title: Metabolism and excretion of piperonyl butoxide in the rat.
abstract: [14C]-piperonyl butoxide (PBO) was administered to male and female rats by gavage at a dose rate of 50 or 500 mg kg-1 body weight. In all cases, the radioactivity was rapidly excreted with 87-99% being found in the 0-48-h excreta and the majority of the dose (64.1-85.0%) being eliminated in faeces. The metabolism of PBO was complex with over 25 peaks of radioactivity being seen by radio-high-performance liquid chromatography (HPLC). Using HPLC/tandem mass spectrometry (MS/MS) and nuclear magnetic resonance (NMR), 12 urine metabolites were assigned structures together with four plus PBO in faeces. Metabolism occurred at two sites: the methylenedioxy ring, which opened to form a catechol that could then undergo methylation, and the 2-(2-butoxyethoxy)ethoxymethyl side-chain, which underwent sequential oxidation to a series of alcohols and acids. The identified metabolites accounted for approximately 60% of the administered dose.
authors.affiliation: AgrEvo UK Ltd, Chesterford Park, Saffron Walden, UK. david.needham@covance.com
authors.forename: J
authors.initials: J
authors.lastname: Byard
authors.forename: D
authors.initials: D
authors.lastname: Needham
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D005260:Female; D008297:Male; D008954:Models, Biological; D010574:Pesticide Synergists / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D010882:Piperonyl Butoxide / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D015262:Xenobiotics / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D010574:Pesticide Synergists; D015262:Xenobiotics; D010882:Piperonyl Butoxide