Cited by 241Per- and polyfluoroalkyl substances researchImmunotoxicology and immune responsesSynthesis and properties of polymers

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Exposure to per-fluoroalkyl and polyfluoroalkyl substances leads to immunotoxicity: epidemiological and toxicological evidence

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DeWitt, Jamie C., Blossom, Sarah J., Schaider, Laurel A.·2019·Journal of Exposure Science & Environmental Epidemiology

DOI 10.1038/s41370-018-0097-yPMC PMC6380927

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Abstract

In this perspective, we evaluate key and emerging epidemiological and toxicological data concerning immunotoxicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) and seek to reconcile conflicting conclusions from two reviews published in 2016. We summarize ways that immunosuppression and immunoenhancement are defined and explain how specific outcomes are used to evaluate immunotoxicity in humans and experimental animals. We observe that different approaches to defining immunotoxicological outcomes, particularly those that do not produce clinical disease, may lead to different conclusions from epidemiological and toxicological studies. The fundamental point that we make is that aspects of epidemiological studies considered as limitations can be minimized when data from toxicological studies support epidemiological findings. Taken together, we find that results of epidemiological studies, supported by findings from toxicological studies, provide strong evidence that humans exposed to PFOA and PFOS are at risk for immunosuppression.

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Self-citation
Methods in molecular biology
Deininger, P. L. (1991) · Analytical Biochemistry · doi:10.1016/0003-2697(91)90283-y · Cited by 894
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Risk assessment in immunotoxicology I. Sensitivity and predictability of immune tests
Luster, M. I. (1992) · Fundamental and Applied Toxicology · doi:10.1016/0272-0590(92)90047-l · Cited by 566
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Dong, G., Tung, K., Tsai, C., Liu, M.-M., Wang, D., Liu, W., Jin, Y., Hsieh, W., Lee, Y. L., & Chen, P. (2013) · Environmental Health Perspectives · doi:10.1289/ehp.1205351 · Cited by 199

Show all 54 references

Research works printed but not linked: 2

Science Advisory Board (SAB). SAB review of EPA’s draft risk assessment of potential human health effects associated with PFOA and its salts. 2006.
Kaplan BLF, Sulentic CEW, Holsapple MP, Kaminski NE. Chapter 12: toxic responses of the immune system. In: Curtis D. Klaassen and John B. Watkins III (eds.). Casarett and Doull’s essentials of toxicology. (McGraw-Hill Education, U.S.) 2015. p. 177–94.

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Authors: DeWitt, J. C., Blossom, S. J., & Schaider, L. A.
Affiliations: East Carolina University (US)
Arkansas Children's Research Institute (US)
Silent Spring Institute (US)
Corresponding author: DeWitt, Jamie C.
ORCID: DeWitt, Jamie C.
Blossom, Sarah J.
Schaider, Laurel A.
Venue: Journal of Exposure Science & Environmental Epidemiology
Publisher: Springer Science and Business Media LLC
Published: 2018-11-27
Volume: 29
Issue: 2
Pages: 148-156
ISSN: 1559-0631 (ISSN-L)
1559-064X
DOI: 10.1038/s41370-018-0097-y
PMC: PMC6380927
OpenAlex: W2903188676
Cited by: 241
References: 54
Citations by year: 2026: 31 · 2025: 34 · 2024: 35 · 2023: 42 · 2022: 27 · 2021: 33 · 2020: 25 · 2019: 13
FWCI: 1.49
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Journal of Exposure Science & Environmental Epidemiology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Environmental Health Sciences (P42ES027706)
Topics: Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
Physical Sciences › Materials Science › Polymers and Plastics › Synthesis and properties of polymers
Keywords: perfluorooctanoic acid, PFOS, per- and polyfluoroalkyl substances, immunotoxicity, immunosuppression, immune enhancement, human exposure, toxicological evidence, epidemiological evidence
MeSH terms: Animals, Immunotoxins, Caprylates, Environmental Exposure, Fluorocarbons, Humans, Alkanesulfonic Acids, Risk Assessment

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Exposure to per-fluoroalkyl and polyfluoroalkyl substances leads to immunotoxicity: epidemiological and toxicological evidence

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