Integrating the lifelong exposure dimension of a chemical mixture into the risk assessment process. Application to trace elements.

Lifelong, the general population is exposed to mixtures of chemicals. Most often, risk assessment is performed to estimate the probability of adverse effects in the population using external exposures to a single chemical and considering one route of exposure. To estimate whole exposure to a chemical, human biomonitoring studies are used to measure chemical concentrations in biological matrices. The limitations of these studies are that is not possible to distinguish the sources or the routes of exposure. Moreover, only the concentrations of a limited number of chemicals are usually determined due to the associated cost. In this study, a methodology has been developed to estimate the internal exposures of the population to a mixture of trace elements (inorganic As, Cd, Pb and Hg) throughout lifetime. This methodology uses realistic lifetime exposure trajectories coupled to physiological based kinetic modeling, considering several sources of exposure. Then, the estimated biomarkers of exposure were compared to human biomonitoring data to estimate the robustness of the methodology. Finally, risk characterization was performed based on the simulated biomarkers of exposure considering an additive effect of chemicals. This methodology allows to determine the contribution of chemicals to the overall risk of renal effect.