Abstract

Application of high-throughput transcriptomics for mechanism-based biological read-across of short-chain carboxylic acid analogues of valproic acid_suppl2

Highlights

  • Experimental System: HepG2 BAC-GFP reporter cell lines are based on HepG2 (ATCC® HB8065TM) cells which were transfected with a bacterial artificial chromosome containing an EGFP-tagged-gene including the flanking regulatory domains

  • 2.3 Tissue, cells or extracts utilised in the assay and the species source See experimental system: HepG2 BAC-GFP reporter cell lines are based on HepG2 (ATCC® HB8065TM) cells which were transfected with a bacterial artificial chromosome containing an EGFP-tagged-gene including the flanking regulatory domains

  • The protocol is based on the measurement of different endpoints that are indicative of hepatotoxicity and steatosis by means of high-content imaging and it has been previously used and published in the context of drug-induced hepatotoxicity ((Donato et al, 2017; Donato et al, 2012; Tolosa et al, 2015a; Tolosa et al, 2015b; Tolosa et al, 2017; Tolosa et al, 2016; Tolosa et al, 2013; Tolosa et al, 2012))

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Summary

15 October 2020

ENVIRONMENT DIRECTORATE JOINT MEETING OF THE CHEMICALS COMMITTEE AND THE WORKING. Annex II: In vivo data and in vitro experiments WITHIN CASE STUDY ON THE USE OF INTEGRATED APPROACHES TO TESTING AND ASSESSMENT FOR PREDICTION OF A 90 DAY REPEATED DOSE TOXICITY STUDY (OECD 408) FOR 2-ETHYLBUTYRIC ACID USING A READ-ACROSS APPROACH FROM OTHER BRANCHED CARBOXYLIC ACIDS. The corresponding monograph to this annex is available under the following cotes: ENV/JM/MONO(2020). This document, as well as any data and map included are without prejudice to the status of or sovereignty over any territory, to the delimitation of international frontiers and boundaries and to the name of any territory, city or area

In vivo repeated dose toxicity data
Experimental description
Known technical limitations and strengths
Limitations
Discussion
Robustness of the method
Part B. Technical description
Method
Experimental Description
Procedure Details
In the meantime
If live imaging
HEPG2- assay
Description of the general features of the test system
Definition of cells used ATCC number
Definition of the test system
Analytical endpoints Actually used method
Test method description
Test method endpoint
General information
5.1.11 Status of method development and uses
Test Method Definition
Scientific principle of the method
Description of the experimental system exposure regime
Response and Response Measurement
Data analysis
Test Method Performance
Acute cytotoxicity assay in primary human hepatocytes
Lipid droplet accumulation in primary human hepatocytes
Resazurin assay
Findings
Lactate Assay
Full Text
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