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Toxic chemicals — “toxicants” — have been studied and regulated as single entities, and, carcinogens aside, almost all toxicants, single or mixed and however altered, have been thought harmless in very low doses or very weak concentrations. Yet much work in recent decades has shown that toxicants can injure wildlife, laboratory animals, and humans following exposures previously expected to be harmless. Additional work has shown that toxicants can act not only individually and cumulatively but also collectively and even synergistically and that they affect disadvantaged communities inordinately — and therefore, as argued by reformers, unjustly. As late as December 2016, the last full month before the inauguration of a president promising to rescind major environmental regulations, the United States federal environmental-health establishment, as led by the Environmental Protection Agency (EPA), had not developed coherent strategies to mitigate such risks, to alert the public to their plausibility, or to advise leadership in government and industry about their implications. To understand why, we examined archival materials, reviewed online databases, read internal industry communications, and interviewed experts. We confirmed that external constraints, statutory and judicial, had been in place prior to EPA’s earliest interest in mixture toxicity, but we found no overt effort, certainly no successful effort, to loosen those constraints. We also found internal constraints: concerns that fully committing to the study of complex mixtures involving numerous toxicants would lead to methodological drift within the toxicological community and that trying to act on insights from such study could lead only to regulatory futility. Interaction of these constraints, external and internal, shielded the EPA by circumscribing its responsibilities and by impeding movement toward paradigmatic adjustment, but it also perpetuated scientifically dubious policies, such as those limiting the evaluation of commercial chemical formulations, including pesticide formulations, to only those ingredients said by their manufacturers to be active. In this context, regulators’ disregard of synergism contrasted irreconcilably with biocide manufacturers’ understanding that synergism enhanced lethality and patentability. In the end, an effective national response to mixture toxicity, cumulative risk, and environmental injustice did not emerge. In parallel, though, the National Institute of Environmental Health Sciences, which was less constrained, pursued with scientific investigation what the EPA had not pursued with regulatory action.

Mixture toxicity, cumulative risk, and environmental justice in United States federal policy, 1980–2016