SPECIES-DIFFERENCES IN THE METABOLISM OF 3-PHENOXYBENZOIC ACID

  • 1 January 1981
    • journal article
    • research article
    • Vol. 9  (4) , 352-359
Abstract
[3-Phenoxybenzoic acid is the major metabolite of pyrethoid insecticides.] The metabolism of 3PBA (10 mg/kg, i.p.) was studied in 10 mammalian and 1 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 3 spp. (sheep, cat and gerbil); in the mouse the taurine conjugate is the principal metabolite. The ferret eliminates similar amounts of each of the metabolites; the glycylvaline dipeptide conjugate is the major metabolite isolated from the excreta of the mallard duck. 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 (i.p. and p.o. [per os]) 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 (< 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.