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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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Consensus Study Report

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001

This project was funded with federal funds from the Centers for Disease Control and Prevention under contract number 200-2011-38807, task order number 75D30121F00099; National Institutes of Environmental Health Sciences, National Institutes of Health, and U.S. Department of Health and Human Services, under Contract No. HHSN2632018000291, task order number 75N98020F00012. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. https://doi.org/10.17226/26156.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
×

The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president.

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
×

Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task.

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Rapid Expert Consultations published by the National Academies of Sciences, Engineering, and Medicine are authored by subject-matter experts on narrowly focused topics that can be supported by a body of evidence. The discussions contained in rapid expert consultations are considered those of the authors and do not contain policy recommendations. Rapid expert consultations are reviewed by the institution before release.

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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COMMITTEE ON THE GUIDANCE ON PFAS TESTING AND HEALTH OUTCOMES

BRUCE N. CALONGE (Chair), University of Colorado School of Medicine and School of Public Health

LAURA ANDERKO, Mid-Atlantic Center for Children’s Health and the Environment, M. Fitzpatrick College of Nursing, Villanova University

DANA BOYD BARR, Emory University Rollins School of Public Health

ERIN BELL, School of Public Health, University at Albany

KEVIN ELLIOTT, Michigan State University

MELISSA GONZALES, Tulane University School of Public Health and Tropical Medicine

ERIN HAYNES, University of Kentucky College of Public Health

JANE HOPPIN, North Carolina State University

TAMARRA JAMES-TODD, Harvard T.H. Chan School of Public Health

ALEX KEMPER, The Ohio State University College of Medicine; Nationwide Children’s Hospital

BRIAN LINDE, Yale School of Medicine

MARC-ANDRÉ VERNER, Université de Montréal

VERONICA VIEIRA, University of California, Irvine

XIAOBIN WANG, Johns Hopkins Bloomberg School of Public Health and School of Medicine

CHRIS WIANT, Caring for Colorado Foundation

Health and Medicine Division Staff

ELIZABETH BARKSDALE BOYLE, Study Director

ALEXIS WOJTOWICZ, Associate Program Officer

ALEXANDRA MCKAY, Senior Program Assistant

ROSE MARIE MARTINEZ, Senior Board Director, Board on Population Health and Public Health Practice

Division on Earth and Life Studies Staff

MARILEE SHELTON-DAVENPORT, Senior Program Officer (until March 2022)

KATE GUYTON, Senior Program Officer

KALEY BEINS, Program Officer

CLIFFORD DUKE, Board Director, Board on Environmental Studies and Toxicology

Consultants

ALLIE BOMAN, Briere Associates, Inc.

RONA BRIERE, Briere Associates, Inc.

CARY HAVER, ICF Resources, LLC

JORDAN KUIPER, Johns Hopkins University

JUDY LAKIND, LaKind Associates

KATE MARQUESS, Johns Hopkins University

MELISSA MILLER, ICF Resources, LLC

JOSH NAIMAN, LaKind Associates

ANNA RUTH ROBUCK, Icahn School of Medicine at Mount Sinai

MARGARET SHANDLING, Briere Associates, Inc.

LAUREN TOBIAS, Maven Messaging

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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Community Liaisons

LAURENE ALLEN, Merrimack Citizens for Clean Water

ANDREA AMICO, Testing for Pease

STEL BAILEY, Fight for Zero

KYLA BENNETT, Public Employees for Environmental Responsibility

KAREN BLONDEL, Public Housing Civic Association, Inc.

PHIL BROWN, Northeastern University

ALBERTO J. CABAN-MARTINEZ, University of Miami

CHERYL CAIL, South Carolina Indian Affairs Commission/SC Idle No More

COURTNEY CARIGNAN, Michigan State University

TRACY CARLUCCIO, Delaware Riverkeeper Network

JAMIE DEWITT, East Carolina University

EMILY DONOVAN, Clean Cape Fear

ALAN DUCATMAN, West Virginia University

PATRICK ELDER, Military Poisons

TERESA GERADE, Don’t Undermine Memphremagog’s Purity

HOPE GROSSE, Buxmont Coalition for Safe Water

LOREEN HACKETT, PFOA Project New York

AYESHA KHAN, Nantucket PFAS Action Group

RAINER LOHMANN, University of Rhode Island Superfund Research Center

SAMRAA LUQMAN, Concerned Residents for South Dearborn

BETH MARKESINO, North Carolina Stop Gen-X In Our Water

AARON MARUZZO, University of California, Berkeley

TOBYN MCNAUGHTON, Resident of Belmont, Michigan

KRISTEN MELLO, Westfield Residents Advocating for Themselves

PAMELA K. MILLER, Alaska Community Action on Toxics

ELIZABETH NEARY, Wisconsin Environmental Health Network

LAURA OLAH, Citizens for Safe Water Around Badger

JACOB PARK, University of Johannesburg, Castleton University

SUE PHELAN,1 GreenCAPE

ANDREA RICH, Save Our Water

DANA SARGENT, Cape Fear River Watch

LAUREL SCHAIDER, Silent Spring Institute

LINDA SHOSIE, Mothers for Safe Air & Safe Water

LENNY SIEGEL, Center for Public Environmental Oversight

MIKE WATTERS, Gray’s Creek Residents United Against PFAS in our Wells and Rivers

LA’MESHIA WHITTINGTON, Meredith College/North Carolina Black Alliance

ALAN WOOLF, Harvard Medical School

CATHY WUSTERBARTH, Need Our Water

SANDY WYNN-STELT, Great Lakes PFAS Action Network

___________________

1 Deceased January 2022.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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Reviewers

This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.

We thank the following individuals for their review of this report:

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report, nor did they see the final draft before its release. The review of this report was overseen by Joshua Sharfstein, Johns Hopkins Bloomberg School of Public Health, and Susan Brantley, The Pennsylvania State University. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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Acknowledgments

Many people were critical in helping the committee accomplish its charge. The committee gratefully acknowledges the work of the community liaisons who provided insight and viewpoints pertinent to planning for our public meetings. In particular, we thank Andrea Amico, Emily Donovan, Patrick Elder, Ayesha Khan, Kristen Mello, and Laura Olah, who provided helpful insights on the perspectives and experiences of their communities that informed our community engagement methods. This engagement ensured that our public meetings would include the relevant perspectives, which allowed us to learn about the social, environmental, public health, and medical challenges central to our charge. In addition, we found the information and perspectives provided by the presentations and discussions at our public meetings immensely helpful in informing our deliberations (see Appendix C).

The committee’s work was enhanced by the technical expertise; writing contributions; data evaluation, visualization, and extraction; and other support provided by Cary Haver, Jordan Kuiper, Judy Lakind, Kate Marquess, Melissa Miller, Josh Naiman, Anna Ruth Robuck, and Lauren Tobias, who served as consultants. We would also like to acknowledge the U.S. Environmental Protection Agency’s Office of Water and Office of Research and Development for sharing publicly available abstracted data from some of the epidemiologic studies included in our literature review, as well as Scott M. Bartell and Nicholas Cuvelier from the University of California, Irvine, for calculating percentiles of per- and polyfluoroalkyl (PFAS) exposure.

Importantly, the committee heard from a number of individuals who shared their personal stories about and experiences with PFAS exposure, testing, and clinical follow-up. These discussions helped ground our work in the lived experiences of the complex issues that had to be tackled in this report, and we are extremely grateful for their courage in sharing those experiences in a public forum.

The committee thanks the staff of the National Academies of Sciences, Engineering, and Medicine who contributed to producing this report, especially the extraordinary, creative, and tireless study staff: Kaley Beins, Elizabeth Boyle, Clifford Duke, Kathryn Guyton, Rose Marie Martinez, Alexandra McKay, Marilee Shelton-Davenport, and Alexis Wojtowicz. Thanks as well go to other staff in the Division on Earth and Life Studies who provided additional support, including Tamara Dawson, Eric Edkin, Elizabeth Eide, Lauren Everett, Nancy Huddleston, Radiah Rose, and Maggie Walser. This project also received important assistance from Megan Lowry (Office of News and Public Information) and Matthew Anderson (Office of Financial Administration). Valuable research assistance was provided by Christopher Lao-Scott, senior research librarian in the National Academies Research Center. Finally, a thank you is extended to Rona Briere and Allison Boman, who assisted the committee with editing the report.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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Preface

The creation of the U.S. Environmental Protection Agency (EPA) in 1970 signaled public recognition of industrial impacts on the environment. The government subsequently acknowledged that three elements essential for life—air, water, and food—could be contaminated by industrial activity and threaten human health. In 1980, two steps were taken in response to the government’s concern: passage of the Comprehensive Environmental Response, Compensation, and Liability Act and creation of the Agency for Toxic Substances and Disease Registry (ATSDR).

The mission of ATSDR is to prevent or mitigate the adverse impacts on human health and diminished quality of life resulting from exposure to hazardous substances in the environment. The earliest contaminants of concern included pesticides; heavy metals from mining; asbestos; munitions and their manufacturing by-products (including radioactive substances); petrochemicals, including solvents; and products and by-products associated with oil and gas extraction, refinement, and use. Over time, additional industrial products with significant potential to affect the population’s health have been identified, including the class of chemicals known as per- and polyfluoroalkyl substances, or PFAS. PFAS have useful properties, such as oil and water repellency, temperature resistance, and friction reduction. For decades, they have been used in numerous applications and products, such as firefighting; chrome-plating; lubricants; insecticides; and coatings and treatments for such surfaces as carpeting, packaging, and cookware. As a result of the production and use of PFAS, many sites across the country are contaminated with PFAS, which in turn can result in contamination of soils and drinking water.

ATSDR faces a critical challenge in protecting people from the potential health impacts of PFAS exposures. Data from the National Health and Nutrition Examination Survey show that nearly 100 percent of people in the United States are exposed to at least one PFAS, but at what level of exposure do harms to human health occur? What PFAS-associated health outcomes might benefit from clinical follow-up or care? Would there be any benefit in testing people to know their PFAS exposure level? What clinical follow-up can help protect people from PFAS-associated harms?

Answering these questions requires bridging approaches used for chemical hazard assessments, such as those carried out by the EPA; public and community health benefits, such as those laid out in the Community Guide to Preventive Services; and medical care health benefit assessments, such as those of the U.S. Preventive Services Task Force. Chemical hazard assessments are conducted to determine whether a chemical exposure causes harm; public health assessments address the impact on and interventions to mitigate threats to the health of a population or community; and medical care health benefit assessments evaluate the effects of medical interventions, including their beneficial effects and potential adverse outcomes. One challenge with blending these different approaches is that in medical care health benefit assessments, the “gold standard” for informing clinical risk/benefit decisions for medical interventions is the randomized controlled trial (RCT). However, RCTs are typically impossible for chemical hazard assessments, for both ethical and practical reasons. For example, most environmental chemicals are not developed to improve human health, making intentional exposures in an RCT unethical. Chemical exposures also vary and may or may not be significant depending on the agent’s toxicity, which sometimes makes controlled trials infeasible. And public health assessments, in which comparative studies are still required to support evidence-based recommendations, usually require many years of data and are challenged by the long-standing and often-lamented separation of health care and public health.

In 2010, researchers Stephen Rappaport and Martyn Smith reported that “70 to 90% of disease risks are probably due to differences in environments” and made the case for a more comprehensive approach to evaluating environmental exposures in order to understand the causes of and contributors to

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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chronic disease.2 Such an approach has, as in the case of lead, and will, for chemicals such as PFAS, ultimately depend on breaking down the barriers between environmental public health and the clinical care setting. These two health sectors have had some limited success in bridging the gap for infectious disease outbreaks and epidemics. Identifying environmental exposures, measuring exposure levels in patients, and providing indicated medical follow-up are elements of a critical frontier that could and should bring the two disciplines closer together to improve the health of those in the nation’s communities.

Another challenge for the study committee was the critical need to include community voices in the study process as an important and credible source of evidence to inform guidance recommendations. To meet that challenge, this study included the testimony of more than 30 people who live in or work with a community impacted by PFAS contamination. Community members provided the committee with much needed data based on their lived experiences with PFAS contamination, and moved the committee’s work from an academic exercise to a personal reality. The committee used the presentations of community members to inform frameworks within the report and to gain an understanding of the social context that the committee’s recommendations will inform.

Atmospheric chemist Susan Solomon has suggested that successfully addressing environmental challenges requires making the problem personal, perceptible, and practical. The voices of affected individuals in contaminated communities make the PFAS issue personal, while the scientists researching the associations with human health make the impacts of PFAS exposure perceptible. In this report, the committee has endeavored to provide practical recommendations that can aid policy makers, state and federal environmental and public health agencies, clinicians, and concerned individuals in addressing this important health problem.

Bruce N. Calonge, Chair
Committee on the Guidance on PFAS Testing and Health Outcomes

___________________

2 Rappaport, S., and M. Smith. 2010. Science 330(6003):460–461. https://doi.org/10.1126/science.1192603.

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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3-1 PFAS Exposure and Risk of SARS-CoV-2 Infection

5-1 Total Organofluorine Testing

5-2 Potential Harms and Benefits of PFAS Testing

5-3 Considerations for Frequency of PFAS Testing

5-4 Clinical Use of Reference Ranges

5-5 PFAS Serum Levels Are Not Directly Comparable to PFAS Drinking Water Levels

D-1 AMSTAR-2 Critical Domains and Overall Confidence in the Results

D-2 Critical Domains Used by the Committee to Assess Risk of Bias

D-3 Bradford Hill Considerations

FIGURES

S-1 Brief history of PFAS manufacturing, regulation, and community exposure

S-2 PFAS contamination across the United States

S-3 Blood (serum) levels of PFAS, United States, 2000–2016

S-4 The committee’s approach to the Statement of Task and the chapters and appendixes where the topics are discussed

S-5 Categories of association used in this report

S-6 Clinical guidance for follow-up with patients after PFAS testing

S-7 Flow chart showing how the committee’s recommendations work together in a clinical setting

S-8 Suggested framework for updating the Agency for Toxic Substances and Disease Registry’s clinical guidance based on new evidence

1-1 Brief history of PFAS manufacturing, regulation, and community exposure

1-2 PFAS contamination across the United States

1-3 Blood (serum) levels of PFAS, United States, 2000–2016

1-4 Pellow’s Environmental Justice Framework

1-5 Serum PFAS concentrations (unadjusted geometric means) from the National Health and Nutrition Examination Survey, 1999–2016, by race/ethnicity, age, and income-to-poverty ratio

1-6 Serum PFAS concentrations (unadjusted geometric means) from the National Health and Nutrition Examination Survey, 1999–2016, by race/ethnicity, for PFOA, PFOS, PFHxS, and PFNA

1-7 Examples of how PFAS enter the environment

1-8 The committee’s approach to the Statement of Task and the chapters and appendixes where the topics are discussed

1-9 The committee’s approach to community engagement

1-10 Hierarchy of controls

2-1 U.S. Preventive Services Task Force’s generic analytic framework for a screening preventive service

2-2 Visual representation of the seven components of the evidence framework for genetic testing developed by the National Academies of Sciences, Engineering, and Medicine

3-1 Evidence map describing the number of studies found, by PFAS, for each health outcome category

3-2 Categories of association used in this report

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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3-3 Regression coefficients for changes in immunoglobulin (IgG) concentrations per 1-log10 nanograms per milliliter (ng/mL) increase in PFAS serum level

3-4 Regression coefficients for percent difference in measles antibody response per doubling of log10 nanograms per milliliter (ng/mL) serum PFOS

3-5 Regression coefficients for percent change in hand, foot, and mouth disease antibody response per doubling of natural logarithm (ln)-nanograms per milliliter (ng/mL) sum of PFAS

3-6 Regression coefficients for changes in total cholesterol in adults

3-7 Regression coefficients for total cholesterol per interquartile range (IQR) increase in PFAS exposure in children

3-8 Kidney cancer adjusted rate ratios and 95% confidence intervals by study and PFOA exposure category

3-9 Testicular cancer adjusted rate ratios and 95% confidence intervals by study and PFOA exposure category

3-10 Breast cancer adjusted rate ratios and 95% confidence intervals by study and PFOS exposure category

3-11 Adjusted risk estimates for preeclampsia, gestational hypertension (hypertension without preeclampsia), and hypertensive disorders of pregnancy and 95% confidence intervals by study and PFAS PFOS exposure category

3-12 Adjusted risk estimates for preeclampsia, gestational hypertension (hypertension without preeclampsia), and hypertensive disorders of pregnancy and 95% confidence intervals by study and PFOA exposure category

3-13 Adjusted risk estimates for preeclampsia, gestational hypertension (hypertension without preeclampsia), and hypertensive disorders of pregnancy and 95% confidence intervals by study and PFuDA and PFDA exposure category

3-14 Adjusted risk estimates for preeclampsia, gestational hypertension (hypertension without preeclampsia), and hypertensive disorders of pregnancy and 95% confidence intervals by study and PFHxS exposure category

3-15 Adjusted risk estimates for preeclampsia, gestational hypertension (hypertension without preeclampsia), and hypertensive disorders of pregnancy and 95% confidence intervals by study and PFNA exposure category

4-1 Conceptual model for PFAS exposure reduction

4-2 Blood (serum) levels of PFAS, United States, 2000–2016

4-3 Measured and estimated breast milk concentrations of PFAS in the United States and Canada, in comparison with children’s drinking water screening values

4-4 Recommendations for reducing PFAS exposure available through the PFAS Exchange

4-5 PFAS Project Lab map showing PFAS contamination sites in the continental United States

5-1 Simplified flow chart of classes of biomarkers

5-2 Distribution of biomarker concentrations in a generic reference population

5-3 Geometric means of PFAS in blood from east metro St. Paul biomonitoring, in nanograms per milliliter (ng/mL)

5-4 Reference- and risk-based serum PFOS and PFOA concentrations that could inform clinical assessments

5-5 Graphical display of the levels of PFAS to inform clinical care for the sum of MeFOSAA, PFHxS, PFOA (linear and branched isomers), PFDA, PFUnDA, PFOS (linear and branched isomers), and PFN in serum or plasma

6-1 Clinical guidance for follow-up with patients after PFAS testing

6-2 Flow chart on how the committee’s recommendations work together in a clinical setting

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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7-1 Suggested framework for updating the Agency for Toxic Substances and Disease Registry’s clinical guidance based on new evidence

8-1 Recommended approach to mitigating PFAS exposure and adverse health outcomes

D-1 Preferred reporting items for systematic reviews and meta-analyses (PRISMA) diagram for the committee’s review of reviews on health effects of PFAS

D-2 Preferred reporting items for systematic reviews and meta-analyses (PRISMA) diagram for the committee’s reviews on the health effects of PFAS

D-3 Evidence map describing the number of studies found by PFAS for each health outcome category

E-1 Human PFAS exposure pathways

E-2 Examples of PFAS content (micrograms per kilogram [μg/kg] wet weight [ww]) in raw and steamed seafood samples and percentages of PFAS content increase (+) and decrease (−) after steaming (mean ± standard deviation [SD])

E-3 Examples of inconsistent changes in selected PFAS concentrations after fish and shellfish preparation

E-4 Variation in PFAS levels above the method reporting limit in drinking water in the United States

E-5 PFAS levels above and below the method reporting limit in drinking water in the United States

E-6 Limited data on PFAS levels in breast milk and infant formula in the United States show general overlapping concentrations, which also overlap with PFAS concentrations in drinking water that could be used to reconstitute formula

E-7 Relative contribution percentiles for various pathways of exposure to PFOA

E-8 Relative contribution percentiles for various pathways of exposure to PFOS

E-9 Estimated daily intakes for male adults and relative source contributions

E-10 Summary of numbers of studies identified for each PFAS exposure source

TABLES

S-1 PFAS Species Currently Included in the Centers for Disease Control and Prevention’s National Report on Human Exposure to Environmental Chemicals

1-1 PFAS Species Currently Included in the Centers for Disease Control and Prevention’s National Report on Human Exposure to Environmental Chemicals

2-1 Evidence-to-Decision Frameworks Reviewed by Norris and Colleagues (2021)

2-2 U.S. Preventive Services Task Force’s Recommendation Grid

2-3 Criteria for Reasonableness of Precautionary Measures

3-1 PFAS Species Currently Included in the Centers for Disease Control and Prevention’s (CDC’s) National Report on Human Exposure to Environmental Chemicals

3-2 Categories of Health Effects Mentioned by Speakers at the Committee’s Town Halls

3-3 Effect Estimates Change in Birthweight per Change in PFAS, from Studies Rated as Having Low Risk of Bias

Annex 3-1 Health Effects of PFAS by Category

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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Acronyms and Abbreviations

AAFP American Academy of Family Physicians
AAP American Academy of Pediatrics
ACOG American College of Obstetricians and Gynecologists
AHRQ Agency for Healthcare Research and Quality
ALT alanine aminotransferase
ANHE Alliance of Nurses for Health Environments
ASTHO Association of State and Territorial Health Officials
ATSDR Agency for Toxic Substances and Disease Registry
BE biomonitoring equivalent
BLL blood lead level
BMI body mass index
CAS Chemical Abstract Services
CDC Centers for Disease Control and Prevention
CERCLA Comprehensive Environmental Response, Compensation, and Liability Act
CI confidence interval
CMS Centers for Medicare & Medicaid Services
CPG clinical practice guideline
CPT Current Procedural Terminology
DNA deoxyribonucleic acid
DOD U.S. Department of Defense
EFSA European Food Safety Authority
EPA U.S. Environmental Protection Agency
EVIDEM Evidence and Value in Decision Making
EWG Environmental Working Group
FDA U.S. Food and Drug Administration
FOSA perfluorooctane sulfonamide
GRADE Grading of Recommendations, Assessment, Development and Evaluations
HBM human biomonitoring
HDL high-density lipoprotein
HHS U.S. Department of Health and Human Services
HMB German Human Biomonitoring Commission
IARC International Agency for Research on Cancer
IOM Institute of Medicine
LDL low-density lipoprotein
LOD limit of detection
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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MCL maximum contaminant level
MeFOSAA methylperfluorooctane sulfonamidoacetic acid
NAS National Academy of Sciences
NHANES National Health and Nutrition Examination Survey
NIEHS National Institute of Environmental Health Sciences
NIOSH National Institute for Occupational Safety and Health
NIST-SRM National Institute of Standards and Technology Standard Reference Material
NRC National Research Council
NTP National Toxicology Program
OECD Organisation for Economic Co-operation and Development
OR odds ratio
OSHA Occupational Safety and Health Administration
PBPK physiologically based pharmacokinetic
PEHSU Pediatric Environmental Health Specialty Unit
PFAS-REACH PFAS Research, Education, and Action for Community Health
PFBA perfluorobutanoic acid
PFBS perfluorobutane sulfonic acid
PFCA perfluorinated aliphatic carboxylic acid
PFDA perfluorodecanoic acid
PFDoDA perfluorododecanoic acid
PFHpA perfluoroheptanoic acid
PFHpS perfluoroheptanesulfonic acid
PFHxA perfluorohexanoic acid
PFHxS perfluorohexane sulfonic acid
PFNA perfluorononanoic acid
PFOA perfluorooctanoic acid
PFOS perfluorooctane sulfonic acid
PFUnA perfluoroundecanoic acid
PFUnDA perfluoroundecanoic acid
QA Quality Assurance
QC Quality Control
RfD reference dose
SD standard deviation
SSEHRI Social Science Environmental Health Research Institute
TSCA Toxic Substances Control Act
USDA U.S. Department of Agriculture
USPSTF U.S. Preventive Services Task Force
VHA Veterans Health Administration
WHO World Health Organization
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2022. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Washington, DC: The National Academies Press. doi: 10.17226/26156.
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Guidance on PFAS Exposure, Testing, and Clinical Follow-Up Get This Book
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In thousands of communities across the United States, drinking water is contaminated with chemicals known as perfluoroalkyl and polyfluoroalkyl substances (PFAS). PFAS are used in a wide range of products, such as non-stick cookware, water and stain repellent fabrics, and fire-fighting foam, because they have properties that repel oil and water, reduce friction, and resist temperature changes. PFAS can leak into the environment where they are made, used, disposed of, or spilled. PFAS exposure has been linked to a number of adverse health effects including certain cancers, thyroid dysfunction, changes in cholesterol, and small reductions in birth weight.

This report recommends that the Centers for Disease Control and Prevention (CDC) update its clinical guidance to advise clinicians to offer PFAS blood testing to patients who are likely to have a history of elevated exposure, such as those with occupational exposures or those who live in areas known to be contaminated. If testing reveals PFAS levels associated with an increased risk of adverse effects, patients should receive regular screenings and monitoring for these and other health impacts. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up recommends that the CDC, Agency for Toxic Substances and Disease Registry (ATSDR), and public health departments support clinicians by creating educational materials on PFAS exposure, potential health effects, the limitations of testing, and the benefits and harms of testing.

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