title: Biliary elimination of oral 2,4-dichlorophenoxyacetic acid and its metabolites in male and female Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters.
abstract: The role of biliary elimination in the metabolic disposition of 2,4-D was evaluated in male and female Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters. Following cannulation of the bile duct, an intragastric (ig) dose of 2,4-D (200 mg/kg) was administered and bile was collected at 30- or 60-min intervals for up to 6 h. Bile flow rates were constant in rats, increased in mice, and decreased in hamsters throughout the collection periods. Total recovery of radioactivity was greatest in male mice (about 7% of administered dose over 4 h). Female mice and rats of both sexes excreted about 3% over the same interval and male and female hamsters about 1%. About 71-88% of the activity in bile was parent compound. The glycine conjugate of 2,4-D was found in bile from mice, rats, and hamsters and the taurine conjugate in bile from mice. The only sex-dependent difference in the metabolite profile was in mice. Male mice excreted twice as much glycine conjugate as female mice. An additional minor metabolite (4-7%) was present in rat and mouse bile. This was tentatively identified as 2,4-D-glucuronide based on its hydrolysis by beta-glucuronidase. One more very minor metabolite (3%) was detected in rat bile but was not characterized due to its lability. The results of this study indicate that there are species-dependent differences in the biliary elimination of 2,4-D but not sex-dependent differences.
authors.affiliation: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Griffin
authors.forename: J
authors.initials: J
authors.lastname: Salemme
authors.forename: J
authors.initials: J
authors.lastname: Clark
authors.forename: P
authors.initials: P
authors.lastname: Myers
authors.forename: L T
authors.initials: LT
authors.lastname: Burka
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000008:administration & dosage / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D005260:Female; D006540:Herbicides / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013045:Species Specificity
chemical_list: D006540:Herbicides; D015084:2,4-Dichlorophenoxyacetic Acid