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WHY DO THE ACUTE BEHAVIORAL EFFECTS OT TOLUENE IN RATS DEPEND ON THE ROUTE OF EXPOSURE?
Samsam, T E., W M. Oshiro, AND P J. Bushnell. WHY DO THE ACUTE BEHAVIORAL EFFECTS OT TOLUENE IN RATS DEPEND ON THE ROUTE OF EXPOSURE? Presented at Society of Toxicology, New Orleans, LA, March 06 - 10, 2005.
Despite evidence suggesting that the acute effects of organic solvents are related to their concentration in the brain, we have observed route-dependent differences in the acute behavioral effects of toluene. Whereas inhaled toluene disrupts the performance of rats on a visual signal detection task (SDT) that assesses sustained attention, toluene given orally in corn oil does not, even with similar concentrations in the blood (see Bushnell et al). Several studies in adult male Long-Evans rats were conducted to determine the source of these route differences. Exp. 1 showed that the time course of the rise in toluene concentrations in blood and brain of rats inhaling 2000 ppm toluene (an effective treatment) matched that of rats given 800 mg/kg of toluene in corn oil by gavage (an ineffective treatment). Further experiments used rats previously trained to perform the SDT. Exp. 2 showed that the pre-test exposure interval (10' vs. 30') did not account for the route difference, and Exp. 3 showed that co-administration of oral corn oil and inhaled toluene did not reduce the effect of toluene. Exp. 4 showed that oral administration of sodium benzoate, a toluene metabolite, did not reduce the effect of inhaled toluene. Exp. 5 showed that oral trichloroethylene (TCE) in corn oil (1200 mg/kg), which yields concentrations of TCE in blood of 10 - 30 ug/mL (Prout et al., 1985), caused slight impairment on the SDT, relative to previous observations of robust effects of inhaled TCE with blood concentrations of 50 - 125 ug/mL. Exp. 6 examined the effects of oral toluene given in a lipophilic but non-absorbable sucrose-esterified fatty acid complex (SEFA soyate). Further experiments will look at the role of physical activity on the kinetics of inhaled and orally-delivered toluene and on the generality of this route dependence across functional endpoints. These findings address the appropriateness of route-route extrapolations in setting reference toxicity values. [This abstract of a proposed presentation does not necessarily reflect EPA policy.]