The influence of dose on the pattern of conjugation of phenol and 1-naphthol in non-human primates.

Abstract

1. The pattern of conjugation of phenol and 1-naphthol was investigated in several primates; three Old World species (rhesus, cynomolgus, patas monkeys), two New World species (capuchin, tamarin), and two prosimians (bushbaby, tree shrew). 2. Following intra-muscular phenol or 1-naphthol (10 mg/kg), sulphation was the major conjugation in the Old World monkeys and prosimians, whereas glucuronidation predominated in the New World species. 3. In rhesus and cynomolgus monkeys, sulphation decreased as dose increased, but remained the major conjugation with both substrates at dose levels of 0.01 to 25 mg/kg. 4. In the capuchin, the conjugation pattern of phenol changed markedly as dose increased; at 0.01 and 1 mg/kg sulphation was the major conjugation, whereas at 10 and 25 mg/kg glucuronidation predominated. With 1-naphthol only small amounts of sulphate were excreted; glucuronic acid conjugation was the major metabolism at all four dose levels. 5. The importance of considering both substrate and dose when making inter-species comparisons, particularly with man, is discussed.