Developmental Toxicity Assessment in Zebrafish
Identifying developmental toxicity and teratogenicity risks early is critical for pharmaceutical development. Regulatory guidelines (ICH S5(R3) for human drugs and VICH GL43 for veterinary drugs) mandate developmental and reproductive toxicity (DART) studies before advancing to clinical or market phases. However, traditional mammalian models are costly and time-consuming.
Our zebrafish-based screening platform provides an ICH/VICH-aligned, high-throughput alternative to anticipate and mitigate developmental toxicity risks early. By bridging the gap between in vitro assays and regulatory mammalian studies, we help you de-risk candidates faster and optimize preclinical development.
Two Services, One Complete Solution
Our Developmental Toxicity assay can be complemented with the Reproductive Toxicity service for full ICH S5(R3) coverage.
Why Choose Our Zebrafish-Based Developmental Toxicity Assay?
Predictability levels referred to rodents and humans above 80%.
Automated platform to process high amounts of larvae.
Mathematical-based approach that increases objectivity of verdicts.
Evaluation of an extensive panel of phenotypes.
Estimation of teratogenic potencies through teratogenic indexes.
Alignment with ICH S5(R3) requirements for Embryo-Fetal Toxicity evaluation.
Method description
1. Solubility Test
- Ensures the test compound does not precipitate.
- Confirms treatment at the intended concentration.
2. Dose-Range Finding
- Zebrafish embryos are exposed to the compound from 6 to 120 hpf.
- Mortality is assessed at 24 hpf and 120 hpf.
- The Benchmark Dose (BMD) is calculated to define the concentration range for developmental toxicity testing.
3. Develomental Toxicity Test
- Embryos are exposed to five concentrations of the test compound, from 6 to 120 hpf.
- Mortality is assessed at 24 hpf and 120 hpf and LC50 (lethal concentration for 50% of embryos) is calculated.
- 17 teratogenic phenotypes are analyzed using automated deep-learning-based phenotype extraction.
- EC50 is calculated based on the most sensitive teratogenic phenotype.
- Teratogenic Index is calcualted to predict the teratogenic potential of test compounds.
Readouts
- LC50: Lethal Concentration 50
- EC50: Effective Concentration 50 (for the most sensitive phenotype)
- TI: Teratogenic index
- Phenotypic Toxicity Profile: Number of teratogenic phenotypes (out of 17) observed per compound, providing insight into teratogenic severity.
Figure 1. Concentration-effect curves for teratogenicity (light blue) and mortality (dark blue) at 120 hpf after exposure of embryos to a toxic compound.
Figure 2. Phenotypical panel: examples of developmental defects in embryos exposed to different toxic compounds.
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References
- Jarque S, Rubio-Brotons M, Ibarra J, Ordoñez V, Dyballa S, Miñana R, Terriente J. 2020. Morphometric analysis of developing zebrafish embryos allows predicting teratogenicity modes of action in higher vertebrates. Reprod Toxicol. 96:337–348.