Application of multielectrode array (MEA) chips for the evaluation of mixtures neurotoxicity.
Cortical neurons grown on multielectrode array (MEA) chips have been shown to be a valuable alternative method to study electrophysiological properties of the central nervous system neurons and to perform functional toxicological screening. Here we studied the effects of binary mixtures on neuronal networks cultured on MEAs. We have considered compounds with similar and different mode-of-action (MoA) to characterize and assess their combined effects. Individual and binary mixture dose-response curves based on spontaneous neuronal activity have been generated and the IC(50) has been considered as the end-point for neurotoxicity assessment. The two classical approaches of mixtures toxicity studies: concentration addition (CA) and independent action (IA) have been applied to compare calculated and experimental results. Nuclear magnetic resonance (NMR) spectroscopy has been employed to confirm no chemical reaction or complexation between mixtures components. The results suggest that both CA and IA are able to predict the toxicity of the mixture and that the combination of in vitro test methods with theoretical dose-response models has a strong potential as an alternative tool for the prediction of mixtures neurotoxicity.
European Commission, Joint Research Centre, Institute for Health and Consumer Protection, Systems Toxicology Unit, Via E. Fermi 2749, TP202, 21027 Ispra (VA), Italy.
Bibiana
B
Scelfo
Matteo
M
Politi
Fabiano
F
Reniero
Taina
T
Palosaari
Maurice
M
Whelan
José-Manuel
JM
Zaldívar
D000818:Animals; D045424:Complex Mixtures / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D046228:Microarray Analysis / Q000379:methods*; D008959:Models, Neurological; D009415:Nerve Net / Q000187:drug effects* / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism; D010575:Pesticides / Q000633:toxicity*; D051381:Rats
D045424:Complex Mixtures; D010575:Pesticides