Study links PFA’s “safe replacement” with lasting male brain effects

According to new research from the University of Rochester, a safer alternative to being touted as a ban on “forever chemicals” may still pose a risk to the development center’s brain.

The study found that even after chemicals were removed from the system, the shorter chain PFAS compound (a shorter PFAS compound) was early exposed to perfluorohexanoic acid (PFHXA) (a shorter PFAS compound).

The results of the study challenge the assumptions about the security of short-chain PFAS. Although the industry has replaced traditional PFA with compounds such as PFHXA, shorter molecular chains believe reduce health effects, this study shows that male brains are still vulnerable to injury in a critical developmental window.

Male effects mirror human disease only

The researchers exposed pregnant mice to PFHXA through treated foods during pregnancy and care. Male offspring showed decreased activity, increased anxiety-like behavior and memory deficits when tested in adults. Female mice exposed to the same dose had no behavioral changes.

“Although these effects are mild, the many neurodevelopmental disorders that are only found in men are reminiscent of male bias,” said Ania Majewska, senior author of the study and professor of neuroscience at the University of Rochester. Males were diagnosed with autism and ADHD, much higher than women.

The team tested multiple behavioral areas in adult mice, including open field exploration, elevated maze performance and novel object recognition. Particularly surprisingly, these effects lasted long after PFHXA levels in the brain returned to normal-to the age of 90 days, exposed mice had the same brain concentration as those of the unexposed controls.

Key research results

• Dosage-dependent brain accumulation: Higher PFHXA doses result in increased brain levels at birth, both doses showing an increase at 21 days
• Targeted brain areas: Previous human studies have found that PFHXA is particularly concentrated in the cerebellum, a region of crucial motor function
• Long-term behavior changes: Despite the chemical clearance of the brain, the effect lasts for adulthood
• Gender-specific vulnerability: Only men showed behavioral changes, reflecting patterns of human neurodevelopmental disorders

Challenge the “safer” chemical assumption

The timing of this study is particularly important. After years of long-chain PFA ban, the EU has restricted PFHXA in 2024. However, the compound found in pregnant women’s blood and breast milk has raised concerns about fetal and infant exposure.

“The discovery of long-term behavioral consequences for developmental exposure to PFHXA in mammalian models, which is of concern when considering short-chain PFA is considered a safer alternative,” said Elizabeth Plunk, lead author of the study and a graduate student in toxicology at the University of Rochester.

Careful design of research methods to reflect the way real-world exposures. Instead of injecting chemicals directly, the researchers used a more natural exposure pathway—providing pregnant mice with PFHXA through mealworm snacks, allowing chemicals to pass through the placenta and into breast milk.

Impact on human health

This study represents the first assessment of the developmental neurotoxicity of PFHXA in mammalian models. The researchers acknowledge that their findings are preliminary, but believe they highlight critical knowledge gaps in PFAS regulation.

The work comes as EPA recently sets the first national drinking water standard for PFA, aiming to reduce the exposure of millions of Americans. These ongoing chemicals resist collapse in the environment and are associated with kidney cancer and developmental problems in infants.

Future studies will need to examine the cellular and molecular mechanisms behind PFHXA effects, especially in brain regions that control motor function, emotion and memory. The researchers stressed that understanding these pathways is crucial to developing appropriate regulations around the chemical.

For now, this study reminds people that shorter meaning does not necessarily mean safer when it comes to industrial chemicals and developing brains.

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