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NTP (1982a) also conducted an carcinogenicity bioassay with TCDD in male and female B6C3F 1
hybrid strain mice. The protocol was similar to that used in the rat study with male mice receiving the
same doses of TCDD. Female rats, however, received larger doses of 0.02, 0.1 or 1.0 µg/kg twice a
week. These dose levels did not have a statistically significant effect on survival of any treatment group.
Male mice in the highest dose group had a significantly increased incidence of hepatocellular
carcinomas. The high-dose female group had significantly increased incidences of subcutaneous tissue
fibrosarcomas, hepatocellular adenomas or carcinomas, and thyroid follicular-cell adenomas. NTP
considered only liver tumors and thyroid tumors to be related to TCDD administration. NTP also
considered histiocytic lymphomas to have been increased in the high-dose female group; however, the
staff of DHS did not consider that these lymphomas were increased when the incidences in all control
subgroups were considered. The observed tumor incidences in both male and female mice are given in
Table 3. Toxic hepatitis was observed in 44 male and 34 female high-dose group animals. It was also
observed in several animals of the other treatment groups.
Table 3:
Tumor incidences in male and female B6C3F 1 mice given 2,3,7,8-Tetrachloro-dibenzop-dioxin
(TCDD) by gavage for two years (NTP, 1982a).
Sex, tumor type
Dose level (µg/kg-week) a
0 0.01 0.05 0.5
(0.04) (0.2) (2.0)
Tumor incidence b
males
liver (hepatocellular carcinoma) 8/73 9/49 8/49 17/50 (p = 0.002)
Hepatocellular adenoma or carcinoma 15/73 12/49 13/49 27/50 (p < 0.001)
females
Subcutaneous tissue, fibrosarcoma 1/74 1/50 1/48 5/47 (p = 0.032)
liver, hepatocellular carcinoma 1/73 2/50 2/48 6/47 (p = 0.014)
hepatocellular adenoma or carcinoma 3/73 6/50 6/48 11/47 (p = 0.002)
thyroid, follicular cell adenoma 0/69 3/50 1/47 5/46 (p - 0.009)
P values determined using Fisher’s exact test.
a Dose administered to male mice; dose administered to female mice in parentheses.
b
Number of animals with tumor over number of animals examined.
Both rat and mouse carcinogenicity bioassays conducted by NTP appear to have been done in an
adequate manner. The number of treatment groups and the large dose range used in the studies are not
typical of NTP bioassays, although it was similar to that used by Kociba et al. (1978). However, it may
not have been large enough to include a dose level which produced no effect. Most significantly
increased tumor incidences only occurred in the high-dose level groups, but a statistically significant
dose-related trend was found in all groups.
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