Neuronal in vitro models for the estimation of acute systemic toxicity

Forsby, A.; Bal-Price, A. K.; Camins, A.; Coecke, S.; Fabre, N.; Gustafsson, H.; Honegger, P.; Kinsner-Ovaskainen, A.; Pallas, M.; Rimbau, V.; Rodriguez-Farre, E.; Sunol, C.; Vericat, J. A.; Zurich, M. G.


The objective of the EU funded integrated project "ACuteTox" is to develop a strategy in which general cytotoxicity, together with organ-specific endpoints and biokinetic features, are taken into consideration in the in vitro prediction of oral acute systemic toxicity. With regard to the nervous system, the effects of 23 reference chemicals were tested with approximately 50 endpoints, using a neuronal cell line, primary neuronal cell cultures, brain slices and aggregated brain cell cultures. Comparison of the in vitro neurotoxicity data with general cytotoxicity data generated in a non-neuronal cell line and with in vivo data such as acute human lethal blood concentration, revealed that GABA(A) receptor function, acetylcholine esterase activity, cell membrane potential, glucose uptake, total RNA expression and altered gene expression of NF-H, GFAP, MBP, HSP32 and caspase-3 were the best endpoints to use for further testing with 36 additional chemicals. The results of the second analysis showed that no single neuronal endpoint could give a perfect improvement in the in vitro-in vivo correlation, indicating that several specific endpoints need to be analysed and combined with biokinetic data to obtain the best correlation with in vivo acute toxicity. (C) 2009 Elsevier Ltd. All rights reserved.

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Título según WOS: ID WOS:000272276600021 Not found in local WOS DB
Título de la Revista: Toxicology in vitro : an international journal published in association with BIBRA.
Volumen: 23
Número: 8
Fecha de publicación: 2009
Página de inicio: 1564
Página final: 1569


Notas: ISI