scholarly journals Response to Comment on “Novel Perfluoroalkyl Ether Carboxylic Acids (PFECAs) and Sulfonic Acids (PFESAs)”: Overlooked Interactions with Perfluorooctanoic Acid

2021 ◽  
Author(s):  
Jingzhi Yao ◽  
Yitao Pan ◽  
Jiayin Dai
Keyword(s):  
Carboxylic Acids ◽  
Perfluorooctanoic Acid ◽  
Sulfonic Acids

Investigating the interaction between three perfluorinated carboxylic acids and the G protein-coupled estrogen receptor: spectroscopic analyses and computational simulations

2020 ◽  
Vol 12 (31) ◽  
pp. 3944-3953 ◽  
Author(s):  
Li Yong ◽  
Manting Huang ◽  
Yuchen Wei ◽  
Jie Xu ◽  
Zhongsheng Yi
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Carboxylic Acids ◽  
Perfluorooctanoic Acid ◽  
Computational Simulations ◽  
Spectroscopic Analyses ◽  
Perfluorinated Carboxylic Acids ◽  
G Protein Coupled

Here, perfluorobutyric acid (PFBA), perfluorooctanoic acid (PFOA) and perfluorododecanoic acid (PFDoA) were selected as typical representatives of perfluorinated carboxylic acids (PFCAs) to study the effects of PFCAs on the G protein-coupled estrogen receptor (GPER).

Accumulation Potentials of Perfluoroalkyl Carboxylic Acids (PFCAs) and Perfluoroalkyl Sulfonic Acids (PFSAs) in Maize (Zea mays)

2015 ◽  
Vol 63 (14) ◽  
pp. 3646-3653 ◽  
Author(s):  
Johanna Krippner ◽  
Sandy Falk ◽  
Hubertus Brunn ◽  
Sebastian Georgii ◽  
Sven Schubert ◽  
...  
Keyword(s):  
Zea Mays ◽  
Carboxylic Acids ◽  
Sulfonic Acids

scholarly journals Predicting the Effects of Per- and Polyfluoroalkyl Substance Mixtures on Peroxisome Proliferator-Activated Receptor Alpha Activity in Vitro

2021 ◽  
Author(s):  
Greylin Nielsen ◽  
Wendy J. Heiger-Bernays ◽  
Jennifer J. Schlezinger ◽  
Thomas F. Webster
Keyword(s):  
Carboxylic Acids ◽  
Receptor Activity ◽  
Luciferase Reporter ◽  
Peroxisome Proliferator ◽  
Sulfonic Acids ◽  
Peroxisome Proliferator Activated Receptor ◽  
Full Agonist ◽  
Partial Agonists ◽  
Perfluorinated Carboxylic Acids

AbstractHuman exposure to per- and polyfluoroalkyl substances (PFAS) is ubiquitous, with mixtures of PFAS detected in drinking water, food, household dust, and other exposure sources. Animal toxicity studies and human epidemiology indicate that PFAS may act through shared mechanisms including activation of peroxisome proliferator activated receptor α (PPARα). However, the effect of PFAS mixtures on human relevant molecular initiating events remains an important data gap in the PFAS literature. Here, we tested the ability of modeling approaches to predict the effect of diverse PPARα ligands on receptor activity using Cos7 cells transiently transfected with a full length human PPARα (hPPARα) expression construct and a peroxisome proliferator response element-driven luciferase reporter. Cells were treated for 24 hours with two full hPPARα agonists (pemafibrate and GW7647), a full and a partial hPPARα agonist (pemafibrate and mono(2-ethylhexyl) phthalate), or a full hPPARα agonist and a competitive antagonist (pemafibrate and GW6471). Receptor activity was modeled with three additive approaches: effect summation, relative potency factors (RPF), and generalized concentration addition (GCA). While RPF and GCA accurately predicted activity for mixtures of full hPPARα agonists, only GCA predicted activity for full and partial hPPARα agonists and a full agonist and antagonist. We then generated concentration response curves for seven PFAS, which were well-fit with three-parameter Hill functions. The four perfluorinated carboxylic acids (PFCA) tended to act as full hPPARα agonists while the three perfluorinated sulfonic acids (PFSA) tended to act as partial agonists that varied in efficacy between 28-67% of the full agonist, positive control level. GCA and RPF performed equally well at predicting the effects of mixtures with three PFCAs, but only GCA predicted experimental activity with mixtures of PFSAs and a mixture of PFCAs and PFSAs at ratios found in the general population. We conclude that of the three approaches, GCA most accurately models the effect of PFAS mixtures on hPPARα activity in vitro.HighlightsPerfluorinated carboxylic acids are full human PPARα agonistsPerfluorinated sulfonic acids are partial human PPARα agonistsGCA predicts human PPARα activity for mixtures of full and partial agonistsGCA predicts human PPARα activity for mixtures of agonists and competitive antagonistsGCA accurately predicts human PPARα activity in response to PFAS mixtures

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