Lack of differential sensitivity to cholinesterase inhibition in fetuses and neonates compared to dams treated perinatally with chlorpyrifos

Pregnant Sprague-Dawley rats were exposed to chlorpyrifos (CPF; O,O-diethyl -O-[3,5,6-trichloro-2-pyridinyl] phosphorothioate) by gavage (in corn oil) from gestation day (GD)6 to postnatal day (PND) 10. Dosages to the dams wer e 0 (control), 0.3 (low), 1.0 (middle) or 5.0 mg/kg/day (high). On GD 20 (4 h post gavage), the blood CPF concentration in fetuses was about one half the level found in their dams (high-dose fetuses 46 ng/g; high-dose dams 10 9 ng/g). CPF-oxon was detected only once; high-dose fetuses had a blood lev el of about 1 ng/g. Although no blood CPF could be detected (limit of quant itation 0.7 ng/g) in darns given 0.3 mg/kg/day, these dams had significant inhibition of plasma and red blood cell (RBC) ChE. In contrast, fetuses of dams given 1 mg/kg/day had a blood CPF level of about 1.1 ng/g, but had no inhibition of ChE of any tissue. Thus, based on blood CPF levels, fetuses h ad less cholinesterase (ChE) inhibition than dams. Inhibition of ChE occurr ed at all dosage levels in dams, but only at the high-dose level in pups. A t the high dosage, ChE inhibition was greater in dams than in pups, and the relative degree of inhibition was RBC approximate to plasma greater than o r equal to heart > brain (least inhibited). Milk CPF concentrations were up to 200 times those in blood, and pup exposure via milk from dams given 5 m g/kg/day was estimated to be 0.12 mg/kg/day. Therefore, the dosage to nursi ng pups was much reduced compared to the dams exposure. In spite of exposur e via milk, the ChE levels of all tissues of high-dosage pups rapidly retur ned to near control levels by PND 5.