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What role for biologically based dose-response models in estimating low-dose risk?
Kenny S Crump1, Chao Chen, Weihsueh A Chiu
1Louisiana Tech University, Ruston, Louisiana 71272 , USA. kennycrump@email.com
Environmental Health Perspectives
|January 9, 2010
Summary
Biologically based dose-response (BBDR) models offer insights into toxicity mechanisms but do not reliably estimate low-dose human risk. Significant uncertainties, including biological heterogeneity, limit their predictive power for future risk assessment.
Area of Science:
- Toxicology
- Risk Assessment
- Computational Biology
Background:
- Biologically based dose-response (BBDR) models integrate molecular and cellular data to connect exposure to adverse effects.
- These models have been utilized to explore toxicity mechanisms and identify research gaps.
Purpose of the Study:
- To evaluate the effectiveness of BBDR models in predicting human health risks at low exposure levels.
- To identify challenges and limitations in applying BBDR models for quantitative risk assessment.
Main Methods:
- A review of existing literature on the application of BBDR models in risk assessment.
- Analysis of the sources of uncertainty introduced by BBDR models.
Main Results:
- BBDR models have not enhanced the reliability of quantitative low-dose human risk predictions.
- Significant impediments include inter- and intraindividual biological heterogeneity and uncertainties in toxicity mechanisms.
- BBDR models shift, rather than eliminate, the need for empirical dose-effect modeling to lower biological organization levels.
Conclusions:
- BBDR models are unlikely to reduce uncertainty in quantitative human risk estimates from low-level exposures in the near future.
- Integrating in vitro data presents new challenges in extrapolation and does not resolve existing issues.
- The inherent complexities and uncertainties appear intractable for current BBDR modeling approaches to low-dose risk assessment.
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