The Environmental Protection Agency (EPA) is the most important U.S. federal agency for the regulation of toxic chemicals. Formed in 1970, EPA is involved in both research and regulation. It is also responsible for the formulation of regulations authorized by several major legislative acts (as briefly discussed in Lecture 1), and the enforcement of those acts.

EPA has exercised important influence over the design and conduct of toxicologic studies, especially those used in the health risk assessment (RA). EPA is empowered by the Toxic Substances Control Act to promulgate standards for different types of toxicologic (and other scientific) investigations. The Federal Insecticide, Fungicide, and Rodenticide Act also requires EPA to weigh all the adverse and economic effects of a pesticide in determining the terms and specifics on which to permit registration.

Under the Food Quality Protection Act of 1996, EPA and FDA are mandated to consider aggregate exposure to pesticide from all sources, not simply from dietary intake or any single path of exposure. In response to the request for an increased stringency of its requirements for neurotoxic and behavioral testing, EPA has since published additional testing data requirements for 160 active ingredients. EPA is now making an effort to consider cumulative exposure to multiple pesticides that have a common mechanism (mode) of toxicity. Organophosphorus insecticides (e.g., chlorpyrifos, diazinon, and malathion) are all capable of exerting similar neurotoxic effects (e.g., ataxia, tremor, death) by inhibition of the enzyme acetylcholinesterase in the human body.