Why is elevation of serum cholesterol associated with exposure to perfluoroalkyl substances (PFAS) in humans? A workshop report on potential mechanisms. (July 2021)

• Record Type: Journal Article
• Authors: Andersen, Melvin E.; Hagenbuch, Bruno; Apte, Udayan; Corton, J. Christopher; Fletcher, Tony; Lau, Christopher; Roth, William L.; Staels, Bart; Vega, Gloria L.; Clewell, Harvey J.; Longnecker, Matthew P.
• Is Part Of: Toxicology. Volume 459(2021)
• Publication Date: 2021-07
• Subjects: ABST apical bile salt transporter -- BAS bile acid sequestrant -- CAR constitutive androstane receptor -- CETP cholesteryl ester transfer protein -- CYP7A1 cholesterol 7α-hydroxylase -- C4 7α-hydroxy-4-cholesten-3-one -- FXR farnesoid X receptor -- HDL high density lipoprotein -- HMGCR 3-hydroxy-3-methyl-glutaryl-Coenzyme A Reductase -- HNF4α hepatic nuclear factor 4-alpha -- LDL low density lipoprotein -- LXR α liver X receptor alpha -- NHANES National Health and Nutrition Examination Survey -- NPC1L1 Niemann-Pick C1 Like 1 -- PCSK9 proprotein convertase subtilism/kexin type 9 -- PFAS perfluoroalkyl substances -- PFOA perfluorooctanoic acid -- PFOS perfluorooctane sulfonic acid -- PK pharmacokinetic -- PPARα peroxisome proliferator-activated receptor alpha -- PPARγ peroxisome proliferator-activated receptor gamma -- PXR pregnane X receptor -- SREBP2 sterol regulatory element-binding protein 2; Fluorocarbons -- Perfluoroalkyl substances -- Serum cholesterol -- Mechanism of action; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2021.152845
• Languages: English
• ISSNs: 0300-483X

Abstract

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.