Thresholds of adversity and their applicability to endocrine disrupting chemicals.

Within the European Union, various legislative acts contain specific provisions on endocrine disruption, requiring the regulation of substances with endocrine disrupting properties via a hazard-based approach. Presumably this is due to an assumed lack of thresholds for the adverse effects of such substances. Conversely, in other jurisdictions, such as USA, Canada, Australia and Japan, endocrine disruptors (EDs) are regulated using a risk-based approach. As a consequence, in recent years there has been increasing controversy on whether thresholds can be inferred for endocrine-mediated effects. There is concern that the endocrine system is too complex to allow estimation of safe levels of exposure to such chemicals. This brief review aims to evaluate the available scientific evidence in this area and offer a sound and robust conclusion supported by this analysis. It is concluded that there is nothing special or unique about endocrine disruption or greater uncertainties in its assessment compared to other non-genotoxic forms of toxicity to justify adopting a non-threshold approach by default. Biology predicts that thresholds of adversity exist and are the rule for all endpoints, including those arising from endocrine disruption. A threshold approach to the risk assessment of endocrine disrupting chemicals is scientifically justified.