A recent article in the New York Times about EPA’s attempt to reject data from the increasingly powerful field of epidemiology, alluded to a particularly dark episode in the recent history of chemical testing. A time when pesticide companies were so desperate to prove their chemicals “safe” that they turned to human testing. This wasn’t in the 1930s or 50s or even 60s, but this particular rash of human tests took place in the late 1990s.

Let that sink in.

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Cuyahoga River

In the 1970s, when the U.S. Environmental Protection Agency emerged from the country’s smog choked cities and combustible rivers the young agency was charged with a nearly impossible task: to ensure that the chemicals flooding into our homes, farms and waters didn’t cause “unreasonable adverse effects.”  But how to evaluate such things? Intentionally exposing humans was clearly unethical (not to mention impractical.) So, in the ensuing years the science of toxicology filled the void by developing toxicity tests, poisoning laboratory animals from rats, rabbits, fish and fowl, in order to protect humans and the environment.

The studies revealed how chemicals like dioxin and PCBs, plasticizers, solvents, insecticides, fungicides and herbicides did what they did: some mimicked hormones fooling our bodies into early or late puberty, or altered fertility. Others kicked off a cancerous cascade and some simply threw a chemical wrench into essential metabolic pathways. Toxicologists discovered, through animal studies, how chemicals wend their way into our brains and cross the placenta, and how some hanging around in leaf litter and lake bottoms can haunt us for decades. Today’s toxicologists are uncovering effects that earlier toxicologists could only have imagined (and many did not).

FUNDAMENTALS_RESEARCH_USE4As the science advanced, regulatory testing guidelines tightened and chemical evaluations remained limited to a slate of endpoints measured through animal testing. But animal tests can sometimes fail when it comes to protecting humans, for example, when a chemical affects the brain – altering behavior. Animal models also fail to capture the human condition. Our lives are complicated: we eat odd foods, drink, take drugs and stress out over our love lives or homework or our health care bills. All of these things can affect our response to toxic chemicals yet none are included in the current animal testing. One approach for crossing this inter-species chasm is to apply “uncertainty factors.” A sort of, we don’t know, so we’ll reduce the acceptable amount of chemical by a factor of ten (sometimes more, sometimes less, depending on how much we really do know.)

Intentionally exposing humans to new chemicals was never a part of the chemical testing plan. And then came the battle over chlorpyrifos and its chemical cousins.

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From Compoundinterest

Approved for use over 65 years ago chlorpyrifos — a relative of the nerve gas sarin — interferes with nerve signaling. Neurons constantly chatter with one another: nerve-to-nerve, or nerve-to-muscle. They communicate using chemical messengers including acetylcholine. Once a chemical signal is received it must then be deactivated. It is like the ringer on your phone turning off once you answer; imagine if it didn’t. The enzyme acetylcholinesterase deactivates acetylcholine, and chemicals like chlorpyrifos deactivate acetcycholinesterase. The result is unabated signaling and potentially lethal overstimulation. It would become one of the most popular insecticides in our country. Traces of the chemical would also cling to the fruits and vegetables in our salads, and fruit smoothies.

Recognizing some of the testing and regulatory short-comings, toxicologists and regulators began questioning the basic model for reigning in chemicals. One of the most troubling of chemical regulatory concessions has been the focus on single chemicals: as if we were exposed only to chlorpyrifos, or mercury, BPA or myriad other chemicals to which we are exposed. Of course we are not, and some of these chemicals may act similarly, or make one another more toxic, or even less toxic. We think about this each time we pop a new pill prescribed by our doctors (or at least we ought to) so why not pesticides and other industrial age pollutants? Regulating chemicals one at a time doesn’t account for the complex chemical cocktails we breath and ingest. Regulations were also based on adult exposures and they worried this might not be so protective for children. And then what about chemicals that interfere more subtly with, say hormones? Or our brains? Advances in the neurosciences suggested that infants and children with their developing brains, maturing metabolic systems and tendency to eat more fruits and vegetables may not be sufficiently protected by current laws.

In 1996 working together the EPA and Food and Drug Administration crafted the Food Quality Protection Act. It was a first attempt to deal with the real world complexity.  Regulators were charged with protecting children’s health in particular, including protecting the very young from cumulative and combined pesticide exposures. One outcome was an additional safety factor accounting for the added uncertainty the and presumably increased susceptibility of children to exposure and effects of pesticides.gerber

Chemicals that acted by the same mechanism, like organophosphate insecticides including chlopyrifos, were obvious targets for reevaluation. It’s like adding apples and apples. For agrochemical manufacturers the implications were clear. Acceptable levels of some pesticides would be lowered; in some cases a pesticide may even be banned. With organophosphates in the crosshairs, manufacturers were desperate for a solution; which is how those human studies came about.

Pesticide producers seeking to eliminate the extra safety factor paid college students to eat chlorpyrifos laced pills while men and women quaffed pesticide laced orange juice. In another study men were paid to ingest a corn oil-pesticide combo. The goal was to show that humans were no more sensitive to acetylcholinesterase inhibition than laboratory animals. As ethically-fraught as human testing is, it was never forbidden. But who would have expected that soon after the new regulation, manufacturers would be requesting that EPA consider data from studies using humans as subjects?  Certainly not the EPA. The influx of human toxicity testing data threw EPA into an ethical and legal quagmire that raged for years. Could they accept such data? Should they? How could it even be possible to submit data from pesticide exposed persons?

And yet, amidst all this turmoil, the EPA still determined that chlorpyrifos was not only too dangerous for home use but it also reduced allowances for food residues. In the years that followed, organophosphate use declined by more than 70%, but chlorpyrifos remained a top seller. Then it became the poster-pesticide for a corrupt agency that ignored its own intentions to ban the pesticide and which was recently ordered to uphold its ban.

And the human studies for pesticides? Provided that you are properly informed you may still participate should the opportunity arise (assuming you are not pregnant, nursing or a child.) So, two decades later, while chlorpyrifos is (or about to be, or may be) banned, pesticide studies on human subjects is not. Surprised? I certainly was.

For more about the historical humans studies see The English Patients: human experiments and pesticide policy, a report by EWG from 1998.

 

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