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Jonathan H. Blum, Stefan Masjosthusmann, Kristina Bartmann, Farina Bendt, Xenia Dolde, Arif Dönmez, Nils Förster, Anna‐Katharina Holzer, Ulrike Hübenthal, Hagen Eike Keßel and 11 more
Developmental neurotoxicity (DNT) is a major safety concern for all chemicals of the human exposome. However, DNT data from animal studies are available for only a small percentage of manufactured compounds. Test methods with a higher throughput than current regulatory guideline methods, and with improved human relevance are urgently needed. We therefore explored the feasibility of DNT hazard assessment based on new approach methods (NAMs). An in vitro battery (IVB) was assembled from ten individual NAMs that had been developed during the past years to probe effects of chemicals on various fundamental neurodevelopmental processes. All assays used human neural cells at different developmental stages. This allowed us to assess disturbances of: (i) proliferation of neural progenitor cells (NPC); (ii) migration of neural crest cells, radial glia cells, neurons and oligodendrocytes; (iii) differentiation of NPC into neurons and oligodendrocytes; and (iv) neurite outgrowth of peripheral and central neurons. In parallel, cytotoxicity measures were obtained. The feasibility of concentration-dependent screening and of a reliable biostatistical processing of the complex multi-dimensional data was explored with a set of 120 test compounds, containing subsets of pre-defined positive and negative DNT compounds. The battery provided alerts (hit or borderline) for 24 of 28 known toxicants (82% sensitivity), and for none of the 17 negative controls. Based on the results from this screen project, strategies were developed on how IVB data may be used in the context of risk assessment scenarios employing integrated approaches for testing and assessment (IATA).
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Blum, J. H., Masjosthusmann, S., Bartmann, K., Bendt, F., Dolde, X., Dönmez, A., Förster, N., Holzer, A., Hübenthal, U., Keßel, H. E., Kilic, S., Klose, J., Pahl, M., Stürzl, L., Mangas, I., Terron, A., Crofton, K. M., Scholze, M., A, A. M., … Fritsche, E. (2022). Establishment of a Human Cell-Based in Vitro Battery to Assess Developmental Neurotoxicity Hazard of Chemicals. Chemosphere, 311(Pt 2), 137035. https://doi.org/10.1016/j.chemosphere.2022.137035
Blum, Jonathan H., et al. "Establishment of a Human Cell-Based in Vitro Battery to Assess Developmental Neurotoxicity Hazard of Chemicals." Chemosphere, vol. 311, no. Pt 2, 2022, pp. 137035, https://doi.org/10.1016/j.chemosphere.2022.137035.
Blum, Jonathan H., Stefan Masjosthusmann, Kristina Bartmann, Farina Bendt, Xenia Dolde, Arif Dönmez, Nils Förster, et al. "Establishment of a Human Cell-Based in Vitro Battery to Assess Developmental Neurotoxicity Hazard of Chemicals." Chemosphere 311, no. Pt 2 (2022): 137035. https://doi.org/10.1016/j.chemosphere.2022.137035.
Blum J. H., Masjosthusmann S., Bartmann K. [и др.] Establishment of a Human Cell-Based in Vitro Battery to Assess Developmental Neurotoxicity Hazard of Chemicals // Chemosphere. — 2022. — Vol. 311, № Pt 2. — P. 137035. — URL: https://doi.org/10.1016/j.chemosphere.2022.137035
@article{blum2022establishment,
title = {{Establishment of a Human Cell-Based in Vitro Battery to Assess Developmental Neurotoxicity Hazard of Chemicals}},
author = {Jonathan H. Blum and Stefan Masjosthusmann and Kristina Bartmann and Farina Bendt and Xenia Dolde and Arif Dönmez and Nils Förster and Anna‐Katharina Holzer and Ulrike Hübenthal and Hagen Eike Keßel and Sadiye Kilic and Jördis Klose and Melanie Pahl and Lynn‐Christin Stürzl and Iris Mangas and Andrea Terron and Kevin M. Crofton and Martin Scholze and Axel Mosig A and Marcel Leist and Ellen Fritsche},
journal = {Chemosphere},
year = {2022},
volume = {311},
number = {Pt 2},
pages = {137035},
doi = {10.1016/j.chemosphere.2022.137035},
url = {https://doi.org/10.1016/j.chemosphere.2022.137035}
}TY - JOUR AU - Blum, Jonathan H. AU - Masjosthusmann, Stefan AU - Bartmann, Kristina AU - Bendt, Farina AU - Dolde, Xenia AU - Dönmez, Arif AU - Förster, Nils AU - Holzer, Anna‐Katharina AU - Hübenthal, Ulrike AU - Keßel, Hagen Eike AU - Kilic, Sadiye AU - Klose, Jördis AU - Pahl, Melanie AU - Stürzl, Lynn‐Christin AU - Mangas, Iris AU - Terron, Andrea AU - Crofton, Kevin M. AU - Scholze, Martin AU - A, Axel Mosig AU - Leist, Marcel AU - Fritsche, Ellen TI - Establishment of a Human Cell-Based in Vitro Battery to Assess Developmental Neurotoxicity Hazard of Chemicals JO - Chemosphere VL - 311 IS - Pt 2 SP - 137035 PY - 2022 DA - 2022/01/01 DO - 10.1016/j.chemosphere.2022.137035 UR - https://doi.org/10.1016/j.chemosphere.2022.137035 ER -
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