Consensus report on the future of animal-free systemic toxicity testing

Marcel Leist, Nina Hasiwa, Costanza Rovida, Mardas Daneshian, David Basketter, Ian Kimber, Harvey Clewell, Tilman Gocht, Alan Goldberg, Francois Busquet, Anna Maria Rossi, Michael Schwarz, Martin L Stephens, Rob Taalman, Thomas B. Knudsen, James McKim, Georgina Harris, David Pamies, Thomas Hartung

Research output: Contribution to journalArticle

Abstract

Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council's vision document for Toxicity Testing in the 21st Century in 2007. It is now possible to provide a more defined roadmap on how to implement this vision for the four principal areas of systemic toxicity evaluation: repeat dose organ toxicity, carcinogenicity, reproductive toxicity and allergy induction (skin sensitization), as well as for the evaluation of toxicant metabolism (toxicokinetics) (Fig. 1). CAAT-Europe assembled experts from Europe, America and Asia to design a scientific roadmap for future risk assessment approaches and the outcome was then further discussed and refined in two consensus meetings with over 200 stakeholders. The key recommendations include: focusing on improving existing methods rather than favoring de novo design; combining hazard testing with toxicokinetics predictions; developing integrated test strategies; incorporating new high content endpoints to classical assays; evolving test validation procedures; promoting collaboration and data-sharing of different industrial sectors; integrating new disciplines, such as systems biology and high throughput screening; and involving regulators early on in the test development process. A focus on data quality, combined with increased attention to the scientific background of a test method, will be important drivers. Information from each test system should be mapped along adverse outcome pathways. Finally, quantitative information on all factors and key events will be fed into systems biology models that allow a probabilistic risk assessment with flexible adaptation to exposure scenarios and individual risk factors.

Original languageEnglish (US)
Pages (from-to)341-356
Number of pages16
JournalAltex
Volume31
Issue number3
DOIs
StatePublished - 2014

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Consensus
Systems Biology
Information Dissemination
Cosmetics
Hypersensitivity
Safety
Skin
Toxicokinetics
Data Accuracy

Keywords

  • Adverse outcome pathways
  • Animal-free testing
  • Safety testing
  • Systemic toxicity

ASJC Scopus subject areas

  • Medical Laboratory Technology
  • Pharmacology
  • Medicine(all)

Cite this

Leist, M., Hasiwa, N., Rovida, C., Daneshian, M., Basketter, D., Kimber, I., ... Hartung, T. (2014). Consensus report on the future of animal-free systemic toxicity testing. Altex, 31(3), 341-356. https://doi.org/10.14573/altex.1406091

Consensus report on the future of animal-free systemic toxicity testing. / Leist, Marcel; Hasiwa, Nina; Rovida, Costanza; Daneshian, Mardas; Basketter, David; Kimber, Ian; Clewell, Harvey; Gocht, Tilman; Goldberg, Alan; Busquet, Francois; Rossi, Anna Maria; Schwarz, Michael; Stephens, Martin L; Taalman, Rob; Knudsen, Thomas B.; McKim, James; Harris, Georgina; Pamies, David; Hartung, Thomas.

In: Altex, Vol. 31, No. 3, 2014, p. 341-356.

Research output: Contribution to journalArticle

Leist, M, Hasiwa, N, Rovida, C, Daneshian, M, Basketter, D, Kimber, I, Clewell, H, Gocht, T, Goldberg, A, Busquet, F, Rossi, AM, Schwarz, M, Stephens, ML, Taalman, R, Knudsen, TB, McKim, J, Harris, G, Pamies, D & Hartung, T 2014, 'Consensus report on the future of animal-free systemic toxicity testing', Altex, vol. 31, no. 3, pp. 341-356. https://doi.org/10.14573/altex.1406091
Leist M, Hasiwa N, Rovida C, Daneshian M, Basketter D, Kimber I et al. Consensus report on the future of animal-free systemic toxicity testing. Altex. 2014;31(3):341-356. https://doi.org/10.14573/altex.1406091
Leist, Marcel ; Hasiwa, Nina ; Rovida, Costanza ; Daneshian, Mardas ; Basketter, David ; Kimber, Ian ; Clewell, Harvey ; Gocht, Tilman ; Goldberg, Alan ; Busquet, Francois ; Rossi, Anna Maria ; Schwarz, Michael ; Stephens, Martin L ; Taalman, Rob ; Knudsen, Thomas B. ; McKim, James ; Harris, Georgina ; Pamies, David ; Hartung, Thomas. / Consensus report on the future of animal-free systemic toxicity testing. In: Altex. 2014 ; Vol. 31, No. 3. pp. 341-356.
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