In a recent review published within the journal Science of The Total Environment, researchers collate and discuss available literature on per- and polyfluoroalkyl substances (PFAS). They highlight PFAS sources within the environment, compare PFAS exposure risk amongst different age groups, and elucidate epidemiological studies on these substances’ hepatotoxicity in vitro and in vivo. They finally indicate the present gaps in PFAS research and supply suggestions for bridging these gaps in future studies.

Study: Dietary exposure to per- and polyfluoroalkyl substances: Potential health impacts on human liver. ​​​​​​​Image Credit: Created with the help of DALL·E 3

What are PFAS and where will we find them?

Per- and polyfluoroalkyl substances (PFAS) are highly persistent synthetic chemicals comprising greater than 4,700 fluorinated substances. PFAS are durable, heat-resistant, and grease- and water-repellent, leading to their extensive application in the buyer sector.

The worldwide footprint of PFAS

Despite being artificial and never found naturally within the environment, their near-ubiquitous incorporation in food packaging, fire-repellent foam, waterproofing material, paints, pesticides, and even cosmetics has resulted in PFAS being found from the height of Mount Everest to the underside of ocean trenches. Global studies have found PFAS within the tropics, the Arctic and Antarctic Poles, and in all places in between.

The biological impact of PFAS

Alarmingly, PFAS have also been present in the bodies of virtually all plants and animals, including humans. Research has demonstrated the bioaccumulation and biomagnification of those substances across terrestrial and aquatic ecosystems, exposing humans to PFAS ingestion via inhalation, dermal contact, and dietary intake. Oral dietary intake predominates, with epidemiological studies linking increased serum PFAS concentrations with fish and shellfish consumption.

How will we devour PFAS?

PFAS have further been identified in vegatables and fruits, livestock, and processed foods, and given their use as food packaging, have been observed to contaminate food to direct migration from the packaging onto the food itself. PFAS have a robust affinity for proteins and bioaccumulate in protein-rich tissue. Research has identified high concentrations of PFAS within the human liver, where it has been related to chronic diseases, including nonalcoholic fatty liver (NAFLD), hepatic fibrosis, and liver cancer.

PFAS and liver health

The current review goals to elucidate the sources and fates of PFAS within the environment, with a special deal with human exposure and PFAS-induced hepatotoxicity studies evaluating in vitro and in vivo murine models. The review is meant to lift public awareness concerning the demerits of PFAS contamination and its impacts on human liver health.

From production to pollution: The lifecycle of PFAS

PFAS, since their discovery and introduction within the Eighties, have been used extensively in consumer and industrial applications on account of their durability and surfactant-like properties. After concerns about their environmental impacts got here to the forefront within the early 2000s, PFAS manufacturers began phasing out long-chain PFAS (called ‘legacy PFAS’) and replacing them with short-chain variants (’emerging PFAS’).

While additional research is required to substantiate claims that short-chain PFAS are environmentally and medically protected, these emerging PFAS allow manufacturers to bypass legacy PFAS restrictions imposed throughout the Stockholm Convention and other global conferences.

How do PFAS get into our food and water?

Studies have identified industry wastewater and exhaust, wastewater treatment plants (WWTPs), untreated domestic wastewater, and aqueous film-forming foams (AFFFs) as the first environmental PFAS pollutant sources. Uptake and use of this water by plants, aquatic organisms, and livestock ends in bioaccumulation and biomagnification. This process, termed ‘trophic transfer,’ forms humans’ predominant dietary source of PFAS.

Food packaging and nonstick cookware are wealthy in PFAS, especially polyfluoroalkyl phosphate esters (PAP) and fluorotelomer alcohols (FTOH). Studies have revealed that PFAS can migrate from packaging material and cookware to the food itself, with the degree and rate of migration depending on PFAS characteristics (chain length) and the food matrix (pH, fat content, temperature, salt content). Migration is the first source of PFAS in processed foods.

Effects of PFAS exposure in humans

Studies have identified PFASS in multiple human tissues, including the blood, brain, kidneys, cerebrospinal fluid, liver, placenta, and lungs. Exposure levels vary based on occupation and age. Firefighters and fluorine-chemical industrial park staff are at much higher exposure risk than most of the people on account of their close contact with PFAS-secreting substances. For many humans, dietary habit is the critical determinant of PFAS exposure, with seafood diets generally leading to higher PFAS concentrations than vegatables and fruits.

While some studies have identified reductions in serum PFAS levels in lactating women and lack of PFAS during menstruation, others have revealed that mother-to-child PFAS transmission can occur via direct umbilical cord blood and breastfeeding. Research has identified high concentrations of PFAS in dairy milk and infant formula, suggesting that infant exposure to PFAS is significantly higher than that of adults.

Following restrictions imposed by the Stockholm Convention and other international agreements, legacy PFAS in human serum shows an encouraging downward trend. Long-term studies in Sweden and the USA have revealed legacy PFAS serum reductions between 61% and 88%. Nevertheless, while the general PFAS concentrations in human serum appear to be in decline, legacy PFAS are being replaced by emerging short-chain PFAS equivalent to chlorinated polyfluoroalkyl ether sulfonic acid (Cl-PFESA). These emerging PFAS have been linked to hostile pregnancy outcomes in Chinese studies.

Biological pathways of PFAS toxicity

In vivo, murine models have revealed PFAS absorption patterns in mammals. PFAS have a robust affinity for fatty-acid binding proteins present in the liver, leading to the liver tissue often having the very best PFAS concentrations in most humans. Most PFAS have chemically robust carbon‑fluorine bonds, stopping their biochemical metabolisms and leading to bioaccumulation in human tissue.

“Several reports have shown that PFAS initially crosses the intestinal barrier and is distributed within the blood, binds to albumin and low-density lipoprotein within the blood, after which disperses into extraintestinal organ following blood circulation.”

What will we learn about PFAS-induced liver damage?

Epidemiological studies have elucidated extensive liver damage led to by PFAS toxicity. PFAS has been related to quite a few liver-damage biomarkers, including alanine transaminase (ALT), Gamma-glutamyltransferase (GGT), and aspartate transaminase (AST). Studies have shown strong evidence for legacy PFAS being liable for liver fibrosis and cancer, especially in women and older adults.

In vitro liver models have found that the cytotoxicity of PFAS relies on exposure duration, PFAS concentration, and carbon chain length. Alarmingly, some studies have found synergistic effects between multiple PFAS, causing more significant damage than the sum of individual PFAS.

In vivo studies have identified PFAS as being liable for higher levels of cholesterol and obesity in humans.

“A recent study showed that exposure to 5 PFAS mixtures (PFOS, PFHxS, PFOA, PFNA, and HFPO-DA) caused cholestasis within the liver and increased cholesterol and bile acid levels within the mice.”

Conclusion

The current review elucidates the sources and environmental transmission of PFAS, a family of nearly 5,000 man-made substances with remarkable persistence. It provides an summary of the exposure routes for PFAS assimilation by humans and the hostile effects of PFAS toxicity in vitro and in vivo. Particular focus is paid to liver cytotoxicity, revealing that PFAS can lead to chronic liver conditions, including cancer.

“This review goals to lift public awareness about food PFAS contamination and its potential risks to human liver health.”