Biologically Based Models in Risk Assessment,
Abstract
Dose-response characterization in the risk assessment process for chemical carcinogens entails extrapolation of tissue dosimetry and tumor response seen at high exposure concentrations in test animals to humans exposed to much lower concentrations. The difficulty in predicting the potential human tumor incidence arises from interspecies differences in tissue susceptibility and from the dose, species, and/or exposure-route dependency of chemical disposition. These extrapolations are usually conducted with 'mandated' models, a linearized, multistage, cancer model for low-dose extrapolation and a body surface or body weight correction for interspecies extrapolation. In recent years, there have been several attempts to provide an increasing level of biological realism to these extrapolation models. Biologically based dosimetry and response modeling approaches enable identification and characterization of critical determinants of chemical disposition and tissue response and form a mechanistic basis for dose, species and exposure-route extrapolations. This paper briefly outlines the utility of biologically based models in predicting tissue dosimetry and response and provides an example of the use of biologically based dosimetry models in cancer risk assessment for methylene chloride
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1993
- Accession Number
- ADP008716
Entities
People
- Kannan Krishnan
- Melvin E. Andersen
- Rory B. Conolly