Document EvGMQDowJEZg1QBamQ2EbKy2g

f 0,3?, 7Sffi~ VmM' 7jT^mj fb.(jfi <-/f* tTM***-, Jtrppn < 7/3 - ^56?T t 'not mXV^ -m*M l,dee*$Gfi{JoTU> fop/itJjkt&fc tPC&ticStif ftusj4*} co-iA^U^ h**y/ ' 71P [0,1,1$] 0,1 uaJ$ P*^ Omum^ SL 070202 90-DAY REPEATED INHALATION TOXICITY STUDY OF VINYLTDENE CHLORIDE IN RATS M. F. Baimer, L. W. Rampy and J. F. Quast Reviewed by: J. M. Norris '/ September 10, 1976 Toxicology Research LaboratoryHealth and Environmental Research Dow Chemical U.S.A. 1803 Building Midland, Michigan 48640 SL 070203 SUMMARY AND CONCLUSIONS Groups of male and female Sprague-Dawley rats have been repeatedly exposed to vinylidene chloride (VDC) vapors by inhalation 6 hrs/day, 5 days/week. Rats were exposed to 25 or 75 ppm VDC vapors 60 times during 90 days. There was an interim kill after 30 days of the study. Another, parallel, study was carried out in the same chambers. The second study was a two-year study. No adverse effects were seen with respect to body weight, hematologic parameters, clinical chemistry values, demeano?: or mortality in animals of either sex. Minimal microscopic changes in the liver in the form of cytoplasmic vacuolation of the hepatocytes occurred in occasional animals in both levels at the 30-day interim kill. The incidence of hepatic changes was greater in animals of the 75 ppm group which were examined at the end of the 90-day study. At this point in time, it is concluded that repeated exposure of rats to 25 or 75 ppm of VDC vapors results in minimal liver injury. SL 070204 INTRODUCTION The toxicity study of rats exposed by inhalation to vinylidene chloride (VDC) vapors, reported heroin, is one of a series of studies being conducted in order to evaluate the toxicity and possible tumorigenesis of VDC. This study was financed by member companies of the Manufacturing Chemists Association and was conducted in the Toxicology Research Laboratory, Health and Environmental Research, The Dow Chemical Company. METHODS Test Material. Production grade vinylidene chloride from the Midland, Michigan plant of The Dow Chemical Company was used in this study. The inhibitor (hydroquinone monomethyl ether) level present was in the range of 130 to 240 ppm with single determinations of 558 and 1600 ppm for single containers from the last portions of two batches used. Vapor Generation, Analysis, and Chambers. The VDC vapor was generated by metering the liquid compound into a glass vapori zation flask at a controlled rate. The temperature of the flask was maintained at approximately 25C. The vapor was swept by air into the exposure chamber at an air-flow rate calculated to produce the desired concentration. SL 070205 Analysis of the chamber atmosphere was normally done 2 to 5 times during the exposure period by infrared spectroscopy. A Perkin-Elmer Model 12A I.R. spectrophotometer was used. A path length of 10 meters and a wavelength of 12.6 \i were used for the analysis. Chamber concentration was determined by interpolating from a standard curve. The standard curve was obtained by preparing known concentrations of VDC in air in the range of concentration. Exposures were carried out in a 3.7 cubic meter stainless steel chamber under dynamic airflow conditions. Control animals were maintained at ambient condi tions in an animal holding room. Animal Exposures. Groups of Sprague-Dawley (Spartan substrain) weanling rats, equally divided by sex, were exposed to 0, 25, or 75 ppm of VDC. Groups of 20 rats/sex were used in each exposure level. Eight rats/sex/exposure level were killed for examination on the 32nd day of the study. The remaining 12 rats/sex/exposure level were killed for examination on day 90 of the study. Male rats were in the body weight range of 275-310 g at the start of the study. Female rats weighed 190-210 g. The duration of exposure was 6 hrs/day 5 days/week. There were 21 exposures in 32 days for rats in the "30" day interim kill and 60 exposures in 90 days for rats in the "90" day group. Food and water were not available to exposed or control animals during the daily exposures. Between exposures food and water were available ad libitum. SL 070206 Two parallel studies were conducted simultaneously in the same exposure chamber. The second study was a long-term inhalation study which continued after termination of the 90-day study. Animal Observation. Rats were observed during the exposure period for changes in appearance or demeanor. Special attention was given to observing possible eye or nasal irritation. Body weights were recorded weekly for the first month, twice during the second month, and at termination. Hematology. Hematologic parameters including red blood cell count, hemoglobin concentration, packed cell volume, and total and differential white blood cell count were determined on 5 rats/sex/level shortly before the 30 and 90-day sacrifices. Blood for the hematological determinations was taken from the tail vein. Clinical Chemistry. Clinical chemistry determinations were carried out on serum samples collected from all animals at both the 30 and 90-day sacrifice. Determinations carried out included serum glutamic pyruvic transaminase (SGPT) activity, blood urea nitrogen (BUN) level, and alkaline phosphatase (AP) activity. Pathology. At the time of sacrifice, each rat was anesthetized with methoxyflurane prior to clamping of the trachea and SL 070207 decapitation. The lungs and trachea were removed as a unit and expanded with 10% buffered formalin. Animals were fasted overnight prior to sacrifice. The heart, liver, kidneys, brain, and testes (males) were removed and weighed. Represen tative specimens of the following organs and tissues were taken from all animals and fixed in .10% neutral buffered formalin: adrenal glands, all gross lesions, heart, aorta, bone marrow, brain, ear canal, esophagus, gonads (testes and ovaries), kidneys, large intestine, larynx, liver, lungs, lymph nodes (mediastinal and mesenteric), mammary tissue, pancreas, parathyroid gland, peripheral nerve (sciatic), pituitary gland, prostate, accessory sex glands, epididymides, salivary gland, seminal vesicles, skeletal muscle, skin, small intestine, spinal cord, sternum, spleen, stomach, thymus, thyroid gland, trachea, urinary bladder, uterus and nasal turbinate. Eyes were fixed in Zenker's fixative. The above tissues were processed by conventional methods, stained with hematoxylin and eosin, and evaluated by light microscopy. Statistical Evaluation. Body weight, clinical chemistry, hematology, and organ weight data have been analyzed using an analysis of variance with comparison of group means by Dunnett's test. SL 070208 RESULTS AND DISCUSSION Analysis. Each batch of production grade vinylidene chloride used in the study was checked by gas chromatography to establish identity and levels of impurities. The impurities and ranges of concentrations found are in Table 1. Also in Table 1 are the calculated concentration of impurities that would be found in a 75 ppm atmosphere of vinylidene chloride, assuming total vaporization of the sample. The mean chamber concentrations, standard deviations and percent of exposures within 10% and 25% of nominal concentration are in Table 2. 'The mean exposure levels were 26.4 ppm and 72.7 ppm. Animal Observation. No signs of eye or nasal irritation or other changes in appearance or demeanor were observed in any of the animals. No significant differences in body weight have been seen between VDC exposed and control groups of either sex in the 90-day study (Figure 1) . Hematology. Mean hematologic values are recorded in Tables 3 and 4. Packed cell volume, red blood cell count, and hemoglobin concentration were statistically significantly lower at 30 days for male rats exposed to 25 ppm of VDC than for control rats. SL 070209 None of these values remained low at the end of the study, nor were other differences seen. For female rats in the 90-day study, red and white blood cell counts and hemoglobin concentration were statistically significantly lower at 30 days exposure for the 25 ppm group than for controls. Of these values, only the hemoglobin concentration remained low at the end of the study. The mean white blood cell count for the 75 ppm group of females was lower than the control group at the end of the study. Although statistically significant differences in hematological values appeared between groups, they did not appear consistently in the same exposure group at different times, nor were they dose-related. The mean values are within the range of values normally seen in the Sprague-Dawley rats used in this laboratory. For these reasons it is concluded that exposure to VDC vapors has produced no toxicologically significant changes in hemato logical parameters. Clinical Chemistry. Clinical chemistry values for rats exposed to VDC are presented in Tables 5 and 6. Male rats exposed to 25 ppm of VDC had a statistically significantly lower mean alkaline phosphatase activity at 90 days* Female rats at the same exposure level had a statistically significantly increased alkaline phosphatase activity. Since changes in this value were not seen at the higher exposure level and were different in the two sexes, they are not thought to be associated with organ damage. SL 070210 SGPT activity was statistically significantly lower at 90 clays for both VDC-exposed groups of males. This value was also low at 30 and 90 days for females exposed to 75 ppm of VDC. Since there was evidence of liver effects in these experiments (see below), elevated SGPT values would be expected instead of lower values. The significance of reduced SGPT activity, if any, is not known. It does not appear to be associated with toxico logical effects in this experiment. Mortality. No deaths occurred in animals in the 90-day exposure. PATHOLOGY Organ Weights. Mean organ weight and organ/body weight ratios are presented in Tables 7 and 8. No significant differences were found in these values at either the 30-day interim kill or the 90-day final kill. 90-Day Exposure - 30-Day Interim Kill. Gross pathologic findings in male and female rats killed at 30 days of the 90-day exposure are presented in Table 9. There were no gross pathologic changes present in either male or female rats considered treatmentrelated. Histopathologic findings in male and female rats are presented in Tables 10 and 11, respectively. Treatment-related histopathologic changes in the liver were found in both male and female exposed rats. The microscopic changes were characterized SL 0?02lj by occasional individual hepatocytes having a vacuolated cytoplasm. This was very minimal in amount at both exposure levels. Histo pathologic changes in the kidneys of female control and exposed rats show a very minimal degree of focal chronic progressive nephrosis. This is a spontaneously occurring lesion in these rats and is qualitatively identical in the control and exposed rats. All other pathologic observations were interpreted to be spontaneous in occurrence and comparable in the exposed and control rats. The pathologic changes observed in the livers of treated rats are interpreted to be of a reversible nature. 90-Day Exposure - Final Kill. Gross pathologic findings in male and female rats killed at the end of the 90-day exposure are presented in Table 12. There were no gross pathologic changes present in either male or female rats considered treatmentrelated. Histopathologic findings in male and female rats are presented in Tables 13 and 14, respectively. Treatment-related histopathologic changes in the liver were found in both male and female exposed rats. The microscopic liver changes are charac terized by a minimal increased degree of vacuolation in the cytoplasm of the hepatocytes. These minimal changes were seen in rats at both exposure levels. Histopathologic changes in the kidneys of exposed or control rats do not show a qualitative or quantitative difference. The remaining microscopic alterations listed in the tables are considered spontaneous in occurrence and of comparable degree in control and exposed rats. The character SL 070212 of the hepatic changes at this time are comparable to those observed after 30 days exposure; however, a greater number of exposed rats show a microscopic change after 90 days exposure. Microscopic examination of the 1 nun sized circumscribed white foci in the epididymis of two rats in the top exposure group revealed the presence of an intratubular sperm granuloma. In view of the unilateral location and localized confinement in the epididymis it is not considered treatment-related. The pathologic changes observed in the livers of treated rats are interpreted to be of a reversible nature. SL 070213 Mean Body W eight (gram s) o+ O Control 600 Q 25 ppm **' 75 ppm 500 400 300 rS O O o j-. Q 0 200 6U Q Q FIGURE 1 Mean Body Weights of Rats on 90 Day Exposure to Vinylidene Chloride Vapors J<* a MALE <3 23 'o' t* B o, FEMAL t 100 to f o o N> 2 Month of Study 3 TABLE 1 Typical Analysis of Vinylidene Chloride and Calculated Chamber Concentrations of Impurities Impurities Vinyl chloride Vinyl bromide cis 1,2-dichioroethylene trans 1, 2-dichloroethylene 1.1.1 trichloroethane 1.1.2 trichloroethane Analysis* 0-0.12%** 0-14 ppm 0.003-0.15% 0.02-0.3% 0-3 ppm 0.0.9 ppm Maximum Concentration (Calculated) in 75 ppm _____ Atmosphere _______ 104 ppb 1.1 ppb 126 ppb 237 ppb 0.2 ppb 0.05 ppb Inhibitors Kydroquinone monomethyl ether Vinylidene Chloride 130-240 ppm*** 119 ppb 74.41 ppm * ** *** Gas chromatographic analysis Analysis from 4 batches 1200 ppm, 50 ppm, 2 ppm, 3 There were single determinations of ppm 558 and 1600 ppm for single , containers rrom the la portions of two batches used. SL 070215 TABLE 2 Chamber Concentration!:; of Vinylidcne Cli.Tor.iclc Vapor Nominal Concentration (ppm) Analytical Concentration +S.D. (ppm) % of Exposure Days Within 10% of Nominal Concentration % of Exposure Days Within 25% of Nominal Concentration 25 26.4 4.0 75 72.7 +3.8 45 63 82 98 SL 070216 SL 070217 Exposure T^ 1 0 25 75 Time 30 days 30 days 30 days TABLE 3 Mean ( S.D.) Hematologic Values for Kale Rats on 90 Day Exposure to Vinylidene Chloride Vapors Differential Count PCV EEC Hgfc EEC Kcut N % x 105/mm5 g/lOOml x 10 3 /.Tim3 Seg. 3/J Lvm * ri. ,0 3 5 58.6+2.0 8.72;0,71 13.4+0.7 16.3il 8 10 0 88 i i 5 52.4+5.0* 7.54+0.67* 17.3+1.3* 18.9+4.4 14 0 35 1 0 5 55.62.9 8.45i0.53 18.0+0.7 17.9+3.1 13 0 85 0 0 81 days 5 53.8+1.6 7.69+0.78 17.9+1.0 13.9+1.1 15 0 77 6 1 25 81 days 5 54.2+3.8 7.45+0.20 18.OiO.9 11.9+1.1 16 0 77 6 1 75 81 days 5 53.9+1.3 7.39+0.39 17.9+0.6 14.6+1.7 17 0 72 8 3 Significantly lower than control group by Analysis of Variance and Dunnett1 s test (P<o.o5:1 . 0 0 0 0 0 0 Level 0 25 75 0 25 75 Time 30 days 30 days 30 days 31 days 81 days 81 days TABLE 4 Kean (i S.D.) Hematologic Values for Female Rats on 90 Day Exposure to Vinylidene Chloride Vapors Differential Count PCV RBC Hgb W3C ---- H % x 10s/mm* q/lOOml x 103/mm3Seg. 3/J Lym Mon. Eos . 3as 5 52.0+3.6 8.2110.31 17.5+0.3 15.211.6 8 0 90 1 i 0 5 49.0+1.8 7.07+C.53* 15.S+0.6* 12.1+3.3* 14 0 84 0 2 0 5 49.813.7 7.42+0.85 16.5+1.3 13.4+2.9 11 0 87 1 1 0 5 46.8+1.7 6.15+0.44 16.4+0.05 12.012.3 12 0 81 5 2 0 5 44.5+2.2 5.92+0.30 15.2+0.4* 10.9+2.9 11 0 84 3 2 0 5 48.013.1 6.13+0.69 16.1+0.9 3.0 + 1.5 + 11 0 84 4 `1 0 Significantly lower than control group by Analysis of Variance and Dunnctt's test (p<0.05). SL 070218 TABLE 5 xposurc Level (ppm) Mean ( S.D.) Clinical Chemistry Values for Male Rats on 90 Day Exposure to Vinylidenc Chloride Vapors SGPT BUN Aik. Phos Time N mU/ml mg/lOOrnl mU/ml 0 30 days 8 33 6 22.24.3 232+52 25 30 days 8 32 + 3 25.4 2.9 21239 75 30 days 8 34 5 23.8 + 4.6 199+28 0 90 days 12 52 + 7 19.7+2.7 224+79 25 90 days 12 387* 21.8+2.5 128+27* 75 90 days 12 41+9* 21.0+3.2 179+40 *Significantly different from control group by Analysis of Variance and Dunnett's test, p<0.05. SL 070219 TABLE 6 Exposure Level (ppm) Mean ( + S.D.) Clinical Chemistry Values for Female Rats on 90 Day Exposure to Vinylidene Chloride Vapors SGPT Time N mU/m]- BUN mg/100ml Alk.` Phos mU/ml 0 30 days 8 28 + 5 26.217.4 154+28 25 30 days 8 25 + 3 25.2+3.8 162+36 75 30 days 8 2 2 + 4* 24.8+7.2 145+32 0 90 days 12 35+6 21.5+4.9 88+11 25 90 days 12 31 4 22.8+3.4 109+33* 75 90 days 12 30 + 4* 24.0+3.1 76+15 *Significantly different from control group by Analysis of Variance and Dunnett's test, p<0.05. SL 07022C TABLE 7 Exposere Level Cw.) Tine 0 30 days 25 30 days 75 30 days 8 8 8 Mean (1 S.D.) Organ Weights and Organ to Body Weight Ratios for Male Eats on 90 Day Exposure to Vir.ylidene Chloride Vapors Body Weight Brain <R) g/lOOg Heart g/100s_. Liver _g/100fi Kid r.c? AJ, p/lOOg 3S3H4.3 X.88+0.04 0.49+0.01 1.20+0.03 0.3210.03 11.36+0.93 2.9710.18 2.7410.16 0.7210,04 Testes 3.6210.27 0.9510.07 378+19.5 1.85+0.06 0.49+0.02 1.1710.07 0.31+0.01 11.20+0.95 2.9610.17 2.7S10.16 0.7410,03 3.8610.13 1.0310.07 390111.4 1.87+0.05 0.48+0.02 1.2210.08 0.31+0.02 11.3910.97 2.9310.24 2.S710.25 0.74+0.07 3.7910.24 0.9710.OS 90 days 12 90 days 12 90 days 12 449.1148.7 1.34+0.12 468.7+20,3 1.91+0.06 467.4+27.0 1.9110.06 0.4210,06 0.41+0.02 0.41+0.02 1.25+0.15 0.2810,02 1.29+0.05 0.27+0,01 1,35+0.09 0.29+0.02 13.4012.35 2.9610.35 12.2211,02 2.6110.21 12.79+0.78 2.74+0.14 2.83+0.42 0.6310.05 3.801(5.27 0.S51C.10 2.96+0.10 0.6310.03 3.9610.18 0.6510.04 3.0010.26 0.6410,03 3.S6;0.41 0.S310.10 Wo significant differences between exposed and control groups by Analysis of Variance and Dunnctt s test, p<0,05. SL 070221 Exposur e Level (p^-> Tine X 0 30 days 8 25 30 days 8 75 30 days 8 TABLE 8 Kean ( S.D.) Organ Weights and Organ to Body Weight Ratios for Female Rats on 90 Day Exposure to Vinylidene Chloride Vapors Body Weight (r) Brain R/100R Heart g/lOOg Liver R/lCOn 244tll,3 246+8.7 243H0.0 1.70+0.04 1.77+0.72 1.71+0.05 0.7010.04 0.72+0.03 0.71+0.03 0.8610.05 0.8610.04 0.8910.07 0.35+0.02 0,35+0.02 0.3710.03 6,95+0.52 7.0810.48 7.0210.48 2.8510.18 2,88+0.14 2.8910.12 R r/IOOr 1.7110.13 1.8110.12 1.7610.10 0.70+0.05 0.7310.04 0.73+0.03 0 90 days 12 25 90 days 12 75 90 days 12 281.7+19.9 271.5+27.2 262.4117.9 1.74+0.08 . 0.62+0.05 1.7810.03 0.6610.07 1.74+0.10 0.67+0.06 0.92+0.03 0.33+0.02 0.91+0.06 0.34+0.03 0.9610.07 0.37+0.03 6.78+0.70 2.41+0.14 6.5810.38 2.4410.24 6.8310.67 2.61+0.25 1.7410.15 1.8010.16 1.3910.13 0.6210.04 0.670.07 0.72i0,03 Xo significant differences between exposed and control groups by Analysis of Variance and Dunnett's test, p<0.05 SL 070222 TABLE 9 GKOS9 PATHOLOGIC HEDINCS IN RATS OK 90 DAY EXPOSURE TO VJKYLIDF.NE CHLORIDE VAPORS - 30 DAY INTERIM KILL Pathologic. Findings Males No visible lesions Dilated renal pelvis, unilateral, right Focal corneal cloudiness Subpleural 1 to 2 nun sized pale gray foci in the lungs Caudate lobe of the liver appears strangulated and pale colored Intestinal nematodiasis Vapor Coneontration (ppm 0 25 75 3/8 1/8 3/8 0/8 1/8 0/8 0/0 1/8 1/8 5/8 5/8 4/8 0/8 1/8 0/8 1/8 3/8 0/8 Females No visible lesions Clear fluid in the uterine horns Subpleural 1 to 2 mm sized pale gray foci in the lungs Intestinal nematodiasis 3/8 3/8 4/8 1/8 2/8 0/8 6/8 0/8 6/8 0/8 2/8 0/8 Data listed as number of rats affected/numb er of rats examined. SL 070223 TABLE 10 HISTOPATHOLOGIC FINDINGS IN MALE EATS ON 90 DAY EXPOSURE VAPORS - 30 DAY INTERIM KILL Microscopic Examination Focal chronic interstitial nephritis Focal renal tubular collapse and atrophy Focal granular casts within the renal tubules Focal dilated renal tubules with eosinophilic staining casts Focal chronic hepatitis Minimal increase in cytoplasmic vacuolation of the hepatocytes Focal subacute to chronic interstitial pneumonia Chronic peribronchial lymphoid cellular infiltrate Focal chronic tracheitis Focal chronic interstitial prostatitis Intestinal nematodiasis Chronic focal myocarditis Focal subacute pancreatitis Vapor Concentration (ppm) 0 25* 75 1/S 1/8 2/8 4/8 1/8 1/8 6/8 2/8 3/8 4/8 3/8 3/8 6/8 4/8 6/8 0/8 1/8 1/8 6/8 7/8 7/8 8/8 3/8 6/8 2/8 0/8 1/8 8/8 0/0 0/0 0/0 0/0 0/0 8/8 4/8 3/8 2/8 2/8 2/8 Data listed as number of rats nffectod/number of rats examined. ^'Microscopic examination only of kidneys, liver, and lung in this group. SL 070224 1 TABLE 11 HISTOPATHOLOGIC FIKDINCS IN FEMALE RATE OH 90 DAY EXPOSURE TO V1HYL1DEHE CHLORIDE VAPORS - 30 DAY INTERIM KILL Microscop :i c Examination Focal renal tubular collapse and atrophy Focal chronic interstitial nephritis Focal granular casts within the renal tubules Focal dilated renal tubules with eosinophilic staining casts Focal chronic hepatitis Minimal increase in cytoplasmic vacuolation of the hepatocytes Focal subacute to chronic interstitial pneumonia Focal peribronchial lymphoid cellular infiltrate Focal chronic tracheitis Intestinal netnatodiasis Focal subacute pancreatitis Focal chronic myocarditis Pituitary gland micrccyst in the pars distalis Vapor Concentration (ppm) 0 25* 75 2/8 2/8 A/8 3/8 0/8 2/8 5/8 5/8 5/8 3/8 A/8 5/8 . 8/8 6/8 8/8 0/8 1/8 2/8 5/8 8/8 A/8 8/8 8/8 8/8 3/8 0/0 A/8 3/8 0/0 1/8 1/8 0/0 1/8 1/8 0/0 1/8 2/8 0/0 0/8 Data listed ns number of rats affcctcd/number of rats examined* ^Microscopic examination only of kidneys, liver, and lung in this group. SL 070225 TABLE 12 GROSS PATHOLOGIC FINDINGS IN RATS OK 90 DAY EXPOSURE TO VIKYL1DENE CHLORIDE VAPORS - FINAL KILL Pathologic Finding Hales No visible lesions Carcass shows a decreased amount of adipose tissue in the abdominal cavity Epididymis contains a 1 mm sized circumscribed white foci in the tunic, unilateral Intestinal neinatodiasis Vapor Concentration (ppm) 0 25 75 A/12 6/12 5/12 1/12 0/12 0/12 0/12 8/12 0/12 6/12 2/12 6/12 Females No visible lesions Clear fluid in the uterine horns Intestinal nematodiasis Focal pneumonia in the apical lobe of the lung Strangulated piece of adipose tissue in the right mesovarium 8/12 2/12 3/12 0/12 0/12 5/12 4/12 1/12 1/12 1/12 6/16 2/12 4/12 0/12 0/12 Data listed as number of rats affected/number of rats examined. SL 070226 'TABLE 13 HISTOPATHOLOGIC FINDINGS II! MALE RATS ON 90 DAY EXPOSURE TO VINYUDENE CHLORIDE VAPORS - FINAL KILL Microscopic Examination Focal chronic interstitial nephritis Focal renal tubular collapse and a trophy Focal granular casts within the renal tubules Focal dilated renal tubules with eosinophilic staining casts Focal chronic hepatitis Minimal Increase in cytoplasmic vacuolation of the hepatocytes Focal subacute to chronic interstitial pneumonia Chronic peribronchial lymphoid cellular infiltrate Focal chronic tracheitis Focal chronic interstitial prostatitis Intestinal nematodiasis Chronic focal myocarditis Vapor Concentration (ppn) 0 25 75 1/5 1/5 0/5 5/5 3/5 4/5 1/5 1/5 1/5 4/5 4/5 5/5 5/5 5/5 4/5 0/5 1/5 2/5 3/5 2/5 2/5 5/5 5/5 5/5 2/5 3/5 2/5 3/5 2/5 4/5 3/5 0/5 0/5 1/5 0/5 0/5 Data listed as number of rats affected/number of rats examined. SL 070227 TABLE 14 HISTOPATHOLOGIC FINDINGS IN FEMALE RATS ON 90 DAY EXPOSURE TO VINYLT.DENE CHLORIDE VAPORS - FINAL KILL Vapor Concentraf Microscopic Examination 0 25 Focal renal tubular collapse and atrophy 4/5 1/5 Focal chronic interstitial nephritis 1/5 1/5 Focal granular casts within the renal tubules 0/5 1/5 Focal dilated renal tubules with eosinophilic staining casts 4/5 1/5 Focal chronic hepatitis ' 5/5 5/5 Minimal increase in cytoplasmic vacuolatiOi'i of the hepatocytes 0/5 1/5 Focal subacute to chronic interstitial pneumonia 2/5 0/5 Focal peribronchial lymphoid cellular infiltrate 5/5 4/5 Focal chronic tracheitis 3/5 2/5 Intestinal nematodiasis 2/5 1/5 Chronic focal myocarditis 1/5 1/5 (Ppm) 75 3/5 0/5 0/5 4/5 5/5 4/5 0/5 4/5 1/5 2/5 0/5 Data listed as number of rats affected/number of rats examined. SL 070228 HO urz&i Dfb&} too}Z&Off*n*^ li?<9 ~JL& br\ ytuf^-dr^j - fti) UnMdiO^lhc ($. 6/ pA/ ^i^Aj jk&izLr) j )tM&tJv }i>d^id^7) \jf TtuXf} jj^ryUtM^ %&>{lftn pCu^Xm r Ajurfmkte CL^^C - *>D tJOP, Q OO fty*r\ f a ^/fT? t&A Vv^A }\uPH^fi SL 070229