PERINATAL METHANOL EXPOSURE IN THE RAT .1. BLOOD METHANOL CONCENTRATION AND NEURAL CELL-ADHESION MOLECULES

Although the acute toxicity of methanol is well documented, few studie s have addressed the consequences of perinatal exposures to the low co ncentrations that are expected to arise from its proposed use as a com ponent of automobile fuel. This report describes the general research design of a series of studies, the effects of methanol exposures on bl ood concentrations in dams and neonates, and indices of brain developm ent, Four cohorts of Long-Evans pregnant rats, each cohort consisting of an exposure (n = 12) and a control (n = 12) group, were exposed who le-body to 4500 ppm methanol vapor or air for 6 hr daily beginning on Gestation Day 6. Both dams and pups were then exposed through Postnata l Day 21 (PND 21). Blood methanol concentrations determined by gas chr omatography from samples obtained immediately following a 6-hr exposur e reached approximately 500-800 mu g/ml in the dams during gestation a nd lactation, Average concentrations for pups attained levels about tw ice those of the darns. Selected offspring from Cohort 4 were exposed for one additional 6-hr session at ages that extended out to PND 52. R egression analyses showed that the blood methanol concentrations of th e pups declined until about PND 48, at which time their levels approxi mated those of their darns. Such pharmacokinetic differences might inc rease the risks posed to developing organisms. Light-microscopic analy sis showed no significant abnormalities in the brains of the methanol- treated animals, However, assays of neural cell adhesion molecules (NC AMs) in brains of pups sacrificed on PND 4 showed staining for both th e 140 and the 180 kDa isoforms to be less intense in the cerebellum of exposed animals. NCAM differences were not apparent in animals sacrif iced 15 months after their final exposure. (C) 1996 Society of Toxicol ogy.