TY - JOUR
T1 - New ideas for non-animal approaches to predict repeated-dose systemic toxicity
T2 - report from an EPAA Blue Sky Workshop
AU - Mahony, Catherine
AU - Ashton, Randolph S.
AU - Birk, Barbara
AU - Boobis, Alan R.
AU - Cull, Tom
AU - Daston, George P.
AU - Ewart, Lorna
AU - Knudsen, Thomas B.
AU - Manou, Irene
AU - Maurer-Stroh, Sebastian
AU - Margiotta-Casaluci, Luigi
AU - Müller, Boris P.
AU - Nordlund, Pär
AU - Roberts, Ruth A.
AU - Steger-Hartmann, Thomas
AU - Vandenbossche, Evita
AU - Viant, Mark R.
AU - Vinken, Mathieu
AU - Whelan, Maurice
AU - Zvonimir, Zvonar
AU - Cronin, Mark T.D.
N1 - Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
KW - ab initio
KW - Alternatives
KW - Chemical legislation
KW - in silico
KW - in vitro
KW - Read-across
KW - Repeated dose toxicity testing
KW - Safety assessment
UR - http://www.scopus.com/inward/record.url?scp=85083897051&partnerID=8YFLogxK
U2 - 10.1016/j.yrtph.2020.104668
DO - 10.1016/j.yrtph.2020.104668
M3 - Article
C2 - 32335207
AN - SCOPUS:85083897051
SN - 0273-2300
VL - 114
JO - Regulatory Toxicology and Pharmacology
JF - Regulatory Toxicology and Pharmacology
M1 - 104668
ER -