New ideas for non-animal approaches to predict repeated-dose systemic toxicity: report from an EPAA Blue Sky Workshop

Research output: Contribution to journalArticle

Authors

  • Catherine Mahony
  • Randolph S. Ashton
  • Barbara Birk
  • Alan R. Boobis
  • Tom Cull
  • George P. Daston
  • Lorna Ewart
  • Thomas B. Knudsen
  • Irene Manou
  • Sebastian Maurer-Stroh
  • Luigi Margiotta-Casaluci
  • Boris P. Müller
  • Pär Nordlund
  • Thomas Steger-Hartmann
  • Evita Vandenbossche
  • Mathieu Vinken
  • Maurice Whelan
  • Zvonar Zvonimir
  • Mark T.D. Cronin

Colleges, School and Institutes

External organisations

  • Procter and Gamble
  • University of Wisconsin, Madison, WI, USA
  • BASF SE
  • National Heart and Lung Institute
  • Unilever
  • Veroli Consulting Limited
  • Emulate Inc.
  • U.S. Environmental Protection Agency
  • European Partnership for Alternative Approaches to Animal Testing (EPAA) Industry Secretariat
  • Technology and Research (A*STAR)
  • National University of Singapore
  • Brunel University
  • Symrise AG
  • Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Institute of Molecular and Cell Biology, A-Star, Singapore
  • Bayer
  • Vrije Universiteit Brussel
  • Joint Research Centre (JRC) - European Commission’s Science Service
  • Liverpool John Moores University

Abstract

The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a ‘Blue Sky Workshop’ on new ideas for non-animal approaches to predict repeated-dose systemic toxicity. The aim of the Workshop was to formulate strategic ideas to improve and increase the applicability, implementation and acceptance of modern non-animal methods to determine systemic toxicity. The Workshop concluded that good progress is being made to assess repeated dose toxicity without animals taking advantage of existing knowledge in toxicology, thresholds of toxicological concern, adverse outcome pathways and read-across workflows. These approaches can be supported by New Approach Methodologies (NAMs) utilising modern molecular technologies and computational methods. Recommendations from the Workshop were based around the needs for better chemical safety assessment: how to strengthen the evidence base for decision making; to develop, standardise and harmonise NAMs for human toxicity; and the improvement in the applicability and acceptance of novel techniques. “Disruptive thinking” is required to reconsider chemical legislation, validation of NAMs and the opportunities to move away from reliance on animal tests. Case study practices and data sharing, ensuring reproducibility of NAMs, were viewed as crucial to the improvement of non-animal test approaches for systemic toxicity.

Bibliographic note

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Details

Original languageEnglish
Article number104668
Number of pages8
JournalRegulatory Toxicology and Pharmacology
Volume114
Early online date23 Apr 2020
Publication statusPublished - Jul 2020

Keywords

  • ab initio, Alternatives, Chemical legislation, in silico, in vitro, Read-across, Repeated dose toxicity testing, Safety assessment

ASJC Scopus subject areas