Why Toxic Equivalency Factors Are Not Suitable for Perfluoroalkyl Chemicals

Peters, Jeffrey M.; Gonzalez, Frank J.

doi:10.1021/tx200316x

Cited by 48Per- and polyfluoroalkyl substances researchToxic Organic Pollutants ImpactFluorine in Organic Chemistry

Why Toxic Equivalency Factors Are Not Suitable for Perfluoroalkyl Chemicals

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Peters, Jeffrey M., Gonzalez, Frank J.·2011·Chemical Research in Toxicology

DOI 10.1021/tx200316xPMC PMC6624430

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Abstract

The pervasive nature of perfluoroalkyl chemicals in the environment has generated considerable interest for developing new strategies for risk assessment. In experimental animal models, exposure to perfluoroalkyl chemicals can cause developmental toxicity and hepatotoxicity. Peroxisome proliferator-activated receptor-α (PPARα) is required to mediate some but not all of these effects. Since PPARα has a role in mediating some of these effects, and there is some overlap in the type of toxicities elicited by perfluoroalkyl chemicals, it has been suggested that a scaling system analogous to the toxic equivalency factor (TEF) system used for polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans (PCDF), and polychlorinated biphenyls (PCB) could be used for perfluoroalkyl chemicals. However, evidence suggests that perfluoroalkyl chemicals can activate/interfere with other receptors, and there is reason to suggest the possibility of species differences in the response mediated by different receptors as well as qualitative differences in toxicities elicited by perfluoroalkyl chemicals. These differences and other data gaps preclude the development of a TEF approach for perfluoroalkyl chemicals.

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Given existing differences in toxicokinetics and mechanisms of action, and the lack of comprehensive data, the development of a TEF approach for perfluoroalkyl chemicals remains a distant goal rather than a scientifically established outcome.
“Overall, given the existing differences in toxicokinetics and mechanisms of action, and the lack of comprehensive data, the development of a TEF approach for perfluoroalkyl chemicals remains a distant goal rather than a scientifically established outcome [53,54,55].”
From The EU’s Per- and Polyfluoroalkyl Substances (PFAS) Ban: A Case of Policy over Science (2023) · cites this paper as [53]

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Authors: Peters, J. M., & Gonzalez, F. J.
Affiliations: Pennsylvania State University (US)
National Institutes of Health (US)
Corresponding author: Peters, Jeffrey M.
ORCID: Peters, Jeffrey M.
Gonzalez, Frank J.
Venue: Chemical Research in Toxicology
Publisher: American Chemical Society (ACS)
Published: 2011-09-28
Volume: 24
Issue: 10
Pages: 1601-1609
ISSN: 0893-228X (ISSN-L)
1520-5010
DOI: 10.1021/tx200316x
PMC: PMC6624430
OpenAlex: W2316105671
Cited by: 48
References: 70
Citations by year: 2026: 2 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 7 · 2014: 6 · 2013: 5 · 2012: 3
FWCI: 0.37
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Chemical Research in Toxicology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Cancer Institute (ZIABC005708, ZIABC005562)
Topics: Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Fluorine in Organic Chemistry
Keywords: toxic equivalency factors, PPARα, developmental toxicity, hepatotoxicity, receptor activation, species differences, environmental risk assessment, perfluorinated compounds
MeSH terms: Pregnane X Receptor, Constitutive Androstane Receptor, Animals, Drug Interactions, Environmental Pollutants, Humans, Hydrocarbons, Fluorinated, Receptors, Steroid, Species Specificity, Surface-Active Agents, Receptors, Cytoplasmic and Nuclear, Risk Assessment, Peroxisome Proliferator-Activated Receptors, Estrogen Receptor alpha

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Why Toxic Equivalency Factors Are Not Suitable for Perfluoroalkyl Chemicals

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