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Identification of training set chemicals to demonstrate the transferability of the developmental neurotoxicity in vitro battery
Citation:
Kreutz, A., T. Shafer, H. Hogberg, AND M. Culbreth. Identification of training set chemicals to demonstrate the transferability of the developmental neurotoxicity in vitro battery. 5th International Conference on Developmental Neurotoxicity (DNT 5), Konstanz, GERMANY, April 07 - 10, 2024. https://doi.org/10.23645/epacomptox.25605564
Impact/Purpose:
Presentation to 5th International Conference on Developmental Neurotoxicity (DNT 5)
Description:
The developmental neurotoxicity (DNT) in vitro battery (IVB) is a group of new approach methods for evaluation of potential compound effects on fundamental neurodevelopmental processes. These assays were developed to enhance efficiency of chemical screening and prioritization relative to the regulatory accepted in vivo guideline DNT studies. With the publication of the initial recommendations on the evaluation of data from the DNT IVB by the Organisation for Economic Co-operation and Development (OECD) in 2023, these approaches are being increasingly applied in the regulatory arena. However, for these approaches to be fully accepted, the transferability and reproducibility between laboratories must first be demonstrated. To do this, novice laboratories will require a training set of compounds that exhibit known performance metrics in each of the 17 DNT IVB assays. In the present work, we have identified potential compounds suitable for this purpose. These compounds include those expected to elicit a response in a particular assay (i.e., an endpoint specific control), as well as those not anticipated to produce an effect. Endpoint specific controls were ascertained from the original publications for each assay and from the ToxTemp forms published in the OECD initial recommendations. In addition, compounds that were selectively active in the individual assays based on the concentration that elicits half maximal response (AC50) in the ToxCast in vitro database, were also included. Furthermore, compounds not anticipated to produce an effect were identified from relevant literature, as well as from the ToxCast in vitro database. From the compounds identified, a training set will be recommended based on but not limited to mechanistic knowledge to support biological relevance, assay specificity, and endpoint consistency. Establishment of this training set of compounds for each assay will facilitate demonstrating the transferability and reproducibility of the DNT IVB, and potentially enhance the regulatory applicability of these approaches. This abstract does not represent EPA or FDA position or policy and was funded in whole or in part with federal funds from the NIEHS, NIH under Contract No. HHSN273201500010C.
URLs/Downloads:
DOI: Identification of training set chemicals to demonstrate the transferability of the developmental neurotoxicity in vitro battery
DNTTRAININGSETPOSTERDNT5_040424_CLEAN_REVISED_CLEARANCE.PDF (PDF, NA pp, 1942.136 KB, about PDF)