The impact of CYP2E1 genetic variability on risk assessment of VOC mixtures

Humans are simultaneously exposed to multiple chemicals in the environment. Many of the chemicals use the same enzymes in their metabolic pathways. Competitive inhibition may occur as one of the possible interactions between the xenobiotics in human body. For example, many volatile organic compounds (VOCs) are metabolized using P450 enzymes, specifically CYP2E1. Inheritable gene alterations may result in changes of function of the enzymes in different human subpopulations. Variations in quantity and/or quality of particular isoenzymes may cause differences in the metabolism of VOCs. These variations may cause higher sensitivity in certain populations. Using examples of three different mixtures, this review paper outlines the variances in CYP2E1 isoenzymes, effect of exposure to such mixtures on sensitive populations, and approaches to mixtures risk assessment.