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Toxicol In Vitro. 2017 Dec;45(Pt 2):233-240. doi: 10.1016/j.tiv.2016.10.007. Epub 2016 Oct 14.

Practical use of the Virtual Cell Based Assay: Simulation of repeated exposure experiments in liver cell lines.

Author information

1
Chemical Safety and Alternative Methods Unit, EURL ECVAM, Directorate F - Health, Consumers and Reference Materials, Joint Research Centre, European Commission, Ispra, Italy. Electronic address: Alicia.paini@ec.europa.eu.
2
Chemical Safety and Alternative Methods Unit, EURL ECVAM, Directorate F - Health, Consumers and Reference Materials, Joint Research Centre, European Commission, Ispra, Italy.

Abstract

The Virtual Cell Based Assay (VCBA) was applied to simulate the long-term (repeat dose) toxic effects of chemicals, including substances in cosmetics and personal care products. The presented model is an extension of the original VCBA for simulation of single exposure and is implemented in a KNIME workflow. This work illustrates the steps taken to simulate the repeated dose effects of two reference compounds, caffeine and amiodarone. Using caffeine, in vitro experimental viability data in single exposure from two human liver cell lines, HepG2 and HepaRG, were measured and used to optimize the VCBA, subsequently repeated exposure simulations were run. Amiodarone was then tested and simulations were performed under repeated exposure conditions in HepaRG. The results show that the VCBA can adequately predict repeated exposure experiments in liver cell lines. The refined VCBA model can be used not only to support the design of long term in vitro experiments but also practical applications in risk assessment. Our model is a step towards the development of in silico predictive approaches to replace, refine, and reduce the in vivo repeated dose systemic toxicity studies in the assessment of human safety.

KEYWORDS:

HepG2; HepaRG; Repeated exposure; Virtual cell based assay (VCBA)

PMID:
27746372
DOI:
10.1016/j.tiv.2016.10.007
[Indexed for MEDLINE]
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