Document k2jJJ72611yQ1nnp6O1GG89B
Jan*24-97 Ol:IIP Huntingdon Ufa Sciences
P .Ol
TOTAL NUMBER OF PAGES INCLUDING THIS PAGE:
12
Huntingdon
Life Sciences
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ATTENTION OF: Dr. J. Knaak
COMPANY:
Occidental Chemical Corporation Dallas, TX 75244
CC: Dr. Hasmukh Shah Chemical Manufacturers Association Arlingon, VA 22209
FROM: DATE:
Raymond E. Schroeder 24 January 1997
MESSAGE:
Study No. 96-4080 - Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats
This fascimile includes the following summary data for the above referenced study for your review:
Tables
1. Summary of In-Life Physical Observations 2. Mean Body Weights 3. Mean Food Consumption 4. Percent Difference in Body Weight from Control
Appendix A. Methodology and References
Please contact me with any questions.
Best Regards,
Raymond E. Schroeder Study Director
J/iL
CMA118863
Jan-24-97 01:11P Huntingdon Llfa Sciences
P . 02
t OF ANIMALS EXAMINED
T 1-1 DRAFT
TABU 1 VINU CHLORIDE COMBINES INHALATION TWO*GENERATION REPRODUCTION
AHO DEVELOPMENTAL TONICITY ETUOY IN CO RATE
SUMMARY OF IN-LIfC PHYSICAL OBSERVATIONS - MALES WEEK: 1 0 1 Z
I 30 II 30 III 30 IV 30
0 30 30 0 30 30 0 30 30 0 30 30
NORMAL
within normal limits
OERMAL-GENERAL ULCERATION - CERVICAL
ALOPECIA EXTREMITIES/SNOUT
I 30
It 30 III 30
IV 30
- 29 29 - 30 29 - 30 29 - 30 30
I C -01 11 0 * 0 0
111 0 - 0 0 IV 0 - 0 0
1a
00
11 0 - 0 1
III 0 0 0
IV 0 - 0 0
M-40S0
ocular
LACRIMA710N UNILATERAL
10
II 0
III 0
IV 0
CHRCMOOACRrORRHEA UNILATERAL
I0 II 0 III 0 IV 0
ORAL/BUCCAL INCISORS MALCCCLUteO
I
II III
IV
10
00 00
00
I0 0s
00
00
CMA 118864
Jan-24-97 01:11P Huntingdon Llfa Sclancas
OF ANIHALS EXAMINED
draft
T 1*2 TABU 1 Ceont.)
VINYL CHLORIDE COMBINED INHALATION TWO-GENERATION REPRODUCTION
AND DEVELOPMENTAL TOXICITY STUDY IN CD RATS
SUMMARY OF IN-LIFE PHYSICAL OBSERVATIONS - FEMALES week: i 0 1 2
I so II 30 III 30 IV 30
0 30 30 0 30 30 0 30 30 0 30 30
NORMAL WITHIN NORMAL LIMITS
OCULAR LACRIMATIQN - UNILATERAL
CHROMOOACRYORRHEA UNILATERAL
ORAL/BUCCAL ORAL SORE
I 30 11 30 III 30 IV 30
10 II 0 III 0 IV 0
10 II 0 III 0 IV 0
I0 II 0 II! 0 IV 0
. 30 30
30 30
* 30 30
30 29
00 00 00 01
00 00 00 01
00 00 00 01
P . 03 W-408Q
CMA 118865
Jan-24-97 Ol : IIP Huntingdon Llfa sdancaj
r z-i
96-4000
TABLE 2
VINYL CHLORIDE COMBINED INHALATION TWO-GENERATION REPHOOUCTION
AND DEVELOPMENTAL TOXICITY STUDY IN CD HATS
DRAFT
$TAT SYMBOL;
WEEK
BODY WEIGHT IN GRAMS MALES
DOSE LEVEL: PPM
0.0000
10.0000
100.0000 1100.0000
A*L4
1 MEAN 161.0
S.D.
9.3
N 30
161.0 9.3 30
161.1 9.4 30
1*0.9 9.4 30
A-L'
0 MEAN 233.3
S.D.
11.6
N 30
237.7 13.3 30
236.6 12.6 30
234.3 14.0 30
A-L-
1 MEAN 274.5
S.O.
13.4
M 30
279.6 19.0 30
277.8 14.5 30
272.4 16.6 30
A-L-
2 MEAN 314.2
S.D.
16.3
N 30
322.1
23.5 30
321.7 17.9 30
318.3 20.5 30
P . 04
CMA 118866
n-24-97 Ol:12P Huntingdon LIfo SclsncflS
T Z-Z
96-4080
tail* Z (sent.)
VINYL chloride combined INHALATION TWO-semination reproduction
AMO DEVELOPMENTAL TOXICITY STUDY IN CD RATS
DRAFT
STAT SYMBOL:
WEEK
BOOT WEIGHT IN GRAMS FEMALES
DOSE LEVEL; PPM
0.0000
10.0000
100.0000 1100.0000
A-L-
-1 MEAN 116.5
S.O.
6.0
N 30
116.Z 6.1 30
116.5 5.7 30
116.7 5.8 30
a-l-
0 MEAN S.O. H
158.0 7.5 30
158.5 9.1
30
156.3 9.3 30
157.0 7.7 30
A-lA-L-
I MEAN 177.1
S.D.
9.7
N 30
z MEAN 196.4
S.O.
11.9
N 30
173.8 9,5 30
197.3 10.4 30
178.1 1Z.1 30
199.1 14.1 30
175.8 9.3 30
197.1 11.7 30
P . 05
CMA118867
Jan-24-97 Ol:12P Huntingdon Llfa Sciences
96-4080 T 3-1 TABLE 3 VINYL CHLORIDE COMBINED INHALATION TWO-GENERATION REPRODUCTION AND DEVELOPMENTAL TOXICITY STUDY IN CD RATS
DRAFT
STAY SYMBOL;
AL-G
FOOD CONSUMPTION G/KG/OAY MALES
DOSE LEVEL: PPM
WEEK
0.0000
10.0000
0 MEAN 122.6
S.D.
6.2
N 29
125.1 6.4 30
100.0000
* 127.1
5.1 30
1100.0000
124.8 6.6 30
A-L* A*L'0*
1 MEAN
S.O. N
86.3 4.1 30
2 MIan
S.D. N
74.3 5.4 30
84.7 3.4 30
76.5 3.5
30
85.3 4.2 30
*4
78.2 3.7 30
83.2 4.1 30
76.4 4.0 30
P . 06
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T 3-2
96-4080
TAIL! J (ont.)
VINYL CHLORIDE COMBINED INHALATION TWO-GENERATION REPRODUCTION
AND DEVELOPMENTAL TOXICITY STUDY IN CO RATS
STAT SYMBOL:
WEEK
FOOD CONSUMPTION G/KO/OAT FEMALES
DOSE LEVEL: PPM
0.0000
10.0000
100.0000 1100.0000
A-L-
0 MEAN 131.8
S.D.
5.9
M 29
133.S 9.4 29
134.9 7.8 28
134.9
8.0 26
Al-h KT-J
1 MEAN S.D. H
92.1 4.5 30
2 MEAN S.D. N
88.8 8.8 30
89.4 4.7 28
89.0 4.7 30
93.6 7.5 29
90.8 8.2 30
90.4 5.7 27
89.1 7.4 30
DRAFT
P.07
CMA 118869
Jan-24-97 01:12P Huntingdon Life Scianc
T 4-1
06-6080
TABLE 4 VINYL CHLORIDE COMBINED INHALATION TWO-GENERATION REPRODUCTION
AND DEVELOPMENTAL TONICITY STUDY IN CO RATS
draft
X DIFFERENCE IN BODY WEIGHT MALES
DOSE LEVEL; PPM
WEEK
1 X DIFF N
0 .0000
0.0 10
10.0000
0.0 30
100.0000
0.1 30
0 X DIFF
0.0
1.9
1.4
N 30 30 30
1 X DIFF
0.0
1.9
1-2
N 30 30 30
2 X DIFF
0.0
2.3
2.4
N 30 30 30
1100,0000
-0.1 30
0.4 30
0.8 30
1.3 30
P . 08
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I
T 4-2
96-4080
TABLE 4 (cont.) VINYL CHLQPIDE COMBINED INHALATION TWO-GENERATION REPRODUCTION
ANO DEVELOPMENTAL TOXICITY STUDY IN CD RATS
DRAFT
X 01FFEREMCe IN BOOT WEIGHT FEMALES
DOSE LEVEL: PPM
0.0000
10.0000
100.0000
IFF N
0.0 30
-0.3 30
0.0 30
IFF H
0.0 30
0.3 -1.1 30 30
DIFF N
0.0 30
*1.9 30
0.6 30
DIFF
0.0
0.3
1.4
N 30 30 30
1100.0000
0.2 30
-0.6 30
-0.7 30
0.4 30
P .09
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P . 10
HP A
A-l tic** Appendix A
96-4080
Vinyl Chloride Combined Inhalation Two-Generation Reproduction
and Developmental Toxicity Study in CD Rats
Methodology and References - Statistical Analysis
Parameters analyzed statistically for this status report: body weights and food consumption
MULTIPLE GROUP ANALYSIS STAT SYMBOL
No Sio psQ,OS psO.Ol Parametric
A-
A A+
L-
L L+ Q Q+
STATISTICAL STATEMENT
No statistical differences among the means (parametric ANOVA). The means differ significantly (parametric ANOVA). The response is not linearly related to the dose levels. The response is linearly related to the dose levels. The response shows a lack of fit. Significantly different from control (Dunnett's).
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draft
A-2 96-4080 Appendix A (cont.) Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats
Methodology and References - Statistical Analysis
MULTIPLE GROUP ANALYSIS STAT SYMBOL
No Sig pjQ.Qg P3Q.Q1 Nonparametric
K-
K K+
JJ J+
* **
NT
STATISTICAL STATEMENT
No statistical differences among the means (Kruskal-Wallis, nonparametric). The means differ significantly (Kruskal-Wallis nonparametric). There is not an ordered response to dosage. There is an ordered response to dosage. Significantly different from control (Dunn's Rank Sum). Not tested due to lack of variance.
Statistical evaluation of equality of means was made by the appropriate one way analysis of variance technique, followed by a multiple comparison procedure if needed. First, Bartlett's test was performed to determine if groups had equal variance. If the variances were equal, parametric procedures were used; if not, nonparametric procedures were used. The parametric procedures were the standard one way ANQVA using the F distribution to assess significance. If significant differences among the means were indicated, Dunnett's test was used to determine which means were significantly different from the control. If a nonparametric procedure for testing equality of means was needed, the Kruskal-Wallis test was used, and if differences were indicated a summed rank test (Dunn) was used to determine which treatments differed from control.
<
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Jan-24-97 01:13P Huntingdon Llfa Sclancas
P.1Z
DRAFT
A-3 96-4080 Appendix A (cont.) Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats
Methodology and References - Statistical Analysis
A statistical test for trend in the dose levels was also performed. the parametric case (i.e., equal variance) standard regression techniques with a test for trend and lack of fit were used. In the nonparametric case Jonckheere's test for monotonic trend was used.
In
The test for equal variance (Bartlett's) was conducted at the 1%,
two-sided risk level. All other statistical tests were conducted at the 5% and 1%, two-sided risk level.
References for these techniques are Snedecor, G.W., and Cochran, W.G., Statistical Methods. 6th edition, Iowa State University Press (1967); Hollander, M. and Wolfe, D.A., Nonparametric Statistical Methods, John
Wiley and Sons, New York (1973); Ounnett, C.W., J. 4m. Sta. Assn. Vol. 50 (1955) and Biometrics. Vol. 20 (1964).
Bartlett's Test
pp. 296-298
ANOVA
pp. 277-279
Dunnett's
pp. 1096-1121
pp. 482-491
Kruskal-Wallis
pp. 114-116
Summed Rank Test (Dunn) p. 131
Regression Analysis
Trend
pp. 135-153
Lack of Fit
pp. 456-459
Jonckheere's Statistic pp. 120-123
S&C S&C D Bio H&W H&W
S&C S&C H&W
CMA 118874