PFAS Forever Chemicals: Health Implications

Polyfluoroalkyl substances (PFAS) create the perfect household items: waterproof, greaseproof, and capable of being non-stick. This convenience has come at a hefty environmental and medical cost. Commonly dubbed “forever chemicals”, PFAS are extremely mobile and do not degrade. The most notorious PFAs are perfluorooctanoic acid (PFOA) and perfluorooctane sulfonamide acid (PFOS). [1]

Becaue of the environmental persistence of PFAS, they frequently end up contaminating major water supplies. Many metropolitan cities in the U.S. have water supplies that are contaminated with PFAS, where the characteristics that earned them the name “forever chemicals” make them difficult to remove and increase residents’ exposure levels. To address this troubling statistic, the U.S. Environmental Protection Agency set a 70 ppt mandate for drinking water to reduce exposure. [3] Gagliano et al. explain that the usual techniques for water purification such as UV irradiation and disinfection by free chlorine fail to extract PFA compounds because of their high stability. Extraction techniques such as adsorption, anion-exchange, high pressure nanofiltration and reverse osmosis membrane processes are preferentially recommeded.3 To further demonstrate the extent of water contamination by PFAs, Pelch et al. write that the blood serum of every modern American has multiple PFAs at detectable levels. There are numerous health implications of exposure to PFAs. [1]

Fenton et al. discuss several of the health implications, beginning with the dangers of prenatal exposure. Pregnant mothers exposed to PFAs have babies/children who demonstrate a depressed vaccine response. By doubling the concentration of perfluorooctane sulfonate (PFOS) in maternal serum, a 39% reduction in diphtheria antibody concentration in children (age 5 yr) was seen. At 7 years old, there was a further decline in clinically protective values against diphtheria and tetanus. Other health implications linked with prenatal exposure include low birth rate, early onset puberty and delayed mammary gland development. Other autoimmune diseases have been linked to PFA exposure as well. [2] While the mechanisms linking PFAS with these conditions are not all clear, the risk posed by forever chemicals is heightened by how long they can linger in the body and environment.

Human thyroid disease occurs when PFAS disruptively interact with thyroid hormone binding proteins and thyroid peroxidase (TPO) enzyme activity. PFAS can accumulate in the hepatocytes of the liver leading to P459 CYP pathways disruption, apoptosis, carcinomas, hepatocellular adenomas and disrupted fatty acid trafficking. PFAs have been linked to steatosis in hepatocytes which is a feature of non-alcoholic fatty liver disPolyfluoroalkyl substances (PFAS) create the perfect household items: waterproof, greaseproof, and capable of being non-stick.ease. PFAS cause kidney disease when they are reabsorbed by the renal tubes and later accumulate in renal tissue. Fenton et al. explain that uric acid is a biomarker for nephrotoxicity since uric acid is retained by the kidney when PFAS are preferentially excreted. Exposure is correlated with impaired human sperm motility and penetration as well as endometriosis. PFOA specifically has been linked to liver adenomas, pancreatic acinar cell tumors and testicular Leydig cell adenomas which is known as the triad cancer series of forever chemicals. The PPAR alpha mediated molecular signaling pathway has been singled out for study to elucidate how these PFOA cancer types develop. Unfortunately, expanding the research on the health implications of exposure to PFAS is a challenge because these forever chemicals have a significantly shorter life cycle in mice. Therefore, modeling human studies from mouse trials and correcting for these differences in elimination kinetics later affects how toxicity and the associated disease profiles are studied. [2]

 

References

1. Pelch KE, Reade A, Wolffe TAM, Kwiatkowski CF. PFAS health effects database: Protocol for a systematic evidence map. Environ Int. 2019 Sep;130:104851. doi: 10.1016/j.envint.2019.05.045. Epub 2019 Jul 5. PMIDpfas: 31284092.

2. Fenton SE, Ducatman A, Boobis A, DeWitt JC, Lau C, Ng C, Smith JS, Roberts SM. Per- and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research. Environ Toxicol Chem. 2021 Mar;40(3):606-630. doi: 10.1002/etc.4890. Epub 2020 Dec 7. PMID: 33017053; PMCID: PMC7906952.

3. Gagliano E, Sgroi M, Falciglia PP, Vagliasindi FGA, Roccaro P. Removal of poly- and perfluoroalkyl substances (PFAS) from water by adsorption: Role of PFAS chain length, effect of organic matter and challenges in adsorbent regeneration. Water Res. 2020 Mar 15;171:115381. doi: 10.1016/j.watres.2019.115381. Epub 2019 Dec 10. PMID: 31923761.

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