Toxicokinetics of organic solvents: A review of modifying factors

This article reviews, with an emphasis on human experimental data, factors known or suspected to cause changes in the toxicokinetics of organic solven ts. Such changes in the toxicokinetic pattern alters the relation between e xternal exposure and target dose and thus may explain some of the observed individual variability in susceptibility to toxic effects. Factors shown to modify the uptake, distribution, biotransformation, or excretion of solven t include physical activity (work load), body composition, age, sex, geneti c polymorphism of the biotransformation, ethnicity, diet, smoking, drug tre atment, and coexposure to ethanol and other solvents. A better understandin g of modifying factors is needed for several reasons. First, it may help in identifying important potential confounders and eliminating negligible one s. Second, the risk assessment process may be improved if different sources of variability between external exposures and target doses can be quantita tively assessed. Third, biological exposure monitoring may be also improved for the same reason.