Testing Pesticides on Humans

Pesticide companies pay volunteers to swallow and inhale the neurotoxins they make. What's wrong with this picture?

By Karen Wright|Wednesday, December 03, 2003
RELATED TAGS: HEALTH POLICY, POLLUTION

‘The dose makes the poison,” said 16th-century Swiss physician Paracelsus, and the modern approach to pesticides proves it. Chemicals for killing bugs and weeds are considered safe at low doses—so safe they have become a fixture of daily life. We eat pesticides on produce, drink them in groundwater, inhale them from flea collars, sprinkle them on lawns, and even spray them on our skin. Yet at high levels they are unquestionably dangerous. So at what dose do they become poisons?  Toxicologists and government regulators have long relied on laboratory tests with rats and other animals to answer that question. The shortcomings of such tests are obvious: The results may not apply to people. But the alternative is to test pesticides directly on humans. And that’s just what pesticide manufacturers are doing. Over the past decade manufacturers have submitted to the Environmental Protection Agency results from more than a dozen experiments in which human subjects have deliberately swallowed or inhaled pesticides or absorbed them through the skin. Last year an industry group sued the agency to force it to consider data from those tests in evaluating pesticide risks. The tests involve anywhere from a single slug to four weeks of daily dosing. Volunteers are paid as much as $200 a day, and their blood and urine are screened for pesticide metabolites and physiological markers that may reveal the chemicals’ action in the body.

Public-health advocates maintain that pesticide manufacturers have turned to human tests in an attempt to get around new rules limiting the use of pesticides. “They assume that most of the time [a human test] is going to work out in their favor, and if it doesn’t, they can stop the study,” says Richard Wiles, a senior vice president of the Environmental Working Group in Washington, D.C., which has challenged the ethics of human testing.

“We have an obligation to understand the potential health effects in people,” counters Ray McAllister, a vice president of CropLife America, also in Washington, D.C., which lobbies for the agrochemical industry. “Without these human studies, you don’t know what you should be looking for in terms of metabolites.”

No law prohibits testing pesticides on people, and no policy guides agency action with regard to tests conducted with private funding, either. The EPA normally establishes so-called tolerances—the amount of pesticide residue in produce, grains, and processed food that is considered tolerable—in a three-step process based on animal tests paid for and conducted by the manufacturers themselves. First the agency defines the highest daily dose that does not seem to affect the most sensitive species of animal studied. The agency then lowers that dosage by a factor of 10 to account for possible variations in response between the most sensitive test animal and humans. Then that figure is reduced by another factor of 10—to 1/100 the original dose—to accommodate the potential for differing responses among people. Tolerances can be adjusted if new data warrant a review—if, for example, field workers inadvertently exposed to pesticides become ill.

 The Food Quality Protection Act of 1996 toughened standards for pesticide exposure in light of evidence that children are sometimes more vulnerable than adults to environmental contaminants. Among its provisions, the act requires the EPA to reduce by an additional factor of 10 the amount of pesticide residue in food. The legislation also requires the agency to evaluate the cumulative risk posed by entire classes of chemicals that share the same mechanism of action instead of evaluating each compound independently. The EPA has been instructed to draw up new limits for hundreds of pesticide ingredients already in use.

The explicit intent of the legislation is to lower the average person’s exposure to pesticides. But an advisory panel convened by the EPA cautioned that the law may have unintended consequences. “When human data have been available and used, it has generally raised the ‘safe dose,’” the panel reported in 2000. “A higher ‘safe dose’ allows greater use of a pesticide. Thus, the [Food Quality Protection Act] may have inadvertently created an incentive to test pesticides in humans.”

Many of the tests under consideration use compounds called organophosphates, which are at the top of the EPA’s list of concerns because they are among the most toxic and widespread pesticides. In the United States, organophosphates are applied to 60 million acres of crops like corn and cotton every year. They are neurotoxins: They poison the nervous system of both insects and humans by disabling an enzyme called cholinesterase that helps regulate signals between nerve cells. First discovered in the 19th century, they were later developed as insecticides and nerve-gas agents in Germany in the 1920s. Nonlethal overdoses of organophosphates can cause headaches, sweating, blurred vision, twitching, abdominal cramps, and in severe cases, paralysis and difficulty breathing. Recent human studies monitor levels of cholinesterase in the blood rather than overt signs of illness. Even so, the ethics of such tests are dubious. Clinical trials of new pharmaceuticals are sanctioned by government and society alike because there may be some benefit to the individuals involved in such a study: protection from disease or relief of an illness—if not for themselves, then for a loved one.

“Where’s the benefit from pesticides?” says Christopher Portier, a biostatistician at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. “The individual benefit of having pesticides in society is really hard to pin down.”

Manufacturers contend that a more refined understanding of the chemicals’ hazards to humans can benefit both individuals and society. “Like it or not, pesticide use is an integral part of our food production and public-health programs,” said Monty Eberhart, director of product safety management at Bayer CropScience, in a presentation to a panel from the National Academy of Sciences this past January. “The fact is that pesticides are used and people are exposed. The people that are participating in these studies have much more of a direct benefit than anybody participating in a phase I clinical trial would have.”

But critics are also worried by the science behind human pesticide tests. Unlike drug trials, the procedures for testing pesticides on people are neither specified nor reviewed by scientists outside the company doing the testing. Many of the experiments involve so few subjects—as few as six in a test of the organophosphate chlorpyrifos—that the results can’t be trusted. There isn’t even agreement that blood levels of cholinesterase should be used as a proxy for damage to the central nervous system, Portier says. “If [the testing] is ethical, but you do it wrong, it’s still not ethical.”

Top Five Pesticides Found in Food*

• 23% DDT (organochlorine) First used as an insecticide in 1939. Once the most commonly used pesticide. Banned in 1972 in the United States because it persists in the environment. Still used abroad (.0001–.031 parts per million found in the samples).

• 20% Chlorpyrifos-methyl (organophosphate) Used on stored grain since 1985. Most applications have been voluntarily canceled. Moderately persistent in the soil (.0001–.537 ppm).

• 18% Endosulfan (organochlorine) Introduced in 1954. Recently limited to agricultural and commercial uses. Moderately persistent in the soil (.0001–.266ppm).

• 16% Malathion (organophosphate) One of the earliest organophosphates—introduced in 1950. Low persistence in the soil (.0007–.080 ppm).

• 15% Dieldrin (organochlorine) Second only to DDT in use between 1950 and 1970. Banned in the United States for crop use in 1974 (.0001–.020 ppm).

*Fourteen other pesticides were found in more than 2 percent, but less than 8 percent, of all foods sampled. See the Total Diet Study for details: www.cfsan.fda.gov/˜dms/pes01rep.html#tdsresults.

“The motivation of people doing the research matters,” adds Jeffrey Kahn, a bioethicist at the University of Minnesota in Minneapolis and a member of the EPA advisory panel. “To ignore that is to ignore a big part of whether you think something is ethical or not.” Doing tests on human subjects for the purpose of circumventing legislation or enhancing profits doesn’t pass muster, he says. “I think under very few circumstances is it ethical to take healthy people and dose them with poison.”

Industry representatives argue that the ethical and scientific procedures they currently use for human pesticide tests are no different from those employed in clinical trials of drugs. “There is no sort of lower standard or different standard used for pesticide products,” says Angus Cameron, a former manager of the firm Inveresk Research International in Scotland, where many of the human tests have been conducted. The companies maintain that the EPA has in the past reviewed test protocols and accepted their results in evaluating risk. They also say there has been no significant increase in the number of human tests carried out since the food quality act was passed.

The EPA panel tried to stake out a middle ground. It named circumstances under which human testing would be ethical: if information on health risks is not available by any other means, and it could “promise reasonable health benefits to the individual or society at large.” At the same time, the panel insisted that children should “in no case” be part of such studies.

Two panel members lambasted the contradictions in this stance. “If children are different, then what information can adult dosing provide that is of use to set standards for protecting children?” wrote pediatricians Herb Needleman of the University of Pittsburgh School of Medicine and Routt Reigart of the Medical University of South Carolina in Charleston in a minority report.

Unable to build a consensus, the EPA last year asked the National Academy of Sciences to conduct an 18-month review of the issue. The academy’s report is due this month. Among other things, it could help the EPA devise strict standards for human pesticide tests as well as measures for auditing them.

In the meantime, we’re all research subjects in the great pesticide experiment. Every apple we eat, every stroll through the park ratchets up our cumulative load of neurotoxins. An ongoing study of thousands of Americans by the Centers for Disease Control and Prevention found organophosphate metabolites in the urine of the majority of survey participants—evidence they had been exposed to the pesticides within days of testing. Concentrations in children ages 6 to 11 were often twice as high as in adults.

 “Whether organophosphate pesticides at the levels of the metabolites reported here are a cause for health concern is not known,” the study cautions. “More research is needed.”

Pesticides in Food

Each year the Food and Drug Administration goes shopping for their Total Diet Study, a survey of pesticides and other contaminants in the food Americans eat. The FDA staff buys 250-plus kinds of food in three cities located in each of the country’s four geographic regions. After preparing the food, the agency screens it for traces of contaminants. The screen, which is far more sensitive than methods used in other programs monitoring pesticide use on foodstuffs, quantifies traces present in parts per million; an equivalent ratio is one gram (.035 ounce) per 1.1 tons of food.

Year after year the Total Diet Study finds that the same five chemicals top the list of pesticides most frequently found in the sampled foods. Two of the five, DDT and dieldrin, are organochlorines that have been banned in the United States for more than 25 years. Their perennial appearance indicates their persistence in the soil here or their continued use on crops imported from other countries. A third organochlorine on the list, endosulfan, is still used in the United States. The remaining two pesticides are the organophosphates chlorpyrifos-methyl and malathion. Since 1996 the EPA has put partial bans on the use of 28 of the 49 organophosphates registered with the agency. And in 2001 the agency began a separate study to track the amount of organophosphates in domestically grown fruits and vegetables that play a large role in children’s diets. The good news is that the number of new pesticides with safer—and less biologically durable—active ingredients has risen sharply over the past 15 years.

Sarah Richardson

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