The metabolism of 3,5-di-tert.-butyl-4-hydroxytoluene in the rat and in man

Abstract

1. The major metabolites of 3,5-di-tert.-butyl-4-hydroxytoluene (BHT) in the rat are 3,5-di-tert.-butyl-4-hydroxybenzoic acid (BHT-acid), both free (9% of the dose) and as a glucuronide (15%), and S-(3,5-di-tert.-butyl-4-hydroxybenzyl)-N-acetylcysteine. 2. The mercapturic acid does not appear to derive from the usually accepted enzyme mechanism, and may involve a non-enzymic reaction between BHT free radical and cysteine. 3. The ester glucuronide and mercapturic acid found in rat urine are also the major metabolites in rat bile and must be responsible for the enterohepatic circulation. 4. Free BHT-acid is the main component in rat faeces. 5. In man, BHT-acid, free and conjugated, is a minor component in urine, and the mercapturic acid is virtually absent. The bulk of the radioactivity is excreted as the ether-insoluble glucuronide of a metabolite in which the ring methyl group and one tert.-butyl methyl group are oxidized to carboxyl groups, and a methyl group on the other tert.-butyl group is also oxidized, probably to an aldehyde group. 6. These differences in metabolism by the rat and by man are sufficient to account for the difference in excretion by the two species.

Distribution, metabolism, and excretion of musk xylene in rats

“…Methyl groups at the 1 and 3 positions are sandwiched between two nitro groups. As for the tert-butyl group, there are some reports on the metabolism of tert-butyl groups of butylated hydroxyanisole (BHA) (Astill et al 1960(Astill et al , 1962Akagi et al 1962;Aoki 1962;Daniel et al 1968). Hydroxylation at the tert-butyl group of BHA was not detectable in the rat, dog (Astill et al 1960(Astill et al , 1962 and rabbit (Dacre et al 1956).…”

The Role of Glutathione and Glutathione S‐Transferases in Mercapturic Acid Biosynthesis

“…These compounds are also metabolites of methyl methanesulfonate (Barnsley, 1968). E. 3,5-DI-TERT-BUTYL-4-HYDROXYTOLUENE Using spectral and chromatographic techniques, Daniel et al (1968) showed that a major metabolite of the food antioxidant 3,5-di-tert-butyl-4-hydroxytoluene (BHT) in the rat was the mercapturic acid (51). Only a trace of this metabolite was present in human urine.…”

Drug Metabolism by Intestinal Microorganisms

“…A similar picture is shown by griseofulvin which is extensively excreted in the bile as a conjugate of 4-demethylgriseofulvin (54). A major biliary metabolite of butylated hydroxytoluene (3,5-di-tert-butyl-4-hydroxytoluene) in the rat is the ester glucuronide of 3,5-di-tertbutyl-4-hydroxybenzoic acid which is believed to be partly responsible for the enterohepatic circulation seen in this species (55). However, the free acid is the main fecal metabolite and it seems likely that intestinal hydrolysis occurs prior to its absorption.…”