Mechanistic and in-vitro toxicology

We offer a broad range of in-vitro test methods that are used for pre-clinical testing of active pharmaceutical ingredients and for assessing the cytotoxic and genotoxic potentials of environmentally and occupationally relevant substances. This also includes alternative test methods in line with the current European chemicals policy (REACH).

Selection of the appropriate cellular test systems and development of the study design is performed in consultation with the sponsor, governed by a variety of criteria such as relevance of the species, organ, and target site, endpoints to be analyzed, compliance with the relevant guidelines (e.g. OECD), and any additional requirements.

Especially for the field of respiratory toxicology, we offer the development of strategies for in-vitro/in-vivo extrapolation (qIVIVE). By combining exposure characterization studies and the application of assessment strategies, this can be used as a supportive tool, for example in the development phase of cosmetic sprays, to ensure safety ("safe-by-design").

• In-vitro exposure of cellular test systems
  Exposure to airborne, soluble, and particulate test substances
• Determination of multiple parameters in cells
  Determination of endpoints and on-line monitoring
• Development of quantitative in vitro to in vivo extrapolation approaches (qIVIVE), for example in the field of cosmetic sprays
• In-vitro ADME assays
  CYP450 monooxygenases, NAT profiling, biochemical parameters
• Characterization of molecular mechanisms of action
• Regulatory assessments by means of standard genotoxicological tests
  in compliance with international regulations (OECD, EU, EPA, FDA)

• Biological test systems:
  
  • Primary cultures of human and animal origin, immortal and transgenic cell lines, co-culture systems, precision-cut liver and lung slices, microsomes
• Exposure:
  • Liquid or soluble test substances
  • Particulate substances in suspensions
  • Airborne test substances (gases, aerosols, particles) in a special culturing and exposure system developed for this purpose
• Detection of biological effects:
  • General toxicity (e.g. cytotoxicity, apoptosis, oxidative stress, proliferation, ATP status, interleukins, DNA damage, transcription factors)
  • Genotoxicity (e.g. comet assay, micronucleus assay, chromosomal aberration test)
  • Molecular mechanisms (expression of toxicologically relevant genes, epigenetics, and DNA analyses)