Superfund Research Program
Pharmacology of Trichloroethylene Metabolites
Project Leader: Peter W. Stacpoole
Grant Number: P42ES007375
Funding Period: 2000-2006
Project Summary (2000-2006)
Project investigators are focusing on the kinetics, metabolism and toxicology of two metabolites of trichloroethylene (TCE): dichloroacetate (DCA) and chloral hydrate (CH). The studies are capitalizing on earlier novel findings in children to determine the in vivo kinetics and biotransformation of CH in healthy adults, and the influence of CH and DCA on each other's metabolism and toxicity. The effect of CH and DCA on tyrosine catabolism in children and adults is being quantified by measuring the plasma and urinary concentrations of tyrosine, its metabolites and the heme precursor 5-aminolevulinate. The studies are also comparing and contrasting in vivo human data with similar experiments conducted in rats. In addition, molecular mechanisms of DCA and CH biotransformation and the effects of biotransformation enzymes are being elucidated using cellular and subcellular fractions of rat and human liver. Postulates regarding earlier molecular events involving DCA biotransformation and the mechanism by which DCA influences maleylacetoacetate isomerase (MAAI, also known as GST-zeta) activity are also being evaluated.