ii 1 1 1 1 1 r- ii . k k 0 (1 -- -- | -- -- 1 0 - L. in 11 1*- 11 1 0 11 V^ 4J ii U 0 -< o 1-1 in n n in 111--111 w ii 1 ii miiiii R * r I I I te^ v.^ ^^ mi------i 1 ^^ in -- in l l in i -, in in i N ^^ <r 1 N c ii 0 ii 1 ii 1 1 10 ii 11 >. 11 a Ii o ii 11 ^^ ii ii 0 11 0 11 ii I t o in n in i--i--iii '- iiii >^^ ^^ K * f- ^ ^Jf hj. miiiii 11 ^^ ----s 11 1 1 > - f-- ft 11 *^*^ mill---- in i /-\ 1 > 1 ft 1 -- k ) ^~f in - i in 1 U1 in i in 1 1 ii V) n UJ ii CC l/l U) J ii <( -1 UJ < -1 1/1 u s Z 11 3 0 < 0 11 o a: . ii"v a. n 3 11 0 1 Q: U UJ a. Q: 0 (3^(3 < 0 11 i-] < Z Z " CC 11 Q; -1 11 >- -J 11 1 - 3 - 1 I/) - Z 11 z ID UJ 0 U-iJ UJ (3 i-i 11 (J -1 U < EC -1 u 3 < u 5 1/1 , 0: < a Q E 11 11 ^a 0. UJ 11 3 uj m ii 0 a u0 i3s 11 ii c3 a z n 11 -t-0 11 (JI/l-IU. 11 -1 Q 0. -1 UJ I- < > a; z u < UJ UJ 0 -1 a >- u u- < z 1- i-iU w < ' l/l < > UJ 3d: -1 " 1- s z u uj 3 UJ l/l Q. 5 < 3 13 > - EC -< -1 -" -1 < a <1E< u 0 I LOUJ3H-UJ -JUUJU !; i-si- 11 <oao 11 3. .OM.I-I 11 11 -l 11 3U3 11 - 1 1 - 1/1 11 .0 t- UJ'-. 11 x-i '3 u-i- a T ii t-uj i- -i < ii t-ZUJllt-< a: o 11 0-11 o-i-i <-i N 11 0-J Q-J t- t- z - n 0-11 -SU3J<UtJ*M> 1-X M . ii -<0 --^1-h-U. I/) Q. 11 i/)-i-3Q>> UJ>-> 11 3-l i-< 11-a. -1 11 tfll-Z OZ ii 11 -JO i- 11 <3- 11 I 11 I-OU 11 t/)(/)-MCJ 11 O-t-3.(3.30<<U<L) -<U<Z < UJUJUJZUOO " 11 - a; i/> > ~ -i < UJ U - 3 -J 1- -1 0 < S 3 > < 1- CJ 0) UJ U U < 0 0 ID 0 0 a. u-UJ -1 0 U. UJ 1- < 1-1 r o: a.- uj u z < I uJJ-- U 3 <3m S 3 U 3 0 < VI UJ Q 1- -l UJ UJ > u z >--< U- < 1-1 t h- 1- U- <-> Q CO < < ^-, 0 Z 3 -J -1 Q U.- l/l UJ 3 3 -i. B 3 I/> 1- UJ UJ 3 > (0 >-< u 3 - - <t Z or UJ 0. < < Z Z 0: S UJ UUJi-* t3 UJ a: > -J a: ^ U. a (/! UJ 0 -1- -J Q: 1/1 UJ (* 0X.*I-/*I -Q<. > u u. u. s U. 1--1 1- k -1 <C -J -1 < -1 -1 S 0 S u 3 < ^ U- s u. \ o t -1 U- U -1 h- t- o 3 < -1 U 1- U. S CC 3 s U- 3 * -J ^ S UJ UJ M -1 < 'uj .d 3 <t z u u a i-< o 3 U <I 1- U. U 0 m -1 Q: < U. 3 M < . f ID 1/1 U. UJ Z 3 Z -J 0 >-i z 3 - < 1- >-( 3 k -1 < t-1 1- --1 -1 1- < (/l U 0; 0 uj u. ^-f Z 1- UJ - -1 -1 3 3 U S in i- UJ Q: 1- 3 -1 i-> U 1- 1/1 in > 3 U u 0 -1 U- < *-< UJ 3- ' u 00 -1-IUJOO !/)> -</)0<->Z Z 11 zzz-- (oTiUzOaoIQ: ujo--'-o QMQ CSI-1-l-r 0 11 a: u.-' uj UJ h- 0 z Z t- Z < <11<<!- o-) << .<t - 11 r < </> " in uj a <t > < > a. z <t < Q: VI 11 U U U S -< 1-1 1-1 UJ Z r U S U 0: UJ > S I ix m I-U-3 -i -j UJ 11 S >/) 1/1 V) 1/1 0: Z 0: 0 E 0 0 0 Q: 13 UJ 13 0 XS >>>< i- -1 11 0 0 0 UJ -UJOUJ 0: -- < I S UJ 1/1 0. < 0: Z 5 o--i <o-i -i -i- i- >--1- ^ 11 Q: a: a </) e a: a. > o o -1 UJ 0 1- >- UJ 11 0:1<<-t<-iZ-Uu.JUJUJ UJI>--J>Q: l/luJi-i2>0 1-> Q:1~Z -l -i 3 11 uu u > o vi o o o s 1/1 u- s o uj a. u. 13/1UsJ zUJ <Z 1U3J 0 V> I h-1- zul-iora. as 11--i i-i I: V) 11 uj u-u-u-1-1 z z z o r a. u s uj UJ Q Q; U 3 in 11 ^ Q Z < z > 1 CC > -< 11 M 1- 11 1 11 -^ . 3 -i uj <t r a. r a. a r 1- I/I < i- 11 46 Company Sanitized. Does not contain TSCA CBI 9 ' i ii ii ii ii ^^ 11 <o in ii N 0 11 >-i . ii -i o in n in in in in in in in in in i M 11 0 11 in i in in in i i in i in in in in i i/i Z. 0 * . ii li (0 11 "- ii 11 n n E 11 0 11 uii-ioinInI 0" >- in 11 4- 0 11 11 4J a) M in in in in in in in in in i 11 ^ 11 i n C 11 0 11 in 1 T /^ i ,-- , i i , i >^ in in t -- in i in in u") in i--i in 11 (/) >> ll UJ > (0 11 -10-0 11 3 -- 11 U (1 -I Ul (/> 2 M 1" < o i |" M C-IO -1 0. *-i < 0 < M 1- >-1 > pq o: ^ 1 3 1/1 Z^ UJ -J J C 0 Q - Z Z SO 3 (-) u0 - 0Q. fZ- 1/1 0 0. UJ U I OH 0 11 1-1 oiInIn iiininininin<rininin i 11 ii i/i . .... n UJ 11 -1 ll < .. l, S Z 11 0 .. 11 M Q. 11 K 3 11 < 0 11 Z " D: 11 U ^ t3 11 M 1 11 U U 2: 0) UJ 3 Q 1/1 1-1 <-> Z 1 " in ^ Z 11 uj 0 -( ii Q E 11 -- CC 11 a. uj ii 3 uj m n 0 1/1 S 11 a: o 3 ii . t< U Q Z 11 11 0. 11 11 " 1 1 1/1 11 UJ 11 1-- 11 1-' 11 UJ 11 Q. .. || i/) 1/1 11 UJ" 11 af n < ii a mn S3 - 11 <M 11 -i-ii Z II 0 - 11 VI 0. 11 UJ '-' 11 -j n ii ii 11 Z 11 uj " s : 3 " " J Z 11 0 11 - M 11 ULJ 1/1 11 c 3 1UJ3iizrz<ujzsszu. f ^- < ffl n in '- uj n in -t " 3 S ci=3 ^ 11 <t 0 X 3 2 4 < (i>//1-11i<i1UIiJI<1Q4(o:-l)</0lQo.U,:o-lZ.-S-33>a0ru3.j3j.uu3j-0oi2S:sJ i-iii-miDvia-i^-.uu in 1 T UJ Q 0 Z Z uj s r 3-I0S>. ! UJ C 3 U C 3 M ^ Q: 0 t UJ 25E 1- 3 UJ. Z (U - 2: UJ M UJ UJ Q; S CO in i i in 1 -I -1 < < OC. Q: UJ UJ 1- t- < <t -I -1 M 0-l3Z3 , (/I </) UJ UJ -1 -1 3 3 CQ m 3 3 H 1- 1/lt/) 3 3 00 Q: Ct UJ UJ -I 1L U. -- < Z Z S ir " S -S . o -l UJ UJ UJ 3 0 1/1 I/) Z a VI < < . . 30 a-i > > c r ii. a. > C CE in at ct: < UJ h-.1- Z 1- <I <: w uj a: a i3. - g; an >- a ': u ii 0i. 13 Un Q: UJ n. 3 1- UJ Ul in in in . u c 1- c U U c U c t. ; 1 (? N> (/ c C. i u lC < 2 0 K 1- S < 0 S EC. a. c S< - 3 U. Z Z (/) n: UJ UJ l-l UJ U) 1/1 > i- 0 0 UJ i/) a 47 Company Sanitized. Does not contain TSCA CBI QP z 0 0 0 -< m i/i c- m -I )... (/) m (-1 o^ z 0 (B a; rn r v 0 m o vi -n no 0 TJ 3) n 31 > m z i/) in c o m 2 X 0 > s (D i- < Z ffl -00 0 M "n 1-10 -1 3) M o m z > n S I t-< -1 0 I 3) 0 -f C I -0 m Z (/I c s c 0 Z m o a rn I/) 73 r 2 Z fn O 0 > 3) ftl z -f z m V) m (/) S I >-* (-> I S 0 n > -< m I 0 s 0 TI -< m z m > n 1 n 3) > 0 m S > M 0 CD I/I m 3) < m 0 0 -i I sro > a> z 0 0) c r > z r < 5 5 z 0 0 m I < o ro 31 -0 r > l/) > < r < S -0 3 C- 11 c 1 Q 1 0 1 0 11 11 11 2 11-1 0 11 " Vi 0 0 (/) (/l M - -- HI Z Z 2 C C Tl T) Tn > > r r- r 2 s > > >" 0C0C3S2333 0 0 in in > > > 3 3 3 M-1 -i-1i --<, rt mmo o 0 a -1 -<'Z. ^ Z2 O D . . r" r" (/) TI > >> con 11 (/) 11 M 11 C it m li ^ 11 r 11 rn 11 M 11 i-i 11 0 11 Z 11 . 11 11 11 11 11 i/i M 01 n c ">i->'>n>rm-i . . c-i - a>Tim</is m0 c c n n r 11--m 11 "0 (/) ii--o 11 -I 11 z 1/1 n (B n "i-Dir>-c3n>i/0) 31 r c > 1->l3?>--)i-fn)'(n 0 m -n- c X (/) 0 CD < "o n s s n hj 11 P HC);O n - > 11 A 0 11 ^ rn 11 1/1 11 11 m-r~>x>o o > - >-< o o- - -< r </i -{ o 3) r > I a; fn ni r < M -o c-i < C-rnO -3<) ;0o) mZ S>-f-I->( M2 -| I 0 m 3) -f r r <m 1~( 5 c -< m g c > K ii ii 11 11 11 11 11 111 1C 200031 113MO n en m c ii m D 11 31" 11 SO - 11 11 2 n o m -s (/) r M a -i CD C *- (/I z > -1 m 0^0 11 11 S Z 11 0 > r\ 11 C 11 -n '-' 11 0 11 2 2 in 11 > 11 r 11 m 11 i/i 11 11 i j i j -j U] 11 1-1 11 01 0 11 ' /^ i ^"i ^ i i 11 0 11 0 . s 11 1 11 ^ . 11 a -- 1 1 11 a 11 >< 11 w - 11 i 1 1 1 11 0 ^ ^"W 11 3 11 I----Ill U1 ^ 11 rt 11 -- II) II 01 0 - M 11 rt 11 0 O ) 11 -fi - 11 U1 ^ J 11 0 - 11 3 | 11 11 .'1 11 | 11 0) '^ 11 11 ^ 11 0 11 >-< 11111 01 11 01 0 " 11 1-1 11 0 KJ 11 UI 01 II! 01 U a . ^a in -D m n >- m in 3) > -i -< Z1 n - l/l 0 c m CD Z n n 1n m OS 3) 0 i/l Z D 0 " 0 -n DC Z 2 -'00^ Z Z -x > M ., c 3 H S !> > Cd 31 l-l < P3 t, l~ m -i > 0 P -- -( O r tP t-' r >- t-i 0 > m z 1/1 -l M M -1 n C o r < m M k-4 0 2 M ^ 1 0 01 0 < Company Sanitized. Does not contain TSCA CBI 6t7 -1 I < C (^ 3) r -< o -ih>( dn/) - o- 0 o 0) r- z > > 2 z 0 n I >-" ^ r n -< w -l i i 01 1 1 U1 1 1 ^ M 1 .> ^ M - | 1 1 " 1 > 0 V o m rn z C1 > m r 2 vr ra p >> -1 Z >- i 0 < l/l m -n 0 n c (/) 01 1 U1 i ui i U1 U1 -i o i -ol ^ < ISme ni m z 3 in 0 > z 2- '>-fo 11 ;o m r o> m > S<-i 0 o 31 > D (/) m so o I s -< rn >- > Cl -1 m m -- i n aa 001-0 00 > z o -f > - > -i c 2 1- -i m or* Z 0 -n 1-101 o a n c o c r .! r "TO r -1 Z ^. < -i S -n m C 0 V r n vi -i > -l " r -i -i -n 0 1-* 0 > > (- r- g 1-4 5 -1 < I 0 n o > (-4 2 0 0 5 ^ m C z 5 -l m 0 5 > n z 0 o I > C) m in U1 1 W 1 1 U1 1 U1 ui M ui ^~-. i N> 1 1 --' 11 01 N U1 ^-k | M 1 .* 1 ^ CJ1 -- U1 ^-i 1 1 --* | - 1 ^ 1 -- U1 ^ \ --i 1 1 - 1 s-' -- U1 ^1. | --* I - t '-'' m i U1 1 1 U1 N) CJ1 ^-^ | M 1 1 ' 1 r- c 2 oo<r -" z M11m r> 1/1 r 3 n M a < D r -<o o31o >3*-o';oD aoa<n>s<n>l oI-l>-i l"-IoCnli z n o (/) c z -' in 1/1 nrzi-- m "n 1/1 a - c > - c -n > ;o r o o n zrcrm -i^ n> >D-Cl ii -f -< "^- i- m m s r c in ?; M 0 sool < cr i<ni0Im2 0 o Oin 7 < m-laom3 --f r r m i/i >-<za) in zn-oicr-onn-ii 0a 1a 02 0>2c3) oo m r r D VI -0 r KI n m ui v i~ -I" 0 m in "o - n 2-1 c > -( (/) -^ oni a> (-< o m > X 0 -i 1-1 m n m r 1-1 < . . . - ( > > > 2r n22n>i n-iiTzi>-n>->n3m) nn3n)-rn---li--li--<i moton o(/) >2 <<< unii-viin-inso>omn rr-czo'-' >-i Z 2 2 o(-1o0n>zOmC1m0Cm1 C>l >0 <-f = ccnitni-'-no 0) o n n --('-<--z<n>'<-'r>-'cn m<<raD'-C'-ti-oi-t/>fn < fn c s - - - > m " 11 n-< 11 >-< 11 In n M n c iim 11^ 11 r n ni 11 ui 11 M i11io2 11" 11 ii 11 11 11 11 11 t~ liii--o" 11-^m 11 o in ll - z z^J ^H i ^^1 01 ^^^B^H^|U0ID <V?i^U sal encs ;o3-n-in ii-ci -l r o 2 > > s m 21 vi > o r oo -ni [B c > e z > z UN n rro ux r>nc-ol>'-o"'>- nm AO -l f- n -n r z > > -l r r:rn z -< n > - -i r n s -i 1-1 -l -f -i-o ai n 11 >-' m c- l'->r->-' -n ^ > c B < CO'- -<ni-n-ior c m 11 ui Mb sosrr n" niifooocoo C 0 C -f r onomcB r > r r 11 m o 'rn r)-)><cn -l -i r -< -n vi c . 11 -" 1-1 0 0 c m m > n ro TiTin .cr'ss><oMr-airi -13-1- M- o o o > r . 11 in 11 n mn r > > r 1-1 r - < > O VI m n c w r < > > a in n c r > m " cm t/i vi -n r </i n -> 0 -< > r>o-nmnm-i z .n >-< -f 0 -I nzai -i < > m . -' rao n m oi-mn i~ r DOZ r c-i z > " aoir m n s m 0 C m r t-4 > M v n 11 11 > 11 2 o o 11 cox -', HiiBSMmOc 11 m o (no nii^a> o c(DmZ niiiz-^ccimn n r" -i 1n1 o31 ^-p 11 o > -f z 0 -' n n nloorwn z -oo in nc"nzosMOTIC. 11-0-' n .. o z z a n c s 11 2 3 - 0 0 P t-3 n - > Z V z^ > ll r~ 3; ' < W 11 m > Z 1--1 5 1111 M r> 0m >-< w -* 1 -* t ^^t ^S 1 1 1 U1 rj I I I I U1 ^-^ t III--IIIU1 >-> 1 ii ll *-i 11 U1 0 11 11 0 11 0 < -l O 01 n t^ r r 0 > m Z (n -1 1/1 >-i . -- 1 M 1 -- l 1 1 l 0 0 11 -( n - ii - e 11 r 1 11 01 < m n '< VI 1 11 U1 i- . . n i 1 1 i 1 11 0 ^- -' ^- ^ 11 3 VI n i 1^111 U1 -j i l l i U1 1--IIIIIU1 ii 11 II U1 0 11 -10 i- 111 * ^-^ /--k '-> 1 l 1 11 . 0 11 0 - 11 U1 ^ rf - 1 i 1 11 0 11 3 11 11 1 .' 1 i 1 ^ "^ -' 11 11 11 . 11 M ---- ^ rt- 11 0 1 M 1 M -- U1 /-. ^^ -^^ 1 1 t (till U1 1 1 1 M 1 1 1 01 " 1 11 - 11 U) 0 >-' 11 -1 11 0 01 11 U1 U N) * * M -- N 1111 '-' 11 I | | 1 11 * 11 1 1 I 1 11 * 11 ( ) | 1 11 ^-* '--"-' ^ 11 11 11 11 >-< 1 -J -- N) ^ U1 f i f t l U1 I l l---IAU) IIU10< 11 <-- ^~\ ^^ ^-n ) ( 1) ---- hJ -^ I I I J . . . 1*1(1 11-1) J lilt .I.I.I 1111 ^r^ ^ 11 U1 11 0 11 -0 - - G) 11 > n a -1 1) 11 11 11 .I.I.I Company Sanitized. Does not contain TSCA CBI 2 CD Ifl rn 0 0 -1 < 1/1 2 m m >- m m a) M z z T1 s c r > 2 > V I V 0 > s. -i " ; > -1 ^ -i n = 3 /) > ^ /i i ^ 3 /i > j n /) 0 -j 0 l 3 0 < n yi 01 U1 01 01 U1 (J1 01 ^ 01 171 Ul 01 rn -0 ~i en o o -' m o a? < S 2 00- ai rn 9 VI Z c r 0 2 > 1 01 1 01 1 01 OS 11 -1 c rn V mncan--cmsrccmz(.0o-nc3oco-"ioi>c-v>oDzwomni>v-iiiiiii/-) oo 1/1 . Cf > > z -l -I -f m > xi x 1/1 71 < tr-0 CD < < r I I > no 0 s 71 m m me UI n rzn z -i -1 S S m > 3K 3-10 m r n 0 r m20z 3 > -1 0 o m 'cS z c n I S 11-1 11 i/i 11 c > rn c> > 11 m 11 ^ c 11 r (/) 11 m 11 (/) n -i 11 0 "" 1/1 (/) 0 < m rn re S r r 2 s a o c c I S S z z m m i-i -i n -n 2 Z Z 0 11 2 11 11 11 11 11 11 m rn 0 11 00 :0 3) m C C MM -1-1 , c c CD CD n r11 -' m ll O in 11 1-1 .11-711-0 11 KJ 11 * C1 c c r r- m m V) (/l * * c: a z -i "- r r > 11 G1 :0 11 11 * 0 n 11 ^ m(/ 11 n 11 11 n -i > -< f71 m a? 33 > 11 ii u ii > r ii r 11 2 0 C1 11 C 0 11 S VI 0 n CD m c 11 m o 11 ii S'-S> o r" 11 - p rn iiii z -- w 11 Cl ^ 0 11 3) 2 11 0 > '- llll C0 -l 11 " 0 ii z. 3 11 " > 11 '" 11 m 11 ui ii 1 I 01 01 Ut -- 01 -- t - 1 1 1 **-/ [ | 01 01 UI 1 01 1 1 01 01 ^ ) 01 11 >-i 1 01 0101010I01U101C11101110 11 0 ll 0 11 11 '-> n a 11 in 11 '< 11 U ll l 11 0 11 3 ii i 1 01 01 01 01 01 01 01 01 01 11 rr 11 M (t 11010-- 01 11 . rt 11 0 11 0 -h 11 01 -1 11 0 11 3 11 11 11 11 N 11 ~1 11 11 f 11 0 11 K inoioioioioioioi 1 01 I 11 oi-o >- 11 11 0 01 ^2;- ^^^B0--1 ^^B^CuD ^C^--0i trt r rn n M rn VI a > -1 '2 - n i-' cm (/) 0 en 2 n r, i nm OS 3) 0 (/l z "0 0 >-i o "n n c 2 Z "00 2 2 3 31 t 2 r m > 0 o r r 0 > Z in -1 in i-t -1 n C c r < m i/> 3 Z VI I/) c 2 1-9 S > h>j :0 5 < MPJ -i > M ,, o <3 r m .' 1 01 LI 01 01 -- 01 1 oi 01 loi 1 01 1 01 II II II '-I n oi o < 81 - Company Sanitized. Does not contain TSCA CBI s z 0 0 0 -< m 1/1. rm-il" (/) m - o z z c 3 oa 3i rn > 31 0 m o in 11 n03o1 3)0 3; > rn z (/i (/) o 0 m 2 X 0 > 5 CD w < Z m O 0 0 w ~n 1-1 0 -IV t-t 0 m 2 > 0 S I -1 CT I 3) 0 -1 C I -0 m 2 W C 2CBCZ m o 3> m 1/1 r 2 Z m T3 0 > 31 m z -1 I m M m 1/1 Z -< n I *-< z 0 -* n > -i m 3 0 S 0 ^-i 3 ffl > 3) Z 0 01 c r > 3; r < S o I 2 0 0 m ti i < -0 m 31 -0 r~ > VI > . r< S -0 I.0 11 0 1 0 1 0 Z 0 w (/> m 0c 0c > > S 3 00 CC (/) 1/1 i-i i-] >i m 2 2 2 -n -n -n r r r S>>3 >3 '-n' 3 S S0 > >> 3 3 3 rn m -1 -1 -1 >* *-i -i ^-f 0 o o o a -> 1>--12 2 2^ o o 00 r r t/i -n > > > C MM CD D C w - > > -1 >>nr m c- . . 3) -n -l m 1/1 s 0- m c c i/i n in n -0 > S > 0 v->-' r c n i/i r c > > -H -f ~- -i 33 i m 1/1 0 m -n- c 33 W 0 (D < 0 n >-> > S3 3 c o- m 33 f- ;< n -o > - i- o -< -i r~ in -l o 3) r > I 3i m m < >/i -( r -D e < i-- m M 33 m c o 3) TO 2 g M ?> 1-1 -) -1 -( Z 3) I 0>> m a> -i r r <m -' S c S -l c m > 33 -< 01 C -< in Z > -( m 1/1 1 10 1 M 1 01 ^^ "^ l i M M - | | 1 1 - | 1 ^^ '--- 1--1--1 U' /-s /~. 1 1 * 1 1 L - 11 -1 11 1/1 11 VI 11 C ii m 11 \ 11 r 11 m 11 U1 it -i 11 0 11 Z ii ii ii ii ii ii n r n 11 ^ni O 1/1 11 H 111 1-0Z 11 M 11 C1 11 U X 11 > 11 .& 0 n ^ rn 11 W n ii ii ii ii 11 n ii ii ii 11 2 0 C1 11 C 033 11 S VI 0 n B m c n m o SO 11 3) --' 11 Cl'-'O 11 -. p fn 11 Z ^.1/1 n r -' 11 11 73 Z 11 0 > 11 C *) 11-0 - 11 0 11 2 3 11 > 11 r~ 11 m 11 VI 11 11 11 1-' 11 Ul 0 11 11 0 11 0 11 11 ^ 11 a 11 01 11 < 11 a 11 i 11 0 11 3 11 11 /+ 11 ^-1 ID 11 U1 0 U1 -i 11 r* 11 -0 11 0 - 11 U1 ^ 11 0 " 3 11 15a> co a *\.^J , M O ffl n m i/) 33 > -1 t*4 Z n (/) 0 c m CD 2 n n I nm 02 33 0 in z o o -10 -n DC z z 3?-2r'^o-^2o s r 3 -0 ^, r 0 > 2 in -< l/l *i n C 0 r- < m M ^-4 0 2 in l w ^ C - S g > > ba 3 [-1 < M 5 a 0) < r rn 0 -n -I m 2 m > n I 0 3) t> 0 m S > w :' 11 J 11 11 \ 1 N 11 -i n ^^ V 11 11 r+ 11 0 1 0 U 1 -- 1 1 U1 11 -< 11 U1 0 " '-^ ^^ 1 1 11 -1 II 0 VI 11 U1 U - 1 11 ' 11 11 * -- 11 11 -- 1 11 1 1 11 -' ^ 11 0 CD 11 Mil--1 W m 1 0 11 -1 U1 11 U1 0 < 33 11 < ----s f-s 11 U1 m 1 1 11 0 0 11 -0 M - 1111 3>) Company Sanitized. Does not contain TSCA CBI -1 I < c r n< aoi -i r o >- ^j --< o 3 0 Cl a r x > > Z z 0 n I *> '" n < VI -< i iU i iU > (/) 0 o r om m m z m Cl > 2 m r z rrrnci > > K-1i 02 <t/l m ti o r> c M 1 Ul Ul 1 Wl Ul . ;A zs 11 n In- r'o rr.z-c--cn -ci->oni <r>r/>-c-coiz>r-oo->i-r-->>" l-i-i-rioo ooo><<< z-rn-aiii(n/s)(nBi oomrr oror-)i0-0no o-riirm-.iinm s1 -) -0 I r y. r I > m < 2 > c z io- 1-1 < m13e -< > o z-13) S<-< o<2'-nitfl -0v1.r00< 0I 2m nZ2if2n>n-<iz-n>->n>T2im3 3 M o 31 T) m o r o> o > "0 (/I m r<3'oTiri-/iio3 SI>-<s o-io3o-wfrot<n nnan)Tri--ii--ii--<i moni-ni I > 33<1 > ci m z oososo -o<><> z-nizc:-an<-/f) oi-oni (-/ii-w'--iossnno MI/)(/)>IIZ o m -i -'-n m o-i'-iorn oa>ioanz>ao) 1-1222 > zono> - > -I -i cznoz vii ' rw(/)i/i t) </) -o o OooOrnozcmicmicmi n m (n a r o o -< c -i4 V >-ic-n? ui o TI c c m (/> i-TI o m o r 20 n -lioc -) z -I (/) ->< >-( - >OO-" O> T-nI 3 "o) .oc o n -2 i 3) > n c > r n-ir. oii I . ;o r < 3) - K 2 n < r c < < o c -" in c r r 1-1 m > r~ -n 1-1 -( m m-is .. x-i rn ci -m- n<i-mi-cios m Z W -< ^ 3 -i 2 -<->m -n m o c r ;> DcSoT)-tn> 1-1 > > m o so coe 3 -< rn o> c > c i > z !! -1 11 1-1 ii ui nr n ui lie uni 11^- 11 m 111/1 11 M niio2 1n1 " n 11 n 11 n 11 r- InI-^OnMi 11-1-1 11 -- o 1111M -2 in iu. cxi rr n vi > -i r M wrn3 c-i-i>r-" -f -i > r cnc-( n-<><c "E i---rfi m-ir-nir-ioir^oo> S0n2'sr>rc- r r>r>-< z > -l -" -l c (-) M a < c m r m -i en > -< r r ffl 2 -l nrn -i-o m-i-nn tiiTo io-ifofl of o>nr>fnB 1n1-^>0 1iliiw1tr/"ni n 11 11 n '--f"r--i'o-nifl c s>or-ir 1-1 3 n-nn crnni> I-i < o o o > o nrnnr n > > o --icnii/i ^< -l -i <- r u> v n r . s - ii m 11 (/) -n r- in n 11 11 -i z) < >r-ir ~.o-l-> 0 o > 2->i-rni-n'--i 3 1-4 o vi i m 2 cniri >-ini -1 sac i-xio m 0--r 0 > jo vi s n > c c-i 0 C X > 0 romni o 1-1 n 2 so < i-i n r n m r orn B) z r aa 3 1. M m a> r niizacoooa niiBmwoc in11ivm'S--B0 n-<cim n11 z^r t/>)- iio-^ei n ll .0 0 7 > 11 c ^ j .r 'o 11-0 n V CO ii D -i 0 C 11 Z s p vi r n > HI - > 11 r V) VI 73 H m 11 Ul 11 11 .1111.1.111..1111..111-..1111 IIIIIIIU1 1 01 1 -- in rf-^ 1 ^ - 1 1 1 ^^ --* 01 ^^ | J - 1 f 1 s^ IMIG1--01 ^^ ^ --< N U - 10 1 - 1 1 01 ^^ -- <-- \-f \^^^ ^^ ^ 11 -< 11010 11 11 0 11 0 1) 11 ^^ II 0. 11 0 11 < 11 w 11 1 11 0 11 3 11 11 r* 11 >-< 0 --IIIIUI --IIIIU1 1 Ul -- 1 01 --t Ul ^^ ^-^ " " ) 1 1 1 * . -J | --. ^ * 11 U] 0 1-1 Ul III--IIIUI -0 11 ft 1 11 0 11 . 11 01 ^ '-'11 1) 0 11 3 II! w (ll ^^P0co) i J ^^ (/> T) ni n 1-t m Ul x > >-. -l 2 o Ul 0-i e m CD Z n n t nm go./, Z DO -' 0 "n OC 2 2 1-'00 Z VI c 3 U ^1 ^ ! r m > 0 < -) o ws. ^ M r r 0 > m 2 </) ^ W t-i -i 0 C 0 r < m w M 0 z (/I 11 1 1 1--1111101 1 1 t 1 1 ^-' ,v-/ >-' --' ^ 1 1M 1 01 Ul 1 Ul -- -- Ul | 01 1 CO - 1 1 01 11-- -- 1 01 1 11 01 11 & 11 . 11 f+ 11 0 I 11 11 01 0 I-i 11 1-1 -^ *-^ 1 1 ^s/-^. 11 - ^ ^ ^ - 1 . . 1 - 110<0 11 Ul 0) 11 - 1 -- 0) - - 1 - 11 11 11 11 1 1 1 11 * - . . . . 11 11 11 t 1 t 11 . . It t 1 *^^^ 11 ^^^^ 11 1 ^^^f' V^ 11 I| 11 11 -(-.iicji - -- N 1 en Ul 1 01 1 -- Ul -.yi i-.-.--im i i i rsj -- i -* ui II *-' 1n1 (jio< ^-^^^ ju -- III 11 - ---^ <-< 1 i /-s^-..--* ^-t ^ ^^^\*"^ 11(7) 11 0 . . 1) -0 1(1 _ 1 1 --> ^ --*---- . .. 1-J 1 1 1 i I*II -II* --I I 1 1 1 i f^J J --. II > 11 x -i 11 11 1 1 1 11 - III 11 . 1 1 1 t 1 1 1 11 III 11 ^ ^-' '*--' '-- ^^/^- --kf ^^^'^/ 11 -- Company Sanitized. Does not contain TSCA CBI & mz-f2o(ro-nn)cnini>c~-ic,'t<fo-n.oosc(>-o/i)-j(>o-Bowopnix>-ij -<-i CD V> m m -) S 0 0 -1 < o m m t/1 2 m fti i-t 1/1 1--t w -" m m 1/1 V) 0 > > -1 2 z z o " m > iii/i Tl 3 m o v jo vi 2niCfT12SS2ni>2II r > s 31 < < a; rn n > -isss csczrn 00 nii> > a r I 23-0-0 3) 0 - 3: 1 < < 3) -1 -1 0) >- o o r n o o 00 > v rn - > fn m -l > (/) 0 r 4 Z (/I (/) 0 ^ 0 c m rn m 3 r r as r 31 -0 C C o - "-i 3: s 3 2 z 2 m rn 11^ 11 n IIM 11 C > rn 11 m c5i>n-^ 3 c 11 r 1/1 n rn ii vi 11 >-i 11 0 11 Z 11 .. 11 li 11 > M M 2 2 2 . 0 II Tl 0 c fn m o -< 3) fn m c0c0 in l/i 11 11 n n r 11 -< m 11 o in c -( - ^ 0 c c 0 OD CD M > cr cr \ m m (/I (/i t/i C * CD a cco : 2 --1 (") -* r" 0 r > 11--0 11 2 11 M 11 0 11 CJ 30 > 11 11 & 0 n '-^m 11 M ii ii ii 11 .' ii l/l > -< ^ -l rn m v ii ii ' 11 33 > ii :o > r rn r ii 11 2 0 0 so M 11 C 0 3> -0 11 S in 0 i-i ii CD m c 31 11 m B >-1 1111 ;0-^ 0 11 -icim 33 11 2 '. Ul < li r" -i m 11 0^--(D 11 31 2 o 11 0 > -< 11 C 11-0 rl " 11 0 11 Z S 11 > 11 1- n rn 11 CO 11 ii UlUlUlUlUIUlOlUlUl 1 01 01 01 Ul 1 Ul 1 1 Ul Ul cn - Ul -- /-s ^~ n i-i 11010 ii 11 0 -- -J 11 0 11 [ 1 1 1 11 ^> 11 0. 11 01 < 1 - 1 11 < 11 Ul 11 1 1 1 S----' *-/ 11 0 11 3 11 1 11 f uluiuiuiuiuiuimul 01 Ul Ul Ul ' 1 Ul 1 1 Ul Ul (J) -- <J] 1 ,-s --1 noioi-i- 11 (D m 11 t+ 11 11 .00 -t. J 11 Ul ^ ( 11 0 - ," 3 1 11 J 11 1 11 - 11 Ul !! t' \ \^ 11 11 ' r 11 0 11 " CJ1 OT Ul 01 1 Ul 1 1 Ul UI M f Ul t ui ui ui ui ui ui ui en ui nuio>- 11 * ^< 11 0 10 11 Ul 0) 1111 '-' 11 11 11 11 11 11 11 11 * 11 U1 Ul & Ul 1 Ul 1 - Ul Ul U nuio< 11 -1 1 Ul 1 ui ui ui ui ui ui ui ui ui 11 .--t 11 UI 1 11 0 . 11 -- 11 11 1 11 11 iCD ^^--cb(P . ------ VI D m n 1-1 m (/i 33 > -1 W 2 n - </) 0 c m CB Z o n I n fn 3) 0 VI nocs22 -'00 Z -0 0 M " o -n c 2 S t1"-31 > 2 31 W 2"2 IBRi < t-' 2 W -00^' r m -i > 0 > ^ >- r r 0 > m z i/) (/ -l n e 0 r < m VI 3 z l/i U o t> 3; -1 . Company Sanitized. Does not contain TSCA CBI z 0 0 0 -< m l/>. mi r -< i/i m M 0 2 Z C 5 P 0) a? m > a 0 m o in *n n o 0 3) 3) o 3) > ro z 1/1 in D o m z x 0 > s n> -i < 2 m a o 0 M -n -i 0 -1 3; -* 0 TO 2 > n S 1 t-4 -< 0 I 33 0 -1 C I -D m z in c 0s) c2 m o 3; m (/) 3; i- '' m O 0 > v m z -i m t/i m i/> S I n I z 0 n > -i m T 0 E 0 -n -1 m z tTl > 0 I 0 v > 0 m > yi 0 0) i/i ni 3 < m 0 0 -1 I 3 m > V z 0 0) c r- > r < 5 o I z 0 0 m I < D m XI D r > in > r < s o i0 . 0 1 0 1 0 1 0 11 n z 0 M 00 (/)(/) 1-1 1-1 f -i m Z Z Z c c -n -n -n >>r r r 00 33 3 S > 3 > >n- CC3 S3 0 n -i n -' ii i/i li m 11 C ii m 11 ~s 11 r n m 11 W m i/i > > > 3 3 3 -l -) -l i- -" -- -4 * mmo o o a > -1 -1 Z Z Z ^-- > - D D on r r (/i -n > >r c -i (/) 1/1 0) 0 C >- -- > > >> nr m . . c-< - 0- 3) -n rn in s m c c (/> o 0) n D > 3 > 0 'x-i.r c r n c in > ?> -i -i \ -( a) i- m i/i 0 m n' c 31 t/l 0 CD < -o n s s -- >>c m 31 r x n ll -" ii 0 11 Z li ii ii ii ii n r 11 ^ rn 11 D l/) 11-0 11 - -i 11 2 11 Is) 11 C1 11 CO 3) li - > 11 6 0 ^m ii 11 i/i n ii ii ii o >- o >- i- -i -o l 7i r r in > X 3) rn o- m < in -l r -o c < - fn i-< 3? m C -D 3) 01 Z s i- > - -i -1 -1 Z 3) I or > m 31 -i r i~ < m -i S c -l (n s c > 3) -1 CO C 1-1 m ii ii ii ii ii 11 11 2 0 0 ne o v 11 S (/1C ii ai m c n m -0 30 11 71-- 11 ll >-i p in 11 Z ^ 1/1 Cl'^0 li r -i 11 11 3; Z 11 0 > z 11 C *-\ p 11-0 i- -) 11 .. 0 m 11 Z in ii > ii r ii m ii </) ii ti 11 M 11111 01 11 01 0 11 11 0 11 0 11 It ^-^ (( a 11 ID li < 11 UI 11 | 11 0 [J 3 iii--i U1 /-s 1 -- - 11 1- 11 ii in o - w ii rt 11 . 0 11 0 -h n in n 11 0 11 3 ii n ui i ii & liiii m ii rt- 11 0 11 Itl 0 - i! o (D 11 U1 01 ii ^ jf ii Ij! in u <p m \^ w -0 m 0 -< m in 11 33 > -4 <- 2 n in 0 c m ffl z n n I n in 3) 0 in 0 3 -00 Z 1-1 n -n n c z z ^"00 r fn > 0 --, D w r 0 > Z w -l in *- r n c 0 r < rn in M 0 2 tn . ' in c ' 4( . s s !,q^ > -( > < 0) r m ^B* 1 0 11 in 11 o ii n Company Sanitized. Does not contain TSCA CBI s 0 ja o m m 2 P > m r m p as r > > -1 Z - 0 < M rn -n 0 0 c i/i in i O 1 : t i : > i71 mise r < 2 t - rn ; > ni S :0 m . 2 -1 31 < -1 Z 3 M 1 Tl V PI 0 ^in r-o 0 > 0 XI rn Z) Cl I 3 < rn > Z CT -1 m m 0i- -n 0 a) > -i Z 0 > - r i-i n n r 0 I- c z -i v m o r Z 0 n M n) 0 Z 0 C n C r > r i-" m t- -i z \ M -i S n m c 0 x r n i/) -l > -f k-t r i-- -n -l 0 h-l n t- > 1- (- - - s 1-- s -1 < I 0 n o > t-- JO 0 0 g m c 2 s -1 m 0 3 > t j x 0 D I > 0 m </i 02 I Z I Z 12 12 2 12 IIZ 12 12 2 I Z 11IZ2 12 iz i2 22 12 I . 12 iz 2 Z 12 IIZ IZ Z Z IZ IIZ IZ Z 2 IZ IIZIZ 2 Z I Z 12 I Z z i-r iz Z 2 12 Z.IZ 12 2 12 z iiz 12 22 12 r c -D r -- 0 IIP r < 2 z -i rn in Tl in3 o r -"1a0) 0 03 ja n s 0:0 nl^ o < > -l j >- -) ^1 o m no vr c 1-- r> -* 1/1 in r- z c rn "n t/) 01 on -i c "n > xs r en -) > n c -- a n > -) z >c r m -n M -f m -l fn ^3 r C -n -< r o Zl 5 n -l n > C 0 1-1 > m-l r -< n > o' -- r n r- ns -n -> > c s: r r 03 i-c n> rc -i -< r -< -n i-i -i 0 -n -n n 0 > no n > m n> . r l- -i r < > -0 1/1 m n a c >-- r < > > XI i/; n F > 3> ^ 1 ^ ( 3 o I ^ n :z 0( 11 n r < n 0 /) 0 < 3 s -l r i/i m 0 m- m z x VI 2 m c n -< r <3 m 5 i a? 0( X) Zio ,0O 0 l/l m D f - r r ^ n m M x r -1 0 m i/) D n C 3> -< z -1 in -D 1--1 I ^ vr < XI 0 >4 m > -f 0 - m n m s Z) 3 z >> rn r r 0 TS z > -l t-1 -1 c n t-4 a < c m r m -l w c 0) c r- m VI "s. fr-t z 0 < n m r r z m n ;o 0 i/i h^ m I I I IZ 111112 111112 111112 111112 1--1 IIIIIZ IIIIIZ 111112 IIIIIZ IIIIIZ iilliz ii-- l i r II.I 112 IIIIIZ 111112 1112 111112 IIIIIZ z - i i i ir iiMiir iiiiiz 112 --illll- r i^ < zfnzmz-r'n-nzi->ni>T>ima) na)r>3n)"rn--<l--<f--fl M0l0/) 0 M >2 <-<;< M -i-i s n n n l/i (n M -> t >1 1> I > . 1-1 2 2 2 n n > o ci ci ci n z rn m fn oo > 1 C- CTO -1 c c m (/) M r c z r- > > (n o -n o o -" n TI -1 -) -i 1-1 < < m n - w > c n CO C i-, > z n oc 1-1 -^ < m -a ' c 2 > C 11 > n <r c o- vi rn c > m3- r o r> -" m 1> Z nm -co > H r r m z -l -s i - > r 1-1 c--l m -n.-( o r m "n D o o (s o - n'm a on s n -i > <-l cr-. >or c r n m > r-1'-3<-1-in v "n-cr mw (/i n 0-1- > n i-i -i > -n n -l r om m n z D rp -i mo r n 0 m 0) 2 L. 1 r 31 > " r 0 CD 0 0 S > > > 0 2 < < 0 - S i/> i/> m s > > r coo z z -n r m mfllIl!nm r s o-i-i n in > < I m v on m o v v " o c TO (/) 0 C r- B < 5 rr XI 3) 0 z c f- > a I 1111112 < CD u 0 -M w 0 N 01 -i 0) m u -0 1/1 O M ! D a n m o n o t-i -- c 2 m n I w -( > VI -- > x> om -< M i i i i i iz I I I I I I IZ -- m u ^j 0 M O <D 0) CD U 0 M--0U-0b-0J) 0 0 -1 -0 0 > 2 ;o l/l 3 -1 m z 0 11111112 00 G1 VI -- i/) --4 -^ rn 0 M0 0 0 -1 < --i/i-^'j CD cj n i -- l M i i i r- o 0 M O U 0) 2 -1 CD u a 11111112 --MtfllO-; A o> o in 0) O r iiiiiz 111112 00 W -^ Mo m o A -- ^ en CD w -- M vi A ~-i A 0) 0 (D 0) III r~ iiiii--ir III i if- i iz CD U - N in CD ^ to 0) 0 G) C) as u t-oN0I) /0I^MI-0J) CD CJ A in (/i o -4 -- ti) 0 -- CD CD U & in 1/1 u ~j -- u o 0 oi CD CO 12 < II I t> 1}1 VI U ~) -- U 0 -4 0> iiiiiiiz IIIIIIIZ CD U AUCOIM0 A~1'0J1 -- CD 0) ^IOflj M0 '0^0'0^1 _. Company Sanitized. Does not contain TSCA CBI UN-15388 TISSUES/OBSERVATIONS TA3LE V:[ f SUBCHRONIC 1INHALATION STUB " POLYMER PROI)UCTS CIEPAF(TMEhIT SPEI:IES: R(AT SEX: MALE GROUP: r DC)SE: CONT ROL ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST; DAYS ON RECOVERY: 376 376 376 376 376 376 376 376 376 825 839 840 870 873 835 841 849 863 SD SO SD SD SD SD SD SD SD 12 12 12 12 12 26 26 26 26 0 0 0 0 0 14 14 14 14 THYROID GLAND CVST ULTIMOBRANCHIAL CYST TRACHEA ESOPHAGUS BRAIN STOMACH DUODENUM JEJUNUM ILEUM CECUM COLON NEMATODE, LUMEN RECTUM NEMATODE. LUMEN MESENTERIC LYMPH NODE URINARY BLADDER TESTES ATROPHY. ATROPHY, SEMINIFEROUS SEMINIFEROUS TUBULES, TUBULES, BILATERAL UNILATERAL EPIDIDYMIDES SPERM GRANULOMA N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N 0 N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N 0 N N N N N N '* N N 0 N 0 N N N L N N N N N - - - 1 N N N N N N N N N EYES ,---" ' --J ----3 HN-153BS ^^^--------^ -- ^ TISSUES/OBSERVATIONS TABLE VI ^ SU6CHRONIC INHALATION STUDY ^ POLYMER PRODUCTS DEPARTMENT SPECIES: RAT SEX; MALE GROUP: I DOSE: CONTROL ANIMAL NUMBER: MODE OP DEATH: DAYS ON TEST: DAYS ON RECOVERY: 376 376 376 376 376 376 376 376 376 625 839 840 870 873 835 841 849 863 SD SD SD SD SD SD SD SD SD " 12 12 12 12 12 26 26 26 26 0 0 0 0 0 14 14 14 1 STERNUM N N N N N N N N N . BONE MARROW N N N N N N N N N NOSE INFLAMMATION. ACUTE, MUCOSA/SUBMUCOSA, RESPIRATORY EPITH. INFLAMMATION, ACUTE. MUCOSA/SUBMUCOSA, VENTRAL MEATUS INFLAMMATION. FOCAL. SUBACUTE, MAXILLOTURBINATE INFLAMMATION, SUBACU1'E, MULTIFOCAL, RESPIRATORY TURBINATES SOUAMOUS METAPLASIA, FOCAL. RESPIRATORY EPITHELI UM SQUAMOUS METAPLASIA, RESPIRATORY EPITHELIUM OTHER MANDIBULAR LYMPH NODE: HYPERPLASIA, LYMPMOID L N 1 - 1 N N N - N N - - L N 1 0 0 0 0 L 0 0 0 0 2 HN-1538E TABLE VI SMBCHRONIC INHALATION STUDY 0 POLYMER PRODUCTS DEPARTMENT SPECIES: RAT SEX; MALE GROUP.- I DOSE; CONTROL TISSUES/OBSERVATIONS ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY: 376 376 376 376 376 807 829 834 661 869 SO SD SO SD SD ' 96 96 96 96 96 84 84 84 84 84 LIVER FATTV CHANGE. DIFFUSE. CENTRILOBULAR FATTY CHANGE, FOCAL, MEDIAN LOBE FATTY CHANGE. INDIVIDUAL HEPATOCYTES,SCATTERED.CENTRILOBULAR INFLAMMATION, SUBACUTE. MULTIFOCAL NECROSIS, ACUTE. INDIVIDUAL HEPATOCVTES, CENTRILOBULAR NECROSIS. COAGULATIVE. ACUTE, FOCAL/MULTIFOCAL NECROSIS. COAGULATIVE. SU8ACUTE, MULTIFOCAL KIDNEYS CHOLESTEROL CLEFTS/REGENERATIVE TUBULES/INDIV. CYST, FOCAL GLOMERULONEPHROPATHY, CHRONIC HYDRONEPHROSIS, UNILATERAL PROTEIN DROPLETS. PROXIMAL TUBULES CELL NECROSIS LUNGS HEMORRHAGE. SUBACUTE. FOCAL/MULTIFOCAL HISTIOCVTOSIS. FOCAL/MULTIFOCAL INFLAMMATION. SUBACUTE. FOCAL/MULTIFOCAL LYMPHOCVTIC INFILTRATE, MULTIFOCAL. PERIVASCULAR POLYMORPHONUCLEAR INFILTRATE, MULTIFOCAL, PERIVASCULAR HEART MYOOEGENERATION, POCAL/MULTIFOCAL, MVOCARDIUM PANCREAS ATROPHY. FOCAL. LOBULE INFLAMMATION,CHRONIC.INTERSTITIAL.WITH PIGMENTED MACROPHAGES THVMUS HEMORRHAGE. ACUTE. MULTIFOCAL SPLEEN ADRENAL GLANDS DEGENERATIVE FOCUS 6S -i (- -) m -( c 5 31 n n -" 0 VI CD m -< o HI ;0 m m 0 m r m C -< JO i/> 31 I -( -i (/) -1 M n r n rn <- 0 0 y- 0 > < i/i (/> 0 > > -) 2 ni 2 -1 2 0 c c c 0 s >-- o 0 C n 3) in o >- -1 -1 fD > 2 m c 3 S 2 m > Z I r <0 C S2 ? -i m o 3) 31 (/) 3) -1 2 5 z 0 m (n i-. m < 3) < m > > 5 c I d > i-i M 00 -10 5 5 O -0 a -1 -1 Z I 01 i-i 0 0 3 c S ^. </) 0 Cl 0 5 o < < r n 0 0 CO r CD v m > M > m m 0 r 31 > in > z m Z 1/1 VI 0 < C m m m Z r r r 2 2 3) o c c 0 -< ^ I 3 s 5 2 2 m m > ii i Tl T1 2 Z 2 0 Z 0 s 0 < I T> >I i--1( r 0 Z rn m 0 31 a m 0 I/) < 00 n c c -^ fi in -i -) c c cc (0 0) r r mm 1/1 in a C CD "r2-i r > > -i -im m B 31 > > r r t/) rn >: 0 0 S > > 0 2 << 0 w i/) m S > > r 000 z z -n r m 3) -i 0 ffl rn rn n 1/1 > O<-1-I l m D 0 !? ^1- (D (1 I rn 3} 31 0 ai 2 < (/) O M O 3) m o 0 0 >-" c m n n 1-3 Jii 1 2 22 12-0112-2Z22222222 2 12 112 12 Q) U CD 10 VI 0 ^J b 0) 0 ~1 0) CO u OCDIOMM'J .> 0) 0 10 0) in -1 w 33 0 > m -1 -0 > r > < -< M 3 2 2Z2ZZ2 3) m u -1 W 2 t-i CD CO LH 0} ^J 3 -1 A 0) 0 b 0) 0 m ' 1222222222 0 2 0 12 112 2 Z -01- 12 2 2 2 2 2 2 Z 2 t 112 CD Cd (/) CDCCMO)-^ m fa 01 0 -- 0) CD u n -1 < U 2 12 I IZ 2.2 12 IZ 2 2 2 2 2 2 2 2 112 CO(Ot/)0)'J & 0) 0 10 0) 0 2 Company Sanitized. Does not contain TSCA CBI HN-15388 TABLE VI 0 0 SBBCHRONIC INHALATION STUDY POLYMER PRODUCTS DEPARTMENT SPECIES: RAT SEX; MALE GROUP: DOSE: CONTROL TISSUES/OBSERVATIONS STERNUM ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST; DAYS ON RECOVERY: 376 376 376 376 376 807 829 834 861 869 SD SD SD SD SD 96 96 96 96 96 84 84 84 84 84 N N N N N BONE MARROW N N N N N NOSE INFLAMMATION. INFLAMMATION. INFLAMMATION, ACUTE, ACUTE, FOCAL. MUCOSA/SUBMUCOSA, RESPIRATORY EPITH. MUCOSA/SUBMUCOSA, VENTRAL MEATUS SUBACUTE, MAXILLOTURBINATE INFLAMMATION, SUBACUTE, MULTIFOCAL, RESPIRATORY TURBINATES SQUAMOUS METAPLASIA. FOCAL. RESPIRATORY EPITHELIUM SDUAMOUS METAPLASIA, RESPIRATORY EPITHELIUM N N N N N OTHER MANDIBULAR LVMPH NODE: HVPERPLASIA. LVMPMOID END OF GROUP I TABLE VI TISSUES/OBSERVATIONS ANIMAL NUMBER; MODE OF DEATH; DAYS ON TEST: DAYS ON RECOVERY: 376 376 376 376 376 376 376 376 376 804 806 818 823 844 810 822 852 876 . SD SD SO SO SO SD SD SD SO )2 12 12 12 V2 26 26 26 26 0 0 0 0 0 14 14 14 14 LIVER FATTY CHANGE. DIFFUSE, CENTRILOBULAR N N L L L N N N L N FATTY CHANGE. FOCAL. MEDIAN LOBE FATTY CHANGE. INDIVIDUAL HEPATOCVTES , SCATTERED , CENTRI LOBULAR INFLAMMATION. SUBACUTE. MULTIFOCAL NECROSIS. ACUTE. INDIVIDUAL HEPATOCVTES, CENTRILOBULAR - - - - - - - - - NECROSIS. COAGULATIVE, ACUTE. FOCAL/MULTI FOCAL NECROSIS. COAGULATIVE, SUBACUTE. MULTIFOCAL N---.-N--_--NI1--N-,-N---N-----N----N--,-N--- " KIDNEYS 0' CHOLESTEROL CLEFTS/REGENERATIVE TUBULES/INDIV. CELL NECROSIS -- CVST. FOCAL GLOMERULONEPHROPATHY, CHRONIC HYORONEPHROSIS, UNILATERAL N-------L---N-----L---N----N-----L_---L----_ PROTEIN DROPLETS. PROXIMAL TUBULES . LUNGS _N- HEMORRHAGE, SUBACUTE. FOCAL/MULTIFOCAL HISTIOCYTOSIS. POCAL/MULTI FOCAL INFLAMMATION, SUBACUTE, FOCAL/MULTIFOCAL - - - - - - - ' - - - LYMPHOCYTIC INFILTRATE, MULTIFOCAL. PERIVASCULAR POLYMORPHONUCLEAR INFILTRATE, MULTIFOCAL, PERIVASCULAR -N----IN---L-1-NI---N----N---L21-N----- HEART MYODEGENERATION, FOCAL/MULTIFOCAL, MYOCARDIUM -N PANCREAS N- -N1NN- -N-N1N-N-N- ATROPHY. FOCAL. LOBULE INFLAMMATION,CHRONIC.INTERSTITIAL,WITH PIGMENTED MACROPHAGES THYMUS N- -N-N-N-N-N-N-N-N- HEMORRHAGE, ACUTE. MULTI FOCAL SPLEEN N-N-N-N-N-N-N-N-N- ADRENAL GLANDS N- '-N-N-N-N-N-N-N-N- DEGENERATIVE FOCUS Z9 -i m m I -i < o m tT/Ol </i 0 > to (n D 1-- m 0 -1 -< rn XI Z i/) 3) < 00 5 5 ?5 M 0 0 S fn > M -<; < 2 </1 (/I C m rn 5 S 0 1-4 1-4 -iZ Z >J> 1-4 fM -n -n m m 00 33 3) c c VI/)I I(//)I -f -1 c c 0) ED c c r r m m 1/1 </> C 0) z i i-i r r > > -i -i m m X) > i> r r 35 c 3> n Z] m rn 0 ^-t i/> n 2 > m z 2 -1 2 0 m c fn z :0 -< < m > > 33 CD -1 0 0 r n 0 0 > HI m 0 r- 0 < m r r a o c s ro m 2 z Z 2 or~ 0 mTO . n m r n m c c 3 C 0 m c(- 0 0 z m c 2 C S in CD m -< -i 1/1 S 0 > 0 > < o n c nlZ Z n r <0 m -1 V) M -i Ci > < 0 Vi 0 CB *> T Z 0 n > . 'r- n < M -1 -4 V) L C m M ^ 0 ED in m v > -i 1-4 0 z V) I^^HtaBU DOS > > o z> rxn < < o M l/i t/i m s 2 I 2 2 l z 2 2 2 2 2 Z 2 '222 2 2 2 2 2 2 2 2 z 2 2 z -2 12 2 2 2 - - 2 2 z 2 2 '2 ]22 2z - 2 2 2 2 2 2 2 ;. 2. 2 IZ IZ222ZZZ2Z o ,,, ,,, , ,. IIZ oooii r z z z xi -i o c m m (n s n M> (B 0 -< -l m < I ai in a < (nu -- in o ^ ONO^OI CD d) o M--owoo) '0;1 i r m 'oH</' o c rBco ?S-<B31"l o v x oz i-/rri> o c M-o-ao)BT-)i .n_, o in oB noBi-i i6>a I- r"nGnBzI 1-1 t-rl 1-1 i/i __> ' r ^i m u o -- M vi o m-- ~j o) m u o 0 -- w N) 0 M ^j c*i CR o (/l 171 CD U o M-t/ol.b.>-0J) r 12201Z12222222222222Z2Znl,- 2 ' 2 ' '2 2 2 l 2 0--M(/)-~i 0 CD U S 4 0) 0 0 01 z Till- cn" -N(/)K)^ t 0) D h) 0) "^-^zzz^^, Z I z G) | r 2 7 i -; 12 I IZ Z 2 1. 2-, -- Is) M 0) 0 CD CO 01 -J M 01 ^ Til- ^" N0)<0/l~0)j0^) 2 12 I I2 2 Z IZZ2222ZZ2 1, 2-. CD U - N (/) CD -^ b 0) 0 -- 0) Z I Z I IZ 2 Z IZZZZZ--Z2ZZZZZ2z iiiiz- , . A- 03 "u0in0o U ^ 0) - - 2l2||7-,_ 122222222Z lz '2Z2Z2ZZ27 2 1222. . "- 2 2 2 2 z z I Z ,1,12 '2 ^ ui ifl ^ ^ - C-l 0 CD 01 '" ^UlMm-S - " o o> o CD C*J A 01 M 0) '< -"00)01 ^^^^zzzz,,.IIZ z ^.OIM-J^I -- Ci) 0 -^ 01 Company Sanitized. Does not contain TSCA CBI MN-15388 TABLE VI I SJLIBCHRONIC INHALATION STUDY POLYMER PRODUCTS DEPARTMENT SPECIES: RAT TISSUES/OBSERVATIONS SEX; MALE GROUP; ANIMAL NUMBER: MODE OP DEATH: DAYS ON TEST: DAYS ON RECOVERY; II DOSE;' LOW 376 376 376 376 376 376 376 376 376 3 804 806 B1S 823 844 810 822 852 876 8 : SO SD SD SD SD SD SD SD SD 12 12 12 12 12 26 26 26 26 0 0 0 0 0 14 14 14 14 STERNUM BONE MARROW I N I I N N N N N NOSE INFLAMMATION. ACUTE. MUCOSA/SUBMUCOSA. RESPIRATORY EPITH. INFLAMMATION, ACUTE. MUCOSA/SUBMUCOSA, VENTRAL MEATUS INFLAMMATION. FOCAL. SUBACUTE, MAXILLOTURBINATE INFLAMMATION, SUBACUTE, MULTIFOCAL, RESPIRATORY TURBINATES SQUAMOUS METAPL'ASIA, FOCAL. RESPIRATORY EPITHELIUM SOUAMOUS METAPLASIA. RESPIRATORY EPITHELIUM OTHER MANDIBULAR LYMPH NODE: HYPERPLASIA, LYMPHOID N N N N N L N N N 1 0000000000 r wHN-153S8_ TISSUES/OBSERVATIONS TABLE VI ,_ ^UBCHRONIC INHALATION STUDY POLYMER PRODUCTS DEPARTMENT SPECIES: RAT SEX: MALE GROUP; ANIMAL NUMBER: MODE DAYS DAYS OF DEATH: ON TEST: ON RECOVERY; II 376 027 SD 96 84 376 B3) SD 96 84 376 862 SD 96 84 DOSE: LOW 376 877 SD 96 84 376 882 SD 96 84 LIVER FATTY CHANGE. DIFFUSE, CENTRILOBULAR FATTY CHANGE. FOCAL. MEDIAN LOBE FATTY CHANGE. INDIVIDUAL HEPATOCVTES, SCATTERED, CENTRILOBULAR ----_-_-_- INFLAMMATION, SUBACUTE, MULTIFOCAL NECROSIS. ACUTE, INDIVIDUAL HEPATOCYTES, CENTRILOBULAR - - - - - NECROSIS. COAGULATIVE, ACUTE, FOCAL/MULTI FOCAL NECROSIS. COAGULATIVE, SUSACUTE. MULTIFOCAL .- -- -- -- -- -- KIDNEYS CT\ CHOLESTEROL CLEFTS/REGENERATIVE TUBULES/I NDIV. CELL NECROSIS 4^, CYST. FOCAL GLOMERULONEPHROPATHY. CHRONIC - - - - - HYDRONEPHROSIS, UNILATERAL - - - - - PROTEIN DROPLETS. PROXIMAL TUBULES - - - - - LUNGS HEMORRHAGE. SUBACUTE, FOCAL/MULTI FOCAL HISTIOCVTOSIS, FOCAL/MULTIFOCAL INFLAMMATION, SUBACUTE, FOCAL/MULTIFOCAL LVMPHOCYTIC INFILTRATE, MULTIFOCAL, PERIVASCULAR POLYMORPHONUCLEAR INFILTRATE. MULTIFOCAL, PERIVASCULAR HEART -------------------- MYODEGENERATION, FOCAL/MULTIFOCAL. MYOCARDIUM PANCREAS ATROPHY, FOCAL, LOBULE INFLAMMATION,CHRONIC,INTERSTITIAL.WITH THYMUS HEMORRHAGE, ACUTE. MULTIFOCAL SPLEEN ADRENAL GLANDS DEGENERATIVE FOCUS PIGMENTED MACROPHAGES ----- '"'- --.--_ 3 MN-15388 TISSUES/OBSERVATIONS ^uu^imw^&k' 1. 1ii min i A U11 J 1 UL. ^POLVMERPRf0131JCTS CIEPAF!TMEI SP!E(C:[ES: E[AT SEX: MALE GROU P ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY: II DOSE'.: L( 376 376 376 376 376 B27 831 862 877 882 . SD 5D SD SD SD 96 96 96 96 96 84 84 84 84 84 THYROID GLAND CVST ULTIMOBRANCHIAL CYST N 0 N N 0 TRACHEA ESOPHAGUS N N N N N N N N N N BRAIN N N N N N STOMACH N N N N N DUODENUM N N N N N JEJUNUM N N N N N ILEUM N N N N N CECUM N N N N N 'COLON NEMATODE, LUMEN N N N N N RECTUM NEMATODE, LUMEN N N L N N P MESENTERIC LYMPH NODE N N N N N . URINARY BLADDER N N N N ' N TESTES ATROPHY, ATROPHY, SEMINIFEROUS TUBULES. SEMINIFEROUS TUBULES, BILATERAL UNILATERAL EPIDIDYMIDES SPERM GRANULOMA N N N N N N N N N N EYES N N N N N r 6 ) HN-15368 TISSUES/OBSERVATIONS STERNUM TABLE VI ,SUBCHRONIC INHALATION STUDY ^ ' POLYMER PRODUCTS DEPARTMENT ' SPECIES: RAT SEX: MALE GROUP: II ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY: 376 827 . SD 96 84 376 83) SD 96 84 376 862 SD 96 84 DOSE: LOW 376 376 877 882 SD SD 96 96 84 84 N N N N N BONE MARROW N N N N N NOSE . N L N N N INFLAMMATION. INFLAMMATION, INFLAMMATION, ACUTE, ACUTE, FOCAL. MUCOSA/SUBMUCOSA, RESPIRATORY EPITH. MUCOSA/SUBMUCOSA, VENTRAL MEATUS SUBACUTE, MAXILLOTURBINATE - - - - - - - - - - INFLAMMATION. SUBACUTE, MULTIFOCAL. RESPIRATORY TURBINATES SOUAMOUS METAPLASIA. FOCAL. RESPIRATORY EPITHELIUM .-)--- C^ SOUAMOUS METAPLASIA, RESPIRATORY EPITHELIUM - - - - 0^ OTHER - - - - - MANDIBULAR LYMPH NODE: HVPERPLASIA, LYMPHOID 0 0 0 0 0 *** END OF GROUP II L3 > 0 3i o m m 2 ms? z m ci 33 > > -I Z -- 0 < l/l m n o n c (/i VI -0 3: r < ro I 2 m m <= 2 </i 0<2nfn 3) ^C-10 -fais-irM 3) D > 2 - >n -2n-31) x m r- o > (/> I? 0030V ooor < > 00 o-'-i 01003) nnn 2 n 00 nn > ggg2n,n,m o r 00 31" ^' m o r on C^ z o nc i5 20- n m rl-r 0S>r?o.? 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' ,' _Z ,' .I '. 2_ i I 1. 2-- I IZ I IZ MinSy - t^ 0) 0 Ci) 01 o co A- M 0) (/) 0 CO 0 ^1 0) m co MM -- .& 0) 0 01 ^1 ~J 0) O) CO -- M 1/1 ~J ^ ! 0) 0 .b 0 0} G3 A 01(/)0 -! -- CO 0 CO 0) 00 CO t> 01 to o ~^ ' z 2 12 .11 2 12 [II-- -. (- 111112 '22 III ,2 II 12 i --i i i r iiiiiz '2 2 Mr I- 12 r- l 111 2 I I I 12 ' If- ' i r~ - CO 003 01 CD ClI A 01 (/l -- ^| - CO 0 - G) 00 CO -tt 01 (/l j^ -^ - CO 0 CO 01 03 CO .b 01 (/i o) -^ - LJ 0 0 01 '-' m nc. t-* wi -l I M vi < 3) 0] > m cr Company Sanitized. Does not contain TSCA CBI TABiLE VI HN-15388 TISSUES/OBSERVATIONS THYROID GLAND CVST ULTIMOBRANCMIAL CYST TRACHEA ESOPHAGUS BRAIN STOMACH SEX: f SUBCHRONIC l NHALA1-ION STUC POLYMER PROD UCTS C1EPAF!TMEf' SPEC IES: P!AT MALE GROUP: III ANIMAL NUMBER; MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY: 376 805 . SO 12 0 376 821 SO 12 0 DOSE:: If.ITERUflEDlyt-TE 376 376 376 376 376 838 851 867 612 813 SO SO SO SO SD 12 12 12 26 26 0 0 0 14 14 376 830 SD 26 14 0 0 H N N N N L P 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 DUODENUM JEJUNUM ILEUM CECUM ' COLON NEMATODE, LUMEN RECTUM NEMATODE, LUMEN MESENTERIC LYMPH NODE N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N 0 0 N N N . URINARY BLADDER TESTES ATROPHY, ATROPHY, SEMINIFEROUS SEMINIFEROUS TUBULES, TUBULES, BILATERAL UNILATERAL EPIDIDVMIDES SPERM GRANULOMA EYES N N N H N N N N N N N N N N N N N N N N N N N N NNNNNNNNN TABLE VI S>UU_BBCCHHRROONNIC INHALATION STUDY _ _ c w HN-15388 . ------------- TISSUES/OBSERVATIONS POLYMER PRODUCTS DEPARTMENT ' SPECIES: RAT ' SEX: MALE GROUP: III ANIMAL NUMBER; MODE OP DEATH; DAYS ON TEST: DAYS ON RECOVERY: 376 805 SD 12 0 376 821 SD 12 0 DOSE: INTERMEDIATE 376 376 376 376 376 838 851 867 812 813 SD SD SO SD SD 12 12 12 26 26 0 0 0 1-4 14 376 830 SO 26 14 376 857 SD 26 14 STERNUM ONNINNNNNN BONE MARROW ONNINNNNNN NOSE INFLAMMATION. ACUTE. MUCOSA/SUBMUCOSA. RESPIRATORY EPITH. N . N N N N N ' N N N INFLAMMATION, ACUTE, MUCOSA/SUBMUCOSA. VENTRAL MEATUS INFLAMMATION, FOCAL, SUBACUTE. MAXI LLOTURBINATE INFLAMMATION. SUBACUTE. MULTIFOCAL, RESPIRATORY TURBINATES --- ----_------------------ 0\ SQUAMOUS METAPLASIA. FOCAL, RESPIRATORY EPITHELIUM SQUAMOUS METAPLASIA. RESPIRATORY EPITHELIUM - \) OTHER 0-0-0-0-0-0-0-0-0- MANDIBULAR LYMPH NODE: HYPERPLASIA, LYMPHOID ' % TABLE VI ^ S.UBCHRONIC IMMOLATION STUDY ,, ^POLVMERPRODUCT^DEPARTME^r SPECIES: RAT TISSUES/OBSERVATIONS SEX: MALE GROUP; III ANIMAL NUMBER; MODE OF DEATH: DAYS ON TEST: DAYS ON' RECOVERY: DOSE: INTERMEDIATE 376 376 376 376 376 6)7 846 855 864 875 SD SD SD SD SD 96 96 96 96 96 84 84 84 84 84 LIVER " N L N N N FATTY CHANGE. DIFFUSE. CENTRILOBULAR - - - - _ FATTY CHANGE, FOCAL, MEDIAN LOBE FATTY CHANGE, INDIVIDUAL MEPATOCYTES,SCATTERED,CENTRILOBULAR INFLAMMATION, SUBACUTE, MULTIFOCAL NECROSIS. ACUTE, INDIVIDUAL HEPATOCVTES, CENTRILOBULAR NECROSIS. COAGULATIVE. ACUTE, FOCAL/MULTIFOCAL NECROSIS. COAGULATIVE, SUBACUTE, MULTIFOCAL KIDNEYS - - - . ----- - , - - - ---------- N N N L N ^1 CHOLESTEROL CLEFTS/REGENERATIVE TUBULES/INDIV. CELL NECROSIS Q CYST. FOCAL - - - P - GLOMERULONEPHROPATMY, CHRONIC - - - 1 - HYDRONEPHROSIS. UNILATERAL - - - - - PROTEIN DROPLETS, PROXIMAL TUBULES LUNGS - - - - - HEMORRHAGE, SUBACUTE. FOCAL/MULTI FOCAL HISTIOCYTOSIS. FOCAL/MULTIFOCAL INFLAMMATION, SUBACUTE. POCAL/MULTIFOCAL ' - - - - - LYMPHOCVTIC INFILTRATE, MULTIFOCAL, PERIVASCULAR POLVMORPHONUCLEAR INFILTRATE. MULTIFOCAL. PERIVASCULAR L L L N N - - - _ _ , - - - _ - - _ _ - 1 1 ) - - HEART N N N N N MYODEGENERATION, FOCAL/MULTIFOCAL, MYOCAROIUM - - - - _ PANCREAS ATROPHY. FOCAL, LOBULE INFLAMMATION,CHRONIC.INTERSTITIAL,WITH PIGMENTED MACROPHAGES THYMUS HEMORRHAGE. ACUTE. MULTIFOCAL SPLEEN ADRENAL GLANDS DEGENERATIVE FOCUS L N N L N - - - ] - 1 - - - .- N N N N N ----- N N N N N N" N N N N ----- HN-153B8 TISSUES/OBSERVATIONS THYROID GLAND CYST ULTtMOBRANCHIAL TRACHEA CYST SEX: TABLE VI gUBCHRONIC INHALATION STUDY POLYMER PRODUCTS DEPARTMENT SPECIES: RAT MALE GROUP: III ANIMAL NUMBER: MODE OF DEATH." DAYS ON TEST; DAYS ON RECOVERY: DOSE: INTERMEDIATE 376 376 376 376 376 817 846 855 864 875 SO SO SD SO SO 96 96 96 96 96 84 84 84 84 84 N 0 I 0 N ESOPHAGUS BRAIN N N N N N N N N N N STOMACH N N N N N DUODENUM N N N N N JEJUNUM N N N N N ILEUM N N N N N CECUM N N N N N COLON NEMATODE. LUMEN RECTUM NEMATODE LUMEN MESENTERIC LYMPH NODE URINARY BLADDER TESTES ATROPHY. ATROPHY. SEMINIFEROUS SEMINIFEROUS EPIDIDYMIDES SPERM GRANULOMA EYES TUBULES, TUBULES, BILATERAL UNILATERAL N N- N N N N N N N N N N N N N I.I N I N N N N N "'"'N N N N N N N N N N N N N N N N MN-15388 TISSUES/OBSERVATIONS STERNUM TABLE VI ,SUBCHRONIC INHALATION STUDY POLYMER PRODUCTS DEPARTMENT SPECIES: RAT SEX; MALE GROUP: III ANIMAL NUMBER; MODE OP DEATH: DAYS ON TEST: DAYS ON RECOVERY: DOSE: INTERMEDIATE 376 376 376 376 376 817 846 855 864 875 SD SD SD SD SD 96 96 96 96 96 84 84 84 84 84 N N N N N BONE MARROW N N N N N NOSE INFLAMMATION, ACUTE. MUCOSA/SUBMUCOSA. RESPIRATORY EPITH. INFLAMMATION. ACUTE. MUCOSA/SUBMUCOSA, VENTRAL MEATUS INFLAMMATION, FOCAL, SUBACUTE. MAXILLOTURBINATE INFLAMMATION. SUBACUTE, MULTIPOCAL, RESPIRATORY TURBINATES SOUAMOUS METAPL-ASIA. FOCAL, RESPIRATORY EPITHELIUM SOUAMOUS METAPLASIA, RESPIRATORY EPITHELIUM OTHER MANDIBULAR LYMPH NODE: HYPERPLASIA, LYMPHOID * END OF GROUP III N N N N N 2 > 0 33 0 m m z ci > m r z m D v r > > -I z >-i o < VI m -i i/i o Z r 7. D ^ > rr c - r > z 0 33 >^ 11 3:0 m D r -< n -o I ci n n 2 rn rn C 2 -1 D < -1 o < 2 rn (/) 3d < r < I m -i z S in 1) 3) fn 0 r 3 n vi 3 0 0 OVI 0 < -or -10 -i 0 r 0> 0 < 3 -i r- M 3> -D (/l rn m 0 m Sir-in nr 33 S I 00302) "Z I 3 < > >- 0 -1 0100 m 1-1 -n 0 0 20 00 & 1> -'- n n r 5-1 -( 0 31 i/) m ai n 3 n i z m c -n 2 -0 < > < > o r o fn TO -1 -1 Cl 3} 33 K M o pi 3) Z > 0 1> 2 (/I- o o mr r -< C 2 -< 0 (/) -0 1-1 0 (/) 1/1 r -< I n 0 r 2 c m i/> 33 r C 2 m -n in CD -1- 0 m . I- fi -1 3) 1-1 c -n l> i/i 0 -n m o r- a) r m o n c> -1 z 0 -n >n c 2 -< </> '- -i -i >- CD 0 33 n > -( C I ^ 3 n c n z > c r" m 33 r < 33 >- -I c r > -n -1 ^- 0 n; i- r -i m "' tn m 3 >; -1 0 -1 2 '* r c n i-' m n m -I - -1 3 r o 3 3) I z "n m C 33 3 -n n > > 33 n -l 0 a n 1/1 -i > -1 -i r >-< -) M 1- > c o - > -1 r n -n r -' m > o - -n -' r n a 0 -n ^ > c n 3 r r rr o z> 2 p -< -' -i C 0 -< 0) < c m 03 > > c r nc -\ r r- r~ > r -- m -f . -1 r- -1 n i/i c S *-* i-i o CD 1-4 3 ' -n -n o C -1 < 0 o 0 > r I 0 n mn r m n > 33 > VI O > r >- r \ S 3) - < 0 > i-i z 3 i-i D 0) 0 m c m n M z S 31 C < -i " r- > m < > 0 > 33 n in m S n r > c r n r a > z 0 3) tn -0 n 1 33 > 0 Cl m m - en in IZ 2 I Z Z 12 il2 I Z l IZ Z I I I I IZ i i iMr I Z Z l Z l IZ I Z Z 12 l IZ 12 Z 12 I- I Z 11112 I I I N) I- 12 Z I Z I IZ I 2 i i--i ir- i z i - i i i. r 12 2 - r Z 1-111 12 Z I Z I IZ 12 2 IZ 112 22 12 112 22 12 --1111- 111112 1 1Z Z 1 1- - | I- r 1-1 < fZn2n2i'm-''n2->n>->n3mi o3) n3) n 33 -n r -) -1 -\ -) -i -I <0/)0!/)0(/> 3 < '-''-' -' 3 o n n I/) tn wi > I ... 11 on oci -i > > > -i 2 2 Z i> ci ci o o n z rn ro rn C. > 3> - - C1C1 -) c c m in 1-1 -n o r c z on r- > > CD o n -n -I -l i- > - > n - - 2 n < r c o e M- tn m rn -< -t u rn < mc S - 1-1. tn 3> o c nc 3 > m r- 0 n -" m >CI > z BC > -l r r m 2 -l 0 fn -1-0 33 C- I >-' > f- -' -l fn 11 ^ o r- m -n -o o o 0) o o > o ri fn tn n -< > < c 23> -< f or c r n fn > r -~ < m 33 "cm -<S -I M n r 1/1 n 0 -f- > n M -i > n n -l r om m >00> 30 > Z n z 31 > -) rn r 31 o M r n 0 m 0 -" tn M fn 3 o22ooT) r 03 Z c r -33l > >- 33 r 0 0) c <" 31.-4 0 C ro fn m 3 ni/i > ffl 0-< 3-l: fn 33 fn 33 <: r > 3) mu - tn M ~j 0 M 0 0 01 CD 0} - t/1 M '4 0 M O CD 0) m u - (n in '^ 0 M 0 6 01 CD U - M 01 ^ 0 N 0 (0 01 ft r m S <? r CD < n 3 I m 3) 0 73 0 3) Z 1 0 W V t-t c -0 33 n H o m o -'(-10 -* c 2 1-1 in n < (/) -< > " 1/1 1- 3> < 33 0 > m -1 M -f -0 0 > Z 33 -1' tn 3 -1 m C z 0 00 -f < 1/1 CD U - VI ^ ^ 0 N 0 <0 01 i iMr CD U --- M W A 0) 0 -' -~1 t>0) I I I I I I CO f- CD U -- M 01 M -^ 6 0) 0 & 0) CD U -- M I/) C<1 ! 6 0) 0 U 01 CD U -- M tfl 01 -J ^ 01 0 CD 01 CD U -i -- M tfl CD A 0) 0 0 01 CD U A in in - ~i -- co o A 0) CD CJ & ui in -- ~j -- Cil C3 U' 0) CD u A ui in Q) 'J -- c*) o M en CD U A (Jl t/1 01 ~J --U00 0 CD U ^ ui in ui J -- c.) o Q) 01 Company Sanitized. Does not contain TSCA CBI .HN-15368. TISSUES/OBSERVATIONS TABLE V][ I SUBCHRONIC I :NHALAT ION STUC POLYMER PROCUCTS DlEPAFiTMErIT SPEC:IES: R:AT SEX: MAL E GROUP;! IV DOSE;; HI:GH ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: DAYS ON R'ECOVERV: 376 376 376 376 376 376 376 376 37 B20 828 854 859 879 819 824 833 85 . SO SD SD SD SD SD SO SD S 12 12 12 12 12 26 26 26 2 0 0 0 0 0 14 14 14 1 THYROID GLAND CVST ULTIMOSRANCHIAL CYST TRACHEA ESOPHAGUS BRAIN STOMACH N N N 0 I N N N L - - - - - P 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 DUODENUM N N N N N N N N N JEJUNUM ILEUM CECUM N N N N.N N 0 N N N N N N N N N N N N N N N N N N N N "COLON NEMATODE, LUMEN RECTUM NEMATODE, LUMEN MESENTERIC LVMPH NODE 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 . URINARY BLADDER TESTES ATROPHY. ATROPHY. SEMINIFEROUS SEMINIFEROUS TUBULES, TUBULES, BILATERAL UNILATERAL EPIDIDVMIDES SPERM GRANULOMA 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 EYES NNNNNNNNN HN-1S3BB^ TISSUES/OBSERVATIONS '1:ABLE \ JI SUBCHRONIC^ INHA.LA1ION SPE CIES; FiAT r :( STUC SEX: MAL E GROUP: IV DOSE:; HI[GH ANIMAL NUMBER: MODE OF DEATH; DAYS ON TEST: DAYS ON RECOVERY: 376 376 376 376 376 376 376 376 3 820 S2S 854 S59 879 819 824 833 8 . SO SO SO SD SD SD SD SD 12 12 12 12 12 26 26 26 0 0 0 0 0 14 14 14 STERNUM N N N N N N N N BONE MARROW N N N N N N I N NOSE INFLAMMATION. INFLAMMATION. INFLAMMATION, INFLAMMATION, ACUTE, ACUTE. FOCAL, MUCOSA/SUBMUCOSA. RREESSPPIIRRAATTOORY EPITMH. MUCOSA/SUBMUCOSA. V'ENTRAL M"--" MtEt=MATI UU,S? SUBACUTE, MAXILLOTUIRBINATE SUBACUTE. MULTIFOCAL, RESPIRATORY TURBINATES SQUAMOUS METAPLASIA, FOCAL, RESPIRATORY EPITHEELLIIUUMM SQUAMOUS METAPLASIA, RESPIRATORY EPITHELIUM OTHER MANDIBULAR LYMPH NODE: HVPERPLASIA, LYMPHOID N N N N 0 N N N - - - - - - - TABLE VI ^ _ajBCHRQNIC INHALATION STUDY _ HN-15388_ -"POLYMER PRODUCTS DEPARTMENT ^ SPECIES: RAT SEX: MALE GROUP: IV DOSE; HIGH TISSUES/OBSERVATIONS ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY: 376 376 376 376 376 816 826 842 645 B6S . SO SO SO SO SD 96 96 96 96 96 84 84 84 84 84 LIVER L L N N L FATTY CHANGE, DIFFUSE, CENTRILOBULAR - - - - 1 FATTY CHANGE, FOCAL, MEDIAN LOBE - _ - - - FATTY CHANGE, INDIVIDUAL HEPATOCVTES.SCATTERED.CENTRILOBULAR - , - - - INFLAMMATION. SUBACUTE. MULTIFOCAL 1 - - - 1 NECROSIS. ACUTE. INDIVIDUAL HEPATOCVTES. CENTRI LOBULAR NECROSIS. COAGULATIVE, ACUTE. FOCAL/MULTI FOCAL NECROSIS. COAGULATIVE. SUBACUTE, MULTIFOCAL - - - - - KIDNEYS " N L N L N ----- J CHOLESTEROL CLEFTS/REGENERATIVE TUBULES/INDIV. CELL NECROSIS 0^ CYST. FOCAL GLOMERULONEPMROPATHV, CHRONIC - - - 1 - HYDRONEPHROSIS, UNILATERAL - - - - - PROTEIN DROPLETS, PROXIMAL TUBULES - 2 - - - ----- LUNGS L L N N N HEMORRHAGE. SUBACUTE, POCAL/MULTI FOCAL HISTIOCVTOSIS. FOCAL/MULTIFOCAL INFLAMMATION. SUBACUTE. FOCAL/MULTIPOCAL LVMPHOCYTIC INFILTRATE. MULTIFOCAL, PERIVASCULAR POLYMORPHONUCLEAR INFILTRATE, MULTIFOCAL. PERIVASCULAR HEART MVOOEGENERATION. FOCAL/MULTIFOCAL, MYOCARDIUM PANCREAS - , - - - - , - - - ) _ - - - ----- N N L N N - - , - - ----- N N N L N ATROPHY. FOCAL, LOBULE - - - , - INFLAMMATION,CHRONIC,INTERSTITIAL,WITH PIGMENTED MACROPMAGES - - - - - THYMUS HEMORRHAGE. ACUTE. MULTIFOCAL SPLEEN ADRENAL GLANDS DEGENERATIVE FOCUS N N N N N ----- N N N N N N' N N N N ----- TABLE VI SHRONIC INHALATION STUDY POLYMER PRODUCTS DEPARTMENT SPECIES: RAT TISSUES/OBSERVATIONS THYROID GLAND CYST ULTIMOBRANCHIAL CYST SEX: MALE GROUP: IV DOSE: HIGH ANIMAL NUMBER: MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY: 376 376 376 376 376 616 B26 842 845 868 SD SO SD SD SD 96 96 96 96 96 84 84 84 84 64 L 0 0 0 L P P TRACHEA N N N N N ESOPHAGUS N N N N N BRAIN N N N N N STOMACH N N N N N DUODENUM N N N N N JEJUNUM N N N N N ILEUM N N N N N CECUM N N N N N COLON NEMATODE. LUMEN N N N N N RECTUM NEMATODE, LUMEN MESENTERIC LYMPH NODE URINARY BLADDER N N N N N N I N N. I N N N N ' N TESTES ATROPHY, ATROPHY. SEMINIFEROUS SEMINIFEROUS TUBULES. TUBULES, BILATERAL UNILATERAL EPIDIDYMIDES SPERM GRANULOMA N N N N L 1 N N N N EYES 8Z 0 z CD ^ ^ 0 0 -j * J in Z m in 2 m (/I (/) -t t-1 fr-1 1^ m m 3> M m > 31 Z ZZZ z c 00 mi z z c c -n 11 S c ni 0 0 >>r r r r > a ui 1-1 3 S > f ~ s ^' 0 0 3) 003333 S Tl c C C S 3 0 (/>S>3>> r l/) t S I/I 0 > "t '"f "^ ~4 m s 3 S *-< n -- w X 0 m ni o o < oo c r -< -1 Z Z Z Z t D < -< 3 O -D i- >>.... tt D r r-1/1 -n > > 0 < I T> c z ono w </> n> n c c I/I Z p - " > > -l -< > > n r rn m 0 - - - c- m 3) -n -\ m vis S m c o- cc I M n Bnn < o > s >oo D " r c (-)(/)</) fn 31- r 31 -cI'is^ -0 > -f -< 73 i m in wi r o m "n- c c > 31 (/) 0 (DO) (/) < D 3 0 2 3 1-4 -" > > c c > rn a r- > r> n - -0 M >- 00 -<oa> r >-< -) r in in < I 31 m 0r--l 3 rn < M V r -o c < x >-< ro " v m m -' -l 0 C.-O 33 (B 2 V) (-* S > 1-1 -\ o 0 -) z a >-i I 0 > > 3) -<rSO m 3) > r <m -< M c S -c i rn 3i > < a -< en cm - in -D z - > -( -l I m yi VI > m 003 z x 0 0 ^i f (/) w rn 000 > s r > ?n z z -n r z rn 31--1 0 c fn m m 5 o (/) > 0) D in c r 0) < 0 m 0-1-1 < I m z < " 3) Cl n X 31 0 3) z 0 </) "0 t-t C c -0 31 n o m o i n o d -' c z t-1 m n I S 03 0) < </> -< -< ca (c to -- ^ " V) & 0) 0 0) G) > I I I I I IZ m u z m (D (/i M s ^ 0) 0 01 0) 3 3) 0 -1 > m -1 D > z I I I I I IZ CD Gl Z (B(D</) A, '4 6 0> 0 KJ 01 3) -1 (/l 5 -\ m ~ z 0 CD U 0 z z CD (0 (/) Jk ^J 0 t. 0) 0 01 0) </1 m OD U -l < 1 ., I I I I I IZ z m (0 1/1 0) i J& CD 0 CD 0> Company Sanitized. Does not contain TSCA CBI - 6L fr8-l7Z 'ON ia0d3a ASOIOHlVd 1V3INI13 IA )(ION3ddV Company Sanitized. Does not contain TSCA CBI 190 VOS1 uiEluoojou-saan'paziilues Auedluoo ESTttUSHEDISO; E. I. DU FONT DE NEMOURS 5t COMPANY INCORPORATED HASKELL LABORATORY FOR TOXICOLOGY AND INDUSTRIAL MEDICINE P.O. BOX 50, ELKTON ROAD NEWARK, DELAWARE 19711 CENTRAL RESEARCH AND DEVELOPMENT DEPARTMENT CLINICAL PATHOL'OGY REPORT NO. 24-84 MEDICAL RESEARCH PROJECT N0.| HASKELL LABORATORY NO. 15388 FEBRUARY 28..1985 Summary. Male Crl:CD(SD)BR rats were exposed, by inhalation, toj lat concentrations of 0 (control), 0.0076, 0.058 an_d _0_.4_8 mg/L. Compound-related effects observed in high-dose (0.48 mg/L) males at the 0-day recovery period included alterations in several hematologic and clinical chemical parameters. The hematologic changes included an increase in red blood cell count, hemoglobin and hematocrit and a decrease in mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. The clinical chemical changes included an increase in alkaline phosphatase, urea nitrogen, urine volume and pH and a decrease in urine osmolality and serum cholesterol. These effects were not present at any of the subsequent recovery periods. The 0.058 mg/L exposure concentration was interpreted to be a no-effect dose level for the hematologic and clinical chemical parameters measured under the conditions of this study. Procedure Four groups of 20 male Crl:CD(SD)BR rats were exposed, by inhalation, for six hours per day for 10 days to Telomer B sulfonic acid at concentra tions of 0 (control), 0.0076, 0.058 and 0.48 mg/L. After the ninth exposure, an overnight (approximately 16-hour) urine specimen was collected from ten rats per group to measure volume (VOL), osmolality (OSMOL), pH and urobilinogen (UROBL); and to determine the presence of blood, sugar (glucose), protein, bilirubin and ketone (acetoacetic acid). The appearance (color and transparency) was recorded and the sediment from each specimen was microscopically examined. After the tenth exposure (0-Day Rec), and at the 14-day recovery period (14-Day Rec) and 41-day recovery period (41-Day Rec), blood was taken from the tail of ten rats per group for measurement of erythrocytes (RBC), hemoglobin (Hb), mean corpuscular volume (MCV), platelets (PLAT), leukocytes (WBC) and relative numbers of neutrophils (Neut), band neutrophlls (Band), lymphocytes (Lymph), atypical lymphocytes (Alym), monocytes (Mono), eosinophils (Eosin) and basophlls (Baso). Absolute numbers of various types of leukocytes were calculated from the leukocytic data. Hematocrit (Ht), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were calculated from the erythrocytic data. Serum activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and concentrations of urea nitrogen (BUN), creatinine (GREAT), total protein (TPROT) and cholesterol (CHLOS) were also measured. After each sampl-ing time, five rat-s f-rom eachgroup were then killed for pathologic evaluation. Following an 84-day recovery period (84-Day Rec), the hematologic and clinical chemical (serum and urine) measurements were repeated on the five remaining rats in each group. Statistics Hematologic and clinical chemical data were statistically analyzed using a one-way analysis of variance for each sampling time. When the F-test was significant, least significant difference (LSD) and Dunnett tests were used to compare the control" group and the groups exposed to Telomer B sulfonic acid. Significance was judged at the 5% probability level using Dunnett criteria. Results Results of hematoiogic and clinical chemical measurements are summarized in Tables I, II and III, statistical analyses in Tables IV and V. Data for individual animals are listed in the computer printouts attached to this report. A legend, preceding the computer printouts, defines terms and criteria used for urinalyses. At the 0-day recovery sampling time, rats in the high-dose (0.48 mg/L) group had an increased erythrocyte count, hemoglobin and hematocrit. Mean corpuscular hemoglobin concentration was increased for the intermediate-dose (0.058 mg/L) rats and decreased for the high-dose rats. Decreased mean corpuscular hemoglobin and platelet count were observed for rats in the high-dose group. Serum alkaline phosphatase and serum aspartate aminotransferase activities and serum urea nitrogen concentration were increased for the high-dose rats. Rats in the high-dose group had decreased serum cholesterol concentration. Urine volume and pH were increased for rats in the high-dose group. Decreased urine osmolality was observed for the high-dose rats. 1 Company Sanitized. Does not contain TSCA CBI At the 14-day recovery sampling time, rats in the high-dose group had decreased hemoglobin, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. Urine pH was decreased for the intermediate- and high-dose rats. At the 41-day recovery sampling time, rats in the high-dose group had a decreased erythrocyte count. The platelet count was increased for the high-dose rats. Decreased serum alanine aminotransferase activity was observed for rats in the low-(0.0076 mg/L) and high-dose groups. At the 84-day recovery sampling time, rats in the intermediate- and high-dose groups had increased leukocyte counts and absolute numbers of lymphocytes. The absolute number of neutrophils was increased for the high-dose rats. Serum urea nitrogen concentration was decreased for rats in the high-dose group. Discussion and Conclusions There was a statistically significant increase in red blood cell count, hemoglobin, hematocrit, alkaline phosphatase, urea nitrogen, urine volume and pH in the high-dose animals at the 0-day recovery sampling time. At this time period, there was also a statistically significant decrease in mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, urine osmolality and serum cholesterol in the high-dose animals. The other hematologic and clinical chemical parameters shown to be statistically significantly changed were within the range of expected biological variation and were not related to the administration of the compound. The 0.058 mg/L exposure concentration was interpreted to be a no-effect dose level for the hematologic and clinical chemical parameters measured under the conditions of this study. DRH:bl CP 3 2/28/85 Report by:^JLjML^.CL- ^-- /^Wt Donna R. Holt Technician Approved by: (1A^JJS^OjLJ^. I^ILS^C^ Charlotte M. Keenan Acting Coordinator Clinical Pathology Section 8Z Company Sanitized. Does not contain TSCA CBI TESTS RBC x1o6/uL Hb g/dL Ht % MCV fL MCH Pg IEXPOSED T ABLE I SUMMAFlY OF HE:MATOLOG 1C FINE)INGS.FCRMALL RATS BY INE1ALATIOK1 T0{11 (FOR 10 GRCUP MEAKIS ^ E y m ANpTsTANDARE IONS(SE>) DAYS DOSE (rng/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-DJ?lY REC 7.4K 0.57) 7.28( 0.54) 7.26( 0.47) 8.55( 0.24) 15.6( 15.3( 15.8( 16.5( 43.( 42.( 42.( 49. ( 57.( 57.( 57.( 57.( 21.( 21.( 22.( 19.( 0.9) 0.5) 0.7) 0.7) 3.) 3.) 2.) 2.) 1.) 1.) 1.) 2.) 1.) 1.) 1.) 1.) SAMIPLING 1IME 14-D'AY REC 41-CAY REC 84-EIAY REC 7.12( 0.56) 7.09( 0.44) 7.48( 0.33) 7.17( 0.55) 7.92( 7.56( 7.59( 7.29( 0.45) 0.44) 0.52) 0.48) 8.15( 0.46) 7.7K 0.79) 8.49( 0.96) 7.84( 0.33) 15.8( 0.5) 15.9( 0.5) 16.0( 0.5) 14.8( 0.6) 15.5( 0.4) 15.5( 0.7) 15.5( 0.5) 15.0( 0.7) 16.0( 0.3) 15.5( 0.6) 15.8( 0.8) 15.1( 0.8) 41.( 2.) 40. ( 2.) 42. ( 1.) 40. ( 3.) 57. ( 2.) 57.( 2.) 56.( 1.) 55. ( 2.) 22. ( 2.) 22.( 1.) 21.( 1.) 21.( 1.) 43.( 2.) 41.(. 2.) 41.( 3.) 40.( 2.) 53.( 2.) 54. ( 1.) 54. ( 2.) 54.( 2.) 20.( 1.) 21.( 1.) 21J 1.) 21.( 1.) 41.( 1.) 39. ( 4.) 43.( 4.) 40.( 3.) 49. ( 1.) 51.( 2.) 51.( 2.) 51.( 2.) 20. ( 1.) 20. ( 2.) 19.( 1.) 19.( 1.) u .... .... OS '- '- r- m (M CM oo t-- <> >- 0 >> CM 3- < Q - CM r- no o o t-- [-- ma-mm ooo(M*- .='-rmin CM CM '- o u .... .... e; !>-' --(M- (cMr>C'M-'-incyin> Q '" '" '" '" M sr S E-< u U CxJ so; 1-1 ^J >-< o, < S Q WaT-- td OS a; t--oococo mmc-im . . . . ^*s ^-^ ^-^ ^~\ (Mc\i-c\) ^^'^'^ v o\ ao t-- mmmm ^^^^ ,-fVJ,-T- oin-t3--"con'>^oo o\ o o '-- ^ - - . . . . /TMs ^"^ ^^ ^^ mmcMvo \o (M vo cy> -<->- '^^'^^ --^tcr>o cooioo-o^ooco '^^^' <oj -0- t(n-' T- o c--t'-com <yim-cr> mmmpo c\)-3'(\)C\j cy> co co t-- M.- M.-3 oor^--ocoooo oo\t--ocoo oo Q0h^O o0o0i0n3co- oOoOmOoao- '-^ 0000 0000 J CO \ H U J E-i ro co z: o < o U E-i U \ S CO J OL, rX - 84 Company Sanitized. Does not contain TSCA CBI <J> Ed EC i>-i a: Q 0 CT m m ^ ---- m m i-- M OJ CM C-- o-> CM r-m in t-- t- T-- 0 0 SO 0 0 cr> t-- t~- 0 in so CM '- CM a- CM '- - - (M CM 0 in CM t-- CO r3- in (y -- -- =r -- a- 0 0 o\ w oo CO 0 CM 0 0 0 on 0 3- t~- a- c-- 00 in oo >-1 T-- m i^- 0 CM CM CM a- t-- so en SO CO C-- t- t- ffn- < ^---- T-- CM t-- r~ cr> CM m a- o so r-- r-- CM Q CM CM in CT\ 0 0^1 PQ 0 so t^ \o in <- CM in a- '- en m oo CM a- in a- cy> m CM ''-- m r- so co cy. t-- m '- CM '- '- o t- (y> CM i^i co o o^ a- '- (M CM m m o o o t-o o o in co so oo co CM in so in - o o o *- CM a- CM t-in f"i t-- CM c-- in in co o in t-- o-i'-- '-- o o-> CM oo o in t- CCMM a<-- in a- co so '[^- a'-- cy> 0 ^ m in ON in CM c- C- o'> m m ;T sr r-- V-- T-- T-- f- CO vO 00 t~- in CM t~0 a- a- SO '-- '-- '-- CO 01 0^ on t~ ^- 00 [- in t^ ON 00 CM CM CM CM 0 000 0 000 a- cr> o CO a- ON in at^ o a- in '-- m a- CM t--- 00 CM m s0 [-- CO 0 a- so a- 00 0 0 V-- t- a- CM - 00 a- (y> CM v-~ '-a- in a- rCT-i a- 0 ^-- u m bJ a 0 CO m (?> 0 CM 0 0 OS CO CM CM m CM 0 CO t-- a- >- 0^ in in < Q o\ o\ in t-- 00 a- 0 * m CO o mo o a- CM nj CM ro CM CM <-- s-- CM SO cy> CM <M CM m c- CO fl m PO in ro 0 so crsoo '- m CM t- CM a- a\ m CT> CO in a- rsj in - <y 00 co cy> CM 0 0\ 00 00 m so t~- 0 00 CM sO a- o a- CM CM *- 0 SO 0 0 0 C-- 00 0 o o in oo o o o a- 0000 0 SO 0 0 0 t-- 00 0 o o in co o o o a- oooo 0 SO 0 0 0 t^ 00 0 o o in co o o o a- oooo o so o o o t-- oo o o o in oo o o o a- 0000 o so o o o t-- co o o o in oo o o o a- oooo -3 I M ' E-< m K> u o bd E-< 61 p x 3 U a m Z 3: t o x c u (B a CQ s 85 S: A Q. X E " 8-.CQ J S bt E X >> C-> r-f 03 '3: :2 Company Sanitized. Does not contain TSCA CBI U .. .... o.o.o.o. M OS . . oj'-ioin ft '- >H in in t-- cr> o o'' cy> <Q >a-!' CO CM t^ - CM 0 C0 M 0m Q 0 .... .... .... oooo oa-om ;3- co '-(M^om - =! CM CM \o t-- (M in '- CM CM in in (M CM u .... .... .... o; >-i \o '^o \o <7> cr>t-=ro c^o-ocoiro>-=mf OCMOO a'^- <3; CM OJ (M Q r- CM S hj s 1-1 ^-< u zee M .-] >-" OL. < S Q ocrm>cmy>cmoo - CM oj ^^^ ^ criinooo srrin- '^ -dr-- ocr>'^-Do3a-t--- <- '- '^ ^ ^ ^ -ifai-t^-o-osro om'-cCMM O ^^^ . oooo COS? '- . . . . y3C\ioi- '- ^ CM en . . . . mCM coonc3'oo o.o.o.o. .... .... .... t-\0lf>0 OOOO til CC 0 0 \0 ^- <>-l c*--- 1C0M or-\ mo >o co vo oooo o s'-rirt-i=irr>\oin co<?>oo ar \o in in ^- in 10 M --^ co j 0 Q -b,0 E 0 0 0 0 0 C~- 00 0 o o in co 0 00V 0000 0 >> 0 0 0 t-- CO 0 o o o o in co o =r oooo 0 10 0 0 o c~ co o 0o0o0o3o- o o in oo C/1 ttt C <l ^ !-> o x r-1 X o x en c u n u m o u 0 CQ o m co m E- M 5 OQ s 86 Company Sanitized. Does not contain TSCA CBI TESTS ALP U/L ALT U/L AST U/L BUN mg/dL I I TABLE SUMMARY OF CLINICAL ;HEMICAL FINDINGS FOR MALE RATS EXPOSED BY INHALATION TOJ GROUP MEANS At BBHJ^ iitiraa'l noNsTsD) 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-DA Y REC 191.( 62.) 199.( 206. ( 325. ( 52.) 49.) 48.) 37.( 5.) 39.( 7.) 44.( 11.) 44.( 8.) 87. ( 14.) 83.( 12.) 91.( 15.) 108.( 17.) 16.( 3.) 17.( 2.) 16.( 3.) 29. ( 4.) <3AMiPLING TIME T 1-D AY REC 4 1-D AY REC 171 .( 179 .( 196 .( 215 .( 35 .( 34 .( 36 .( 36 .( 76 .( 75 .( 79 .( 70 .( 17 .( 17 .( 17 .( 19 .( 58.) 56.) 38.) 59.) 4.) 7.) 5.) 5.) 11.) 10.) 15.) 11.) 3.) 2.) 3.) 4.) 131 .( 151 .( 157 .( 152 .( 40 .( 32 .( 37 .( 33 .( 76 .( 73 .( 76 .( 77 .( 17 .( 17 .( 17 .( 17 .( 30.) 40.) 42.) 55.) 7.) 4.) 4.) 6.) 12.) 12.) 14.) 11.) 2.) 1.) 2.) 2.) 84-D,AY REC 97. ( 134.C 126.( 120.( 37.) 41.) 56.) 73.) 34.( 5.) 29.( 5.) 43.( 25.) 35.( 11.) 66. ( 11.) 60. ( 6.) 83.( 35.) 71.( 17.) 20. ( 4.) 19.( 1.) 19.( 3.) 15.( 2.) u QS >-i < Q ^r oo u cc >-i a; Q '-- 3' [xj s M E-i u Sos M _l>^ o.; a; Z: Q cosr '-- in o a- 'o oo.oo.oo.oo. m cr> t-- a" ^o^ovOtf? * oooo o.o.o.o. -3-\oot>- 0 0 00 ir^ oo i-- ir> so^o^o^o oooo . . . . vooo^ooa-to^- oooo cyicr'000 mmin^o OOOO . . . '--a-mro '--ooo . . . . iri o t-- ff> ^0 &'- P"-- ^0 . minvo-a- oooo ^^i a" CM '-- .. ^0 <0 \Q \Q . . . . ^-a-oom oooo . . . . oj'-'-io \0 VO ^0 vO . . . . mro'^--oc\vj o'- . '-c-- oj .a- in '~~ 0^ 0^ ^ . . . . pQ(y>cr>(\) ^T--- ^. CT^ ,-- pn ^Q \Q ^-- \Q . . . ro -- -- -r-- .o\ . . . . -c\jfn<y> ^"- ^0 vD ITt .... .... oooo oooo ooo*- M t-- in vo =r CMrnmin os mf~'~-inio >- < l o =rcr>f"i^ inir>o\o 0000 . . . . <y> o '-- (M in'o>'> . . . . ttT- i(^y\-oina'-\ 0^ td--s M _3 0^000 0 t-- CO 0 OOlTtOO 0O^v-O0O0O0 OOlTlOO 0Ot^--0O0Q0O OOlnco QUO 0003- 0003- 0003- '-^ oooo oooo oooo W E-i J E-i CO J E-" < T3 0 -J 0 O M M \ K o J -^ M CC tlO &. ^ X hO E-" U E E-i hO U E 88 Company Sanitized. Does not contain TSCA CBI TESTS VOL mL OSMOL mOs 03 . '43 pH UROBL mg/dL RATS II T/IBLE I EXSPU<13WSAERDY BOYF INCHLAILNAK'nSAoLN UfRoH^f--NAL'ysis FII^IDINGS IFO^RFOMARLE 10 GRC)UP MEA]US AND. cTAN ^ffiviAlJONS(SlD) 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-D/IY REC 7.2( 3.7) 5.2( 1.6) 7.5( 3.3) 11.9( 2.5) 1714.( 1795.( 1610.( 850. ( 296.) 350.) 389.) 171.) 7.3( 0.7) 6.8( 0.6) 7.0( 0.7) 8.3( 0.7) 0.9( 0.3) 0.9( 0.3) 1.0( 0.0) 0.6( 0.5) SA(11PLI NG riME 14-r)AY REC 41-r)AY REC 84-E)AY REC 13.2( 12.4( 12.5( 12.0( 4. 3) 4. 5) 4. 5) 1. 8) 13.5( 4.9) 13.8( 5.0) 13.3( 4.6) 13.5( 7.0) 13.5( 17.4( 16.3( 17.0( 6.4) 13.7) 5.4) 9.0) 1447.( 1316.( 1566.( 1538.( 406 .) 411 .) 335.) 312.) 1895.( 1633.( 1821,,( 1626.( 370.) 373.) 523.) 467.) 1784.( 1602.( 1364.( 1446.( 756.) 663.) 361.) 551.) 8.K 0. 7) 7.6( 0. 5) 7.K 0. 6) 7.2( 0. 4) 7.2( 0.4) 7.3( 0.5) 7.0( 0.5) 7.0( 0.5) 7.4( 0.5) 7.0( 0.0) 7.4( 0.5) 7.2( 0.4) 1.0( 0. 0) 0.8( 0.4) 1.0( 0.0) 1.0( 0.0) 1.0( 0.0) 1.0( 0.0) 1.0( 0.0) 1.0( 0.0) 0.3( 0.4) 0.6( 0.5) 0.6( 0.5) 0.5( 0.5) I I I TABLE (continued) SUMMARY OF CLINICAL URINE ANALYSIS FINDINGS FOR^MALERATS EXPOSED BY INHALATION TOJi^------^------------------B^^ ^ DAYS Sampling Time Pose (mg/L) Measurement Blood Number Positive Sugar (Glucose) Number Positive Protein Number Abnormal _> + 3 Bilirubin Number Positive Ketone Number Positive Appearance (Color and Transparency) Microscopic Number Abnormal 0-Day Recovery 0 .0076 .058 .48 1/10* 3/10 1/10 0/10 2/10 3/10 1/10 3/10 0/10 0/10 0/10 0/10 6/10 3/10 2/10 3/10 9/10 8/10 10/10 0/10 0/10 0/10 0/10 0/10 4/10 1/10 1/10 0/10 14-Day Recovery 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 2/10 7/10 6/10 9/10 8/10 9/10 8/10 0/10 0/10 0/10 0/10 6/10 1/10 4/10 3/10 * Number of abnormal or positive findings/number of individual specimens examined 90 Company Sanitized. Does not contain TSCA CBI I I I TABLE (continued) SUMMARY OF CLINICAL URINE ANALYSIS FINDINGS FOR MALE RATS EXPOSED n'i1 iiiihMiinii \i}f^mfmmwv\^\' 1111^1' Sampling Time Dose (mg/L) Measurement Blood Number Positive Sugar (Glucose) Number Positive Protein Number Abnormal 2+ 3 Bilirubin Number Positive Ketdtie Number Positive Appearance (Color and Transparency) Microscopic Number Abnormal 41-Day Recovery 0 .0076 .058 .48 0/10 1/10 0/10 1/10 1/10 2/10 1/10 2/10 1/10 1/10 0/10 2/10 2/10 2/10 6/10 6/10 10/10 10/10 10/10 9/10 0/10 0/10 0/10 0/10 1/10 1/10 2/10 0/10 84-Day Recovery 0 .0076 .058 .48 3/5 4/5 3/5 5/5 3/5 3/5 3/5 5/5 2/5 0/5 0/5 0/5 2/5 2/5 1/5 0/5 4/5 3/5 3/5 4/5 0/5 0/5 0/5 0/5 0/5 2/5 0/5 1/5 91 Company Sanitized. Does not contain TSCA CBI SUMMARY OF CHEMICAL TABLE IV STATISTICAL ANALYSES OF HEMATOLOGIC AND CLINICAL FINDINGS FOR MALE RATS EXPOSED BY INHALATION TO Sampling Time Statistic 0-Day Recovery p* Dunnett Measurement Hematology RBC Hb Ht MCVMCH 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 . 0.000 ** ALT 0.135 AST 0.003 ** BUN 0.000 ** CREAT 0.057 TPROT 0.120 CHLOS 0.000 ** Clinical Chemistry (Urine) VOL 0.000 ** OSMOL 0.000 ** pH 0.000 ** UROBL 0.069 14-Day Recovery p Dunnett 0.270 0.000 ** 0.353 &.-32-3 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-statistic ** = Significantly different from controls at 57, 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 Sampling Time Statistic 41-Day Recovery p Dunnett Measurement Hematology RBC Hb Ht MCV MCH MCHC PLAT WBC Neut Band Lymph Alym Mono Eosin Baso 0.045 ** 0.170 0.053 0.789 0.100 0.179 0.014 ** 0.289 0.259 0.404 0.472 0.168 0.412 0.316 0.554 Clinical Chemistry (Serum) ALP 0.532 ALT 0.008 ** AST 0.933 BUN 0.980 GREAT 0.496 TPROT 0.511 CHLOS 0.686 Clinical VOL OSMOL pH UROBL Chemistry (Urine) 0.998 0.425 0.382 1.000 84-Day Recovery p Dunnett 0.313 0.165 0.207 0.375 0.302 0.050 0.335 0.000 ** 0.000 ** 0.418 0.005 ** 0.611 0.552 0.500 1.000 0.727 0.487 0.355 0.048 ** 0.299 0.412 0.227 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 T0| Sampling Time 0-Day Rec Measurement Hematology RBC Hb -BfeMCH MCHC PLAT WBC Neut Lymph +IV -t-IV -t-I-V +IV +111, IV -HV Clinical ALP ALT AST BUN CHLOS Chemistry (Serum) +IV -f-IV +IV IV Clinical VOL OSMOL pH Chemistry (Urine) +IV + IV +IV 14-Day Rec +IV +IV 4-IV +III,IV j> 1-Day jRec____84-Day Rec -HV +IV +11,IV t-III.IV HV +III,IV +IV -t- = Significantly higher than controls by Dunnett criteria + = Significantly lower than controls by Dunnett criteria Group II III IV Designation and Dose Concentration = Low Dose (0.0076) = Intermediate Dose (0.058) = High Dose (0.48) (mg/L) 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 = LY = DY = A = DA = G = BL = R = C = CL = PPT = F = FEC = Yellow Light Yellow Dark Yellow Amber Dark Amber Green Bloody Red Clear Cloudy Precipitate Feed Feces Abbreviations for Descriptive Terms Used for Microscopic Evaluation of Urine TNTC Epith = hpf = Ipf = RBC = WBC = (99-99) = Epithelial Cells high power field low power field Red Blood Cells White Blood Cells Too Numerous to Count Definition of "Normal" and "Abnormal" Designations Used for Gross and Microscopic Appearance of Urine Appearance Color Microscopic Red Blood Cells Normal Light to dark yellow or amber Average of 0 to 4 red blood cells per high power field Abnormal Color other than yellow or amber Average of more than 4 red blood cells per high power field Casts None observed Average of more than 0 per low power field Epithelial Cells White Blood Cells Average of 0 to 9 per high power field Average of 0 to 9 per . high 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 15388 HASKELL CODE^QfQ " DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 07/20/84 ANIMAL?: 376825 376835 376839 376840 376841 376849 376863 376870 376872 376873 RBC x10/uL 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 Ht % 42. 40. 43. 45. 37. 41. 44. 44. 50. 42. AVG. S. D. S-. E. 7.409 0.570 0.180 15.56 0.90 0.28 42.7 3.3 1.0 SPECIES: RAT BIRTH DATE: 05/14/84 MCV MCH MCHC PLAT fL Pg g/dL X1Q3/UL 57. 21. 36. 1068. 58. 23. 38. 952. 56. 21. 37. 984. 58. 20. 35. 716. 58. 22. 38. 1030. 57. 21. 37. 1008. 58. 21. 35. 842. 57. 21. 37. 876. 58. 21. 35. 1044. 55. 21. 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 SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376804 376806 376810 376818 376822 376823 376844 376852 376876 376881 RBC xlO^uL 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 Ht MCV % fL 42. 57. 42. 56. 40. 59. 36. 58. 41. 59. 42. 57. 43. 56. 43. 58. 44. 55. 47. 57. MCH MCHC PLAT Pg g/dL x1o3/uL 21. 37. 814. 23. 40. 1032. 22. 37. 758. 23. 40. 22. 38. 802. 984. 21. 37. 20. 35. 21. 35. 20. 35. 936. 728. 876. 776. 20. 34. 720. AVG. S. D. S. E. 7.275 0.542 0.171 15.32 0.53 0.17 42.0 2.7 0.8 57.2 1.3 0.4 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 MR: COMPOUND:^____ PERIOD: 0-DAY REC SEX; MALE 15388 HASKELL CODE:(JH DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SAMPLE DATE; 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376805 376812 376813 376821 376830 376838 376851 376857 376867 376874 RBC xlO^uL 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 MCV % fL 46. 56. 41. 58. 43. 58. 39. 57'. 42. 57. 41. 58. 40. 55. 44. 56. 38. 57. 43. 56. MCH MCHC PLAT Pg g/dL X103/UL 21. 37. 22. 37. 722. 692. 22. 38. 724. 24. 41. 1164. 22. 38. 806. 22. 38. 836. 22. 39. 21. 38. 22. 38. 890. 804. 852. 21. 37. 722. AVG. S. D. S. E. 7.262 0.468 0.148 15.80 0.66 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 SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 RBC Hb Hfc MCV ANIMALS: xiO^uL g/dL % fL 376819 8.67 16.6 49. 56. 376820 8.65 16.1 50. 57. 376824 8.18 16.1 48. 58. 376828 8.90 17.4 51. 57. 376833 8.21 15.8 48. 58. 376854 8.67 17.9 53. 61. 376858 8.58 16.6 49. 57. 376859 8.30 16.3 48. 58. 376879 8.74 17.0 51. 57. 376880 8.63 15.6 48. 55. MCH MCHC PLAT . Pg g/dL X103/UL 19. 34. 19. 32. 20. 34. 20. 34. 19. 33. 21. 34. 19. 34. 20. 34. 20. 34. 18. 33. 690. 590. 808. 524. 670. 864. 766. 806. 846. 722. AVG. S. D. S. E. 8.553 16.54 49.4 57.4 19.4 33.5 0.240 0.72 1.8 1.6 0.7 0.6 0.076 0.23 0.6 0.5 0.2 0.2 728.6 111.5 35.3 97 Company Sanitized. Does not contain TSCA CBI HASKELL NUMBER;_15388 HASKELL CODE^B ____BIBMMB1^ 3-DAY REC DEPARTMENT! POLYMER PRODUCTS REPORT DATE: 17-OCT-84 MALE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376825 376835 376839 376840 376841 376849 376863 376870 376872 376873 WBC X1Q3/UL 13.6 14.8 8.9 10.5 13.3 16.0 10.5 9.1 18.5 9.5 Neufc WBCxjE 2992. 3700. 2136. 1785. 1330. 3520. 2100. 1092. 1295. 2280. Band WBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. Lymph WBCx? 9792. 10508. 6141. 7875. 11172. 11680. 7560. 7735. 16095. 6365. Alym WBCx? 408. 148. 89. 210. 266. 160. 105. 0. 185. 95. Mono WBCx? 408. 444. 534. 525. 532. 640. 735. 182. 740. 665. Eos in WBCx? 0. 0. 0. 105. 0. 0. 0. 91. 185. 95. Baso WBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. AVG. S. D. S. E. 12.47 3.28 1.04 2223.0 0.0 919.6 0.0 290.8 0.0 9492.3 166.6 540.5 47.6 0.0 3032.7 112.3 169.6 66.6 0.0 959.0 35.5 53.6 21.1 0.0 GROUP: 2M DOSE: .0076 mg/L SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE; 05/14/84 ANIMALS: 376804 376806 376810 376818 376822 376823 376844 376852 376876 376881 WBC a ^O3/!! L 9. 5 11. 1 13. 0 13.6 13. 2 10. 1 13. 0 10. 4 15. 0 8. 3 Neut WBCx? 2185. 4107. 2730. 1904. 3300. 1717. 3770. 1456. 4050. 1162. Band VIBCxf, 0. 0. 0. 0. 132. 0. 0. 0. 0. 0. Lymph WBCxjt 6270. 6327. 8580. 11288. 9372. 7373. 8710. 8528. 9750. 6640. Alyn WBCx? 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 WKCx% 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. AVG. S. D. S. E. 11.72 2. 14 0.68 2638.1 1107.9 350.4' 13.2 41.7 13.2 8283.8 240.3 475.4 69.2 0.0 1636.5 180.1 260.5 86.4 0.0 517.5 57.0 82.4 27.3 0.0 98 Company Sanitized. Does not contain TSCA CBI MR: COMPOUND: PERIOD: SEX: 0-DAY REC MALE 15388 HASKELL CODE:Jf|| lt DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALtf: 376805 376812 376A13 376821 376830 376838 376851 376857 376867 376874 WBC xlO^uL 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 WBCxj6 1122. 2160. 1872. 2106. 1768. 1598. 3302. 2000. 1980. 1386. Band WBCxjE 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 1929.4 0.0 583.3 0.0 184.5 0.0 Lymph WBCx? 4884. 11376. 11-376. 9009. 7280. 7332. 8636. 9500. 8470. 7722. Alym WBCx? 66. 144. 432. 117. 416. 94. 254. 125. 330. 99. Mono WBCx? 528. 720. 576. 468. 832. 376. 381. 750. 220. 693. Eosin WBCx? 0. 0. 144. 0. 104. 0. 127. 125. 0. 0. Baso WBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 8558.5 207.7 554.4 50.0 0,0 1952.8 139.3 195.6 65.2 0.0 617.5 44.1 61.9 20.6 0.0 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 WBC X1Q3/UL 10.9 8.5 16.7 9.8 13.5 11.1 12.7 14.0 9.0 17.8 Neut WBCxjC 2180. 1700. 2338. 1862. 2160. 3663. 2667. 2800. 2070. 2848. Band WBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. Lymph WBCx? 7739. 6545. 13360. 7546. 10800. 6105. 9144. 10220. 6390. 13884. Alym WBCx? 218. 85. 167. 98. 0. 222. 127. 140. 180. 178. Mono WBCx? 763. 170. 835. 294. 540. 1110. 762. 840. 360. 890. Eosin WBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. Baso WBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. AVG. S. D. S. E. 12.40 3.14 0.99 2428.8 0.0 579.0 0.0 183.1 0.0 9173.3 141.5 656.4 0.0 0.0 2833.1 67.6 301.4 0.0 0.0 895.9 21.4 95.3 0.0 0.0 99 Company Sanitized. Does not contain TSCA CBI ----fHn DAY MALE HASKELL REC NUMBER;_15388 HASKELL CODE;^ DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376825 376835 376839 J9*776<H0H4|/0V 376841 376849 376863 376870 376872 376873 ALP U/L 130. 339. 237. 137. 161. 184. 183. 211. 140. 185. ALT U/L 35. 44. 42. 46. 33. 31. 32. 37. 37. 32. 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 6.56 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. AVG. S. D. S. E. 190.7 62.1 19.6 '36.9 5.4 1.7 86.9 14.0 4.4 16.0 2.9 0.9 0.542 0.068 0.021 5.88 0.20 0.06 56.7 12.8 4.0 --- GROUP: 2M DOSE: SAMPLE DATE: 07/20/84 ANIMALS: 376804 376806 376810 376818 376822 376823 376844 376852 376876 376881 ALP U/L 98. 166. 177. 265. 262. 242. 153. 211. 206. 207. ALT U/L 35. 46. 43. 41. 41. 54. 33. 28. 35. 37. AVG. S. D. S. E. 198.7 52.0 16.4 39.3 7.4 2.3 .-0-07.6..n.g./-L --.--. SPECIES: RAT BIRTH DATE-.:.-- 05/14/84 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. CO -3J. 69. 52. 50. U^ TJf 34. 41. 34. 82.8 12.1 3.8 16.9 2.4 0.7 0.595 0.051 0.016 5.99 0.32 0.10 48.6 11.0 3.5 00 Company Sanitized. Does not contain TSCA CBI LwJH------MHHO HASKELL MOMBER; 0-DAY REC MALE 15388 HASKELL CODE:^a DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 31 DOSE: SAMPLE DATE; 07/20/84 ANIMALS: 376805 376812 376813 37682.1 376830 376838 376851 376857 376867 376874 ALP U/L 299.. 127. 229. 228. 210. 240. 204. 187. 141. 199. ALT U/L 71. 43. 43. 40. 35. 40. 50. 46. 39. 33. AVG. S. D. S. E. 206.4 49.1 15.5 44.0 10.7 3.4 .058mg/L SPECIES: RAT BIRTH DATE: 05/14/84 AST U/L 116. 72. 83. 7B. 102. 105. 96. 99. 79. 76. BUN mg/dL 15. 13. 15. 16. 19. 14. 14. 24. 12. 17. CREAT mg/dL 0.67 0.53 0.70 0.-68 0.55 0.72 0.61 0.63 0.61 0.59 TPROT g/dL 6.3 6.1 6.2 6.4 5.9 6.4 6.7 5.8 5.6 6.0 CHLOS ng/dL 47. 61. 53. 50. 48. 49. 50. 42. 49. 52. 90.6 14.9 4.7 15.8 3.4 1.1 0.629 0.063 0.020 6.14 0.33 0.10 ^9.9 4.8 1.5 GROUP: 4M DOSE: SAMPLE DATE: 07/20/84 ANIMALS: 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 .480 mg/L SPECIES: RAT BIRTH DATE: 05/14/84 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 0.70 0.62 0.71 0.29 0.74 0.76 0.71 0.60 0.62 0.68 TPROT g/dL 6.1 5.9 6.4 6.1 5.4 6.3 6.2 6.0 7.1 6.9 CHLOS mg/dL 32. 18. 19. 19. 20. 16. 18. 9. 18. 16. 108.0 28.9' 0.643 6.24 18.6 17.0 4.2 0.135 0.49 5.5 5.4 1.3 0.043 0.15 1.7 10 Company Sanitized. Does not contain TSCA CBI ( I f MR: I HASKELL NUMBER; 15388 COMPOUND: f^^^^--------------------9D1EPARTMENT: HASKELL CODE:Cft POLYMER PRODUCTS PERIOD: 0-DAY REC REPORT DATE; 17-OCT-84 SEX: MALE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE; 05/14/84 ANIMALS: 376825 376835 376839 376840 376841 376849 376863 376870 376872 376873 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 pH BILI- UROBL Ke- ROBIN mg/dL tone 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 AVG. S. D. S. E. 7.20 1714.1 3.67 296.2 1.16 93.7 7.30 0.67 0.21 0.91 0.28 0.09 GROUP: 2M DOSE: .0076 mg/L SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376804 376806 376810 376818 376822 376823 376844 376852 376876 376881 AVG. S. D. S. E. VOL OSMOL BLOOD mL m0s 4.6 1966. 5.1 1607. 7.4 1641. 4.6 1926. + 5.0 1666. 4.2 2130. + 7.7 1664. 2.2 1868. + 6.5 1090. -' 4.4 2388. - 5.17 1794.6 1.64 350.5 0.52 110.8 SUGAR -- - + + + - PRO TEIN +2 +1 +1 +1 +1 +1 +1 +1 +1 +1 ' 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 CODE:^^ 15388 to DEPARTMENT: HASKELL POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 34 DOSE: .058 mg/L SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376805 376812 376813 376821 376830 376838 376851 376857 376867 376874 VOL fflL 5.0 7.3 6.2 8.3 6.7 5.0 9.0 7.1 4.6 16.0 OSMOL m0s 2062. W. 1763. 1398. 1471. 1976. 1322. 1669. 2080. 821. BLOOD - + - SUGAR ! - + - 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 + AVG. S. D. S. E. 7.52 1609.6 3.31 389.0 1.05 123.0 7.00 0.67 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 ANIMALS: 376819 376820 376824 376828 376833 376854 376858 376859 376879 376880 VOL mL 11.0 9.1 12.0 16.0 15.0 11.0 10.0 8.7 14.0 12.0 OSMOL m0s 1039. 955. 944. 886. 730. 1099. 537. 861. 725. 723. BLOOD - SUGAR + + - + - PRO TEIN +1 +1 +1 + +1 +1 + +1 +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 - 8.0 - 0.1 9.0 +1 1.0 -- 9.0 - 1.0 8.0 - 1.0 - AVG. S. D. S. E. 11.88 2.45 0.78 849.9 171.0 54.1 8.30 0.64 0.67 0.46 0.21 0.15 05 Company Sanitized. Does not contain TSCA CBI 5388 HASKELL CODE^jR DEPARTMENT: POLYMER PRODOCTS REPORT DATE: 17-OCT-84 GROOP: 1CM DOSE: CONTROL SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376825 376835 376839 376MO' 376841 376849 376863 376870 376872 376873 RBC /hpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-2 0-0 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 /Ipf 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 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 fflg/L SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 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 Epifch /hpf 0-1 0-1 3-6 0-1 0-1 0-2 0-0 0-2 0-0 0-1 Cast /Ipf 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 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 15388 HASKELL CODE: OK DEPARTMENT: POLYMER PRODOCTS REPORT DATE: 17-OCT-84 GROUP: 31 DOSE: .058 mg/L SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 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 /Ipf 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 CL PPT FEED Y C PPT FEED DY CL PPT FEED Y C PPT FEED Y C PPT FEED DY CL PPT PEED LY CL PPT FEED GROUP: 4M DOSE: .480 mg/L SAMPLE DATE: 07/20/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 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 /Ipf 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 05 Company Sanitized. Does not contain TSCA CBI 5388 HASKELL CODE;(jB ' 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 xloS/uL 6.73 6.49 7.63 7.75 6.39 7.93 7.27 7.28 7.26 6.51 Hb g/dL 15.2 16.4 16.0 16.0 14.8 15.8 15.8 15.9 16.4 16.0 Ht % 39. 39. 43. 43. 38. 42. 42. 41. 42. 38. AVG. S. D. S- E. 7.124 0.561 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 P6 g/dL x1o3/uL 57. 23. 39. 940. 59. 25. 43. 1262. 56. 21. 37. 1138. 54. 21. 38. 944. 59. 23. 39. 1190. 52. 20. 38. 1158. 58. 22. 38. 56. 22. 39. 954. 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 1080.8 163.4 51.7 GROUP: 2M DOSE: .0076 mg/L SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 RBC Elb Hfc MCV ANIMAL#: 3doS/uL g/d,L % fL 376800 7.25 16. 2 41. 56. 376810 6.68 15. 0 40. 59. 376822 6.23 16. 1 37. 58. 376848 6.74 15. 5 38. 57. 376852 7.49 16. 4 44. 58. 376856 376866 376871 376876 376881 7.72 16. 3 43. 55. 7.03 16. 3 40. 56. 7.43 15. 8 . 42. 55. 7.20 15. 1 39. 54. 7.18 16. 3 41. 57. MCH MCHC PLAT Pg g/dL 3d03/uL 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 06 Company Sanitized. Does not contain TSCA CBI 5388 I . HASKELL CODE:^BI) DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROOP: 3M DOSE: .058 mg/L SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376803 376808 376811 376812 376813 376830 376843 376857 376860 376874 RBC xlO^uL 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 Ht % 41. 42. 44. 42. 41. 43. 40. 44. 40. 42. MCV fL 54. 55. 54. 58. 57. 57. 54. 55. 56. 55. MCH P6 .21. 21. 20. 23. 22. 21. 21. 21. 22. 21. MCHC g/dL 39. 39. 37. 40. 39. 38. 38. 38. 38. 38. PLAT X103/UL 1064. 1126. 768. 1300. 878. 1060. 1026. 1134. 1282. 1050. AVG. S. D. S. E. 7.477 0.329 0.104 16.01 0.47 0.15 41.8 1.5 0.5 55.5 1.4 0.5 21.4 0.8 0.2 38.3 0.8 0.2 1068.8 161.8 51.2 GROUP: 4M SAMPLE DATE; I >OSE: 08/03/ 84 .480 mg/L SPECI ES; RA T BIRTH DATE: 05/14/84 ANIMALS: 376814 376815 376819 376824 376832 376833 376850 376853 376858 376880 RBC xlO^uL 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 Hfc % 41. 40. 38. 35. 37. 44. 43. 43. 43. 37. MCV fL 54. 54. 56. 56. 55. 60. 55. 53. 57. 54. MCH PS 20. 20. 21. 23. 22. 21. 20. 19. 21. 20. MCHC g/dL 37. 37. 38. 40. 40. 35. 36. 36. 35. 37. PLAT X103/UL 1052. 1140. 900. 1146. 1078. 1256. 1036. 1120. 1074. 998. AVG. S. D. S. E. 7.168 0.546 0.173 14.84 0.64 0.20 40.0 3.1 1.0 5S.4 2.0 0.6 20.8 1.0 0.3 37.2 1.7 0.6 1080.0 QC 3J' 7 1 30.3 107 Company Sanitized. Does not contain TSCA CBI ( f j MR: COMPOUND:! PERIOD: '14-DAY SEX; MALE HASKEL1 . REC NUMBE:R; 153188 HASICELL CODE^fl DEPABTMElIT: POL}fMER PRODUCTS REPORT DlITE: 17--OCT-84 GROUP: 1CMI DOSE: CONTRO L SAMPLE DATE: 08/0 3/84 SPECIES: RAT BIRTH DA'FE: 05/'14/84 ANIMALS: 376801 376835 376836 376-837 376841 376847 376849 376863 376872 376878 ALP U/L 166. 307. 151. 10T. 168. 201. 207. 128. 139. 139. ALT AST BUN GREAT TPROT CHLOS U/L U/L mg/dLi mg/dL g/dL mg/dL 39. 71. 22. 0.63 6.2 63. 39. 103. 16. 0.68 6.4 67. 32. 70. 15. 0.60 6.5 63. 38. 77. 12. 0.55 7".4 76. 35. 78. 19. 0.58 7.5 72. 29. 75. 18. 0.49 5.4 64. 37. 59. 16. 0.64 5.7 101. 28. 71. 21. 0.60 5.7 61. 37. 83. 18. 0.54 5.8 61. 35- 77 16. 0.56 5.8 87. AVG. S. D. S. E. 170.7 57.7 18.2 34.9 4.0 1.3 76.4 11.3 3.6 17.2 3. 0 1. 0 0.587 0.055 0.017 6.24 0.72 0.23 71.5 13.2 4.2 GROUP: 2M DOSE: .0076 mg/L SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ALP ALT AST BUN GREAT TPROT CHLOS ANIMALS: U/L U/L U/L mg/dL mg/dL g/dL mg/dL 376800 219. 39. 72. 16. 0.53 6.0 50. 376810 127. 32. 70. 15. 0.60 6.3 64. 376822 261. 46. 70. 20. 0.69 6.6 64. 376848 87. 24. 98. 17. 0.57 6.1 65. 376852 137. 30. 81. 15. 0.59 6.2 66. 376856 145. 31. 76. 16. 0.56 6.2 55. 376866 176. 28. 59. 17. 0.61 6.8 86. 376871 180. 36. 67. 16. 0.61 6.3 50. 376876 242. 39. 79. 19. 0.63 5.7 51. 376881 219. 39. 75. 15. 0.49 5.2 65. AVG. S. D. S. E. 179.3 55.8 17.6 34.4 6.6 2.1 74.7 10.3 3.3 16. 6 1. 6 0. 5 0.588 0.055 0.017 6.14 0.45 0.14 61.7 10.8 3.4 08 Company Sanitized. Does not contain TSCA CBI | f MR: & HASKEL1 ^ COMPOUND:!^^^^^^^^^^^^^^-- PERIOD: TCDA^EC^ SEX: MALE B l iJ NUMBEIL- 15388 HJISKELL (;ODE:1 DEPAR'IMENT: P()LYMER I'RODUCTS1 REPOR'r DATE: 16-OCT-fi4 GROUP: 1C(4 DOSE: CONTR01 SAMPLE DA'FE: 08/03/84 SPECI1ES: RAT BIRTH DATE: O!5/14/84 ANIMALS; 376801 376835 376836 376837 376841 376847 376849 376863 376872 376878 WBC x1o3/uL 9.9 12.4 14.4 13.8 14.1 15.5 14.9 10.6 11.6 13.8 AVG. S. D. S. E. 13.10 1.88 0.60 Neufc WBCx? 1287. 3720. 3168. 4002. 2961. 1860. 3725. 2332. 1624. 1104. Band WBCx;( 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 2578.3 0.0 1078.5 0.0 341.0 0.0 Lymph WBCxf, 8514. 8680. 11232. 9798. 11139. 13485. 11026. 8268. 9976. 12558. Alym WBCx{6 0. 0. 0. 0. 0. 0. 0. 0. 0. 138. Mono WBCx? 0. 0. 0. 0. 0. 155. 0. 0. 0. 0. Eosin WBCx? 99. 0. 0. 0. 0. 0. 149. 0. 0. 0. Baso WBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 10467.6 13.8 15.5 24.8 0.0 1743.6 43.6 49.0 53.6 0.0 551.4 13.8 15.5 16.9 0.0 GROUP: 2M DOSE: .0076 mg/L SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE; 05/14/84 ANIMALS: 376800 376810 376822 376848 376852 376856 376866 376871 376876 376881 WBC x1o3/uL 14.7 13.1 13.8 16.7 10.4 16.4 12.0 18.0 13.2 8.3 Neut WBCx? 5292. 2882. 3174. 1169. 1560. 2460. 1680. 2160. 5148. 1660. Band mcx% 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. Lymph WBCx;6 9261. 9563. 10488. 15030. 8528. 13612. 10320. 15660. 7788. 6474. Alyn WBCx? 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. 0. AVG. S. D. S. E. 13.66 2.97 0.94 2718.5 0.0 1456.0 0.0 460.4 0.0 10672.4 44.5 141.6 83.0 0.0 3099.0 72.2 154.7 77.0 0.0 980.0 22.8 48.9 24.4 0.0 109 Company Sanitized. Does not contain TSCA CBI A f l MR: H COMPOUND:' PERIOD: 14-DAY SEX: MALE HASKELL REG 1 ] :ODE:0(|| NuMBElfl: 15388 H.ASKELL ( DEPAR'IMENT: P(3LYMER 1PRODUCT;3 REPOR'r DATE; 16-OCT-)34 GROUP: 3M DOSE: .058 m(/L SAMPLE DA'IE: 08/03/84 SPECIJ3S: RAT BIRTH DATE: 0'5/14/8,4 ANIMALtf: 376803 376808 376811 376812 376813 376830 376843 376857 376860 376874 WBC x1o3/uL 11.3 24.4 10.6 21.2 10.7 12.2 15.2 12.4 21.2 8.2 AVG. S. D. S. E. 14.74 5.55 1.75 Meut WBCx? 2260. 4148. 2014. 3392. 1712. 1586. 4104. 3100. 5936. 1640. Band WBCx?6 0. 0. 0. 0. 0. 0. 0. 0. 0. ' 0. 2989.2 0.0 1427.8 0.0 451.5 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 90.8 125.6 47.9 0.0 4450.2 90.9 118.1 84.5 0.0 1407.3 28.7 37.4 26.7 0.0 GROUP: 4M DOSE: .480 mg/L SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376814 376815 376819 376824 376832 376833 376850 376853 376858 376880 WBC x1o3/uL 16.7 17.3 11.6 16.7 11.5 12.2 19.0 13.8 12.6 17.7 Meut Band WBCx? WBCx? 2672. 2422. 2552. 4008. 2300. 2684. 4180. 3036. 2394. 2478. 0. 0. 0. 0. 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 WBCxjt 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. Baso WBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. AVG. S. D. S. E. 14.91 2.85 0.90 2872.6 0.0 676.5 0.0 213.9 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 -DAY MALE HASKELL NUMBER; J5388 HASKELL CODE^Wl "^~--------------"" DEPARTMENT: POLYMER PRODUCTS REC REPORT DATE: 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376803 376808 376811 376812 376813 376830 376843 376857 376860 376874 ALP U/L 185. 236. 171. 11T. 252. 200. 209. 178. 213. 196. ALT AS T BUM CREAT 'rPROT (:HLOS U/L U/ L nig/dL mg/dL g/dL rng/dL 40. 104 22. 0.56 6.5 52. 36. 72 17. 0.53 6.9 84. 36. 81 17. 0.66 6.5 68. 42. 69 15. 0.59 6.6 70. 37. 74 18. 0.63 6.3 54. 27. 79. 19. 0.57 5.5 48. 36. 56 14. 0.62 4.0 56. 43. 107 21. 0.53 6.3 57. 31. 73 15. 0.57 6.4 71. 32. 79 13. 0.54 6.4 67. AVG. S. D. S. E. 195.6 37.5 11.9 36.0 5.0 1.6 79.4 15 .5 4.9 17.1 2.8 0.9 0.580 0.044 0.014 6.14 0.83 0.26 62.7 11.2 3.6 GROUP: 4M DOSE: .480 mg/L SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ALP ALT AST BUN CREAT TPROT CHLOS ANIMALS: U/L U/L 376814 210. 46. 376815 277. 31. 376819 234. 38. 376824 233.: 41. 376832 139. 38. 376833 239. 35. 376850 122. 33. 376853 247. 32. 376858 150. 27. 376880, 294. 36. U/L mg/dL mg/dL 64. 16. 0.60 61. 16. 0.64 88. 19. 0.49 68. 27. 0.72 90. 16. 0.58 65. 18. 0.69 60. 16. 0.58 63. 22. 0.58 77. 19. 0.62 65. 17. 0.50 g/dL 6.4 6.8 6.9 7.5 6.5 6.9 6.4 6.3 5.9 5.9 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 3.7 1.2 0.600 0.073 0.023 6.55 0.49 0.16 59.2 8.8 2.8 111 Company Sanitized. Does not contain TSCA CBI i -- MR: RHASKEL1,, NUMBER; 15388 HASKELL COI)E:(JWO COMPOUND :fl^^^^--------------------DE^PARTMENT: POLYMER PRODUCTS PERIOD: 14-DAY REC REPORT DATE: 17-OCT-84 SEX: MALE GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 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 - - SUGAR - - 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 - 1.0 - 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 SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS; 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 m0s 1603. 642. 1455. 932. 834. 1874. 1151. 1694. 1332. 1640. BLOOD - 12.43 1315.7 4.54 411.3 1.44 130.1 SUGAR + - PRO TEIN +2 +1 +1 +1 + +2 +1 +1 +1 +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 12 Company Sanitized. Does not contain TSCA CBI | MR:^JB HASKEL1L NUMBER; J5388 HASKELL COI)E:(JB COMPOUND: fi--------------||------------|D3EPARTMENT: POLYMER PRODUCTS PERIOD: 14-DAK HEC REPORT DATE: 17-OCT-84 SEX: MALE GROUP: 3M DOSE: .058 mg/L SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALft: 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. 14J.3. 1063. 1707. 1573. 1682. 1532. 1785. 957. BLOOD - - + - 12.48 1566.4 4.53 334.9 1.43 105.9 SUGAR - - + - + PRO TEIN +1 +1 +3 +2 +2 +2 +2 +2 +1 +2 pH BILI- UROBL Ke- RUBIN mg/dL tone 7.0 - 1.0 + 6.0 +1 1.0 +1 8.0 +1 1.0 + 7.0 - 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 GROOP; 4M DOSE: .480 mg/L SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 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 m0s 1570. 1754. 1775. 1303. 1413. 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 7.0 +1 1.0 + 1.0 + 7.0 8.0 - 1.0 + 1.0 - 7.0 +1 1.0 + 7.0 +1 8.0 - 1.0 + 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 ^5388 HASKELL CODE:(|R DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 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 Epifch /hpf 0-1 0-2 1-2 1-3 2-4 2-4 0-1 4-6 0-2 0-2 Cast /Ipf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 APPEARANC E Y C 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: 2M DOSE: .0076 mg/L SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 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 /Ipf 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 114 Company Sanitized. Does not contain TSCA CBI 14-DAY MALE HASKELL REC NUMBER; J5388 HASKELL CODE:QR DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376803 376808 376811 376812 376813 376830 376843 376857 376860. 376874 RBC /hpf 0-0 0-0 0-0 0-0 0-0 0-1 0-0 0-0 0-0 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 /Ipf 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 SAMPLE DATE: 08/03/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 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 /Ipf 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 115 Company Sanitized. Does not contain TSCA CBI MR: COMPOUND:! PERIOD: SEX: 41-DAY MALE R_EC_ 388 HASKELL CODE:^H DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 27-FEB-85 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/30/84 ANIMALi?: 376801 376807 376829 37683.4 376836 376837 376847 376861 376869 376878 RBC x1o6/uL 7.55 7.25 8.34 7-.5Q 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 Hfc % 43. 39. 44. 40. 41. 43. 46. 43. 42. 45. AVG. S. D. S. E. 7.917 0.451 0.143 15.53 0.38 0.12 42.5 2.1 0.7 SPECIES: RAT BIRTH DATE: 05/14/84 MCV MCH MCHC PLAT fL Pg g/dL x103/uL 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 19.6 36.6 1.6 0.8 1.1 0.5 0.3 0.4 950.4 129.3 40.9 GROUP: 2M DOSE: . 0076 mg/L SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL)?; 376800 376827 376831 376848 376856 376862 376866 376871 376877 376882 RBC x1o6/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 Ht MCV % fL 41. 55. 39. 56. 40. 54. 40. 55. 43. 53. 42. 54. 42. 54. 41. 53. 39, 51. 46. 55. MCH MCHC PLAT Pg g/dL x103/uL 21. 38. 23. 41. 21. 38. 21. 39. 20. 37. 20. 37. 20. 37. 19. 36. 1158. 1236. 1266. 1094. 904. 1086. 994. 1046. 20. 39. 20. 37. 920. 1038. AVG. S. D. S. E. 7.563 0.443 0.140 15.54 0.69 0.22 41.2 2.3 0.7 54.0 1.4 0.4 . 20.6 1.0 0.3 37.8 1.3 0.4 1074.2 121.0 38.3 116 Company Sanitized. Does not contain TSCA CBI MR:Q^BR COMPOUND^ PERIOD: 41-DAY SEX: MALE i-1ASKELL B;EC NUMBER: 15388 HASKE:LL CODE\r 1 DEPAfETMENT: POLYM:ER PRODUCTS .REPOF!T DATE : 27-F:EB-85 GROUP: 3M SAMPLE DA'rE: DOSE: 08/30i/84 . 058 mg/L SPECIE S: RAT BIRTE1 DATE: 05/14,/84 ANIMALS: 376803 376808 376811 376817 376843 376846 376855 376860 376864 376875 RBC x1o6/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 MCV % fL 45. 53. 41. 53. 39. 53. 42. 52. 42. 53. 44. 55. 41. 52. 44. 59. 37. 56. 39. 55. MCH MCHC PLAT Pg g/dL X103/UL 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 SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376814 376815 376816 376826 376832 376842 376845 376850 376853 376868 RBC xlO6/^ 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 Hfc MCV % fL 39. 55. 43. 53. 38. 52. 41. 53. 40. 53. 41. 55. 36. 56. 39. 55. 4'1. 52. 39. 56. MCH MCHC PLAT Pg g/dL X103/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 1.6 0.5 20.7 0.9 0.3 37.9 1.2 0.4 1165.8 159.2 50.4 H7 Company Sanitized. Does not contain TSCA CBI H i MR: COMPOUND:___ PERIOD: 41-DAY REC SEX: MALE 5388 HASKELL CODE DEPARTMENT: POLYMER __ PRODUCTS REPORT DATE: 27-FEB-85 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL//: 376801 376807 376829 37'6'83'4" 376836 376837 376847 376861 376869 376878 WBC x1o3/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 WBCxl 0. 0. 0. 6. 0. 0. 0. 0. 0. 0. Lymph WBCxt 10384. 7462. 10086. 10836. 10005. 10008. 10004. 8080. 9900. 10981. Alym WBCxt 0. 91. 0. 0. 0. 0. 122. 101. 132. 0. Mono WBCx% 0. 91. 123. 6. 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 0.0 838.6 0.0 265.2 0.0 9774.6 44.6 90.3 90.0 0.0 1127.7 58.6 96.4 81.4 0.0 356.6 18.5 30.5 25.8 0.0 GROUP: 2M DOSE: .0076 mg/L SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL//: 376800 376827 376831 376848 376856 376862 376866 376871 376877 376882 WBC x1o3/uL 15.7 19.3 13.2 15.4 14.0 13.4 10.0 13.3 11.8 17.0 . AVG. S. D. S. E. 14.31 2.65 0.84 .Neut WBCx? 3768. 4632. 2772. 2464. 2800. 3350. 1400. 3458. 2360. 2210. Band WBCx? 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 2921.4 0.0 912.7 0.0 288.6 0.0 Lymph WBCxiE 11618. 14282. 10164. 12782. 10500. 9916. 8500. 9576. 9086. 14110. Alym WBCxit 157. 0. 132. 0. 140. 134. 0. 0. 118. 0. Mono WBCx^E 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. 11053.4 2055.8 650.1 68.1 72.4 22.9 193.4 216.4 68.4 60.5 80.2 25.4 13.2 41.7 13.2 1 18 Company Sanitized. Does not contain TSCA CBI f l f MR: 1 COMPOUND:{ PERIOD: 41-DAY SEX: MALE ^ HASKEL LJtUMBER : 9 3 REG 15388 H.ASKELL CODE:f| DEPARTMENT: P OLYMER PRODUCT REPORT DATE: ,27-FEB-,85 GROUP: 3M DOSE: .058 mig/L SAMPLE DA'iFE: 08/30/84 SPECIES: RAT BIRTHI DATE: 0'5/14/84 ANIMALtf: 376803 376808 376811 376817 376843 376846 376855 376860 376864 376875 WBC xi03/uL 9.4 22.2 7.8 18.9 12.4 9.7 17.8 24.2 15.8 14.4 Neut WCx% 1316. 4662. 1482. 3402. 4.7-1.2. 1552. 2492. 6776. 2528. 2448. Band WBCx? 0. 0. 0. 0. 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 VBCx% 94. 222. 156. 189. 124. 97. 356. 0. 158. 0. Baso WBCxiE 0. 222. 0. 0. 0. 0. 0. 0. 0. 0. AVG. S. D. S. E. 15.26 5.56 1.76 3137.0 0.0 1762.2 0.0 557.3 0.0 11557.3 4067.7 1286.3 171.2 227.8 72.0 232.7 245.7 77.7 139.6 105.3 33.3 22.2 70.2 22.2 GROUP: 4M DOSE: .480 mg/L SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL//: 376814 376815 376816 376826 376832 376842 376845 376850 376853 376868 WBC xi03/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 VBCxl WCx% 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!6 9213. 10625. 14740. 11250. 8265. 11786. 12688. 11224. 7938. 10086. Alym VBCx% 0. 250. 0. 300. 190. 0. 208. 368. 98. 0. Mono WCx% 111. 125. 0. 450. 0. 332. 416. 552. 98. 0. Eosin WBCx% 0. 0. 660. 150. 0. 166. 208. 552. 0. 0. Baso VBCx% 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 10781.5 141.4 208.4 173.6 0.0 , 2057.9 140.2 209.2 243.2 0.0 650.8 44.3 66.1 76.9 0.0 n9 Company Sanitized. Does not contain TSCA C81 f l i MR: COMPOUND:! PERIOD: 41-DAY SEX: MALE HASKEL1L REC NUMBE R: 1538.8 HAS KELL CODE:fB|^ S EPARTME;NT: EPORT D.ATE: POLYMER PRODUCTS 27 -FEB-85 GROUP: 1Ch1 DOSE: CONTRO:L SAMPLE DA1E: 08/3!0/84 SPEICIES: RAT B IRTH DA"TE: 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. S. D. S. E. , 130.8 30.1 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 SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL//: 376800 376827 376831 376848 376856 376862 376866 376871 376877 376882 . ALP U/L 197. 134. 174. 99. 102. 219. 156. 139. 120. 173. ALT AST BUN CREAT TPROT CHLOS U/L U/L mg/dL mg/dL g/dL mg/dL 36. 101. 31. 77. 39. 65. 31. 68. 37. 66. 28. 78. 31. 63. 35. 71. 28. 61. 28. 84. 16. 0.66 6.0 47. 19. 0.64 6.4 55. 19. 0.61 . 6.6 70. 16. 0.63 6.1 60. 15. 0.64 5.3 52. 17. 0.75 6.9 95. 18. 0.72 7.3 102. 17. 0.69 6.5 58. 19. 0.66 6.3 64. 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:[1 COMPOUND:) PERIOD: 41-DAY SEX: MALE HASKELL REC NUMBE R: 1538 8 HASKELL CODE(^ ^ s EPARTMEMT: POLYMER PRODUCT; EPORT D.ATE: 27 -FEB-85 GROUP: 3M DOSE: .058 m g/L SAMPLE DA'TE: 08/:50/84 SPEICIES: RAT BIRTH DA'TE: 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 40. 87. 18. 0.62 32. 75. 18. 0.64 41. 73. 18. 0.59 38. 65. 17. 0.59 41. 83. 14. 0.74 36. 95. 15. 0.69 30. 60. 15. 0.68 41. 62. 19. 0.71 33. 64. 18. 0.67 5.8 41. 5.8 75. 5.3 55. 5.6 64. 5.8 48. 6.4 88. 6.7 88. 6.5 81. 7.2 102. 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 SAMPLE DATE: 08/30/84 SPECIES: RAT 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. ALT AST BUN GREAT 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. AVG. S. D. S. E. 152.4 54.7 17.3 32.8 6.3 2.0 76.6 11.1 3.5 17.5 2.5 0.8 0..646 0.073 0.023 6.09 0.40 0.13 62.7 12.4 3.9 12 Company Sanitized. Does not contain TSCA CBI 15388 HASKELL CODE(fl^ h' DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 27-FEB-85 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 m0s 1961. 2420. 2280. 1967. 1877. 1164. 2170. 1537. 1915. 1655. BLOOD -- -- -- -- - SUGAR -- + - PRO TEIN +1 +3 +2 +1 +2 +1 +2 +2 +2 +2 pH BILI- UROBL Ke- RUBIN ing/dL tone 7.0 +1 7.0 +1 .0 +1 .0 +1 7.0 - .0 +1 7.0 - .0 + 7.0 - .0 + 8.0 - .0 + 7.0 - 1.0 +1 8.0 - 1.0 + 7.0 -- 1.0 + 7.0 - 1.0 + AVG. S. D. S. E. 13.52 1894.6 4.88 369.7 1.54 116.9 7.20 0.42 0.13 1.00 0.00 0.00 GROUP: 2M DOSE: .0076 mg/L SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE : 05/14/84 ANIMAL//: 376800 376827 376831 376848 376856 376862 376866 376871 376877 376882 AVG. S. D. S. E. VOL mL 16.0 15.0 10.5 9.0 11.0 9.0 22.5 11.5 11.5 22.0 OSMOL m0s 1608. 1365. 1889. 2126. 1761. 2064. 1389. 1536. 1726. 865. BLOOD SUGAR -- +3 -- -- - -- + -- -- - + -- ' -- - PRO TEIN +2 +2 +2 +2 +1 +3 +2 +1 +2 +1 13.80 1632.9 5.00 372.8 1.58 117.9 pH BILI- UROBL Ke- RUBIN mg/dL tone 7.0 1.0 +1 7.0 7.0 +1 1.0 + 1.0 + 7.0 1.0 + 7.0 7.0 +1 1.0 +1 1.0 + 8.0 1.0 + 7.0 1.0 +1 8.0 1.0 +1 8.0 - 1.0 + 7.30 0.48 0.15 1.00 0.00 0.00 22 Company Sanitized. Does not contain TSCA CBI MR:(r'1HASKELL NUMBER: 15388 . HASKELL CODE:(H coMpomm:(^^^^------|^^^1 DEPARTMENT : POLYMER PRODUCTS PERIOD: 41-DAY REC REPORT DATE: 27-FEB-85 SEX: MALE GROUP: 3M DOSE: .058 mg/L SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL//: 376803 376808 376811 376817 376843 376846 376855 376860 376864 376875 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 -- -- - SUGAE! + -- - PRO TEIN +2 +2 +2 +1 +2 +1 +1 +1 +2 +2 pH BILI- UROBL Ke- RUBIN mg/dL tone 7.0 +1 1.0 + 7.0 +1 7.0 +1 1.0 +1 1.0 + 7.0 - 1.0 +1 6.0 +1 1.0 + 8.0 - 1.0 +1 7.0 - 1.0 + 7.0 - 1.0 + 7.0 +1 1.0 + 7.0 +1 1.0 +2 AVG. S. D. S. E. 13.30 1820.9 4.60 522.8 1.45 165.3 7.00 0.47 0.15 1.00 0.00 0.00 GROUP: 4M DOSE: .480 mg/L SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE ; 05/14/84 ANIMALS: 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 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 AVG. S. D. S. E. 13.49 1625.9 6.97 466.7 2.20 147.6 7.00 0.47 0.15 1.00 0.00 0.00 23 Company Sanitized. Does not contain TSCA CBI MR: _ _ _ COMPOUND; PERIOD: SEX: MALE ?388 HASKELL CODE:W\ DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 27-FEB-85 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL//: 376801 376807 376829 37-6834 376836 376837 376847 376861 376869 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 10-15 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 /Ipf 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 SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL//: 376800 376827 376831 376848 376856 376862 376866 376871 376877 376882 RBC /hpf 0-0 0-0 0-0 0-0 0-0 7-10 0-0 0-0 0-0 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 /Ipf 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 Y CL PPT FEED 24 Company Sanitized. Does not contain TSCA CBI MK:(------ COMPOUND: PERIOD: SEX: MALE HASKEI-L NUMBE;R: 153'88 HASKELL CODE:(^) R DEP.ARTMENT: POLYMER PRODUCTS REPIORT DATE: 27-FEB-85 GROUP: 3M DOSE:; .058 irlg/L SAMPLE DA'FE: 08 /30/84 SiPECIES: RAT IBIR'I-H DATE: 05/14/84 ANIMAL//: 376803 376808 376811 37-6817 376843 376846 376855 376860 376864 376875 RBC /hpf 0-3 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 WBC /hpf 4-6 1-2 3-5 1-2 0-2 5-10 2-4 10-20 5-8 0-4 Epifch /hpf 0-2 0-2 1-2 0-1 0-1 0-3 0-2 1-4 0-3 0-3 Cast /Ipf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 AlPPEARANCE 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 SAMPLE DATE: 08/30/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL//: 376814 376815 376816 376826 376832 376842 376845 376850 376853 376868 RBC /hpf 0-0 0-0 0-1 0-0 0-1 0-0 0-0 0-0 0-0 0-0 WBC /hpf 1-2 0-2 1-2 1-2 0-0 0-1 1-2 0-1 1-2 0-1 Epifch /hpf 4-6 1-2 1-3 3-5 0-1 0-2 1-3 1-2 3-5 1-3 Cask /Ipf 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 Y CL PPT FEED Y C PPT Y C PPT LY CL PPT FEED Y CL PPT FEED Y C PPT Y C PPT FECES 125 Company Sanitized. Does not contain TSCA CBI MR: COMPOUND: PERIOD; SEX: 84-D_A_Y_R_E_C MALE ^5388 HASKELL CODE^^| DEPARTMENT: POLYMER PRODOCTS REPORT DATE: 17-OCT-84 GROOP: 1CM DOSE: CONTROL SAMPLE DATE: 10/12/84 RBC Hb Ht ANIMALS: x10/uL g/dL % 376807 7.80 16.1 40. 376829 8.60 16.1 42. 376834 8.31 15.7 41. 376861 8.51 16.5 41. 376869 7.54 15.8 39. AVG. S^ D. S. E. 8.152 0.462 0.206 16.04 0.31 0.14 40.7 1.2 0.5 SPECIES: RAT BIRTH DATE; 05/14/84 MCV MCH MCHC PLAT fL P8 g/dL xlO^uL 50. .21. 40. 1120. 48. 19. 39. 1288. 49. 19. 38. 1154. 48. 19. 40. f120. 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 ing/L SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE; 05/14/84 ANIMALS: 376827 376831 376862 376877 376882 RBC xlO^uL 7.08 7.54 6.91 8.21 8.81 Hb g/dL 15.4 16.2 14.8 15.2 16.0 AVG. S. D. S. E. 7.710 0.795 0.355 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 MCHC PLAT Pg g/dL x1o3/uL 22. 41. 1434. 22. 41. 1324. 22. 42. 1446. 19. 39. 1074. 18. 36. 826. 20.3 1.8 0.8 39.6 2.5 1.1 1220.8 266.6 119.2 126 Company Sanitized. Does not contain TSCA CBI 15388 HASKELL CODE:f9) "L DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 34 DOSE: .058 mg/L SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALff: 376817 376846 376855 376864 376875 RBC x10/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 x1o3/uL 17. 34. 1022. 20. 38. 1162. 18. 36. 1180. 21. 39. 1312. 19. 36. 1028. AVG. S. D. S. E. 8.488 0.958 0.429 15.82 0.79 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 SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376316 376826 376842 376845 376868 RBC x10/uL 7.53 7.90 8.13 7.47 8.18 Hb g/dL 14.9 14.7 15.6 14.1 16.2 Ht MCV .% fL 37. 49. 39. 49. 43. 52. 40. 53. 43. 53. MCH MCHC PLAT Pg g/dL x1o3/uL 20. 40. 1208. 19. 37. 1174. 19. 37. 894. 19. 36. 20. 38. 972. 926. AVG. S. D. S. E. 7.842 15.10 40.5 51.2 19.3 37.4 1034.8 0.330 0.82 2.5 2.0 0.5 1.7 145.8 0.148 0.36 1.1 0.9 0.2 0.7 65.2 127 Company Sanitized. Does not contain TSCA CBI 15388 HASKELL CODE:^|| DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP; 1CM DOSE; CONTROL SAMPLE DATE: 10/12/84. SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS; 376807 376829 376834 376861 376869 WBC xlO^uL 11.9 10.9 13.0 10.4 12.0 AVG. S. D. S. E. 11.64 1.02 0.45 . Neut Band WBCx!( WBCxj? 2142. 0. 1744. 0. 1560. 0. 1872. 0. 1320. 0. 1727.6 0.0 311.1 0.0 139.1 0.0 Lymph WCx% 8449. 8938. 11050. 8112. 10320. Alym WCx% 476. 109. 130. 0. 120. Mono WBCxjE 714. 109. 130. 104. 0. Eosin WBCxjt 119. 0. 130. 312. 240. Bago WCx% 0. 0. 0. 0. 0. 9373.8 167.0 211. 4 160.2 0.0 1259.2 180.5 285. 5 120.1 0.0 563.1 80.7 127. 7 53.7 0.0 GROUP: 2M DOSE: .0076 mg/L SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALtf: 376827 376831 376862 376877 376882 WBC xloS/uL 13.3 13.5 15.5 10.1 12.8 AVG. S. D. S. E. 13.04 1.94 0.87 Neut WBCx% 2926. 2700. 2325. 1111. 1536. Band WBCxj6 0. 0. 0. 0. 0. 2119.6 0.0 772. 5 0.0 345. 5 0.0 Lymph WBCx% 9709. 10125. 12710. 8787. 10752. Alym WBCx% 133. 270. 155. 0. 384. Mono WBCxjE 399. 270. 310. 101. 128. Eoain WBCx? 133. 135. 0. 101. 0. Baso WBCx% 0. 0. 0. 0. 0. 10416.6 188.4 241.6 73. 8 0.0 1467.4 145.4 125.4 68.7 0.0 656.3 65. 0 56.1 30.7 0.0 28 Company Sanitized. Does not contain TSCA CBI HASKELL NUMBER: J.5388 HASKELL CODE:fl| DEPARTMENT! POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376817 376846 376855 376864 376875 WBC xlO^uL 17.1 18.1 16.5 12.2 21.4 AVG. S. D. S. E. 17.06 3.31 1.48 Neufc WBCxf, 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 WBCx? 342. 362. 0. 0. 428. Baso WBCx? 0. 0. 0. 0. 0. 13068.8 274.6 525. 6 226.4 0.0 2126.6 451.5 677. 3 209.1 0.0 951.0 201.9 302.9 93.5 0.0 GROUP: 4M DOSE: .480 mg/L SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMAL)?: 376816 376826 376842 376845 376868 WBC xiO^uL 24.2 17.9 23.1 18.0 17.1 AVG. S. D.. S. E. 20.06 3.32 1.48 Neufc WBCx% 7260. 3938. 5775. 6300. 3078. Band WBCx? 0. 0. 0. 0. 0. 5270.2 0.0 1721.6 0.0 769.9 0.0 Lymph WBCxjt 15972. 12351. 15708. 10800. 13338. Alym WBCx5( 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 0.0 2209.8 197. 5 519.1 303. 4 0.0 988.3 88. 3 232.1 135. 7 0.0 129 Company Sanitized. Does not contain TSCA CBI G------------------------------A :Q| MR: 1----R____HASKELL NUMBER; COMPOUND: PERIOD: SEX: W-DK^EC MALE 153 88 HASKELL CODE DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 1CM SAMPLE DATE: DOSE: 10/12/84 ANIMALff: 376807 376829 376834 376861 376869 AVG. S. 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 CONTROL SPECIES: RAT BIRTH DATE: 05/14/84 AST 0/L 65. 81. 69. 64. 49. BUN mg/dL 21. 16. 17. 21. 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 19.7 3.5 1.6 0.628 0.050 0.022 6.46 1.10 0.49 117.5 53.3 23.8 GROUP: 2M SAMPLE DATE: DOSE: 10/1,;2/84 ANIMAL)?: 376827 376831 376862 376877 376882 AVG. S. D. S. E. ALP U/L 110. 136. 190. 83. 150. 133.8 40.5 18.1 ALT U/L 30. 35. 32. 26. 23. 29.2 4.8 2.1 .0076 mg/L SPECIES; RAT BIRTH DATE: 05/1J4/84 AST U/L 60. 68. 65. 53. 56. BUN mg/dL 21. 19. 19. 20. 18. CREAT mg/dL 0.65 0.64 0.74 0.65 0.77 TPROT g/dL 6.4 7.2 7.3 7.1 7.2 ( MLOS nig/dL 73. 94. 118. 83. 94. 60.4 6.2 2.8 19.5 1.0 0.4 0.690 0.060 0.027 7.04 0.36 0.16 92.3 16.9 7.5 50 Company Sanitized. Does not contain TSCA CBI HASKELL NUMBER: ^15388 HASKELL CODE:QB! DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376817 376846 376855 376864 376875 ALP U/L 84. 156. 92. 211. 89. ALT AST BUN CREAT TPROT CHLOS U/L U/L mg/dL mg/dL g/dL mg/dL 33. 70. 87. 145. 26. 70. 40. 66. 30. 65. 23. 0.67 16. 0.62 19. 0.74 19. 0.65 18. 0.67 6.9 71. 6.8 96. 7.3 99. 7.4 124. 6.9 81. AVG. S. D. S. E. 126.4 55.7 24.9 43.2 25.0 11.2 83.2 34.6 15.5 19.2 2.7 1.2 0.670 0.044 0.020 7.06 0.27 0.12 94.4 20.1 9.0 GROUP: 4M DOSE; .480 ing/L SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ALP ALT AST BUN CREAT TPROT CHLOS ANIMALS: 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 224. 43. 97. 19. 0.71 6.4 49. 376845 70. 36. 74. 15. 0.63 6.7 93. 376868 72. 23. 53. 14. 0.67 7.0 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 2.1 0.9 0.642 0.059 0.027 6.88 0.34 0.15 75.0 16.1 7.2 15'! Company Sanitized. Does not contain TSCA CBI MR: f------ COMPOUND:) PERIOD: SEX: 84-DAY MALE HASKEL L NUMB ER: J53!88 HAS?:ELL COE DEPARTME)IT: POLKMER PRCDUCTS REPORT DjATE: 17-OCT-84 GROUP: 1CI4 DOSE: CONTRI3L SAMPLE DA'FE: 10/ 12/84 SPECIES: RAT BIRTH DA'rE: 05/114/84 ANIMALS: 376807 376829 376834 376861 376869 AVG. S. D. S. E. VOL mL 6.4 10.5 19.5 21.0 10.0 OSMOL m0s 2636. 2348. 763. 1337. 1836. BLOOD - + + - + SUGAR + - + + - PROTEIM +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 0.1 +1 8.0 - 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 SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376827 376831 376862 376877 376882 VOL mL 41.0 ' 8.4 10.2 9.4 18.0 OSMOL m0s 721. 2070. 1849. 2272. 1100. BLOOD + +1 +1 - + SUGAR +1 - +1 - + PRO TEIN +1 +2 +2 +2 +1 PH BILI- UROBL Ke- RUBIN mg/dL fcone 7.0 7.0 +1 7.0 +1 7.0 - 7.0 - 0.1 1.0 + 1.0 + 1.0 +1 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 0.49 0.22 32 Company Sanitized. Does not contain TSCA CBI 15388 HASKELL COOE:(|BB DEPARTMENT! POLYMER PRODUCTS REPORT DATE: 17-OCT-84 GROUP: 3M DOSE: .058 mg/L SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 376817 376846 376855 376864 376875 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 PH BILI- UROBL Ke- RUBIN mg/dL fcone 8.0 - 1.0 +1 7.0 - 0.1 + 7.0 - 7.0 8.0 +1 0.1 1.0 1.0 +1 AVG. S. D. S. E. 16.30 1363.6 5.43 361.3 2.43 161.6 7.40 0.55 0.24 0.64 0.49 0.22 GROUP: 4M DOSE: .480 mg/L SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALtf: 376816 376826 376842 376845 376868 AVG. S. D. S. E. VOL mL 18.5 18.5 5.7 30.0 12.5 OSMOL mOs 1292. 1372. 2348. 839. 1381. BLOOD + + + +1 + SUGAR + + +1 + + PRO TEIN +1 +2 +2 +1 +1 17.04 1446.4 8.96 551.2 4.01 246.5 PH BILI- UROBL Ke- RUBIN mg/dL fcone 8.0 7.0 7.0 7.0 7.0 - 0.1 + 1.0 +1 1.0 + 0.1 0.1 + 7.20 0.45 0.20 0.46 0.49 0.22 35 Company Sanitized. Does not contain TSCA CBI 15388 HASKELL CODEflj DEPARTMENT: POLYMER PRODOCTS REPORT DATE: 17-OCT-84 GROUP: 1CM DOSE: CONTROL SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALtf: 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 /Ipf 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 PECES GROUP: 2M DOSE: .0076 mg/L SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALff: 376827 376831 376862 376877 376882 RBC /bpf 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 /Ipf 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 134 Company Sanitized. Does not contain TSCA CBI HASKELL NUMBER: 15388 HASKELL CODE:(|B> DEPARTMENT: POLYMER PRODOCTS REPORT DATE: 17-OCT-84 GROOP: 3M DOSE: .058 mg/L SAMPLE DATE: 10/12/84 SPECIES: RAT BIRTH DATE: 05/14/84 ANIMALS: 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 /Ipf 0-0 0-0 0-0 0-0 0-0 APPEARANCE Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y GL PPT Y CL PPT GROUP: 4M DOSE: .480 mg/L SAMPLE DATE: 10/12/84 SPECIES: RAT 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 /Ipf 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 55 Company Sanitized. Does not contain TSCA CBI APPENDIX VII BLOOD FLUORINE ANALYTICAL REPORTS -136- Company Sanitized. Does not contain TSCA CBI ESTAfitlSHEO 1802 E. I. DU PONT DE NEMOURS S COMPANY .INCORPORATED WILMINGTON, DELAWARE 19898 CHEMICALS AND PIGMENTS DEPARTMENT JACKSON LABORATORY October 18. 1984 TO: y FROM: L. A. Kinney CR&D, Haskell Lab. E. Kissa ,^*-^ -<^^<- C&P, Jackson Lab. FLUORINE IN BLOOD We have analyzed--tat blood samples of the inhalation subchronic blood sampireswereanaTyzedfortota^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^^od, Cb> was found to increase exponentially with the increasingflfm; oncentration in air, Cg (/ FiT" ; g-- . D. 1 ^ e--x--p--re-*s_s---ed---Aa-s_:- ~ ^ n c. = k c The values of the coefficient, k, and to a lesser extent, the values of the exponent n. decreased with the increasing recovery time. (Table I). 137 Company Sanitized. Does not contain TSCA CBI .Page 2 October 18. 1984 L. A. Kinnev TABLE I ORGANIC FLUORINE IN RAT BLOOD Exposure Coonne^. of B^jnaZm3! ppm Organic Fluorine in Blood* 2-Weeks 6-Weeks Initial Recovery 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. 2.87 1.31 0.67 n 0.64 0.56 0.54 During the recovery period the logarithm of organic fluorine content of blood decreased with the square root of the recovery time (Fig. 2), suggesting that fluorine is eliminated by a diffusion controlled process: log (Ct/Co) = kctO.5 where c^ is the organic fluorine concentration at time t, Cg the initial'organic fluorine concentration, and kjc the recovery coefficient. TABLE II DESORPTION RATE OF FLUORINE FROM BLOOD Eoxf o(If--lBu--re--CinoAneir. (mg/m3)____ Recovery time (weeks) Needed for the Fluorine Values to Return to Normal k, (1 ppm or less) Values 0 7.6 58 480 -0.31 11 -0.32 26 -0.39 31 The value of the desorption coefficient k^ for human blood differs probably from that of cat blood, but the desorption mechanism may be similar. The inorganic (ionic) fluorine in rat blood increased slightly, but perhaps significantly, If the slight increase as a result of exposure toftHj^(Table III). was significant, the ionic ^Luorine returned to normal values in a relatively short time. ]38 Company Sanitized. Does not contain TSCA CBI ^^k-UUCJ- JL U , J. 7 01 L. A. Kinnei ;ure Jconc, in Air (mq./m3) 0 0 0 0 480 480 480 480 TABLE III INORGANIC (IONIC) FLUORINE IN RAT BLOOD Recovery Time (Weeks) Organic Fluorine (PPnO 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 if the significance of samples will the apparent be io n an ic al f yz lu ed ori f n o e r e i l o e n v ic at i flu on obryi nfleB. f, _ u 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 uccooer 1B, 1984 L__A^ Kinney___ FLUORINE IN BLOOD TABLE IV TOTAL FLUORINE IN RAT BLOOD OF THE INHALATION SUBCHBONIC STUDY ON TOTAL FLUORINE (PPM) !roup I - Control II - Low [I - Inter. V - High Cone. in Air 0 ins/in3 7.6 ing/m3 58 mg/m3 480 ing/in3 !nitia;L Rat Number PPIP F 376839 376870 376840 376873 376825 376804 376844 376806 376823 376818 376805 376838 376851 376821 376867 376854 376879 376828 376820 376859 1..5 1.,7 1.4 4.6 1.0 10. 8 7. 6 10. 5 10. 8 11. 1 44. 3 46. 0 44. 4 47.4 28. 0 140. 0 168. 0 112. 0 176. 0 138. 0 Avg. 2.0 Avg. 10.2 Avg. 42.0 Avg. 147 2-Weel:s R(icovrery Rat Number EESn F 376872 1..0 376849 0. 7 376835 1.1 376841 0.7 376863 1.1 376810 3. 4 376876 4. 4 376852 3. 4 376822 4. 0 376881 4. 7 376874 376812 376813 376857 376830 15. 1 12. 9 10. 3 11. 8 14. 9 376858 376824 376880 376833 376819 41. 2 34. 7 33. 6 37. 9 55. 0 Avg. 0.9 Avg. 4.0 Avg. 13.0 Avg. 40.5 6-Weeks Rec;overy Rat Number PPn F 376801 376836 376837 376878 376847 376871 376800 376848 376866 376856 376808 376811 376803 376843 376860 376815 376814 376853 376850 376832 0,,8 1.,3 0.5 0.7 1.0 1.6 1.4 2. 0 2. 1 1. 7 8. 2 8. 6 5. 3 6. 9 7. 0 16. 8 11.. 1 17. 7 18. 7 18. 8 Avg. 0.9 Avg. 1.8 Avg. 7.2 Avg. 16.6 :jve 24J 140 Company Sanitized. Does not contain TSCA CBI /^^ ^ Fig. 1. Concentration of organic fluorine in blood as a function of(m^;oncentratlon in air. 41 Company Sanitized. Does not contain TSCA CBI ^===^^iiii^i^ll^llilllll|illlll lIllllllll-simiE! Elhs--li^ EEElEEE^E^E^^^^f^-rtiT^' g^EE^^E^S^^:^^^ :^^::=^^::^::==:===::^lt:=:=3::^:=== =- ; =?== = : = ^ S = = =da= -^ =: = t=== =^==1= ==3=c= = ------J----4- - 1,1|.- 3 ) j - --1-p-1---j-- - - ----{ * ----------(----l-t-p------------*--T-1---- -^--' ' i IT' 1 I 1 ' 1 l 7-* T -^---------------------t:.-!:^--..^4.. '^ST+T-------------------I--^+-------- J 1 I-:--:S:^--^-t:-:~::--^-4--:-:--:-:-:-:-:-:-:-:--:-:-:-:-:-:-:--:-:-:-:-:-^- - 1 ^-^^1^ ? ^-------------- ^--------..------ ..;E;E::::E::l:::::::::^llim^i ^===^====-^-l-L-^=;^S=^^:^=;;=;^^;^ 8 ==^===El===^^====-|===^:==p=:=:====EEE^IEEEEEEEEEEEEE^EEEEEEl-EEEE-i-E , EE|EE===EE|EE|!-|EEE=^rE::E:::E::=1:E!:=::=::=::E:::E::E:::::::::::::::::::: U T B --------------------+1--------4----+--------J----1,i,g----l--(t--+----------------------- ,s -: -: -: -:-:-:-:-:-:-: : - : : :- :^:-:-:-:-:- :- :- -:-:-:-:-:.:, ^^ -;-,-:-:-:-:-:-:-:-:- ^ ^ |"S0 :::::::::::::::::":::::::::::::::^- ::"::: -----------------s----a------------. igS2 ---------------- ---------------------'S '^ ----------------.--------------.-------- ====i===EEE=E=^shii==|i===!=====EE|=!=E B ===============5ESs============::===== B------------------S,------,.----. a ---------------------------U---^-------L-- -.-5-^-.--.-,-.-,-..^^^Z^ s ^TM g------------------..--. '< Jl '* ^ y ^^ /.,^ ^.^ ^\ ^) ^.^' ^ 5'.^ ' y ^' r^^^^< Company Sanitized. Does not contain TSCA CBI ESTABUSHEO IB02 E. 1. DU PONT DE NEMOURS & COMPANY INCORPORATED WiLMINGTON, DELAWARE 19898 CHEMICALS AND PIGMENTS DEPARTMENT JACKSON LABORATORY December 19, 1984 TO: ^L. A. Kinney /^CR&D. Haskell Lab. FROM: E. Kissa ^e*^ ^^yc^ 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 .hefluorine data of the inhalation subchronic study on To compare the recovery rate of fSrelated 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 riot 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/Co) = kr t0.5. (1) where c^ is the organic fluorine concentration in blood at time t. CQ the initial organic fluorine concentration in blood, and k^ the recovery coefficient. (Fig. 2 in Kissa to Kinney, October 18, 1984.) 143 Company Sanitized. Does not contain TSCA CBI December 19, 1984 L. A. Kinne\ - FLUORINE IN BLOOD The average fluorine values of the 12-veeks 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 PPIP______ Fluorine Cone. after 12-weeks Recovery _Pr_e_d_ic_te_d_______Efin_____F_ou_n_d____ 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 reco've.r'y..P^lod than those calculated for the 0 to 6-weeks r-fr&overy period, but the correlation with equation (I) is still reasonable: ExDpsure Cone. ofj----Tin Air (mq./m^ Linear Correlation Coefficient ffor log c vs. t0-5) 0-6 weeks 0-12 weeks Recovery Coefficient kg 0-6 weeks 0-12 weeks 0.9991 0.995 0.9998 I reported in ORBi^mO that the period of a perfluorooctanoic acid first-order kinetics. 0.993 0.992 0.995 -0.31 -0.32 -0.39 -0.35 -0.36 -0.43 decay of fluorine during recovery feeding study approximates log Ct/Co = 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 recovfijjv time than predicted by equation (2). The first-order plot of|^|Rjdata also shows curvature (Fig. 2). Conceivably the rate at which a fluorocompound is eliminated from blood is not the same for different[aBE}teloiaes. 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 type of a mechanism is needed to explain its decreasing coefficient of the-elimination rate. Perhaps perfluorooctanoic acid dissolved in blood is eliminated from blood at a fast rate. but perfluorooctanoic acid bound to protein in blood at a slower rate, perhaps together with the protein on which it is adsorbed. Whatever the true mechanism, the expected result is a decrease of the recovery rate (fluorine elimination rate) coefficient with increasing time. 144 Company Sanitized. Does not contain TSCA CBI WWUtUVl. if, i101 FLUORINE IN BLOOD The average fluorine removal rate coefficient k^ during a time interval At can be calculated from the equation ft - ^a- <3^ where Ac is the average fluorine concentration decrease and Cg the average fluorine concentration during time interval At. It follows that log (Ac) = log k^ + z log Cg (4) At A plot ofQHUrecovery data according to the equation (4) yields straight lines with the average z value of one. However, the log k^. and consequently, the k^' values are not constant, but de wi cre th ase my with expla the natio in n cr of e asing curva t rec ure o ve in r y f i tine rst o ( r T d a e b r l e p l I o I t ) s , in accord (Fig. 3 and 4). Hence log (Ct/Co) = ktt (5) where k^ is the time dependent rate coefficient at time t. l^data The question remains, why does the ^^^dl fit equation (5) and also, as a reasonable approximation, equation (1). Since the left side of the equations is the same. the right side has to be the same function of time. This is the case when kt = kr/tV. (6) where y is an exponent. If y = 0.5 kt = kr/tO-5' (7) and the equation (5) becomes equation (1) log (c,/c,) = _^= k,t0-5. (8) Although the time intervals ofUm^recovery data are not suited for redefining the time dependence oftne rate coefficients, the kf values seem to vary approximately with the square root of time. (Table III). 45 Company Sanitized. Does not contain TSCA CBI uecemoer if, i^yi .L. A. Kinney FLUORINE IN BLOOD In summary, the elimination of organic fluorine from blood can be described by a time dependent rate coefficient ki and an exponent z, that is approximately equal to one. A logarithmic plot log (Ac/At) = log k^ + z log Cg (9) or regression analysis using a pocket calculator, yields k^. A comparison of^flBRtand perfluorooctanoic acid decay in blood suggests that k^ values of anionic fluorosurfactants in blood may not be largely different. However,[fHQis 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 PERIOD Exposure Control : (0 ng/m3) Low: (7.6 mg/m3) Intermediate; (58 mg/n3) 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 PPP 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 PPP 0.40 0.61 2.16 4.38 147 Company Sanitized. Does not contain TSCA CBI TABLE II KINETICS OF FLUORINE ELIMINATION FROM RAT BLOOD Recovery Period (weeks)___ 0-2 2-6 6-12 Fluorochemical (inhan^ion) Rate Coefficient __kt____ 0.36 0.17 0.16 Average Exponent z 1.10 1.03 1.07 1.07 0-2 Perfluorooctanoic 0.73 . 0.92 2-6 Acid (feeding) 0.33 1.03 Average 0.98 Recovery Period (weeks) 0-2 2-6 6-12 TABLE III RATE COEFFICIENTS AS A FUNCTION OF TIME Average Recovery Time (weeks) Square Root of Average Recovery Time_____ Found 0.36 0.17 0.16 Rate Coefficients Perfluorooctanoic Calc.* _Fo_u_n_d AcCida_lc_._* __ 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 n: u u a 5?i 55 g -I Q -^------------.------------^^^ 7~ / /^ ^ C ^^p^iv^fSf^.e^' Dbes not contain TSCA CBI 1<: L ; 3 'r a u a n. tE^" ( > i> 0 i in uj ^ i o u < ^ r/ ^^ '^^"^m^an/Sanitized. ^ Does not contain ' TSCACBI ^^ 51 Company Sanitized. Does not contain TSCA CBI ^ ^ ^ / ^a ^ 152 Company Sanitized. Does not contain TSCA CBI APPENDIX VIII BLOOD FLUORINE STATISTICS 153 Company Sanitized. Does not contain TSCA CBI ^ MEAN BLOOD FLOURINE CONCENTRATIONS ^TC?sinLog(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 1.243K 2.0028( 2.6159( 3.161-2 ( 0.000) 0.000)# 0.000)# 0.000)# TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST 0.000 0.000 0.034 0.9546( 1.596K 2.1095( 2.6001( 0.000) 0.000)# 0.000)# 0.000)# 0.000 0.000 0.818 0.9122( 1.2408( 1.8513( 2.2129( 0.000) 0.000)# 0.000)# 0.000)# 0.000 0.000 0.425 GROUP 84 DAYS POST EXPOSURE CONTROL 7.6 MG/CM 58 MG/CM 480 MG/CM 0 .560K 0 .7820( 1 .2889( 1 6300( 0.000) 0.054) 0.000)ft 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 154 Company Sanitized. Does not contain TSCA CBI