Butylated hydroxyanisole mechanistic data and risk assessment: conditional species-specific cytotoxicity, enhanced cell proliferation, and tumor promotion.

Butylated hydroxyanisole (BHA), at high doses, has been found to induce forestomach squamous cell carcinomas in rodents, but not glandular cell or other types of neoplasms. BHA is not DNA-reactive, and the epigenetic mechanism of tumor formation involves cytotoxicity and enhanced cell proliferation, which are mostly reversible. Humans lack a forestomach and, therefore, are predicted to be much less sensitive than rodents to the effects of BHA. Also, the exposures to humans are well below doses producing the epigenetic effects in rodents. It has been concluded that BHA is an agent whose rodent carcinogenicity is conditionally species-specific and not relevant to humans.