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Reference Guide
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GenX/HPFO-DA
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2,3,3,3-tetrafluoro-2-(heptafluoropropoxy) propanoate

GenX/HPFO-DA refers to a group of perfluoroalkyl substances (PFAS) that have raised concern due to their presence in the environment and potential adverse health effects on humans.  

"Forever chemicals" such as Per- and Polyfluoroalkyl Substances (PFAS) have come under scrutiny due to their environmental persistence and potential health risks.  These synthetic chemicals, characterized by their strong carbon-fluorine bonds, are notoriously resistant to natural degradation, earning them their foreboding nickname. 

Among the newer generations of PFAS is Hexafluoropropylene oxide dimer acid, commonly known as GenX/HPFO-DA are synthetic chemicals used in various industrial processes, notably in the manufacturing of non-stick coatings.  

Initially introduced as a safer alternative to older PFAS compounds like PFOA, GenX is now facing its own controversies regarding environmental impact and safety, highlighting the complexities of managing and understanding the long-term effects of these chemical substances.

What is GenX/HPFO-DA?  [1., 2.]

GenX, chemically known as hexafluoropropylene oxide-dimer acid (HFPO-DA), is a synthetic compound used as a processing aid in the manufacture of high-performance fluoropolymers like Teflon. 

As a successor to PFOA, a PFAS known for its long persistence in the environment, GenX is touted for its supposedly safer profile and faster degradation. However, it has been found in surface and drinking water near industrial sites, particularly where fluorochemicals are manufactured, leading to concerns about its potential environmental and health impacts due to its persistence and toxicity.

GenX was developed as a replacement for perfluorooctanoic acid (PFOA), following its phase-out due to environmental and health concerns. HFPO-DA is known for its role in the GenX processing technology and has been studied for its toxicological effects, particularly regarding developmental toxicity in animal models.

 It has been studied for its effects on developmental toxicity in rats, revealing potential health risks such as dysregulation of carbohydrate and lipid metabolism, reductions in maternal thyroid hormone levels, and increased neonatal mortality at certain exposure levels.  

GenX's biological impact is mediated through mechanisms like PPAR signaling pathways, indicating its profound metabolic and developmental influence.

GenX/HPFO-DA Toxicological Implications and Health Risks  [3.]

In 2021, the EPA completed a human health toxicity assessment for GenX chemicals, identifying and assessing the health risks from exposure. The evaluation focused on the toxic effects of oral exposure, such as liver and kidney damage, immune system effects, developmental issues, and potential cancer risks. 

The liver seems particularly susceptible to damage from GenX/HPFO-DA.  One study explored GenX's effects on human liver cells (HepG2) and found that GenX exposure reduces cell viability, enhances apoptosis, and increases intracellular reactive oxygen species (ROS), suggesting oxidative stress induction.  [4.] 

It also significantly upregulated apoptosis-related genes and proteins, indicating its toxic potential through ROS-mediated apoptosis. The findings underline the need for a deeper understanding of GenX's molecular and toxicological mechanisms.

Reference doses (RfDs) established for these effects aim to define safe ingestion levels, with chronic exposure RfDs being particularly stringent at 0.000003 mg/kg-day, indicating the severity of potential health impacts from prolonged exposure.

Lab Testing for Environmental Toxins

GenX/HFPO-DA is one example of the increasing numbers of environmental toxins to which we are exposed.  Increasingly, lab companies are offering test panels to assess for the presence of such toxins.  

Some companies also offer blood testing to assess immune responses to these toxic chemicals.  

Additionally, many companies are now offering genetic testing to assess an individual’s genetic susceptibility to the presence of certain toxins; defects in particular detoxification pathways may indicate an increased likelihood of toxin buildup and therefore, increased exposure over time.  

Testing for toxin exposure may be done via blood, urine, stool, or hair.

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See References

[1.] Conley JM, Lambright CS, Evans N, et al. 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. 2021;146:106204. doi:https://doi.org/10.1016/j.envint.2020.106204

[2.] Mullin L, Katz D, Riddell N, Plumb R, Burgess JA, Yeung LWY, Jogsten IE. Analysis of hexafluoropropylene oxide-dimer acid (HFPO-DA) by Liquid Chromatography-Mass Spectrometry (LC-MS): Review of Current Approaches and Environmental Levels. Trends Analyt Chem. 2019;118:828-839. doi: 10.1016/j.trac.2019.05.015. PMID: 31501636; PMCID: PMC6733277. 

[3.] US EPA O. Human Health Toxicity Assessments for GenX Chemicals. www.epa.gov. Published October 21, 2021. https://www.epa.gov/chemical-research/human-health-toxicity-assessments-genx-chemicals 

[4.] Yoo HJ, Pyo MC, Park Y, Kim BY, Lee KW. Hexafluoropropylene oxide dimer acid (GenX) exposure induces apoptosis in HepG2 cells. Heliyon. 2021 Oct 28;7(11):e08272. doi: 10.1016/j.heliyon.2021.e08272. PMID: 34765786; PMCID: PMC8571496.

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