Reproductive and developmental toxicity of toluene: a review

Toluene is a widely used industrial solvent, and humans may also have high exposures to toluene from the deliberate inhalation ("sniffing") of paint reducer, paint thinner, or paint for their narcotic effects. A number of case reports describe neonatal effects that have been attributed to toluene abuse during pregnancy. These effects may include intrauterine growth retardation, premature delivery, congenital malformations, and postnatal developmental retardation. The possibility of exposures to other fetotoxic agents, either as impurities or admixtures in toluene-containing products, or by deliberate or accidental exposures to other chemicals or drugs, cannot be excluded in these cases. The fetotoxic effects of toluene have been demonstrated in controlled studies in animals and are comparable to those observed in humans who have abused toluene-containing products before or during pregnancy. Intrauterine developmental retardation is the most clearly established effect in animals, as evidenced by decreased late fetal weight and retarded skeletal development. There is also limited evidence in rodents for skeletal and kidney abnormalities, as well as some evidence for effects on postnatal physical and possibly neurobehavioral development. Estimated daily exposures from experimental studies in animals are compared to estimated human daily intakes at the occupational permissible exposure level and at the level reported to produce euphoria in humans. Acceptable human intakes under California's Proposition 65 and under U.S. Environmental Protection Agency procedures are discussed.