Evidence map›Paper›PMID 21163906›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2011

Estrogen-like activity of perfluoroalkyl acids in vivo and interaction with human and rainbow trout estrogen receptors in vitro.

Abby D Benninghoff, William H Bisson, Daniel C Koch, David J Ehresman, Siva K Kolluri, David E Williams

Open access · bronzeAbstract read
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 3 pooled it
5.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

87 citing papers in PubMed, 3 syntheses or guidelines pooled it, 248 citations in OpenAlex.

  1. Pooled it
  2. Prenatal exposure to persistent organic pollutants and childhood obesity: A systematic review and meta-analysis of human studies.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022
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27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 2 countries.

Abby D BenninghoffDepartment of Animal, Dairy, and Veterinary Sciences and Graduate Program in Toxicology, Utah State University, 4815 Old Main Hill, Logan, Utah 84322-4815, USA. abby.benninghoff@usu.edu
William H Bisson
Daniel C Koch
David J Ehresman
Siva K Kolluri
David E Williams
Oregon State University · US3M (United States) · USUniversity of Geneva · CHUtah State University · US

Funding

Reducing Susceptibility to Environmental Stress Throughout the Life SpanP30ES000210 · NIEHS · OREGON STATE UNIVERSITY · PI BECKMAN, JOSEPH S · 1985 to 2015
$21.4M
MODE OF ACTION OF ENVIRONMENTAL TOXICANTST32ES007060 · NIEHS · OREGON STATE UNIVERSITY · PI Jamie DeWitt, Siva Kumar Kolluri · 1985 to 2026
$11.6M
PILOT--EFFECT OF TEMPERATURE ACCLIMATION ON PEROXISOMES OF TROUTP30ES003850 · NIEHS · OREGON STATE UNIVERSITY · PI WILLIAMS, DAVID E. · 1988 to 2006
$2.8M
Ultra-Low Dose Carcinogen Testing with the Trout ModelR01ES013534 · NIEHS · OREGON STATE UNIVERSITY · PI WILLIAMS, DAVID E · 2005 to 2009
$2.0M
NIEHS NIH HHS P30 ES00210NIEHS NIH HHS P30 ES03850NIEHS NIH HHS R01 ES013534NIEHS NIH HHS T32 ES07060
6 · The paper itself

Abstract

The objectives of this study were to determine the structural characteristics of perfluoroalkyl acids (PFAAs) that confer estrogen-like activity in vivo using juvenile rainbow trout (Oncorhynchus mykiss) as an animal model and to determine whether these chemicals interact directly with the estrogen receptor (ER) using in vitro and in silico species comparison approaches. Perfluorooctanoic (PFOA), perfluorononanoic (PFNA), perfluorodecanoic (PFDA), and perfluoroundecanoic (PFUnDA) acids were all potent inducers of the estrogen-responsive biomarker protein vitellogenin (Vtg) in vivo, although at fairly high dietary exposures. A structure-activity relationship for PFAAs was observed, where eight to ten fluorinated carbons and a carboxylic acid end group were optimal for maximal Vtg induction. These in vivo findings were corroborated by in vitro mechanistic assays for trout and human ER. All PFAAs tested weakly bound to trout liver ER with half maximal inhibitory concentration (IC(50)) values of 15.2-289 μM. Additionally, PFOA, PFNA, PFDA, PFUnDA, and perlfuorooctane sulfonate (PFOS) significantly enhanced human ERα-dependent transcriptional activation at concentrations ranging from 10-1000 nM. Finally, we employed an in silico computational model based upon the crystal structure for the human ERα ligand-binding domain complexed with E2 to structurally investigate binding of these putative ligands to human, mouse, and trout ERα. PFOA, PFNA, PFDA, and PFOS all efficiently docked with ERα from different species and formed a hydrogen bond at residue Arg394/398/407 (human/mouse/trout) in a manner similar to the environmental estrogens bisphenol A and nonylphenol. Overall, these data support the contention that several PFAAs are weak environmental xenoestrogens of potential concern.

Indexed as

Acids, AcyclicAnimalsBinding, CompetitiveBiomarkersDose-Response Relationship, DrugEnvironmental PollutantsEnzyme-Linked Immunosorbent AssayEstrogen Receptor alphaEstrogens, Non-SteroidalFluorocarbonsHumansLiverMolecular StructureOncorhynchus mykissProtein BindingReceptors, EstrogenAcids, AcyclicBiomarkersEnvironmental PollutantsEstrogen Receptor alphaEstrogens, Non-SteroidalFluorocarbonsReceptors, EstrogenVitellogenins

Identifiers

PMID21163906
PMCPMC3044205
OpenAlexW2064507515

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.