In-vitro / in-vivo toxicity models (GLP-like / GLP)

 

Fig.: Toxicity / immunotoxicity of substances is evaluated in vitro using various approaches, e.g. toxicity of a substance to adherent cells can be monitored in real-time using the xCELLigence® system.

Species

  • Human (primary cells / cell lines)
  • Mouse

Field of application

The analysis of toxicity / immunotoxicity of substances is essential to establish limit values for toxic compounds and maximum tolerable doses (MTDs) for drugs. The toxicity of a substance is not only based on its reactivity in a healthy organism, but can be substantially modified during an active immune response. We supply a wide range of in-vitro models to investigate toxicity and immunotoxicity of potentially hazardous agents or drug candidates. We also provide mouse models to analyse the impact of substances in vivo, either in the healthy organism or in the presence of an active immune response following infection.

  • Testing of toxic / immunotoxic substances
  • Safety studies for drug approval (GLP)

Endpoints/Outcome parameter

  • Cell viability / proliferation
  • Clinical symptoms / mortality
  • Analysis of inflammatory cells and markers in blood, spleen and liver
  • Phenotyping of immune cell subtypes
  • Cytokine / Chemokine secretion
  • Changes in gene expression
  • Functional activity of different immune cell subtypes (phagocytosis, NO production, cytokine / antibody response etc.)

Readout parameter

  • Viability assays (xCELLigence®, WST-1, MTT, BrdU)
  • Daily evaluation of body weight / clinical symptoms
  • Periodic blood sampling
  • Flow cytometric analysis / Cell sorting / Imaging flow cytometry
  • ELISA / Multiplex analysis
  • Quantitative real-time PCR
  • Reporter assay for Aryl hydrocarbon receptor (AhR) activation
  • Histology
  • Immunohistochemistry / Immunofluorescence

Quality management measures

  • Internal quality management (certified GLP test facility)
  • Use of reference compounds (Standard-of-care therapies)
  • Randomisation
  • Blinded induction, data acquisition and analysis
  • Biometric expertise