Differential toxicity of water versus gavage exposure to trichloroethylene in rats

Trichloroethylene (TCE) is a persistent environmental contaminant that causes male reproductive toxicity. We investigated whether transient increases in TCE exposure modulated male reproductive toxicity by exposing rats via daily oral to repeated gavage exposures (1000 mg/kg/day) and through drinking water (0.6% TCE) for 14 weeks. The gavage route resulted in reversible reduction of epididymis weight, and reduced body weight that persisted for up to 12-weeks after cessation of exposure. Physiologically-based pharmacokinetic modeling predicted that the gavage route results in higher C_max and AUC exposure of TCE compared to drinking water exposure, explaining the observed differences in toxicity between dosing regimens.