Splenotoxicity Associated With Splenic Sarcomas in Rats Fed High Doses of D & C Red No. 9 or Aniline Hydrochloride23

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Abstract
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 HCl (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 HCl. 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≥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.