Absorption, distribution, metabolism and excretion of daily oral doses of [14C]methyl parathion in hens

Adult hens were given oral daily doses of 2 mg (2 muC(i))/kg/day (14% of oral LD50 in male rats) of [C-14]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 sulfric 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. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.