Human civilization has produced amazing technologies that enable almost eight billion people to live on this planet. In the process, we have produced countless toxic pollutants, including some that are called forever chemicals and persistent environmental pollutants (POPs). They do not break down in the environment and bioaccumulate in the animals that we eat and in us. Some that were identified decades ago include organochlorine pesticides such as DDT, as well as polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDD, or dioxins) and dibenzofurans (PCDF)1. More recently, a new class of toxic POPs called per- and polyfluoroalkyl substances (PFAS) were identified2. They are a large, complex group of synthetic chemicals that have been used in consumer products since the 1950s. They are in many products. For example, PFAS have been used to keep food from sticking to packaging or cookware, make clothes and carpets resistant to stains, and create firefighting foam that is more effective.

They have a polar end group (such as COOH) and a chain of carbons with fluorine atoms attached to them in covalent bonds. Because the carbon-fluorine bond is one of the strongest, these chemicals do not degrade easily in the environment. Two of them, perfluorooctanoic acid (PFOA) and the sodium salt of perfluorosulfonic acid (PFOS) were removed from consumer products in the early 2000s. They are called legacy PFAS. They were mixed with polytetrafluoroethylene (also known as Teflon, made by Tefal) and used in non-stick cookware. A recent study found both PFOA and PFOS in the blood of many people in the USA, China and other countries3-5. One report by the Centers for Disease Control and Prevention in the USA, using data from the National Health and Nutrition Examination Survey (NHANES), found PFAS in the blood of 97% of Americans6-7. Another NHANES report suggested blood levels of PFOS and PFOA in people have been reduced since those chemicals were removed from consumer products in the early 2000s. However, new PFAS chemicals have been created and exposure to them is difficult to assess.

Concerns about the public health impact of PFAS have arisen because of their widespread use and occurrence. More than 9000 have been identified. They remain in the environment for an unknown amount of time – possibly for centuries. Over time, people can take in more of the chemicals than they excrete. This leads to bioaccumulation in bodies. The research conducted to date reveals possible links between human exposures to PFAS and adverse health outcomes8. These health effects include altered metabolism, fertility, reduced fetal growth and increased risk of being overweight or obese and reduced ability of the immune system to fight infections. While knowledge about the potential health effects of PFAS has grown, many questions remain unanswered. Therefore, NIEHS continues to fund or conduct research to better understand the effects of PFAS exposure7.

The NIEHS does this through the National Toxicology Program (NTP)7. The NTP is an interagency testing program headquartered at NIEHS. In 2016, based on evidence from prior studies, NTP concluded that PFOA and PFOS were hazardous to immune system function in humans. NTP is leading multi-faceted toxicology studies to evaluate and identify the adverse effects of important chemicals. They have done animal studies, including a two-year study on PFOA and 28-day studies on these seven PFAS chemicals: PFBS, PFHxS, PFOS, PFHxA, PFOA, PFNA, and PFDA. A long-term study showed a link between PFAS exposure and increased risk of Type 2 diabetes in women.

Researchers are also studying the health effects of PFOA and a PFOA replacement on the offspring of exposed mice. Serum concentrations of legacy PFASs in humans are decreasing globally but total exposures to newer PFASs and precursor compounds have not been well characterized. Human exposures to legacy PFASs from seafood and drinking water are stable or increasing in many regions, suggesting observed declines reflect phase-outs in legacy PFAS use in consumer products. Many regions globally are continuing to discover PFAS-contaminated sites from aqueous film-forming foam (AFFF) use, particularly next to airports and military bases. Exposures from food packaging and indoor environments are uncertain due to a rapidly changing chemical landscape where legacy PFASs have been replaced by diverse precursors and custom molecules that are difficult to detect.

Several studies find significant associations between PFAS exposure and adverse immune outcomes in children. Dyslipidemia is the strongest metabolic outcome associated with PFAS exposure. Evidence for cancer is limited to manufacturing locations with extremely high exposures and insufficient data are available to characterize the impacts of PFAS exposures on neurodevelopment. Preliminary evidence suggests significant health effects associated with exposure to emerging PFASs. Lessons learned from legacy PFASs indicate that limited data should not be used as a justification to delay risk mitigation actions for replacement PFASs.

Exposure to PFASs is ubiquitous and has been associated with an increased risk of several cardiovascular and metabolic diseases9. Three hundred twelve overweight/obese adolescents from the Study of Latino Adolescents at Risk (SOLAR) and 137 young adults from the Southern California Children’s Health Study (CHS) were included in the analysis10. Plasma PFAS concentrations and the effects on metabolism (the metabolome) were determined. PFAS exposure was linked to changes in tyrosine metabolism and de novo fatty acid biosynthesis. For example, higher concentrations of PFASs led to an increase in thyroxine (T4), a thyroid hormone related to tyrosine metabolism. Similarly, the important fat, arachidonic acid, increased. Exposure to PFAS is associated with changes in amino acid metabolism and lipid metabolism in adolescents and young adults.

So, the United States Food and Drug Agency (FDA) has been developing and validating analytical methods to determine the concentrations of hundreds of PFASs in a variety of foods. The FDA already analyzes about 180 food items for about 800 environmental toxins, including heavy metals, pesticides, herbicides, mycotoxins and environmental chemicals. They are also starting to analyze human milk for these substances. So, even though much has yet to be learned, many scientists and government agencies are planning and performing many more studies.

In the meantime, avoiding meat and consuming dietary fiber can support the neuroendocrine immune system and human health.

Notes

1 World Health Organization. Food safety: persistent organic pollutants (POPs). 2020.
2 Mohammed, A.N. et al. Impact of household cooking on release of fluorinated compounds PFOA and PFOS from Tefal coated cookware to foods. World Journal of Advanced Research and Reviews. 2019. Volume 03, pp. 24–35.
3 Agency for Toxic Substances and Disease Registry. PFAS in the U.S. Population, 22 Dec., 2022.
4 Liu, D. et al. Distribution of per- and poly-fluoroalkyl substances and their precursors in human blood. Journal of Hazardous Materials. Volume 441, article 129908.
5 Chang, X. et al. Plasma PFOA and PFOS levels, DNA methylation, and blood lipid levels: a pilot study. Environmental Science & Technology. 2022. Volume 56, p. 17039-17051.
6 Lewis, R.C. et al. Serum biomarkers of exposure to perfluoroalkyl substances in relation to serum testosterone and measures of thyroid function among adults and adolescents from NHANES 2011–2012. International Journal of Environmental Research & Public Health. 2015. Volume 12, p. 6098–6114.
7 National Institute of Environmental Health Sciences. Perfluoroalkyl and polyfluoroalkyl substances. 9 March, 2023.
8 Fenton, S.E. et al. Per‐ and polyfluoroalkyl substance toxicity and human health review: current state of knowledge and strategies for informing future research. Environmental Toxicology and Chemistry, 2021. Volume 40, pp. 606–630.
9 Sunderland, E.M. et al. A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects. Journal of Exposure Science & Environmental Epidemiology. 2019. Volume 29, p. 131-147.
10 Goodrich, J.A. Metabolic signatures of youth exposure to mixtures of per- and polyfluoroalkyl substances: a multi-cohort study. Environmental Health Perspectives, 22 Feb. 2023. Volume 131, article 027005.