The metabolism of butylated hydroxytoluene and its related phenols

Abstract

Butylated hydroxytoluene (BHT) can cause hemorrhagic death in the rat. Although the quinone methide of BHT may take part in this hemorrhagic effect, 2,4,6-tri-t-butylphenol, which is structurally related to BHT and has stronger hemorrhagic effect than BHT, cannot be converted to the corresponding quinone methide by biological oxidation. If the hemorrhagic effects of these two chemicals involve the same mechanism, a common active metabolite other than the quinone methide must be involved. Single oral doses of 2,4,6-tri-t-butylphenol (260 mg/kg) were well absorbed. Peak plasma levels of this compound were reached in 15-60 min. The plasma elimination half lives were 18.2 min in the rapid α phase and 11.8 hours in the slower β phase. This compound and its metabolites could not be excreted in the urine. Only a metabolite, but not the parent compound, was detected in the feces. This metabolite was considered to be the 2,4,6-tri-t-butylphenoxy radical (m/z=261). This radical was also detected in the bile of rats after oral administration of a parent phenol. 4-T-butyl-2,6-diisopropylphenoxy radical was also detected in feces after dosing of a parent phenol. The toxicological implication of the metabolism of this compound and BHT was discussed.