Developmental Neurotoxicity of Toluene: in vivo and in vitro Effects on Astroglial CellsBurry M. · Guizzetti M. · Oberdoerster J. · Costa L.G.
aToxicology Program, University of Washington, Seattle, Wash., bToxicology Department, Aventis CropScience, Research Triangle Park, N.C., USA; cDepartment of Pharmacology and Physiology, University of Bari Medical School, Bari, Italy
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.
Dr. Lucio G. Costa
Toxicology Program, Department of Environmental Health
University of Washington, 4225 Roosevelt Way NE, 100
Seattle, WA 98105-6099 (USA)
Tel. +1 206 543 2831, Fax +1 206 685 4696, E-Mail email@example.com
Received: October 7, 2002
Accepted: December 18, 2002
Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 2, Number of References : 35
Vol. 25, No. 1, Year 2003 (Cover Date: January-February (Released July 2003))
Journal Editor: A.T. Campagnoni, Los Angeles, Calif.
ISSN: 0378–5866 (print), 1421–9859 (Online)
For additional information: http://www.karger.com/journals/dne