Changing risk assessment landscape in the context of exposure to mixtures of metals and gene-environment interaction

Risk assessment, as a regulatory science, is used to inform decision making at scales ranging from site-specific remediation to policy development. Current risk assessment guidance dictates a largely chemical-by-chemical evaluation of exposures and risks which fails to adequately address potential interactions with other chemicals, other non-chemical stressors, and genetic influences. The Superfund Research Program at the Harvard School of Public Health is exploring these issues in the context of exposures to mixtures of metals, including lead, arsenic, and manganese and neurodevelopmental health outcomes in children. We first provide an overview of emerging issues in risk assessment methodology including cumulative risk, distributional effects (e.g., susceptible populations and environmental justice and equity), epigenetics and timing of exposure, and the proliferation of high-throughput assay data rather than the traditional animal studies. We discuss the policy implications of these issues using specific examples from our research program. Finally, we identify and propose methodological strategies to support environmental decision making in the face of increased scientific complexity.