Lab Rats (Web-only Feature)

Most people agree that children should never be exposed to pesticides, yet millions are every day. Think of the herbicides and pesticides sprayed on school grounds and public parks; mosquito repellent in children’s sunscreens; food with pesticide residues; parents’ contaminated clothing or breast milk; and fumes that waft invisibly from neighbors’ yards or the farm down the road. In some cases, researchers have even considered deliberately exposing children to these chemicals to assess their toxicity.

It sounds abhorrent, but consider this: If nobody is allowed to study the effects of pesticide exposure in humans—especially tiny ones who are more vulnerable than adults—how can regulators decide which pesticides to allow, restrict, or ban outright? “If you don’t have the information proving a chemical is harmful and that people are being exposed, it can’t be regulated,” explains Robin Whyatt, deputy director of the Columbia Center for Children’s Environmental Health. “In this country—unlike in Europe, where manufacturers have to prove a new chemical is safe—you have to prove something is a hazard if you want to regulate or restrict it.”

Kids stand squarely at the center of the pesticide testing controversy. Since 1996, the way the Environmental Protection Agency has calculated thresholds for pesticide exposure has involved a safety “factor of ten,” taking into account children’s special vulnerability to many chemicals (see sidebar). But if manufacturers can show that their chemical has no added effects on children, they can pressure officials to lower the safety threshold. “The chemical companies would like to be able to say that, for example, maybe a factor of three is acceptable,” Whyatt says.

Testing toxins on people is an ethical dilemma that American regulators have struggled with for years. Since 1991, all research conducted by federal agencies, including the EPA, has been governed by the Common Rule, a policy designed to minimize risk to human subjects and ensure their informed consent. The Common Rule has its roots in 1947’s Nuremberg Code, developed after World War II, as a reaction to Nazi experimentation on prisoners. In 2009 the EPA accepted some modifications to the Common Rule to allow the results of experiments previously conducted on human subjects—experiments that would not be allowed under the EPA’s rules today—to be considered when assessing the toxicity of certain pesticides. These guidelines allow for case-by-case decisions, which the EPA’s critics say is too vague a standard.

EPA watchers worry that pesticide makers will try to use the ongoing confusion about human testing to get dangerous chemicals approved based on flimsy, older studies. On the flip side, other researchers worry that important research on pesticide exposure will be disallowed for ethical reasons, making it easier for companies to keep dangerous chemicals on the market. For chemical companies, a lot is at stake: Failure to be recertified by the EPA for use in agribusiness or households would mean big losses. Many common chemicals—including the insecticide aldicarb and the herbicide paraquat dichloride—are slated for review or re-review. With a new EPA administration in town, both sides will press the agency for an advantage.

Disturbing questions, little consensus

There is little consensus on many of the key issues surrounding childhood pesticide exposure: How far should the EPA allow researchers to go to better understand the chemicals that have become part of modern life? Do the EPA’s rules on the type of studies it will accept actually protect children? Are pesticide companies using loopholes in the rules to do an end-run around safety factors that provide an extra margin of protection for children, as well as for vulnerable adults, such as those with asthma or allergies?

“There’s a central tension to human studies that’s always there and won’t ever totally go away,” says Whyatt, who has done groundbreaking observational health studies that document childhood and fetal pesticide exposure. “You always have to protect the interests of the people involved, but at the same time, we need to understand exposure and the effects of exposure if we’re going to protect people’s health,” she says. “Sometimes people even have to stop a study because it becomes clear that the potential risk is too great.”

Stopping a study—two studies, actually—is exactly what the EPA did last fall, when the agency “cancelled until further notice” funding for two studies on infants and children. Most of the information regarding the studies, one to understand the pesticide exposure of infants and toddlers in Las Vegas, another involving school-age children, was wiped from the agency’s Web site. In its place was an announcement—meant to calm—that “to ensure the utmost confidence in the conduct of the [studies],” the two had been cancelled until after the EPA’s policies on pesticide testing on children could be finalized.

Some researchers, like Whyatt, say they were surprised that the studies were cancelled; rather than exposing the children to new chemicals, they would have documented the quantity and types of pesticides that they were already encountering in their everyday lives. But perhaps the EPA was being cautious because outrage over studies involving kids and pesticide had previously landed the agency in hot water. The worst testing-related dispute, hands down, was dubbed CHEERS, for Children’s Environmental Exposure Research Study. It would have provided camcorders and small monetary incentives to parents in impoverished Duval County, Florida, to spray measured amounts of pesticides into their kids’ rooms. When proposed in 2004, the CHEERS study provoked Senate hearings and an announcement by several senators that they would block the nomination of Stephen Johnson to head the EPA unless the study was canceled, which it eventually was. The incident made the agency reluctant to revisit the subject of human testing. That’s why, many observers say, the EPA’s guidelines continue to be murky, a situation likely to lead to more pesticide exposure, not less.

Two very different types of studies

Much of the current controversy focuses on how the EPA handles two different types of studies. The first category involves intentionally exposing subjects to toxins: In 2006, the EPA announced that it would no longer fund, or accept the results of, new intentional dosing research in its regulatory work. The battle over these studies now focuses on whether the EPA should accept results from studies begun before 2006.

Allowing use of that data on a case-by-case basis is too big a loophole, argues Jeff Ruch, executive director of Public Employees for Environmental Responsibility: “EPA can use any human dosing study conducted before the new rule’s effective date on a case-by-case basis, applying the ethical norms prevalent at the time. Since, prior to the rule, EPA recognized no ethical standards at all, this means that all previous human studies can come in through EPA’s wide-open door.”

Some bioethicists believe that the EPA should be cautious about dosing studies. “You can only do [these types of studies] if there is no permanent damage and you serve a really important social purpose, such as better regulation of public health,” says David Resnik, a bioethicist at the National Institutes of Health. “That’s a problem when pesticide companies do these studies. It’s hard for them to argue that they’ll be improving public health.” Still, Resnik doesn’t rule out the possibility that such research might generate positive outcomes. “You might improve public safety if you find out that the existing rules aren’t strict enough,” he says.

A second kind of testing is less controversial: observational studies document pesticides’ effects on people who are already exposed to them in their daily lives. However, even these studies can raise ethical issues. “We still have a duty to let these families know if they’re being exposed to something dangerous,” argues Robert Gould, a San Jose doctor and president of the San Francisco chapter of Physicians for Social Responsibility. “Even if we’re just watching something that is already happening, we need to protect these children.”

Furthermore, he says, there’s an efficacy question: long-term effects often turn up many years after a drug or pesticide has been approved based on short-term studies. “The problem is that a lot of effects only show up many years after a child has been exposed, sometimes even a generation later, when the child grows up and has children,” Gould says. “We just don’t know many of the long-term effects upon these children, so to allow them to be exposed seems unethical. We should do everything we can to stop their exposure.”

But in the US, where the burden of proof is on the permitting agency rather than the chemical company, some researchers say that observational studies are the best hope for protecting the millions of children—and their adult family members—who cannot get away from pesticide exposure. “The real tragedy is that if good studies don’t get done, there’s not going to be any data to stop harmful pesticides,” says Columbia University’s Whyatt.

Ironically, she says, not accepting well-designed, tightly monitored observational studies could backfire, resulting in more childhood chemical exposure. “It’s actually in Dow Chemical’s interest to have such requests for applications killed, because that would mean there would be no regulation of these chemicals at all,” says Whyatt.

Margaret Reeves, senior scientist at the Pesticide Action Network, agrees. “Lots of people live with exposure every day,” says Reeves. “That’s why we absolutely need well-designed observational studies that tell people the risks of their exposure, and the good ones are wonderful. They generate the data to make the arguments to push for better rules.”

Sometimes, Reeves says, observational data provides scientific arguments about whether to regulate or ban a pesticide—and generates an emotional response among the regulators. “Pesticide companies are really fighting tooth and nail to keep chlorpyrifos,” she says, an insecticide that has been linked to delays in children’s cognitive development, Attention-deficit/Hyperactivity Disorder (ADHD), low birthweight in babies exposed to the chemical prenatally, and possibly to an increase in cancer risk. “EPA scientists have told us that what really moved them was when three women who had been pregnant talked about how much of the pesticide was in their bodies,” Reeves says. “They wouldn’t have had that information if there hadn’t been good observational studies.” As a result, she says, the EPA banned the residential use of chlorpyrifos, though it is still available for restricted use in commercial agriculture.

Breaking the Nuremberg Code?

One of the most contested “loopholes” in the EPA’s rules is the possibility of using data from old studies performed during an era of looser ethical guidelines. Almost everyone agrees that a study that, for example, fed pesticides directly to participants, would never be allowed under today’s rules. (It has happened—for example, in 1992 in Scotland, investigators for Rhone-Poulenc Agro conducted tests in which subjects were given the insecticide aldicarb mixed with orange juice.) In the US today, any such proposal would almost certainly be rejected by a research institution’s ethics board and denied EPA funding.

But what if important information was gained through such a study? Is it ethical to use the information anyway? Experts differ radically on this issue.

For example, the National Resources Defense Council opposes the use of all studies involving intentional exposure, both past and present. In early 2008, it joined forces with organizations like Farmworker Justice and Earthjustice to sue the EPA to prevent its reliance upon older dosing studies when it makes regulatory decisions, arguing that they violate the Nuremberg Code. “We think that the only rule that is scientifically sound and ethical is one that says that the EPA can’t rely on research conducted using intentional human dosage experiments,” says Aaron Colangelo, NRDC’s counsel for the suit.

The EPA counters that using information from studies already conducted could help it make crucial regulatory decisions that would protect the public. After all, the studies are finished, and the information in them is already known. EPA officials declined to be interviewed for this story, instead supplying a statement from Dr. Warren Lux, the agency’s top ethics official, arguing that “the ethical and regulatory standards that are being applied are clearly set forth, are based upon the Common Rule, and are consistent with the standards being applied across all Common Rule agencies.  As in all applied ethics, however, the rules and standards must be applied on a case-by-case basis with knowledge and consideration of the detailed particulars of each case in order to determine whether that particular case is (or is not) consistent with the standards being applied.”

Colangelo argues that there are other ways of getting such data, both through animal testing and observational studies. “They could use animal studies and build in safety factors, or they could look at exposure to, say, farm workers, without intentionally causing greater exposure,” he says. “It’s not as if they need these studies to regulate effectively.”

Decisions about which studies are acceptable often have a profound effect on the use of particular toxic chemicals; Colangelo cites the EPA’s acceptance of the safety of DVVP—or diclorvos, common in flea collars and pest strips—based on an old study in which only six adults were dosed with the toxic chemical. Experts familiar with the study agree that such research would never be allowed or accepted today—in part because of problems extrapolating results from adults to children. Yet because the EPA has been willing to accept older research that does not conform to present ethical standards, Colangelo says that the study is used to justify the continued use of diclorvos in homes where children live. “This study has let EPA keep this chemical on the market. Otherwise, it wouldn’t still be in use,” he says.

Colangelo expects that the issue of using data from older studies will remain contentious, and the fight could intensify as pesticide manufacturers are required to seek new or renewed certification. “The good news is that periodically, all pesticides are now up for review. The bad news is that the incentive is greater now for companies that make the chemicals to try to rely on bad studies,” he says.

A new sheriff in town

Many researchers have expressed hope that Lisa Jackson, President Obama’s choice for head of the EPA, will take action to reverse what they see as years of mishandling and neglect of children’s environmental issues, including human testing. Yet it’s not clear yet whether the administration will address these outstanding issues. “I have high hopes for this administration, that they will make protecting children’s health a priority,” says Whyatt.

“We’re hopeful that the new administration will take a different approach and reverse the previous administration,” agrees Colangelo, who is still awaiting a decision on the NRDC lawsuit.

Jackson will face intense pressure from both sides to set the rules of the game in their favor. With millions of dollars hanging on the nuances of unclear guidelines, the only sure bets are that political jockeying will be intense, and any victory—if there is a one—will be hard-fought.


Lower Standards

The so-called Rules of 10, a standard routinely used in toxicity calculations, starts at the level at which animals experience toxic effects, then lowers that amount by a “safety factor” of a multiple of ten to convert to allowable human exposure levels. This is called the interspecies factor.

Next, researchers must lower by another factor of ten (called the intraspecies factor) to account for the fact that people differ in how much of a pesticide they can tolerate. For example, asthmatics are often more sensitive to inhaled chemicals than the general population.

Finally, the Food Protection Act of 1996, which only recently has begun affecting the EPA’s decision-making, requires a third safety factor of ten to account for the fact that children are often more sensitive to chemical exposures because of their size and continuing development. Says Earthjustice attorney Jan Hasselman, “When you’re basing your testing on animals, you’re talking about a safety factor of a thousand. This drives the pesticide companies nuts.”

If chemical companies are able to provide data showing that children are not impacted differently, one factor of ten disappears. Hasselman says manufacturers could argue for exposure levels up to ten times less stringent than today’s, making the standard easier to meet.

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