Automation of an in vitro cytotoxicity assay used to estimate starting doses in acute oral systemic toxicity tests

Mounir Bouhifd, Gilles Bories, Juan Casado, Sandra Coecke, Hedvig Norlén, Nicholaos Parissis, Robim M. Rodrigues, Maurice P. Whelan

Research output: Contribution to journalArticle

Abstract

Application of High Throughput Screening (HTS) to the regulatory safety assessment of chemicals is still in its infancy but shows great promise in terms of facilitating better understanding of toxicological modes-of-action, reducing the reliance on animal testing, and allowing more data-poor chemicals to be assessed at a reasonable cost. To promote the uptake and acceptance of HTS approaches, we describe in a stepwise manner how a well known cytotoxicity assay can be automated to increase throughput while maintaining reliability. Results generated with selected reference chemicals compared very favourably with data obtained from a previous international validation study concerning the prediction of acute systemic toxicity in rodents. The automated assay was then included in a formal ECVAM validation study to determine if the assay could be used for binary classification of chemicals with respect to their acute oral toxicity, using a threshold equivalent to a dose of 2000. mg/kg. b.w. in a rodent bioassay (LD50). This involved the blind-testing of 56 reference chemicals on the HTS platform to produce concentration-response and IC50 data. Finally, the assay was adapted to a format more suited to higher throughput testing without compromising the quality of the data obtained.

Original languageEnglish (US)
Pages (from-to)2084-2096
Number of pages13
JournalFood and Chemical Toxicology
Volume50
Issue number6
DOIs
StatePublished - Jun 2012
Externally publishedYes

Fingerprint

Toxicity Tests
Validation Studies
Automation
automation
Cytotoxicity
toxicity testing
Toxicity
cytotoxicity
Rodentia
mouth
Assays
Chemical Safety
Throughput
Computer Security
Lethal Dose 50
assays
dosage
screening
Screening
Biological Assay

Keywords

  • Acute oral toxicity
  • Alternative methods
  • Cytotoxicity
  • High throughput screening
  • Safety assessment
  • Validation

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

Bouhifd, M., Bories, G., Casado, J., Coecke, S., Norlén, H., Parissis, N., ... Whelan, M. P. (2012). Automation of an in vitro cytotoxicity assay used to estimate starting doses in acute oral systemic toxicity tests. Food and Chemical Toxicology, 50(6), 2084-2096. https://doi.org/10.1016/j.fct.2012.03.046

Automation of an in vitro cytotoxicity assay used to estimate starting doses in acute oral systemic toxicity tests. / Bouhifd, Mounir; Bories, Gilles; Casado, Juan; Coecke, Sandra; Norlén, Hedvig; Parissis, Nicholaos; Rodrigues, Robim M.; Whelan, Maurice P.

In: Food and Chemical Toxicology, Vol. 50, No. 6, 06.2012, p. 2084-2096.

Research output: Contribution to journalArticle

Bouhifd, M, Bories, G, Casado, J, Coecke, S, Norlén, H, Parissis, N, Rodrigues, RM & Whelan, MP 2012, 'Automation of an in vitro cytotoxicity assay used to estimate starting doses in acute oral systemic toxicity tests', Food and Chemical Toxicology, vol. 50, no. 6, pp. 2084-2096. https://doi.org/10.1016/j.fct.2012.03.046
Bouhifd, Mounir ; Bories, Gilles ; Casado, Juan ; Coecke, Sandra ; Norlén, Hedvig ; Parissis, Nicholaos ; Rodrigues, Robim M. ; Whelan, Maurice P. / Automation of an in vitro cytotoxicity assay used to estimate starting doses in acute oral systemic toxicity tests. In: Food and Chemical Toxicology. 2012 ; Vol. 50, No. 6. pp. 2084-2096.
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