home edit2 whole TSD November 2002 PDF format - OEHHA

eported by Kociba et al. (1978) was an adequately conducted chronic carcinogenicity bioassay of
TCDD, with significant effects observed at the two higher dose levels.
The National Toxicology Program (NTP 1982a) conducted an oncogenicity bioassay of TCDD in male
and female Osborne-Mendel rats. They were administered TCDD in a 9:1 corn oil:acetone vehicle by
gavage at dose levels of 0.005, 0.025, or 0.25 µg/kg twice a week for 104 weeks. The treatment
groups consisted of 50 rats of each sex and a vehicle control group that was made up of three
subgroups of 25 rats of each sex. An untreated control group, also made up of three subgroups of 25
rats of each sex, was included in the study, but not in the statistical analysis of the results by NTP. At
the dose levels used, TCDD did not have a significant effect on survival of any treatment group. The
high-dose group of male rats did have a statistically-significant increased incidence of subcutaneous
tissue fibromas, but it was not considered biologically significant because of the variability found. All
male treatment groups had significantly (p < 0.05) increased incidences of thyroid follicular cell
adenomas or adenomas and carcinomas, although the low- and intermediate-dose level group
incidences were not significant when compared to the untreated control group by CDHS staff. The
female high-dose group had significantly (p < 0.05) increased incidences of several tumor types,
including subcutaneous tissue fibrosarcomas, liver neoplastic nodules or hepatocellular carcinomas, and
adrenal cortical adenomas. Of these 3 tumors, NTP considered only the liver tumors to be related to
TCDD administration. The incidences of these tumors are given in Table 2. Toxic hepatitis was found
in 14 male and 32 female high-dose level rats.
Table 2: Tumor incidences in male and female Osborne-Mendel rats given 2,3,7,8-
Tetrachlorodibenzo-p-dioxin (TCDD) by gavage for two years (NTP, 1982a)
Sex, tumor type
Dose level (µg/kg-week)
0 0.01 0.05 0.5
Males
Tumor incidence a
Thyroid
Follicular cell adenoma 1/69 5/48 (p = 0.042) 6/50 (p = 0.021) 10/50 (p = 0.001)
Follicular cell adenoma/carcinoma 1/69 5/48 (p = 0.042) 8/50 (p = 0.004) 11/50 (p < 0.001)
Females
Subcutaneous tissue, fibrosarcoma 0/75 2/50 3/50 4/49 (p = 0.023) [3] b
Liver
Neoplastic nodules/ hepatocellular 5/75 1/49 3/50 14/49 (p = 0.001)
carcinoma
Adrenal
Cortical adenoma or adenoma NOS 11/73 8/49 4/49 14/46 (p = 0.039)
a Number of animals with tumor over number of animals examined.
b
Number of animals with hepatocellular carcinoma.
NOS Not otherwise specified
P values determined using Fisher’s exact test.
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