Nitrobenzene Carcinogenicity (1998)
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Nitrobenzene (NB, CAS No. 98-95-3) oxidizes to p-aminophenol and p-nitrophenol in animals and humans, while being reduced also to nitrosobenzene, phenylhydroxylamine, and aniline. The reductants are known to cause methemoglobinemia and anemia. NB is negative for mutagenicity systems in Salmonella, hepatocyte repair, or sister chromatid exchange assays.
No human studies cancer data are available, therefore this analysis is based on a Chemical Industry Institute of Toxicology (CIIT) NB inhalation study. The study involves both sexes of B6C3F1 mice (0, 5, 25, 50 ppm NB) and F344/N rats (0, 1, 5, 25 ppm NB), but only male Sprague-Dawley (CD strain) rats (0, 1, 5, 25 ppm NB). All are exposed at 6 hrs/day, 5 days/wk, for 104 wks. Mouse results show increased benign male tumors in the alveolus, bronchus, and thyroid, whereas female mice indicated mammary cancers. F344/N rats responded with male liver cancer and benign responses in the follicular thyroid and kidney, whereas females had benign endometrial polyps. Male CD rats has benign hepatocellular adenomas. Because NB causes tumorigenicity at 8 sites, 6 organs, both sexes, among 3 test species, NB is classified as a B2 carcinogen or a likely human carcinogen by any route by the proposed EPA Cancer Guidelines (U.S.EPA, 1986).