Forever Chemicals Linked to Altered Brain Genes and Impulsivity in Rats

Early exposure to per- and polyfluoroalkyl substances (PFAS), commonly known as “forever chemicals,” is linked to changes in brain gene expression and increased impulsive behavior in rats, according to a new study published in the journal Environmental Health Perspectives. The research, conducted by scientists at the University of California, Riverside, found that male rat offspring exposed to low doses of PFAS during gestation and early life showed altered activity in genes related to neurodevelopment and neurotransmitter signaling, alongside measurable increases in impulsivity-like behaviors in adulthood.

The study focused on two prevalent PFAS compounds: perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). Pregnant rats were given drinking water containing these chemicals at levels designed to mirror human exposure ranges observed in biomonitoring studies. After birth, the offspring continued to receive the same exposure through maternal milk and direct consumption until weaning. Researchers then assessed the animals’ behavior and brain tissue when they reached young adulthood, approximately 60 days after birth.

To evaluate impulsivity, researchers used a delay discounting task, a behavioral test that measures an individual’s tendency to choose a smaller, immediate reward over a larger, delayed one. Rats exposed to PFAS consistently chose the smaller, sooner reward more often than control animals, indicating heightened impulsive tendencies. This pattern persisted even after exposure ended, suggesting lasting neurological effects.

Gene expression analysis of the prefrontal cortex—a brain region critical for decision-making, impulse control, and executive function—revealed significant alterations in pathways related to synaptic plasticity, dopamine signaling, and thyroid hormone regulation. Notably, genes involved in the development and function of neurons showed downregulation, while others associated with stress response and inflammation were upregulated. These molecular changes aligned with the observed behavioral shifts.

“We’re seeing that early-life PFAS exposure doesn’t just cause transient effects—it appears to reprogram brain development in ways that endure into adulthood,” said Dr. Margarita Curras-Collazo, lead author of the study and a professor of neuroscience at UC Riverside. “The fact that we observed these changes at exposure levels relevant to humans raises concerns about the long-term neurodevelopmental risks of these persistent pollutants.”

PFAS are a class of over 12,000 synthetic chemicals used since the 1940s in nonstick cookware, water-repellent fabrics, firefighting foam, and food packaging. Their defining trait—extreme resistance to degradation—has led to widespread environmental contamination and accumulation in human bodies. Studies have detected PFAS in the blood of over 98% of Americans, according to the Centers for Disease Control and Prevention (CDC), with dietary intake and drinking water being primary exposure routes.

While previous research has associated PFAS exposure with altered thyroid function, reduced vaccine response, and increased cancer risk, this study adds to growing evidence of their potential impact on brain health. Animal models have previously shown links between PFAS and anxiety-like behaviors, memory deficits, and changes in motor activity. However, this research is among the first to connect early exposure with specific molecular alterations in prefrontal cortex genes tied to impulse regulation.

Experts caution that while rodent studies provide valuable mechanistic insights, direct translation to humans requires careful interpretation. “Rat models allow us to control exposure and examine brain tissue in ways impossible in human studies, but we must be cautious about assuming identical outcomes,” said Dr. Linda Birnbaum, former director of the National Institute of Environmental Health Sciences (NIEHS), who was not involved in the study. “Still, the consistency of findings across animal models strengthens the case for treating PFAS as a potential neurodevelopmental hazard.”

The study authors note several limitations, including the focus on only two PFAS compounds and the use of exposure levels that, while environmentally relevant, may not capture the complex mixtures humans encounter. They also emphasize that impulsivity in rats is an analog for human behavior and not a direct diagnosis. Future work will need to explore sex differences—this study observed effects primarily in males—and examine whether similar patterns appear in other brain regions or across generations.

From a public health perspective, the findings reinforce calls for stricter regulation of PFAS. In recent years, the U.S. Environmental Protection Agency (EPA) has moved to designate certain PFAS as hazardous substances under Superfund law and has proposed national drinking water limits for PFOA and PFOS. Several states have already enacted stricter standards, and some manufacturers have begun phasing out legacy PFAS in favor of shorter-chain alternatives, though concerns persist about the safety of these substitutes.

As research continues to uncover the long-term consequences of early-life chemical exposure, scientists stress the importance of reducing preventable risks. “We may not be able to eliminate all PFAS from the environment overnight, but we can limit further contamination and protect vulnerable populations, especially pregnant women and children,” said Dr. Curras-Collazo. “Studies like this one help us understand not just what these chemicals do, but why limiting exposure matters for lifelong health.”