The toxicological implications of the interaction of butylated hydroxytoluene with other antioxidants and phenolic chemicals

Butylated hydroxyanisole (BHA) enhanced both the in vitro peroxidase-catalysed covalent binding of butylated hydroxytoluene (BHT) to microsomal protein and the formation of BHT-quinone methide. Eugenol, methylparaben, vanillin, guaiacol, ferulic acid and several other phenolic compounds commonly used in food and cosmetic products also enhanced the metabolic activation of BHT. BHA was the most effective compound tested. Microsomes from lung, bladder, kidney medualla and small intestine of various animal species, including man, were also able to support this interaction of BHA and BHT using either hydrogen peroxide or arachidonic acid as the substrate. These in vitro observations were extended to an in vivo mouse lung model. Subcutaneous injections of BHA significantly enhanced the lung/body weight ratio of mice given intraperitoneal injections of subthreshold doses of BHT. The toxicological implications of the interactions of BHT with other antioxidants and phenolic chemicals and their potential relevance to human risk are discussed.