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Absorption, distribution, metabolism and excretion of daily oral doses of [ 14C]methyl parathion in hens
Ist Teil von
Toxicology letters, 2001-12, Vol.125 (1), p.1-10
Ort / Verlag
Shannon: Elsevier Ireland Ltd
Erscheinungsjahr
2001
Quelle
Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)
Beschreibungen/Notizen
Adult hens were given oral daily doses of 2 mg (2 μC
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 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.