Abstract

The metabolism of 3-phenoxybenzoic acid (3PBA) (10 mg/kg, ip) has been studied in ten mammalian and one avian species in comparison with that of benzoic acid. 3PBA exhibits wide species diversity in its metabolism, unlike benzoic acid, of which benzoylglycine (hippuric acid) is the major urinary metabolite in all species studied. With 3PBA, glycine conjugation is the major route of metabolism in three species (sheep, cat, and gerbil), whereas in the mouse the taurine conjugate is the principal metabolite. The ferret eliminates similar amounts of each of these metabolites, whereas the glycylvaline dipeptide conjugate is the major metabolite isolated from the excreta of the mallard duck. Conversely, glucuronic acid conjugates of 3PBA and its 4'-hydroxy derivative (4'HO3PBA) are the major urinary metabolites in the marmoset, rabbit, guinea pig, and hamster; the rat appears unique in eliminating the O-sulfate conjugate of 4'HO3PBA as the principal urinary metabolite. In most cases, where amino acid conjugates are the major excretory products, the proportions of hydroxylated metabolites present are minimal. The pattern of metabolism of 3PBA does not significantly vary with dose (0.1-100 mg/kg) or route (ip and po) in the sheep, gerbil, or mouse. When administered 4'HO3PBA, the gerbil and mouse eliminate principally glucuronide and sulfate conjugates rather than amino acid conjugates, which are only minor components (less than 10% of the dose) in each case. This implies that hydroxylation is a primary metabolic event in determining the eventual fate of 3PBA in many species.