Assessing human health risks of chemicals and drugs: An overview

Abstract

The risk assessment process for non-carcinogens involves extrapolation of toxicological animal data to humans by applying uncertainty factors (UF). A 10-fold UF is most commonly used to account for underlying variability in different areas of uncertainty. The purpose of this investigation is to evaluate whether the magnitude of the 10X UF can be reduced when pharmacokinetic and pharmacodynamic data are incorporated especially into interspecies extrapolation and interindividual variability. A compilation and comparison of kinetic and dynamic data between animal/human and sensitive human/human were made. The composite UFs were calculated using the highest ratios for available kinetic and dynamic 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.

Intra-Species Extrapolation in Risk Assessment of Different Classes of Antimicrobials

“…They suggested that a factor less than 10 could be used for intrasepecies variability in kinetics. The kinetic and dynamic data of some drugs were compiled and compared between animal and human and between human and sensitive human (Kadry et al 1997;Suh and Abdel-Rahman 1997;Suh et al 1999). They concluded that the composite factor for most of the drugs examined was far less than 100.…”