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GenX

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This article is about the organic chemical. For the open source energy system model, see open energy system models § GenX. For other uses, see GenX (disambiguation).

GenX is a Chemours trademark name for a synthetic, short-chain organofluorine chemical compound, the ammonium salt of hexafluoropropylene oxide dimer acid (HFPO-DA). It can also be used more informally to refer to the group of related fluorochemicals that are used to produce GenX.[1][2] DuPont began the commercial development of GenX in 2009 as a replacement for perfluorooctanoic acid (PFOA, also known as C8), in response to legal action due to the health effects and ecotoxicity of PFOA.[3][4][5]

Although GenX was designed to be less persistent in the environment compared to PFOA, it has proven to be a “regrettable substitute.”[6] Its effects may be equally harmful or even more detrimental than those of the chemical it was meant to replace.[7][6][8]

GenX is one of many synthetic organofluorine compounds collectively known as per- and polyfluoroalkyl substances (PFASs).

Uses

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The chemicals are used in products such as food packaging, paints, cleaning products, non-stick coatings, outdoor fabrics and firefighting foam.[9] The chemicals are manufactured by Chemours, a corporate spin-off of DuPont, in Fayetteville, North Carolina.[10]

GenX chemicals are used as replacements for PFOA for manufacturing fluoropolymers such as Teflon,[2][11] the GenX chemicals serve as surfactants and processing aids in the fluoropolymer production process to lower the surface tension allowing the polymer particles to grow larger. The GenX chemicals are then removed from the final polymer by chemical treatment and heating.[12]

Chemistry

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The manufacturing process combines two molecules of hexafluoropropylene oxide (HFPO) to form HFPO-DA. HFDO-DA is converted into its ammonium salt that is the official GenX compound.[3][2]

The chemical process uses 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid (FRD-903) to generate ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate (FRD-902) and heptafluoropropyl 1,2,2,2-tetrafluoroethyl ether (E1).[13]

When GenX contacts water, it releases the ammonium group to become HFPO-DA. Because HFPO-DA is a strong acid, it deprotonates into its conjugate base, which can then be detected in the water.[3]

Pollution

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In North Carolina, the Chemours Fayetteville plant released GenX compounds into the Cape Fear River, which is a drinking water source for the Wilmington area. A documentary film, The Devil We Know; a fictional dramatization, Dark Waters; and a nonfiction memoir, Exposure: Poisoned Water, Corporate Greed, and One Lawyer's Twenty-Year Battle Against DuPont by Robert Bilott, subsequently publicized the discharges, leading to controversy over possible health effects.[14]

HFPO-DA was first reported to be in the Cape Fear River in 2012[15] and an additional eleven polyfluoroalkyl substances (PFAS) were reported 2014.[16] These results were published as a formal paper in 2015.[17] The following year, North Carolina State University and the EPA jointly published a study demonstrating HFPO-DA and other PFAS were present in the Wilmington-area drinking water sourced from the Cape Fear river.[18]

In September 2017, the North Carolina Department of Environmental Quality (NCDEQ) ordered Chemours to halt discharges of all fluorinated compounds into the river. Following a chemical spill one month later, NCDEQ cited Chemours for violating provisions in its National Pollutant Discharge Elimination System wastewater discharge permit.[19] In November 2017, the Brunswick County Government filed a federal lawsuit alleging that DuPont failed to disclose research regarding potential risks from the chemical.[20]

In spring 2018, Cape Fear River Watch[21] sued Chemours for Clean Water Act violations and sued the NCDEQ for inaction.[22] After Cape Fear River Watch's suits were filed, NCDEQ filed a suit against Chemours, the result of all 3 lawsuits culminated in a consent order.[23] The order signed by all 3 parties requires Chemours drastically reduce PFAS containing water discharges and air emissions, as well as sampling and filtration for well owners with contaminated wells, among other requirements. All materials relative to status of consent order requirements must be published to a public website,https://www.chemours.com/en/about-chemours/global-reach/fayetteville-works/compliance-testing. One requirement under the order was for non-targeted analysis which found 257 "unknown" PFAS being released from Fayetteville Works, (aside from the 100 'known' PFAS which can be quantified.[24] Cape Fear River Watch published[25] that their research of the NC DEQ permit file [26] indicates that the first PFAS byproducts were likely released from Fayetteville Works in 1976 with the production of Nafion which uses HFPO in production (otherwise known as GenX) and creates byproducts termed Nafion Byproducts 1 through 5, some of which have been found in the blood of Cape Fear area residents.[27]

In 2020 Michigan adopted drinking water standards for 5 previously unregulated PFAS compounds including HFPO-DA which has a maximum contaminant level (MCL) of 370 parts per trillion (ppt). Two previously regulated PFAS compounds PFOA and PFOS had their acceptable limits lowered to 8 ppt and 16 ppt respectively.[28][29]

In 2022 Virginia's Roanoke River had become contaminated by GenX at levels reported to be 1.3 million parts per trillion.[30]

Health Effects

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GenX has been shown to cause a variety of adverse health effects. While it was originally marketed as a safer alternative to legacy PFAS, research suggests that GenX poses significant health risks similar to those associated with its predecessor.[6][7][8][9][31]

Liver and Kidney Toxicity

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Studies have demonstrated that the liver is especially vulnerable to GenX exposure.[31][32][33] Animal research has shown that even low doses of GenX can cause liver enlargement and damage.[32][34] Similarly, the kidneys are also sensitive to GenX, with chronic exposure leading to renal toxicity.[34] These effects highlight the potential dangers of prolonged exposure to even small amounts of the chemical.[35][32]

Cancer Risk

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There is increasing concern about the carcinogenic potential of GenX. Research in animal models has linked exposure to various cancers, including liver, pancreatic, and testicular cancers.[31][32][36] Although data on humans are limited, the results from these studies have prompted further investigation into the possible cancer risks posed by GenX.[32][36]

Neurotoxicity and Developmental Effects

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Two 2023 studies have identified potential neurotoxic effects of GenX, particularly during critical developmental windows.[37][38] Pre-differentiation exposure of human dopaminergic-like neurons (SH-SY5Y cells) to low-dose GenX (0.4 and 4 µg/L) resulted in persistent alterations in neuronal characteristics. The study reported significant changes in nuclear morphology, chromatin arrangement, and increased expression of the repressive marker H3K27me3, which is associated with neurodegeneration.[38]

These changes were accompanied by disruptions in mitochondrial function and an increase in intracellular calcium levels, which are critical markers of neuronal health. Notably, GenX exposure led to altered expression of α-synuclein, a protein closely linked to the development of Parkinson's disease. The findings suggest that developmental exposure to GenX may pose a long-term risk for neurodegenerative disorders, particularly Parkinson's disease, due to its impact on key neuronal processes.[38]

Recent research has also underscored the potential for GenX to disrupt glucose and lipid metabolism during critical developmental periods. A 2021 study published in Environment International investigated the effects of prenatal exposure to GenX in Sprague-Dawley rats, revealing significant maternal and neonatal adverse outcomes, such as increased maternal liver weight, altered lipid profiles, and reduced glycogen accumulation in neonatal livers, resulting in hypoglycemia. Additionally, neonatal mortality and lower birth weights were observed at higher doses of GenX .[39]

A 2024 study in Science of The Total Environment expanded upon these findings in mice, demonstrating that gestational exposure to GenX led to increased liver weight, elevated liver enzyme levels (e.g., ALT and AST), and decreased glycogen storage capacity in the liver. Disruptions in gut flora and the intestinal mucosal barrier were also noted, further linking GenX exposure to hepatotoxicity.[33]

Both studies revealed significant alterations in gene expression, particularly in pathways regulating glucose and lipid metabolism. Genes such as CYP4A14, Sult2a1, and Igfbp1 were upregulated, which may have long-term implications for metabolic health. These findings suggest that gestational GenX exposure could trigger metabolic disorders and liver toxicity, posing potential health risks for populations exposed to GenX through contaminated water sources .[33][39]

Immune System and Metabolic Effects

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Studies have demonstrated that exposure to GenX, a replacement for long-chain PFAS chemicals, can lead to complex health effects. GenX has been linked to alterations in immune responses and metabolic processes, as observed in both human and animal studies. For instance, in a study using Monodelphis domestica, GenX exposure upregulated genes associated with inflammation and fatty acid transport.[40] Another study on mice showed that GenX suppressed innate immune responses to inhaled carbon black nanoparticles, while simultaneously promoting lung cell proliferation, including macrophages and epithelial cells.[41] These findings suggest that GenX may have immunosuppressive effects, potentially increasing susceptibility to respiratory agents while encouraging cellular growth in the lungs, raising concerns about respiratory health risks.

This research highlights the potential health implications of GenX exposure, particularly its impact on immune system function and cell proliferation, which may contribute to both immune suppression and adverse health outcomes like inflammation or respiratory diseases. These findings raise concerns about the long-term impact on human health, especially in vulnerable populations.[35]

Drinking water health advisories

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In June 2022 the U.S. Environmental Protection Agency (EPA) published drinking water health advisories, which are non-regulatory technical documents, for GenX and PFBS.[42][43] The lifetime health advisories and health effects support documents assist federal, state, tribal, and local officials and managers of drinking water systems in protecting public health when these chemicals are present in drinking water.

EPA has listed recommended steps that consumers may take to reduce possible exposure to GenX and other PFAS chemicals.[44]

See also

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References

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  1. ^ "C3 Dimer Acid and PFAS". Chemours. Retrieved 23 January 2020.
  2. ^ a b c Beekman, M.; et al. (2016-12-12). "Evaluation of substances used in the GenX technology by Chemours, Dordrecht" (PDF). National Institute for Public Health and the Environment (RIVM, The Netherlands). Retrieved 2017-07-23.
  3. ^ a b c Hogue, Cheryl (2018-02-12). "What's GenX still doing in the water downstream of a Chemours plant?". American Chemical Society (ACS). Retrieved 2019-08-21.
  4. ^ Gillam, Carey (2023-06-02). "Top US chemical firms to pay $1.2bn to settle water contamination lawsuits". the Guardian. Retrieved 2024-10-14.
  5. ^ Rich, Nathaniel (2016-01-06). "The Lawyer Who Became DuPont's Worst Nightmare". The New York Times. Retrieved 2024-10-14.
  6. ^ a b c Ahearn, Ashley (2019-03-24). "A Regrettable Substitute: The Story of GenX". Podcasts: The Researcher's Perspective. 2019 (1). doi:10.1289/EHP5134. ISSN 2169-2181.
  7. ^ a b "US EPA deems two GenX PFAS chemicals more toxic than PFOA". Chemical & Engineering News. Retrieved 2024-10-14.
  8. ^ a b "Fact Sheet: Human Health Toxicity Assessment for GenX Chemicals" (PDF). United States Environmental Protection Agency. March 2023. Retrieved October 14, 2024.
  9. ^ a b "Basic Information on PFAS". PFOA, PFOS and Other PFASs. Washington, D.C.: U.S. Environmental Protection Agency (EPA). 2018-02-18.
  10. ^ "GenX Frequently Asked Questions" (PDF). GenX Investigation. Raleigh, NC: North Carolina Department of Environmental Quality (NCDEQ). 2018-02-15.
  11. ^ "What is the difference between PFOA, PFOS and GenX and other replacement PFAS?". PFOA, PFOS and Other PFASs. EPA. 2018-02-18.
  12. ^ "What is GenX? | Get the Facts".
  13. ^ "DuPont GenX Processing Aid for Making Fluoropolymer Resins" (PDF). 2016-02-09. Archived from the original (PDF) on 2018-02-08. Retrieved 2019-08-21.
  14. ^ "N.C. drinking water tainted with chemical byproduct for decades?". CBS News. 2017-06-26.
  15. ^ Strynar, Mark J.; Dagnino, Sonia; Lindstrom, Andrew; Andersen, Eric; Mcmillan, Larry; Thurman, Michael; Ferrer, Imma; Ball, Carol (2012). Identification of novel polyfluorinated compounds in natural waters using accurate mass TOFMS. SETAC. Long Beach, CA – via ResearchGate.
  16. ^ Strynar, Mark J.; McMahen, Rebecca; Liang, Shuang; Dagnino, Sonia; Lindstrom, Andrew; Andersen, Erik; McMillan, Larry; Thurman, Michael; Ferrer, Imma; Ball, Carol (November 9–13, 2014). Determination of perfluoroalkyl ether carboxylic acids (PFECAs) and sulfonic acids (PFESAs) in North Carolina surface water using high resolution mass spectrometry. SETAC. Vancouver, BC – via ResearchGate.
  17. ^ McCord, James; Strynar, Mark (2019-05-07). "Identification of Per- and Polyfluoroalkyl Substances in the Cape Fear River by High Resolution Mass Spectrometry and Nontargeted Screening". Environmental Science & Technology. 53 (9): 4717–4727. Bibcode:2019EnST...53.4717M. doi:10.1021/acs.est.8b06017. ISSN 0013-936X. PMC 7478245. PMID 30993978.
  18. ^ Sun, Mei; Arevalo, Elisa; Strynar, Mark; Lindstrom, Andrew; Richardson, Michael; Kearns, Ben; Pickett, Adam; Smith, Chris; Knappe, Detlef R. U. (2016-12-13). "Legacy and Emerging Perfluoroalkyl Substances Are Important Drinking Water Contaminants in the Cape Fear River Watershed of North Carolina". Environmental Science & Technology Letters. 3 (12): 415–419. Bibcode:2016EnSTL...3..415S. doi:10.1021/acs.estlett.6b00398.
  19. ^ "GenX Timeline". NCDEQ. Archived from the original on 2018-12-24. Retrieved 2018-04-22.
  20. ^ Clabby, Catherine (2017-11-02). "Newest GenX Lawsuit Attacks DuPont Science". Chapel Hill, NC: North Carolina Health News.
  21. ^ "PFAS - Cape Fear River Watch". 20 September 2019.
  22. ^ Alder, Cole (2018-05-16). "Cape Fear River Watch to file suit against Chemours". Per- and Polyfluoroalkyl Substances; News. Boston, MA: Northeastern University, Social Science Environmental Health Research Institute.
  23. ^ "PFAS - Cape Fear River Watch". 20 September 2019.
  24. ^ "Consent Order Compliance".
  25. ^ "PFAS - Cape Fear River Watch". 20 September 2019.
  26. ^ "Str_Error_Page_Title".
  27. ^ https://genxstudy.ncsu.edu/ [bare URL]
  28. ^ Matheny, Keith (3 August 2020). "Michigan's drinking water standards for these chemicals now among toughest in nation". Detroit Free Press. Archived from the original on 31 January 2022. Retrieved 31 March 2022.
  29. ^ "New state drinking water standards pave way for expansion of Michigan's PFAS clean-up efforts". Michigan.gov. 3 August 2020. Archived from the original on 3 January 2022. Retrieved 5 April 2022.
  30. ^ "Source of 'forever chemical' in the Roanoke River traced to Elliston plant". 10 November 2022.
  31. ^ a b c Caverly Rae, JM; Craig, Lisa; Stone, Theodore W.; Frame, Steven R.; Buxton, L. William; Kennedy, Gerald L. (2015). "Evaluation of chronic toxicity and carcinogenicity of ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate in Sprague–Dawley rats". Toxicology Reports. 2: 939–949. doi:10.1016/j.toxrep.2015.06.001. PMC 5598527. PMID 28962433.
  32. ^ a b c d e Chappell, Grace A.; Thompson, Chad M.; Wolf, Jeffrey C.; Cullen, John M.; Klaunig, James E.; Haws, Laurie C. (2020-03-06). "Assessment of the Mode of Action Underlying the Effects of GenX in Mouse Liver and Implications for Assessing Human Health Risks". Toxicologic Pathology. 48 (3). SAGE Publications: 494–508. doi:10.1177/0192623320905803. ISSN 0192-6233. PMC 7153225. PMID 32138627.
  33. ^ a b c Zhang, Qin-Yao; Xu, Ling-Ling; Zhong, Mei-Ting; Chen, Yu-Kui; Lai, Ming-Quan; Wang, Qi; Xie, Xiao-Li (2024). "Gestational GenX and PFOA exposures induce hepatotoxicity, metabolic pathway, and microbiome shifts in weanling mice". Science of the Total Environment. 907. Elsevier BV: 168059. doi:10.1016/j.scitotenv.2023.168059. ISSN 0048-9697. PMID 37884144.
  34. ^ a b Xu, Ling-Ling; Chen, Yu-Kui; Zhang, Qin-Yao; Chen, Li-Jian; Zhang, Kai-Kai; Li, Jia-Hao; Liu, Jia-Li; Wang, Qi; Xie, Xiao-Li (2022). "Gestational exposure to GenX induces hepatic alterations by the gut-liver axis in maternal mice: A similar mechanism as PFOA". Science of the Total Environment. 820. Elsevier BV: 153281. doi:10.1016/j.scitotenv.2022.153281. ISSN 0048-9697. PMID 35066053.
  35. ^ a b "FACT SHEET: GenX Chemicals Toxicity Assessment - March 2023 Update" (PDF). US EPA. Retrieved 2024-10-15.
  36. ^ a b "What do researchers know about the health impacts of GenX?". WVTF. 25 January 2023. Retrieved 2024-10-13.
  37. ^ Wasel, Ola; King, Hanna; Choi, Youn J.; Lee, Linda S.; Freeman, Jennifer L. (2023-11-09). "Differential Developmental Neurotoxicity and Tissue Uptake of the Per- and Polyfluoroalkyl Substance Alternatives, GenX and PFBS". Environmental Science & Technology. 57 (48). American Chemical Society (ACS): 19274–19284. doi:10.1021/acs.est.3c05023. ISSN 0013-936X. PMC 11299994. PMID 37943624.
  38. ^ a b c Wu, Shichen; Xie, Junkai; Zhao, Han; Sanchez, Oscar; Zhao, Xihui; Freeman, Jennifer L.; Yuan, Chongli (2023). "Pre-differentiation GenX exposure induced neurotoxicity in human dopaminergic-like neurons". Chemosphere. 332. Elsevier BV: 138900. doi:10.1016/j.chemosphere.2023.138900. ISSN 0045-6535. PMID 37172627.
  39. ^ a b Conley, Justin M.; Lambright, Christy S.; Evans, Nicola; McCord, James; Strynar, Mark J.; Hill, Donna; Medlock-Kakaley, Elizabeth; Wilson, Vickie S.; Gray, L. Earl (2021). "Hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX) alters maternal and fetal glucose and lipid metabolism and produces neonatal mortality, low birthweight, and hepatomegaly in the Sprague-Dawley rat". Environment International. 146. Elsevier BV: 106204. doi:10.1016/j.envint.2020.106204. ISSN 0160-4120. PMC 7775906. PMID 33126064.
  40. ^ Cao, Wenqi; Horzmann, Katharine; Schemera, Bettina; Petrofski, Myra; Kendall, Trisha; Spooner, Jennifer; Rynders, Patricia E.; VandeBerg, John L.; Wang, Xu (2023-02-15). "Blood transcriptome responses to PFOA and GenX treatment in the marsupial biomedical model Monodelphis domestica". Frontiers in Genetics. 14. Frontiers Media SA. doi:10.3389/fgene.2023.1073461. ISSN 1664-8021. PMC 9974665. PMID 36873954.
  41. ^ Lee, Ho Young; You, Dorothy J.; Taylor-Just, Alexia J.; Linder, Keith E.; Atkins, Hannah M.; Ralph, Lauren M.; De la Cruz, Gabriela; Bonner, James C. (2022-06-15). "Pulmonary exposure of mice to ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX) suppresses the innate immune response to carbon black nanoparticles and stimulates lung cell proliferation". Inhalation Toxicology. 34 (9–10). Informa UK Limited: 244–259. doi:10.1080/08958378.2022.2086651. ISSN 0895-8378. PMC 9731146. PMID 35704474.
  42. ^ "EPA Announces New Drinking Water Health Advisories for PFAS Chemicals, $1 Billion in Bipartisan Infrastructure Law Funding to Strengthen Health Protections". EPA. 2022-06-15. News release.
  43. ^ "Drinking Water Health Advisories". EPA. 2022-06-15.
  44. ^ "Meaningful and Achievable Steps You Can Take to Reduce Your Risk". PFOA, PFOS and Other PFAS. EPA. 2022-08-18.
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