Review of noncancer risk assessment: Applications of benchmark dose methods

Abstract

The overall goal of this project is to evaluate and compare risk assessment methods traditionally used for noncancer health risks and to compare them with new approaches. These methods include the no observed adverse effect level (NOAEL), lowest observed adverse effect level (LOAEL), and the more recently proposed benchmark dose (BMD), in which a dose is identified using a curve‐fitting procedure and a prespecified effect level. Applications of the BMD method are reviewed for developmental toxicity, reproductive toxicity, neurotoxicity, ecological toxicity, carcinogenicity, and other biological impacts.

Evaluations have shown that the benchmark method is generally no more conservative than the NOAEL approach and confers several significant advantages for safety assessment. In addition, traditional safety factor approaches used for RfD calculation based on LOAEL values are overly conservative. Studies show that exposures at NOAELs are not “risk free”; but may represent effect levels ranging from 3% up to 21%. An important advantage of BMD approaches is that regulatory limits can be consistently set at a given response level rather than being dictated by study design. BMD methodology also allows for easy transition to biologically based dose response modeling as such models are developed.

Key words:

• environmental toxicology
• developmental toxicity
• dose‐response models
• BMD
• NOAEL

Notes

Correspondence Address: Institute for Risk Analysis and Risk Communication, Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA 98105–6099; Tel: [phone]; Fax: [phone]; email: [email protected]

This research was supported with funding from National Institute of Environmental Health Sciences UW Center Grant #P30‐ES07033 and from Department of Energy Cooperative Agreement #DE‐FCOl‐95EW55084. Special thanks to the President's Risk Commission and Chair Gilbert Omenn for their encouragement and financial support of the white paper on benchmark doses that formed the basis of this article.