Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that have been widely used since the 1940s in industries and consumer goods. They are found in products like water-repellent clothing, stain-resistant fabrics, cosmetics, firefighting foams, and grease-, water-, and oil-resistant items. For instance, PFAS are commonly present in non-stick cookware used in everyday life. Their persistence and long biological half-lives have resulted in measurable levels in nearly all people in developed countries, with associated PFAS human health effects reported worldwide.

Evaluating PFAS health risks requires understanding their adverse health effects at real-world exposures, particularly during sensitive life stages, along with their modes of action, toxicokinetics, and dose-response relationships. This knowledge supports risk estimates that guide public health limits, exposure reduction, and environmental cleanup efforts.

PFAS have a chemical structure with a perfluorinated carbon tail that repels both water and oil and an anionic head group that attracts water, making them highly resistant and persistent. As a result, they do not break down and instead accumulate in the bodies of people and animals worldwide through food and repeated exposures. They even bio-magnify through the food web. Growing evidence has raised concerns about the harmful effects of PFAS on human health.

In the human body, PFAS bind strongly to proteins due to their polar, hydrophobic nature and have been detected in serum, cord blood, and breast milk. Unlike many other bio-accumulative contaminants, they do not tend to accumulate in fat tissue.

PFAS have a chemical structure with a perfluorinated carbon tail that repels both water and oil and an anionic head group that attracts water, making them highly resistant and persistent. As a result, they do not break down and instead accumulate in the bodies of people and animals worldwide through food and repeated exposures. They even bio-magnify through the food web. Growing evidence has raised concerns about the harmful effects of PFAS on human health.

In the human body, PFAS bind strongly to proteins due to their polar, hydrophobic nature and have been detected in serum, cord blood, and breast milk. Unlike many other bio-accumulative contaminants, they do not tend to accumulate in fat tissue.

While animal studies show that most PFAS are primarily excreted through urine, renal clearance in humans is much slower, raising significant concerns for PFAS human health. The slow elimination contributes to the long-term effects of PFAS on humans.

PFAS have extended half-lives, with perfluorooctanoic acid (PFOA) persisting for approximately 3.5 years and perfluorooctane sulfonic acid (PFOS) for roughly 4.8 years. Some studies also report a range of 2.3 to 3.3 years. These findings highlight serious PFAS health risks, demanding the need for continued monitoring and risk assessment.

Epidemiological studies have shown that PFAS exposure is linked to weakened immune responses, including reduced antibody levels after vaccinations such as diphtheria, tetanus, rubella, and mumps, with these effects persisting into adolescence and adulthood.

Prenatal and early-life exposure to PFAS has been linked to higher risks of infections such as airway, throat, and gastrointestinal illnesses, as well as conditions like atopic dermatitis. Overall, the evidence on PFAS and human health suggests that exposure to PFAS during infancy and childhood can suppress the immune system, though some effects may differ by sex.

The liver is a major site for long-chain PFAS accumulation, with experimental studies showing toxic effects such as fat infiltration in liver cells, apoptosis, disrupted fatty acid metabolism, and even tumor development. Animal toxicology and histology studies indicate that PFAS can alter liver metabolism, causing increased bile acid reuptake and lipid buildup. These findings demonstrate the effects of PFAS on liver function and long-term disease risk.

PFAS exposure has been consistently linked to higher uric acid levels, a biomarker of increased risk for kidney disease, in both adults and children. The prolonged half-lives of long-chain PFAS are largely due to strong kidney reabsorption. Human studies link legacy PFAS such as PFOA and PFOS exposure to reduced kidney function and chronic kidney disease. PFOA and PFOS health effects can also be seen in the body where these substances tend to accumulate in kidney tissues causing nephrotoxicity.

Exposure to PFOA has been linked to reduced sperm motility, lower sperm concentration and count, and hormonal changes in young men. PFAS can also cross the placenta and accumulate in breast milk, allowing transfer from mother to child. As a result, young children often have higher serum PFAS levels than their mothers.

Human exposure to PFAS occurs through multiple pathways. These may vary from exposure to indoor air and dust to ingestion of contaminated water and food, particularly in areas near industrial sites. Thus, PFAS human health concerns may arise from:

• Water: PFAS contaminate public and private drinking water sources, rivers, and groundwater near industrial areas, landfills, and waste sites. Firefighting foams (AFFFs) used at airports, military bases, and training facilities are a major contributor, raising concerns about PFAS chemicals health effects on the communities dependent on these resources.
• Soil and Air: They spread through soil and air around hazardous waste sites, manufacturing facilities such as chrome plating, electronics, textiles, paper, and through biosolids used as fertilizers.
• Food: PFAS enter the food chain through contaminated fish, seafood, dairy, meat, crops, and animal products. Food packaging such as grease-resistant paper, fast-food wrappers, and microwave popcorn bags also contribute PFAS to the environment.
• Water: PFAS contaminate public and private drinking water sources, rivers, and groundwater near industrial areas, landfills, and waste sites. Firefighting foams (AFFFs) used at airports, military bases, and training facilities are a major contributor, raising concerns about PFAS chemicals health effects on the communities dependent on these resources.
• Household and Consumer Products: Everyday items like stain- and water-resistant fabrics, non-stick cookware, cleaning agents, paints, sealants, and certain personal care products (shampoo, dental floss, cosmetics) release PFAS into homes.
• Exposure Pathways: This is an area of growing research, it is currently understood that people are being exposed to PFAS through various means, including drinking contaminated water, eating contaminated food, inhaling polluted air or dust, swallowing soil, using PFAS-containing products, or working in high-risk occupations such as firefighting and chemical manufacturing.

Accurate PFAS testing solutions are essential to measure the presence of environmental chemicals and metabolites in human tissues and fluids. Testing can provide a clearer picture of total internal exposure from all sources and pathways. The wide diversity of PFAS, with varying chemical and physical properties, requires the development of tailored analytical procedures that depend on the sample type and medium.

The choice of biological sample depends on the specific PFAS of concern, with serum most often used to measure those with long half-lives, while urine or whole blood may be better for short-lived compounds. PFAS can also be detected in plasma, breast milk, and hair, each providing unique insights into exposure at different life stages. For example, hair can reflect historical exposures, and breast milk testing helps estimate infants intake, which is a significant concern for many communities that have been exposed to these substances.

Because PFAS detection limits are 1,000 times lower (ppt) than routine analyses (ppb), strict precautions such as verifying PFAS-free supplies are essential to prevent sample contamination, which can still occur from vendor or manufacturing changes. Extremely low detection limits and regulatory criteria is in the parts per trillion (ppt) range. Hence, field QC sample collection and analysis are crucial in investigating the effects of PFAS on humans.