BK/TD models for analyzing in vitro impedance data on cytotoxicity.

S Teng (1) , S Barcellini-Couget (2) , R Beaudouin (1) , C Brochot (1) , Georges de Sousa (3) , Roger Rahmani (3) , Alexandre R.R. Pery (4, 1)

1 INERIS - Institut National de l'Environnement Industriel et des Risques
2 ODESIA NeoSciences
3 ToxAlim - ToxAlim
4 ECOSYS - Ecologie fonctionnelle et écotoxicologie des agroécosystèmes

The ban of animal testing has enhanced the development of new in vitro technologies for cosmetics safety assessment. Impedance metrics is one such technology which enables monitoring of cell viability in real time. However, analyzing real time data requires moving from static to dynamic toxicity assessment. In the present study, we built mechanistic biokinetic/toxicodynamic (BK/TD) models to analyze the time course of cell viability in cytotoxicity assay using impedance. These models account for the fate of the tested compounds during the assay. BK/TD models were applied to analyze HepaRG cell viability, after single (48h) and repeated (4 weeks) exposures to three hepatotoxic compounds (coumarin, isoeugenol and benzophenone-2). The BK/TD models properly fit the data used for their calibration that was obtained for single or repeated exposure. Only for one out of the three compounds, the models calibrated with a single exposure were able to predict repeated exposure data. We therefore recommend the use of long-term exposure in vitro data in order to adequately account for chronic hepatotoxic effects. The models we propose here are capable of being coupled with human biokinetic models in order to relate dose exposure and human hepatotoxicity.

Keywords: In vitro modeling; Cell viability; Hepatotoxicity; Acute to chronic extrapolation; Impedance

Domains: Toxicology

S Teng, S Barcellini-Couget, R Beaudouin, C Brochot, Georges de Sousa, et al.. BK/TD models for analyzing in vitro impedance data on cytotoxicity.. Toxicology Letters, 2015, 235 (2), pp.96-106. ⟨10.1016/j.toxlet.2015.03.011⟩. ⟨hal-01146616⟩