Determination of Partition Coefficients for Trichloroethanol (TCOH) and Chioral

摘要

Trichioroethylene (TCE), a common groundwater contaminant, has been shown to becarcinogenic in some animal species. To determine the risk in humans, the use of physiologically-based pharmacokinetic models (PBPK) has become increasingly the method of choice. Formerly it was a common practice to calculate risk estimates on the basis of administered dose-toxicity/tumor incidence, it is now recognized that the dose delivered to the target organ is more accurate. Determination of partition coefficients (the solubility of the chemical in tissue) is one element important in the development of the PBPK model. This study focuses on two metabolites of TCE, chloral hydrate (CII) and trichloroethanol (TCOII). All studies were conducted in B6C3F1 mice since this species was used in the NCI/NTP carcinogenicity studies on TCE. Partition coefficients for CII and TCOII were determined using the nonvolatile method of Jepson et al., (Fund. and Appl. Tox 22:1994). Tissues used in CII studies were pre-treated with 20% lead acetate to insure no metabolism occurred during the incubation period.