Medical Policy

This document addresses testing for per- and polyfluoroalkyl substances (PFAS). PFAS are a large group of synthetic chemicals that have been used by numerous industrial and commercial sectors for products that benefited from PFAS' unique properties, including their chemical and thermal stability, water-, heat-, grease-, and oil-resistant qualities. PFAS have been shown to bioaccumulate and biomagnify in wildlife as well as readily accumulate in human tissues such as the lungs, liver, brain, and circulatory system of humans. Because PFAS do not fully biodegrade in the environment, they have been referred to as “forever chemicals.” Research has revealed possible associations between human exposures to certain PFAS and some adverse health outcomes.

PFAS testing may include some of the most studied PFAS substances such as: perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), 2-(N-Methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA).

Note: Please see the following related document for additional information:

• MED.00059 Idiopathic Environmental Illness (IEI)

Note: Please check applicable plan benefits. Benefit language supersedes this document. Some benefit contracts may not include coverage relating to occupational health exposure or testing of non-member samples (for example, PFAS in animals or the environment [food, water, air, soil, etc.]). 

Investigational and Not Medically Necessary:

Testing for PFAS substances is considered investigational and not medically necessary for all indications.

PFAS are a large and ubiquitous group of synthetic chemicals that have been utilized worldwide in consumer products and industry since the 1940s. PFAS have the capability to reduce friction, so they are used in various industries including aerospace, automotive, building, construction, and electronics. They are used for fire suppression because they can quickly extinguish fuel fires. They are also used to manufacture food packaging resistant to grease absorption, to keep food from sticking to cookware, to make mattresses and clothing waterproof and to make sofas and carpets resistant to stains. Other consumer products containing these chemicals include, but are not limited to, cleaning products and personal care products like shampoo, eye makeup, dental floss, and nail polish.

PFAS compounds do not occur naturally in the environment and are referred to as “forever chemicals” because due to the strong fluorine–carbon bonds, PFAS have high chemical stability and are not likely to degrade under typical environmental conditions. As a result of their widespread use and their persistence in the environment, many PFAS have been detected in the blood of people and animals all over the world (Agency for Toxic Substances and Disease Registry [ATSDR], 2021; National Toxicology Program [NTP], 2016).

According to the chemicals database (CompTox) maintained by the U.S. Environmental Protection Agency (EPA), there are approximately 15,000 PFAS chemicals (EPA, 2022).

Health Implications

Ingestion of contaminated food and water is the primary route of PFAS exposure. However, individuals may also experience exposure by inhaling air containing PFAS. Individuals that work in industries that manufacture or use products containing PFAS are at increased risk for PFAS exposure. For the general population, major ingestion sources for PFAS include, but are not limited to: 

• Ingestion: Consuming foods like fish and shellfish grown or raised with PFAS contaminated water or soil;
• Ingestion: Consuming food packaged in materials containing PFAS (e.g., pizza boxes, popcorn bags, fast food containers);
• Inhalation: Breathing PFAS-contaminated dust in the air (e.g., dust can be contaminated by particles and fibers from carpets, upholstery, clothing, other PFAS treated products like certain fabric sprays, and from soil);
• Contact: Absorption of PFAS through the skin is limited and is of minimal concern as an exposure route;
• Transplacental: Several PFAS have been shown to cross the placenta and enter umbilical cord blood.

For infants and toddlers PFAS sources unique to this population may include, but are not limited to:

• Ingestion: Formula mixed with PFAS contaminated water;
• Ingestion: Breastmilk from women who have past or current exposure to PFAS;
• Ingestion: Hand-to-mouth behaviors place infants and young children at increased risk of exposure to a variety of pollutants due to the time they spend crawling and playing on the floor. If surfaces were treated with PFAS-containing stain protectants, toddlers may be exposed through these behaviors.
  (ATSDR, 2024; EPA, 2024; National Academies of Science, Engineering, and Medicine [NASEM], 2022).

Because PFAS breaks down slowly, if at all, humans and animals are repeatedly exposed to them, and blood levels of some PFAS can accumulate over time. PFAS are a public health concern because they can be retained in the body for long periods of time and have been linked to harmful health effects in humans. While the estimated half-lives in the human body are estimated to range from 2 to 8 years, once in surface water, apparent half-lives of PFOA and PFOS are 92 and 41 years, respectively. According to a 2016 report using data from the National Health and Nutrition Examination Survey (NHANES), PFAS chemicals have been detected in the blood of 98% of Americans. Complete avoidance of PFAS is not believed to be possible because the products are so prevalent in the environment. The same chemical properties that make PFAS useful in the above-mentioned products are the same properties that make them difficult to remove from the environment (ATSDR, 2021; National Institute of Environmental Health Sciences [NIEHS], 2024; NTP, 2016).

Multiple agencies and researchers have explored the possible health impacts of PFAS exposure. The ATSDR evaluated peer-reviewed epidemiological studies to assess whether the majority of the evidence suggested an association between perfluoroalkyl exposure and a particular health effect. This method took into consideration the consistency of the findings across studies, the quality of the studies, dose-response, and plausibility. ATSDR pointed out that although the data may provide evidence for an association, it does not always indicate that the observed effect is biologically relevant because the degree of the change may be within the normal limits or not indicative of an adverse health outcome. ATSDR concluded the following:

The available epidemiological data suggest associations between perfluoroalkyl exposure and several health outcomes; however, cause-and-effect relationships have not been established for these outcomes:

• Hepatic effects. Increases in serum enzymes and decreases in serum bilirubin, observed in studies of PFOA, PFOS, and PFHxS, are suggestive of liver alterations. In addition, the results of epidemiological studies of PFOA, PFOS, PFNA, and PFDA suggest an association between perfluoroalkyl exposure and increases in serum lipid levels, particularly total cholesterol and LDL cholesterol;
• Cardiovascular effects. There is suggestive epidemiological evidence for an association between serum PFOA and PFOS and pregnancy-induced hypertension and/or pre-eclampsia;
• Immune effects. Evidence is suggestive of an association between serum PFOA, PFOS, PFHxS, and PFDA levels and decreased antibody responses to vaccines; there is also limited evidence for PFNA, PFUnA, and PFDoDA;
• Developmental effects. Evidence is suggestive of an association between serum PFOA and PFOS and small decreases in birth weight; the decrease in birth weight is ≤2.0 g (0.7 ounces) 1 ng/ml increase in blood PROA or PFOS level (ATSDR, 2021).

The National Toxicology Program (NTP, 2016) conducted a systematic review to evaluate the evidence on exposure to PFOS or PFOA and immune-related health effects to determine whether exposure to either chemical is associated with immunotoxicity for humans. With regards to PFOA, the NTP concludes that:

PFOA is presumed to be an immune hazard to humans based on a high level of evidence that PFOA suppressed the antibody response from animal studies and a moderate level of evidence from studies in humans. … However, the mechanism(s) of PFOA-associated immunotoxicity is not clearly understood and effects on diverse endpoints such as suppression of the antibody response and increased hypersensitivity may be unrelated (NTP, 2016)

The NTP reached the following conclusions with regards to PFOS:

PFOS is presumed to be an immune hazard to humans based on a high level of evidence that PFOS suppressed the antibody response from animal studies and a moderate level of evidence from studies in humans. Although the strongest evidence for an effect of PFOS on the immune system is for suppression of the antibody response, there is additional, although weaker, evidence that is primarily from studies in experimental animals that PFOS suppresses disease resistance and natural killer (NK) cell activity. The evidence indicating that PFOS suppresses multiple aspects of the immune system supports the overall conclusion that PFOS alters immune function in humans. Although the mechanism(s) of PFOS-associated immunotoxicity is not clearly understood, suppression of the antibody response and NK cell function are both potential mechanisms by which PFOS may reduce disease resistance (NTP, 2016).

The EPA provides the following information on the health implications of PFA exposure in humans.:

Current scientific research suggests that exposure to certain PFAS may lead to adverse health outcomes. However, research is still ongoing to determine how different levels of exposure to different PFAS can lead to a variety of health effects. Research is also underway to better understand the health effects associated with low levels of exposure to PFAS over long periods of time, especially in children (EPA, 2024).

Reduction in Environmental Exposure 

Due to growing awareness of the harmful effects of PFAS, the legacy PFAS (such as PFOA and PFOS), have been phased out of production and use in the United States, however, other countries may still manufacture and utilize them. While emissions of PFOA and PFOS have been significantly reduced, due to the permanence and bioaccumulation of these chemicals, there is continued widespread exposure to both PFOA and PFOS. Various studies have reported potential PFOA- and PFOS-associated immunotoxicity in both humans and animals (NIEHS, 2024; NTP, 2016).

While the legacy PFAS were phased out of use in the United States, industry has replaced them with new compounds belonging to the PFAS category. Exposure to new PFAS is difficult to measure. Because there are very few scientific studies on new PFAS, more research is necessary to determine whether they pose a health concern because of their inability to biodegrade (NIEHS, 2024).

Testing for PFAS

PFAS testing is based on a direct measurement of environmental chemicals or their metabolites in human tissues and fluids, such as blood (whole blood, serum, and plasma), urine, hair, nails, and breast milk. Currently there is a lack of oversight and standardization of PFAS laboratory testing methods. In its Guidance on PFAS Exposure, Testing, and Clinical Follow-op, the NASEM states:

There are no standard methods for PFAS exposure biomonitoring; some, but not all, laboratories use methods similar to those used by the CDC. Unlike most clinical laboratories, laboratories that offer PFAS testing are not subject to measurement standardization through external proficiency testing programs that evaluate laboratory performance against preestablished criteria. Laboratories that offer PFAS testing also need not comply with clinical certification, such as Clinical Laboratory Improvement Amendments (CLIA) certification, for reporting of results to patients (NASEM, 2022).

NASEM’s Guidance on PFAS Exposure, Testing and Clinical Follow-Up -2022, recommends PFAS blood testing for individuals “who are likely to have a history of elevated exposure.” Examples of individuals with elevated exposure includes those with occupational exposures (such as firefighters), those who live near PFAS-contaminated facilities and those who live in communities where PFAS contamination has been documented (e.g., drinking water that exceeds regulatory limits). However, the report points out that PFAS blood testing “only assesses body burden at the time of sample collection” and does not identify the sources of exposure or predict future health outcomes. For example, an individual with low blood PFAS levels today may have had more elevated levels in the past. The report points out that:

Interpretation of PFAS blood or urine results is challenging because the specific level of exposure at which harms may occur is unknown, and the science on the potential health effects of exposure to PFAS is advancing quickly, making it difficult to provide advice to clinicians about what follow-up tests might be helpful (NASEM, 2022).

Additionally, many of the conditions or health outcomes that the committee found to be associated with PFAS exposure are common in the general population. The report also recommends that individuals be counseled that there is currently no way to remove or enhance excretion of the PFAS chemicals from the body (NASEM, 2022).

According to the Centers for Disease Control and Prevention (CDC), potential benefits of PFAS blood testing include providing information to individuals that may guide exposure reduction, greater recognition of PFAS-associated health effects, and possible psychological relief from knowing one’s PFAS blood level. The CDC indicates that PFAS testing has several important limitations, including the following: PFAS blood testing results do not provide information for treatment or predict future health problems; there are potential risks associated with PFAS blood testing including the potential for unnecessary further testing and treatment related to false positives from additional screening tests; and there are no approved medical treatments available to reduce PFAS in the body. Furthermore, while exposure reduction is ideal, currently, it is not possible to eliminate all sources of PFAS exposure (ATSDR 2024; NASEM, 2024).

At this time, the ASTDR and CDC have not developed health-based screening recommendations based on PFAS blood levels and encourage clinicians to follow usual standards of care for health concerns. Additional research is still needed to elucidate the health effects of PFAS and inform the benefits and risks of PFAS blood testing, including evidence that such testing ultimately results in clinically meaningful outcomes (ATSDR, 2024).

PFAS testing has become more widely accessible to the public. Traditionally, PFAS testing was obtained via a healthcare provider with physician oversight and consultation with a licensed physician. However, other options are now available. Some clinical laboratories offer consumer-initiated PFAS blood tests that entails the consumer visiting one of the clinical laboratories service centers for a blood draw. Once testing is completed, the results are made available online via a secure portal. The consumer has the option to have a phone consultation with a physician to review the test results. Another option is for the consumer to order a PFAS blood test kit that is delivered at the doorstep. After completing the finger prick collection, the sample is mailed back to the laboratory and results are made available to the consumer online. The consumer is encouraged to review the test results with their physician.

Conclusion

PFAS are extremely persistent chemicals that, due to their high chemical stability, are not expected to degrade under typical environmental conditions. It is thought that exposure to PFAS is impossible to avoid because these chemicals are ubiquitous in the environment. Research currently suggests high levels of PFAS may be associated with several adverse health outcomes however, definitive cause-and-effect relationships have not been established for these outcomes. Furthermore, at this time, PFAS testing has no established impact on clinical decision-making. Additional focused research is needed to demonstrate how PFAS testing may impact disease management in a manner that modifies net health outcomes.

PFAS are a group of thousands of synthetic chemicals that all contain a partially or fully fluorinated carbon chain. The carbon-fluorine bonds are exceptionally strong, so these compounds do not fully break down in the human body or environment. Their chemical properties permit them to resist oil and water as well as reduce friction. As a result, PFAS containing products have been widely used in industry and consumer products.

In humans, properties of the most extensively studied PFAS include the following:

• Absorption: Absorbed in the lungs and intestines, and to a lesser degree, in the skin;
• Distribution: Binds to serum proteins and to a lesser extent, to tissue proteins (such as, brain, liver, and kidneys);
• Metabolism: Most are not metabolized, however; some are metabolized to other PFAS;
• Elimination: Excreted primarily in urine (clearance rate may vary based on kidney function and gender) but also, excreted through menstruation, defecation, breastfeeding, and placental transfer;
• Half-life: Ranges from a few days to 8 years or more, depending on the specific PFAS type (ATSDR, 2024)

Current scientific research suggests that exposure to certain PFAS may be linked to harmful health outcomes, but definitive cause-and-effect relationships have not been established for these outcomes. As technology related to the diagnosis and treatment of PFAS exposure continues to be studied, the role of PFAS testing may evolve. However, at this time, there is insufficient evidence in the published literature demonstrating that the results of PFAS testing alter clinical management and result in improved net health outcomes.

Bioaccumulation: The process of a substance, especially a contaminate, to become concentrated in the bodies of living organisms.

Biomagnification: The process of a toxic substance (especially pesticide or pollutant) increasing it concentration in the tissues or organisms as a result of having ingested other plants or animals which contain the toxic substances.

Half-life: The time required for a substance to reduce to half of its initial size.

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:
For the following procedure codes, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Peer Reviewed Publications:

1. Conder JM, Hoke RA, De Wolf W, et al. Are PFCAs bioaccumulative? A critical review and comparison with regulatory criteria and persistent lipophilic compounds. Environ Sci Technol. 2008; 42(4):995-1003.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Agency for Toxic Substances and Disease Registry (ATSDR). Per- and Polyfluoroalkyl Substances (PFAS) and Your Health. PFAS Information for Clinicians – 2024. Last reviewed January 18, 2024. Available at: https://www.atsdr.cdc.gov/pfas/resources/pfas-information-for-clinicians.html. Accessed on June 5, 2024.
2. Agency for Toxic Substances and Disease Registry (ATSDR). PFAS in the United States population (2023). Last reviewed January 18, 2024. Available at: PFAS in the US population | ATSDR (cdc.gov) Accessed on June 5, 2024.
3. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Perfluoroalkyls (2021). Last updated May 2021. Available at: https://www.ncbi.nlm.nih.gov/books/NBK592143/pdf/Bookshelf_NBK592143.pdf. Accessed on June 5, 2024.
4. Crowley R, Mathew S, Hilden D; et al. Environmental health: A position paper from the American College of Physicians. Ann Intern Med. 2022; 175(11):1591-1593.
5. National Academies of Science, Engineering, and Medicine (NASEM) Guidance on PFAS Exposure. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up (2022). The National Academies Press. Available at: https://nap.nationalacademies.org/download/26156. Accessed on June5, 2024.
6. National Institute of Environmental Health Sciences (NIEHS, 2024). Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS). Last reviewed May 3, 2024. Available at: National Institute of Environmental Health Sciences: Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS) (nih.gov). Accessed on June 5, 2024.
7. National Toxicology Program (NTP) 2016. Monograph on immunotoxicity associated with exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Research Triangle Park, NC: National Toxicology Program. Published September 2016. Available at: pfoa_pfosmonograph_508.pdf (nih.gov). Accessed on June 5, 2024.
8. U.S. Department of Health and Human Services Agency for Toxic Substances and Disease Registry (ATSDR). 2021 Annual Report. Available at: ATSDR-2021-Annual-Report-H.pdf (cdc.gov). Accessed on June 5, 2024.
9.  U.S. Environmental Protection Agency (EPA). Our Current Understanding of the Human Health and Environmental Risks of PFAS. Updated May 16, 2024. Available at  Our Current Understanding of the Human Health and Environmental Risks of PFAS | US EPA Accessed on June 5, 2024.
10. U.S. Environmental Protection Agency (EPA). Navigation on Panel to PFAS Structure Lists (2022). Available at: CompTox Chemicals Dashboard (epa.gov). Accessed on June 5, 2024.

1. Agency for Toxic Substances and Disease Registry (ATSDR). Per- and Polyfluoroalkyl Substances (PFAS) and Your Health. What are PFAS? Last reviewed January 18, 2024. Available at: PFAS chemicals overview | ATSDR (cdc.gov). Accessed on June 4, 2024.
2. National Institute of Environmental Health Sciences. Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS). Last reviewed May 3, 2024. Available at: https://www.niehs.nih.gov/health/topics/agents/pfc#:~:text=PFAS%20are%20a%20group%20of,the%20U.S.%20Environmental%20Protection%20Agency. Accessed on June 5, 2024.

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.