Standard: API 30-32008

Introduction

Clinical and epidemiologic evidence has implicated toluene as an agent that may cause persisting neurotoxicity associated with solvent abuse by humans, especially children and adolescents [1 2]. However, well-controlled experimental animal studies that would resolve the issue of persisting toluene-induced neurotoxic effects, vis-a-vis transient pharmacologic effects, are lacking [see 3 and 4 for recent reviews of the health effects of toluene]. Therefore, we studied toluene in a subchronic inhalation experiment using behavioral and neurophysiologic tests that are sensitive to a wide variety of neurotoxicants [5,6]. The known neurotoxicant hexane [7] was included in the study as a positive control. Because many, if not most, solvent abusers are very young [8], and so might be at particular risk with respect to any neurotoxic effects of toluene, we began exposing the rats in this study just after weaning. The schedule of exposure, which was established in preliminary experiments, was such that the highest concentration of toluene that we examined was just below the lethal concentration for repeated daily exposures. Such an intense exposure schedule is not inconsistent with reports of severe and prolonged solvent abuse by humans [9,10].