The New EPA Regulations for Protecting Human Subjects: Haste Makes Waste

The Environmental Protection Agency's new regulations for research on human subjects, adopted February 6, 2006, and effective on April 7, 2006, mark the culmination of a vociferous, eight-year debate between environmental and industry groups concerning pesticide testing on human subjects. Unfortunately, despite the eight years of struggle, the EPA's decision-making was rushed at key points; the battle never moved beyond shouting to careful, deliberative attention, and the policy that came out of it will ill serve the EPA's goals. The storm began in 1998 with the publication of a report titled "The English Patients" by the Environmental Working Group, which described privately funded studies on the effects of intentionally exposing human subjects to pesticides. (1) Pesticide companies were sponsoring the studies in response to the Food Quality Protection Act (FQPA), which Congress had passed in 1996. Prior to 1996, the EPA determined the allowable human exposure to pesticides found on foods by performing a simple mathematical calculation on the "no observable ad verse effect level" (NOAEL), which applies to rodents and is established by research. First, the EPA divided the NOAEL by a "safety factor" of ten, which it called the "rodent-human safety factor," so that the average human would get only one-tenth the exposure to pesticides that rodents can tolerate. Then it divided this result by ten again--a "human variation safety factor"--on the theory that some humans might be much more sensitive to pesticides than others, so that the actual human exposure would be only one-tenth that which the average human should be able to tolerate. The FQPA then required the EPA to divide this result by ten once more--the "adult-child safety factor"--to provide yet another layer of protection for children. Ultimately, then, the allowable human exposure would be one-one thousandth of the level that had been shown not to have any observable effects in rodents. The pesticide companies planned to submit their data on human pesticide exposure to the EPA as part of an effort to avoid the more stringent restrictions imposed by the FQPA. (2) The Environmental Working Group argued, however, that the studies were scientifically and ethically flawed and that the EPA should not accept the data. At that time, the EPA did not have any detailed regulations concerning human research conducted by private companies. Instead, it had a policy that human exposure experiments conducted by third parties would be evaluated on a case-by-case basis, by applying the federal Common Rule (45 CFR 46) and other statutory and ethical requirements. The agency had already adopted the Common Rule for EPA (first party) research and EPA-sponsored (second party) research, but had not formally adopted it for third party research (that is, research conducted by private companies). The EPA decided that it would not accept the data. (3) The EPA's decision angered pesticide companies, which wanted the EPA to accept human exposure data. In 2001, the EPA decided to ask the National Research Council to study these issues, and it announced that it would not consider data from third party human exposure studies until the NRC submitted its report. Several organizations representing the agricultural industry then sued the EPA, claiming that by refusing to accept third party data, the EPA had engaged in unlawful rule-making because it had not issued an official public notice, with a public comment period, concerning its decision. A federal court sided with the plaintiffs and ordered the EPA to engage in appropriate rule-making. (4) In 2003, the EPA gave public notice of a proposed regulation that would be, in effect, a return to its previous case-by-case policy. This announcement infuriated environmental groups, which regarded the case-by-case policy as unethical. In 2004, after holding a series of open meetings and soliciting opinions from both sides of the controversy, the NRC issued a report in which it recommended that some types of third party intentional exposure studies could be conducted, provided that they meet strict scientific and ethical standards. …