ASSESSMENT OF OFFSPRING DEVELOPMENT AND BEHAVIOR FOLLOWING GESTATIONAL EXPOSURE TO INHALED METHANOL IN THE RAT

The prospect of widespread human exposure associated with its use as a n alternative fuel has sparked concern about the toxic potential of in haled methanol (MeOH). Previous studies have revealed congenital malfo rmations in rats following inhaled MeOH (Nelson et al. (1985). Fundam. Appl. Toxicol. 5, 727-736) but these studies did not include postnata l behavioral assessment. In the present study, pregnant Long-Evans rat s were placed in exposure chambers containing 15,000 ppm MeOH or air f or 7 hr/day on Gestational Days (GD) 7-19. The total alveolar dose of methanol was estimated at about 6.1 g/kg/day, for a total dose of abou t 42.7 g/kg for the entire study. Maternal body weights were recorded daily and blood methanol concentrations were determined at the end of exposure on GD 7, 10, 14, and 18. Following birth (Postnatal Day 0 [PN D 0]), a number of tests were performed at various points in developme nt, including: offspring mortality and body wt (PND 1, 3), motor activ ity (PND 13-21, 30, 60), olfactory learning (PND 18), behavioral therm oregulation (PND 20-21), T-maze learning (PND 23-24), acoustic startle response (PND 24, 60), reflex modification audiometry (PND 60), puber tal landmarks (PND 31-56), passive avoidance (PND 72), and visual-evok ed potentials (PND 160). Maternal blood MeOH levels, measured from sam ples taken within 15 min after removal from the exposure chamber, decl ined from about 3.8 mg/ml on the first day of exposure to 3.1 mg/ml on the 12th day of exposure. MeOH transiently reduced maternal body wt ( 4-7%) on GD 8-10, and offspring BW (5%) on PND 1. No other test reveal ed significant effects of MeOH. Prenatal exposure to high levels of in haled MeOH appears to have little effect on this broad battery of test s beyond PND 1 in the rat. (C) 1995 society of Toxicology