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...
Main Authors: | , , , , , , , |
---|---|
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 |
_version_ | 1827777386832199680 |
---|---|
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. |
first_indexed | 2024-03-11T14:17:40Z |
format | Article |
id | doaj.art-d91bd155976c4a21aaf702312294dc11 |
institution | Directory Open Access Journal |
issn | 0147-6513 |
language | English |
last_indexed | 2024-03-11T14:17:40Z |
publishDate | 2023-11-01 |
publisher | Elsevier |
record_format | Article |
series | Ecotoxicology and Environmental Safety |
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 |
work_keys_str_mv | AT rebeccajbrown arechangesinvitellogeninconcentrationsinfishreliableindicatorsofchemicalinducedendocrineactivity AT gracehpanter arechangesinvitellogeninconcentrationsinfishreliableindicatorsofchemicalinducedendocrineactivity AT natalieburden arechangesinvitellogeninconcentrationsinfishreliableindicatorsofchemicalinducedendocrineactivity AT edwardrsalinas arechangesinvitellogeninconcentrationsinfishreliableindicatorsofchemicalinducedendocrineactivity AT lennartweltje arechangesinvitellogeninconcentrationsinfishreliableindicatorsofchemicalinducedendocrineactivity AT jamesrwheeler arechangesinvitellogeninconcentrationsinfishreliableindicatorsofchemicalinducedendocrineactivity AT yvonnewolf arechangesinvitellogeninconcentrationsinfishreliableindicatorsofchemicalinducedendocrineactivity AT laurentlagadic arechangesinvitellogeninconcentrationsinfishreliableindicatorsofchemicalinducedendocrineactivity |