A variety of genetic polymorphisms in human populations can affect the quantity and quality of CYP450 and glutathione S-transferase enzymes and, in turn, the outcomes of exposure to solvents. There are marked interindividual differences in activity of hepatic CYP2E1, the primary isozyme responsible for metabolic oxidation of TCE. This interindividual difference is not believed to be toxicologically significant, however, for persons exposed to very low concentrations of TCE and other well-metabolized VOCs. The interindividual difference in oxidative capacity may be important, however, in the extent of metabolic activation and response to poorly-metabolized VOCs, such as PCE.
Lifestyle can potentially influence an individual’s responses to VOCs in a number of ways. Dietary habits and components, physical activity, ethanol intake, and certain drugs can affect metabolism and deposition of solvents. Serious illness, impaired metabolism and systemic clearance of parent compounds, and obesity are some additional factors that can affect the way the body handles exposure to TCE and PCE.
Many occupational and environmental exposures to VOCs involve multiple chemicals. Knowledge of mechanisms of chemical interactions largely involves the effect of one VOC on the metabolic activation of a second. Concurrent exposures to sufficiently high doses typically involve competitive metabolic inhibition, which results in increased concentrations of parent compounds and lower production of metabolites. Such interactions will not occur at very low exposure concentrations.