INTERETHNIC DIFFERENCES IN XENOBIOTIC METABOLISM

The aim of safety assurance procedures is to determine a level of inta ke (the acceptable daily intake (ADI) or tolerable daily intake (TDI)) that is without adverse health effects in the human population. The m ajority of studies on inter-ethnic differences in xenobiotic metabolis m have concentrated in the incidence of expression of the poor metabol iser phenotype for a number of drug metabolising enzymes. Such ethnic differences can result in different incidences of individuals at highe r risk, but this would not affect the safety assurance/risk assessment outcome unless poor metaboliser status was not recognised in the data base used for the initial assessment and calculation of ADI or TDI. Of far greater importance are ethnic differences which result in populat ion differences in the mean values, and/or the extent of variability w ithin the population, for key kinetic parameters such as the internal dose or area under the plasma concentration time curve (AUG). There ar e few studies on inter-ethnic differences in sensitivity and most of t hese relate to in vivo differences for therapeutic/pharmacological age nts, so that the reported data reflect both kinetic and dynamic variab ility. Inter-ethnic differences are limited in extent and well within the uncertainty factor of 10 used for human variability.