New research with roundworms investigates the effects of “forever chemicals” PFOS and PFOA on dopamine levels.
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PFOS and PFOA, perfluorooctane sulfonate and perfluorooctanoic acid respectively, can make life easier. They make our kitchen pans non-stick, our athletic wear water-repellent, and firefighting chemicals more efficient. But, these human-made chemicals are believed to linger in the body and environment indefinitely.
Scientists have many questions about the long-term effects. Consumers are using them less, and companies that once championed them are stepping away. But they still have important military and industrial applications, especially in firefighting foams. Even if production completely stopped, the world will still live with them forever.
“These chemicals are detectable in the blood of almost every human. They are often found in other species, as well, including polar bear and whale brains,” says Jason Cannon, an associate professor of toxicology at Purdue University.
“The carbon-fluorine bond is one of the strongest in nature, and it is difficult to break down, especially when there is more than one fluorine atom on the carbon atom. Most chemicals that we consume or absorb will leave the body in a different chemical form. To the best of our knowledge, these chemicals are not very well metabolized so they bioaccumulate.”
Cannon calls these forever chemicals a major public health issue because adverse health effects have been shown to affect hormones and other aspects of the endocrine system. Both PFOS and PFOA are per- and polyfluoroalkyl substances, more commonly known as PFAS, and are potentially neurotoxic. But to what extent is unknown, especially for the years and decades they may accumulate in the brain.
“And which regions they accumulate within the brain is unknown,” says Cannon, who studies dietary toxins and neurological disease, including gene-environment interactions in Parkinson’s disease.
Cannon’s recent study in Toxicological Sciences determines that PFOS is selectively neurotoxic and relevant to specific neurological diseases. In this study, he exposed roundworms to PFOS and PFAS, which showed that their dopamine levels and dopamine neurons were highly sensitive and declined. In mammals, dopamine is key to movement, reward, and addiction.
“As a Parkinson’s disease lab, seeing dopamine level depletions is a hallmark feature of the disease, but starting here, we need to be careful of our interpretation,” Cannon says. “Beyond Parkinson’s disease, there are a number of dopamine regions in the brain that could be affected and imply neurodegenerative issues or mental health issues. More research is needed.”
Cannon’s earlier research, which appeared in Toxicology and Applied Pharmacology, took a step toward uncovering effects on dopaminergic function. That study found that PFOS exposure led to selective decreases of dopamine levels in Northern leopard frogs, a sentinel species. The study used Northern leopard frog larvae for testing because their brains feature certain chemical bio features that are more similar to those in humans than those in rodents. This frog species has a breakdown product of dopamine called neuromelanin that binds with toxins.
The three doses evaluated in a laboratory setting reflected high-level amounts from possible military site contaminations. The dopamine decreased significantly in the brains of frogs treated with PFOA at 1,000 parts per billion and PFOS at 100 and 1,000 parts per billion.
“The 1,000 is really pushing it, but the 100, well, there have been some contaminated sites that have been reported to be close to that level,” he says. “This is one of the difficulties in conducting toxicology studies; you want environmentally relevant dose but you also are trying model years of exposure over a short time frame. Certainly, the highest dose is probably pretty weak for environmental relevance, but the two lower doses do bear some environmental relevance. We are conducting studies at even lower doses.”
Alternatives to PFOS and PFOAs are in the works. “It is thought that the shorter chain PFOAs are less toxic,” Cannon says. “But I would say we truly don’t know that. The data is not there. We have all these alternatives in the environment with little to no toxicity testing. In some cases that may be true. They may metabolize and leave the body faster, but from a neurological standpoint the smaller compounds usually penetrate the brain better. So that is something we need to pay attention too.”