Placental Transfer and Pharmacokinetics of a Single Dermal Dose of [14C]Methyl Parathion in Rats

Abstract

The pharmacokinetics and placental transfer of a single dermal 10.0 mg (10microCi)/kg dose of uniformly phenyl-labeled [14C] methyl parathion (0,0-dimethyl 0-4-nitrophenyl phosphorothioate) were investigated in pregnant Sprague-Dawley rats at 14-18 days of gestation. Three rats were killed at each time 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 absorbed radioactivity was excreted in the urine (91%). Only 3% of the 14C was recovered in the feces. One h after the administration, radioactivity was detected in all tissues, including fetal tissue. The peak maternal plasma concentration of radioactivity (ng methyl parathion equivalent/ml) was 1005 at 2 h, compared to 318 ng for fetal plasma at 12 h. The maximum concentrations of radioactivity (ng methyl parathion equivalent/g), detected in most tissues within 12 h of dosing, were, in descending order: adipose tissue (67,532), kidney (1,571), spleen (1,256), spinal cord (1,004), 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 identified in plasma and tissues. The maximum concentration detected was in plasma, at 513 ng/ml, and in the following tissues (ng/g fresh tissue): kidney (819), fetus (668), placenta (394), liver (375), and brain (282). The metabolite 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 respectively, while p-nitrophenol was only detected in liver at a maximum concentration of 21 ng/g 72 h after dosing. Pharmacokinetic studies showed that methyl parathion disappeared monoexponentially from plasma and tissues. The half-life of elimination of methyl parathion from plasma was 11 h corresponding to a constant rate value of 0.06 h(-1). The results indicate that skin and placenta are poor barriers against methyl parathion permeability, resulting in a rapid and extensive dermal absorption of this insecticide and extensive placental transfer. This is indicated by the relative residence (R(R)) of methyl parathion in the plasma, which was largest in the placenta followed by the fetus. This study suggests that pregnant women and fetuses may be at risk of cholinergic toxicity following dermal exposure to methyl parathion.

Testing the vulnerability of the phylotypic stage: On modularity and evolutionary conservation

“…In rats the onset is slightly earlier than the start of neurulation on day 7. However, it has to be kept in mind that there is often a delay of several hours between the treatment and the time the teratogen reaches the embryo and that the teratogen can persist for up to 24 hr in the embryo (Shenefelt, 1972;Tagashira et al, 1981;Payan et al, 1995;Rogers and Mole, 1997;Kuno et al, 1999;Abu-Qare et al, 2000). Mortality is not limited to this sensitive window, but it is always by far the highest in this period.…”

Teratogenicity and Embryotoxicity of Organophosphorus Compounds in Animal Models - A Short Review

“…Abu-Qare et al [9,[14][15] conducted pharmacokinetic studies on the placental transfer of methyl parathion in rats and reported that the placenta is a poor barrier against methyl parathion. This results in a rapid and extensive placental transfer and the concentration was found to be the highest in the placenta followed by the concentration in rat fetuses.…”

“…Secondly, a transfer of compounds to fetuses through placenta [9,14] and a higher sensitivity of the young ones [86] also makes the topic critical.…”

“…Pesticides like OP have been detected in amniotic fluid, umbilicord blood, (Umbilical cord blood is blood that remains in the placenta and in the attached umbilical cord after childbirth. It is a reservoir of stem cells which can be used to treat hematopoietic and genetic disorders), meconium and infant urine, indicating exposure of the human fetus to pesticides [6][7][8][9].…”

Organophosphorous Pesticides Exacerbate the Demographic Consequences of Intersexual Selection in Fish

“…They can cause neurotoxic damage by AChE inhibition as shown in the mosquitofish (Gambusia affinis; Boone & Chambers, 1996), induce chromosome aberrations such as those observed in the green chromide (Etroplus suratensis), a cichlid fish from India and Sri Lanka (Das & John, 1999), and compromise growth and neural development in mammals (e.g. Abu-Qare et al, 2000). Citotoxic effects and damage to organs such as liver, intestine and gills have also been reported (Fanta et al, 2003), and can lead to reduced behavioural performance.…”