The central nervous system and exposure to toluene: a risk characterization

The principal health outcome of exposure to toluene is dysfunction of the central nervous system. Effects range from fatalities and severe neurological disorders in toluene abuse situations to deficits in neurobehavioral function in occupational populations. An Inhalation Reference Concentration (RfC) of 0.4 mg toluene/m3 or 0.1 ppm was developed by the U.S. EPA to protect general populations chronically exposed to toluene. The RfC was derived from results of an occupational study involving Asian workers who developed neurobehavioral deficits at a mean toluene exposure level at the time of the study of 88 ppm. The derivation incorporated several uncertainty factors, one of which was a factor of 10 to account for sensitive subpopulations. Recent evidence indicates that some Japanese and possibly other Asian populations harbor a defective gene for aldehyde dehydrogenase, and thus exhibit a decreased rate of toluene metabolism. Although it is not known if reduced metabolism by aldehyde dehydrogenase also was a factor in the occupational study, preshift blood levels of toluene were considerably higher than preshift levels from non-Asian workers exposed to similar air levels of toluene. The elevated blood levels are consistent with defective metabolism but remain to be confirmed. Inasmuch as air levels of toluene in urban environments are about 10-fold lower than the RfC, an adequate measure of protection is afforded by the RfC with or without an uncertainty factor for sensitive subgroups. However, the uncertainty factor for sensitive subgroups should be retained because there is no information regarding toluene metabolism in children.