In the field of modern toxicology, a progressive paradigm shift has long taken place: in the last twenty years there has been a transition from a research mainly based on animal models, to animal-free methods, in which in vitro, silico systems are preferred and which integrated together are believed to have greater relevance for the study of physiology and toxicology in humans. The document published in 2007 in the United States entitled “Toxicity Testing in the 21st Century: A Vision and a Strategy” (1), as well as Directive 2010/63/EU of the European Parliament and of the Council on the Protection of Animals Used for Scientific Purposes (2), encourage the use of alternatives to animal testing. In 2012 the OECD has introduced the concept of Adverse Outcome Pathways (AOPs) framework.
AOPs are created to summarize information about the effects of environmental chemicals or any other substance, detailing the cellular and molecular mechanisms (at the level of genes and proteins) underlying these effects, taking into account different levels of biological complexity (population, individual, organ, tissue, cell, and molecules).
The New Approach Methodologies (NAMs) are all those technologies, methodologies, advanced non-animal approaches that can be used, even in an integrated way, to obtain information on the risk associated with chemicals (3, 4).
The organisation of knowledge about the effects of chemicals through these types of conceptual approaches can be easily applied to the field of biomedical research, for example to identify molecular signals that are altered by the onset of a certain pathology (5, 6).
Examples of initiatives that aim to promote this type of approach in biomedical research are BioMed 21 and Alliance for Human-relevant Science, which bring together scientists and institutions internationally, to overcome the current research paradigm and the adoption/development of new approaches and methodologies, based on the knowledge that traditional models (both in vivo and in vitro) are inadequate.
1.NRC Toxicity Testing in the 21st Century: A Vision and a Strategy. Washington, DC: The National Academies Press; 2007. 216 p.
2.Directive 2010/63/EU on the protection of animals used for scientific purposes 2010.
3.Afsa [Available from: https://www.afsacollaboration.org/ ]
4.HumamToxomeProject. [Available from: http://human-toxome.com/]
5.Langley GR, Adcock IM, Busquet F, Crofton KM, Csernok E, Giese C, et al. Towards a 21st-century roadmap for biomedical research and drug discovery: consensus report and recommendations. Drug Discov Today. 2017;22(2):327-39.
6.Langley G, Austin CP, Balapure AK, Birnbaum LS, Bucher JR, Fentem J, et al. Lessons from Toxicology: Developing a 21st-Century Paradigm for Medical Research. Environ Health Perspect. 2015;123(11):A268-72.