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- Title
A Comparison of Regulatory Implications of Traditional and Exact Two-Stage Dose-Response Models.
- Authors
Chiu, Weihsueh A.; Hassenzahl, David M.; Kammen, Daniel M.
- Abstract
We compare the regulatory implications of applying the traditional (linearized) and exact two-stage dose-response models to animal carcinogenic data. We analyze dose-response data from six studies, representing five different substances, and we determine the 'goodness-of-fit' of each model as well as the 95% confidence lower limit of the dosecorresponding to a target excess risk of 10-5 (the targetrisk dose TRD). For the two concave datasets, we find that the exactmodel gives a substantially better fit to the data than the traditional model, and that the exact model gives a TRD that is an order of magnitude lower than that given by the traditional model. In the othercases, the exact model gives a fit equivalent to or better than the traditional model. We also show that although the exact two-stage model may exhibit dose-response concavity at moderate dose levels, it isalways linear or sublinear, and never supralinear, in the low-dose limit. Because regulatory concern is almost always confined to the low-dose region extrapolation, supralinear behavior seems not to be of regulatory concern in the exact two-stage model. Finally, we find thatwhen performing this low-dose extrapolation in cases of dose-response concavity, extrapolating the model fit leads to a more conservativeTRD than taking a linear extrapolation from 10% excess risk. We conclude with a set of recommendations.
- Subjects
CARCINOGENESIS; CARCINOGENICITY; TRICHLOROETHYLENE; CHLOROHYDROCARBONS; RISK assessment; CANCER research; EXTRAPOLATION
- Publication
Risk Analysis: An International Journal, 1999, Vol 19, Issue 1, p15
- ISSN
0272-4332
- Publication type
Article
- DOI
10.1023/A:1006946008515