The Metabolism of Biphenyl. IV. Phenolic Metabolites in the Guinea Pig and the Rabbit

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Abstract
The phenolic metabolites of biphenyl in guinea pigs and rabbits were qualitatively and quantitatively analyzed 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. In the urine of guinea pigs, 32.9% of the dose was detected 96 h after dosing, while the major part (29.5%) was eliminated during the 1st day as conjugates. The main metabolite was 4-hydroxybiphenyl (25.5%). During the 1st 24 h fecal 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 1st day, and 4-hydroxybiphenyl was the major metabolite. In the urine of rabbits 49.1% of the dose was recovered 96 h after dosing, and most of this (25.4 and 15.9%, respectively) was eliminated during the 1st 2 days as conjugates. The major metabolite was 4-hydroxybiphenyl (35.3%). On the 1st day fecal recovery was 1.6%, of which 1.4% was detected as biphenyl itself. Less than 1% of the dose was found in the 7 h rabbit bile, and exclusively as 4-hydroxybiphenyl. The experiments show that 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.