Predictive toxicology of cobalt nanoparticles and ions: Comparative in vitro study of different cellular models using methods of knowledge discovery from data

Limor Horev-Azaria, Charles James Kirkpatrick, Rafi Korenstein*, Patrice N. Marche, Oded Maimon, Jessica Ponti, Roni Romano, Francois Rossi, Ute Golla-Schindler, Dieter Sommer, Chiara Uboldi, Ronald E. Unger, Christian Villiers

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

The toxicological effects of cobalt nanoparticles (Co-NPs) aggregates were examined and compared with those of cobalt ions (Co-ions) using six different cell lines representing lung, liver, kidney, intestine, and the immune system. Dose-response curves were studied in the concentration range of 0.05-1.0mM, employing 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide test, neutral red, and Alamar blue as end point assays following exposures for 48 and 72 h. Data analysis and predictive modeling of the obtained data sets were executed by employing a decision tree model (J48), where training and validation were carried out by an iterative process. It was established, as expected, that concentration is the highest rank parameter. This is because concentration parameter provides the highest information gain with respect to toxicity. The second-rank parameter emerged to be either the compound type (Co-ions or Co-NPs) or the cell model, depending on the concentration range. The third and the lowest rank in the model was exposure duration. The hierarchy of cell sensitivity toward cobalt ions was found to obey the following sequence of cell lines: A549 > MDCK > NCIH441 > Caco-2 > HepG2 > dendritic cells (DCs), with A549 being the most sensitive cell line and primary DCs were the least sensitive ones. However, a different hierarchy pattern emerged for Co-NPs: A549 5 MDCK 5 NCIH441 5 Caco-2 > DCs > HepG2. The overall findings are in line with the hypothesis that the toxic effects of aggregated cobalt NPs are mainly due to cobalt ion dissolution from the aggregated NPs.

Original languageEnglish
Pages (from-to)489-501
Number of pages13
JournalToxicological Sciences
Volume122
Issue number2
DOIs
StatePublished - Aug 2011

Funding

FundersFunder number
European Commission under the Sixth Framework Program for Research, Technological Development and DemonstrationNMP-CT-2006-032731

    Keywords

    • Cobalt nanoparticles
    • Comparative cytotoxicity
    • Data mining

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