Perspectives on the health issues and the regulatory actions for PFAS

Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic chemicals. They have been used in consumer products since the 1940s. 

PFAS basically have a carbon-fluorine covalent bond which is very strong and thus, PFAS have a long half-life, meaning that they do not breakdown easily. For example, the estimated mean half-life of perfluorooctanoic acid (PFOA) in the human body is 1.48 to 5.1 years and 2.84 to 8.5 years for perfluorohexanesulfonic acid (PFHxS) based on a scholarly study.

The literature discusses legacy and replacement PFAS. Legacy PFAS are PFAS that have been around for decades and have been mostly phased out or have decreased uses. Examples include PFOA and perfluorooctane sulfonic acid (PFOS). Replacement PFAS are those that have replaced legacy PFAS because they are thought to have fewer health effects and/or shorter half-lives. Examples are perfluorobutanesulfonic acid (PFBS) and GenX with half-lives of 665 hours (27.7 days) and 72-81 hours (3-3.3 days), respectively.

Studies have found PFAS in human blood in the U.S. population. Notably, the Agency for Toxic Substances and Disease Registry’s (ATSDR) website reports that the concentration of some of the common PFAS: PFOA, PFOS, PFHxS, and perflourononanoic acid (PFNA) in the blood is declining. This is attributed to the decline in production and uses of these PFAS.

Occurrence of PFAS in wastewater

PFAS are widespread in the environment. PFAS can bioaccumulate in the environment depending on their high half-life. 

A scholarly study detected PFAS in raw water and drinking water. These included linear and branched PFOA, with a total PFOA average concentration of 4.08 ± 2.42 ng/L in drinking water produced from surface water and 0.79 ± 0.47 ng/L in drinking water produced from groundwater from samples collected from 18 different drinking water treatment locations in the Netherlands.

Replacement PFAS such as 6:2 fluorotelomer sulfonate (6:2 FTS) were also detected, at an average concentration of 0.07 ± 0.06 ng/L in drinking water produced from surface water and at an average concentration of 0.11 ± 0.08 ng/L in drinking water produced from groundwater.

Another study in Washington state measured the concentration of several PFAS in samples from wastewater treatment plants (WWTPs). These included:

• PFOA in the range of 5.0-12.3 ng/L with the average for U.S. WWTPs of 8.4 ng/L;
• PFNA of 0.6-11 ng/L and the U.S. WWTPs average of 3.9 ng/L; and
• PFHxS of 1.0-6.0 ng/L with the US WWTPs average of 4.8 ng/L. 

The maximum for the concentration range of PFAO and PFNA in the effluent of wastewater treatment plants were above the Washington state action level (SAL) while they were lower than the SAL for PFHxS. The Washington state SAL is 10 ng/L for PFOA, 9.0 ng/L for PFNA, and 65 ng/L for PFHxS.

Health effects of PFAS

PFAS are a group of manufactured chemicals and there are thousands of these chemicals, each with different toxicity level effects. Some PFAS are regulated and as the above section shows, there are several exposure routes to PFAS. All these issues make it challenging to specify the health effects of PFAS.

Because PFAS break down very slowly, they can accumulate in living things. Federal and state reports have shown that exposure to PFAS can lead to a range of health effects. Below are some of the sources of reporting and their health effects.

• US EPA in 2024: Interference with the body’s natural hormones, reduced immunity to infections, increased risk of certain cancers, reproductive health effects such as decreased fertility, and developmental effects in children including behavioral changes.
• The health effects of PFAS have also been reported by the US Department of Veterans Affairs, the National Institute of Environmental Health Sciences, the CDC/ATSDR (Agency for Toxic Substances and Disease Registry), and by the ITRC (Interstate Technology & Regulatory Council).

The American Cancer Society has summarized studies on exposure to PFAO and the increased risk of cancer while the UN Environment Program not only summarized the health effects of PFAS but also provided informative weblinks for subgroups of PFAS as industrial persistent organic pollutants currently listed under the Stockholm Convention. These include several PFAS and their salts.

Several state websites have also reported the health effects of PFAS and these include the State of Alaska Department of Health, Minnesota Department of Health, and the Michigan Department of Health and Human Services Toxicology.

Scholarly studies directly link PFAS to human medical and health issues

In a peer reviewed scholarly article from the National Institute of Health:

• Prenatal exposure to PFOS and PFHxS has been linked with immunosuppression. The immunosuppression in a recent review concluded due to exposure to PFAS in infancy and childhood was characterized by an increased incidence of atopic dermatitis and lower respiratory tract infection. 

• The study also reported that there is a “probable link” for exposure to PFOA and thyroid disease and “some evidence” that PFAS cause childhood hypothyroidism. There is also association between PFAS exposure and altered levels of thyroid-stimulating hormones in newborns.

• A clinic-based study showed that in 85% of obese children aged 7 to 19 years old with nonalcoholic fatty liver disease, there was an association between exposure to PFOS and PFHxS linked with nonalcoholic fatty liver disease pathogenesis.

• While only a handful of PFAS with enough health effects are known, there are still hundreds of PFAS and PFAS-replaced chemicals that lack data on their health effects. Carefully designed studies are required to identify the health effects of these PFAS and PFAS-replaced chemicals to formulate risk assessment and regulatory strategies.

The association between PFAS and autism

Reviews

In the journal Toxics, the review comprehensively explores the interactions between gut, liver, and brain, the link between PFAS and liver inflammation and neurotoxicity, the link between acetaminophen and autism, and the potential interactions between PFAS and acetaminophen in autism spectrum disorder.

In the journal Current Environmental Health Reports, the review aims to highlight research gaps with the purpose to guide future studies on the effects of PFAS on neurodevelopment besides presenting current evidence on the effects of PFAS on developmental disabilities and autism. Some of the research gaps it mentions are:

• There are few studies that examined how the combination of prenatal and postnatal exposure to PFAS jointly and cumulatively affect neurodevelopment across multiple development stages. Additionally studies are needed to understand the effect of PFAS exposure on adolescence and adulthood.
• There is little information on how genetics or other biological susceptibility factors may affect the body’s response to PFAS exposure.
• More studies are needed to understand how PFAS interact with other classes of chemicals because multiple chemicals occur in polluted water and air.
• More studies are needed on the effects of replacement PFAS such as PFBS and GenX that are shown in experimental studies to have neurotoxic potential.

Clinical studies

A published scholarly study assessed the association between cord blood concentration of certain PFAS with autistic traits. Using a cohort group, 430 samples were used to measure the cord blood concentration of eight PFAS and to look for association with autistic traits. The study showed a positive association between PFAS and SRS-2 (Social Responsiveness Scale Second Edition) cognition sub-scores with PFNA being the strongest contributor. SRS-2 is a measure of autistic traits.

A study done by the NIH found that while most PFAS in maternal blood were not strongly associated with child Social Responsiveness Scale (SRS) and rather showed a weak, positive effects, a quantitative measure of autism related traits, prenatal blood concentration of PFNA showed the strongest association. The study suggested that larger studies are needed using dimensional, quantitative measures of neurobehavior and gestational measurement to clarify the relationship between legacy and emerging PFAS such as PFNA and early brain development. 

Another scholarly study showed the importance of considering multiple chemical classes for links to autism spectrum disorder compared to studying separate chemical classes of chemicals. This study examined the effects of various chemicals including PFAS on the risk of autism spectrum disorder by assessing children at age 3 and quantifying biomarkers in blood and urine of expectant mothers. The study showed four distinct chemical clusters including PFAS as cluster 1 showed increased risk of autism spectrum disorder (at a value of 1.14). 

Health advisory levels

Do the Health Advisory Levels that U.S. EPA issued in 2022 correlate with the levels listed in scholarly studies?

In 2022, the EPA issued interim health advisory levels (HAL) for drinking water for PFOA and PFOS that replaced those issued in 2016. 

These interim health advisory levels are:

• 004 ppt for PFOA
• 02 ppt for PFOS

The EPA also issued final health advisory levels for PFBS and for hexafluoropropylene oxide-dimer acid (HFPO-DA) and their salts and these values are:

• 10 ppt for Gen X chemicals
• 2,000 ppt for PFBS

The Health Advisory Levels that U.S. EPA issued in 2022 correlate with the levels listed in scholarly studies, and these values were issued by the EPA based on human studies, as mentioned in the announcement for the HAL levels. According to the EPA, the lifetime noncancer interim health advisory for PFOA is derived from chronic RfD (reference dose) and RSC (relative source contribution) values and also relies on the best available science, which as of 2022 was undergoing peer review by the SAB (Science Advisory Board) PFAS Panel. 

As also mentioned in the 2022 EPA’s health advisories announcement (cited): “Health advisories are non-regulatory and reflect EPA’s assessment of the best available peer-reviewed science.”

Maximum contaminant levels of PFAS

In 2023

Table 1 summarizes EPA’s action in 2023 for the maximum contaminant levels (MCLs) for several PFAS. Additionally in 2023, the EPA finalized the maximum contaminant level goals (MCGLs) for PFOA and PFOS at zero and finalized a hazard index of 1 (unitless) as the MCL for any mixture containing two or more of four following PFAS: PFHxS, PFNA, HFPO-DA (a GenX chemical), and PFBS. 

Table 1: MCLs promulgated by the EPA in 2023

Source: https://www.govinfo.gov/content/pkg/FR-2024-04-26/pdf/2024-07773.pdf

The Hazard Index (HI) MCL indicates if action is required and a value of one (cited from source): “indicates a level at which no known or anticipated adverse effects on the health of a person occur and allows for an adequate margin of safety with respect to health risks associated with a mixture of PFAS in finished drinking water.”

The formula for the HI MCL in Figure 1 contains the Health Based Water Concentration (HBWC) for four PFAS which are 10 ng/L for PFHxS, PFNA, and HFPO-DA, and 2,000 ng/L for PFBS. 

Figure 1: HI MCL according to the 2023 EPA's actions

Source: https://www.federalregister.gov/documents/2024/04/26/2024-07773/pfas-national-primary-drinking-water-regulation

Current state

On May 14, 2025, the EPA announced:

• It would keep the current National Primary Drinking Water Regulations (NPDWR) for PFOA and PFOS. The MCGLs and MCLs are part of the NPDWR under the Safe Drinking Water Act. 
• Its intent to the compliance deadlines for the MCLs for PFOA and PFOS.
• Its intent to rescind the regulations and to reconsider the regulatory determinations for PFHxS, PFNA, HFPO-DA, and the HI for these, ensuring that the regulatory determinations follow the SDWA process.

Additionally, the final rule requires:

• Public water systems (PWSs) complete initial monitoring for these PFAS by 2027 followed by ongoing compliance monitoring and providing the public with information on the levels of these PFAS in their drinking water beginning in 2027.
• By 2029, PWSs must implement solutions to reduce the levels of these five PFAS if monitoring shows that they exceed the MCLs.
• Beginning in 2029, PWSs must take actions to reduce the levels of PFAS that have exceeded the MCLs.

U.S. EPA Fifth Unregulated Contaminant Monitoring Rule (UCMR5)

As per SDWA requirements, the U.S. EPA must issue a list of unregulated contaminants for monitoring by the PWSs once every five years. The fifth Unregulated Contaminant Monitoring Rule (UCMR5), published in 2021, specifies that all public water systems serving between 3,300 to 10,000 people (small and large public water systems) must monitor for 29 PFAS, most of which are monitored using EPA Method 533 including HFPO-DA (also known as Gen X) and some using EPA Method 537.1, including perfluorotetradecanoic acid (PFTA).

Selection of UCMR5 contaminants

The contaminants in the UCMR5 list were selected by EPA using a three step process:

1. Identifying contaminants that were not monitored under previous UCMRs.
2. The contaminants are associated with one or more of the following: they have available health assessment for determining their regulations; high public health concern; they are a likely or suggestive carcinogen; they have active use, e.g. as pesticides; and/or there is a data gap for them.
3. Considering inputs from stakeholders for the identified contaminants; looking at cost-effectiveness of analytical methods including single methods that could address multiple contaminants of interest; implementation factors of the methods, e.g. laboratory capacity; available data on health effects; occurrence, and environmental persistence/mobility of the contaminants.

Websites for UCMR5 data

The analytical results for contaminants on the UCMR list are available on the National Contaminant Occurrence Database (NCOD) and the summary of the results on the UCMR Occurrence. On the NCOD website, there is a weblink for Unregulated Contaminant Monitoring Rule 5 Data.

This website, in addition to the summary of data for UCMR 5 that was updated in April 2025, also contains zip files for data including by state and methods. These data are also available on the website for UCMR Occurrence.

Minimum Reporting Level (MRL) and MCL

The UCMR5 Minimum Reporting Level (MRL) data for the contaminants in the UCMR5 list are presented in the UCMR5 Data Summary (pages 8-9). These data, established by the EPA, are the lowest data that laboratories may report to the EPA using UCMR5 reporting.

The definition of MRL

Specifically, MRL is the (cited): “quantitation limit for a contaminant that is considered achievable with 95% confidence, by at least 75% of the laboratories nationwide using a specified analytical method.”

UCMR5 MRL and MCL for PFAS

The UCMR5 Data Summary (pages 8-9), shows that the UCMR5 MRL is 0.004 µg/L (4 ng/L) for PFOS and PFOA, which meets the MCL value of each, which also are 4 ng/L.

However, the UCMR5 MRL cites 0.005 µg/L (5 ng/L) for HFPO-DA, 0.003 µg/L (3 ng/L) for PFHxS, and 0.004 µg/L (4 ng/L) for PFNA, all of which have an MCL of 10 ng/L, showing that their UCMR5 MRL is lower than their MCLs. There are also other PFAS reported in the UCMR5 Data Summary.

How does the U.S. EPA UCMR5 data align with the citations listed for its regulatory actions against PFAS?

As shown in the UCMR5 Data Summary (pages 8-9), the UCMR5 MRL for PFOS and PFOA is the same as their MCLs, 4 ng/L while it is lower for HFPO-DA, PFHxS, and PFNA compared to their MCLs. So the U.S. EPA UCMR5 MRL data aligns with the citations listed for its MCLs based on these values only and there are issues that are discussed further in this article. 

Additionally, and as also mentioned above, EPA announced in May 2025 that it intends to rescind the regulations and to reconsider the regulatory determinations for HFPO-DA, PFHxS, and PFNA. Therefore based on this announcement, it still needs to be seen in the future how the U.S. EPA UCMR5 MRL data for HFPO-DA, PFHxS, and PFNA will compare with their MCLs. 

Issues concerning the UCMR5

While EPA in 2021 discussed several topics in response to 75 set of comments it received for the UCMR5 proposal including those relating to sampling designs and methods, there are still some concerns with UCMR5 MRL data on the lowest (minimum) concentration and percentage of laboratories in the definition of UCMR MRL and data on PWSs concerning the UCMR5 data.

There are also issues including on the challenges of compliance, the disconnect between science and policy, and technical issues. 

Issues with definitions and data

Lowest concentration in the definition of UCMR MRL and associated data

MRL is the lowest concentration that laboratories may report to the EPA during the UCMR5 monitoring. Considering that the UCMR5 MRL for perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), UCMR5 Data Summary (pages 8-9) is the same value, 4 ng/L, as their MCLs, this should be of concern. 

As stated above in the definition of UCMR MRL, specified analytical methods are used and these are EPA Method 533 including for HFPO-DA (Gen X) and some using EPA Method 537.1 including PFTA. Both methods, EPA Method 533 and Method 537.1 use solid phase extraction liquid chromatography-tandem mass spectrometry, which is considered a sensitive method for chemical quantitation.

However, the concern is that the MRL is the same as the MCL, the minimum being the same as the maximum for PFOS andPFOA at 4 ng/L. 

Percentage of laboratories in the definition of UCMR MRL

For the percentage of laboratories in the definition of UCMR MRL, the definition as also stated above (cited): “UCMR MRL is the contaminant’s quantitation limit that is considered achievable, with 95% confidence, by at least 75% laboratories nationwide using a specified analytical method.”

The concern here is “by at least 75% laboratories” because what about the other 25% of laboratories?

Data on percentage of PWSs with PFAS greater than the MCLs

The UCMR5 Data Summary (page 12) presents the number of PWSs that have averages greater than the MCL. Below follows a list of the chemicals as well as the percentage of PWSs with concentrations greater than the MCL. Large PWS is defined as greater than 10,000 people, a medium PWS is 3,300 to 10,000 people, and a small PWS is less than 3,300 people.

PFOS

• 12% of large PWSs (serving >10,000 people);
• 6.3% of medium PWSs (serving 3,000-10,000 people); and
• 6.6% of small PWSs (serving less than 3,300 people). 

PFOA 

• 10% for large PWSs;
• 5.3% for medium PWSs; and
• 5.0% for small PWSs.

HFPO-DA

• 0.03% for large PWSs;
• 0.03% for medium PWSs; and
• none for small PWSs.

PFHxS

• 1.0% for large PWSs;
• 0.4% for medium PWSs; and
• 0.6% for small PWSs.

PFNA

• 0.03% for large PWSs;
• 0.1% for medium PWSs; and
• none for small PWSs. 

The number of people served by these PWSs and exposed to these PFAS could be significant considering the number of people these PWSs serve, especially large PWSs, and other risk and toxicity factors. 

Challenges with technicality and compliance

Monitoring

UCMR5 requires all PWSs serving 3,300 or more people to perform monitoring (Exhibits 1 and 2). As Exhibit 1 shows, the monitoring cost is expensive, an estimated average annual national total of 20.8 million dollars, making it challenging for impoverished communities, especially those with PFAS “hotspots” to afford monitoring.

Sample collection

Sample collection for UCMR5 is at the entry point to the distribution system (in IV, D, 1). Approval is required for sampling at representative sampling locations rather than at each groundwater entry point to the distribution system for large groundwater systems or large surface water systems with groundwater sources that have multiple groundwater entry points.

Analytical methods

EPA Method 533 and Method 537.1 use solid phase extraction liquid chromatography-tandem mass spectrometry, while considered a sensitive method for chemical quantitation, can also be complex depending on the contaminant being detected. A 2025 scholarly study could not recover PFAS from mixtures using standard EPA methods including methods 533 and 537.1. Severe matrix effects were observed for long-chain and nitrogen-containing PFAS. 

PFAS are found in wastewater, in both raw and treated water and scholarly studies have linked PFAS to a range of health issues including with neurodevelopment in children. However studies have also pointed out research gaps despite the 2022 health advisories. There are also several issues with the UCMR5 for PFAS, ranging from concerns on reported data to technical and compliance issues.