Neurobehavioral consequences of intermittent prenatal exposure to high concentrations of toluene

The effects of several concentrations of toluene on physical and behavioral development were examined in CD-1 mice prenatally exposed during the last week of gestation. Pregnant mice were exposed to either 200, 400, or 2000 ppm toluene (TOL) for 60 min three times a day during gestational days 12-17. A sham group was exposed concurrently to filtered air. No group differences were observed in maternal weight gain or food consumption, common measures of maternal toxicity. Initial litter characteristics including gestation length, number of litters delivered, and litter size were also similar. At birth, mean initial individual pup weight from representative male and female 2000 TOL-exposed pups was less than sham-exposed pups; however, entire litter weight did not differ. Pups were evaluated on postnatal days 1-20. Pups exposed to 2000 TOL gained less weight and performed more poorly on the behavioral tests of the righting reflex, grip strength, and inverted screen. In contrast, pups exposed to either 200 or 400 TOL did not differ from sham-exposed pups on any of the measures of development or behavior. These data provide evidence for the neurobehavioral teratogenicity of prenatal exposure to high levels of toluene late in gestation. Because this exposure regimen of intermittent high-concentration exposure was designed to simulate human exposures that might occur with toluene abuse, these results are consistent with case reports of adverse consequences of inhalant abuse by pregnant women.