Per- and Polyfluoroalkyl Substances (PFAS)

This section provides reviews from a variety of sources on the toxicology (human and ecological) of PFASs. The largest amount of information concerns PFOA, PFOS, and their salts and precursors. Individual specific studies are not called out but can be found in the extensive bibliographies of the resources listed. The resources below also include links to publicly available databases that can be searched for information on the toxicology of PFOA, PFOS, and other PFAS compounds.

Human Health Effects

PFOS

Data on the effects of PFOS in humans and animals demonstrate ready absorption of PFOS and distribution of the chemical throughout the body by noncovalent binding to serum albumin and other plasma proteins. In animal models, PFOS is detected predominantly in liver, serum, and kidney. Studies of postmortem human tissues identify its presence in liver. Both experimental data and pharmacokinetic models show higher levels of PFOS in fetal serum and brain compared with the maternal compartments. PFOS is not readily eliminated from humans as evidenced by the estimated average half-life values of 4.1-8.67 years (USEPA 2016a).

Because of uncertainties associated with the human data, EPA is currently relying on animal data to quantitatively assess effects; however, the epidemiology studies provide important data to establish probable links between PFOS exposure to humans and health effects. In particular, effects on the liver enzymes indicative of liver effects, low birth weight, antibody response, and cancer in laboratory animals are supported by human epidemiology studies coupled with PBPK modeling to extrapolate to humans (USEPA 2016b).

PFOA

Extensive data on the effects of PFOA in humans and animals indicate ready absorption of PFOA and distribution of the chemical throughout the body by noncovalent binding to plasma proteins. In the mouse, PFOA is detected predominantly in liver, serum, and kidney. Studies of postmortem human tissues identify its presence in liver, lung, kidney, and bone. PFOA is not readily eliminated from the human body as evidenced by the half-life of 2.3 years among members of the general population (EPA 2016c).

Human epidemiology data report associations between PFOA exposure and high cholesterol, increased liver enzymes, decreased vaccination response, thyroid disorders, pregnancy-induced hypertension and preeclampsia, and cancer (testicular and kidney) (EPA 2016d).

Because of uncertainties associated with the human data, EPA is currently relying on animal data to quantitatively assess effects; however, the epidemiology studies provide important data to establish probable links between PFOA exposure to humans and health effects. In particular, effects on the liver enzymes indicative of liver effects, low birthweight, immunological (acquired and innate) responses, and tumor induction in laboratory animals are supported by human epidemiology studies and PBPK modeling (USEPA 2016d).

Top of Page

Ecological Effects

Environmental toxicity tends to be chemical and species specific and hence is not easily summarized. Giesy et al. (2010) states: "Results available in the literature on the toxicity of PFCs to aquatic organisms indicate that toxicity of fluorinated chemicals is related to length of the fluorinated carbon chain; the nature of functional groups has relatively little effect on the toxic potency of these compounds." A summary of some older studies on PFOS effects on selected plants and animals can be found in OECD (2002). The overview documents in the Ecological Health section generally contain extensive reference lists relevant to ecological effects.

Top of Page

Databases and Websites

The C8 Science Panel Website
During 2005-2013, the C8 Science Panel carried out exposure and health studies in Mid-Ohio Valley communities potentially affected by releases of PFOA (i.e., C8) emitted since the 1950s from the Washington Works plant in Parkersburg, West Virginia. The investigators then assessed the links between C8 exposure and a number of diseases. The C8 Science Panel has completed its work and no longer exists; results are summarized on this website.

ECOTOX
The U.S. EPA ECOTOXicology knowledgebase (ECOTOX) is a comprehensive, publicly available database that provides single-chemical environmental toxicity data on aquatic life, terrestrial plants, and wildlife.

HERO
EPA's Health and Environmental Research Online (HERO) database contains more than 600,000 scientific references and data from the peer-reviewed literature used by EPA to develop its regulations. The assessments supported by HERO characterize the nature and magnitude of health risks to humans and the ecosystem from pollutants and chemicals in the environment. HERO is an evergreen database, which means that new studies are added continuously. Imported references are systematically sorted, classified, and made available for search and citation.

PubMed
PubMed comprises tens of millions of citations for literature from MEDLINE, life science journals, and online books in the fields of biomedicine and health, covering portions of the life sciences, behavioral sciences, chemical sciences, and bioengineering. PubMed is a free resource developed and maintained by the National Center for Biotechnology Information at the National Library of Medicine®.

TOXNET
TOXNET is a gateway to a variety of databases, including HSDB, the Hazardous Substances Data Bank, which offers peer-reviewed toxicology data for over 5,000 hazardous chemicals, and TOXLINE, which contains 4 million references to literature on biochemical, pharmacological, physiological, and toxicological effects of drugs and other chemicals.

Top of Page

Human Health

A Critical Review of Perfluorooctanoate and Perfluorooctanesulfonate Exposure and Cancer Risk in Humans
Chang, E.T., H.-O. Adami, P. Boffetta, P. Cole, T.B. Starr, and J.S. Mandel.
Critical Reviews in Toxicology 44(sup1):1-81(2014)

This Open Access journal article contains a detailed review of epidemiologic evidence concerning the association between PFOA and PFOS exposure and cancer risk in humans.

Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS)
U.S. EPA, Office of Water.
EPA 822-R-16-004, 88 pp, 2016

EPA issued a lifetime drinking water health advisory for PFOS of 0.07 µg/L based on review of recent health effects information as described in EPA's 2016 Health Effects Support Document for Perfluorooctane Sulfonate (PFOS).

Drinking Water Health Advisory for Perfluorooctanic Acid (PFOA)
U.S. EPA, Office of Water.
EPA 822-R-16-005, 103 pp, 2016

EPA issued a lifetime drinking water Health Advisory for PFOA of 0.07 µg/L based on review of recent health effects information described in EPA's 2016 Health Effects Support Document for Perfluorooctanoic Acid (PFOA).

Environmental and Health Risk Assessment of Perfluoroalkylated and Polyfluoroalkylated Substances (PFASs) in Sweden
Borg, D. and H. Hakanson.
Swedish Environmental Protection Agency, Report 6513, 139 pp, 2012

The risk assessment consisted of (1) an exposure assessment with Swedish biomonitoring data for 23 PFASs measured in humans, mammals, birds, and fish; (2) a hazard assessment with toxicological data from studies on mammals, birds, and fish for the selected compounds; and (3) a risk characterization for humans, mammals, birds, and fish. The investigators reviewed a large number of PFASs individually and in combination.

Hazard Assessment of Perfluorooctane Sulfonate (PFOS) and Its Salts
OECD (Organisation for Economic Co-operation and Development), Environment Directorate.
ENV/JM/RD(2002)17/FINAL, 362 pp, 2002

Separate sections of this overview cover physical-chemical properties, environmental behavior and fate, human health hazards, and hazards to the environment (fish, invertebrates, aquatic plants, and terrestrial organisms and plants).

Health Effects Support Document for Perfluorooctane Sulfonate (PFOS)
U.S. EPA, Office of Water.
EPA 822-R-16-002, 245 pp, 2016

Information is provided on PFOS toxicokinetics, hazard identification (human effects, animal studies, and hazard characterization), and dose-response assessment.

Health Effects Support Document for Perfluorooctanic Acid (PFOA)
U.S. EPA, Office of Water.
EPA 822-R-16-003, 322 pp, 2016

This document covers PFOA toxicokinetics, hazard identification (human effects, animal studies, and hazard characterization), and dose-response assessment.

Provisional Peer Reviewed Toxicity Values for Perfluorobutane Sulfonate and Related Compound Potassium Perfluorobutane Sulfonate
U.S. EPA, Office of Research and Development, 50 pp, 2014

Provisional Peer-Reviewed Toxicity Values (PPRTVs) are second-tier human health toxicity values for the EPA Superfund and RCRA hazardous waste programs.

Screening Assessment Report: Perfluorooctanoic Acid, Its Salts, and Its Precursors
Environment Canada and Health Canada, 97 pp, 2012

The assessment is based on a weight-of-evidence approach regarding the persistence, bioaccumulation, temporal trends in some species (e.g., the polar bear), long-range transport, and the widespread occurrence and concentrations of PFOA in the environment and biota (including remote areas of Canada). The report discusses ecological risk assessment and human health risk assessment with supporting data and 26 pages of bibliographic references.

Short-Chain Polyfluoroalkyl Substances (PFAS): A Literature Review of Information on Human Health Effects and Environmental Fate and Effect Aspects of Short-Chain PFAS
Danish Ministry of the Environment, Environmental Protection Agency. Environmental project No. 1707, 106 pp, 2015

The literature review was conducted to provide an overview of the human health and environmental fate and effects aspects of short-chain polyfluorinated substances introduced as alternatives to PFOS, PFOA, and other long-chain PFASs.

Toxicology of Perfluorinated Compounds
Stahl, T., D. Mattern, and H. Brunn.
Environmental Sciences Europe 23(38):1-52(2011)

This Open Access journal article describes both external and internal exposures to PFCs, the toxicokinetics (uptake, distribution, metabolism, excretion), and the toxicodynamics (acute toxicity, subacute and subchronic toxicities, chronic toxicity [carcinogenesis, genotoxicity, and epigenetic effects], reproductive and developmental toxicities, neurotoxicity, effects on the endocrine system, immunotoxicity and potential modes of action, combinational effects, and epidemiological studies).

Toxicological Profile for Perfluoroalkyls
ATSDR (Agency for Toxic Substances and Disease Registry). 2021.

The ATSDR toxicological profile succinctly characterizes the toxicology and adverse health effects information for perfluoroalkyls. This peer-reviewed profile identifies and reviews the key literature that describes a substance's toxicological properties.

Ecological Health

AFFF PFAS Terrestrial Ecological Risk Model Tool User's Manual
Conder, J., J. Arblaster, and K. Bridges. SERDP Project ER18-1614, 33 pp, 2021

This document is a user's manual for the customizable Microsoft™ food web and wildlife exposure modeling tool ("Model Tool") to assess the potential ecological risks associated with exposure to PFAS for common, threatened, and endangered species in terrestrial habitats potentially impacted by aqueous film-forming foam. The Model Tool (a multi-worksheet Excel file) enables ecological risk assessors to enter site-specific data, exposure factors for site-relevant wildlife species, and available toxicological information for common PFAS. Model outputs consist of an evaluation of the potential for direct effects to terrestrial communities and model-predicted concentrations of PFAS in food webs and wildlife diet items. The model also features tables that provide ecological risk assessment effects assessment and risk characterization (i.e., hazard quotients) and useful information to facilitate ERA-based decision making. Additional information: Terrestrial Ecological Risk Model Tool

Aquatic Toxicology of Perfluorinated Chemicals
Giesy, J., J. Naile, J.S. Khim, P. Jones, and J. Newsted.
Springer Science. Reviews of Environmental Contamination and Toxicology 202:1-52(2010)
DOI: 10.1007/978-1-4419-1157-5_1

Following a general discussion of PFC fate in the environment, specific acute and chronic toxicity of PFOS in aquatic organisms is discussed along with the derivation of PFOS and PFBS toxicity reference values for predatory birds.

Development of Per and Polyfluoroalkyl Substances Ecological Risk-Based Screening Levels
Zodrow, J.M., M. Frenchmeyer, K. Dally, E. Osborn, P. Anderson, and C. Divine.
Environmental Toxicology and Chemistry 40(3): 921-936(2021) [Abstract]

Risk-based screening levels (RBSLs) were developed to evaluate the potential for toxicity associated with ecological receptor exposure to PFAS. Wildlife RBSLs were developed using surrogate receptors representative of threatened and endangered species with different habitat types, feeding guilds, and trophic levels. Published uptake and toxicity data were combined with receptor exposure factors to derive RBSLs for terrestrial and aquatic wildlife for several PFAS, including PFNA, PFOS, PFOA, PFHxA, PFBS, and PFBA. Uptake information for surrogate PFAS was considered to calculate RBSLs for PFAS with toxicity data and insufficient bioaccumulation data to develop an RBSL. Both no-observed-adverse-effect level (NOAEL)- and lowest-observed-adverse effect level-based wildlife RBSLs were calculated to allow for a range of risk estimates appropriate to individual threatened and endangered species and populations of non-listed wildlife receptors, respectively. Recommended water quality RBSLs protective of aquatic life were developed for 23 PFAS based on published literature reviews, peer-reviewed aquatic toxicity studies, and the Great Lakes Initiative methodology. For wildlife receptors, NOAEL RBSLs ranged from 0.013 to 340 mg/kg for soil, 0.0014 to 370 mg/kg for sediment, and 0.000075 to 1600 mg/L for surface water. Chronic RBSLs ranged from 0.00022 to 3.4 mg/L for aquatic life. The no-observed-effect concentration screening levels ranged from 0.084 to 642 mg/kg and 1 to 50 mg/kg for terrestrial plants and soil invertebrates, respectively.

Environmental Risk Evaluation Report: Perfluorooctanesulphonate (PFOS)
Brooke, D., A. Footitt, and T. Nwaogu.
Environment Agency, United Kingdom, SCHO1009BRBL-E-P, 104 pp, 2004

Potential exposure pathways in the environment via the major uses for PFOS-related substances are described, followed by a review of toxicity information relevant to aquatic organisms and subsequent effects on the ecological food chain.

Evaluation of Published Bioaccumulation Data for Per- and Polyfluoroalkyl Substances (PFAS) Across Aquatic Species
Burkhard, L. | International Conference on Remediation and Management of Contaminated Sediments, Nashville, TN, 24-27 January, poster, 2022.

This presentation summarizes published data for biota-sediment accumulation factors (BASFs) for use in risk assessments at contaminated sediment sites. A series of chemical-based search terms were developed to search for literature on PFAS chemicals, including chemical names and Chemical Abstracts Service registry numbers, synonyms, tradenames, and other relevant forms (i.e., metabolites, degradants, parent compounds, and related chemicals). Seven database searches resulted in 8,200 potentially relevant papers. Relevant papers were identified by searching Swift-Review software using appropriate search terms. Data from the papers were extracted into a database for analysis and review, and BSAF data for 11 taxonomic classes were found. Taxonomic classes with the most measurements were, in descending order, Teleostei (fish), Bivalvia, and Magnoliopsida (plants). Most measurements were for the carbonyl and sulfonyl PFAS classes. For Teleostei (fish), PFOS and PFOA had median BSAFs of 2.61 and 0.499 for whole body tissues, respectively. For Bivalvia, PFOS and PFOS had median BSAFs of 0.858 and 0.171, respectively. Summaries and analyses of data gaps and limitations in BSAFs are discussed. Additional information: Journal Article

Guidance for Assessing the Ecological Risks of PFASs to Threatened and Endangered Species at Aqueous Film Forming Foam-Impacted Sites
Conder, P., J. Arblaster, E. Larson, J. Brown, and C. Higgins.
SERDP Project ER18-1614, 177 pp, 2019

This guide provides key recommendations and information to support quantitative ecological risk assessment for threatened and endangered species exposed to 18 PFASs commonly found at AFFF sites.

Using Geospatial Data and Random Forest to Predict PFAS Contamination in Fish Tissue in the Columbia River Basin, United States
DeLuca, N.M., A. Mullikin, P. Brumm, A.G. Rappold, and E.C. Hubal.
Environmental Science & Technology 57(37):14024-14035(2023)

Decision makers in the Columbia River Basin (CRB) are currently challenged with identifying and characterizing the extent of PFAS contamination and human exposure. A methodology was developed and piloted to help decision-makers target and prioritize sampling investigations and identify contaminated natural resources. Random forest models were used to predict ΣPFAS in fish tissue; understanding PFAS levels in fish is particularly important in the CRB as fish are a major component of tribal and indigenous people's diets. Geospatial data, including land cover and distances to known or potential PFAS sources and industries, were leveraged as predictors for modeling. Models were developed and evaluated for Washington state and Oregon using limited available empirical data. Mapped predictions show several areas where detectable PFAS concentrations in fish tissue are predicted to occur, but sampling has not yet been confirmed. Variable importance is analyzed to identify potentially important sources of PFAS in fish in this region. The cost-effective methodologies demonstrated here can help address the sparsity of existing PFAS occurrence data in environmental media in other regions while also providing insights into potentially important drivers and sources of PFAS in fish.

Top of Page