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Toxicol Lett. 2015 Jun 1;235(2):96-106. doi: 10.1016/j.toxlet.2015.03.011. Epub 2015 Mar 28.

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

Author information

1
INERIS (METO), Verneuil-en-Halatte 60550, France. Electronic address: sophie.teng-etudiant@ineris.fr.
2
ODESIA Neosciences, Sophia Antipolis F- 31076, France. Electronic address: s.barcellini@odesia-neosciences.com.
3
INERIS (METO), Verneuil-en-Halatte 60550, France. Electronic address: remy.beaudouin@ineris.fr.
4
INERIS (METO), Verneuil-en-Halatte 60550, France. Electronic address: celine.brochot@ineris.fr.
5
INRA Toxalim, Sophia Antipolis F- 31076, France. Electronic address: desousa@sophia.inra.fr.
6
INRA Toxalim, Sophia Antipolis F- 31076, France. Electronic address: roger.rahmani@sophia.inra.fr.
7
INERIS (METO), Verneuil-en-Halatte 60550, France; AgroParisTech, UMR 1402 INRA-AgroParisTech EcoSys, Thiverval-Grignon F- 78850, France. Electronic address: alexandre.pery@ineris.fr.

Abstract

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 (48 h) 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:

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

PMID:
25827406
DOI:
10.1016/j.toxlet.2015.03.011
[Indexed for MEDLINE]
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