In six carcinogenicity bioassays, male and female F344 rats were fed diets containing
aniline hydrochloride (CAS: 142-04-1; hydrochloride benzenamide),
p-chloroaniline (CAS: 106-47-8),
azobenzene (CAS: 103-33-3),
o-toluidine hydrochloride (CAS: 636-21-5),
dapsone (CAS: 80-08-0; 4,4'-
sulfonyldianiline), or
D & C red No. 9 [CAS: D85500000; 5-chloro-2-[2-hydroxy-1-naphthalenyl)azo)-4-methylbenzenesulfon ic
acid,
barium salt]. The rats, from 6 weeks to 2 years old, were given the compounds at two dose levels, the estimated maximum tolerated dose and one-half that dose. In all six bioassays, dose-dependent incidences of splenic
sarcomas and
fibrosis were seen, with the highest incidences in male rats.
Fibrosis occurred in the splenic parenchyma and/or the
capsule. Fatty infiltration also was seen in the spleen.
Sarcomas appeared to arise in the splenic red pulp or splenic
capsule, usually in association with areas of parenchymal and capsular
fibrosis and pigmentation. Larger
tumors metastasized to the peritoneal cavity and abdominal organs. In some rats there was marked osseous
metaplasia when the primary
tumor metastasized to peritoneal surfaces. Other, less common,
splenic neoplasms included
hemangiosarcoma and
hemangiopericytoma. Some rats had such extensive peritoneal involvement that the site of origin of their
sarcoma was difficult to determine.