The metabolism of biphenyl. IV. Phenolic metabolites in the guinea pig and the rabbit.

The phenolic metabolites of biphenyl in guinea pigs and rabbits were qualitatively and quantitatively analysed as trimethylsilyl (TMS) ethers by combined gas chromatography/mass spectrometry and gas chromatography, respectively. The parent compound was hydroxylated to monohydroxylated biphenyls and minor amounts of dihydroxylated derivatives, and the main route of body clearance appeared to be by the urine in both species. Thus, in the urine of guinea pigs 32.9% of the dose was detected 96 hrs after dosing, while the major part (29.5%) was eliminated during the first day as conjugates. The main metabolite was 4-hydroxybiphenyl (25.5%). During the first 24 hrs faecal recovery was 20.3% of the dose, and most of this (14.3%) consisted of biphenyl itself. Biliary excretion of the metabolites of biphenyl origin amounted to 3.3% of the dose during the first day, and 4-hydroxybiphenyl was the major metabolite. In the urine of rabbits 49.1% of the dose was recovered 96 hrs after dosing, and most of this (25.4 and 15.9%, respectively) was eliminated during the first two days as conjugates. The major metabolite was 4-hydroxybiphenyl (35.3%). On the first day faecal recovery was 1.6%, of which 1.4% was detected as biphenyl itself. Less than 1% of the dose was found in the 7 hrs rabbit bile, and exclusively as 4-hydroxybiphenyl. The experiments thus show that both qualitative and quantitative differences in the metabolism of biphenyl exist between the guinea pig and the rabbit even though 4-hydroxybiphenyl was the most prominent metabolite of biphenyl in both species.