Please use this identifier to cite or link to this item:
http://bura.brunel.ac.uk/handle/2438/27319
Title: | The impact of biostatistics on hazard characterization using in vitro developmental neurotoxicity assays |
Authors: | Keßel, HE Masjosthusmann, S Bartmann, K Blum, J Dönmez, A Förster, N Klose, J Mosig, A Pahl, M Leist, M Scholze, M Fritsche, E |
Keywords: | biostatistics;benchmark concentration;hazard characterization;developmental neurotoxicity;concentration-response data analysis |
Issue Date: | 27-Jun-2023 |
Publisher: | ALTEX Edition |
Citation: | Keßel, H.E.et al. (2023) 'The impact of biostatistics on hazard characterization using in vitro developmental neurotoxicity assays', ALTEX : Alternatives to Animal Experimentation, 40 (4), pp. 619 - 634. doi: 10.14573/altex.2210171. |
Abstract: | In chemical safety assessment, benchmark concentrations (BMC) and their associated uncertainty are needed for the toxicological evaluation of in vitro data sets. A BMC estimation is derived from concentration-response modelling and results from various statistical decisions, which depend on factors such as experimental design and assay endpoint features. In current data practice, the experimenter is often responsible for the data analysis and therefore relies on statistical software often without being aware of the software default settings and how they can impact the outputs of data analysis. To provide more insight into how statistical decision-making can influence the outcomes of data analysis and interpretation, we have developed an automatic platform that includes statistical methods for BMC estimation, a novel endpoint-specific hazard classification system, and routines that flag data sets that are outside the applicability domain for an automatic data evaluation. We used case studies on a large dataset produced by a developmental neurotoxicity (DNT) in vitro battery (DNT IVB). Here we focused on the BMC and its confidence interval (CI) estimation as well as on final hazard classification. We identified five crucial statistical decisions the experimenter must make during data analysis: choice of replicate averaging, response data normalization, regression modelling, BMC and CI estimation, and choice of benchmark response levels. The insights gained in are intended to raise more awareness among experimenters on the importance of statistical decisions and methods but also to demonstrate how important fit-for-purpose, internationally harmonized and accepted data evaluation and analysis procedures are for objective hazard classification. |
Description: | Data availability: The raw data of this study was submitted to the US-EPA and published via the ToxCast database assessable via this link: https://clowder.edap-cluster.com/spaces/62bb560ee4b07abf29f88fef |
URI: | https://bura.brunel.ac.uk/handle/2438/27319 |
DOI: | https://doi.org/10.14573/altex.2210171 |
ISSN: | 1868-596X |
Other Identifiers: | ORCiD: Stefan Masjosthusmann https://orcid.org/0000-0003-1493-7980 ORCiD: Kristina Bartmann https://orcid.org/0000-0002-1988-9140 ORCiD: Arif Dönmez https://orcid.org/0000-0002-7241-075X ORCiD: Nils Förster https://orcid.org/0000-0003-4226-754X ORCiD: Jördis Klose https://orcid.org/0000-0002-2924-555X ORCiD: Axel Mosig https://orcid.org/0000-0001-7266-8323 ORCiD: Melanie Pahl https://orcid.org/0000-0003-4002-0738 ORCiD: Martin Scholze https://orcid.org/0000-0002-9569-7562 ORCiD: Ellen Fritsche https://orcid.org/0000-0002-7454-679X |
Appears in Collections: | Dept of Life Sciences Research Papers |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
FullText.pdf | Copyright © The Authors 2023. This work is licensed under a Creative Commons Attribution 4.0 International License. Articles are distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is appropriately cited (CC-BY). Copyright on any article in ALTEX is retained by the author(s). | 1.79 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License