The relationship between maternal and fetal effects following maternal organophosphate exposure during gestation in the rat.
Organophosphates, a widely used class of insecticidal compounds, have been shown to cross the placental barrier, and thus potentially affect the developing fetus. This study compared the maternal and fetal effects, including cholinesterase inhibition, following gestational exposure to six organophosphates: tribufos, oxydemeton-methyl, azinphos-methyl, fenamiphos, isofenphos, and fenthion in the Sprague-Dawley rat. All test compounds were administered via oral gavage on gestation days 6-15. Maternal cholinesterase activities (plasma, PChe; erythrocyte, RChe; and brain, BChe) were measured on gestation days 16 and 20, and fetal brain cholinesterase activity was measured on gestation day 20. Effects on gestational parameters (clinical signs, food consumption, and body weight) in adult rats, when observed, were only observed at the highest dose tested for each compound. The inhibition of maternal cholinesterase activities associated with these clinical findings was, for all compounds, always greater than 20%. Moreover, cholinesterase activities were inhibited at dose levels below that which elicited clinical effects. Statistically significant inhibition of at least two of the three cholinesterase enzymes (PChe, RChe, or BChe) was observed on gestation day 16, 24 h following exposure, with all of the organophosphates tested. By gestation day 20, the inhibition of cholinesterase activity was reduced; however, the high dose for all test compounds (except BChe in fenamiphos-treated dams) continued to demonstrate statistically significant inhibition of RChe and BChe. Despite significantly affected cholinesterase activity in the dams, no remarkable effects on fetal BChe were observed with any test compound. No embryotoxicity or teratogenicity were observed with any of the test compounds. These results demonstrate that for the six organophosphates tested: (1) inhibition of maternal cholinesterase activity was the most sensitive indicator of organophosphate exposure; (2) the level of cholinesterase inhibition associated with clinical findings was always greater than 20%; and (3) no effect on fetal cholinesterase activity (BChe) was observed, even at dose levels that continued to demonstrate significant inhibition of maternal cholinesterase activity.
Astroff
A B
AB
Bayer Corporation, Toxicology Department, Stilwell, Kansas, USA.
Young
A D
AD
D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002802:Cholinesterases / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D008297:Male; D010755:Organophosphates / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D010755:Organophosphates; D002802:Cholinesterases