Developmental Neurotoxicity of Toluene: in vivo and in vitro Effects on Astroglial Cells

Abstract

Toluene, an inexpensive and available industrial solvent, has become increasingly popular as a drug of abuse. Inhaling toluene leads to a feeling of euphoria and several reports have shown that children born to women who had abused toluene during pregnancy present a syndrome (toluene embryopathy or fetal solvent syndrome) that is characterized by CNS effects (e.g. microencephaly), growth retardation and facial dysmorphologies. The characteristics of the fetal solvent syndrome are very similar to those observed in the fetal alcohol syndrome. As exposure of rats to ethanol during the brain growth spurt has been shown to cause microencephaly and to affect glial cell proliferation and maturation, the present study examines the effects of toluene administration (250, 500 and 750 mg/kg) in neonatal rats from postnatal day 4 to 10. This treatment resulted in a significant decrease in both brain and body weights, and in a significant reduction of levels of glial fibrillary acidic protein, but not of neuron-specific enolase in rat brain. In vitro experiments demonstrate that pharmacologically relevant concentrations of toluene (250–1,000 µM) significantly inhibit proliferation of rat cortical astrocytes without causing overt cytotoxicity. These results indicate that toluene does not cause selective microencephaly; however, it affects brain weight, and appears to target developing astrocytes, possibly by inhibiting their proliferation.