The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Determination of benchmark concentrations and their statistical uncertainty for cytotoxicity test data and functional in vitro assays
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.
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“Where sufficiently resolved concentration-response data are available, benchmark concentration approaches can provide an additional quantitative basis for defining cytotoxicity-related decision points and their uncertainty (Krebs, 2019).”
From Cytotoxicity across OECD methods is not a single endpoint: context-dependent roles, variability and implications for decision-making (2026) · cites this paper as Krebs, 2019
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A new method for determining allowable daily intakes*1
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Reference dose (RfD): Description and use in health risk assessments
Barnes, D. G., Dourson, M. L., Dourson, M. L., Preuss, P. W., Barnes, D. G., Bellin, J. S., DeRosa, C. T., Engler, R., Erdreich, L. S., Färber, T. M., et al. (1988) · Regulatory Toxicology and Pharmacology · doi:10.1016/0273-2300(88)90047-5 · Cited by 810
Toward a unified approach to dose–response modeling in ecotoxicology
Ritz, C. (2010) · Environmental Toxicology and Chemistry · doi:10.1002/etc.7 · Cited by 329
Introduction to benchmark dose methods and U.S. EPA's benchmark dose software (BMDS) version 2.1.1
Davis, J. A., Gift, J. S., & Zhao, Q. J. (2010) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2010.10.016 · Cited by 272
Benchmark dose (BMD) modeling: current practice, issues, and challenges
Haber, L. T., Dourson, M. L., Allen, B. C., et al. (2018) · Critical Reviews in Toxicology · doi:10.1080/10408444.2018.1430121 · Cited by 229
Krug, A. K., Kolde, R., Gaspar, J. A., Rempel, E., Balmer, N. V., Meganathan, K., Vojnits, K., Baquié, M., Waldmann, T., Enseñat‐Waser, R., et al. (2012) · Archives of Toxicology · doi:10.1007/s00204-012-0967-3 · Cited by 228
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Behl, M., Hsieh, J., Shafer, T. J., Mundy, W. R., Rice, J. R., Boyd, W. A., Freedman, J. H., Hunter, E. S., Jarema, K. A., Padilla, S., et al. (2015) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2015.09.003 · Cited by 218
Cited by
Blum, J., Masjosthusmann, S., Bartmann, K., Bendt, F., Dolde, X., Dönmez, A., Förster, N., Holzer, A.-K., Hübenthal, U., Keßel, H. E., et al. (2023) · Chemosphere · doi:10.1016/j.chemosphere.2022.137035 · Cited by 105
Thoma, T., Löhr, L., Demuth, P., Hambruch, N., Oesch, F., & Landsiedel, R. (2026) · NAM Journal · doi:10.1016/j.namjnl.2026.100126
Metadata
- Authors
- Krebs, A.
- Venue
- ALTEX
- Publisher
- ALTEX Edition
- Published
- 2019
- ISSN
- 1868-596X
- Cited by
- 13
- References
- 33
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