Thursday, May 26, 2022

Here’s what it will take to get answers about GenX’s health effects

“I can say this. I’m approximately mid-career. I don’t expect to see this one substance fully understood by the end of my career.”

The most notorious of perflouroalkyl ether carboxxylic acids is the one named GenX. What will it take to find out how dangerous it is? (Port City Daily photo / BENJAMIN SCHACHTMAN)
The most notorious of perflouroalkyl ether carboxxylic acids is the one named GenX. What will it take to find out how dangerous it is? (Port City Daily photo / BENJAMIN SCHACHTMAN)

WILMINGTON — After weeks of conferences, forums and investigations, one major question remains: how dangerous is GenX?

It’s an understandable question for residents of the Cape Fear, but it’s hardly simple — and it leads to a slew of other questions. What does it take to assess a substance’s threat? How long does it take? How much does it cost? Who decides which substances get tested? How accurate – and how trustworthy – are those tests?

What do you mean, ‘further study?’

Detleff Knappe is the chemical engineer and professor at North Carolina State University who published the study that brought attention to GenX in the Cape Fear River. At several public forums, he has repeatedly called for further study. That’s good science. It has also been frustrating for the public.

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Behind the public frustration over perfluoro-2-propoxypropanoic acid (PFPrOPrA), the chemical know as GenX, is the fact that it’s relatively new. While the DuPont company produced the chemical for decades as a by-product, it has only been deliberately manufactured since around 2009, when companies began replacing PFOAs with GenX.

Knappe acknowledged public frustration, but said “sadly, the only way we can truly understand how (dangerous it is) is to generate data. Given what we know about PFOA, we should focus on cancer, developmental toxicity, and immunotoxicity.”

Knappe recommended a broad range of tests, looking at different potential effects in a range of animals.

To complicate matters, GenX has a big family — a group of chemicals called perflouroalkyl ether carboxylic acids (PFECAs), or perflourinated ethers (the full list is available in Knappe’s study).

According to Knappe’s research, many of GenX’s chemical relatives were found at much higher levels in the Cape Fear watershed than GenX itself. However, much less is known about them.

According to Knappe, GenX’s cousins are “much more difficult to filter … but are perhaps also more quickly eliminated from the human body.”

So, the other ethers may be harder to filter but less dangerous. But maybe not. Toxicity isn’t Knappe’s field. As he said, “we really don’t know about the toxicity part”

Toxicity 101

Professor Jamie DeWitt, who runs her own lab at East Carolina University. DeWitt has studied compounds similar to GenX for nearly fifteen years. (Port City Daily photo / COURTESY JAMIE DEWITT)
Professor Jamie DeWitt, who runs her own lab at East Carolina University. DeWitt has studied compounds similar to GenX for nearly 15 years. (Port City Daily photo / COURTESY JAMIE DEWITT)

Toxicity is very much the specialty of Jamie DeWitt, a professor of pharmacology and toxicology who runs her own lab at East Carolina University. DeWitt has studied PFOAs and other similar chemicals for nearly 15 years, focusing on their effect on the immune and nervous system. DeWitt is on the front line, studying emerging contaminants like GenX. Work like hers is part of how state and federal regulators decide how dangerous a substance is.

For obvious reasons – moral, ethical, legal, etc. – DeWitt doesn’t experiment on humans, and so, as Knappe suggested, the “next best thing” is long-term or “chronic exposure” animal tests. But animals don’t always react the same way to chemicals as humans do, even mice and rats show differences, according to DeWitt.

“It would be premature to say, just test mice and then extrapolate a chemical’s effect on humans,” DeWitt said. “Ideally, we would want to look at a whole bunch of chronic studies – so, exposure over most of an animal’s lifetime. We’d want to look at studies in rats, in mice, in turtles, in monkeys, in birds. The idea is that we’re getting as much data as possible to help understand what might happen in human exposure.”

As DeWitt pointed out, this is only the beginning of what makes testing such a complicated process.

“In my work, in my lab, we’re looking at the immune system and the nervous system, but you’d also want to look at kidneys, liver, functional studies,” DeWitt said.

Time and money

These studies take a lot of work. Some larger labs have dozens of graduate students and multiple post-doctorates. But even DeWitt’s lab, which she described as being comparatively small, has eight members — a technician, two doctoral students, three undergraduates and two high school assistants.

A single study of one substance, performed on one animal group and looking at one or two areas of impact can take three to four months, according to DeWitt. After additional tests to reproduce the results, followed by the process of peer review, DeWitt said a single study can take between 12 and 24 months.

When you factor in a variety of experimental subjects and the number of possible organs or systems studied, it adds up to a lot of people, time and money.

The cost of laboratory mice for a single study can reach into the thousands of dollars. (Port City Daily photo / FILE PHOTO)
The cost of laboratory mice for a single study can reach into the thousands of dollars. (Port City Daily photo / FILE PHOTO)

“If you consider just the mice, which are $25 each, without the animal husbandry costs, it adds up,” DeWitt said. “We’re taking six to eight per group, three groups plus a control, after you’ve run the test and reproduced it, you’re looking at several thousand dollars — for one experiment. That gives you a small idea of the larger cost, a small idea of how long the process takes.”

DeWitt could not say exactly how long it would take to get solid answers on GenX’s toxicity, but she was confident it would not happen quickly.

“I can say this. I’m approximately mid-career. I don’t expect to see this one substance fully understood by the end of my career,” Dewitt said.

And that’s just GenX, not the other perflourinated ethers that bear similarities to it.

Can you trust a study?

The EPA, where DeWitt did her postdoctoral training, studies a limited number of emerging contaminants at a time, performing studies of about 30 substances in five-year research cycles called the Unregulated Contaminant Monitoring Rule (more about the UCMR and other testing questions for the EPA here).

There are many more chemicals than the EPA can cover in the UCMR, so many state agencies have to look elsewhere for toxicology data. Sometimes, that means studies performed on chemicals by the companies that manufacture them — a situation that raises some questions of integrity and transparency.

Recently the North Carolina Department of Health and Human Services updated its health assessment of GenX, based in part on a “new animal study” that had come to light. The study was funded by DuPont, and carried out in part by DuPont employees. (You can read the DHSS assessment of GenX here, and the DuPont study here).

DeWitt said she understands how that might sound, but said the common practice is nothing villainous.

“I can see what someone might think, but an industry sponsored study is going to be a good study – you can be assured that it will be conducted with best practices,” DeWitt said. “They do take place in broad daylight, you’re not going to be able to fake results.”

According to DeWitt, the industry studies are usually meticulously documented and get reproduced by independent labs.

“The problem isn’t the study,” DeWitt said. “The problem is interpretation. The studies are objective, the interpretations are subjective.”

That is, in part, why researchers like Knappe and DeWitt would want multiple studies to be run.

“The interpretation is biased, it’s biased by your expectations, your background, your experience,” DeWitt said. “DuPont’s interpretation is biased, my interpretation is biased.”

According to DeWitt, reproducing studies doesn’t just verify them, it helps ensure that the right aspects of the data are getting the attention they deserve.

How does a chemical get picked for study?

Industry tests do raise another issue: DuPont has the money for testing and ready access to substances like GenX, while other labs don’t. In fact, funding and access are what testing comes down to, according to DeWitt.

“A lot of these chemicals are proprietary, I can’t just send away for some. So in part a study depends on whether you have the right chemical to actually test. As for picking which chemical to test, if I say, ‘Hey, I’m interested in this chemical and I’d like to study it,’ it really depends on whether there’s a grant out there, whether there’s funding,” DeWitt said.

Media attention - a "frenzy" as Professor Jamie DeWitt called it - can bring some chemicals under the microscope, while potentially leaving others examined. (Port City Daily photo / FILE PHOTO)
Media attention – a “frenzy” as Professor Jamie DeWitt called it – can bring some chemicals under the microscope, while potentially leaving others not examined. (Port City Daily photo / FILE PHOTO)

Funding is not distributed equally for all possible contaminants, DeWitt said.

“If there’s a chemical and it’s been in the news and there’s kind of a frenzy around it, then is there more likely to be grant funding to study it? Yes, probably, it’s more likely,” DeWitt said.

This is the double-edged sword of media attention on GenX, DeWitt said. While perfluoro-2-propoxypropanoic acid has a fairly good amount of name recognition as GenX, a different PFECA like perfluouro-2-methoxy-acetic acid does not. The recent notoriety of GenX will likely bring it under the microscope sooner, but it is less clear when – or if – its relatives will get the same scrutiny.

Sacrifice

The need for answers about emerging chemicals is understandable. But for those running the experiments, it is hard to ignore the sacrifices made by animal subjects. (Port City Daily photo / FILE PHOTO)
The need for answers about emerging chemicals is understandable. But for those running the experiments, it is hard to ignore the sacrifices made by animal subjects. (Port City Daily photo / FILE PHOTO)

There’s a final issue, often glossed over in the rush for answers: the inevitable death of a large number of animals.

“It’s an issue I deal with every day I’m in the lab,” DeWitt said. “I study the immune and nervous system, which have a very complicated set of interactions. There is no non-animal model for that.”

According to DeWitt, there are a lot of safeguards to make sure the animals are treated as well as possible, including protocols for each experiment reviewed by peers and veterinarians that must meet American Veterinarian Society standards.

“But at the end of the day, it’s hard,” DeWitt said. “I have euthanized animals myself and I do cry, I have shed a tear. Because these animals had no choice. It is their sacrifice that gives us the potential to understand these chemicals. That’s how we get answers.”


Send comments and tips to Benjamin Schachtman at ben@localvoicemedia.com, @pcdben on Twitter, and (910) 538-2001.

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