An Exhaled Breath Chamber System for Assessing Rates of Metabolism and Rates of Gastrointestinal Absorption with Volatile Compounds

Abstract

The in vivo kinetic constants for chemical metabolism and the rate constant for uptake of chemical from the gastrointestinal (GI) tract following oral dosing are critical parameters for assessing the internal dosimetry of volatile compounds in rodents. An in vivo technique is presented that relies on determining chamber time courses under conditions where the only input to the chamber is from the exhaled breath of animals in the chamber. This is referred to as an exhaled breath chamber system and is used with animals previously exposed by constant concentration inhalation or by gavage dosing. The exhaled breath chamber profiles were analyzed using a physiologically based pharmacokinetic (PB-PK) model in which either metabolic constants or oral absorption rate constants were varied until agreement was achieved between simulated and experimental results. The exhaled breath system and approaches for data analysis are described. Previous studies are reviewed that estimate metabolic constants for 1, 1, 2-trichloroethane in the rat. Oral absorption kinetics for 1, 1, 1-trichloralethane in the mouse are also presented. This technique proved a successful alternative to in vivo gas uptake studies for determining metabolic rates for chemicals not suited to gas uptake and offers a noninvasive approach for assessing GI absorption of chemicals.

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