TEF's for DBPs Based on Transgenic Models

Objective/Intended Use

The purpose of this project is to evaluate data from alternative testing approaches for their use in cancer risk assessments for disinfection byproducts (DBPs). The task is to examine the mechanistic basis for employing data from alternative cancer bioassays (i.e., transgenic models) to estimate cancer risks for DBPs. NCEA will use these data to explore the application of TEF approach as well as other comparative potency models for estimating cancer risks DBPs.

Abstract

A number of short term bioassays have been developed to assess potential carcinogenicity of contaminants. This research seeks to evaluate alternative testing data and assay systems for their use in human risk assessments. This task will examine the mechanistic basis for employing data from alternative cancer bioassays (i.e., transgenic models) to estimate cancer risks for DBPs. Assays include, but are not limited to, p53 and TgAc rodent transgenic bioassays, newborn mouse assay and in vitro assays. Response data developed from transgenic assays will be compared with data developed from the traditional 2 yr bioassays. The toxicity equivalence factor (TEF) approach as well as other comparative potency models will be explored in the planned development of a formalized framework for estimating carcinogenic risk associated with DBPs that lack rigorous 2 yr rodent bioassay data. In order to qualitatively and - quantitatively characterize the risks of cancer associated with exposure to disinfectants and DBPs, a weight of evidence approach and dose response modeling have traditionally applied to both existing human data and chronic long-term animal bioassay laboratory data. These studies are costly, as well as time consuming.

Project Status

Ongoing: Internal review draft on the application of transgenic models for estimating carcinogenic risks for untested DBPs has been completed. External review has been completed and changes are being incorporated to produce the final report.

Project Start Date

08/01/2000