title: Absorption, distribution, metabolism and excretion of daily oral doses of [14C]methyl parathion in hens.
abstract: Adult hens were given oral daily doses of 2 mg (2 microC(i))/kg/day (14% of oral LD(50) in male rats) of [14C]methyl parathion (O,O-dimethyl O-4-nitrophenyl phosphorothioate) for 10 consecutive days. Five treated hens were sacrificed at 1, 2, 4, 8, 12, 24, and 48 h after the last dose. Methyl parathion was absorbed from the gastrointestinal tract and distributed rapidly. Maximum radioactivity was detected in tissues within 8 h of dosing, (ng methyl parathion equivalent/g fresh tissue or ml plasma): Plasma (189.2), liver (94.7), kidney (146.2), brain (61.4), gastrointestinal tissues (106.7). Methyl parathion was detected in the plasma, kidney and liver, while methyl parathion metabolite p-nitrophenol was detected in the liver and in the kidney. Elimination of methyl parathion from plasma was monophasic with a terminal half-life of 17.5 h, corresponding to an elimination rate constant of 0.039 ng/hr. Most of the absorbed radioactivity was excreted in the combined fecal-urine excreta (98%). Analysis of the metabolites in the excreta revealed that non-conjugated metabolites accounted for 13% of the total excretion. Conjugated metabolites accounted for 87% of the total excretion; of that, 6% as p-nitrophenyl-glucoronide conjugate, 7% as p-nitrophenyl-sulfate conjugate, 23% as bound hot sulfuric acid hydrolyzable residues, and 51% as water soluble metabolites. The presence of majority of radioactivity in the excreta as conjugated metabolites indicates that determining only unbound p-nitrophenol as a biological marker for methyl parathion exposure underestimates total fecal-urine excretion of p-nitrophenol. The slow elimination rate of methyl parathion is significant, since hens are more comparable to humans with respect to their cytochrome P450 activities.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Abu-Qare
authors.forename: A A
authors.initials: AA
authors.lastname: Abdel-Rahman
authors.forename: H
authors.initials: H
authors.lastname: Ahmad
authors.forename: A M
authors.initials: AM
authors.lastname: Kishk
authors.forename: M B
authors.initials: MB
authors.lastname: Abou-Donia
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D002645:Chickens; D005260:Female; D007306:Insecticides / Q000493:pharmacokinetics*; D008743:Methyl Parathion / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D007306:Insecticides; D008743:Methyl Parathion