The U.S. Environmental Protection Agency (EPA) is currently conducting separate Toxic Substances Control Act (TSCA) risk evaluations for seven phthalates: dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), di-(2-ethylhexyl) phthalate (DEHP), diisobutyl phthalate (DIBP), dicyclohexyl phthalate (DCHP), di-isodecyl phthalate (DIDP), and diisononyl phthalate (DINP). Phthalates are highly abundant plastic additives used primarily to soften materials and make them flexible, and biomonitoring shows widespread human exposure to a mixture of phthalates. Evidence supports biological additivity of phthalate mixture exposures, including the enhancement of toxicity affecting common biological targets. Risk estimates based on individual phthalate exposure may not be protective of public health. Thus, a cumulative risk approach is warranted. While EPA initially did not signal that it would incorporate cumulative risk assessment (CRA) as part of its current risk evaluation for the seven phthalates, the agency recently announced that it is reconsidering if CRA for phthalates would be appropriate. Based on our review of existing chemical mixtures risk assessment guidance, current TSCA scoping documents for the seven phthalates, and pertinent peer-reviewed literature, we delineate a CRA approach that EPA can easily implement for phthalates. The strategy for using CRA to inform TSCA risk evaluation for existing chemicals is based upon integrative physiology and a common adverse health outcome algorithm for identifying and grouping relevant nonchemical and chemical stressors. We recommend adjustments for how hazard indices (HIs) or margins of exposure (MOEs) based on CRA are interpreted for determining “unreasonable risk” under TSCA.
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