The metabolism of 3:5-di-tert.-butyl-4-hydroxytoluene and 3:5-di-tert.-butyl-4-hydroxybenzoic acid in the rabbit

Abstract

The metabolism of the antioxidant 3,5-di-tert.-butyl-4-hydro-xytoluene (BHT) and its oxidation product, 3,5-di-tert.-butyl-4-hydro-xybenzoic acid, has been studied in the rabbit. Rabbits excreted BHT mainly as glucuronides, some 16.0% as an ester glucuronide and 19.4% as an ether glucuronide. Unconjugated phenol (8.4%), ethereal sulphate (8.0%) and a glycine conjugate (1.8%) were also excreted. The distribution and recovery of metabolites when 4 and 5 daily doses were given was not significantly different from that of single doses of BHT. After 3 consecutive daily doses of 3,5-di-tert.-butyl-4-hydroxybenzoic acid, a rabbit excreted 84.0% of the total doses as ester glucuronide, 8.8% as a glycine conjugate and 5.2% was not conjugated. The ester glucoronide, isolated from the urine after both BHT and the acid as the triacetyl methyl ester, is 3,5-di-tert.-butyl-4-hydrobenzoyl-[beta]-D-glucosiduronic acid. The ether glucuronide, isolated from BHT urine as the triacetyl methyl ester, is[beta]-(3-tert.-butyl-2-hydroxy-5-methylphenyl) - [beta][beta] -di-methylethyl [beta]-D-glucosiduroni acid. The glycine conjugate of both BHT and the acid is 3,5-di-tert^-butyl-4-hydroxyhippuric acid.