Per- and polyfluoroalkyl substances, also known as PFAS, are a large group of man-made chemicals that have been used in industrial and consumer products worldwide since the 1940s.
Research is now showing that these “forever chemicals” can accumulate in the human body and brain, causing neurotoxic effects.
Key Facts:
- PFAS are used in non-stick cookware, waterproof clothing, firefighting foam, and many other products. They do not break down easily in the environment or human body.
- PFAS have been detected in human blood, breast milk, and brain tissue worldwide, indicating widespread exposure.
- Studies show PFAS can cross the blood-brain barrier and accumulate in the brain, especially during development.
- Exposure is linked to behavioral effects like hyperactivity, impaired memory, and motor deficits in humans and animals.
- Underlying mechanisms include disruption of neurotransmitters, calcium signaling, and hormone regulation.
Source: Front Toxicol 2022
PFAS Exposure is Widespread
PFAS have been mass produced since the 1940s for their useful properties like oil, stain, and water repellency.
They are found in many consumer products and industrial applications.
However, PFAS are very stable compounds that break down extremely slowly over time.
These “forever chemicals” have contaminated water, soil, and air worldwide through manufacturing processes and waste disposal.
PFAS have now been detected nearly ubiquitously in human blood samples globally, indicating widespread exposure.
High levels are found in populations living near PFAS production sites or consuming contaminated drinking water.
PFAS have also been measured in human breast milk, showing they are passed from mother to infant.
Developing babies and children have some of the highest daily PFAS intakes per body weight.
PFAS Accumulation in the Brain & Body
PFAS tend to accumulate in protein-rich tissues like the liver and blood.
However, studies show they can also cross the blood-brain barrier and accumulate in the brain.
In general, more PFAS accumulates in the brain after longer-term environmental exposures compared to short high-dose lab experiments.
Within the brain, PFAS concentrations are highest in the hypothalamus, brain stem, thalamus and cerebellum.
The developing brain allows more PFAS to enter compared to the mature brain.
PFAS may exploit immature barrier mechanisms, transport proteins, and intracellular binding proteins in the fetal and infant brain.
Neurotoxic Effects of PFAS Exposure
A growing body of research shows that PFAS exposure, even at low doses, can impact brain development, structure, and function.
However, exactly how PFAS cause neurotoxicity is still unclear.
Most studies focus on two compounds, PFOS and PFOA.
More research is needed on the thousands of other PFAS in use.
In humans, higher PFAS exposure is associated with ADHD and impulsivity in children.
However, human studies are limited by the inability to control dosing and timing.
Animal studies allow researchers to make causal links between PFAS and adverse effects.
Developmental Exposures
Many studies show that exposure to PFAS during early development causes more severe and persistent harm compared to adult exposures.
Impacts include:
- Hyperactivity and impaired habituation in rodents and fish
- Disrupted locomotion and coordination in rodents
- Impaired learning and memory in rodents and chicks
- Anxiety-like behaviors in mice
- Brain asymmetry in chicks
PFAS likely interfere with the intricate developmental processes that shape the brain, like neurogenesis, migration, and synapse formation.
Even small disruptions during critical windows can alter the brain long-term.
Adult Exposures
In adult animals, studies link high doses of PFAS to:
- Impaired spatial learning and memory
- Subtle anxiety-like behaviors
- Decreased motor coordination at very high doses
Underlying mechanisms driving these effects seem to differ between developing and mature brains. Nonetheless, PFAS can elicit neurotoxicity at all life stages.
Mixture Exposures
In real life, people are exposed to PFAS as mixtures, not individual chemicals.
Co-exposures with other contaminants like mercury can also occur. Studies analyzing mixtures are limited but suggest:
- Co-exposures may alter how PFAS distribute in the body and brain
- Mixtures and co-exposures can cause different effects than PFAS alone
- Impacts likely depend on the specific combination of chemicals
Clearly, more research is needed on complex PFAS mixtures at relevant exposure levels.
PFAS Neurotoxicity (Mechanisms)
Several mechanisms likely underlie PFAS-induced neurotoxicity, but specifics remain unclear.
Main mechanisms studied so far include:
Disruption of Calcium Signaling
- PFAS can increase calcium levels in neurons, disrupting electrical signaling
- May contribute to cell death, altered gene expression, and neurotransmitter release
Alterations in Neurotransmitters
- PFAS alter levels of neurotransmitters like dopamine, serotonin, acetylcholine
- Can broadly impact neuronal signaling and circuit function
Neuroendocrine Disruption
- PFAS disrupt regulation of hormones like thyroid, sex steroids, cortisol
- Altered hormone levels can impair neurodevelopment and function
Other possible mechanisms and indirect effects have been proposed but require more research, including mitochondrial toxicity, neuroinflammation, and activation of PPAR nuclear receptors.
Sensitive Populations to PFAS
Certain groups are especially vulnerable to PFAS exposure due to higher contact, immature detoxification, or underlying health conditions.
Those at higher risk of neurotoxic effects include:
- Fetuses, infants, and children
- Adolescents undergoing puberty
- Pregnant women
- Older adults
- People with diseases that compromise the blood-brain barrier like multiple sclerosis
- People with conditions like diabetes, liver disease, or suppressed immunity
Future Research Directions: PFAS & the CNS
Major gaps exist in our understanding of how PFAS impact the brain and nervous system:
- Most data is for PFOS and PFOA only
- Few mixture exposure studies at low doses
- Mechanisms are not fully characterized
- Differences between PFAS classes unknown
- Sensitive groups understudied
Key needs for future research identified by experts include:
- Analyze more PFAS classes and real-world mixtures
- Elucidate mechanisms using multiple models
- Target low dose, long-term exposures
- Focus on developmental neurotoxicity
- Assess effects in vulnerable groups
Conclusion: PFAS a Neurotoxic Risk
In summary, a diverse and growing body of evidence suggests PFAS pose a neurotoxic risk, especially during early development.
However, major research gaps limit our ability to fully predict long-term neurological consequences in humans.
Understanding the impacts of complex PFAS exposures on the brain remains an important frontier in the journey towards ensuring these ubiquitous chemicals do not impair neurological function and children’s futures.
References
- Study: A critical review and meta-analysis of impacts of per- and polyfluorinated substances on the brain and behavior
- Authors: Hannah M. Starnes et al. (2022)
