Transfer of leptophos in hen eggs and tissues of embryonic rats.
To estimate the delayed neurotoxic effect of OPs on the next generation, we tried two examinations; one was on the distribution of leptophos in tissues and eggs of hens which are highly susceptible to the delayed neurotoxic effect of OPs but have no placenta, and the other was on the concentration of OPs in tissues of both pregnant and embryonic rats which are not susceptible to the delayed neurotoxic effect but have placenta, after leptophos was administered to the mother in both experiments. First, organophosphorus compound-induced delayed neurotoxicity (OPIDN) was checked in 4 hens and the concentration of leptophos was determined in the other 16 hens after 20 adult laying hens were given 30 mg/kg leptophos (iv), a neurotoxic organophosphate. Three out of 4 hens treated with leptophos showed OPIDN. The concentration of leptophos decreased sharply in the blood, liver, brain and spinal cord from 24 to 48 hr after leptophos administration, but clearance of leptophos was relatively slow in the ovary. Leptophos in laid egg yolk was detected every day for 10 days, and the highest concentration of leptophos in egg yolk was observed on the 6th day after administration to hens. Secondly, in order to investigate the transfer of leptophos to the embryo through the placenta, we divided the thirty-two pregnant rats into 2 groups. The first group received 10 mg/kg leptophos intraperitoneally on the 17th day of pregnancy and the second received 20 mg/kg leptophos on the same day. The time-course of leptophos concentration in the tissues of pregnant and embryonic rats was checked, and the correlation between findings in the pregnant rats and the embryos was determined. The time-course of leptophos concentration in the blood, liver, brain and placenta of the rats was similar to that in hens. Leptophos concentration in the liver and brain of the embryos was equal to approximately 60% of leptophos concentration in each tissue of the pregnant rats, and the concentration of leptophos in the liver and brain of embryonic rats correlated with that in the blood and placenta of pregnant rats (p < 0.01). In both groups treated with 10 and 20 mg/kg leptophos, the concentrations of leptophos in the liver and brain of embryos were lower than that of pregnant rats in the early period after dosing, but the concentrations in embryos were inversely higher than those in pregnant rats in the latter period (48 hr). Compared with the biological half-lives of leptophos in the liver and brain of pregnant rats, these parameters in embryonic rats were 1.58 and 1.87 times, respectively. These results indicate that some of the fat-soluble organophosphorus compounds readily pass through the blood-placenta barrier into the embryos and accumulate there. Therefore, the neurobehavioral development of F1 rats exposed to some organophosphorus compounds through the placenta of pregnant rats should be further examined.
Piao
F Y
FY
Department of Public Health, School of Medicine, Mie University, Japan.
Xie
X K
XK
Kitabatake
M
M
Yamauchi
T
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D002642:Chick Embryo / Q000187:drug effects / Q000378:metabolism; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D004530:Egg Yolk / Q000737:chemistry / Q000187:drug effects; D005260:Female; D006207:Half-Life; D007274:Injections, Intraperitoneal; D007306:Insecticides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D010773:Leptophos / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D008297:Male; D009498:Neurotoxins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D010053:Ovary / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D014018:Tissue Distribution
D007306:Insecticides; D009498:Neurotoxins; D010773:Leptophos