Construction de valeurs toxicologiques de référence adaptées à la prise en compte des mélanges en évaluation des risques sanitaires : méthodes existantes et applications récentes

Derivation of toxicological reference values for taking mixtures into account in health risk assessment: Existing methods and recent applications Human beings are exposed through their environment to numerous chemicals. Several approaches to cumulative risk assessment, including the sum of hazard quotients, toxic equivalent factors (TEF), and the pointofdeparture index (PODI), have been developed to estimate the risks due to these exposures. Their principles are based on the assumption of effect or dose additivity, and their main purpose is to provide tools to help decisionmakers in a context where uncertainty predominates. They also highlight the lack of adequate data, especially for toxicity data and dose-response relations. The objective of this article is to propose a brief history of these approaches and to describe their current applications through examples from the literature. While few institutional recommendations allow mixtures to be taken into account in cumulative risk assessment approaches, manyapproacheshavebeenpublishedinrecent years.AlthoughthedevelopmentofTEFs requires precise knowledge about the toxic mechanisms of action, other approaches, less