Extracted from Law360
On Aug. 17, the U.S. Environmental Protection Agency released the first data collected under the fifth Unregulated Contaminant Monitoring Rule.[1]
The rule's stated aim is to improve the EPA's understanding of the levels and frequency of 30 chemical contaminants — 29 types of per- and polyfluoroalkyl substances, or PFAS, and lithium — in U.S. drinking water systems.
The data will assist the EPA in making regulations, inform future regulatory actions on the acceptable levels of PFAS in waterways, and dramatically affect a wide variety of stakeholders.[2]
PFAS have soared to the top of environmental regulatory agendas, and dominated environmental news headlines. Many articles have discussed the possible effects of PFAS exposure on human health.
On Aug. 16, the New York Times published "'Forever Chemicals' Are Everywhere. What Are They Doing to Us?"[3] The article described a variety of health conditions purportedly associated with exposure to PFAS, and painted a grim picture of the seemingly limitless adverse effects that PFAS may have on human health.
But how much science supports the conclusion that environmental exposure to PFAS is associated with adverse human health effects? And if such support exists, how strong is the evidence underpinning that conclusion?
The Times article contains material shortcomings and information gaps. It fails to mention the significant limitations of the available scientific research suggesting that PFAS are associated with disease in humans.
The article fails to note the contradictory findings of the scientific studies on the relationship between PFAS and adverse human health effects. It does not address the statements and publications of relevant agencies that question the potential carcinogenic properties of PFAS.
Articles like this contribute to the public's misconceptions of what science says about PFAS exposure and human health and unjustifiably alarm readers, causing unnecessary anxiety and fears of cancer.
In this article, we highlight a few of the substantial limitations of the available research suggesting a causal relationship between PFAS exposure and adverse human health effects. We also address some of the misconceptions about the strength of the scientific evidence that apparently supports such a relationship.
Inconsistent Findings
Studies on the supposed causal relationship between PFAS and adverse human health effects have notably inconsistent results. Toxicologists and environmental chemists with specific expertise on PFAS maintain there is no confirmed evidence establishing a causal relationship between exposure to PFAS and adverse human health effects.[4]
The same experts go a step further and maintain that even the reported associations between PFAS and chronic disease in humans are based on limited evidence and are not definitive.[5] These scientific limitations and inconsistencies are too often ignored, and this information gap can create misconceptions about the strength and relevance of the studies.
One example of these inconsistencies is the irregular dose-response relationship that studies have found between PFAS and human development.[6]
Virtually all substances exhibit a dose-response curve that displays, in a graphical representation, the relationship between the amount of exposure to a substance and the resulting changes in body function or health.[7] The dose-response relationship for substances with adverse health effects is generally expected to show that as the dose of the substance increases, the health effects also increase.
The dose-response curves found in studies on PFAS exposure are inconsistent. Studies on serum lipids indicate a dose-response curve that's steeper at lower concentrations but flattens out at higher serum PFAS concentrations.[8]
This is a particularly interesting result because PFAS are accumulators — meaning they accumulate in the body and are not metabolized. If PFAS exposure is associated with adverse health effects and PFAS accumulate in the body over time, the dose-response curve should show adverse health effects associated with PFAS increasing with exposure. However, this is not the case.
The findings of studies focused on specific health effects are also at odds with one another. One review analyzed 23 scientific studies on the relationship between PFAS exposure and certain measures of human development in infancy, childhood, adolescence and early adulthood, and found inconsistencies in the effects of PFAS exposure on body mass index and other measures of postnatal adiposity, or body fat — such as waist circumference, skinfold thickness and fat mass.[9]
Epidemiological studies on the effects of PFAS exposure on immunosuppression outcomes are similarly contradictory.[10] While some studies have reported an association between PFAS exposure and decreased disease resistance and antibody responses, other studies have reported the opposite.[11]
The Agency for Toxic Substances and Disease Registry highlighted a few of these studies in its most recent Toxicological Profiles for Perfluoroalkyls report, including a study that found no association between the level of perfluorooctanoic acid, or PFOA, one of the PFAS, and the frequency of the common cold or flu in adults.[12]
The ATSDR also cited studies that reported no associations between maternal PFOA levels and inner ear infections in 1.5- to 3-year-old children;[13] between maternal PFOA and the risk of hospitalization for infectious diseases in young children;[14] between maternal PFOA and the number of days with cough, nasal discharge, diarrhea or vomiting;[15] or between maternal serum PFOA and the number of infectious diseases between birth and 2 years of age.[16]
Further, the ATSDR made clear that "although a large number of epidemiological studies have examined the potential of perfluoroalkyls to induce adverse health effects, most of the studies are cross-sectional in design and do not establish causality."[17]
Notably, even when data may provide evidence of an association between perfluoroalkyl exposure and a health effect, the ATSDR said, "it does not always imply that the observed effect is biologically relevant because the magnitude of the change may be within normal limits or not indicative of an adverse health outcome."[18]
Relevance of Animal Studies
Many studies of PFAS exposure have been conducted with animals, as is customary in scientific research. However, animal studies that suggest a correlation between PFAS exposure and adverse health effects provide limited support for such assertions about humans, due to the differences in responses across species.
The ATSDR has noted that "there are profound differences in the toxicokinetics of perfluoroalkyls between humans and experimental animals."[19] These differences, along with other issues and limitations, make it difficult to determine the relevance of animal studies to the possible adverse health effects in humans.[20]
The ATSDR also noted that, generally, adverse health effects shown in animal studies involved PFAS exposure concentrations or doses resulting in levels of PFAS in the blood that were significantly higher than those reported in individuals who work with PFAS or in the general population.[21]
Carcinogenicity
PFOA has been classified as a possible human carcinogen, but the carcinogenic effects of PFAS exposure have not been established.[22] However, the EPA has proposed a national primary drinking water regulation to establish legally enforceable maximum contaminant levels, or MCLs, for PFOA and five other PFAS found in drinking water.[23]
The EPA has proposed an MCL goal of zero and an enforceable MCL of 4 nanograms per liter, or parts per trillion, for PFOA and perfluorooctane sulfonic acid, another PFAS.[24] This level is orders of magnitude lower than the current MCLs for known human carcinogens, such as benzene and arsenic, which have MCLs in micrograms per liter.[25]
Takeaway
Many publications have discussed the potential health effects of PFAS exposure. Few have noted the limitations of scientific studies and support for such conclusions. This imbalance has contributed to misconceptions about the strength of scientific studies in this realm, and caused unwarranted fear in the general population.
As the regulatory environment becomes more active, a heightened focus will be placed on establishing acceptable levels of PFAS exposure, and it will be increasingly important for the various stakeholders to understand the state of the science on PFAS and human health.
Science can inform a sensible regulation of PFAS that protects human health and the environment, and we can move away from a cost-prohibitive and unjustifiable model that simply adopts as limits the lowest detectible concentrations that can be found using modern chemistry.
[1] EPA Releases Initial Nationwide Monitoring Data on 29 PFAS and Lithium, News Release, EPA (Aug. 17, 2023), https://www.epa.gov/newsreleases/epa-releases-initial-nationwide-monitoring-data-29-pfas-and-lithium.
[2] Id.
[3] Kim Tingley, "'Forever Chemicals' Are Everywhere. What Are They Doing to Us?" The New York Times (Aug. 16, 2023).
[4] See PFAS, An Overview of the Science and Guidance for Clinicians on Per- and Polyfluoroalkyl Substances (PFAS), ATSDR at 8 (Rev. Dec. 6, 2019) ("Although causal relationships have not been established, some studies find positive associations between PFAS exposure and adverse health effects. These studies are limited by the lack of exposure monitoring data associated with epidemiological studies and the limited analysis of other routes of exposure"), https://www.atsdr.cdc.gov/pfas/docs/clinical-guidance-12-20-2019.pdf.
[5] See id.
[6] Yun Jeonhg Lee et al., Early-Life Exposure to Per- and Poly-Fluorinated Alkyl Substances and Growth, Adiposity, and Puberty in Children: A Systematic Review, Front. Endocrinol. (Sept. 9, 2021), https://doi.org/10.3389/fendo.2021.683297.
[7] See "Dose Response," Science Direct, https://www.sciencedirect.com/topics/medicine-and-dentistry/dose-response.
[8] Toxicological Profile for Perfluoroalkyls, U.S. Department of Health and Human Services – Agency for Toxic Substances and Disease Registry at 751 (Released May 2021), https://www.atsdr.cdc.gov/toxprofiles/tp200.pdf (citing Steenland et al. 2010a).
[9] Lee et al.
[10] Toxicological Profile for Perfluoroalkyls, at 324-325.
[12] Toxicological Profile for Perfluoroalkyls, at 325 (citing Looker et al. 2014).
[13] Toxicological Profile for Perfluoroalkyls, at 325 (citing Granum et al. 2013; Okada et al. 2012).
[14] Toxicological Profile for Perfluoroalkyls, at 325 (citing Fei et al. 2010).
[15] Toxicological Profile for Perfluoroalkyls, at 325 (citing Dalsager et al. 2016).
[16] Toxicological Profile for Perfluoroalkyls, at 325 (citing Goudarzi et al. 2017).
[17] Toxicological Profile for Perfluoroalkyls, at 325.
[18] Id. at 26.
[19] Id. at 7.
[20] Id.
[21] Id.
[22] PFAS Exposure and Risk of Cancer, National Cancer Institute, https://dceg.cancer.gov/research/what-we-study/pfas.
[23] Preliminary regulatory determination and proposed rule; request for public comment; notice of public hearing, EPA Proposed Rule (March 29, 2023), https://www.federalregister.gov/documents/2023/03/29/2023-05471/pfas-national-primary-drinking-water-regulation-rulemaking#addresses.
[24] Id.
[25] National Primary Drinking Water Regulations, EPA, https://www.epa.gov/ground-water-and-drinking-water/national-primary-drinking-water-regulations#two.