A TOLUENE-INDUCED MOTOR SYNDROME IN RATS RESEMBLING THAT SEEN IN SOME HUMAN SOLVENT ABUSERS

The purpose of these experiments was to determine the extent to which subchronic exposure of rats to toluene might cause symptoms similar to those seen in some heavy abusers of toluene-containing products. In the first exploratory experiment, weanling mate Fischer-344 rats were exposed to air, toluene, n-hexane, or a mixture of toluene, n-hexane, and methyl ethyl ketone (8 h per day, 7 days per week) for 11 weeks. A mild peripheral neuropathy was revealed by measures of grip strength in the rats exposed to n-hexane alone or in the mixture, but not in the rats exposed to toluene. Instead, the rats exposed to toluene alone developed a persisting motor syndrome characterized by a shortened and widened gait and a widened landing foot splay. The rats exposed to toluene alone or in the mixture were also hearing impaired, but not the rats exposed to n-hexane alone. In the second experiment, done to confirm and extend these results, weanling male Fischer-344 rats were exposed to toluene under three different daily schedules-2,200 ppm continuously for 8 h per day; 4,400 ppm, 30 min each h, 8 h per day; or 6,200 ppm, 15 min each h, 8 h per day. The exposures were 7 days per week for 23 weeks. The motor syndrome and hearing impairment were replicated in all essential respects in all toluene-exposed groups with no appreciable differences attributable to the daily exposure schedules. The effects were still evident 15 weeks after the last exposure. Toluene inhibited weight gain in both experiments, and in the second experiment, it was found that skeletal growth (torso length, rump width) was also inhibited. Toluene did not significantly impair rotorod performance in either experiment or acquisition of a spatial-navigation task in the second experiment. No neuropathologic correlates of the persisting motor syndrome were found in either experiment when the rats were sacrificed 9 and 16 weeks after the last exposure, respectively. These results demonstrate that toluene can cause a persisting motor syndrome in rats that resembles, to some extent at least (i.e., wide-based ataxic gait), the syndrome seen in some heavy abusers of toluene-containing products.