ASSESSING HUMAN HEALTH RISKS OF CHEMICALS AND DRUGS - AN OVERVIEW

The risk assessment process for non-carcinogens involves extrapolation of toxicological animal data to humans by applying uncertainty factor s (UF). A 10-fold UF is most commonly used to account for underlying v ariability in different areas of uncertainty. The purpose of this inve stigation is to evaluate whether the magnitude of the 10X UF can be re duced when pharmacokinetic and pharmacodynamic data are incorporated e specially into interspecies extrapolation and interindividual variabil ity. A compilation and comparison of kinetic and dynamic data between animal/human and sensitive human/human were made. The composite UFs we re calculated using the highest ratios for available kinetic and dynam ic data and default subfactors. When relevant kinetic and dynamic data are available, UFs are significantly reduced by replacing the default factors with actual data derived-values.