Replacement of animal testing by integrated approaches to testing and assessment (IATA): a call for in vivitrosi

Abstract

Alternative methods to animal use in toxicology are evolving with new advanced tools and multilevel approaches, to answer from one side to 3Rs requirements, and on the other side offering relevant and valid tests for drugs and chemicals, considering also their combination in test strategies, for a proper risk assessment.While stand-alone methods, have demonstrated to be applicable for some specific toxicological predictions with some limitations, the new strategy for the application of New Approach Methods (NAM), to solve complex toxicological endpoints is addressed by Integrated Approaches for Testing and Assessment (IATA), aka Integrated Testing Strategies (ITS) or Defined Approaches for Testing and Assessment (DA). The central challenge of evidence integration is shared with the needs of risk assessment and systematic reviews of an evidence-based Toxicology. Increasingly, machine learning (aka Artificial Intelligence, AI) lends itself to integrate diverse evidence streams.In this article, we give an overview of the state of the art of alternative methods and IATA in toxicology for regulatory use for various hazards, outlining future orientation and perspectives. We call on leveraging the synergies of integrated approaches and evidence integration from in vivo, in vitro and in silico as true in vivitrosi.

Application of AOPs to assist regulatory assessment of chemical risks – Case studies, needs and recommendations

“…IATA are science-based approaches that integrate NAMs and mechanistic knowledge for hazard characterization, in a specific regulatory context ( Caloni et al, 2022 ). The AOP framework can be particularly useful in this case to facilitate the identification of the most suitable assays for measurement of MIE or KEs to predict adverse health effects ( Tollefsen et al, 2014 ; Willett, 2019 ), as demonstrated by the examples in the following paragraph.…”

Use of laboratory animals and issues regarding the procurement of animals for research in Korea

“…time, skills and experiences, animal housing, special equipment, and consumables, including food), despite its impacts in human health while minimizing the safety and well-being of animals and research practitioners [ 20 ]. In the field of toxicology, many alternatives have been proposed [ 21 ], and implementation of replacement using organoids etc. have been actively proposed even in veterinary research [ 22 ].…”

A call for a Human Exposome Project

“…The central call of Tox-21c to move to a mechanistic toxicology of perturbed pathways of toxicity implies the use of multiple tests and types of evidence. These integrated testing strategies (ITS), termed integrated approaches to testing and assessment (IATA) by the Organisation for Economic Cooperation and Development (OECD) (Tollefsen et al, 2014), and defined approaches, have been discussed in this series (Hartung et al, 2013a), a workshop (Rovida et al, 2015a), and a more recent review (Caloni et al, 2022). Some progress, especially the defined approaches on skin sensitization 2 , is noted (Kleinstreuer et al, 2018;Kolle et al, 2020).…”

“…High-throughput data generation for relevant big data that answers important safety questions, e.g., realistic exposures, potencies, mixtures, interindividual differences. Andersen et al, 2019;Jacobs et al, 2019;de Souza Santos et al, 2018;Aschner et al, 2017;Gordon et al, 2015;Patlewicz et al, 2014;Juberg et al, 2014;Smirnova et al, 2014;Hartung and Corsini, 2013;Parks Saldutti et al, 2013;Rossini and Hartung, 2012;Basketter et al, 2012;Kuegler et al, 2010;Hartung and Hoffmann, 2009;Leist et al, 2008a; Krewski et al, 2022;Maertens et al, 2022;Farhat et al, 2022;Caloni et al, 2022;Hoffmann et al, 2022a,b;Hartung, 2017cHartung, , 2021bHoffmann et al, 2017;Linkov et al, 2015;Hartung, 2009bMetabolomics Lippa et al, 2022Evans et al, 2020;Beger et al, 2019; ALTEX 35, 306-352. doi:10.14573/altex.1712081 Basketter, D. A., Clewell, H., Kimber, I. et al (2012). A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing.…”