Citation:

Sachana, M., A. Bal-Price, K. Crofton, S. Bennekou, Tim Shafer, M. Behl, AND A. Terron. International regulatory and scientific effort for improved developmental neurotoxicity testing. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 167(1):45-57, (2019). https://doi.org/10.1093/toxsci/kfy211

Impact/Purpose:

This manuscript provides an overview of activities of the Organization for Economic Cooperation and Development's activities on the establishment and evaluation of a screening battery for Developmental Neurotoxicity (DNT) testing. It provides an overview of recent and planned activities that OECD is sponsoring, including the formation of an Expert group for DNT testing, review and proposal of a battery of in vitro DNT screens, and selection of a set of compounds to evaluate the screening battery. In addition, it discusses the use of Integrated Alternative Testing Approaches (IATAs) for DNT. This manuscript will be of interest to those in OPPTS evaluating chemicals under TSCA, and OPP who evaluate pesticides for DNT using the DNT Guideline study.

Description:

The Organisation for Economic Co-Operation and Development (OECD) coordinates international efforts to enhance developmental neurotoxicity (DNT) testing. In most regulatory sectors, including the ones dealing with pesticides and industrial chemicals registration, historical use of the in vivo DNT test guideline has been limited. Current challenges include a lack of DNT data and mechanistic information for thousands of chemicals, and difficulty in interpreting results. A series of workshops in the last decade has paved the way for a consensus among stakeholders that there is need for a DNT testing battery that relies on in vitro endpoints (proliferation, differentiation, synaptogenesis, etc.) and is complemented by alternative species (eg, zebrafish) assays. Preferably, a battery of in vitro and alternative assays should be anchored toward mechanistic relevance for applying an integrated approach for testing and assessment (IATA) framework. Specific activities have been initiated to facilitate this OECD project: the collation of available DNT in vitro methods and their scoring for readiness; the selection of these methods to form a DNT testing battery; the generation of a reference set of chemicals that will be tested using the battery; the case studies exemplifying how DNT in vitro data can be interpreted; and the development of an OECD guidance document. This manuscript highlights these international efforts and activities.

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