ECVAM Strategy for in vitro Neurotoxicity Testing for regulatory purposes: application of nano- and emerging technologies

AUTHORS: Anna Price

ADDRESS: ECVAM European Centre for the Validation of Alternative Methods, IHCP, European Comission Joint research Centre, 21020 ISPRA (VA) Italy  


Prediction of neurotoxic effects is a key feature in the toxicological profile of many compounds and therefore, is required by regulatory testing schemes. Current OECD and EC guidelines for the evaluation of neurotoxic effects of chemicals for hazard and risk assessment are based solely on in vivo studies evaluating mainly effects on neurobehaviour and neuropathology. Such an approach is not suitable for testing a large number of chemicals (since it is time-consuming, expensive and high number of animals is required), therefore, an alternative testing strategy, where a battery of in vitro mechanistic assays is incorporated, might prove useful. Implementation of alternat i ve in vitro tests to assess neurotoxic e ffects of chemicals and pharmaceuticals would accelerate the rate at which compound kn owledge and mechanistic data are produced. In vitro neurotoxicity test systems are commonly used to study the mechanisms of neurotoxicants but are rarely used to predict hazards to human health.

ECVAM’s core activities are driven by REACH and the 7 th amendment to the Cosmetic legislation where the application of in vitro testing strategy is required. In this presentation the available in vitro models that range in complexity from simple cell lines to complex brain reaggregates will be discussed. The sensitive and cell specific endpoints that are available to assess the impaired function of mature (and/or immature) neurons or glial cells and to discriminate between neurotoxicity and general cytotoxicity effects will be reviewed . Especially, the application of new nano technologies and emerging technologies (measurements of electrical activity using multielectrode array and metabolite profiling) and and their performance and suitability for in vitro neurotoxicity assessment will be discussed.



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