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ECVAM and New Technologies for Toxicity Testing

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New Technologies for Toxicity Testing

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 745))

Abstract

The development of alternative empirical (testing) and non-empirical (nontesting) methods to traditional toxicological tests for complex human health effects is a tremendous task. Toxicants may potentially interfere with a vast number of physiological mechanisms thereby causing disturbances on various levels of complexity of human physiology. Only a limited number of mechanisms relevant for toxicity (‘pathways’ of toxicity) have been identified with certainty so far and, presumably, many more mechanisms by which toxicants cause adverse effects remain to be identified. Recapitulating in empirical model systems (i.e., in vitro test systems) all those relevant physiological mechanisms prone to be disturbed by toxicants and relevant for causing the toxicity effect in question poses an enormous challenge. First, the mechanism(s) of action of toxicants in relation to the most relevant adverse effects of a specific human health endpoint need to be identified. Subsequently, these mechanisms need to be modeled in reductionist test systems that allow assessing whether an unknown substance may operate via a specific (array of) mechanism(s). Ideally, such test systems should be relevant for the species of interest, i.e., based on human cells or modeling mechanisms present in humans. Since much of our understanding about toxicity mechanisms is based on studies using animal model systems (i.e., experimental animals or animal-derived cells), designing test systems that model mechanisms relevant for the human situation may be limited by the lack of relevant information from basic research. New technologies from molecular biology and cell biology, as well as progress in tissue engineering, imaging techniques and automated testing platforms hold the promise to alleviate some of the traditional difficulties associated with improving toxicity testing for complex endpoints. Such new technologies are expected (1) to accelerate the identification of toxicity pathways with human relevance that need to be modeled in test methods for toxicity testing (2) to enable the reconstruction of reductionist test systems modeling at a reduced level of complexity the target system/organ of interest (e.g., through tissue engineering, use of human-derived cell lines and stem cells etc.), (3) to allow the measurement of specific mechanisms relevant for a given health endpoint in such test methods (e.g., through gene and protein expression, changes in metabolites, receptor activation, changes in neural activity etc.), (4) to allow to measure toxicity mechanisms at higher throughput rates through the use of automated testing. In this chapter, we discuss the potential impact of new technologies on the development, optimization and use of empirical testing methods, grouped according to important toxicological endpoints. We highlight, from an ECVAM perspective, the areas of topical toxicity, skin absorption, reproductive and developmental toxicity, carcinogenicity/genotoxicity, sensitization, hematopoeisis and toxicokinetics and discuss strategic developments including ECVAM’s database service on alternative methods. Neither the areas of toxicity discussed nor the highlighted new technologies represent comprehensive listings which would be an impossible endeavor in the context of a book chapter. However, we feel that these areas are of utmost importance and we predict that new technologies are likely to contribute significantly to test development in these fields. We summarize which new technologies are expected to contribute to the development of new alternative testing methods over the next few years and point out current and planned ECVAM projects for each of these areas.

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Authors and Affiliations

  1. REACH Unit, DG Enterprise and Industry, European Commission, Brussels, Belgium

    Michel Bouvier d’Yvoire, Annett Roi & Valérie Zuang

  2. European Centre for the Validation of Alternative Methods (ECVAM), Institute for Health and Consumer Protection (IHCP), DG Joint Research Centre (JRC), European Commission, Ispra, Italy

    Susanne Bremer, Silvia Casati, Mara Ceridono, Sandra Coecke, Raffaella Corvi & Claudius Griesinger

  3. SeCAM, Agno, Switzerland

    Chantra Eskes

  4. Molecular Biology and Genomics Unit, Institute for Health and Consumer Protection (IHCP), DG Joint Research Centre (JRC), European Commission, Ispra, Italy

    Laura Gribaldo

  5. Skirball Institute, Langone Medical Center, New York University, New York, USA

    Holger Knaut

  6. Global Security and Crisis Management Unit, Institute for the Protection and Security of the Citizen (IPSC), DG Joint Research Centre (JRC), European Commission, Ispra, Italy

    Jens P. Linge

Authors
  1. Michel Bouvier d’Yvoire
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  2. Susanne Bremer
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  3. Silvia Casati
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  4. Mara Ceridono
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  5. Sandra Coecke
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  6. Raffaella Corvi
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  7. Chantra Eskes
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  8. Laura Gribaldo
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  9. Claudius Griesinger
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  10. Holger Knaut
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  11. Jens P. Linge
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  12. Annett Roi
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  13. Valérie Zuang
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Corresponding author

Correspondence to Claudius Griesinger .

Editor information

Editors and Affiliations

  1. FRAME, Nottingham, UK

    Michael Balls DPhil

  2. Norwich, UK

    Robert D. Combes PhD (Independent Consultant) (Independent Consultant)

  3. Nottingham, UK

    Nirmala Bhogal PhD (Independent Consultant) (Independent Consultant)

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© 2012 Landes Bioscience and Springer Science+Business Media

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Bouvier d’Yvoire, M. et al. (2012). ECVAM and New Technologies for Toxicity Testing. In: Balls, M., Combes, R.D., Bhogal, N. (eds) New Technologies for Toxicity Testing. Advances in Experimental Medicine and Biology, vol 745. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3055-1_10

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