Urinary excretion of metabolites following a single dermal dose of [14C]methyl parathion in pregnant rats.
The identification and kinetics of urinary excretion of metabolites of uniformly phenyl-labeled O,O-dimethyl O-4-nitrophenyl phosphorothioate ([14C]methyl parathion) were carried out following a single dermal dose of 10.0 mg (10 microCi)/kg in pregnant Sprague-Dawley rats at 14-18 days of gestation. Urine was collected at each time interval of 1, 2, 4, 12, 24, 48, 72, and 96 h after dosing. Total p-nitrophenol in the conjugated and non-conjugated metabolites was measured as a marker of methyl parathion exposure. Elimination of radioactivity in the urine was rapid. Of the total 14C urinary excretion, 30% of the dose was excreted within 4 h, while 50 and 90% of the dose were recovered in the urine by 24 and 96 h, respectively. Excretion rate of total radioactivity was 60 microgram methyl parathion equivalent/h (1.4 mg/day). By the end of the 96-h experiment, conjugated and non-conjugated metabolites accounted for 78.1 and 21.9%, respectively. Of the non-conjugated metabolites, p-nitrophenol and O,O-dimethyl O-4-nitrophenyl phosphate (methyl paraoxon) were identified by high performance liquid chromatography (HPLC) that accounted for 20%, and 1.9% of total urinary excretion, respectively. Appearance and disappearance rate constants of p-nitrophenol in urine were 0.12 and 0.048 microgram/h, respectively. Conjugated metabolites were classified as: glucuronides 12% of urinary excretion, sulfates 3%, hot sulfuric acid hydrolysable residues 47% and 16.1% remained as unidentified water soluble metabolites. Direct hot acid hydrolysis of urine yielded 49% of extractable 14C-radioactivity compared to 62% when hot acid hydrolysis followed the enzymatic hydrolysis. The presence of the conjugated metabolites as the major class of metabolites of the total excretion indicates that determining only unbound p-nitrophenol as a biological marker for methyl parathion exposure underestimates total urinary excretion of p-nitrophenol. Sequential enzymatic and acid hydrolyses of urine prior solvent extraction are necessary for complete recovery of p-nitrophenol. The results indicate that the present method would show that the pregnant field worker or a housewife being at a greater risk than previously thought.
Abu-Qare
A W
AW
Department of Pharmacology and Cancer Biology, Duke University Medical Center, PO Box 3813, 27710, Durham, NC, USA.
Abou-Donia
M B
MB
D000279:Administration, Cutaneous; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007306:Insecticides / Q000378:metabolism*; D008743:Methyl Parathion / Q000008:administration & dosage / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007306:Insecticides; D008743:Methyl Parathion