Document YnJ8XoQgX8zRzDnM3b8YxM5D
FOR DISCUSSION AND REV EW
NOT FOR Results of a 90-Day Study Incorpora.ting Vinylidene Chloride (Vdc) in the Drinking
Rats
by C. G. Humiston, S. B. McCollister
and J. F. Quast
reviewed by J. M. Norris and B. A. Schwetz
June 12, 1975
Toxicology Research Laboratory Health and Environmental Research
Dow Chemical U.S.A. Midland, Michigan 48640
SL 081919
RESULTS OF A 90-DAY STUDY INCORPORATING VINYLIDENE CHLORIDE (VDC) IN THE DRINKING WATER OF RATS
C. G. Humiston, S. B. McCollister and J. F. Quast
SUMMARY Groups of male and female rats ingested vinylidene chloride (VDC) in their drinking water at concentrations of 0, 60, 100 or 200 ppm for 90 days. These concen trations were equivalent to the respective average doses of 0, 6, 10 or 19 mg VDC/kg body weight/day for male rats; and 0, 8, 13 or 26 mg/kg/day for female rats. Body weights, food consumption and water consumption were recorded, and the rats were observed for signs of toxicity. Clinical parameters were evaluated just prior to termi nation of the study and at intervals during the treatment period; these included hematological studies, urinalyses, and determinations of blood urea nitrogen, serum alkaline phosphatase activity, serum glutamic pyruvic transaminase activity, and non-protein free sulfhydryl content in liver and kidney. Gross examination was conducted at necropsy after 90 days on experiment; organ weights were recorded and tissues were saved for histopathological evaluation.
SL 081920
-2Microscopic examination of the livers from some of the rats ingesting 200 ppm VDC in their drinking water revealed minimal changes characterized by an increase in cytoplasmic vacuolation of occasional individual hepatocytes. None of the other parameters examined revealed any evidence of toxicological effects associated with the ingestion of 60, 100 or 200 ppm VDC by male and female rats in their drinking water.
SL 081921
-3INTRODUCTION A 90-day study incorporating vinylidene chloride (VDC) in the drinking water of rats, reported herein, is one of a series of toxicological investigations being con ducted to aid in the evaluation of the safety of VDC for food packaging applications. Vinylidene chloride was administered to rats in their drinking water in preference to the feed since the concentration could be held relatively constant in water during a 24 hour period whereas the material was rapidly lost from the feed. 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.
SL 081922
-4-
EXPERIMENTAL PROCEDURES Test Material. The test material used in this study is described as follows:
chemical name: vinylidene chloride synonym: 1,1-dichloroethylene, VDC
molecular formula: ^02 2^2 structural formula: CH2=CC12
molecular weight: 96.95 description: clear, colorless liquid having a characteristic sweet smell
The VDC samples were aliquots of production material, minimum purity 99.5%, obtained from The Dow Chemical Company, Freeport, Texas. The specifications of this production mateiral were as follows: acetylenes, 25 ppm maximum; acidity as HC1, 15 ppm maximum; water, 75 ppm maximum; peroxides, 25 ppm maximum; color APHA, 30 maximum; iron, 0.5 ppm maximum; specific gravity at 25/25C, 1.202-1.212; polymer content, free, clear; inhibitor MEHQ (monomethylether of hydroquinone), 180-220 ppm; di-N-propylamine, 0.1 ppm maximum. Since the vinylidene chloride used to prepare various copolymers for food packaging applications is distilled to remove the inhibitor MEHQ, this study was conducted on distilled VDC having residual MEHQ in the range of 1-5 ppm.
SL 081923
-5-
Four of the samples were analyzed for impurities, using a gas chromatographic method. Results are as follows:
Impurity
Concentration (ppm) in Sample: 1 2 34
Vinyl bromide
4
Vinyl chloride
50
trans 1,2-dichloroethene 1700
cis 1,2-dichloroethane 680
1,1,1-trichloroethane
60
1,1,2-trichloroethane
48
MEHQ
2
ND 4
169 53 2 ND ND
ND 3
162 52 2 ND ND
ND ND 138 24 ND ND ND
ND - not detected
The sample was kept at -15 to -20C at all times except during preparation of the water solutions.
General Design. Sprague-Dawley, Spartan substrain, SPF-derived rats, 6-7 weeks old, were used in this study. Treatment groups consisted of 10 rats of each sex randomly selected to receive concentrations of 0, 60, 100 or 200 ppm VDC in their drinking water for 90 days. Each of these rats was housed in a suspended wirebottom cage with a rat on a two-year study on VDC that was initiated at the same time and at the same treatment
SL 081924
-6-
concentrations as this 90-day study. Since the rats were housed together, data on food and water consumption, which are recorded for each cage, include the 10 rats/ sex/group on the two-year study. These later rats were not used for any of the other parameters measured in this 90-day study. Additional groups of 8 rats of each sex at each treatment level were set up for interim sulfhydryl determinations.
Food (ground laboratory chow, Ralston-Purina Co.) and water were available ad libitum. Water was supplied from glass bottles with plastic screw caps fitted with stainless steel sipper tubes containing stainless steel balls. The bottles were emptied and refilled daily from freshly prepared stock solutions. Because of the volatility of VDC, the concentrations of the stock solutions were made up to exceed the nominal concentrations so that the mean levels of VDC during the 24 hours would be at least as high as the nominal treatment concentrations o^ 60, 100 and 200 ppm.
SL 081926
-7-
Analysis of Drinking Water. Analyses for VDC content were conducted on 16 of the daily preparations of water solutions using a gas chromatograph under the following conditions: Column, 1/4" Porapak Q, 80-100, 6 feet; oven temperature, 180C; detector, dual flame ionization; carrier gas, helium, flow rate, 20 ml/minute; attenuation, 80; sample volume, 4.2-4.5 ul (normalized to 1 yl). The chromatograms obtained were compared with those from standard solutions of vinylidene chloride to determine the concentrations in the test solutions.
The means + S.D. of these 16 analyses were 68+13 ppm, 106+22 ppm, and 22035 ppm for the respective nominal treatment concentrations of 60, 100 and 200 ppm VDC.
Observations and Records. The rats were observed twice weekly for signs of toxicity. Food consumption was recorded twice weekly and the average amount consumed/ rat/day was calculated. Water consumption was measured on 14 of the first 29 days of the study and twice weekly during months 2 and 3. These measurements were made byweighing the water bottles when filled and again before being emptied 24 hours later. Body weights were recorded weekly.
SL 081927
-8Clinical Studies. Hematological studies, including determinations of packed cell volume (PCV), erythrocyte counts (RBC), hemoglobin concentrations (Hgb), and total and differential leucocyte counts (WBC), were conducted on 5 rats/sex/group on days 30 and 86 of treatment. Urine samples were obtained from these same 5 rats/sex/ group on days 30, 62 and 85 for urinalyses that included determinations of specific gravity, pH, sugar, protein, ketones, occult blood and bilirubin.
Clinical chemistry studies were conducted on blood collected orbitally from 5 rats/sex/group after 30 days of treatment and on blood obtained upon decapitation of the 10 rats/sex/group necropsied after 90 days of treatment. The studies included determinations of blood urea nitrogen (BUN), serum alkaline phosphatase activity (AP) and serum glutamic pyruvic transaminase activity (SGPT). Non-protein free sulfhydryl content was measured in the livers and kidneys of 2 rats/sex/group killed on days 1, 3, 9 and 31, and 2 of the 10 rats/sex/group necropsied after 90 days on test.
SL 081928
-9-
Patholoqy. At the end of the 90-day treatment period, the 10 rats of each sex per group were fasted overnight, weighed, and killed by decapitation for gross examination. The brain, heart, liver, kidneys and testes were removed and weighed. Representative portions of the following tissues were preserved in 10% buffered formalin: adrenal glands, parathyroid glands, thyroid glands, heart, aorta, sternum, bone marrow, kidneys, urinary bladder, prostate, accessory sex glands, epididymides, testes, ovaries, urethra, uterus, brain (3 levels), pituitary gland, spinal cord, peripheral nerve (sciatic), large intestine, small intestine (3 levels), esophagus, salivary gland, stomach, pancreas, liver, lung, larynx, trachea, lymph nodes (mediastinal and mesenteric), spleen, thymus, skeletal muscle, mammary tissue and any grossly abnormal tissue. Both eyes of each rat were examined using a glass microscope slide technique under fluorescent illumination and were preserved in Zenker's fixative. All of the tissues, except sternum and bone marrow, from five rats of each sex in the control and 200 ppm treatment groups, were prepared by routine histologic procedures. In addition, sections of liver and kidney from 5 rats per sex from the remaining treatment levels were prepared.
SL 081929
-10The sections were stained with hematoxylin and eosin and were examined microscopically. Statistical Evaluation. Hematology, clinical chemistry, food consumption, water consumption, body weight and organ weight data were evaluated statistically by an analysis of variance and Dunnett's test (Steel and Torrie, I960).''' The level of significance selected for all cases was p<0.05 .
1Steel, R.C.D. and Torrie, H. H. (1960), Principles and Procedures of Statistics, McGraw-Hill Book Company, Inc., New York, pages 101-112.
SL 081930
-11RE5ULTS AND DISCUSSION General Observations. None of the rats exhibited any signs of toxicity throughout the study. All of the rats survived the 90-day experimental period.
Body Weights. Body weight gains were similar for groups of treated rats and controls, with no dose-related differences to suggest an effect related to treatment (Table 1). Individual body weights are given in Appendix Tables A-l and A-2.
Food Consumption. Food consumption data are summarized in Table 2. Individual values are presented in Appendix Tables A-3 and A-4. Average values for all groups of treated male rats were essentially the same as the control means. The mean food consumption values of all groups of female rats ingesting VDC in their drinking water were slightly lower than the control values. These decreases were sporadic throughout the 90-day period and were not dependent upon dose.
Water and Chemical Consumption. The mean daily water consumption of male and female rats ingesting 60, 100 or 200 ppm VDC in their drinking water was similar
SL 08193!
-12-
to the amounts of untreated water consumed by the control rats. Water consumption data are summarized in Table 3. Individual values are presented in Appendix Tables A-5 and A-6.
The average doses of VDC, calculated weekly from mean body weight and water consumption data, for groups of male rats receiving 60, 100 or 200 ppm VDC in their drinking water were 5.90.6, 10.0+1.2 or 19.3+2.7 S.D. mg/kg/day, respectively. Comparable doses (mean S.D.) for females were 7.5 + 0.4, 12.6 + 1.1 or 25.6 + 2.4 mg/kg/day.
Clinical Studies
Hematology. Results of hematologic studies are summarized in Table 4. Individual values are presented in Appendix Tables A-7 and A-8. None of the parameters evaluated showed any differences between control rats and those receiving VDC in their drinking water that could be associated with treatment.
Urinalyses. Urinalyses conducted after 30, 62 and 85 days of treatment gave similar values for treated and control rats. These results are summarized in Table 5, and individual values are given in Appendix Tables A-9 and A-10.
SL 081932
f
-13-
Clinical Chemistry. Determinations of BUN, and AP and SGPT activity, summarized in Table 6, revealed a few random statistically significant differences between groups of treated and control rats. The only one of these differences that was probably associated with treatment is the increase in mean SGPT activity of the female rats that had ingested 200 ppm VDC for 30 days. However, the magnitude of the increase is not great enough to be considered toxicologically significant. No such increase was observed l . the values obtained after 90 days. BUN, and AP and SGPT activities for individual rats are presented in Appendix Table A-ll.
Sulfhydryl Determinations. Results of determinations of non-protein free sulfhydryl values in kidney and liver are presented in Table 7. The data do not show any consistent, dose-related differences that would indicate an effect associated with treatment.
Pathology. Terminal body weights, organ weights, and organ/body weight ratios are summarized in Table 8. Values for individual rats are presented in Appendix Tables A-12 and A-13. There were no dose-related differences between treated and control rats for any of
SL 081933
-14-
the absolute or relative organ weights. The only statistically significant variation was a decrease in mean kidney/body weight ratio of the group of male rats receiving the lowest concentration of VDC.
Gross examination at necropsy revealed no changes that were considered relatable to treatment (Table 9). Results of histopathologic examination are presented in Tables 10 and 11. The livers of one of five male rats and three of five female rats maintained on water containing 200 ppm VDC showed minimal changes characterized by an increase in cytoplasmic vacuolation of occasional individual hepatocytes. These changes were not observed in the livers of control rats or the rats having ingested the lower concentrations of VDC. The remaining histopathologic observations were comparable in the treated and control rats and are considered to be spontaneous in occurrence.
CONCLUSIONS Results of this study indicate that male and female rats may ingest water containing at least 100 ppm VDC for a period of 90 days without untoward effects on any of the parameters evaluated. Effects observed in rats ingesting water containing 200 ppm VDC for 90 days were limited to minimal reversible changes in the liver.
SL 081934
Table 1
MEAN BODY WEIGHTS OF MALE AND FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS3
ppm VDCDays on Test
In water
0
8
MALES
0
310+8
341+15
60 310+10 340118
100
310+20 332+23
200
305 + 9
335+13
13
364+19 367+19 356127 360+18
20
39222 390+19 378+32 385+19
27
405+27 402+22 393+39 398+21
34
41132 405+23 391+35 407124
41
432+35 425+23 412+36 428+27
48
435+35 436+26 421+40 438+30
55
453+35 451+29 44 04 3 458132
62
455138 463129 446+43 461+30
69
454133 476+30 4 5644 470+30
76
442+38 466+28 44 5+48 459136
83
467140 488129 470152 474135
89
461159 486+44 475+49 487+36
FEMALES 0
60 100 200
213 + 7 225+9* 225+8* 226+6*
225 + 9 2329 235+8* 239+9*
240+11 251+14 248+10 260+13 242+10 261+9 25311* 264+13
257+14 263+14 264+10 269+13
258+15 271116 266+13 275+13 270+13 278+12 274+15* 283+16
275+17 276+15 282+16 287+16
283118 284113 284114 292+19
283+20 286115 289115 300+16
281127 270+21 297121 292+14 294116* 296112 294+16 284116 299115 304+17* 291118* 308119
290126 302112 302118 313117
aWeights are in grains, mean + SD, for 10 rats/group. See Appendix Tables A-l and A-2 for indiv idual values. *Significantly different from controls by Dunnett's test, p<0.05.
SL 081935
Table 2
MEAN FOOD CONSUMPTION (GRAMS/RAT/DAY) OF MALE AND FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS3
Days on test
0
ppm VDC in Drinking Water
MaTes
Females
60
r^5
ZTO
~U"
60
100
200
0-1
26 + 2
27 + 1
26+2
26+1
20 + 2
20 + 1
2012
19 + 3
8-12
25+1
26 + 1
24 + 2
25 + 2
20 + 2
18+1
1811*
18 + 1
13-15
26 + 3
26 + 2
24+2
25 + 3
19+2
20 + 2
22 + 3*
1812
16-19
26 + 2
26 + 1
25 + 2
2612
1911
18 + 1
1911
1911
20-22
26+2
26 + 1
24 + 2
26 + 2
20 + 2
1911
1911
19 + 1
23-26
26 + 2
26 + 1
24+2
25+1
20+1
19 + 2
1911
19+1
27-29
25 + 2
26 + 4
24+3
24+1
18 + 6
18 + 2
18 + 2
18 + 1
30-33
25 + 3
26 + 5
24+2
24 + 1
19 + 0
18+1
18 + 1
1811
34-36
25 + 2
25 + 2
2413
24+1
20 + 2
1711*
17 + 1*
1811
37-40
27 + 2
26+1
25 + 2
25 + 1
2313
19 + 2*
19 + 1*
19 + 1
41-43
27 + 6
26 + 4
25 + 2
25 + 1
23 + 9
1411*
1713*
18 + 1
44-47
26 2
27 + 2
29 + 7
2611
18 + 5
2216
2213
22 + 1
48-50
26+2
26 + 2
25+2
25 + 1
24 + 8
19 + 1
18+1*
20+1
51-54
25+3
27+1
27+2
26 + 1
2112
21 + 4
21+2
20 + 1
55-57
28 6
26 + 1
26 + 10
2611
2313
19 + 1*
19 + 2*
2012
58-61
228
27+1*
26 + 2
26+1
22 + 3
20 + 1
20 + 2
21 + 1
62-64
25+5
27 + 1
2614
26 + 2
21 + 2
19 + 2
20 + 1
20 + 1
65-68
26+2
262
24 + 2
2415
2212
1911*
20 + 2
2012
69-71
262
27 + 4
26 + 4
25+2
22 + 2
21 + 3
20 + 2*
2011
72-75
292
281
28 + 2
27 + 2
26 + 3
1911*
2212*
2211
76-78
22 1
2311
2212
2312
2013
1912
1812
1812
79-82
254
2511
25 + 2
25 + 2
21 + 2
19 + 1
2011
2011
83-84 MeaniS.D
24+3 26 2
26 + 2 26 + 1
25 + 2 2512
23 + 3 2511
20 + 2 2112
18 + 2 1912*
19 + 1 19+1*
19 + 1 1911
Values are means + SD of 20 rats/group. See Appendix Tables A-3 and A-4 for individual values. `Significantly different from controls by Dunnett's test, p<0.05.
^Time-weighted mean+S.D. of the group values.
SL 081936
Table 3
MEAN WATER CONSUMPTION (GRAMS/RAT/DAY)OF MALE AND FEMALE RATS MAINTAINED. ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS*
Day on test
~--------
ppm VDC in Drinking Water
Males
Females
60
100 "--Itt
O' '^0
100
200
0
4 3 5
41 + 5
40 + 3
42 + 2
35 + 8
33+7
31 + 2
31 + 4
1
42 + 4
43 + 2
43 + 3
43 + 3
30 + 7
34+2
34+5
35 + 4
2
45 + 8
43 + 4
44 + 3
42 + 3
34 + 6
33 + 4
34 + 4
35 + 2
8
42 + 5
44+7
41 + 4
41 + 4
32 + 9
32+4
32 + 3
32 + 3
9
42 + 6
41 + 3
38 + 3
41 + 2
33 + 11
32+2
33 + 3
32 + 3
10
37 + 5
41 + 4
41 + 9
41 + 4
35+10
33 + 3
32 + 3
33+4
11
43 + 3
41 + 3
40 + 3
43 + 6
34+4
33 + 2
30 + 2
33 + 8
12
37+5
41 + 3
39 + 3
38 + 6
33 + 5
32 + 3
29 + 6
32 + 3
13
44+9
39 + 4
37 + 4*
44+6
34+6
31 + 4
35 + 7
31 + 4
15
365
38 + 10
34 + 4
37+4
27 + 4
27 + 4
27 + 4
30+4
19
40 + 5
42 + 4
37 + 3
42 + 4
31 + 4
33 + 8
31 + 2
30 + 3
22
40 + 5
41+4
39 + 4
41 + 3
35 + 6
31 + 5
34 + 4
32 + 5
26
36 + 13
42 + 8
38 + 2
39+2
35 + 4
33+4
33 + 4
32 + 3
29
36 + 7
40 + 4
40 + 9
40 + 6
30 + 5
36+14
30 + 4
31 + 2
33
39 + 4
37 + 6
36 + 3
37+4
30 + 5
32+4
32 + 4
34 + 3
36
42 + 5
42 + 4
40 + 3
40 + 4
36 + 4
32+3
32 + 6
35+4
40
43 + 6
43 + 2
47+10
45+4
35+6
32 + 3
32+3
33 + 3
43
44 + 12
42 + 4
43 + 2
42+4
33 + 6
36 + 5
36 + 3
34+4
47
37 + 4
36 + 4
30 + 2*
31 + 3*
32 + 4
29 + 5
30 + 3
28 + 6
50
42 + 5
44 + 4
44 + 4
40 + 5
36 + 6
35 + 4
33 + 5
44+11
54
43+5
45 + 6
46 + 7
42 + 7
36+6
38+4
35 + 7
40 + 6
57
44 + 6
44 + 5
40 + 3
40 + 5
37 + 4
33 + 4
35 + 4
39 + 4
61
44 + 4
40 + 5
38+4*
38 + 7
41 + 3
35 + 3*
35 + 5*
37 + 5
64
35 + 12
43 + 7
41 + 3
41 + 7
37 + 4
35 + 4
36 + 4
35 + 5
68
40 + 6
42 + 5
42 + 4
39 + 6
40 + 16
36 + 3
36 + 4
38 + 5
71
42 + 3
4113
47 + 25
40 + 8
38+4
37 + 5
35 + 4
36 + 9
75
52 + 5
47 + 3
49 + 5
43+10* 47+8
38 + 7*
44 + 5
46 + 5
78
45 + 6
36 + 4*
40 + 3
40 + 6
--
--
--
--
82
44+6
44 + 4
41 + 3
39 + 9
39 + 5
37 + 3
36 + 4
36 + 5
85 Mean+S.D.
39 + 7 41 + 4
43 + 4 42 + 2
41+4 40 + 4
38+9 40 + 3
38+12 35 + 4
37 + 4 34+3
37 + 7 33 + 3
39 + 4 34+4
Values are means + SD of 20 rats/group of the water consumed on the See Appendix Tables A-5 and A-6 for individual data.
Significantly different from controls by Dunnett's test, p<0,05.
indicated day.
^
SL 081937
Table 4
MEAN HEMATOLOGIC VALUES FOR MALE AND FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VI NT'LI DENE CHLORIDE FOR 90 DAYS3
ppm VDC in water MALES
0 60
100
200
PCV Percent 30b 86
5212 5414
5U2 53 + 2
5413 5311
5212 5311
xlO6 /mm3 30 86 7.4910.35 8.3310.51 7.7210.28 8.1210.79 7.7610.49 8.45+0.21 7.7010.19 8.3510.38
Hgb r/100ml 30 86
16.9+0.6 17.411.2
17.110.3 17.210.9
17.710.9 17.010.4
17.210.6 17.5+0.6
xlO 3/mm3 30 86
15.2+1.4 12 .111. 5
14.5+2.1
9.712.3
14.4+2.1 11.5+2.5
15.7+2.9 12.910.8
Neut 30 86 12 9 12 13
9 12 6 10
WBC Differential Count (%)
Lymph 30 86
Mono 30 86
Eosin 30 86
85 91 2 2 1 1
86 81 0 4 2 1
90 83 0 3 1 1
93 86 0 3 1 2
Ha so 30 86
00 00 00 00
FEMALES
0 502 4711 7.79+0.40 7.55+0.36 16.610.8 16.010.6 15.9+2.1 9.411.0 10 9 88 85 1 4 1 2 0 0 60 5113 5112* 7.6210.57 7.53+0.41 16.610.7 17.1i0.6* 14.3+2.6 12 .412 .4 11 12 87 82 1 4 1 2 0 0
100 5012 4813 7.5610.37 7.7210.52 16.310.5 16.5+0.8 18.4+1.5 13.4+2.3 8 8 89 86 1 5 1 2 1 0
200
5111 4711 7.84+0.29 7.51+0.32 16.8+0.3 16.1+0.3 16.1+2.3 9.112.0 12 10 87 84 1 4 0 2 0 0
aValues are mean J SD of 5 rats/group. See Appendix Tables A-7 and A-8 for Individual values. bDays on test
*SionifIcantly different from controls by Dunnett's test, p<0.05.
Table 5
SUMMARY OF URINALYSES ON MALE AND FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS3
Days on test
MALES 30
62
85
FEMALES 30
ppm VDC in water
0 60 100 200
0 60 100 200
0
60
100 200
0 60 100 200
Specific gravity mean SD
1.047+0.007 1.04910.015 1.05810.007 1.06010.009
1.04410.010 1.049+0.011 1.049+0.010 1.050+0.012
1.05210.010
1.050+0.017
1.05010.009 1.044+0.018
1.048+0.013 1.03810.014 1.047+0.015 1.049+0.015
pH Range
6.0-6.5 6.0-6.5 6.0-6.5 6.0-6.0
6.0-6.5 6.0-6.0 6.0-6.5 6.0-7.0
6.0-7.0
6.0-7.0
5.5-6.5 6.0-6.5
6.0-7.0 5.5-7.5 6.0-6.5 6.0-8 .0
Protein Range
+ 1 to +2 tr to + 2 + 2 to + 3 +2 to + 3
tr to +1 tr to + 3 +i to + 3 +i to + 3
+i to +2
+ 2 to + 3
+1 to + 3 +2 to + 3
+ 1 to + 3 tr to + 2 tr to +3 +i to + 3
Sugar
neg neg neg neg
c>) (5) (5) (5)
neg neg neg neg
(5) (5) (5) (5)
neg (5)
neg (5)
neg (5) neg (5)
neg neg neg neg
(5) (5) (5) (5}
( ) =No . of rats affected
Ketones
Occult Blood
neg (5) neg (5) neg (4), tr neg (3), tr
(1) (2)
neg
neg (5) neg (5) (4) , mod neg (5)
(1)
neq (4), tr neg (5)
ne g (4), tr neg (3), tr
(1)
(1) (2)
neg (5) neg (5)
neg (4) , sm (1) neg (5)
neg
neg
neg neg
(1), tr sm (3)
(1), tr sm (3) (4), tr (4), sm
(1) ,
(1) ,
(1) (1)
neg (5)
neg (4) , sm (1)
neg (5) neg (4) , sm (1)
neg neg neg neg
(5) (5) (51 (5)
neg neg neg neg
(5) (5) (5) (5)
Bilirubin
neg neg neg neg
(5) (5) (5) (5)
neg neg neg neg
(5) (5) (5)
(5)
neg (5)
neg (5)
neg (5) neg (5)
neg neg neg neg
(5)
(5) (5) (5)
62
0
1.034+0.008
6.0-7.0 tr to + 3 neg (5)
neg (5)
60
1.045+0.013
6.0-6.0
tr to + 3 neg (5)
neg (3), tr (2)
100
1.035+0.012
6.0-7.0 tr to +-1 neg (5)
neg (5)
200
1.041+0.013
6.0-7.0 tr to +3 neg (S)
neg (4), tr (1)
86
0
1.03910.015
6.0-7.5 tr to + 3 neg (5) neg (2), tr (3)
60
1.047+0.015
6.0-7.5 tr to + 3 neg (5) neg (1), tr (3) ,
100 200
1.043+0.006 1.043+0.012
6.0-6.5 6.0-7.0
+1 to +2 tr to +2
neg (5) neg (5)
sm (1) neg (3), tr (2) neg (2), tr (2) ,
sm (1)
roups consisted of 5 rats/sex. See Appendix Tables1 A-- 9 and A- 10 for individual data .
neg neg neg neg
(5) (5) (5) (5)
neg (5) neg (5)
neg (5) neg (5)
neg neg neg neg
(5) (5) (5) (5)
neg (5) neg (5)
neg (5) neg (5)
SL 081939
Table 6
MEAN CLINICAL CHEMISTRY VALUES FOR MALE AND FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS
Days on test
30
ppm VDC in water
0 60
100 200
BUN mg % 28 + 1 27 + 2
261 25 + 2*
Males AP
mU/ml ____b
--
--
--
SGPT mU/ml 49 + 5 47 + 3 49 + 3 50 + 6
BUN mg % 262 21 + 1 25 + 2
28 + 5
Females AP
mU/ml ____b
--
--
--
SGPT mU/ml 43+4
45 + 5 46 + 4 56 + 9*
90
0
203
125+21
42 + 6
204
94 + 25
28 + 4
60
194
104+25
34+7*
203
78 10
25 + 3
100
18 + 1
114+16
35 + 6
20 + 2
83+16
25 + 3
200
203
122+24
35 + 5*
20 + 3
95 + 31
28 + 4
aValues are means + SD of 5 rats/group at 30 days and 10 rats/group at 90 days See Appendix Table A- 11 for individual values.
DAP values at 30 days were not analyzed statistically ; blood samples were from non-fasted rats, which gave some AP values that were too high to measure. Individual Values are given in Appendix Table A-ll.
*Significantly different from controls by Dunnett's test p<0.05.
SL 081940
Iy
Table 7
SLLFHYDRlI ^AlL'Pb "ROM KIDNE5 AND LIVER Or MAI i AS'D FEMALE PATS MAINTAINED ON DRINKING WArFR CONTAINING VIVY' IDSNfc. CHLORIDE FOR 1, J, Q, li OR 40 DaY9
-nr LA MALIC
ID if, - ema: is
: >o /"i
Dr 1,
A.U'Li. N; , moles xlO ' me
Day 3
Animal Nij
-9 mcies xIC me
Animai
K Idnev Dav 9
-9 No, moles *10 'ms
Dav 31
_9 Animal No , moles xlO /rjip
Dr ''>
Aninwl N,,
...*9, noiea <10 me
-- n3 ,o
- .18'. , 7-4-Jb4 A
7-*-.i8 3*) 74-3340
74-3311 ,4- n-30
3,37 ..99
1 22 j , 18
24 1*n'
1,10 3.30
74-380 74-3854
74-3845 74-jg46
"4-3837 '4-1838
'--3829 74-3330
4 19 3.23
3 33 4.12
3. s 1 3 84
3 94 3 75
74-3851 74-3852
74-384' 74-3844
74-3835 74-3536
74-3827 74-3828
4 .08 3.48
3.68 4,03
3.11 3 95
3.90 4.05
74-3849 "4-3850
74-3841 74-3842
74-3833 74-3834
7 4 -- 36 2 3 .'4-3826
3.83 3.80
3,7 3 3.71
3 84 4,30
4,06 4.03
74-347] 74-3473
74-354 5 7-- 354 7
74-3511 74-3513
74-3497 74-3499
3 15 2,9m
J
3,50
3 52 2.72
3.13 3.27
-4-J82J 74-382-
74-381' 7 --78l6
74-507
.-3/99 7.-3800
4.27 3 38
3.90 3.74
4 27 : 97
4 ,ib 4 In
74-3821 74-3822
74-381 3 74- 3814
74-3805 ` <-3806
74-3797 "4-3798
4.88 4,55
< . 7fc 5 26
4.28 4.8O
4. oO 4,90
74-3819 74-3820
74-361^ 74-3812
7--J803 74-3804
74-5795 74-3790
4 72 4 94
4,42 4.73
4.48 4 83
5 09 - 72
74-3817 74-3818
74-3804 74-3810
74-380' "4-3802
74-3793 74-j79<,
4,65 4.80
4.80 5.07
5.49 5 10
5.35 5.26
74-3551 74-3553
74-3611 74-3613
74-3591 74-3593
74-3571 74-3573
3.99 3.51
3.61 2.58
3.27 3.45
J,-'7 2.20
in water
Oav t
Animal No
-9 , moles xlO 'mg
Day 3
-9 Animal No.. moles *10 /me
Animal
Liver Dav 9
No . moliss
-9 xlO 'me
Dav 31
-9 Animal No- m< lies xlO /me
Da% Animal No. ifloii v s \10 ^/me
MALIC
V 74-3855 74-3856
60 7 *- 38,.7 74-3848
6. '7 7.37
6.34 6,44
/ 4-385 3 "4-3854
74-3845 74-3846
7.72 7 S2
50 8 05
74-3851 74-3852
74-3843 74-3844
7 ,01 7 26
8 17 7 ,17
74-3849 74-18 50
"4-3841 /<* -384 2
8.46 7 82
7 71 8.46
74-3471 7 4 - 34 7 3
74-3545 74-354
5.88 4 76
5.5 5 5 31
2 00
74-3839 74-3840
7.50 6,82
74-3837 74-38 38
6,99 ', 54
74-3835 74- 38 36
6.80 7 59
74-3833 74-3814
8,40 8.24
"4-3--! I 74-31'', 3
b 45.13
200 7 - - 3 6 31 74-3832
6 25 7.17
74-3829 74-3830
6 66 7.12
74-3827 74-3828
\72 7 58
'4-3825 "4-3826
7 91 8.*4
74- 3**9 7 74-3499
- 56 5,06
SHALES 0
60
74-3823 74-3824
74-3815 74-3816
6.36 6.57
6 99 6.20
74-3821 74-3822
74-3813 74-3814
7 85 7 "2
7 45 6.82
74-3819 74-3820
74-3811 74-3812
7,8 5
R . 04 7 54
7.4-3817 74-3818
7--3809 74-381C
7,40 7,48
8.37 7.32
74-35 5 1
74-361! 74-361 1
,, )_ 1 J4
Ul
100 74-3807 74-3808
200 74-3799 74-3800
6.99 6.44
6.66 6..31
74-3805 74-3806
74-3797 74-3798
7 . 5C 7.15
' .89 8 18
74-3803 74-3804
74-3795 74-3796
9,15 ',37
7, !(J 7.79
74-3801 7m-3HO?
'4-3793 7--3794
7.50 7.76
8 18 7,91
"4-3391 '4-3593
7-- 557 ] <`4-37 j
.. 37 ..15
5 15 3.92
SL 081941
Table 8
MEAN TERMINAL BODY AND ORGAN WEIGHTS OF MALE AND FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS3
ppm VDC in water MALE
0 60
100 200
Terminal Body Wt. , Starved, g
438+45 464+28 4484 7 458135
Bra in R R/lOOg
Oreau we ights (g and g/!0()g body we i?,,ht)
Heart
Liver
K idnev
g/100g R r/100r
r/IOOr
Testes
. _e_
r/100r
1.90+0.03 1.89+0.07 1.87+0.09 1.8710.07
0.44 + 0.04 0.41+0.02 0.4210.05 0.4110.03
1.3810.14 1.3810.06 1.34+0.16 1.40+0.13
0.3210.01 0.3010.01 0.3010.02 0.30+0.02
1 2 . u 2 + 1 .83 12.49+1.17 ! 2.29 + 2.01 12.39+1.11
2.83+0.17 2.69+0.16 2.7310.18 2.70+0.15
3.2410.38 3.1910.20 3.3610.41 3.27+0.21
0.74+0.06 3.98+0.17 0.69+0.04* 3.92+0.16 0.75+0.04 3.99+0.30 0.71+0.04 3.8910.2 3
0.92+0.11 0.85+0.06 0.90+0.09 0.85+0.10
FEMALE 0 60
100 200
273+21 267+30 278+16 288+17
1.78+0.05 1.8010.06 1.77+0.04 I .78+0.07
0.6510.06 0.68+0.10 0. L4+0.05 0.62+0.04
0.93+0.06 0.97+0.05 0.9410.08 0.96+0.05
0.34+0.02 0.37+0.06 0.34+0.02 0.3410.02
7.03+0.72 7.27+0.38 7.1510.56 7.48+0.66
2.5710.09 2.76+0.43 2.5710.15 2.5910.17
1.96+0.13 1 .8810.35 1.9610.14 2.05+0.13
0. 72+0,0.3 0.7110.18 0.70+0.04 0.71+0.03
aVaIues are mean t SD for 10 rats/group. See Appendix Tables A-12 and A-l 1 lor individual values. *Significantly different from control by DunneLL's test, p<0.05.
Cfi t1
O
00
H1
CD
it*
to
TABLE 9
GROSS PATHOLOGIC FINDINGS IN MALE AND FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS
Pathologic Findings (Male) Gross Examination No visible lesion Intestinal nematodiasis Focal corneal cloudiness, unilateral
ppm VDC in Drinking Water
0 60 100 200
2/10
5/10
4/10
5/10
7/10
4/10
6/10
5/10
0/10
1/10
0/10
0/10
Pathologic Findings (Female) Gross Examination No visible lesion Clear fluid in the uterine horns Intestinal nematodiasis Hematocyst in a strangulated piece of mesentery Tumor of the left kidney
5/10 2/10 5/10
0/10 0/10
2/10 2/10 9/10
0/10 1/10
1/10 2/10 9/10
0/10 0/10
4/10 3/10 6/10
1/10 0/10
Data listed as number of rats affected/number of rats examined.
SL 081943
TABLE 10
HISTOPATHOLOGIC FINDINGS IN MALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS
Microscopic Examination
Focal chronic interstitial nephritis
Focal renal tubular collapse and atrophy
Focal granular cast within the renal tubules
Focal dilated renal tubules with eosinophilic casts
Focal chronic hepatitis
Minimal increase in cytoplasmic vacuolation of the hepatocytes
Chronic peribronchial lymphoid cellular infiltrate
Focal chronic tracheitis
Intestinal nematodiasis
Chronic focal myocarditis
Focal chronic pancreatitis
Focal chronic interstitial prostatitis
ppm VDC in Drinking Water 0 60* 100* 200 1/5 0/5 0/5 0/5
4/5 3/5 4/5 4/5
1/5 0/5 0/5 0/5
4/5 4/5 4/5 4/5 4/5 3/5 3/5 5/5
0/5 0/5 0/5 1/5
5/5 0/0 0/0 5/5 2/5 0/0 0/0 1/5 1/5 0/0 0/0 3/5 2/5 0/0 0/0 2/5 1/5 0/0 0/0 0/5
2/5 0/0 0/0 2/5
*Microscopic examination only of liver and kidneys in these groups. Data listed as number of rats affected/number of rats examined.
SL 081944
TABLE 11
HISTOPATHOLOGIC FINDINGS IN FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS
Microscopic 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 inter stitial pneumonia
Focal peribronchial lymphoid cellular infiltrate
Focal chronic tracheitis
Intestinal nematodiasis
Focal chronic pancreatitis
Focus of mesenteric fat necrosis
ppm VDC in Drinking Water 0 60* 100* 200
3/5 3/5 2/5 3/5 3/5 1/5 0/5 1/5
4/5 3/5 3/5 1/5
3/5 4/5 2/5 3/5 4/5 3/5 3/5 4/5
0/5 0/5 0/5 3/5
1/5 0/0 0/0 0/5
5/5 0/5 0/5 4/5 1/5 0/0 0/0 0/5 1/5 0/0 0/0 0/5 1/5 0/0 0/0 2/5 0/5 0/0 0/0 1/5
*Microscopic examination only of liver and kidneys in these groups. Data listed as number of rats affected/number of rats examined.
SL 081945
APPENDIX SL 081946
Table A-l INDIVIDUAL AND MEAN BODY WEIGHTS IN GRAMS OF MALE RAIS MAINTAINED UN DRINKING WATER f ON IA S N ING V] NYI I DENE < 0 [ OR 1 HE h>R 90 DAYS
pp VDC In water
0
60
100
200
Animal_____________________________________________________________________________Days on Test
Number
0
8
13 20 27 34 41 48
74-3471 74-1473 74-3475 74-3477 74-1479 74-34B1 74-3481 74-3485 74-3487 74-3489
302 302 309 307 323 312 313 300 312 322
334 329 330 317 368 350 357 335 340 348
360 336 348 338 376 385 388 360 372 377
381 372 367 364 424 410 422 395 391 396
378 387 377 372 447 428 435 41 L 396 417
38 6 380 381 375 4 66 4 34 445 418 400 429
407 395 394 394 492 455 466 447 422 448
397 4 00 4 00 399 *96 46 J 6H jJ 428 452
MEAN +SD 310+8
341+15 364+19 392+22 405+27 411*32 432+35 415135
74-35 11
300
339
369
400
407
393
439
452
74-1333
306
334
357
385
392 4 00 419 434
74-3535
317
361
392
4)9
4 30
442
453
465
74-J337
331
371
403
421
448
447
4 68
481
74-3539
298
317
34 3
374
385
385 40 7
418
74-3541
308
331
354
371
377
389
411
411
74-3543
315
353
374
402
4 09
413
436
4 56
74-3545
304
318
349
373
384
384
4 02
410
74-3547
312
339
369
383
39 5
399
410
412
74-3549
305
332
355
375
391
397
406
41 6
MEAN + SD 310+10 340+18 367+19 390+19 402+22 405+23 425+23 436+26
74-3511 74-3513 74-3515 74-3517 74-3519 74-3521 74-3523 74-3525 74-3527 74-3529
318 350 289 285 319 298 292 119 323 311
34 3 375 316 295 34 0 320 316 332 354 326
369 413 340 324 366 341 336 341 384 350
392 440 357 334 390 366 359 362 415 361
399 4 56 376 346 456 378 367 361 423 366
400 462 381 344 404 383 374 365 4 34 367
418 482 399 360 433 4 08 394 393 4 54 381
415 500 406 370 442 417 402 391 465 384
HEAN+SD 310+20 332+23 356+27 378+32 393+39 391+35 412+36 421+40
74-3491
301
332
358
334
399
399 416 4 J 7
74-3493
303
325
355
376
379
388
406
4 02
74-3495
319
340
369
388
403
415
430
447
74-1497
312
348
377
411
419
428
453
469
74-3499
315
3 38
335
382
404
4 09
428
434
74-3501
291
335
368
382
397 409
4 38
453
74-3503
308
34 5
376 405
419
432
453
462
74-3505
312
346
374
391
412 429
453
469
74-3507
297
3 38
362
392
39B 413
433
445
74-3509
295
302
325 340
348
352
367
377
HEAN+SD 305+9
335+13 360+18 385+19 398+21 407+24 428+27 438+30
55
416 413 423 420 514 W4 'tii l t! o 4^6 _466__
453135
428 448 498 501 439 433 473 422 435 429
451+29
455 522 415 388 465 437 417 407 490 401
440+43
432 419 467 493 456 473 488 490 465 399
458+32
62 69 76 83
4IO 42 1 422 417 526 475 491 47 3
44? _46 7 _
413 425 423 415 504 463 494 473 4 58 467
402 408 411 4 04 522 4-4 1 476
4^6 442 _454___
416 425 433 423 5*7 4b? 506 489 457 484
455+38 454+33 442138 h67 +40
473 467 500 512 438 437 486 440 440 435
487 479 512 530 455 449 496 448 4 54 4 50
469 479 500 520 442 437 482 440 447 447
493 474 bJ4 54 0 473 461 505 457 479 468
463+29 476+30 46628 488+29
461 536 430 398 453 440 416 416 498 410
466 549 4 38 409 471 451 422 423 507 421
457 544 425 387 468 430 414 411 498 415
478 581 451 4 02 492 453 4 39 4 34 524 442
446+43 456+44 445+48 470152
4 28 426 4 66 491 461 477 491 491 471 408
429 440 465 507 473 477 500 505 478 426
409 420 455 502 463 440 501 505 472 427
433 450 480 523 480 499 425 516
491 4 38
46U30 470+30 459+36 474+35
89
427 415 426 345 651 *72 515 491 472 _4_9_3___
461+59
488 503 5 38 552 482 463 504 459 473 395
486+44
408 577 456 422 501 452 443 4 34 529 448
475+49
4 30 449 477 520 475 504 529 530 503 4 51
487+36
SL 081947
There were no sign Ificant diIfferences between treated and1 control groups by Dunnett 's test t p<0.05. \
Table A-2
INDIVIDUAL AND MEAN BODY WEIGHTS IN GRAMS OF FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIEJFNE CHLORIDE FOR 90 DAYS
ppm VDC In water
0
60
100
200
Animal Number
0
74-3551 74-3553 74-3555 74-3557 74-3559 74-3561 74-3563 74-3565 74-3567 74-3569
227 206 210 219 217 203 209 212 221 208
MEANtSD 21317
74-3611 74-3613 74-3615 74-3617 74-3619 74-3621 74-3623 74-3625 74-3627 74-3629
223 226 221 224
249 219 222 224 224 218
MEANtSD 225t9*
74-3591 74-3593 74-3595 74-3597 74-3599 74-3601 74-3603 74-3605 74-3607 74-3609
211 220 226 230 226 222 214 228 232 236
HLANtSD 225t8*
74-3571
74-3573 74-3575 74-3577 74-3579 74-3581 74-3583 74-3585 74-3587 74-3589
238 223 223 217 227 227 232 223 228 221
MEANtSD 226+6*
8
244 213 223 232 226 222 214 226 2 30 219
22519
233 233 230 226 257 224 228 229 233 226
232*9
217 232 2 38 233 235 2 39 229 239 241 245
23518*
256 233 242 227 2 39 241 245 225 244 237
239+9*
13 20 27
Dave on Test 34 41 48
55
2 59 277 290 286 307 315 325 241 246 250 261 276 278 290 239 241 253 2 54 271 270 284 256 263 256 2 68 273 284 285 231 251 250 254 263 263 272 229 237 24 2 241 261 264 271 223 229 236 235 24 4 .'5 2 257 245 256 259 265 275 282 277 242 255 261 259 278 282 290 235 251 263 255 261 264 277
240111 251+14 257+14 258+15 271+16 275+17 283+18
245 248 257 261 266 276 278 246 257 262 2 62 269 280 206 254 261 263 267 275 276 278 243 255 259 256 271 267 200 271 293 290 296 306 308 311 237 254 251 257 269 268 279 238 24 3 249 250 2 58 250 262 2 54 263 270 271 281 282 288 251 263 262 269 276 276 293 239 2 60 261 267 278 276 288
248110 260+13 263+14 266113 275+13 276+15 284+13
226 241 244 242 256 249 251 242 258 257 271 289 280 285 24? 262 266 272 28 L 287 287 235 256 261 262 266 270 275 247 257 254 261 265 273 280 235 270 274 280 288 301 297 240 257 260 266 276 280 279 236 267 267 282 291 300 302 258 272 275 283 288 296 295 256 267 277 277 282 284 287
242110 26119
264110 270+13 278112 282116 284114
272 287 246 262 251 264 237 250 251 258 260 272 2 59 274 236 242 265 268 250 265
253111* 264113
293 264 274 253 270 268 276 24 5 276 266
269+13
301 313 269 280 284 289 255 268 273 280 276 290 284 290 240 255 278 284 269 275
274+15* 2B31I6
314 282 285 265 290 297 300 2 62 293 281
287+16
325 291 297 270 298 297 306 257 296 283
292+19
62
329 293 283 290 27? 273 2 56 269 292 276
283+20
290 28 3 279 285 317 279 2 58 294 288 285
286+i 5
258 294 292 281 284 308 276 300 304 296
289+15
332 295 299 275 304 310 315 286 296 291
300+16
69 76 83
no 3L6 341
293 283 308
283 2 64 291
297 280 313
275 244
276
268 260 293
2 59 24 5 266
281 264 290
298 279 306
227 263 289
261127 270+21 297+21
293 285 307 291 279 293 284 274 285 293 298 293 316 325 3 L 8 290 293 28 7 261 2 78 281 295 309 311 301 296 295 292 300 293
292+14 294116* 296112
260 250 266 298 293 304 295 203 295 283 204 290 292 276 303 312 299 318 284 271 288 303 297 311 315 302 311 298 286 306
294+16 284+16 299115
335 325 341 298 281 304 297 292 302 279 262 279 310 296 3 L 6 313 301 326 324 309 319 286 273 284 302 290 31 1 292 283 301
304+17* 291+18* 308+19
89
34 2 303 259 314 260 283 266 287 300 289
290+26
305 302 291 297 J24 295 280 307 308 312
302+12
265 311 291 294 296 325 289 320 316 310
302+18
3 38 306 115 293 314 327 332 284 318 305
313+1/
:SIgnlfIrani!y different from controls by Durmett's test, p<0.05.
SL 081948
Table A-J
INDIVIDUAL AND MEAN POOD CONSUMPTION (GRAMS/RAT/DAY) OF MALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS3: DAYS 0-47
ppm VDC m water
0
60
100
200
Animal Number
0-1
74-3471, 74-3473, 74-3475, 74-3477, 74-3479, 74-3481, 74-3483 r 74-3485, 74-3487, 74-3489,
72 74 76 78 80 82 84 86 88 90
26 25 26 26 30 28 28 25 27 26
MEANtSD
2612
74-3531, 74-3533, 74-3535 f 74-3537, 74-3539, 74-3541, 74-3543, 74-3545, 74-3547, 74-3549,
32 34 36 38 40 42 44 46 48 50
26 28 29 26 26 28 27 25 27 27
MEAN+SD
27 1
74-3511, 74-3513, 74-3515, 74-3517, 74-3519, 74-3521, 74-3523, 74-3525, 74-3527, 74-3529,
12 14 16 18 20 22 24 26 28 30
25 27 24 23 30 26 24 24 27 26
MEANtSD
26 + 2
74-3491, 74-3493 , 74-3495, 74-3497, 74-3499, 74-3501, 74-3503, 74-3505, 74-3507, 74-3509,
92 94 96 98 3500 02 04 06 08 10
25 28 25 26 28 26 27 25 25 24
MEANtSD
261
8-12
24 25 24 22 26 26 27 24 26 24
25+1
25 26 27 26 24 26 25 26 26 26
26+1
25 26 23 23 20 24 22 24 26 24
24+2
25 27 24 26 24 25 27 25 26 22
25 + 2
U-15
23 29 25 23 33 26 27 24 24 22
26+3
_
24 26 26 26 24 24 32 25 26
26+2
24 24 22 23 29 23 22 22 27 22
24+2
23 25 22 25 31 24 26 24 24 21
25+3
16-19
24 27 25 25 32 28 28 25 26 24
262
26 26 29 25 26 25 24 26 26 25
26+J
26 26 23 23 29 25 22 23 28 22
252
24 23 24 26 29 26 27 25 25 22
26 + 2
DayS on Test
2TT-T3 ' 23-56
27-59
24 21
23
25 25 24
25 26 24
24 25 22
31 30 30
27 20 26
27 20 26
25 25 24
25 25 23
25 25 24
26+2
26+2
25+2
26 36 25 25 24 28 28 27 26 26 24 26 25 25 26 26 27 24 24 24 27 28 26 25 26 26 27 25 26
26 + 1
26 + 1
26+4
25 24 26 26 26 24 23 24 23 23 24 21 29 28 29 24 24 25 22 22 22 23 23 23 27 27 27 22 23 23
24+2
24 + 2
24 + 3
24 26 24 26 30 25 26 25 26 22
26 + 2
24 26 24 26 28 25 27 26 26 23
25+1
22 26 24 24 25 24 27 25 25 23
24 + 1
30-33
20 24 24 24 30 20 26 26 24 25
25 + 3
39 26 26 25 25 26 23 25 25 25
26 + 5
25 26 23 22 29 24 22 23 26 22
24+2
23 26 24 25 26 24 22 25 24 23
24il
34-36
25 23 26 24 30 26 25 25 21 25
25i2
26 24 24 24 24 25 24 30
--
25
25 + 2
24 25 23 23 31 24 22 22 25 21
2413
24
--
23 26 27 23 24 24 24 23
2411
17r47j" ~ 41-45
26 23 25 24 26 25 25 24 31 44 27 27 26 26 29 26 26 25 25 25
27+2
27+6
27 27 25 25 24 25 25 39 26 25 26 25 25 25 27 25 25 25 25 25
26+1
26+4
25 25 26 26 24 24 24 23 30 29 25 24 23 22 25 25 26 26 24 23
25+2
25+2
24 23 26 25 24 24 27 27 27 26 25 24 26 27 25 25 25 25 24 24
25 + 1
25+1
44-47
22 25 26 26
--
28 28 27 26 26
26+2
27 29 27 20 28 26 23 20 20 30
27+2
26 28 25 48 29 26 25 26 28 26
29 + 7
26 26 26 29 27 25 26 27 27 25
26 + 1
SL 081949
Individual values are means of 2 rats caged together
Table A-3, continued
INDIVIDUAL AND MEAN FOOD CONSUMPTION (GRAMS/RAT/DAY) OF MALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS: DAYS 48-84
ppm VDC in water
0
60
100
200
Animal Number
40-50
74-3471, 74-3473, 74-3475, 74-3477, 74-3479, 74-3481, 74-3483, 74-3485, 74-3487, 74-3489 f
72 74 76 78 BO 82 84 86 88 90
23 25 25 26 31 28 25 27 27 26
MEAN+SD
26 + 2
74-3531, 74-3533, 74-3535, 74-3537, 74-3539, 74-3541, 74-3543, 74-3545, 74-3547, 74-3549 ,
32 34 36 38 40 42 44 46 48 50
26 33 26 26 26 26 25 25 25 26
MEAN+SD
26+2
74-3511, 74-3513, 74-3515, 74-3517 , 74-3519, 74-3521, 74-3523, 74-3525, 74-3527, 74-3529,
12 14 16 18 20 22 24 26 28 30
25 27 24 24 28 24 23 24 27 24
MEANISD
25+2
74-3491, 74-3493, 74-3495, 74-3497, 74-3499, 74-3501, 74-3503, 74-3505, 74-3507, 74-3509,
92 94 96 98 3500 02 04 06 08 10
23 25 25 26 26 24 26 25 26 25
MEANiSD
25 + 1
51-54
20 25 26 25 30 22 26 26 26 24
253
__ 28 28 27 27 27 26 28 26 25
27 + 1
26 28 25 24 32 26 27 25 28 25
27+2
24 26 26 26 27 25 27 26 25 24
26 + 1
Days on Test 55-57 " 56-61 "TS-S'4 T5-TS 69-71
22 18 15 24 26 25 27 26 26 28 26 26 26 26 27
26 35 -- 30 26
-- 19 31 28 31 27 22 28 26 26 30 15 ?5 2 6 25 26 27 2 / 26 26 42 8 -- 23 23 25 25 24 25 27
28+6
2218
25 + 5
26+2
26+2
25 27 26 25 38 2B 29 29 20 27 27 28 28 31 27 26 28 28 27 27 25 28 25 25 26 26 27 26 25 26 26 27 27 26 25 26 26 28 25 24 26 27 27 26 26 26 25 26 25 26
26+1
2711* 27 + 1
26*2
27+4
28 25 20 25 25 28 28 27 28 27
3 25 24 23 25 45 25 25 22 25
31 -- 35 -- 35 25 27 26 25 24 21 23 22 24 23 24 26 25 24 24 27 28 28 27 27 24 25 25 22 24
26110 26+2
26 + 4
24+2
2614
24 25 22 22 21 25 26 25 26 __ 26 26 25 24 25 28 -- 28 28 26 28 28 28 28 28 24 25 23 22 22
28 -- 29 28 28 26 27 27 26 26 27 28 26 26 26 25 25 27 13 24
26+1
26 + 1
26 + 2
2415
25+2
72-75
27 30 28 2B 33 29 27 29
--
32
29 + 2
26 29 29 29 31 27 28 23 28 29
28+1
27 30 27 27 33 26 26 27 29 26
28+2
26 29 27 28 29 21 27 27 27 27
2712
22 22 20
2_2
23 21 23 25 23
22+1
21 23 24 23 23 23 24 22 23 25
23+1
21 24 20 21 26 21 21 21 24 22
22+2
19 22 21 26 25 22 26 25 23 20
2312
70-B2
25 25 27 16 32 27 24 25 2B 26
25+4
23 24 27 25 24 25 24 24 26 25
25 + 1
24 27 24 23 29 24 22 24 26 26
25 + 2
23 25 24 26 26 21 26 26 26 24
25+2
03-8
23 22 25
2_7
19 24 24 29 24
24 13
20 28 27 27 26 25 26 25 26 25
26+2
23 26 23 24 30 24 22 25 26 24
25+2
22 22 23 25 27 17 26 25 24 23
23 + 3
SL 081950
individual values are means of 2 rats caged together. `Significantly different from controls by Dunnett's test, p<0.05.
Table A-4
INDIVIDUAL AND MEAN FOOD CONSUMPTION (GRAMS/RAT/DAY) OF FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS3: DAYS 0-47
ppm VDC in water
0
60
100
200
Animal Number
0-1
74-3551, 74-3553, 74-3555, 74-3557, 74-3559, 74-3561, 74-3563, 74-3565, 74-3567, 74-3569,
52 54 56 50 60 62 64 66 68 70
19 22 IB 21 20 22 21 17 18 22
MEAN+SD
20 *2
74-3611, 74-3613, 74-3615, 74-3617,, 74-3619, 74-3621, 74-3623, 74-3625, 74-3627, 74-3629,
12 14 16 ia 20 22 24 26 29 30
10 19 20 20 22 20 19 20 20 19
MEANtSD
20 + 1
74-3591, 74-3593, 74-3595, 74-3597, 74-3599, 74-3601,
74-3603, 74-3605, 74-3607, 74-3609,
92 94 96 98 3600 02
04 06 09 10
20 22 18 19 17 20
20 23 19 20
MEANtSD
2012
74 - 3 57 1 , 74-3573, 74-3575, 74-3577, 74-3579, 74-3591, 74-3SB3, 74-3595, 74-3587,
74-3589,
72 74 76 78 00 02 04 06 08 90
21 18 21 10 25 19 17 17 20 ia
MEANtSD
I'Ji 3
0-12 " T 3-15
18 17 20 19 19 16 22 20 23 21 17 17 20 20 19 10 19 17 18 22
20+2 19+2
ia 20 17 10 19 20 19 25 21 22 18 19 18 16 18 23 19 21 19 18
18 + 1 20 + 2
17 17 18 24 18 24 18 22 16 17 16 24 18 23 19 25 18 18 18 26
18+1* 22+3*
20 20 10 17 18 19 17 16 19 17 18 18 18 21 18 17 20 18 10 20
18 + 1* 18 + 2
IC^ll "20-32
19 20 19 20 18 IB 19 19 20 20 19 21 20 20 20 19 18 20 20 25
19 + 1
20*2
18 19 17 17 10 18 18 19 22 22 18 20 17 17 19 18 19 18 18 19
is+i
19+1
18 10 19 18 18 19 ia 19 17 17 21 20
19 19 20 20 20 18 20 21
19+1
191
21 21 18 18 19 19 16 17 20 20 19 18 19 18 1 9 21 10 20 1 9 20
1 9+1
19 1
Days on Test 23-26 27^25 T-35
20 ia 20 20 4 19 19 17 18 18 20 18 21 17 19 19 30 20 21 19 19 19 19 19 20 21 19 20 16 19
20 + 1
18 + 6
19+0
18 16 17 18 18 18 18 17 18 22 17 17 22 20 20 21 21 18 17 17 17 IB 17 18 19 19 IB 20 20 19
19+2
18+2
18+1
IB 16 18 20 17 18 18 10 17 19 16 17 17 17 17 19 19 20 18 19 19 21 20 19 19 20 19 19 21 19
19 + 1
10+2
18 + 1
20 20 20 10 18 17 10 18 19 17 17 17 20 20 18 18 18 IB 18 18 18 19 18 20 19 18 19 20 19 19
19+1
18 + 1
10 il
34-3S~" 37-40" 41-43
19 21 19 20 23 18 21 20 22 21 23 19 26 31 20 19 22 20 18 24 10 18 19 16 20 24 44 20 21 31
20+2
23 + 3
23 + 9
16 16 14 19 21 14 IB 19 15 17 18 14 17 20 17 18 20 14 16 1 9 12 20 17 14 17 20 1 3 18 18 14
17+1 * 19 i2 * 14 n*
10 18 16 19 20 18 17 17 17 17 18 19 15 17 17 19 20 21 16 -- 12 17 -- 14 17 19 14 18 20 21
17 + 1*
1 9 tl *
17+3*
18 21 18
18 18 17 18 20 18 18 19 16 18 20 10 18 20 18 17 18 17
17 20 19 17 18 17 18 19 20
18 + 1 * 19 + 1* 18+1
4T47T7
20 19 21 23
5 19 24 ]9 16 15
1 85
24 24 22 24 26 27 21 22
5 24
22+6
19 16 20 21 19 24 23 24 22 28
22+3
23 21 21 19 22 21 23 21 22 22
22 + 1
SL 081951
aIndividual values are means of 2 rats caged together. *Significantly different from controls by Dunnett's test, p<0.05.
Table A-4 ,__continued
INDIVIDUAL AND MEAN FOOD CONSUMPTION (GRAMS/RAT/DAY) OF FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS: DAYS 48-84
ppm VDC in water
0
60
100
200
Animal Number
74-3551, 74-3553, 74-3555, 74-3557 , 74-3559, 74-3561, 74-3563, 74-3565, 74-3567, 74-3569,
52 54 56 58 60 62 64 66 68 70
20 20 20 20 32 18 22 17 23 42
MEANiSD
2410
74-3611, 74-3613, 74-3615, 74-3617, 74-3619, 74-3621, 74-3623, 74-3625, 74-3627, 74-3629,
12 14 16 18 20 22 24 26 20 30
19 19 18 19 20 1 Ft 18 16 20 19
MEANiSD
19 + 1
74-3591, 74-3593, 74-3595, 74-3597, 74-3599, 74-3601, 74-3603, 74-3605, 74-3607, 74-3609,
92 94 96 9B 3600
02 04 06 08 10
IB 10 IB 18 IB 19 17 IB 19 1B
MEAN+SD
1011*
74-3571, 74-3573, 74-3575, 74-3577, 74-3579, 74-3501, 74-3503, 74-3505, 74-3507, 74-3509,
72 74 76 7B 80 82 84 86 88 90
22 19 20 18 20 19 19 22 20 20
MEANiSD
20+1
51-54
20 21 25 21 23 19 22 18 20 22
21 + 2
33 20 19 19 22 20 19 19 19 19
21+4
19 21 18 19 19 22 20 22 21 24
2112
22 19 20 19 22 20 22
--
19 20
20!1
22 28 22 20 26 26 24 20 21 20
23+3
20 17 17 i9 21 18 18 19 10 10
18+1*
15 22 20 10 17 23 17 19 22 20
19 + 2*
20 IB 20 19 21 20 24 21 21 IB
2012 +
5 b-61
20 22 21 21 29 19 23 IB 21 22
22 + 3
20 18 20 21 22 20 19 19 21 20
20 + 1
19 19 IB 20 20 24 19 20 2l 21
20+2
21 20 22 21 22 19 19 22 21 21
21+1
Days on Test 62-64 '65-EB 69-71
10 21 21 21 23 25 19 20 19 22 22 22 21 23 25 1 fi 2 1 22 24 24 23 20 19 22 22 22 21 20 Zb
2112
22 + 2
22 + 2
20 20 24 21 19 -- 21 20 -18 21 -21 21 25 20 19 18 15 20 20 17 1 6 21 20 18 -17 20 20
19+2
19 + 1* 21+3
19 19 21 18 20 20
IB 19 18 20 21 21
19 20 IB 21 23 22 -- 18 18 -- 18 18 21 21 21 21 24 20
20 + 1
20 + 2
20 + 2*
21 21 20 19 19 20 19 19 10 20 20 21 21 21 21
19 21 20 20 24 20 22 21 20 20 19 22 20 21 22
20 + 1
20+2
20+1
w
24 30 22 29 -25 28 21 27 27
26 + 3
19 --
__
21 20 10 20 19 18
19i1*
21 22 20 24 21 23 19 -- 23 24
22+2*
23 21 23 22 22 22 22 22 22 24
22 + 1*
76-70
IB 19 19 22 27 IB 19 17 18 IB
20 + 3
18 17 17 19 21 20 20 20 20 21
19*2
17 17 16 18 19 20 17 16 IB 24
1812
18 16 20 15 19 18 19 17 18 10
J 812
79-62 '33-04
20 20 24 22 19 21 19 21 22 -19 16 22 21 23 18 20 19 20 1J5_
21+2
20+2
20 18 18 20 19 17 19 1 8 1 ? 19 10 20 19 10 19 1 6 20 19 19 16
1911
1012
20 J 9 20 18 19 18 20 19 22 21
21 20 19 18 21 18 19 20 21 20
2011
19 + 1
20 10 19 19 20 18 20 20 18 20 J 7 20 19 21 19 20 20 21 20
20 + 1
19+1
SL 081952
aIndividual values are means of 2 rats caqed together. *Significantly different from controls by Uunnett's test, p<0.05.
Table A-5
INDIVIDUAL AND KEAN WATER CONSUMPTION (GRAMS/RAT/DAY) OF MALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS3: DAYS 0-33
ppm VDC in water
0
60
100
200
Animal Number
__ _________________________________________________________________ Day on Test
6 ___1_
e 3 10 11 12 13 15 19
74-3471, 72
38
46
42
40
42
37
40
37
40
36
30
74-3473, 74
41
36 40
50 46
38
44
35
55
37
41
74-3475, 76
42
42 62
38
38
36
40
38
42
34
40
74-3477, 78
38
39
37
34
32
28
40
10 34 34 34
74-3479, 80
52
48
52
46
45
44
47
3s
62
44
48
74-3481, 82
47
44
50
45
47
40
44
44
40
30
46
74-3483, 84
50
41
47
47
45
40
46
40
44
36
41
74-3485, 86
44
38
42
42
38
40
40
45
40
37
39
74-3487, 88
44
42
44
44
48
35
48
39
42
36
37
74-3489, 90
36
38
35
35
34
33
30
32
35
26
34
MEANiSD
4 3 ! 5 4 2 14 4510 4 2 IS 42 + 6 3715 4 3 i s 37+5 44+9 36+5 40+5
74-3531, 32
38
__
41
42
42
42
39 42 __
34 40
74-3533, 34
44
44
46
46
44
44
42
43
42
37
74-3535, 36
46
48
50 47
45
48
44
48
44
65
47
74-3537, 38
41
42
42
40
41
36
40
39
36
32
30
74-3539, 40
39
44
43
38
39
40
40
39
35
36
41
74-3541, 42
46
45
47
46 46
44
45
42
44
34 48
74-3543, 44
42
40
41
42
36
36
38
38
36
37
--
74-3545, 46
31
42
38
60
38
__
37
36
37
32
42
74-3547, 48
44
44
42
30
44
38
44
41
40
36
38
74-3549, 50
38
42
42
40
38
42
42
38
35
36
MEAN+SD
41+5
43+2
43+4
44+7
41+3
4114
41+3
41+3
39*4
30110 42+4
74-3511, 12
37
42
46
38
36
35
40
30
35
32
38
74-3513, 14
44
45
43
44
38
42
40
40
30
34
40
74-3515, 16
39
42
44
3B
37
40
38
40
34
38
37
74-3517, 18
40
42
38
38
36
40
36
3B
32
33
34
74-3519, 20
47
48
45
46
--
66
42
45
44
42
40
74-3521, 22
40
46
49
39
42
40
42
38
40
33
38
74-3523, 24
36
40
41
36
36
36
38
36
34
32
33
74-3525, 26
38
38
42
39
38
30
38
34
32
30
36
74-3527, 28
42
44
47
44
44
41
46
40
40
34
40
74-3529, 30
42
43 44
44
39
37
43
38
35
27
30
MEANiSD
4013
4313
44+3
41+4
38 + 3
41 + 9
40 + 3
39 + 3
37+4* 34+4
37 + 3
74-3491, 92
40
40
42
40
44
40 __
36
38
34
37
74-3493, 94
43
42
42
46
39
42
42
38
45 42
42
74-3495, 96
39
41
42
40
40
40
40
39
41
32 42
74-3497, 98
44
48
44
44
__
44
56
45
44
40 46
74-3499, 3500 41 40 40 40 44 34 42 22 60 38 38
74-3501, 02
44
38
42
39
42
41
39
30
39
34
36
74-3503, 04
44
48
49
50
45
50
50
44
45
42
43
74-3505, 06
44
40
39 36
40
42
41
39
42
35 44
74-3507, 08
38
46
42
39
42
38
40
39
44
35
50
74-3509, 10
42
41
41
38
3B
40
38
37
40
35
42
MEAN+SD
4212
4313
4213
4114
41 +2
41+4
43+6
38+6
44+6
37+4
4214
_2i_
38 40 40 32 54 40 42 40 40 36
40 + 5
40 43 52 42 40 43 30 35 39 38
41+4
40 40 43 36 44 40 34 40 40 33
39 + 4
40 41 42 44 43 36 44 40 30 30
41+3
26 29
4 23 24 37 43 34 36 30 45 45 45 46 44 39 43 32 39 36 36 36
36*13 36 + 7
60 38 42 40 48 44 38 32 36 44 46 46 30 38 34 39 40 44 36 40
42 + 8 40+4
38 40 37 64 40 35 38 20 42 44 30 38 34 36 39 40 40 40 35 34
30+2 40 + 9
38 30 37 54 42 41 42 40 -- 34 40 45 40 40 42 42 39 36 36 36
39 + 2 40+6
33
42 30 40 36 46 42 36 36 38 33
39+4
26 30 44 36 30 44 35 34 40 33
37 + 6
36 38 36 35 42 33 36 38 38 32
36+3
36 34 40 43 39 35 40 36 32 34
37+4
^Individual values are means of 2 rats caged together of the water consumed on the indicated day. *Significantly different from controls by Dunnett's test, p<0
SL 081953
Table A-5, continued
INDIVIDUAL AND MEAN WATER CONSUMPTION (GRAMS/RAT/DAV) OF MALE RATS MAINTAINED ON DRINK TNG WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS&: DAYS 36-85
ppm VDC in water
Number
Day on Test -- 40 43 4? TT----~ 57 61 64 66
74-3471, 72
40
30
38
__
38
39
36
16
37
28
74-3473, 74
44
44
44
36
41
46
48
49
44
44
74-3475, 76
41
41
42
35
40
41
39 44
40 46
74-3477, 78
38
30
36
30
40
39
40
45
28
38
74-3479, 80
52
55
29
43
53
48
52
18
49 --
74-3401, 82
46
40
47
40
44
47
52
4b
11
46
74-3493, 04
35
42
40
34
36
34
44
42
7 34
74-3405, 06
42
46
76
40
45
49
45
46
46
42
74-3407, 80
--
40
46
38
44
46
42
44
36
42
74-3409, 90
40
37
41
35
38
41
40
40
34
38
MEANiSD
4 2 i 5 43+6 4 4 12 37+4 425 43*5 44+6 44 + 4 35+] 2 40 + 6
74-3531, 32
44
44
42
32 4]
38 48 42
38 36
74-3533, 34
42
40
44
30
44
50
44
43
47
48
74-3535, 36
46
44
50
3B
49
56
49
50
51
44
74-3537, 38
38
40
44
37
44
44
44
40
42
36
74-3539, 40
40
44
42
36
48
46
46
30
42
48
74-3541, 42
46
46
46 42 51
49
44
46 52
46
74-3543, 44
40
42
41
32
46 44
41
37
37
40
74-3545, 46
35
40
40
30
42
38
36
16
34
36
74-3547, 40
45
44
J5
36
40
50
47
19
50
39
74-3549, 50
40
42
39
32
37
39
35
12
36
46
MEANISD
4214 43+2 42 + 4 36 + 4 44+4 45 + 6 44+5 40 + 5 43+7 4 2+5
74-3511, 12
40
75
40
30
41
64
42
42
40
43
74-3513, 14
41
44
42
34
42
42 41
19 41 44
74-3515, 16
41
46
42 30
52
44
34
--
40 49
74-3517, 10
40
42
38
26 41 42 44
36
40 48
74-3519, 20
48
52
46
32
50
47
41
29
49
36
74-3521, 22
40
44
43
28
42
40
39
35
39
39
74-3523, 24
37
41
44
30
42
42
46
36
40
40
74-3525, 26
40
46
44
34
44
48
40
42
42
42
74-3527, 28
38
40
44
30
42
45
40
3B
42
38
74-3529, 30
36
42
42
31
42
46
37
40
42
38
MEANiSD
4Q3 47 + 10 43*2 10*2* 44 + 4 46*7 40+3 3B + 4* 41+3 42*4
74-3491, 92
40
44
40
12
34
42
36
34
36
38
74-3493, 94
36
40
44
26
32
36
36
35
38
35
74-3495, 96
42
42
47
12 42
42
43
42
50
38
74-3497, 90
45
50
47
37 46
60
50
42
45
49
74-3499, 3500 40
47
39
--
46 42
42
40
42
40
74-3501, 02
32
38
30
20
34
34
32
28
29
24
74-3503, 04
42
52
48
31
41
44
43
38
46
40
74-3505, 06
38
43
40
31
42
42
42
36
43
40
74-3507, 00
42
45
37
29
38
42
40
34
34
42
74-3509, 10
40
44
44
31
44
41
40
53
47
42
MEANISD
40i4 45 + 4 42+4 31*3* 40+5 42*7 40+5 38*7 41+7 39+6
71 ~TT-- 78
52
38 49 40 38 45 S5 46 46 44 46 -- 39 38 48 56 54 44 60 50 51 46 56 49 46 40 45 38 38 42 54 43 45 39 51 -- 40
40 51 40 41
42*1 5215 4516 44+6
40 44 32 46 44 52 36 --
43 50 41 44 37 46 36 -- 42 51 -- 44
46 50 40 42
40 46 34 48 30 42 30 __
44 47 36 45
40 46 32 35
41+1 47+3 36+4* 44+4
40 46 34 37 39 54 40 40 118 52 45 42 39 44 40 -- 42 45 42 46 36 44 41 30 38 44 37 36 39 58 42 45 38 50 38 37 41 54 40 42
47 + 25 49 + 5 4013 4113
38 48 38 43 38 46 38 39 42 52 45 30 52 54 47 --
42 42 45 40
24 21 27 23 45 44 46 59 44 34 40 30 32 42 35 36
40 48 40 37
4018 43+10* 40 + 6 39+9
B*+
33 29 40
--
52 42 36 41 41 3B
3917
46 43 40 42 45 44 38 40 47 38
4314
44 42 44 34 42 41 40 48 40 _37_
41 + 4
38 -- 35 44 43 18 45 41 30 46
38+9
values are means of 2 rats caged together of the water consumed on the indicated day. *Significantly different from controls by Dunnett's test, p<0.05.
SL 081954
,4' I
SL 081955
Table A-6
INDIVIDUAL AND MEAN WATER CONSUMPTION (GRAMS/RAT/DAY} OF FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDBNE CHLORIDE FOR 90 DAYS : DAYS 0-33
ppm VDC
in water
0
60
100
200
Animal 1N.11u1 mmkbaewr
74-3551, 74-3553, 74-3555, 74-3557, 74-3559, 74-3561, 74-3563, 74-3565, 74-3567, 74-3569,
52 54 56 58 60 62 64
66 68 70
_____________ ________________________________________________Day on Test
c .11
21------
na ---A5--~T^ iaT'~ iIT
1V2h
1n"
_30 32 30 34 35
36 36 26
36 36 38 46 42 46 44 34 37
32 31 3B 36 48 45 -- 40 34
35 30 35 38 36 34 35 38 41
33 28 33 33 33 32 31 30 36
34 34 36 22
8 44 32 15 31
36 34 40 40 30 37 34 33 44
26 28 32 31 27 26 31 30 26
56 11 36 34 28 33 34 32 31
28 32 18 14 32 16 20 24 30
n
26 34 23 30 24 25 30 22 28 27
MEAN1SD
35 + 0
30+7
3416
32 + 9
33111 35+10 14+4
33+5
34+6 27 + 4
74-3611, 12
32
34
36
33
33
32
30
32
34
26
74-3613, 14
34
36
32
30
32
34
30
31
35
26
74-3615, L6
38
38
37
40
34
33
34
34
33 28
74-3617, 18
33
34
34
32
32
31
34
31
28
27
74-3619, 20
42
36
40 40
32
30
38
30
36
34
74-3621, 22
38
33
34
30
30
32
33
30
32
30
74-3623, 24
31
34
36
28
33
34
36
34
30
28
74-3625, 26
16
34
25
28
30
20
32
26
25
26
74-3627, 28
35
32
33
30
34
31
30
30
31
--
74-3629, 30
28
30
28
34
27
34
72
30
27
20
MEAN1SD
33+7
34+2
33+4
32+4
32 + 2
33 + 3
33 + 2
32 + 3
3114
27 + 4
74-3591, 92
33
36
32
27
32
32
30
27
28 28
74-3593, 94
34
32
30
35
34
33
28
26
30
30
74-3595, 96
30
26
27
29
28
28
26
25
27
24
74-3597, 98
34
41
40
32
38
39
32
33
34
28
74-3599, 3600 31 30 34 32 34 32 -- 32 30 30
74-3601, 02
30
38
36
30
31
32
32
20
50
21
74-3603, 04
34
31
36
35
32
30
30
32
36 28
74-3605, 06
32
38
33
36
30
33
30
19
44
34
74-3607, 08
28
34
34
34
36
30
31
40
35
26
74-3609, 10
28
30
36
31
32
28
32
32
35
25
MEAN1SD
31+2
34 + 5
34*4
3213
33 + 3
32+3
30+2
29 + 6
35 + 7
27+4
74-3571, 72
36
33
33
31
34
37
32
31
29
34
74-3573, 74
32
38
37
33
31
31
30
36
32
28
74-3575, 76
31
34
32
32
--
36
28
35
38
25
74-3577, 70
28
30
32
26
26
30
31
26
24
28
74-3579, 80
26
36
37
31
30
30
28
30
29
39
74-3581, 82
31
28
38
32
32
--
26
27
28
27
74-3583, 84
30
34
36
33
30
30
33
31
28 20
74-3585, 66
23
39
35
36
36
35
38
35
32
30
74-3587, 88
34
38
36
36
31
--
52
34
31
32
74-3589, 90
28
36
33
30
34
38
35
30
36
30
MEANiSD
31+4
35 + 4
35+2
32 + 3
32 + 3
33 + 4
33+8
32+3
3114
30 + 4
T5~ "
--n ------T5------ nr
2B 31 36 30 30 32 38 40 30 32 30 46 40 30 34 33 39 28 30 38 32 26 35 28 34 24 32 35 24 28 38 42 38 43 34 26 28 31 28 24 34 34 36 30 2B -- 32 34 24 20
3114 35 + 6 35+4 30+5 3015
56 37 35 30 28 32 30 30 32 30 32 36 36 31 34 30 -- 34 30 30 -- 40 42 34 41 32 30 30 34 32 28 30 32 74 31 28 24 29 30 30 32 28 30 32 30
29 30 30 31 30
33+8 3115 3314 36+14 3214
31 32 30 24 28 32 27 29 31 32 26 28 25 22 24
32 41 39 30 35 32 36 34 30 37 30 34 38 32 32 30 36 34 29 32 32 34 30 32 30 30 36 33 34 36 32 34 36 30 30
31 + 2
34+4
33i4
3014
32+4
32 36 33 32 34 34 32 35 32 35 26 32 32 28 36 28 26 28 28 32 27 28 32 28 28 30 30 28 32 32 20 26 29 30 34 30 40 36 30 34 33 37 34 34 36 33 36 36 34 36
30 + 3
32 + 5
32 + 3
31+2
34+3
a Individual values are means of 2 rats caged together of the water consumed on the indicated day.
Table A-6, continued
INDIVIDUAL AND MEAN WATER CONSUMPTION l GRAMS/RAT/DAY) OF FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS3: DAYS 36-85
ppm VDC in water
0
60
100
200
Animal Number
36
74-3551, 74-3553, 74-3555, 74-3557, 74-3559, 74-3561 , 74-3563, 74-3565, 74-3567, 74-3569,
52 54 56 58 60 62 64 66 68 70
38 36 40 36 36 38 32 29 44 33
MEAN+SD
36 + 4
74-3611, 74-3613, 74-3615, 74-3617 , 74-3619, 74-3621, 74-3623, 74-3625, 74-3627, 74-3629,
12 14 16 18 20 22 24 26 28 30
33 32 38 31 34 32 32 30 26 36
MEAN+SD
32 + 3
74-3591, 74-3593, 74-3595, 74-3597, 74-3599, 74-3601,
74-3603, 74-3605, 74-3607, 74-3609,
92 94 96 98 3600 02 04 06 08 10
33 36 30 31 20 41 32 32 38 30
MEAN+SD
326
74-3571, 74-3573, 74-3575, 74-3577, 74-3579, 74-3581, 74-3583, 74-3585, 74-3587, 74-3589,
72 74 76 70 80 82 84 86 88 90
36 32 40 34 34 32 34 36 44 33
MEAN+SD
35 !4
40
37 39 36 34 26 39 38 24 42 36
356
35 30 30 32 34 30 34 27 32 33
32+3
35 36 27 27 32 32 34 33 34 28
32 + 3
34 36 36 32 28 34 33 32 39 30
33+3
43
32 36 38 34 33 31 40 30 39 20
33 + 6
41 36 42 34 42 37 37 30 34 26
36 + 5
36 36 30 40 35 36 30 37 40 34
3613
35 36 33 30 30 37 36 34 33 42
34+4
47
32 31 32 33 26 34 36 25 30 36
324
37 33 31 22 36 28 27 29 25 22
29+5
__
30 24 32 31 34 28 32 25 32
303
26 28 25 18 20 32 30 34 39 32
28+6
56 54
40 40 40 40 40 38 20 34 41 40 36 32 36 42 22 24 39 35 35 34
36+6 36 + 6
40 44 41 42 35 40 36 34 34 41 35 38 36 33 28 34 31 39 34 32
35 + 4 38*4
34 38 30 35 22 28 3B 42 36 40 36 38 34 42 34 39 36 22 30 30
33 + 5 35 + 7
42 47 36 44 44 36 36 36 74 33 40 36 47 34 44 37 42 50 37 42
4 4 111 40 + 6
Day on Test 57 61
64
40 32 36 32 40 3u 42 34 39
~~
37 + 4
42 40 44 43 42 4(i 46
--
41 34
41+3
37 41 40 34 41 32 40 30 40 33
37+4
38 36 40 30 30 32 36 36 35 28 34 34 38 42 36 34 35 38 30 34 32 32 34 28 28 32 34 34 32 37
3314 35 + 3* 35+4
34 30 33
42 39 45
30 20
32
40 38 34
34 38 39
36 36 30
36 34 34
32 28 38
36 40 38
32 34 36
35+4 35 + 5* 36*4
44 41 33
34 34 40
36 35 36
40 28
34
34 34 29
40 38 31
40 35 35
39 42 39
46 46 45
38 42 32
39 + 4 37*5 35 + 5
6ft ' 71 ~7r" 02
38 38 48 40 41 38 50 40 42 42 48 42 41 38 50 33 40 40 28 16 30 38 49 40 40 42 55 50 76 30 40 36 40 42 54 43
9 34 45 34
40*16 38+4 4 7 0 39+5
30 44 50 40
34 33 44 40
42 39 48 41
34 40 36 33
35 40 42
57
38 32 34 --
32 36 36 38
35 44 36 30
38 34 32 32
30 30 27 35
36+3 37 + 5 30+7* 373
39 35 45 34 36 39 48 33 28 27 37 20 30 42 50 42 30 36 42 -- 34 38 40 37 40 34 45 38 39 36 44 36 40 34 52 40 37 34 40 35
36+4 35*4 44 + 5 36*4
35 44 52 42
36 39 44 36
33 36 46 --
34 32 42 28
35 35 42 34
36 3B 42 34
42 37 44
34
43 42 44 36
47 46 58 40
36 12 44 42
38 + 5 36+9 46*5 36 + 5
85
40 34 67 32 20 34 43 26 40 30
18+12
38 36 42 33 40 38 34 30 37 42
37+4
37 44 31 40 50 34 43 31 26 34
3717
40 36 42 30 32 42 30 35 42 46
39+4
aIndividua1. values are means of 2 rats caged together of the water consumed on the indicated day, *Significant1y different from controls by Dunnett^s test, p<0.05.
SL 081956
Table A-7
INDIVIDUAL AND MEAN HEMATOLOGIC VALUES FOR MALE RATS MAINTAINED ON DRINRING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS
ppm VDC Animal In water Number
0 74-3471 74-3472 74-3473 74-3474 74-3475
KEAN+SD
60 74-3531 74-3532 74-3533 74-3534 74-3535
MEANiSD
100 74-3511 74-3512 74-3513 74-3514 74-3515
MEAN+SD
200 74-3491 74-3492 74-3493 74-3494 74-3495
MEAN+SD
Percent
30 86
52 48 52 53 54 56 55 57 49 55
52+2 54t4
54 56 50 52 52 55 48 52 50 51
51 + 2 532
52 52 52 53 58 53 56 54 52 53
54+3 53+1
50 52 53 54 54 5 5 55 52 50 54
52+2 5311
xlO6 /mnf* 30 86
7.68 6.89 7.67 7.75 7.48
7.58 8.27 8.27 8.99 8.56
7.49+0.35 8.33+0.51
8.13 7.46 7.84 7.72 7.46
8.92 8.25 8.74 7.02 7.65
7.7210.28 8.120.79
7.46 7.96 8.39 7.11 7 .88
8.74 8.31 8.19 8.51 8.49
7.76+0.49 8.45+0.21
7.56 7.72 8.00 7.72 7.51
8.24 8.89 8.08 7.96 8.59
7.70+0.19 8.3510.38
g/XOO ml 30 86
16.9 16.7 17.4 17.5
15.9
15.6 17.1 17.7 18.5 18.3
16.9+0.6 17.4+1.2
17.2 17.2 17.6 16.9 16.7
18.5 16.9 17.6 ] 7 .1 16.1
17.1+0.3 17.2+0.9
17.1 17.3 19.1 18.1 17 .1
16.6 16.8 17.2 17.6 16.7
17.710.9 17.0+0.4
16.7 17.0 17.8 17.8 16.7
16.9 17.7 17.2 17 .2 18.4
17.2+0.6 17.5+0.6
3 xlO /ram 30
86
UBC Dlfferential Count (%>
Lymph
Mono
tosin
30 86 30 86 30 86 30 86
13.8
Hi. i
14. J 13.8 16.8
11.6 12.9 10.2 14.1 11.7
8 19 87 98 5 3 0 0 4 7 93 89 2 1 0 3
10 7 86 91 2 ] 2 1
7 9 92 88 1 1 0 2
29 _5 70 91 0 4 1 0
15.2+1.4 12.1+1.5 12 9 85 91 2 2 1 1
13.8
n.a
16.7
16.3
11.7
6.6 8.1 11.0 10.3 12,4
14 20 83 72 0 4 3 4
4 6 93 90 0 4 2 0
7 18 89 79 0 3 4 0
18 6 81 88 0 6 i 0
17_ 17_ 82 T
0
3
1
3
14.512.1 9.7 + 2.3 12 13 86 81 0 4 2 1
15.0 15.4 13.3 11 .4 16.9
12.9 8.1
12.5 14.2 10.0
13 17 86 79 0 3 0 1 5 18 94 78 0 3 1 1 4 9 93 88 0 3 3 0 3 13 96 82 0 2 1 3
16 _3 81 90 1 1 l 2
14.4+2.1 11.5+2.5
9 12 90 83
0
3
1
1
13.5 18.0 15.3 19.2 12.4
11.8 12.7 13.8 12.7 11.7
3 15 97 82 0 1 Q 2 7 6 92 92 0 2 1 0 5 10 94 85 0 2 1 3 7 11 89 85 2 2 2 2 J8 __9 90 84 0 6 i 1
15.7+2.9 12.9+0.8 6 10 93 86 0 3 1 2
Baso 30 86
00 00 00 00 00
00
00 10 00 00 00
00
10 00 00 00 10
00
00 00 00 00 10
00
aDays on test No values were significantly different from controls by Dunnett's test, p<0.05.
SL 081957
Table A-8
INDIVIDUAL AND MEAN HEMATOLOGIC VALUES FOR FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS
ppm VDC In water
Animal Number
PCV Percent
30a 86
RBC 30 86
Hgb g/100 ml
30 86
WBC xlO 3/mm3
30 86
WBC DifFerential Count CO
Mono
Baso
30 86 30 86 30 86 30 86 30 86
0
74-3551 53
48
8.39
74-3552 48
47
7.62
74-3553 49
46
7.40
74-3554 49
48
7.56
74-3555 54
46
7.97
7.79 7.90 7.49 7.59 6.98
17.6 16.2 15.6 16.2 17.2
16.2 15.7 15.2 16.9 16.1
14.1 14.2 19.3 16.0 15.8
8.7 8.6 9.0 10.7 10.2
6 2 93 90 0 6 1 2 0 0
6 12 91 85 2 1 0 2 1 0
12
6 86 88
1
4
1
2
00
11 15 88 81 0 2 1 2 0 0
15 12 81 82 3 5 1 1 0 0
MEAN+SD 50+2 4 7 1 7.79+0.40 7.55+0.36 16.6+0.8 16.0+0.6 15.92.1 9.4 + 1.0 10 9 88 85 1 4 1 2 0 0
60
74-3611 48
50
7.53
74-3612 49
52
7.12
74-3613 51
48
7.73
74-3614 55
54
8.53
74-3615 52
52
7.18
7.10 7.42 7.77 8.11 7.27
15.6 16.3 16.9 17 .4 16.6
16.1 17.3 17.4 17.6 17.1
13.3 11 .3 17.6 13.0 16.3
12.5 14.5
8.7 14.7 11.7
8 8 92 85 0 5 0 2 0 0 16 19 80 74 z 4 2 3 0 0
6 10 91 84 2 4 1 2 0 0 7 11 89 86 3 2 i 1 0 0 15 10 84 82 0 7 i 1 0 0
MEAN+SD 51 + 3 512* 7.62+0.57 7.53+0.41 16.6+0.7 17.10.6* 14 . 3t2.6 12.4+2.4 11 12 87 82 1 4 1 2 0 0
100
74-3591 50
48
7.80
74-3592 50
46
6.98
74-3593 54
54
7.79
74-3594 48
48
7.81
74-3595 50
46
7.40
7.62 7.23 8.53 7.90 7.32
16.5 15.5 17.0 16.2 16.3
16.2 16.1 17.9 16.6 15.9
16.4 19.9 17.5 18.2 19.9
11.9 15.6 10.4 13.8 15.5
13 7 85 86 0 5 2 2 0 0 4 3 93 90 2 6 1 L 0 0 9 7 87 87 2 5 0 i 2 0
12 13 86 79 1 5 1 2 0 0 4 9 91 86 2 3 2 2 1 0
MEAN+SD 50+2 48+3 7.56+0.36 7.72+0.52 16.3+0.5 16.5+0.8 18,4+1.5 13.4+2.3 8 8 89 86 1 5 1 2 1 0
200
74-3571 50
47
7.64
74-3572 52
46
7.46
74-3573 53
48
8.17
74-3574 51
48
7.92
74-3575 51
48
8.00
7.65 6.94 7.70 7.56 7.70
16.6 16.6 17.2 16.5 16.9
16.6 15.8 16.3 15.9 15.9
18.9 17.7 12.9 15.0 16.1
7.8 10.8
7.4 11.8
8.1
19 12 79 81 2 6 0 1 0 0 6 7 93 88 0 3 1 2 0 0
11 15 89 77 0 4 0 4 0 0 9 10 90 84 0 5 1 1 0 0
14 4 82 91 4 4 0 1 0 0
MEANiSD 51 + 1 4 7+1 7.84+0.29 7.51+0.32 16.8+0.3 16.1+0.3 16.1+2.3 9.1 + 2.0 12 10 87 84 1 4 0 2 0 0
Days on test *SIgnifIcantly different from controls by Dunnett's test, p<0.05.
, SL 081958
Table A-9
ppm VDC in water
0
60
100
200
RESULTS OF URINALYSES OBTAINED FROM MALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYLIDENE CHLORIDE FOR 90 DAYS
Anloal Number
Specific Gravity
30a 62
85
pH Sugar Protein 30 62 85 30 62 85 30 62 85
74-3471 74-3472 74-3473 74-34 74 74-3475
1.035 1.060 1.065 6.5 6.5 6.0 neg neg neg 1.053 1.035 1.048 6.0 6.5 6.5 neg neg neg 1.053 1.045 1.043 6.0 6.0 7 .0 neg neg neg 1.048 1.035 1.043 6.0 6.0 6.0 neg neg neg 1.047 1.043 1.059 6.0 6.0 6.0 neg neg neg
+2 +1 41 4-1 4-1
4-1
41 trace
4-1 4-1
42 41 41 42 41
74-3531 74-3532 74-3533 74-3534 74-3535
1.055 1.044 1.065 6.0 6.0 6.0 neg neg neg +2
4-3
1.050 1.064 1.066 6.5 6.0 6.0 neg neg neg 4-2
+2
1.055 1.053 1.053 6.0 6.0 6.0 neg neg neg 4-1
4-1
1.060 1.050 1.04 2 6.0 6.0 7.0 neg neg neg 4-2
+3
1.023 1.033 1.025 6.5 6.0 6.5 neg neg neg trac e trace
43 43 42 42 +2
74-3511 1.054 1.040 1.04 7 6.0 6.5 6.0 neg neg neg 4-2 4-2 42 74-3512 1.059 1.04 3 1.048 6.5 6.0 5.5 neg neg neg 4-2 +1 41 74-3513 >1.066 1.061 1.057 6.0 6.0 6.0 neg neg neg 4-3 4-3 43 74-3514 1.063 1.040 1.062 6.0 6.5 6.0 neg neg neg +2 +1 42 74-3515 1.049 1.059 1.038 6.0 6.0 6.5 neg neg neg 4-3 4-2 42
74-3491 1.064 1.056 1.030 6.0 6.0 6.5 neg neg neg 4-2 4-3 43 74-3492 1.043 1.060 >1.066 6.0 6.0 6.0 neg neg neg 42 4-2 43 74-3493 >1.066 1.060 1.054 6.0 6.0 6.5 neg neg neg 4-3 42 42 74-3494 1.064 1.039 1.04 5 6.0 7.0 6.0 neg neg neg 4-3 43 43 74-3495 1.061 1.036 1.023 6.0 7.0 6.0 neg neg neg 4-2 41 42
Ketones
30 62
85
Occult Blood
30 62
85
Bilirubin 30 62 85
neg t race small neg neg neg neg neg neg
neg neg smal 1 neg neg neg neg neg neg
neg neg trace neg neg neg neg neg neg
neg neg
neg neg neg neg neg neg neg
neg neg small neg neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
smal 1 trace small
neg sma 11
neg neg neg neg neg
neg neg neg neg neg neg neg neg neg neg neg neg neg smal 1 neg
neg neg neg neg neg
neg neg neg neg neg
neg neg trace neg neg
neg neg neg neg trace trac e neg neg neg neg
neg neg neg neg neg neg neg neg neg mod, neg neg neg small neg
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
trace neg trace trace
neg neg neg trace neg neg
neg neg sma 11 neg neg
neg neg neg neg neg
neg neg neg neg neg neg neg neg neg neg neg neg neg small neg
neg neg neg neg neg
neg neg neg neg neg
^ays on test
SL 081959
Table A-10
ppm VDC In water
0
60
100
200
RESULTS OF URINALYSES OBTAINED FROM FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VINYI.IDENE CHLORIDE FOR 90 DAYS
Animal Number
Specific Gravity
30a 62
86
pH Sugar Protein 30 62 86 30 62 86 30 62 86
Ketones
30 62
86
Occult Blood
30 62
86
Billrubin 30 62 86
74-3551 >1.066 1.033 1.027 6.0 7.0 7.5 neg neg neg 74-3552 1.039 1.032 1.027 7.0 6.5 7.5 neg neg neg 74-3553 1.044 1.047 1.063 6.0 6.5 6.0 neg neg neg 74-3554 1.034 1.030 1.044 7.0 6.0 6.0 neg neg neg 74-3555 1.058 1.028 1.033 6.0 6.5 6.5 neg neg neg
+3 +1 +2 +1 +2
3-3 trace
+3 3-1 3-1
trace trace
33 32 trace
neg neg neg neg neg
neg neg neg neg neg
neg neg trace trace trace
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
74-3611 74-3612 74-3613 74-3614 74-3615
1.032 1.027 1.052 1.024 1.055
1.029 1.041 1.045 1.045 1.065
1.028 1.058 1.035 1.049 1.064
7.0 6.0 6.5 neg neg neg 6.5 6.0 6.0 neg neg neg 6.0 6.0 7.5 neg neg neg 7.5 6.0 6.5 neg neg neg 5.5 6.0 6.0 neg neg neg
trace +i +2 +1 +2
trac e 3-2 +3 3-1 +3
trace 32 33 31 33
neg neg neg neg neg
neg neg trace neg trace
trace small trace
neg t race
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
74-3591 74-3592 74-3593 74-3594 74-3595
1.057 1.026 1.041 >1.066 1.044
1.033 1.035 1.031 1.021 1.055
1.051 1.04 3 1.035 1.046 1.042
6.0 6.0 6.0 neg neg neg 6.5 6.0 6.0 neg neg neg 6.0 6.0 6.0 neg neg neg 6.0 7.0 6.0 neg neg neg 6.0 6.0 6.5 neg neg neg
+1 trace
+2 +3 +1
3-1 3-1 +1 trace 3-1
31 31 32 31 31
neg neg neg neg neg
neg neg neg neg neg
trace neg neg
trace neg
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
74-3571 74-3572 74-3573 74-3574 74-3575
1.028 1.064 1.044 1.064 1.04 7
1.034 1.056 1.038 1.054 1.025
1.044 1.043 1.033 1.035 1.062
6.0 7.0 6.0 7.0 8.0
6.0 6.0 6.0 6.0 7.0
6.0 6.5 6.5 7.0 6.0
neg neg neg neg neg
neg neg neg neg neg
neg neg neg neg neg
+2 +2 +1 3-2 3-3
3-2 32 neg neg trace neg neg neg neg neg neg
31 31 neg trace small neg neg neg neg neg neg
trace trace neg neg
neg neg neg neg neg neg neg
+i 31 neg neg neg nog neg neg neg neg neg
33 32 neg neg t race neg neg neg neg neg neg
aDays on test
SL 081960
4 ji
O
o
081961
Table A"ll
INDIVIDUAL AND MEAN CLINICAL CHEMISTRY VALUES FOR MALE AND FEMALE RATS MAINTAINED ON drinking water containing vinylidene chloride for 90 days
Days on test
90
ppm VDC in water
60 1Q0 200
0
60
100
200
Animal Number
74-3476 74-3477 74-3478 74-3479 74-3480
MEAN+SD
74-3536 74-3537 74-3538 74-3539 74-3540
MEAN+SD
74-3516 74-3517 74-3518 74-3519 74-3520
MEAN+SD
74-3496 74-3497 74-3498 74-3499 74-3500
MEANlSD
74-1471 74-1473 74-3475 74-3477 74-3479 74-3481 74-3483 74-3485 74-3487 74-3489
MEAN+SD
74-3531 74-3533 74-3535 74-3537 74-3539 74-3541 74-3543 74-3545 74-3547 74-3549
MEANlSD
74-3511 74-3513 74-3515 74-3517 74-3519 74-3521 74-3523 74-3525 74-3527 74-3529
MEAN+SD
74-3491 74-3493 74-3495 74-3497 74-3499 74-3501 74-3503 74-3505 74-3507 74-3509
MEANlSD
Males
BUN
AP
mg %
mU/ml
27 28 30 28 28
2811
481 479 460 >500 446
____a
29 27 24 28 27
2712
422 471 >500 437 469
--
26 >500 24 >500 26 >500 24 439 27 457
26rl
--
22 24 26 25 23
25 + 2*
482 482 >500 >500 460
___
20 18 22 14 19 22 17 20 24 22
20 + 3
19 16 19 20 15 17 18 23 27 16
19 + 4
19 19 20 18 20 17 17 18 16 16
18 + 1
20 20 18 19 18 18 20 27 20 20
20 + 3
108 83
108 152 141 150 134 128 128 117
125+21
106 107
93 120
89 108
84 159
65 112
104+25
114 98
108 108 104 111 149 124 113 125
114+16
91 100 149 104 100 122 149 119 162 125
122+24
SGPT raU/ml
44 49 47 58 47
49 + 5
45 46 52 49 45
47 + 3
50 49 53 45 49
49 + 3
53 50 48 43 58
50 + 6
49 37 34 46 45 47 41 48 40 31
42 + 6
41 34 38 46 33 35 -> 7 34 22 31
34t7*
36 31 37 39 32 34 43 44 27 29
35 + 6
41 39 28 35 44 30 36 34 33 30
355*
Animal Number
74-3556 74-3S57 74-3550 74-3559 74-3560
MEAN+SD
74-3616 74-3617 74-3618 74-3619 74-3620
MEAN+SD
74-3596 74-3597 74-3598 74-3599 74-3600
MEAN+SD
74-3576 74-3577 14-3578 74-3579 74-3580
MEAN+SD
74-3551 74-3553 74-3555 74-3557 74-3559 74-3561 74-3563 74-3565 74-3567 74-3569
MEAN+SD
74-3611 74-3613 74-3615 74-3617 74-3619 74-3621 74-3623 74-3625 74-3627 74-3629
MEAN+SD
74-3591 74-3593 74-3595 74-3597 74-3599 74-3601 74-3603 74-3605 74-3607 74-3609
MEANlSD
74-3571 74-3573 74-3575 74-3577 74-3579 74-3581 74-3583 74-3585 74-3587 74-3589
MEANlSD
Females
BUN
AP
mg %
mU/ml
26 438 26 463 26 393 23 377 28 451
2612
*--
21 325 22 387 24 402 20 >500 20 460
21*1
--
28 353
26 438 25 475 25 384 22 348
25 + 2
--
27 23 26 36 28
28 + 5
446 477 >500 >500 493
--
20 26 20 18 19 18 26 14 22 18
2014
19 24 21 17 23 21 13 22 21 22
20 + 3
22 22 18 17 15 21 18 22 19 21
20 + 2
18 19 26 18 21 17 22 17 18 20
2013
82 142
83 101
80 70 118 60 84 117
94+25
70 74 82 74 99 86 83 74 65 77
78 + 10
80 98 55 73 66 80 90 88 109 90
83 + 16
61 100
63 114 120
96 159
91 76 67
95131
aNot analyzed statistically because of values that were too high to measure, Significantly different from controls by Dunnett`s test, p<0.05.
SGPT mU/ml
38 43 46 47 42
4314
48 37 45 44 49
45 + 5
51 42 49 45 45
46+4
42 64 54 65 56
5619*
28 26 23 28 23 29 35 25 26 32
28i4
31 27 26 22 25 26 28 21 23 25
2513
25 31 24 23 21 28 26 26 22 27
25 + 3
28 25 29 34 34 27 29 20 23 30
2814
cn
Tab1e A-l2
INDIVIDUAL AND MEAN TERMINAL BODY WFIGHTS, ORGAN WEIGHTS AND ORGAN/BODY WEIGH! RATIOS iV* MAT h KA1S MAINTAINED ON DRINKING WATER CONTAINING VI NYU DENE CHLORIDE FOR 90 DAYS
ppm VDC Animal to water Number
Ternlna 1____________________________ _____________________________ Organ Weights (g and _/| 0(]g_ Body Welght)
Body wt,,
Brain
Hear t
l.iver
Kidney
starved.g
8
fi/lOOe &. s/IOOr
r/IOOr
Vioog.
0
74-3471
403
74-3473
395
74-3475
408
74-3477
373
74-3479
524
74-3481
440
74-3483
475
74-3485
4 58
74-3487
442
74-3489
461
1.88 1.89 1.96 1.89 1.96 1.90 1.69 1 .69 1 .87 1.90
0.47 0.48 0.48 0.51 0.37 0.43 0.40 0.41 0.42 0.41
1,29 1.22 1,29 1.13 1 .55 1 .50 1 47 1.52 3 .40 1.38
0. 32 0-31 0.32 0.30 0.30 0.34 0.31 0.33 0.32 0.30
10.27 11 .52 10 95 10.36 16.49 13.0G 12.69 13.26 12.28 13.26
2.55 2.92 2.69 2.78 i.l 5 . 9/ 2.6/ 2.90 2.78 2.86
3,25 2.92 2.75 3 08 4.09 3.28 2.90 3.49 3.20 3.48
0.81 0.74 0 67 0.6 5 0.7 8 0.75 0,61 0.76 0,73 0.76
Testes
4.08 4 00 4 00 4.10 3.86 3.63 4.27 4.09 3,87 3.92
] .01 1 .01 0.98 1.10 0. 74 0.8J 0.90 0.89 0.88 0,65
MEAN+SD 438*45
1.90+0 .03 0.44+0.04 1 38+0.14 0.32+0,01 12.42+1.83 2 .83+0,17 3.2h + 0.38 0.74+0.06 3.98+0.17 0.92+0.M
00
74-3531
4 64
1 ,82
74-3533
466
1 .95
74-3535
498
1.93
74-3537
520
2.00
74-3539
450
l. 9h
74-3541
437
1.8?
74-3543
477
1 .84
74-3545
4 34
1 .88
74-354?
44 6
1 .90
74-3549
441
_1. 7 7
0 39 0 42 0.39 0.38 0.4 h 0,42 0,39 0.43 0.43 0.40
1 38 1 .40 1 .45 1 46 1 , 36 I Ji 1.27 1.33 1.34 1 .4 3
0.30 0.30 0.29 0.28 0.30 0.31 0.27 0.31 0.30 0.32
12.31 ] J .75 13.34 J4 , 36 11.76 12.71 14.10 10.50 12.05 12.00
2.65 2.51 2.68 2.76 2.61 2.91 2.96 2.42 2 70 2.72
3.28 5.29 1 02 J .4 3 3.0 5 2.92 3.37 2.94 3.45 _ 3_.1_1 _
0.71 0.70 0.61 0.66 0.66 0,67 0.71 0.68 0.77 CL 7 l _ __
4.29 L9* 4.07 3, 74 3.92 3.82 3.95 3.66 3.82 3^_80_
0.93 0.84 0.8 2 0. 72 0.8? 0.87 0.83 0.89 0.86 0,66
HEAN+SD 464*28
1.89+0. 07 0.41t0.02 1.38+0.06 0.30*0.01 12.49+1.17 2 .69+0.16 3 19+0.20 0.69+0.04* 3.92+0.16 0.85+0.06
100
74-3511
450
74-3513
541
74-3515
427
7^-3517
386
74-1519
486
74-3521
439
74-3523
412
7h-3 525
418
74-3527
496
74-3529
4 20
1 .73 1.92 1.99 1 .64 ] . 73 1.94 1 .85 1.92 1 .88 1 .88
0.38 0.35 0.47 0.48 0.16 0.44 0 45 0.46 0.38 0.45
1 .30 1 .60 1.17 ] .1] 1.37 1,40 1 23 1.39 1.54 1.24
0.29 0.29 0.27 0.29 0.28 0.32 0.30 0.33 0.31 0.29
1L 86 16.44 10.46
9.69 13.36 12.53 10.69 11.23 14.48 11.93
2.63 3.04 2.45 2.56 2.75 2.85 2.60 2.69 2.92 2.84
3.55 4 .09 3.01 2.93 3.62 3.45 2.91 2.94 3.79 3.32
0.79 0.76 0.70 0.76 0.74 0.76 0.71 0.70 0.76 0.79
3.72 4.45 4.05 3.79 3.87 3,79 3.55 4.43 4.18 4.10
0.83 0.82 0.95 0.98 0.79 0.86 0.86 1.06 0.84 0.98
HEANtSD 448*47
1 .87*0.09 0.42*0.05 1 , 34+0.16 0.30+0.02 12.29+2.01 2 .73+0.18 3.36+0,41 0.75+0.04 3.99+0.30 0.90J0.09
200
74-34 91
399
74-3493
418
74-3495
449
74-3497
486
74-3499
476
74-3501
473
74-3503
502
74-3505
494
74-3507
467
74-3509
418
1.62 1.92 1.96 1 .85 1 .80 ] .85 1 .99 1 .01 l .92 1 .62
0.46 0.46 0.44 0.38 0.38 0.39 0,40
0.37 0.41 0.43
1.25 1 .23 1.34 1.56 1 .60 ] .30 l .50 1,40 1 .38 1 .44
0.31 0.29 0.30 0.32 0.34 0.27 0.30 0.2B 0.29 0.34
10.46 11.50 10.99 12.86 13.00 1 2.44 13.07 14.21 12.85 12.36
2.62 2.75 2.45 2.65 2.73 2.63 2.61 2.88 2,75 2.96
2.99 3.10 3.10 3.44 3.69 3.38 3.32 3.23 3.34 3.13
0.75 0.74 0.69 0.71 0.77 0.71 0.66 0.65 0.71 0.75
3.82 4.23 3.49 3.95 3.61 3.89 3.62 4.00 3.89 4.18
0.96 l 01 0.7B 0.81 0.76 0-82 0.76 0.81 0.83 1.00
HEAN+SD 458135
1.87+0.,07 0,41+0.03 1 .40 + 0.13 0.30+0.02 12.39+1.11 2 .70+0.15 3.27+0.21 0.71+0.04 3.89+0.23 0.85+0.10
SL 081962
*Slgn if leant 1y different from controls by Dunnett's test, p<0.05.
Table A-13
INDIVIDUAL AND KEAN TERMINAL BODY WEIGHTS, ORGAN WEIGHTS AND ORGAN/BODY WEIGHT RATIOS OF' FEMALE RATS MAINTAINED ON DRINKING WATER CONTAINING VTNYLIDENE CHLORIDE FOR 90 DAYS
ppm VDC in water
0
60
100
200
Animal Number
74-3551 74-3553 74-3555 74-3557 74-3559 74-3561 74-3563 74-3565 74-3567 74-3569
MEAN+SD
74-1611 74-3613 74-3615 74-3617 74-3619 74-3621 74-3623 74-3625 74-3627 74-3629
MEANiSD
74-3591 74-3593 74-3595 74-3597 74-3599 74-3601 74-3603 74-3605 74-3607 74-3609
MEANiSD
74-3571 74-3573 74-3575 74-3577 74-3579 74-3501 74-3503 74-3505 74-3587 74-3589
MEANISD
TerminalOrgan weights (q and g/lOOq body weight)
Body wt.,,
Brain
Heart
Liver
starved,g
g
q/I0Uq
9 q/1OOq
g q/LOOg
323 279 262 289 260 260 246 267 277 268
1.73 1.70 1.72 1.80 1.79 1.69 1.05 1.85 1.77 1 .78
0.53 0.64 0.66 0.62 0.69 0.65 0.75 0.69 0.64 0.67
1.00 0.92 0.09 1.06 0.06 0.94 0.90 0 . 86 0.89 0.97
0.31 0.33 0.34 0.3'? . i i
0.it 0.37 0.32 0.3 2 0. 36
0 . 67 7.24 6.45 7.67 6.45 6.61 6.51 6.77 7 . 35 6.62
2.68 2 . 59 2.47 2.66 2.47 2.54 2.65 2.53 2.66 2.47
27 3+2L
1.7810.05 0 .6510. 06
0 .93+0.,06
0.3410.02
} . 0 3'0.7 2
2.5/10.09
202 274 267 108 296 268 257 284 276 282
1.87 1 .B 7 1.76 1 . 79 1.85 1.72 1.80 1 .86 1.75 1.75
0.66 0.6B 0.66 0.95 0.62 0.64 0.70 0.66 0.63 0.62
0.93 0.92 0.98 0.99 1.03 0.92 1.00 1.06 0.90 0.97
0.33 0.34 0.37 0.62 0.35 0.34 0.39 0.37 0.33 0.35
6,89 7.2S 6.87 7.41 7 . 99 7.03 7 . 02 7.23 7.14 7.03
2 .44 2.65 2 57 3.95 2.70 2.62 2.73 2 . 54 2 . 59 2.78
267+30 1.80+0.06 0 . 680. 10 0 .97+0., 05 0.370,06 7 .27 +0.38 2.76+0.43
244 287 273 270 273 298 267 291 298 282
1.79 1.85 1.01 1.76 J .77 1.73 1.77 1.72 1.74 1.75
0.73 0.64 0.66 Q . 65 0.65 0.50 0.66 0.59 0.58 0.62
0.82 0.93 0.91 0.88 0.93 1.06 0.05 1.03 0.91 1.05
0.34 0 . 32 0.34 0.32 0.34 0.36 0.32 0.35 0.30 0.37
6.33 6.52 7 . LI 7.54 6.93 7.41 6.5J 7.85 7.55 7.77
2 . 59 2.27 2.61 2.79 2 . 54 2.49 2.44 2.70 2.53 2.75
278 il6 1.7710.04 0 .6410. 05 0 ..9410,.08
0.34+0.02
7 .15+0.56 2.57+0.15
313 283 291 267 291 306 307 262 292 273
1.B0 1.65 1.78 1.73 1.74 1.05 1.02 1.72 1.00 1.B8
0.57 0.58 0,61 0.65 0.60 0.60 0.59 0.66 0.62 0.69
0.96 0.86 1.04 0.92 0.95 0.95 1.01 0.93 1.02 1.00
0.31 0.31 0.36 0.34 0.33 0.31 0.33 0.36 0.35 0.36
0.36 6.74 7.49 6.73 7.56 8.03 7 .54 6.44 7.63 8.25
2.67 2,39 2.50 2.52
2 . 59 2.63 2.46 2.45 2.61 3.02
288+1? 1.7010.07 0 .6210. 04 0 .9610,,05 0.34+0.02 7 .40+0.66 2.59+0.17
Kidney g q/1OOq
2.23 ] . 96 L . 93 2.03 2.07 1 . 08 1 . B0 1 . 08 2 . 00 1 .86
0.69 0.70 0.74 0,70 0.00 0.72 0.73 0.70 0 . 72 0.70
l .96+0., 1 i 0.72`0.0 3
1 .90 1 . H6 1.76
2.10 2.33 1.77 1.88 1 . 92 1.03 2.21
0.6 7 0.68 0.66 1 12 0.79 0.66 0.73 0.67 0 . 37 0.78
1.88+0..35 0.71+0.18
J .76 1 .82 1.93 1.80 1.93 1 . 9B 1.89 2.21 1.99 2.16
0.72 0.63 0.71 0 .69 0.71 0.67 0.71 0.76 0.67 0.77
1.96tO,,14 0.70+0.04
2 .16 1 . 99 2.10 1, 80 2.06 2 .16 2 .07 1.87 2 .14 2 .16
0.69 0.70 0.72 0.68 0.71 0.71 0.60 0.71 0.73 0.79
2.05+0.,13 0.71+0.03
There were no significant differences between treated and control groups by Dunnett's test, p^'0.05.
SL 081963
j'D dAp J
3 HJUk-5/2^
, too0,(0
f 100Jj?cJ
-yi&
-f)l
1U) /jjjpt^7 in Unhdi O^jdit [s>- Bj p^/
f jhpiztrf i )^ks^v ^ppxdi^-^jiMit^^)
-m
fj f jnsUfj
iwfbfhr)
Clu^uc'* SO^OV, 700 ftynrs
SL 081964
M a miw v^1a
SI 081965