Biotransformation of butylated hydroxytoluene (BHT) to BHT-quinone methide in rats.

Abstract

2,6-Di-tert-butyl-4-methylene-2,5-cylohexadien-1-one (BHT-quinone methide, BHT-QM) was detected in the bile of rats given butylated hydroxytoluene (BHT). The biliary excretion of BHT-QM during 24 h after administration of BHT, 3,5-di-tert-butyl-4-hydroxybenzyl alcohol (BHT-alcohol) or 2,6-di-tert-butyl-4-hydroxy-4-methyl-2,5-cyclohexadien-1-one (4-hydroxy-BHT) was determined by high-performance liquid chromatography. BHT-alcohol gave .apprx. 7-fold as much BHT-QM as did BHT but no BHT-QM was detected after administration of 4-hydroxy-BHT. The transformation of BHT to BHT-QM proceeded mainly through BHT-alcohol. Although 1,2-bis(3,5-di-tert-butyl-4-hydroxyphenyl)ethane (BHT-dimer) was reported as a biliary metabolite of BHT in rats, most of the BHT-dimer was formed artificially by dimerization of BHT-QM during the isolation process.