Testing: Advance Notice of Public Rulemaking
August 1, 2003
and Records Integrity Branch
Re: Human Pesticide Testing, Docket ID OPP-2003-0132
Beyond Pesticides appreciates the opportunity to comment on the EPA's rulemaking on criteria and standards that would be applied in deciding the extent to which EPA will consider or rely on various types of research with human subjects to support its actions. By allowing the citizens to participate in the rulemaking process by soliciting public comments and suggestions, EPA is acknowledging the critical role public dialogue plays in the promulgation of sound public policy. We are grateful to have a chance to voice our concerns. These comments are intended to supplement the comments being submitted by the Farmworker Justice Fund (see FJF comments) and the Children's Environmental Health Network (see CEHN comments), which we have joined.
Agreeing to accept data collected from clinical trials using human subjects will cause a dramatic increase in human testing endeavors by chemical companies aiming to avoid additional regulations set forth in the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Food Quality Protection Act (FQPA). These regulations were designed to limit their pesticides' use because of the toxicity of the agent and possible threats they pose to human and environmental health. Beyond Pesticides is committed to pesticide safety and the adoption of alternative pest management strategies which reduce or eliminate a dependency on toxic chemicals. We believe that EPA's consideration of data collected from human subjects in pesticide trials poses serious threats to public health. We also question the scientific ethics involved in such testing. In addition, the no observed adverse effects level (NOAEL) and the subsequent series of numerical safety (or uncertainty) factors that are applied to a NOAEL in arriving at the reference dose, or RfD, is jeopardized by pesticide companies that seek to show that uncertainty factors are either too high or unnecessary. Beyond Pesticides recognizes that pesticide manufacturers would have strong economic incentives to conduct human subject studies in order to get acceptable limits of their pesticides raised and therefore be able to sell and spray more of their product.
What follows is a detailed analysis of the adverse effects of EPA considering human subject tests when reviewing pesticides for their possible toxic effects on average people, children, and other vulnerable and chemically sensitive members of the population. Specifically, Beyond Pesticides worries that regulations set forth by the Federal Policy for the Protection of Human Subjects or the "Common Rule," will be threatened or ignored. In addition to concern over the Common Rule, ethical concerns, problems relating to sample size in studies, and scientific validity of the studies in general, also arise when contemplating the consequences of moving towards a policy more accepting of this type of study.
Federal Policy for the Protection of Human Subjects ("Common Rule")
For research involving human subjects, a large majority of federal agencies simultaneously published a regulation or "Common Rule" on June 18, 1991 to regulate the conduct or support of those studies. According to the Department of Health and Human Services, National Institutes of Health, Office for Protection from Research Risks, this policy "includes research conducted by Federal civilian employees or military personnel, except that each Department or Agency head may adopt such procedural modifications as may be appropriate from an administrative standpoint. It also includes research conducted, supported, or otherwise subject to regulation by the Federal Government outside the United States."
Because local research facilities and organizations are responsible for making sure the obligations of the Common Rule are met, human test subjects are at the will of the researchers performing the studies and the institutional review boards (IRB) reviewing the practices. The Department of Energy's Advisory Committee on Human Radiation Experiments states that "the ability of the Common Rule to protect the rights and interests of human subjects is, however, at least partially dependent on how the departments and agencies to which the Common Rule applies implement and oversee its provisions." The inability of EPA to oversee the implementation of Common Rule practices by researchers means that the rights and safety of the test subjects are not guaranteed. By accepting these studies with no way to ensure Common Rule practices, EPA is in effect allowing chemical companies interested in contracting out these studies leeway to endanger and mislead the subjects used to test their toxic pesticides.
The Ethics of Human Testing
The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research points out that three basic ethical principles need to be kept in mind when considering using humans as test subjects: respect for persons, beneficence, and justice. Human-based research in order to alter pesticide tolerance levels mandated by EPA, and subsequently increase profits for the pesticide companies sponsoring the studies does not qualify as an ethical endeavor. This position is strengthened by the fact that EPA does not generally review efficacy data on pesticides, many of which are not necessary or cost-effective in achieving pest management goals. Since EPA, as a matter of policy, allows the marketplace to define product benefit, the agency has no way of knowing whether pesticide products achieve anything other than sales for the registrants. Ethical scientific studies are those whose results are meant for the betterment of society and the test subjects. In her January 8, 2003 remarks to the Committee on the Use of Third Party Toxicity Research with Human Research Participants, Vera Hassner Sharav, the president of the Alliance for Human Research Protection (AHRP), testified that "pesticide experiments in human beings are morally unconscionable and scientifically dubious-they fail to meet fundamental standards of permissible research-as they offer no potential therapeutic benefit to the subjects or society."
Codes of medical ethics were specifically designed to prevent potentially harmful experiments from being performed on humans. The Nuremberg Code reaffirmed the Hippocratic maxim "do no harm," but one questions the intentions of chemical companies lobbying for these testing reforms. Studies using humans as test subjects "do harm" by the nature of the tests. Pesticides are proven poisons used to kill insects, plants diseases, weeds, rodents, and germs, and administering these toxic materials to people, as part of a controlled experiment, is a practice that can only do harm to the test subjects involved. Regardless of the results, these scientists are dosing participants with highly toxic chemicals; there are no possible health benefits to the human test subjects from being exposed to specifically designed poisons. EPA does not even evaluate whether a pesticide registration contributes to increased food production, lower food costs, better nutrition or any other socially valuable result. The agency does not evaluate whether there is a less toxic method to achieve the same pest management goal.
Human subjects for pesticide testing are not being treated in an ethical manner because they are not being protected from harm. Their well-being is being jeopardized so chemical companies can profit. Beyond Pesticides also worries about the pressures a particular subject might feel to be involved in a study. We recognize the right to self-determination and realize people are free to make their own decisions; however, circumstances exist that severely restrict a person's liberty and ability to evaluate risks and rewards in an objective fashion. People in dire economic situations might be more willing to put themselves at risk for a certain amount of financial compensation. These people risk exploitation if EPA accepts human testing data for pesticides.
Problems Relating to Sample Size
Thorough scientific inquiry involves sample sizes large enough to represent a cross-section of the people being impacted by the results of the study. If a study is seeking to provide data to policy makers that will eventually make a decision that affects all United States citizens, one would hope that either the subjects in the study represent a subset of the U.S. population, or additional safety precautions are taken when applying that information to the general population. The current human subject test data that has been submitted to EPA do not give results that can be realistically applied to the entire nation because of the sample sizes.
Human studies typically have extremely small sample sizes. This fact alone would be a solid argument to keep the 10-fold safety factor applied to animal-based test results. The Environmental Working Group's report, The English Patients: Human Experiments and Pesticide Policy, tells of recently submitted studies to EPA on dichlorvos that involved only six exposed adult makes and three controls. The report states, "in effect, the regulatory assumption presumes that each of the six individuals in the study accurately represents the genetic and biological diversity of 44 million individuals in the U.S. population. EPA has also based its decision to allow the use of Dursban after reviewing a 25-year old study that used 12 adult males and four adult male controls as their subjects. The 12 men exposed to the pesticide were also employees of Dow Chemical."
The case of Bruce Turnbull of Edinburgh, Scotland, illustrates the point that using humans for subjects in testing pesticides is a strategy to undermine FQPA and raise the maximum acceptable levels of pesticides allowed to show up in food. Chemical companies are clearly putting their profit hopes above the safety of the test subjects. According to a September 2002 article in Scotland's Sunday Herald, in 1998, Mr. Turnbull volunteered to participate in a "drug" trial at Inveresk Research laboratories in East Lothian, Scotland, where he was paid £700 ($1,157.03) to ingest a single dose of azinphos-methyl (AM). The 50 participants in the study were each given one dose and then observed for seven days.
Mr. Turnbull and the other subjects were neither informed that the chemical they were ingesting was deemed "highly hazardous" by the World Health Organization nor that the study that they were participating in was actually funded by the chemical company, Bayer, in an effort to undermine the recent passing of a protective policy by EPA. The subjects in the test were never called in for subsequent follow-up visits to test for long-term effects and after the seven-day observation period, Bayer claimed that AM had no effect on humans. This is the key to their case to raise allowable limits on this pesticide's exposure level for use by farmers in the U.S.
The article continues that "Turnbull, now 51 and suffering ill-health he believes is connected to the test, says he feels bitter and cheated. 'I was under the impression I would be helping farmers, not helping a major company sell more pesticide that would end up on food. I don't think I was told who was paying for the test.'" Mr. Turnbull's case is an example of how human test subjects can be taken advantage of and exploited. He was clearly not fully informed of all the risks involved in the study. Bayer contracted this trial in order to have evidence to back up its claim to EPA that AM was safe to use by farmers. If studies where humans are used as test subjects are not deemed acceptable by EPA for use when making regulations regarding pesticides, this type of incident would not occur. If a straight forward policy is stated by EPA and companies are clear that human test results will not be considered when reviewing the health effects of pesticides, there will be no financial incentive to design and execute such experiments.
After summarizing how dozens of college-aged youths from Nebraska answered a school-newspaper advertisement urging students to "earn extra money," a 2002 Time Magazine article affirms, "chemical companies like Dow [AgroSciences] got into the [clinical trial] business after Congress passed the 1996 Food Quality Protection Act, which tightened safety standards on thousands of pesticides. The manufacturers responded by unleashing a flurry of small, short-term clinical trials aimed at persuading the Environmental Protection Agency to relax the rules that govern exposure to toxic chemicals." These students were ill-informed participants in a study where they ingested a known poison. This is certainly not a true scientific investigation and it would not be in the public's best interest for EPA to review data from studies like the ones mentioned above.
Scientists and Physicians Question Legitimacy of Human Testing
A number of prominent physicians and scientists have publicly denounced the idea of humans being used as subject for pesticide tests and EPA accepting data from such tests. These distinguished members of the scientific and public health community disagree with human pesticide testing for a variety of reasons, but they all agree that this is a dangerous step in the wrong direction for people's safety.
Philip J. Landrigan, M.D., a pediatrician at Mount Sinai School of Medicine and director of the Mount Sinai Center for Children's Health and the Environment, told a Reuters reporter that he believes the chemical companies are conducting human pesticide testing in order to collect data that would justify more relaxed pesticide standards and allow the application of higher amounts of pesticides to our food and homes. Dr. Landrigan worries that testing pesticides in humans involves an attempt by pesticides makers to avoid the child protective safety factor when setting standards for maximum allowable use. These tests, he added, can only be deemed ethically acceptable if they offer the promise of some benefit to the individual involved in the study or society at large.
Lynn R. Goldman, M.D., a professor of public health at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, who was assistant administrator in the EPA's Office of Prevention, Pesticides and Toxic Substances during the Clinton administration, told the same Reuters reporter that regulatory approval of a pesticide can be worth hundreds of millions of dollars in profits for the chemical company who manufactures it. She implied that this huge incentive encourages companies to do human testing studies.
Herbert L. Needleman, M.D., a professor of pediatrics at the University of Pittsburgh in Pennsylvania, voiced his concern about human testing at a recent New York Academy of Sciences meeting when he mentioned that most of the human pesticide studies he had seen included sample sizes of fewer than 20 subjects. Tests used in drug trials to establish safe levels of exposure require the use of thousands of people. Drug trials also have the possible outcome of benefiting the participants, whereas pesticides offer no health benefits to human participants in testing studies.
Safety Comes Second
An EPA decision to accept trial data with humans as test subjects would unleash an unprecedented amount of chemical experimentation on people. Besides the ethical and scientific flaws that have been cited above, it is important to keep the motivations of the chemical companies lobbying for this decision in mind. Human pesticide testing provides no benefits to the health of the test subjects or the public at large; it only benefits pesticide makers looking to expand their market.
Thank you for your consideration of our comments.
Edward J. Lubarsky