Citation:

BUSHNELL, P. J., W. M. OSHIRO, AND T. E. SAMSAM. The Role of Physical Activity and Feeding Schedule on the Kinetics of Inhaled and Oral Toluene in Rats. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. Taylor & Francis, Inc., Philadelphia, PA, 70(21):1806-1814, (2007).

Impact/Purpose:

This manuscript provides new information regarding factors that affect the toxicokinetics of toluene, a hazardous air pollutant with acute neurotoxic activity. Toluene is a prototype compound of the class of volatile organic compounds (VOCs), which have similar CNS activity and kinetic behavior. Using a rat model, this paper demonstrates that physical activity increases the uptake of inhaled toluene but not of oral toluene: this factor can be used to improve modeling of the kinetics of VOCs in general. In addition, the experiments show that exposure to toluene in conjunction with feeding greatly speeds the rate at which orally-administered toluene is removed from the blood and brain, but does not affect the kinetics of inhaled toluene. These data raise questions about the utility of kinetic studies of orally-administered lipophilic compounds, which typically involve dosing nocturnal rodents during the day when the gastrointestinal and metabolic processes involved in digestion of foods and chemicals are relatively inactive. The data also point to the need for further work to understand the roles of such processes in the kinetics of xenobiotic compounds.

Description:

This manuscript provides new information regarding factors that affect the toxicokinetics of toluene, a hazardous air pollutant with acute neurotoxic activity. Toluene is a prototype compound of the class of volatile organic compounds (VOCs), which have similar CNS activity and kinetic behavior. Using a rat model, this paper demonstrates that physical activity increases the uptake of inhaled toluene but not of oral toluene: this factor can be used to improve modeling of the kinetics of VOCs in general. In addition, the experiments show that exposure to toluene in conjunction with feeding greatly speeds the rate at which orally-administered toluene is removed from the blood and brain, but does not affect the kinetics of inhaled toluene. These data raise questions about the utility of kinetic studies of orally-administered lipophilic compounds, which typically involve dosing nocturnal rodents during the day when the gastrointestinal and metabolic processes involved in digestion of foods and chemicals are relatively inactive. The data also point to the need for further work to understand the roles of such processes in the kinetics of xenobiotic compounds.

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