A comparison of three methods for calculating confidence intervals for the benchmark dose.

Various methods exist to calculate confidence intervals for the benchmark dose in risk analysis. This study compares the performance of three such methods in fitting nonlinear dose-response models: the delta method, the likelihood-ratio method, and the bootstrap method. A data set from a developmental toxicity test with continuous, ordinal, and quantal dose-response data is used for the comparison of these methods. Nonlinear dose-response models, with various shapes, were fitted to these data. The results indicate that a few thousand runs are generally needed to get stable confidence limits when using the bootstrap method. Further, the bootstrap and the likelihood-ratio method were found to give fairly similar results. The delta method, however, resulted in some cases in different (usually narrower) intervals, and appears unreliable for nonlinear dose-response models. Since the bootstrap method is more time consuming than the likelihood-ratio method, the latter is more attractive for routine dose-response analysis. In the context of a probabilistic risk assessment the bootstrap method has the advantage that it directly links to Monte Carlo analysis.