‘Forever Chemicals’ Are Everywhere. Most of Their Health Effects Are Unknown
Duke researchers hope to learn which ones are more toxic, and for whom – using tiny worms.

The substances are called “forever chemicals” because of their longevity. PFAS consist of chains of carbon and fluorine atoms linked together. It’s one of the strongest chemical bonds known.
“It's these strong carbon-fluorine bonds that make PFAS so durable but also make them impossible to degrade,” Leuthner said.
That’s why, once they’re produced they tend to stick around. They build up and essentially never break down.
“Any PFAS that’s already in the environment is there to stay,” Leuthner said.
That’s what happened in North Carolina’s Cape Fear River, where into the waterway by a chemical manufacturing plant have left downstream communities struggling with for decades.
That’s also what befell service members and residents living near North Carolina’s and across the country, where PFAS from firefighting foam has made its way into the groundwater, used by nearby residents.

Municipalities are collaborating with universities to deploy emerging technologies to filter and remove PFAS from drinking water sources, but these are still being tested and are expensive to implement.
Today, in the U.S. have . Their use is so widespread that PFAS have even turned up in and in the .
These chemicals exist in more than 14,000 forms. While several to , such as , and , the vast majority have never been tested. The potential health effects from exposure are unknown.
And while some PFAS are in the U.S., they are still found in older or imported goods, and newer replacement chemicals continue to take their place.
So what do we do? Duke researchers say there may be a way to help close the knowledge gap – using tiny transparent worms.
Toxicity Isn’t One-Size-Fits-All
In a , a Duke team led by Leuthner, Baugh and of Duke’s Nicholas School of the Environment exposed C. elegans worms to different doses of 13 PFAS chemicals – some old, some newer – and then measured the effects of the chemicals on their growth.
When they compared the PFAS-treated worms to worms that were not exposed, they found that all of the chemicals they tested stunted the worms’ growth. But some PFAS took a toll at much lower doses than others, the researchers found.
The most toxic chemical, PFOSA, was a thousand times more toxic than the least toxic chemical, PFBA.
What’s more, not every worm strain responded in the same way. Some strains suffered adverse effects at lower doses of certain chemicals than others, suggesting differences in sensitivity that are rooted in their genes.
“This is the first evidence that genetic variation contributes to susceptibility to PFAS toxicity,” Leuthner said.
The health risks to worms might seem like a trivial concern.
But many disease-causing genes in humans have counterparts in the worms. And humans and worms also share many of the same metabolic and developmental pathways, Leuthner said.

Worms Mean High-Throughput Testing
What’s more, the worms’ small size and fast development means researchers can study the effects of diverse chemicals on large numbers of them in a relatively short amount of time.
Traditional toxicity testing in animals such as mice and rabbits can take more than a year to complete; whereas similar experiments in worms take less than a week.
The work is part of a larger aimed at using worm genetics to better predict which chemical exposures are most likely to hurt people’s health.
The idea is to pinpoint gene variants that, if counterparts exist in humans, could help identify people who may be more sensitive to some environmental pollutants than others due to their genetic makeup.
“This is really critical, because humans are genetically diverse,” Leuthner said.
As a next step, the researchers are working to pin down which genes are responsible for the differences they found.
The work could help identify people or populations who might be particularly susceptible, or help pinpoint untested PFAS with the most potential for harm and flag them for future study.
“This could really speed up testing and regulation,” Leuthner said.
This research was funded by the National Institutes of Health (R01ES029930, P42 ES010356 and F32-ES034954) and the Duke Department of Biology.
Citation
"Structure-Specific Variation in Per- and Polyfluoroalkyl Substances Toxicity Among Genetically Diverse Caenorhabditis elegans Strains," Tess C. Leuthner, Sharon Zhang, Brendan F Kohrn, Heather M. Stapleton, and L. Ryan Baugh. Toxicological Sciences, Feb. 22, 2025. DOI: .