On the use of hierarchical probabilistic models for characterizing and managing uncertainty in risk/safety assessment.
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.
Kodell
Ralph L
RL
Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA. rlkodell@uams.edu
Chen
James J
JJ
D000818:Animals; D001499:Bayes Theorem; D015386:Hazardous Substances; D006801:Humans; D015233:Models, Statistical; D009010:Monte Carlo Method; D019055:No-Observed-Adverse-Effect Level; D011336:Probability; D012306:Risk; D018570:Risk Assessment; D012449:Safety; D035501:Uncertainty
D015386:Hazardous Substances