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Review
. 2021 Jul:459:152845.
doi: 10.1016/j.tox.2021.152845. Epub 2021 Jul 8.

Why is elevation of serum cholesterol associated with exposure to perfluoroalkyl substances (PFAS) in humans? A workshop report on potential mechanisms

Melvin E Andersen  1 , Bruno Hagenbuch  2 , Udayan Apte  3 , J Christopher Corton  4 , Tony Fletcher  5 , Christopher Lau  6 , William L Roth  7 , Bart Staels  8 , Gloria L Vega  9 , Harvey J Clewell 3rd  10 , Matthew P Longnecker  11
Affiliations
Review

Why is elevation of serum cholesterol associated with exposure to perfluoroalkyl substances (PFAS) in humans? A workshop report on potential mechanisms

Melvin E Andersen et al. Toxicology. 2021 Jul.

Abstract

Serum concentrations of cholesterol are positively correlated with exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) in humans. The associated change in cholesterol is small across a broad range of exposure to PFOA and PFOS. Animal studies generally have not indicated a mechanism that would account for the association in humans. The extent to which the relationship is causal is an open question. Nonetheless, the association is of particular importance because increased serum cholesterol has been considered as an endpoint to derive a point of departure in at least one recent risk assessment. To gain insight into potential mechanisms for the association, both causal and non-causal, an expert workshop was held Oct 31 and Nov 1, 2019 to discuss relevant data and propose new studies. In this report, we summarize the relevant background data, the discussion among the attendees, and their recommendations for further research.

Keywords: Fluorocarbons; Mechanism of action; Perfluoroalkyl substances; Serum cholesterol.

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Conflict of interest statement

Declaration of Competing Interest

3M was not involved in the preparation of the manuscript. The authors retained sole control of the manuscript content and the findings, and statements in this paper are those of the authors and not those of the author’s employer or the sponsors. No authors were directly compensated by 3 M. This project was funded through a contract between 3 M and Ramboll, an international science and engineering company that provided salary compensation to the authors. None of the authors are currently engaged to testify as experts on behalf of the sponsors in litigation related to the compound discussed in this manuscript. Dr Fletcher has served in the past as a paid consultant to law firms conducting litigation involving PFAS, for both plaintiffs and defendants. The information in this document has been subjected to review by the Center for Public Health and Environmental Assessment, Office of Research and Development, EPA and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

Figures

Fig. 1.
Fig. 1.
Serum cholesterol (mg/dl) in relation to serum PFOA (ng/mL) – schematic representation of the relation*. *Based on the results of Steenland et al. (2009). Steenland et al.’s Fig. 2 was scanned and a cubic model was fit to the data. Steenland et al.’s results were adjusted for age, sex, use of cholesloterol-lowering medication, smoking, education, physical activity, alcohol consumption, and body mass index. See the original article for details about reference categories used in predicting values. The average serum cholesterol among adults in the U.S. was 202 mg/dl (Nelson et al., 2010).
Fig. 2.
Fig. 2.
Distribution of LDL cholesterol among NHANES subjects 2003–2016. Results calculated using NHANES sampling parameters, to make them representative of the U.S. population. Those taking cholesterol-lowering drugs were excluded, as were those aged < 20 y. N = 2129 (PFOA) or 2128 (PFOS); in other words, the number of subjects under each curve shown above is roughly 1,000 (total n of subjects was 10,647). LDL cholesterol (mg/dl) was adjusted for age, sex, ethnicity, and an index indicating survey wave. The deciles were determined for PFOA or PFOA based on the distribution of values after adjusting for age, sex, ethnicity, and an index indicating survey wave and calculated using the sampling parameters. The smoothed curves are from a normal distribution with mean and standard deviation calculated from the observations.
See this image and copyright information in PMC

References

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