Consideration of Toxicokinetics and Toxicodynamics in Evaluating Interspecies and Intraspecies Uncertainty and Variability. A. G. Renwick, University of Southampton
The default values for toxicokinetics and toxicodynamics to allow for inter-species differences and human variability are based on the long-established uncertainty factors of 100 and 10 for NOAELS in animals and humans respectively. The scientific rationale for these values was not given when they were introduced about 40 years ago. All regulatory toxicologists can think of examples where the default values for toxicokinetics and toxicodynamics may be inappropriate, but there have been limited international discussions of the types of data appropriate to replace the default. Since there will rarely be the luxury of a full biologically-based, dose-response model, subdivision and replacement of part of the 10-fold factors offers the potential for the introduction of more science into a largely pragmatic approach. This will allow refinement of the risk assessment process for those examples where the default does not fit. The key question for the replacement of default values is "Is the default better than the data?" This paper will describe the theoretical support for the concept of Compound-Specific Adjustment Factors.
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