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

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.


Publication:
Toxicology
Pub Date:
July 2021
DOI:

10.1016/j.tox.2021.152845

Bibcode:
2021Toxgy.45952845A
Keywords:
  • 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
full text sources
Elsevier
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