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Applications of Zebrafish Embryo Models to Predict Developmental Toxicity for Agrochemical Product Development.

Enrica Bianchi1, Beas Bhattacharya1, Andrew J Bowling1

  • 1Corteva Agriscience, Indianapolis, Indiana 46268, United States.

Journal of Agricultural and Food Chemistry
|August 1, 2024
PubMed
Summary

Zebrafish models effectively identify mammalian developmental toxicity in early agrochemical discovery. This approach offers a robust, cost-effective alternative to traditional animal testing for safer crop protection products.

Keywords:
biomarkerdevelopmental toxicityskeletal toxicityvascular toxicityzebrafish

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Area of Science:

  • Toxicology
  • Developmental Biology
  • Agrochemical Research

Background:

  • Traditional crop protection product development heavily relies on animal testing for hazard identification.
  • Developing safer agrochemicals requires efficient and sustainable methods for early-stage toxicity assessment.
  • Alternative models are needed to reduce animal use and improve product development pipelines.

Purpose of the Study:

  • To evaluate the utility of the zebrafish model for identifying mammalian-relevant developmental toxicity.
  • To assess the accuracy of zebrafish assays in predicting teratogenicity.
  • To identify toxicogenomic biomarkers for teratogen exposure.

Main Methods:

  • Utilized transgenic zebrafish to assess developmental toxicity after exposure to known mammalian teratogens.
  • Monitored larval morphological malformations, including bone and vascular defects.
  • Applied toxicogenomics to detect common biomarker signatures associated with teratogen exposure.

Main Results:

  • The larval malformation assay demonstrated high accuracy (82.35%), specificity (87.50%), and sensitivity (77.78%) in predicting teratogenicity.
  • Vascular and bone assays showed similar predictive capabilities.
  • Identified a panel of 20 biomarkers that effectively distinguished teratogenic from non-teratogenic chemicals.

Conclusions:

  • Zebrafish serve as valuable, robust, and cost-effective models for early-stage toxicity testing in product development.
  • This model aids in the development of safer crop protection products.
  • The findings support the integration of zebrafish toxicity testing into agrochemical discovery programs.