A systematic evidence map of chronic inflammation and immunosuppression related to per- and polyfluoroalkyl substance (PFAS) exposure

Luoping Zhang; Allen Louie; Gabrielle Rigutto; Helen Guo; Yun Zhao; Stacy Ahn; Sarah Dahlberg; Michael Sholinbeck; Martyn T Smith

doi:10.1016/j.envres.2022.115188

A systematic evidence map of chronic inflammation and immunosuppression related to per- and polyfluoroalkyl substance (PFAS) exposure

Environ Res. 2023 Mar 1:220:115188. doi: 10.1016/j.envres.2022.115188. Epub 2022 Dec 30.

Authors

Luoping Zhang¹, Allen Louie², Gabrielle Rigutto³, Helen Guo³, Yun Zhao³, Stacy Ahn³, Sarah Dahlberg³, Michael Sholinbeck⁴, Martyn T Smith³

Affiliations

¹ Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, 94720, USA. Electronic address: luoping@berkeley.edu.
² Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, 94720, USA; Molecular Toxicology Interdepartmental Program, Fielding School of Public Health, University of California, Los Angeles, CA, 90095, USA.
³ Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, 94720, USA.
⁴ Bioscience, Natural Resources & Public Health Library, University of California, Berkeley, CA, 94720, USA.

Abstract

Background: The ability to induce chronic inflammation and immunosuppression are two key characteristics of carcinogens and important forms of immunotoxicity. The National Toxicology Program (NTP) evaluated the immunotoxicity of two per- and polyfluoroalkyl substances (PFASs), PFOA (perfluorooctanoic acid) and PFOS (perfluorooctane sulfonate), in 2016. However, the potential pro-inflammatory and immunosuppressive effects of other PFASs remain largely uncharacterized.

Methods: We developed an expanded set of search terms pertaining to the chronic inflammatory and immunosuppressive effects of PFASs based on those of the International Agency for Research on Cancer (IARC) and NTP. To confirm searching effectiveness and scope, we compared our search term results with those of IARC and NTP for both PFASs and two other known carcinogens, chromium (VI) and benzene. Systematic evidence maps (SEMs) were also produced using Tableau to visualize the distribution of study numbers and types reporting immunotoxic effects and specific biomarkers elicited by PFAS exposures.

Results: In total, 1155 PFAS studies were retrieved, of which 321 qualified for inclusion in our dataset. Using our search terms, we identified a greater number of relevant studies than those obtained using IARC and NTP's search terms. From the SEM findings, increased cytokine production strengthened an association between PFAS exposure and chronic inflammation, and decreased B-cell activation and altered levels of T-cell subtypes and immunoglobulins confirmed PFAS-induced immunosuppression.

Conclusion: Our SEM findings confirm that several PFASs commonly found in both in the environment, including those that are lesser-known, may induce immunosuppression and chronic inflammation, two key characteristics of carcinogens. This approach, including development of search terms, study screening process, data coding, and evidence mapping visualizations, can be applied to other key characteristics of chemical carcinogens.

Keywords: Carcinogens; Environmental exposures; Immunotoxicity; Inflammasome; PFOA/PFOS.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alkanesulfonic Acids*
Carcinogens
Environmental Pollutants*
Fluorocarbons* / analysis
Fluorocarbons* / toxicity
Immunosuppression Therapy

Substances

Alkanesulfonic Acids
Fluorocarbons
Carcinogens
Environmental Pollutants

Grants and funding

P42 ES004705/ES/NIEHS NIH HHS/United States