Despite being marketed as a safer alternative, perfluorohexanoic acid (PFHxA)—a short-chain per- and polyfluoroalkyl substance (PFAS)—may not be as harmless as once thought. New research from the Del Monte Institute for Neuroscience at the University of Rochester reveals that early-life exposure to PFHxA can cause long-term behavioral changes in male mice, including increased anxiety and memory deficits.
Male Mice Show Greater Vulnerability
Researchers exposed pregnant and nursing mice to PFHxA through mealworm treats, allowing their offspring to ingest the chemical during gestation and lactation. As the mice matured, the male offspring displayed mild but concerning changes: reduced activity levels, elevated anxiety-like behaviors, and impaired memory. Interestingly, female mice exposed in the same way showed no such behavioral effects.
“Although these effects were mild, observing them only in males echoes trends seen in male-biased neurodevelopmental disorders like autism and ADHD,” said Dr. Ania Majewska, senior author and professor of Neuroscience. “This suggests the male brain may be more vulnerable to environmental insults during development.”
Behavioral Effects Persist into Adulthood
As reported by medicalxpress, the team tracked the mice into adulthood and found that behavioral changes in males continued long after exposure ended. This persistence raises concerns about PFHxA’s potential long-term effects on the developing brain.
Majewska said, “Researchers have not previously evaluated PFHxA for developmental neurobehavioral toxicity in rodent models. Our findings highlight a critical gap in understanding the impact of short-chain PFAS.”
Reevaluating the Safety of Short-Chain PFAS
Dr. Elizabeth Plunk, first author and alumna of the University of Rochester’s Toxicology program, emphasized the need for caution:
“Short-chain PFAS like PFHxA have been seen as safer alternatives to legacy chemicals. But our results challenge that assumption and stress the need for further studies.”
Broader Implications for Public Health
PFAS chemicals—used to repel water, oil, and stains—contaminate food, water, animals, and humans. Researchers link them to various health problems, including developmental delays and kidney cancer. Although many once believed shorter-chain PFAS like PFHxA to be less harmful, recent evidence shows they may still pose serious risks. In fact, the European Union restricted PFHxA in 2024, and the U.S. Environmental Protection Agency recently introduced its first national drinking water standards for PFAS.
Call for Further Research
Majewska concluded that future studies must investigate the cellular and molecular impacts of PFHxA, particularly in brain regions tied to memory, motor control, and emotional regulation. “Understanding the full spectrum of PFHxA’s effects is essential before labeling it a safe alternative,” she said.