Placental transfer and pharmacokinetics of a single dermal dose of [C-14]methyl parathion in rats

The pharmacokinetics and placental transfer of a single dermal 10.0 mg (10 mu Ci)/kg dose of uniformly phenyl-labeled [C-14] methyl parathion (0,0-dim ethyl 0-4-nitrophenyl phosphorothioate) were investigated in pregnant Sprag ue-Dawley rats at 14-18 days of gestation. Three rats were killed at each t ime interval: 1, 2, 4, 12, 24, 48, 72, and 96 h after dosing. Radioactivity disappeared biexponentially from the administration sites, which retained 50% and 3% of the dose after 1 h and 96 h, respectively. Most of the absorb ed radioactivity was excreted in the urine (91%). Only 3% of the C-14 was r ecovered in the feces. One h after the administration, radioactivity was de tected in all tissues, including fetal tissue. The peak maternal plasma con centration of radioactivity (ng methyl parathion equivalent/ml) was 1005 at 2 h, compared to 318 ng for fetal plasma at 12 h. The maximum concentratio ns of radioactivity (ng methyl parathion equivalent/g), detected in most ti ssues within 12 h of dosing, were, in descending order: adipose tissue (67, 532), kidney (1571), spleen (1256), spinal cord (1004), heart (729), liver (706), brain (546), placenta (389), and fetus (256). The metabolism studies showed that methyl parathion, detected by HPLC, was the major compound ide ntified in plasma and tissues. The maximum concentration detected was in pl asma, at 513 ng/ml, and in the following tissues (ng/g fresh tissue): kidne y (819), fetus (668), placenta (394), liver (375), and brain (282). The met abolite methyl paraoxon was detected in maternal brain and liver at maximum concentrations (ng/g fresh tissue) of 135 and 64 after 12 h and 4 h respec tively, while p-nitrophenol was only detected in liver at a maximum concent ration of 21 ng/g 72 h after dosing. Pharmacokinetic studies showed that me thyl parathion disappeared monoexponentially from plasma and tissues. The h alf-life of elimination of methyl parathion from plasma was 11 h correspond ing to a constant rate value of 0.06 h(-1). The results indicate that skin and placenta are poor barriers against methyl parathion permeability, resul ting in a rapid and extensive dermal absorption of this insecticide and ext ensive placental transfer. This is indicated by the relative residence (R-R ) of methyl parathion in the plasma, which was largest in the placenta foll owed by the fetus. This study suggests that pregnant women and fetuses may be at risk of cholinergic toxicity following dermal exposure to methyl para thion.