Statistical Issues Related to the Implementation of Benchmark Dose MethodEPA Grant Number: R825385
Title: Statistical Issues Related to the Implementation of Benchmark Dose Method
Investigators: Patil, G. P. , Banga, S. , Sciullo, C. , Stiteler, W. M. , Taillie, C.
Current Investigators: Patil, G. P. , Banga, S. , Stiteler, W. M. , Taillie, C.
Institution: Pennsylvania State University
EPA Project Officer: Hahn, Intaek
Project Period: January 1, 1997 through December 31, 2002
Project Amount: $299,823
RFA: Environmental Statistics (1996) RFA Text | Recipients Lists
Research Category: Environmental Statistics , Health , Ecosystems
Description:The current approach to risk assessment for toxic noncarcinogenic chemicals is based on the assumption that there exists a threshold below which no adverse noncancer health effects are expected under lifetime exposure. Various regulatory agencies estimate a "safe" exposure by first determining an exposure level which has been shown to cause no adverse effect in animals or humans and then apply "uncertainty" factors to account for missing information.
Problems were identified with this methodology shortly after it was adopted some 30 years ago. The risk assessment community has been searching for improved methods since that time. One suggestion that has received a great deal of attention is to base the methodology on dose-response modeling. The idea is to estimate the effective does (ED) that causes some critical effect in a specified percentage of the test animals (e.g., ED05 or ED10) and then to designate the lower confidence limit for the effective dose as the "benchmark dose." This benchmark dose may then be adjusted by uncertainty factors to arrive at the reference dose (RfD) or reference concentrations (RfC).
In spite of the fact that it is generally agreed that the benchmark dose method addresses many of the shortcomings of the current methodology, more than a decade has passed since the benchmark dose method was suggested as an alternative. One reason for this delay is that there are a number of difficult statistical issues remaining. While the potential benefits have been recognized, risk assessors have been understandably reluctant to adopt a methodology which is not yet completely understood.
The proposed research will examine specific statistical and modeling issues that have been identified as impediments to widespread adoption of the benchmark dose method for risk assessment. The specific questions to be addressed by the proposed research are:
- How should continuous response data be handled in modeling for the benchmark dose?
- What is the best method for calculating a lower confidence limit in determining the benchmark dose?
- Under what conditions might the estimated slope at the ED10 (or ED05) be useful in modifying the uncertainty factor?
Once satisfactory answers are obtained for these questions, the way will be paved for adoption of a methodology that should lead to improved human health risk assessment for noncancer endpoints.