Toluene abuse embryopathy: longitudinal neurodevelopmental effects of prenatal exposure to toluene in rats.

To determine the longitudinal effects of prenatal exposure to toluene in rats, dams received daily gavage doses of toluene diluted in corn oil on Days 6 through 19 of gestation, whereas control dams received corn oil. Litters were evaluated either on Gestational Day 19, Postnatal Day 10, or Postnatal Day 21; morphometric analysis of brain and measurements of brain DNA, cholesterol, and protein were made. Prenatal toluene exposure produced growth retarded fetuses with smaller brain and caudate-putamen volumes, fewer forebrain cell nuclei (DNA), and a reduction in both hindbrain cell size (protein/DNA) and myelination per cell (cholesterol/DNA). Postnatal catch-up growth occurred in the prenatally toluene-exposed pups, and by Postnatal Day 21 these differences had resolved. However, on Postnatal Day 21, a significant reduction in forebrain myelination/cell was present in the prenatally toluene-exposed pups. Therefore, whereas the effects of toluene administered prior to the time of the brain growth spurt were, for the most part, reversible, these exposures resulted in reduced forebrain myelination that may be permanent.