Superfund Research Program

Perchloroethylene (PCE) in Drinking Water and Cancer Risk

Project Leader: Ann Aschengrau
Grant Number: P42ES007381
Funding Period: 1995 - 2000

Project-Specific Links

Final Progress Reports

Year:   1999  1998  1997  1996  1995 

The binding of trichloroethylene (TCE) to DNA and protein, a measure of the biologically active dose, in mice at doses between 2 µg/kg and 200 mg/kg has been determined. These doses span an exposure range equivalent to animal bioassay doses and low-level human exposure. Accelerator mass spectrometry was utilized to measure attomoles of adduct in mg sized samples. These studies allowed direct exploration of dose response relationships over large exposure ranges and should be useful in risk assessment for dose extrapolation and potency determinations. In B6C3F1 mouse liver, project investigators found that the greatest protein binding occurs 1 hour after exposure while DNA binding peaks between 24 and 72 hours after exposure. Binding to both DNA and protein is linear with dose over the large dose range studied here. The binding of TCE metabolites to DNA is approximately 100-times lower per unit dose than to proteins. However, the TCE protein adducts formed may be unstable as adduct levels rapidly declined after the exposure. These data show that TCE metabolites bind to DNA and proteins in a dose dependent fashion in liver, even at doses relevant for human exposure. These data also suggest that no threshold phenomena occurs and the use of linear extrapolation of animal bioassay data to human exposure doses may be acceptable.