| Abstract: | The aim of safety assurance procedures is to determine a level of intake (the acceptable daily intake (ADI) or tolerable daily intake (TDI)) that is without adverse health effects in the human population. The majority of studies on inter-ethnic differences in xenobiotic metabolism have concentrated in the incidence of expression of the poor metaboliser phenotype for a number of drug metabolising enzymes. Such ethnic differences can result in different incidences of individuals at higher risk, but this would not affect the safety assurance/risk assessment outcome unless poor metaboliser status was not recognised in the database used for the initial assessment and calculation of ADI or TDI. Of far greater importance are ethnic differences which result in population differences in the mean values, and/or the extent of variability within the population, for key kinetic parameters such as the internal dose or area under the plasma concentration time curve (AUC). There are few studies on inter-ethnic differences in sensitivity and most of these relate to in vivo differences for therapeutic/pharmacological agents, so that the reported data reflect both kinetic and dynamic variability. Inter-ethnic differences are limited in extent and well within the uncertainty factor of 10 used for human variability. |
