Alternative Developmental Toxicity Screening Methods Using Chick Embryo-Based Models

Nonclinical developmental toxicity studies are used to investigate the potential toxicities of drugs and chemical candidates on normal embryonic and fetal development during pregnancy, generally using mammalian laboratory animals such as rats and rabbits. Despite being well-established, these models have ethical concerns, high costs, and long study durations. Consequently, alternative models, including in vitro human cell cultures, stem cell differentiation, 3D organoids, and zebrafish, are actively being studied; however, they have limitations in replicating whole-body physiological complexity and homeostasis. Therefore, this study reviewed the use of chick embryo-based models in developmental toxicity screening to overcome the limitations of other alternative models. Notably, chick embryos have been already utilized in cardiovascular development, cancer, and vaccine development. This study provides an overview of the advantages of chick embryo-based models, including developmental relevance, cost-effectiveness, and ethical alleviation, along with their limitations and future directions. Our review suggests that chick embryo-based models can complement current mammalian laboratory animal-based models and bridge the gap between in vitro and in vivo systems. However, continued research toward standardization of protocols, validation of methods, and technological integration is required to position chick embryo-based models as a more practical and efficient model for nonclinical developmental toxicity studies.