Determination of benchmark concentrations and their statistical uncertainty for cytotoxicity test data and functional in vitro assays

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  • dc.contributor.author Krebs, Alice
  • dc.contributor.author Nyffeler, Johanna
  • dc.contributor.author Karreman, Christiaan
  • dc.contributor.author Schmidt, Béla Z.
  • dc.contributor.author Kappenberg, Franziska
  • dc.contributor.author Mellert, Jan
  • dc.contributor.author Pallocca, Giorgia
  • dc.contributor.author Pastor Maeso, Manuel
  • dc.contributor.author Rahnenführer, Jörg
  • dc.contributor.author Leist, Marcel
  • dc.date.accessioned 2021-02-12T09:27:13Z
  • dc.date.available 2021-02-12T09:27:13Z
  • dc.date.issued 2020
  • dc.description.abstract Many toxicological test methods, including assays of cell viability and function, require an evaluation of concentration-response data. This often involves curve fitting, and the resulting mathematical functions are then used to determine the concentration at which a certain deviation from the control value occurs (e.g. a decrease of cell viability by 15%). Such a threshold is called the benchmark response (BMR). For a toxicological test, it is often of interest to determine the concentration of test compound at which a pre-defined BMR of e.g. 10, 25 or 50% is reached. The concentration at which the modelled curve crosses the BMR is called the benchmark concentration (BMC). We present a user-friendly, web-based tool (BMCeasy), designed for operators without programming skills and profound statistical background, to determine BMCs and their confidence intervals. BMCeasy allows simultaneous analysis of viability plus a functional test endpoint, and it yields absolute BMCs with confidence intervals for any BMR. Besides an explanation of the algorithm underlying BMCeasy, this article also gives multiple examples of data outputs. BMCeasy was used within the EU-ToxRisk project for preparing data packages that were submitted to regulatory authorities, demonstrating the real-life applicability of the tool.
  • dc.description.sponsorship This work was supported by the BMBF, EFSA, the DK-EPA, and the DFG (Konstanz Research School of Chemical Biology; KoRS-CB). It has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreements No. 681002 (EU-ToxRisk) and No. 825759 (ENDpoiNTs). We are grateful to collaborators R. von Hellfeld and T. Braunbeck (University of Heidelberg), and H. Vrieling and J. Boei (Leiden University Medical Center) of the EU-ToxRisk con-sortium for providing the experimental data. We are indebted to S. Förster for triggering this work and to other colleagues for in-sightful discussions.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Krebs A, Nyffeler J, Karreman C, Schmidt BZ, Kappenberg F, Mellert J. et al. Determination of benchmark concentrations and their statistical uncertainty for cytotoxicity test data and functional in vitro assays. ALTEX. 2020; 37(1):155-63. DOI: 10.14573/altex.1912021
  • dc.identifier.doi http://dx.doi.org/10.14573/altex.1912021
  • dc.identifier.issn 1868-596X
  • dc.identifier.uri http://hdl.handle.net/10230/46462
  • dc.language.iso eng
  • dc.publisher Spektrum Akademischer Verlag
  • dc.relation.ispartof ALTEX. 2020; 37(1):155-63
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/681002
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/825759
  • dc.rights This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is appropriately cited.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Benchmark calculation
  • dc.subject.keyword Concentration-response curve
  • dc.subject.keyword Screening
  • dc.subject.keyword Test battery
  • dc.subject.keyword Test methods
  • dc.title Determination of benchmark concentrations and their statistical uncertainty for cytotoxicity test data and functional in vitro assays
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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