Toxicological Sciences 66, 298-312 (2002)
Copyright © 2002 by the Society of Toxicology
RISK ASSESSMENT |
Dose-Response Modeling of Continuous Endpoints
National Institute of Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands
ABSTRACT
A family of (nested) dose-response models is introduced herein that can be used for describing the change in any continuous endpoint as a function of dose. A member from this family of models may be selected using the likelihood ratio test as a criterion, to prevent overparameterization. The proposed methodology provides for a formal approach of model selection, and a transparent way of assessing the benchmark dose. Apart from a number of natural constraints, the model expressions follow from an obvious way of quantifying differences in sensitivity between populations. As a consequence, dose-response data that relate to both sexes can be efficiently analyzed by incorporating the data from both sexes in the same analysis, even if the sexes are not equally sensitive to the compound studied. The idea of differences in sensitivity is closely related to the assessment factors used in risk assessment. Thus, the models are directly applicable to estimating such factors, if data concerning populations to be compared are available. Such information is valuable for further validation or adjustment of default assessment factors, as well as for informing distributional assessment factors in a probabilistic risk assessment. The various applications of the proposed methodology are illustrated by real data sets.
Key Words: dose-response modeling; benchmark dose; continuous endpoints; critical effect size; probabilistic assessment factor.
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