Toxicity to Chinese hamster ovary (CHO) cells of the products of reaction of butylated hydroxyanisole with nitrite at low pH.

ABSTRACT

Butylated hydroxyanisole (BHA) was found to react readily with nitrite in acidified physiological saline. With low concentrations of reactants at pH 2, HPLC analysis demonstrated the formation of two products, tert-butylquinone (BQ) and a second, unidentified compound. Neutralized BHA/nitrite reaction mixtures were highly toxic to cultured Chinese hamster ovary (CHO) cells. At non-lethal concentrations, causing some cell cycle delay, there was a statistically significant but variable induction of endoreduplication and tetraploidy and a very weak induction of chromosome breakage. The effects were similar to those of pure BQ. It is suggested that the formation of toxic products from BHA, by an oxidative reaction such as that described with nitrite, might be involved in the mechanism of BHA carcinogenesis in the rat forestomach.