Alternative methods to animal experimentation for testing developmental toxicity

Abstract

The available alternative methods for testing developmental toxicity comprise either cellular models or whole embryos of rodents, fish, or amphibian. The simplest cellular models consider the use of human or animal embryonic stem cells (embryonic or of induced pluripotency) under differentiation and one of the most widely used endpoints in these methods is the alterations in differentiated beating cardiomyocytes, although determination of other molecular markers is also extended. More complex cellular models consider the use of cocultures or 3D cultures or the so-called organoids. These models mimic the physiological environment in a much better way than the simple monolayer cultures. The use of whole embryos allows the determination of which teratogenic effects are expectable after exposure to developmental toxicants, which is one of the main disadvantages of the cellular methods. The appropriate assessment of chemical safety for development needs of a battery of alternative methods applied. Integrated Approaches to Testing and Assessment (IATA) would allow in the close future to perform safe and reliable assessment of developmental toxicity based on alternative methods.