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On the use of hierarchical probabilistic models for characterizing and managing uncertainty in risk/safety assessment
1Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA. rlkodell@uams.edu
Abstract:
A general probabilistically-based approach is proposed for both cancer and noncancer risk/safety assessments. The familiar framework of the original ADI/RfD formulation is used, substituting in the numerator a benchmark dose derived from a hierarchical pharmacokinetic/pharmacodynamic model and in the denominator a unitary uncertainty factor derived from a hierarchical animal/average human/sensitive human model. The empirical probability distributions of the numerator and denominator can be combined to produce an empirical human-equivalent distribution for an animal-derived benchmark dose in external-exposure units.
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