PFAS have been synthesized since the 1950s and are broadly used in the production of firefighting agents, cosmetics, and herbicides. Their numerous industrial applications, combined with an exceptionally long half-life in the human body and extreme environmental persistence, result in common and chronic exposure of the general population.
PFAS chemicals can affect our biology by mimicking fatty acids—the building blocks of fat in our bodies as well as the foods we eat. This molecular mimicry allows them to infiltrate biological systems that normally process fats and lipids, leading to widespread disruption.
Contrary to other persistent organic pollutants, PFAS are amphiphilic—they contain both strongly hydrophilic (charged end of the perfluorocarbon chain) and strongly oleo- and hydrophobic regions. This unique structure allows them to interact with both water-soluble and fat-soluble systems in your body.
Every year, an average of 2.5 million pounds of pesticides containing the "forever chemicals" known as PFAS are sprayed on California crop fields, according to recent analysis. Between 2018 and 2023, nearly 15 million pounds of PFAS pesticides were applied to California farmland, potentially contaminating produce, soil, and drinking water.
PFAS are used in textile products to provide properties such as water repellence, oil repellence, stain resistance, durability and thermal stability. Textiles account for approximately 35% of total global PFAS demand.
PFAS are used for their ability to create 'non-stick' surfaces, typically associated with cookware such as frying pans. They're also found in oils, lubricants, bike oils, and ski waxes.
PFASs have been in large-scale production since the 1950s and in paper- and plant-fiber-based food contact materials, PFASs are used as sizing agents and chemical barriers against moisture and grease.
Certain PFAS are authorized for limited use in cookware, food packaging, and food processing equipment, including materials used to produce gaskets and o-rings that require chemical and physical durability.
PFAS are added to cosmetics and toiletries to provide a smooth, glossy or water-resistant finish, appearing in makeup, sunscreen, dental floss, and other everyday items.
Firefighting foams represent major sources of environmental PFAS pollution, concentrated around airports, military bases and fire training centres.
PFAS in paints and coatings improve glossiness, decrease bubbling and peeling, and enhance stain and water resistance of painted surfaces.
PFAS are used in furniture to provide a water or stain resistant coating, appearing in upholstered furniture, carpets, and home textiles.
The widespread use of PFAS pesticides is a significant but overlooked source of contamination and exposure, affecting millions in California alone. For most people, food and drinking water are the primary routes of exposure to PFAS, making the use of these chemicals in agriculture especially concerning.
PFAS are a group of at least 16,000 chemicals commonly used to make products resistant to water, stains, and heat. These chemicals are used in pesticides either as active ingredients or as inert ingredients that improve a pesticide's overall functions.
In vivo and in vitro studies have reported that PFAS can bind to nuclear receptors, such as estrogen receptors (ERs), androgen receptor (ARs) and thyroid hormone receptor (TRs); therefore, they can alter steroidogenesis.
PFOS interacts with ERα and disrupts estrogen functions in a concentration-dependent manner. PFOA, PFOS, PFNA and PFDA exposure significantly enhanced human ERα-dependent transcriptional activation.
PFAS can compete with thyroxine (T4) for binding to the human thyroid hormone transport protein transthyretin (TTR), which may lead to reduced thyroid hormone levels.
PFCs may act as endocrine disruptors once in circulation, ultimately leading to genital disorders, such as impaired spermatogenesis and reproductive defects, and antiandrogenic-driven conditions.
In liver cells, PFAS activate peroxisome-proliferator-activated receptor (PPAR), which induces heterodimerization with retinoid x receptor (RXR). The complex binds to specific DNA sequences (PPREs) in gene promoter regions and modulates transcription.
PFOA competes with calcitriol on the same binding site of the vitamin D receptor (VDR), leading to an alteration of the structural flexibility of the receptor.
Endocrine disruption may be facilitated at the molecular level either by interaction of PFAS with the estrogen and/or androgen receptor or by interference with sex hormone biosynthesis.
PFAS could modulate the expression of estrogen-responsive genes, which are responsible for the maintenance of gonadotropin releasing hormone neurons in the hypothalamus. They could also interfere with the negative feedback regulation of FSH by E2 at the receptor level.
Thyroid hormones are involved in several biological processes, including regulation of energy expenditure, growth, and neurodevelopment, starting from intrauterine life throughout infancy. During fetal life, thyroid hormones are crucial for normal brain development, being essential for orchestrating the processes of neurogenesis, migration, synaptogenesis, and myelination.
PFAS enter the brain through two potential mechanisms: initiating blood-brain barrier (BBB) disassembly through disrupting tight junctions and relying on transporters located at the BBB.
PFAS may cross and injure the blood-brain barrier, potentially fostering increased penetration of other compounds into the brain. PFAS are also able to cross the placenta during pregnancy, allowing for PFAS to accumulate in the fetal brain.
Highly reproduced decreased dopamine levels in the whole brain after PFAS exposure, with increased catecholamine levels in the hypothalamus.
Highly reproduced increased glutamate levels in the hippocampus after PFAS exposure.
Multiple studies demonstrated PFOS-treated male rats had decreased dopamine or serotonin turnover in the hypothalamus and hippocampus.
PFAS disrupt key neurotransmitter systems such as acetylcholine, dopamine, and glutamate, and impair calcium homeostasis and synaptic function.
Multiple PFAS are attributed to disrupting calcium homeostasis, impacting tissues throughout the body, including the brain. Changes in calcium homeostasis can cause disruption in neurotransmission, neuron plasticity (through inhibiting long-term potentiation [LTP] and long-term depression [LDP]), protein synthesis/degradation, and mitochondrial function.
PFOA exposure altered the expression of almost 600 genes—no other compound altered more than 147. Specifically, PFOA decreased the expression of genes involved in synaptic growth and neural function.
These genes, some involved in processes vital for neuronal health, were found to be consistently affected by PFAS exposure. For example, all compounds caused a gene key for neuronal cell survival to express less, and another gene linked to neuronal cell death to express more.
Developmental exposure appears to cause more pronounced neurobehavioral effects than adult exposure.
Fatty acid binding proteins have greater expression during embryonic development, offering a potentially unique avenue for increased intracellular sequestration of PFAS in the developing brain.
Evidence suggests that PFAS may be neurotoxic and associated with chronic and age-related psychiatric illnesses and neurodegenerative diseases.
After years of exposure to these contaminants, they accumulate in human serum and organs with low elimination rates and long elimination half-lives.
PFAS exposure impacts thyroid homeostasis and can cross the placental barrier. PFAS have shown multi-transgenerational effects in laboratory experiences and animal models.
PFAS disrupt human biology through multiple, interconnected molecular mechanisms. Their ability to mimic fatty acids allows them to bind to nuclear hormone receptors throughout the body, interfering with thyroid, reproductive, and metabolic hormones. In the brain, they cross the blood-brain barrier, accumulate in critical regions, and disrupt neurotransmitter systems essential for cognition, mood, and neurological development.
Despite a large body of scientific evidence, the mechanisms of action of per- and polyfluoroalkyl substances (PFAS) are still unclear. However, research continues to uncover the intricate ways these persistent chemicals interact with our most fundamental biological systems.