Panel Paper: Mixture Toxicity and Cumulative Risk at the United States Environmental Protection Agency, 1980-2016: Why Was so Little Done When so Much Was Known?

Saturday, November 10, 2018
Taylor - Mezz Level (Marriott Wardman Park)

*Names in bold indicate Presenter

Robert Hunt Sprinkle and Devon C. Payne-Sturges, University of Maryland

Background. The United States Environmental Protection Agency (EPA) began considering toxicant mixtures in 1980 but never developed a coherent strategy either to protect against them or to communicate to the public the risks posed by them. Environmental toxicants have traditionally been assessed and regulated as single chemicals. Their mixing, while inevitable, was long ignored by toxicologists and, in the United States, is still considered only rarely by legislators and regulators. Yet toxicants in doses once thought harmlessly low can act individually, cumulatively, or synergistically to harm life forms, including humans, notably affecting reproductive and neurological function. Moreover, biocide formulations regulated only according to their “declared active principal” components may owe much of their lethality to their nominally “inert” components.

Question. Why was so little done when so much was known?

Methods. We reviewed the environmental mixture-toxicity and cumulative-risk literatures in MEDLINE (; we examined the EPA’s publications and related holdings of the National Archives and Records Administration and internal industry documents released fortuitously through court order; and we queried living memories in semi-structured interviews.

Findings. The EPA was reluctant to move beyond the techniques of laboratory toxicology or to consider mixtures beyond the additivity of two, or perhaps several, similar toxicants. Defense of these analytical preferences — additivity and similarity — invited an industry suggestion, which the EPA did not reject, that biocide formulations, having many components dissimilar one-from-another, should not be considered mixtures. Subsequently, mixture-toxicity efforts were largely subsumed under a cumulative-risk initiative notable for the inconsistency of its methods.

Conclusion. Fearing regulatory futility and industry displeasure, the EPA, over the years examined, consistently declined either to lead its field or to educate the public and seems never to have contemplated a transition to “closed-loop” industrial-ecological standards.