Abstract

Alkylphenols are weak oestrogenic environmental contaminants and have been implicated in the disruption of endocrine function in wildlife. The influence of biotransformation, tissue distribution, and elimination on biological activity was investigated in juvenile rainbow trout following a single iv dose of [³H]4-nonylphenol. Distribution and elimination of [³H]4-nonylphenol residues in tissues sampled 1, 2, 4, 24, 48, 72, and 144 hr after dosing was determined by sample combustion and liquid scintillation counting (LSC). Total ³H-labeled residue concentrations in trout 144 hr after dosing were in order: bile ≫ faeces ≫ liver > pyloric caecae > kidney > brain, gill, gonad, heart, plasma, skeletal muscle, and skin. The depletion kinetics of [³H]residues from tissues and plasma was biphasic with prolonged β-phase half-lives in muscle and liver of 99 hr. Radio-HPLC analysis of metabolites in bile, liver, pyloric caecae, and faeces samples demonstrated similar profiles and contrasted with muscle where only parent compound was found. The predominant metabolite in bile was a glucuronide conjugate of 4-nonylphenol. Other metabolites included glucuronide conjugates of ring or side chain hydroxylated 4-nonylphenol. Liver contained a low level (1.7%) of covalently bound residues. Metabolism studies using isolated trout hepatocytes produced a similar range of metabolites and a sulfate conjugate of hydroxylated 4-nonylphenol. Despite rapid metabolism and excretion, a substantial depot of parent compound remained in muscle which will have implications for the maintenance of 4-nonylphenol residues and associated biological activity.