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

Adult hens were given oral daily doses of 2 mg (2 muC(i))/kg/day (14% of or al LD50 in male rats) of [C-14]methyl parathion (O,O-dimethyl O-4-nitrophen yl phosphorothioate) for 10 consecutive days. Five treated hens were sacrif iced 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. Maxim um radioactivity was detected in tissues within 8 h of dosing, (ng methyl p arathion 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 parat hion 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 fec al-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 conju gate, 23% as bound hot sulfric acid hydrolyzable residues, and 51% as water soluble metabolites. The presence of majority of radioactivity in the excr eta as conjugated metabolites indicates that determining only unbound p-nit rophenol as a biological marker for methyl parathion exposure underestimate s total fecal-urine excretion of p-nitrophenol. The slow elimination rate o f methyl parathion is significant, since hens are more comparable to humans with respect to their cytochrome P450 activities. (C) 2001 Elsevier Scienc e Ireland Ltd. All rights reserved.