Applications of zebrafish embryo models to predict developmental toxicity for agrochemical product development

Development of safe crop protection products is a complex process that traditionally relies on intensive animal use for hazard identification. Methods that capture toxicity at early stages of agrochemical discovery programs enable a more efficient and sustainable product development pipeline. Here we have explored whether the zebrafish model can be leveraged to identify mammalian-relevant toxicity. We used transgenic zebrafish to assess developmental toxicity following exposures to known mammalian teratogens, and captured larval morphological malformations, including bone and vascular perturbations. We further applied toxicogenomics to identify common biomarker signatures of teratogen exposure. The results show that the larval malformation assay predicted teratogenicity with 82.35% accuracy, 87.50% specificity, and 77.78% sensitivity. Slightly lower accuracy was obtained with the vascular and bone assays. A set of 20 biomarkers were identified that efficiently segregated teratogenic chemicals from non-teratogens. In conclusion, zebrafish are valuable, robust, and cost-effective models for toxicity testing at early stages of product development. RNAseq transcriptomics profiling on zebrafish embryos after treatments with a set of agrochemicals, with known developmental toxicity endpoints, at multiple doses