Emerging research alarmingly suggests that forever chemicals potentially cause detrimental effects on male brain development.
Per- and polyfluoroalkyl substances (PFAS), often referred to as ‘forever chemicals,’ have been used in consumer and industrial products since the 1940s for their ability to resist water, oil, and stains.
Their chemical stability makes them effective in everything from non-stick cookware to waterproof fabrics, but also nearly impossible to break down in the environment.
Over time, concerns about the health risks of long-chain PFAS compounds have prompted regulatory action and a move toward shorter-chain alternatives.
One such alternative, perfluorohexanoic acid (PFHxA), has been widely regarded as less harmful. However, new research from the Del Monte Institute for Neuroscience at the University of Rochester suggests this assumption may be misguided.
The study found that early-life exposure to PFHxA can disrupt brain development in male mice, leading to lasting behavioural and cognitive changes.
This discovery is challenging previous beliefs about the safety of short-chain PFAS and raising renewed questions about their long-term effects on human health.
Early life exposure may affect male brain development
In the study, pregnant mice were fed mealworm treats laced with PFHxA throughout gestation and lactation.
The researchers monitored the behavioural and developmental outcomes of the offspring into adulthood. While female mice showed no measurable changes, male mice exposed to PFHxA exhibited decreased activity, increased anxiety-like behaviours, and signs of memory impairment.
These changes, though classified as mild, align with patterns seen in human neurodevelopmental disorders that disproportionately affect males, such as autism spectrum disorder and ADHD.
This male-specific vulnerability suggests that environmental toxins like PFHxA may influence brain development differently based on sex, with male brains potentially more susceptible to chemical disruption during critical growth periods.
Lingering effects into adulthood
One of the most concerning findings was the persistence of behavioural changes in male mice long after the exposure to PFHxA had ended.
The study tracked the mice into adulthood and confirmed that the cognitive and emotional impairments remained, indicating that early life exposure may cause permanent changes to brain structure or function.
This evidence challenges the assumption that short-chain PFAS, like PFHxA, are safe simply because they are less bioaccumulative than their longer-chain predecessors.
The research underscores the need to examine not just how long a chemical stays in the body, but how it interacts with the developing brain during formative stages of life.
Regulatory gaps and the need for broader testing
PFHxA has been detected in water supplies and was recently restricted by the European Union in 2024.
In the United States, the Environmental Protection Agency has begun to implement national drinking water standards for PFAS, aiming to limit exposure for millions.
However, regulations have historically focused on long-chain variants, leaving gaps in oversight for short-chain alternatives like PFHxA.
Given its widespread use and environmental persistence, the lack of comprehensive neurotoxicity data on PFHxA presents a significant regulatory blind spot.
Researchers are calling for more targeted studies to evaluate its cellular and molecular impacts, particularly in brain regions related to emotion, memory, and motor function.
Ania Majewska, PhD, professor of Neuroscience and senior author of the study, explained: “This work points to the need for more research in short-chain PFAS.
“To our knowledge, PFHxA has not been evaluated for developmental neurobehavioral toxicity in a rodent model.
“Future studies should evaluate the cellular and molecular effects of PFHxA, including cell-type specific effects, in regions associated with motor, emotional/fear, and memory domains to elucidate mechanistic underpinnings.”
A wake-up call for public health and policy
The findings serve as a stark reminder that not all ‘safer’ chemical alternatives are truly safe.
PFHxA’s potential role in disrupting brain development, particularly in males, adds to a growing body of evidence that underscores the importance of evaluating environmental toxins through a developmental lens.
As research continues, policymakers and regulators may need to reconsider current safety standards and expand testing requirements to include the long-term neurobehavioral effects of all PFAS compounds, not just the legacy ones.
