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Interpretation of In Vitro Concentration-Response Data for Risk Assessment and Regulatory Decision-making: Report from 2022 IWGT Quantitative Analysis Expert Working Group Meeting
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  • Marc Beal,
  • Guangchao Chen,
  • Kerry Dearfield,
  • Min Gi,
  • Bhaskar Gollapudi,
  • Robert Heflich,
  • Katsuyoshi Horibata,
  • Alexandra Long,
  • David Lovell,
  • Barbara Parsons,
  • Stefan Pfuhler,
  • John Wills,
  • Andreas Zeller,
  • George Johnson,
  • Paul White
Marc Beal
Health Canada

Corresponding Author:[email protected]

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Guangchao Chen
Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), the Netherlands
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Kerry Dearfield
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Min Gi
Department of Environmental Risk Assessment, Graduate School of Medicine, Osaka Metropolitan University
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Bhaskar Gollapudi
Toxicology Consultant
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Robert Heflich
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Katsuyoshi Horibata
National Institute of Health Sciences
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Alexandra Long
Health Canada
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David Lovell
University of London
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Barbara Parsons
US FDA/National Center for Toxicological Research
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Stefan Pfuhler
Procter & Gamble, Cosmital SA
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John Wills
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Andreas Zeller
F. Hoffmann-La Roche Ltd.
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George Johnson
Swansea University
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Paul White
Health Canada
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Quantitative risk assessments of chemicals are routinely performed in rodents; however, there is growing recognition that non-animal approaches can be human-relevant alternatives. There is an urgent need to build confidence in non-animal alternatives given the international support to reduce the use of animals in toxicity testing where possible. In order for scientists and risk assessors to prepare for this paradigm shift in toxicity assessment, standardization and consensus on in vitro testing strategies and data interpretation will need to be established. To address this issue, an Expert Working Group (EWG) of the 8th International Workshop on Genotoxicity Testing (IWGT) evaluated the utility of quantitative in vitro genotoxicity concentration-response data for risk assessment. The EWG first evaluated available in vitro methodologies and then examined the variability and maximal response of in vitro tests to estimate biologically relevant values for the critical effect sizes considered adverse or unacceptable. Next, the EWG reviewed the approaches and computational models employed to provide human-relevant dose context to in vitro data. Lastly, the EWG evaluated risk assessment applications for which in vitro data are ready for use and applications where further work is required. The EWG concluded that in vitro genotoxicity concentration-response data can be interpreted in a risk assessment context. However, prior to routine use in regulatory settings, further research will be required to address the remaining uncertainties and limitations.
05 Jun 2023Submitted to Environmental and Molecular Mutagenesis
06 Jun 2023Submission Checks Completed
06 Jun 2023Assigned to Editor
06 Jun 2023Review(s) Completed, Editorial Evaluation Pending
13 Jun 2023Editorial Decision: Accept
19 Jun 2023Reviewer(s) Assigned
15 Sep 20231st Revision Received
18 Sep 2023Submission Checks Completed
18 Sep 2023Assigned to Editor
18 Sep 2023Review(s) Completed, Editorial Evaluation Pending
18 Oct 2023Reviewer(s) Assigned