The Role of Physical Activity and Feeding Schedule on the Kinetics of Inhaled and Oral Toluene in Rats

Abstract

Published studies of the kinetics of toluene in rats have shown that its concentration in the blood rises during inhalation and falls after exposure stops; a similar uptake profile and longer persistence in blood typify the kinetics after oral exposure. Because rats in these studies are typically inactive during exposure, and behavioral tests of the acute effects of toluene require physical activity and altered feeding schedules, this study examined the role of physical activity and feeding status on the uptake of toluene given by the two routes. Two groups of adult male Long-Evans rats were conditioned to eat in the lab during the day. A group of “conditioned-active” (C-A) rats performed a lever-pressing task (LPT) for 1 h, either while inhaling toluene vapor (2000 ppm) or after a gavage dose (800 mg/kg toluene in corn oil). Another group of “conditioned-sedentary” (C-S) rats was dosed similarly but did not perform the LPT. A third group of “home cage” (HC) rats was not conditioned to eat during the day, but was maintained under typical laboratory conditions (eating at night in the home cage) before receiving toluene by gavage. In the conditioned rats, physical activity during inhalation exposure increased the concentrations of toluene in blood (from 35.8 ± 2.5 to 45.2 ± 3.2 mg/L after 60 min) and brain (from 73.4 ± 5.3 to 103.0 ± 3.8 mg/L after 60 min), but did not affect those concentrations after oral toluene. The time course of the uptake of toluene into blood and brain of HC rats followed that of published data. In contrast, toluene concentrations in the blood and brain of orally dosed conditioned rats fell rapidly compared to HC rats and published data (at 60 min after dosing, blood concentrations were: C-S rats, 17.2 ± 1.7 mg/L; HC rats, 69.4 ± 9.6 mg/L; and brain concentrations were: C-S rats, 30.9 ± 5.0 mg/L; HC rats, 96.6 ± 18.5 mg/L). These studies demonstrate the importance of physical activity for the uptake of inhaled toluene, and the importance of feeding conditions for the elimination of oral toluene.

We thank E. M. Kenyon and R. B. Conolly for reviews of an early draft of this article, Q. T. Krantz for inhalation support, K. Rigsbee for diligent animal care, and C. Hamm and E. B. Bailey for electronic support.

This article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the policies of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.