The effect Route and Dose on the toxicity of Trichloroethylene and Trichloroethane

The Kinetics and toxicity of volatile organic compounds (VOCs) are affected by several factors such as the rate of metabolism, route of administration, and dose. This study is designed to characterize the effects of dose and compound administration rate on the bioavailability of two model compounds, TCE and TRI. TCE is a well-metabolized VOC, while TRI is poorly metabolized, but extensively cleared by the lung through Blood-air exchange. Thus, the relative importance of first- pass hepatic metabolism and first pass pulmonary elimination on the bioavailability of low doses of the two VOCs were determined. Male Sprague-Dawley rats were given 8mg/kg or 50mg/kg of TCE either as an oral bolus (PO) or by gastric infusion (GI) over 2 hours in a 1% Alkamuls aqueous emulsion. Serial arterial blood samples were obtained from the arterial cannula of each animal and analyzed by headspace GC-ECD. Pharmacokinetic parameters were estimated using WinNonLin. The bioavailability of TRI was comparable for all doses utilized. Bioavailability and clearance were dose-independent for TRI. The TRI bioavailability was independent of compound administration rate. First-pass pulmonary elimination had relatively little influence on the bioavailablity of TRI. First-pass metabolism had no seen effect with TRI. TCE data is still being analyzed.