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noted; however, the study duration was short, a small number of animals was used, only one sex was
used, and the primary aim of the study was to develop methods of detecting carcinogens inducing
mammary tumors.
The potential carcinogenicity of 4,4' methylenedianiline dihydrochloride was studied using Fischer 344
(F344) rats and B6C3F 1 mice (50 animals/sex/species/group) (NTP, 1983). Animals were exposed to
150 mg/l or 300 mg/l 4,4' methylenedianiline dihydrochloride in drinking water for 103 weeks followed
by one week without treatment. Untreated control groups were included. A significantly increased
incidence of thyroid follicular-cell adenomas was observed in male and female mice and rats.
Significantly increased incidences of hepatocellular adenomas and carcinomas were observed in female
and male mice; increased incidences of neoplastic nodules were observed in male rats. Tumor
incidence data is listed in Table 1.
Table 1
4,4' methylenedianiline dihydrochloride-induced tumor incidences in male and female
F344 rats and B6C3F 1 mice (NTP, 1983; Weisburger et al., 1984)
Sex/species
Dose
group
Average dose 1
(mg/kg-day)
Tumor type Tumor incidence 2
male mice control 0 thyroid tumors 0/50
low dose 24.5 3/50
high dose 49.5 16/50
control liver tumors 17/50
low dose 43/50
high dose 37/50
female mice control 0 thyroid tumors 0/50
low dose 29.4 1/50
high dose 59.1 15/50
control liver tumors 4/50
low dose 15/50
high dose 23/50
male rats control 0 thyroid tumors 1/50
low dose 7.36 4/50
high dose 14.7 10/50
control hepatic neoplastic nodules 1/50
low dose 12/50
high dose 25/50
female rats control 0 thyroid tumors 0/50
low dose 8.41 5/50
high dose 16.7 22/50
1. Doses as reported by Gold et al. (1987).
2. Tumor incidences as reported by Gold et al. (1987).
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