A histopathologic review of F344 rat spleens from the National Toxicology Program-National Cancer Institute bioassays of
barium salt of 5-chloro-2-(2-hydroxy-1-naphthalenyl)-azo-4-methylbenzenesulfonic
acid [(
D & C Red No. 9) CAS: 516-00-21] and
aniline HCI (CAS: 142-04-1) was conducted to assess splenotoxic changes associated with splenic
sarcomas induced by these aromatic
amines. Four splenic changes--fatty metamorphosis (FM), splenic
fibrosis (FIB),
capsule hyperplasia (CH), and
hemorrhage--were markedly increased in incidence and severity in males treated with high doses of either
D & C Red No. 9 or
aniline HCI. Females treated with high doses of either of these compounds showed similar but less severe changes. FIB and FM showed strong group correlations with
tumor incidence (r greater than or equal to 0.87). All groups that demonstrated FM also demonstrated splenic
sarcomas; groups without the FM lesions did not exhibit splenic
tumors. The morphologic similarity of the FIB and CH lesions to the induced splenic
sarcomas suggests that these lesions are preneoplastic. Moreover, the treatment-related splenic lesions appear to be precursors of the induced splenic
sarcomas. Carcinogenicity studies with serial sacrifices at varying intervals will be required for experimental verification of these conclusions. A schema, based on the findings of the study, suggests a hypothetical pathway for the progression of the treatment-related splenic lesions from onset to
tumor formation.