Are changes in vitellogenin concentrations in fish reliable indicators of chemical-induced endocrine activity?

Vitellogenin (VTG), a biomarker for endocrine activity, is a mechanistic component of the regulatory assessment of potential endocrine-disrupting properties of chemicals. This review of VTG data is based on changes reported for 106 substances in standard fish species. High intra-study and inter-labo...

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Main Authors: Rebecca J. Brown, Grace H. Panter, Natalie Burden, Edward R. Salinas, Lennart Weltje, James R. Wheeler, Yvonne Wolf, Laurent Lagadic
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651323010679
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author Rebecca J. Brown
Grace H. Panter
Natalie Burden
Edward R. Salinas
Lennart Weltje
James R. Wheeler
Yvonne Wolf
Laurent Lagadic
author_facet Rebecca J. Brown
Grace H. Panter
Natalie Burden
Edward R. Salinas
Lennart Weltje
James R. Wheeler
Yvonne Wolf
Laurent Lagadic
author_sort Rebecca J. Brown
collection DOAJ
description Vitellogenin (VTG), a biomarker for endocrine activity, is a mechanistic component of the regulatory assessment of potential endocrine-disrupting properties of chemicals. This review of VTG data is based on changes reported for 106 substances in standard fish species. High intra-study and inter-laboratory variability in VTG concentrations was confirmed, as well as discrepancies in interpretation of results based on large differences between fish in the dilution water versus solvent control, or due to the presence of outlier measurements. VTG responses in fish were ranked against predictions for estrogen receptor agonist activity and aromatase inhibition from bioactivity model output and ToxCast in vitro assay results, respectively. These endocrine mechanisms explained most of the VTG responses in the absence of systemic toxicity, the magnitude of the VTG response being proportional to the in vitro potency. Interpretation of the VTG data was sometimes confounded by an alternative endocrine mechanism of action. There was evidence for both false positive and negative responses for VTG synthesis, but overall, it was rare for substances without endocrine activity in vitro to cause a concentration-dependent VTG response in fish in the absence of systemic toxicity. To increase confidence in the VTG results, we recommend improvements in the VTG measurement methodologies and greater transparency in reporting of VTG data (including quality control criteria for assay performance). This review supports the application of New Approach Methodologies (NAMs) by demonstrating that endocrine activity in vitro from mammalian cell lines is predictive for in vivo VTG response in fish, suggesting that in vitro mechanistic data could be used more broadly in decision-making to help reduce animal testing.
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spelling doaj.art-d91bd155976c4a21aaf702312294dc112023-11-01T04:45:54ZengElsevierEcotoxicology and Environmental Safety0147-65132023-11-01266115563Are changes in vitellogenin concentrations in fish reliable indicators of chemical-induced endocrine activity?Rebecca J. Brown0Grace H. Panter1Natalie Burden2Edward R. Salinas3Lennart Weltje4James R. Wheeler5Yvonne Wolf6Laurent Lagadic7wca, Brunel House, Volunteer Way, Faringdon, Oxfordshire SN7 7YR, UK; Corresponding author.wca, Brunel House, Volunteer Way, Faringdon, Oxfordshire SN7 7YR, UKNC3Rs, Gibbs Building, 215 Euston Road, London NW1 2BE, UKBASF SE, Agricultural Solutions – Ecotoxicology, Speyerer Strasse 2, 67117 Limburgerhof, Germany; Bayer AG, R&D, Crop Science Division, Environmental Safety, Alfred-Nobel Strasse 50, 40789 Monheim am Rhein, GermanyBASF SE, Agricultural Solutions – Ecotoxicology, Speyerer Strasse 2, 67117 Limburgerhof, GermanyCorteva Agriscience, Zuid-Oostsingel 24D, 4611 BB Bergen op Zoom, The NetherlandsBayer AG, R&D, Crop Science Division, Environmental Safety, Alfred-Nobel Strasse 50, 40789 Monheim am Rhein, GermanyBayer AG, R&D, Crop Science Division, Environmental Safety, Alfred-Nobel Strasse 50, 40789 Monheim am Rhein, GermanyVitellogenin (VTG), a biomarker for endocrine activity, is a mechanistic component of the regulatory assessment of potential endocrine-disrupting properties of chemicals. This review of VTG data is based on changes reported for 106 substances in standard fish species. High intra-study and inter-laboratory variability in VTG concentrations was confirmed, as well as discrepancies in interpretation of results based on large differences between fish in the dilution water versus solvent control, or due to the presence of outlier measurements. VTG responses in fish were ranked against predictions for estrogen receptor agonist activity and aromatase inhibition from bioactivity model output and ToxCast in vitro assay results, respectively. These endocrine mechanisms explained most of the VTG responses in the absence of systemic toxicity, the magnitude of the VTG response being proportional to the in vitro potency. Interpretation of the VTG data was sometimes confounded by an alternative endocrine mechanism of action. There was evidence for both false positive and negative responses for VTG synthesis, but overall, it was rare for substances without endocrine activity in vitro to cause a concentration-dependent VTG response in fish in the absence of systemic toxicity. To increase confidence in the VTG results, we recommend improvements in the VTG measurement methodologies and greater transparency in reporting of VTG data (including quality control criteria for assay performance). This review supports the application of New Approach Methodologies (NAMs) by demonstrating that endocrine activity in vitro from mammalian cell lines is predictive for in vivo VTG response in fish, suggesting that in vitro mechanistic data could be used more broadly in decision-making to help reduce animal testing.http://www.sciencedirect.com/science/article/pii/S0147651323010679VitellogeninBiomarkerFishEndocrine activityEstrogen-receptor agonist activitySteroidogenesis
spellingShingle Rebecca J. Brown
Grace H. Panter
Natalie Burden
Edward R. Salinas
Lennart Weltje
James R. Wheeler
Yvonne Wolf
Laurent Lagadic
Are changes in vitellogenin concentrations in fish reliable indicators of chemical-induced endocrine activity?
Ecotoxicology and Environmental Safety
Vitellogenin
Biomarker
Fish
Endocrine activity
Estrogen-receptor agonist activity
Steroidogenesis
title Are changes in vitellogenin concentrations in fish reliable indicators of chemical-induced endocrine activity?
title_full Are changes in vitellogenin concentrations in fish reliable indicators of chemical-induced endocrine activity?
title_fullStr Are changes in vitellogenin concentrations in fish reliable indicators of chemical-induced endocrine activity?
title_full_unstemmed Are changes in vitellogenin concentrations in fish reliable indicators of chemical-induced endocrine activity?
title_short Are changes in vitellogenin concentrations in fish reliable indicators of chemical-induced endocrine activity?
title_sort are changes in vitellogenin concentrations in fish reliable indicators of chemical induced endocrine activity
topic Vitellogenin
Biomarker
Fish
Endocrine activity
Estrogen-receptor agonist activity
Steroidogenesis
url http://www.sciencedirect.com/science/article/pii/S0147651323010679
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