Toxicology

The zebrafish is one of the recommended species for fish toxicity tests that are part of the Environmental Risk Assessment (ERA) required for drugs and chemicals.

 

This vertebrate model is a simple, well characterized in vivo tool for toxicity and efficacy testing, and constitutes an alternative and complementary approach to the use of mammals (mice, rats or dogs), in accordance with the European Directive 86/609/CE and with the 3R’s rules.

 

As Chakravarthy et al rightly wrote, the zebrafish is “a powerful, sensitive, quantitative, noninvasive, and high-throughput whole-animal assay to screen for toxicity

The zebrafish meets indeed all criteria for being an ideal preclinical model in safety pharmacoly and to perform drug screening or genotoxicity tests.

In addition to its intrinsic qualities, the zebrafish has several inherent advantages for drug screening, making in vivo assays highly cost-effective 1) larvae can be kept for several days in 96- or 384-well plates, therefore only small amount of compound are needed 2) larvae are very permeable to hydrophilic drugs (through the skin or gills) but highly hydrophobic compounds can also be injected directly into the yolk sac or the circulation 3) statistically significant numbers of zebrafish can be used for each assay in record time

 

We can evaluate the toxicity and teratogenicity of your compounds on zebrafish embryos for different lethal and sublethal endpoints. Acute toxicity tests (LC50) can also be performed.

 

Which endpoints can be assessed?

  • Mortality : LC50 on adults or embryos
  • Embryonic development (epiboly, gastrulation, segmentation): detection of growth delay, malformations or morphological abnormalities
  • Target organ development (with reporter protein quantification): endocrine and exocrine pancreas, liver, blood vessels, retina, red blood cells, …
  • Cardiovascular endpoints: heart beat measurement, detection of arrhythmia, peripheral blood circulation, hemorrhage
  • Cartilage and / or bone formation, bone density
  • CNS endpoints: locomotor activity measurement for potential assessment of drug addiction, proconvulsant liability, cognition impairment
  • Gastrointestinal motility
  • Specific gene expression (by whole in situ hybridization)
  • HSP70 activation
  • Metabolic endpoints: cytochrome P450s activities