The value of alternative testing for neurotoxicity in the context of regulatory needs

Sandra Coecke, Chantra Eskes, Joanne Gartlon, Agnieszka Kinsner, Anna Price, Erwin Van Vliet, Pilar Prieto, Monica Boveri, Susanne Bremer, Sarah Adler, Cristian Pellizzer, Albrecht Wendel, Thomas Hartung

Research output: Contribution to journalArticle

Abstract

Detection and characterisation of chemical-induced toxic effects in the central and peripheral nervous system represent a major challenge for employing newly developed technologies in the field of neurotoxicology. Precise cellular predictive test batteries for chemical-induced neurotoxicity are increasingly important for regulatory decision making, but also the most efficient way to keep costs and time of testing within a reasonable margin. Current in vivo test methods are based on behavioural and sensory perturbations coupled with routine histopathological investigations. In spite of the empirical usefulness of these tests, they are not always sensitive enough and often, they do not provide information that facilitates a detailed understanding of potential mechanisms of toxicity, thus enabling predictions. In general, such in vivo tests are unsuitable for screening large number of agents. One way to meet the need for more powerful and comprehensive tests via an extended scientific basis is to study neurotoxicity in specific cell types of the brain and to derive generalised mechanisms of action of the toxicants from such series of experiments. Additionally, toxicokinetic models are to be developed in order to give a rough account for the whole absorption, distribution, metabolism, excretion (ADME) process including the blood-brain barrier (BBB). Therefore, an intensive search for the development of alternative methods using animal and human-based in vitro and in silico models for neurotoxic hazard assessment is appropriate. In particular, neurotoxicology represents one of the major challenges to the development of in vitro systems, as it has to account also for heterogeneous cell interactions of the brain which require new biochemical, biotechnological and electrophysiological profiling methods for reliable alternative ways with a high throughput.

Original languageEnglish (US)
Pages (from-to)153-167
Number of pages15
JournalEnvironmental Toxicology and Pharmacology
Volume21
Issue number2 SPEC. ISS.
DOIs
StatePublished - Feb 2006
Externally publishedYes

Keywords

  • In vitro
  • Neurotoxicity
  • Regulatory toxicology
  • Toxicokinetics

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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  • Cite this

    Coecke, S., Eskes, C., Gartlon, J., Kinsner, A., Price, A., Van Vliet, E., Prieto, P., Boveri, M., Bremer, S., Adler, S., Pellizzer, C., Wendel, A., & Hartung, T. (2006). The value of alternative testing for neurotoxicity in the context of regulatory needs. Environmental Toxicology and Pharmacology, 21(2 SPEC. ISS.), 153-167. https://doi.org/10.1016/j.etap.2005.07.006