Individual susceptibility in occupational and environmental toxicology

By prudent interpretation of toxicological and epidemiological evidence, susceptibility could become a very useful notion, both in a scientific sense and for prevention of adverse effects. Based on presumed aetiology, susceptibility can often be separated into genetic, constitutional, and environmental categories, although some overlapping between these groups will be apparent. Inherited factors seem to be involved in determining many toxic effects of environmental chemicals, including carcinogenic responses, although some of the evidence is equivocal. Among constitutional factors, sex, age and pregnancy are major determinants of individual susceptibility. An individual's resistance toward chemical toxicity may also be affected by other environmental exposures, including those associated with diet and lifestyle. The mechanisms involved are only partially known but are likely to include both toxicokinetic and toxicodynamic interactions. Three major types can be recognised: (1) factors that increase the concentration of the biologically active substance at the active site; (2) factors that augment the reaction of the chemical substance with target molecules in the body, thereby initiating the response; and (3) factors that promote the sequence of events between the initial reaction and the final manifestation of an adverse health effect. Specifically, a decrease in the body's reserve capacity may not be readily observable and may only reveal itself as a weakening of the defence mechanisms. The causes of hypersusceptibility and its effects on toxic responses are little known and deserve to be explored systematically.