Revolutionizing developmental neurotoxicity testing - a journey from animal models to advanced in vitro systems.

ABSTRACT

Developmental neurotoxicity (DNT) testing has seen enormous progress over the last two decades. Preceding even the publication of the animal-based OECD test guideline for DNT testing in 2007, a series of non-animal technology workshops and conferences that started in 2005 has shaped a community that has delivered a comprehensive battery of in vitro test methods (DNT IVB). Its data interpretation is now covered by a very recent OECD guidance (No. 377). Here, we overview the progress in the field, focusing on the evolution of testing strategies, the role of emerging technol­ogies, and the impact of OECD test guidelines on DNT testing. In particular, this is an example of the targeted development of an animal-free testing approach for one of the most complex hazards of chemicals to human health. These developments started literally from a blank slate, with no proposed alternative methods available. Over two decades, cutting-edge science enabled the design of a testing approach that spares animals and enables throughput to address this challenging hazard. While it is evident that the field needs guidance and regulation, the massive economic impact of decreased human cognitive capacity caused by chemical exposure should be prioritized more highly. Beyond this, the claim to fame of DNT in vitro testing is the enormous scientific progress it has brought for understanding the human brain, its development, and how it can be perturbed.

Developmental neurotoxicity (DNT) testing predicts the hazard of exposure to chemicals to human brain development. Comprehensive advanced non-animal testing strategies using cutting-edge technology can now replace animal-based approaches to assess this complex hazard. These strat­egies can assess large numbers of chemicals more accurately and efficiently than the animal-based approach. Recent OECD test guidance has formalized this battery of in vitro test methods for DNT, marking a pivotal achievement in the field. The shift towards non-animal testing reflects both a com­mitment to animal welfare and a growing recognition of the economic and public health impacts associated with impaired cognitive function caused by chemical exposures. These innovations ulti­mately contribute to safer chemical management and better protection of human health, especially during the vulnerable stages of brain development.