Per- and polyfluoroalkyl substances—or PFAS—are increasingly in the spotlight these days. As concern mounts regarding humans’ impact on the environment and on our own health, these long-lived contaminants are seeing increasing testing, regulation, and even litigation. But what does this have to do with the clinical lab? Read on for answers to some common questions about the clinical concerns surrounding PFAS.
What are PFAS?
Chemically, a PFAS is an organic substance that contains at least one fully fluorinated methyl or methylene carbon atom (without a hydrogen, chlorine, bromine, or iodine atom attached). These synthetic chemicals have a wide range of applications due to their water, grease, and stain resistance. Unfortunately, the same chemical stability that makes PFAS valuable in everything from fabrics to firefighting foam1,2 also leads to long-term persistence in human bodies and the environment. Nicknamed “forever chemicals,” their ability to contaminate large areas and bioaccumulate in tissues has caught the attention of both researchers and policymakers.
Where are PFAS found?
PFAS are widespread in products used today, from ubiquitous household goods to specialty medical devices. You’ve likely come into contact with PFAS on your cookware, clothing, or carpets, or in your beakers, graduated cylinders, flexible tubing, and even the screens of your lab devices. The high chemical resistance of these molecules make them well-suited to precision lab work in which inert, low-extractable materials are key.
In the lab, PFAS are most often found in analytical instruments and consumables, but are present in many other products as well (see Table 1).3
|Bottles, vials, and caps||Made of polymeric PFAS to minimize reactivity and leaching|
|Cell culture surfaces||Nanofibrillar structure can create biomimetic surface, improving consistency and reproducibility4|
|Chromatography columns||Some based on polymeric PFAS|
|Chromatography instruments||Polymeric PFAS in solvent degasser, likely to minimize reactivity|
|Chromatography solvents||Some contain PFAS, potentially due to their hydrophobic or oleophobic nature|
|Filters||The low surface tension of PFAS reduces sorption of compounds of interest to filters|
|General seals and membranes||Used in chromatography, sterilization (e.g., autoclaves), and heating (e.g., oven) due to their corrosion resistance and stability over a broad temperature range|
|General solvents||PFAS used for their hydrophobic and oleophobic nature|
|Lubricants (oils and greases)||Used due to minimal reactivity, flammability, and corrosion|
|Personal protective equipment (PPE)||Latex gloves and materials with moisture or flame resistance barriers often contain PFAS5|
|Protein sequencing membranes||Made of polymeric PFAS, possibly due to their non-reactivity or ability to be stretched to form pores of specific sizes6|
|Sterilization medium||Used to sterilize insulated vessels|
|Tap water||Present in many labs’ public water supplies, often used for washing reusable equipment7|
|Tape||Made of polymeric PFAS to minimize reactivity and leaching|
|Tubing||Some types contain PFAS due to their inertness, low coefficient of friction, or cell adhesion8|
|Table 1. Laboratory equipment applications of PFAS. Data from Glüge et al. (2020); Ebnesajjad (2017); Oklahoma Environmental Quality (2022); Smalling et al. (2023); 3M (2019).|
What are the health effects of PFAS?
These chemicals are associated with numerous negative effects on human health, including respiratory issues, nephrotoxicity, hepatotoxicity, thyroid dysfunction, elevated serum lipids, osteoarthritis, immunotoxicity, and irritation or damage to the skin or eyes.9 The immune system is a particular target of PFAS toxicity, with associations found between PFAS exposure and immunosuppression (especially decreased antibody response to vaccines),10 hypersensitivity,11 and autoimmunity.12
PFAS are also known to accumulate in the placenta and pass into fetal organs and tissues during pregnancy.13 They have been associated with diseases of pregnancy, including gestational diabetes and preeclampsia,14 and higher rates of miscarriage.15 In terms of fetal outcomes, PFAS may be associated with lower birth weight and gestational age,16 slower childhood growth,17 reduced bone density,18 neurobehavioral problems, immunosuppression,19 and higher rates of cerebral palsy.20
Perfluorooctanoic acid (PFOA), the most extensively studied PFAS, is classified by the International Agency for Research on Cancer as a possible human carcinogen due to associations between high PFOA exposure and elevated rates of kidney and testicular cancers.21 Ongoing investigations are examining potential links between PFAS and ovarian, endometrial, prostate, and thyroid cancers, as well as lymphoma and childhood leukemia.22
With these concerns, it’s no surprise that clinical PFAS testing is garnering increasing attention.
Why should clinical labs test for PFAS?
Humans can be exposed to PFAS through a variety of routes: occupational hazards, airborne pollutants, PFAS-based products or packaging, or even contaminated food or drink. True to their “forever” nickname, these chemicals can accumulate in the human body, increasing the risk of deleterious effects. PFAS testing can establish baseline levels, help monitor exposure, provide information on patients’ risk of associated health outcomes, and guide medical advice going forward.
Not everyone requires PFAS testing. Biomonitoring is rarely included in routine clinical care due to the cost and lack of necessity—and PFAS are no exception. Furthermore, two decades of surveys have revealed that over 95 percent of the US population has measurable serum PFAS levels,23 so universal testing may cause pain or anxiety without yielding clinically useful information.
The committee on the Guidance on PFAS Testing and Health Outcomes recommends that clinicians offer testing to patients with a likely history of elevated exposure.24 These may include people who work with fluorochemicals, contaminated materials, or products containing PFAS, as well as people who live in, work in, or obtain food or water from contaminated areas. Retesting is recommended for confirmatory purposes, if a patient’s likelihood of exposure changes, or after at least a year for routine follow-up. The guidance adds that the benefits of PFAS testing generally outweigh its harms for people who request it and that the principles of justice, autonomy, and shared decision-making support the granting of such requests. Finally, the Committee’s report states, “When clinicians discuss results of PFAS with patients, the results will be most useful if accompanied by information on how exposure occurs, the potential associated health effects, and strategies that may reduce exposure.”24
How do you test for PFAS?
Although there is no standard method for PFAS testing, many labs use protocols based on that of the Centers for Disease Control and Prevention (CDC). The CDC’s protocol involves analyzing a serum sample using a combination of solid phase extraction, chromatographic separation, and mass spectrometry.25 Other labs use different protocols, test different sample types, offer additional assays (such as total oxidizable precursors or branched isomer separation),26 or even design custom assays for clinical or industrial clients. Point-of-care and self-collection testing are also increasing, with new technologies making finger-prick sampling a viable option for PFAS analysis.27
But testing is not without its challenges. PFAS are so prevalent and so tenacious that contamination is a threat in every phase of the testing process. Careful controls and specialized supplies that comply with stringent regulatory requirements for PFAS testing are vital to alleviate this risk.
The plethora of testing protocols can also create confusion when patients’ samples are analyzed using different methods at different times or in different locations.28 This is especially true when using different sample types; for instance, although a common “rule of thumb” is an approximate 2:1 ratio between PFAS concentrations in serum and in whole blood, true values may vary widely depending on the types of PFAS under investigation.29
Additionally, some recommended limits for PFAS contamination are so low that not all labs are capable of testing at those levels, or of doing so reliably and reproducibly. Even regulatory requirements differ between states and countries, making it difficult for labs and suppliers to keep up with compliance. And with new PFAS formulations arising regularly, the scope of testing is only expanding.
PFAS Testing Reimbursement
ICD-10 diagnostic codes
|ICD-10 Z77.11||Contact with and (suspected) exposure to environmental pollution|
|ICD-10 Z77.111||Contact with and (suspected) exposure to water pollution|
|ICD-10 Z77.29||Contact with and (suspected) exposure to other hazardous substances|
|ICD-10 Z13.88||Encounter for screening for disorder due to exposure to contaminants|
CPT billing codes
|CPT 82542||Column chromatography/mass spectrometry, analyte not elsewhere specified; quantitative, single stationary and mobile phase|
|CPT 83921||Chemistry procedures; organic acid, single, quantitative|
|Individually determined||Specific to relevant PFAS-related health screenings; may include lipid panels, endocrine function testing (especially thyroid), screenings for cancer (especially kidney, testicular, and breast) and autoimmune diseases (especially ulcerative colitis), and assessment for pregnancy-related health effects (such as hypertensive disorders) if applicable|
|Table 2. Diagnostic and billing codes for US reimbursement of PFAS testing and, if needed, assessment for PFAS-related health outcomes. Data from Calonge et al. (2022);30 PFAS Community Campaign (2020).31|
How can people avoid—or treat—PFAS exposure?
“Forever chemicals” last for years or even decades in the human body and in the environment. So how can laboratory medicine professionals keep their distance? Water, whether for drinking or lab applications, should be purified using a filter capable of removing PFAS. Where possible, consider PFAS-safe alternatives to common lab products—for instance, nitrile gloves rather than latex or PVC, or bottles, vials, and caps made from polypropylene or high-density polyethylene rather than Teflon-lined or low-density polyethylene consumables.5
Because there are currently no treatments capable of reducing PFAS concentrations in human tissues, exposure reduction is vital—particularly given these chemicals’ persistence. However, for patients with past or ongoing exposures, clinical screening for the potential health effects of PFAS exposure may enable early diagnosis and treatment of related conditions—making PFAS a key consideration for clinical laboratory professionals now and in the future.
Labs That Offer PFAS Testing
|empowerDX||Blood (finger prick)||$249||10–15 days|
|Eurofins Scientific SE||Serum||Not provided||5 days|
|Blood (finger prick)||Not provided||15–20 days|
|NMS Labs||Serum/plasma||$470||7–14 days|
|SGS AXYS||Blood/serum||$420–570||30 days|
|Table 3. Laboratories offering clinical PFAS testing. Data from PFAS-REACH (2022).32|
- PFAS in the textile and leather industries. Minnesota Pollution Control Agency. May 2023. https://www.pca.state.mn.us/sites/default/files/gp3-06.pdf.
- Firefighting foams. Interstate Technology Regulatory Council. July 2023. https://pfas-1.itrcweb.org/3-firefighting-foams.
- Glüge J et al. An overview of the uses of per- and polyfluoroalkyl substances (PFAS). Environ Sci Process Impacts. 2020;22(12):2345–2373. doi:10.1039/d0em00291g.
- Ebnesajjad S. Chapter 7: Properties, characteristics, and applications of expanded PTFE (ePTFE) products. In: Expanded PTFE Applications Handbook. William Andrew Applied Science Publishers; 2017;163–170.
- Per- & Polyfluoroalkyl Substances (PFAS) General Sampling Guidance. Oklahoma Department of Environmental Quality. April 2022. https://www.deq.ok.gov/wp-content/uploads/land-division/PFAS-Sampling-Guidance.pdf.
- Ebnesajjad S. Chapter 10: Filtration. In: Expanded PTFE Applications Handbook. William Andrew Applied Science Publishers; 2017;213–231.
- Smalling KL et al. Per- and polyfluoroalkyl substances (PFAS) in United States tapwater: comparison of underserved private-well and public-supply exposures and associated health implications. Environ Int. 2023;178:108033. doi:10.1016/j.envint.2023.108033.
- PFAS in the Medical Industry. 3M. February 1, 2019. https://news.3m.com/PFAS-in-the-Medical-Industry.
- Toxicological Profile for Perfluoroalkyls. Agency for Toxic Substances and Disease Registry. May 2021. https://www.atsdr.cdc.gov/ToxProfiles/tp200.pdf.
- von Holst H et al. Perfluoroalkyl substances exposure and immunity, allergic response, infection, and asthma in children: review of epidemiologic studies. Heliyon. 2021;7(10):e08160. doi:10.1016/j.heliyon.2021.e08160.
- Jackson-Browne MS et al. PFAS (per- and polyfluoroalkyl substances) and asthma in young children: NHANES 2013-2014. Int J Hyg Environ Health. 2020;229:113565. doi:10.1016/j.ijheh.2020.113565.
- Fart F et al. Perfluoroalkyl substances are increased in patients with late-onset ulcerative colitis and induce intestinal barrier defects ex vivo in murine intestinal tissue. Scand J Gastroenterol. 2021;56(11):1286–1295. doi:10.1080/00365521.2021.1961306.
- Mamsen LS et al. Concentrations of perfluoroalkyl substances (PFASs) in human embryonic and fetal organs from first, second, and third trimester pregnancies. Environ Int. 2019;124:482–492. doi:10.1016/j.envint.2019.01.010.
- Szilagyi JT et al. Perfluoroalkyl substances (PFAS) and their effects on the placenta, pregnancy, and child development: a potential mechanistic role for placental peroxisome proliferator-activated receptors (PPARs). Curr Environ Health Rep. 2020;7(3):222–230. doi:10.1007/s40572-020-00279-0.
- Jensen TK et al. Association between perfluorinated compound exposure and miscarriage in Danish pregnant women. PLoS One. 2015;10(4):e0123496. doi: 10.1371/journal.pone.0123496.
- Zhang Y et al. Association of early pregnancy perfluoroalkyl and polyfluoroalkyl substance exposure with birth outcomes. JAMA Netw Open. 2023;6(5):e2314934. doi:10.1001/jamanetworkopen.2023.14934.
- Sevelsted A et al. Effect of perfluoroalkyl exposure in pregnancy and infancy on intrauterine and childhood growth and anthropometry. Sub study from COPSAC2010 birth cohort. EBioMedicine. 2022;83:104236. doi:10.1016/j.ebiom.2022.104236.
- Carwile JL et al. Serum PFAS and Urinary Phthalate Biomarker Concentrations and Bone Mineral Density in 12-19 Year Olds: 2011-2016 NHANES. J Clin Endocrinol Metab. 2022;107(8):e3343–e3352. doi:10.1210/clinem/dgac228.
- Granum B et al. Pre-natal exposure to perfluoroalkyl substances may be associated with altered vaccine antibody levels and immune-related health outcomes in early childhood. J Immunotoxicol. 2013;10(4):373–379. doi:10.3109/1547691X.2012.755580.
- Liew Z et al. Prenatal exposure to perfluoroalkyl substances and the risk of congenital cerebral palsy in children. Am J Epidemiol. 2014;180(6):574–581. doi:10.1093/aje/kwu179.
- Bartell SM, Vieira VM. Critical review on PFOA, kidney cancer, and testicular cancer. J Air Waste Manag Assoc. 2021;71(6):663–679. doi:10.1080/10962247.2021.1909668.
- PFAS Exposure and Risk of Cancer. National Cancer Institute. https://dceg.cancer.gov/research/what-we-study/pfas.
- Kato K et al. Trends in exposure to polyfluoroalkyl chemicals in the U.S. Population: 1999-2008. Environ Sci Technol. 2011;45(19):8037-45. doi:10.1021/es1043613.
- Calonge BN et al. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. National Academies Press; 2022.
- Botelho J, Pirkle JL. Laboratory Procedure Manual: Perfluoroalkyl and Polyfluoroalkyl Substances. CDC Environmental Health. https://wwwn.cdc.gov/nchs/data/nhanes/2017-2018/labmethods/PFAS-J-MET-508.pdf.
- Per-and Polyfluoroalkyl Substances (PFAS) Analysis. SGS AXYS. https://www.sgsaxys.com/sampling-analysis/pfas.
- Carignan CC et al. Self-collection blood test for PFASs: comparing volumetric microsamplers with a traditional serum approach. Environ Sci Technol. 2023;57(21):7950–7957. doi:10.1021/acs.est.2c09852.
- Sampling and Analytical Methods. Interstate Technology Regulatory Council. July 2023. https://pfas-1.itrcweb.org/11-sampling-and-analytical-methods.
- Ehresman DJ et al. Comparison of human whole blood, plasma, and serum matrices for the determination of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and other fluorochemicals. Environ Res. 2007;103(2):176–184. doi:10.1016/j.envres.2006.06.008.
- Calonge BN et al. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up: Consensus Study Report Highlights. National Academy of Sciences. July 2022. https://nap.nationalacademies.org/resource/26156/PFAS%20Guidance%20Highlights.pdf.
- Medical Testing for PFAS. PFAS Community Campaign. April 28, 2020. https://cswab.org/wp-content/uploads/2020/04/Fact-Sheet-Medical-Testing-PFAS-Community-Campaign-FINAL-28-April-2020.pdf
- PFAS Blood Testing. PFAS-REACH. May 2022. https://docs.google.com/spreadsheets/d/1kUdZIkpA-cIaKbEwv_7vm8_l1q6kOu-r3zErxwYwr08.