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Review
. 2024 May;98(5):1271-1295.
doi: 10.1007/s00204-024-03703-8. Epub 2024 Mar 13.

Recent advances and current challenges of new approach methodologies in developmental and adult neurotoxicity testing

Melania Maria Serafini  1 , Sara Sepehri  2 , Miriam Midali  3 , Marth Stinckens  2 , Marta Biesiekierska  4 , Anna Wolniakowska  4 , Alexandra Gatzios  2 , Elise Rundén-Pran  5 , Edyta Reszka  4 , Marina Marinovich  3   6 , Tamara Vanhaecke  2 , Joanna Roszak  4 , Barbara Viviani  3   6 , Tanima SenGupta  5
Affiliations
Review

Recent advances and current challenges of new approach methodologies in developmental and adult neurotoxicity testing

Melania Maria Serafini et al. Arch Toxicol. 2024 May.

Abstract

Adult neurotoxicity (ANT) and developmental neurotoxicity (DNT) assessments aim to understand the adverse effects and underlying mechanisms of toxicants on the human nervous system. In recent years, there has been an increasing focus on the so-called new approach methodologies (NAMs). The Organization for Economic Co-operation and Development (OECD), together with European and American regulatory agencies, promote the use of validated alternative test systems, but to date, guidelines for regulatory DNT and ANT assessment rely primarily on classical animal testing. Alternative methods include both non-animal approaches and test systems on non-vertebrates (e.g., nematodes) or non-mammals (e.g., fish). Therefore, this review summarizes the recent advances of NAMs focusing on ANT and DNT and highlights the potential and current critical issues for the full implementation of these methods in the future. The status of the DNT in vitro battery (DNT IVB) is also reviewed as a first step of NAMs for the assessment of neurotoxicity in the regulatory context. Critical issues such as (i) the need for test batteries and method integration (from in silico and in vitro to in vivo alternatives, e.g., zebrafish, C. elegans) requiring interdisciplinarity to manage complexity, (ii) interlaboratory transferability, and (iii) the urgent need for method validation are discussed.

Keywords: Adult neurotoxicity; Adverse outcome pathways; Developmental neurotoxicity; New approach methodologies.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
The approximate number of animals used for scientific purposes in the European Union and Norway, including re-uses, in 2019 (data from EURL ECVAM status report 2022 (https://data.europa.eu/doi/10.2760/500414 (accessed on Jan 9, 2023)). Figure created with Biorender.com
Fig. 2
Fig. 2
Advantages of the C. elegans model. Figure created with Biorender.com
Fig. 3
Fig. 3
Advantages of the zebrafish model. Figure created with Biorender.com
See this image and copyright information in PMC

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