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quite high; 50% mortality occurred at day 450 and 100% mortality at day 750. No tumors were
observed in the treated animals; however, only the bladder, liver, spleen and kidney were evaluated for
tumors.
Male and female Fischer 344 (F344) rats and B6C3F 1 mice were fed diets containing aniline
hydrochloride for 103 weeks (NCI, 1978). Rats were fed diets containing 0, 3000 or 6000 mg/kg diet
aniline hydrochloride; mice were fed diets containing 0, 6000 or 12000 mg/kg diet aniline
hydrochloride. Group sizes were 50/sex/group, except for high dose female mice (n = 49), and control
rats (25/sex). Surviving rats and mice were sacrificed at 107-108 and 107 weeks, respectively. No
significantly increased treatment-related tumor incidences were noted in treated mice. Male rats
demonstrated significantly elevated incidences of hemangiosarcomas in the spleen, as well as
fibrosarcomas and sarcomas (not otherwise specified) in multiple organs of the body cavity and spleen.
There were also significant dose-related trends in the incidence of hemangiosarcomas, sarcomas or
fibrosarcomas and malignant pheochromocytomas. For female rats, a dose-related trend was observed
in the incidence of fibrosarcomas and sarcomas in the spleen and in multiple organs of the body cavity.
No fibrosarcomas, or sarcomas of the spleen or multiple organs of the body cavity were observed in
pooled (249 female and 250 male) control animals. Tumor incidence data is listed in Table 1.
Table 1.
Aniline hydrochloride-induced tumor incidence data in male and female Fischer 344 rats
(NCI, 1978)
Tumor type Sex Tumor incidence
aniline hydrochloride dietary
concentration (mg/kg diet)
0 3000 6000
spleen hemangiosarcoma male 0/25 19/50 20/46
spleen fibrosarcoma/sarcoma NOS male 0/25 7/50 9/46
multiple organ fibrosarcoma/sarcoma NOS male 0/25 2/50 9/48
female 0/24 1/50 7/50
adrenal pheochromocytomas male 2/24 6/50 12/44
NOS = not otherwise specified
Hagiwara et al. (1980) administered aniline in the diet at a concentration of 300 mg/kg diet to 28 male
Wistar rats over a period of 80 weeks. An untreated control group of 28 rats was also included. No
significant increase in tumor incidences were observed as a result of aniline exposure. However, the
treatment group sizes used were relatively small, and the exposure was relatively low and less than
lifetime.
Male and female CD-F rats (130/sex/exposure group) were exposed to aniline hydrochloride in the diet
for 2 years at exposure levels of 0, 10, 30 and 100 mg/kg body weight/day (CIIT, 1982). An
increased incidence of primary splenic sarcomas was noted in the male 100 mg/kg exposure group (high
dose group); stromal hyperplasia and fibrosis of the splenic red pulp, a potential sarcoma precursor
lesion, was also observed in high dose males, and to a lesser degree, in high dose females. No
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