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Article | REF: RE295 V1

In vitro and in silico alternatives to animal models in toxicology

Authors: Arnaud TETE, Elias ZGHEIB, Sana AL AWABDH, Louise BENOIT, Kévin BERNAL, Carolina DUARTE HOSPITAL, Lucie LARIGOT, Lorena LOPEZ SUAREZ, Karine ANDREAU, Caroline CHAUVET, Min Ji KIM, Meriem KOUAL, Céline TOMKIEWICZ-RAULET, Xavier COUMOUL, Étienne BLANC, Karine AUDOUZE, Sylvie BORTOLI

Publication date: June 10, 2022

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ABSTRACT

The toxicity of xenobiotics cannot be tested in humans. Animal models and in particular rodents are still widely used in experimental toxicology, although the extrapolability of toxicity mechanisms in animals is not always relevant for humans. This article presents different techniques and in vitro and in silico models, often combined to assess the impact of exposure to contaminants at the cellular, organ and human organism levels. These methods exist at varying degrees of maturity in their design and integration to the regulatory toxicology guidelines.

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AUTHORS

  • Arnaud TETE: Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Elias ZGHEIB: Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Sana AL AWABDH: Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Louise BENOIT: Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Kévin BERNAL: Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Carolina DUARTE HOSPITAL: Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Lucie LARIGOT: Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Lorena LOPEZ SUAREZ: Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Karine ANDREAU: Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Caroline CHAUVET: Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Min Ji KIM: Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France Université Sorbonne Paris Nord, Bobigny, INSERM UMR-S 1124, Paris, France

  • Meriem KOUAL: Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Céline TOMKIEWICZ-RAULET: Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Xavier COUMOUL: Égale supervision Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Étienne BLANC: Égale supervision Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Karine AUDOUZE: Égale supervisionUniversité Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

  • Sylvie BORTOLI: Equal supervision - Corresponding author Université Paris Cité, T3S, Inserm UMR S-1124, F-75006 Paris, France

 INTRODUCTION

The challenges of toxicology are to assess the influence of xenobiotics on health and to characterize the toxicity mechanisms involved. It also aims to identify new biomarkers (of exposure and effect) and to develop toxicity prediction systems. The assessment of the toxicity of environmental pollutants by regulatory procedures has historically been linked to the use of in vivo models, including in particular rats and mice, but also rabbits and dogs. The observation of certain differences in toxicity mechanisms between animals and humans, combined with ethical concerns linked to animal welfare, have led the scientific community to multiply technological efforts to produce in vitro and in silico models relevant to toxicology. Without being exhaustive, this article presents various methods for exploring in vitro toxicity mechanisms, as well as alternatives to animal experimentation. These models are used not only in environmental toxicology, but also in pharmaco-toxicology, to predict the toxicity of drugs or cosmetics. They include 2D human cell cultures, 3D organotypic cultures, innovative co-culture models of several cell types, and emerging technologies such as bioprinting and organ-on-chip microfluidic devices. Finally, systemic approaches to computational toxicology are discussed, enabling us to integrate the complexity of biological responses and extrapolate predictions of adverse effects of contaminants on human health.

Key points

Field: Toxicology

Technologies involved: 2D and 3D cell culture, omics, microfluidics, 3D printing, computational toxicology

Areas of application: Mechanistic toxicology research, predictive toxicology, regulatory evaluation tests

Contact: [email protected] ; https://t3s-1124biomedicale.parisdescartes.fr/nos-equipes-de-recherche/team-1/

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KEYWORDS

toxicology   |   environnemental polluants   |   in vitro models   |   in silico technology

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