Biotransformation of the xenoestrogen 4-tert-octylphenol in hepatocytes of rainbow trout (Oncorhynchus mykiss).
1. The biotransformation of a 4-tert-alkylphenol in rainbow trout (Oncorhynchus mykiss) liver was studied to determine the possible fate and activity of these xenoestrogens in fish. 2. Primary trout hepatocytes were incubated with 30 microM 4-(1',1',3',3'-tetramethyl-butyl)[U-14C]phenol (4-tert-octylphenol; 4-t-OP) for up to 3 h. Radiolabelled metabolites were detected by radio-HPLC and the structures were determined by GC-MS analysis of the conjugated or aglycone products. 3. During the first 15 min, 4-t-OP was metabolized at 1.06 pmol x min(-1) x 10(-6) cells. The amount of parent compound metabolized was maximum after a 1-h incubation, when 86% of 4-t-OP was transformed to five other products. 4. The major metabolite comprised 61% of the total recovered radioactivity and was identified as 4-t-OP-beta-glucuronide. 5. The remaining metabolites were formed from the hydroxylation of 4-t-OP on either the C2 (omega-3) or C4 (omega) positions of the alkyl chain, or ortho on the aromatic ring to form a catechol. These oxidized products were also metabolized to glucuronide derivatives conjugated on the phenol ring. 6. The results suggest that oestrogenic alkylphenols could be rapidly transformed in fish liver by both phase I and II metabolic pathways to a number of conjugated products which are unlikely to be active at the oestrogen receptor.