Mechanism-based models in reproductive and developmental toxicology

Abstract

This chapter discusses the study of the currently available models for testing developmental toxicity (embryotoxicity and teratogenicity). The main alternative models for testing developmental toxicity are described. These models are divided between validated models (whole-embryo culture test (WEC), micromass test (MM) and embryonic stem cell test (EST)) and those that are not currently validated (although have proven scientific validity) as is the case of zebrafish, frog embryo teratogenesis assay (FETAX), in silico models for predicting embryotoxicity, in vitro cellular models different from the EST method, and methods using fragments of embryos. The non-validated alternative models for testing developmental toxicity are also explained here. To date, only three in vitro methods (MM, EST and WEC) have been validated by an international agency (ECVAM) in order to be used for testing the embryotoxicity potential of chemicals, although other models such as FETAX and zebrafish have also proved their validity for this purpose. Methods based on the employment of embryos allow the specific malformation expected after exposure to the chemical to be determined, while methods based on cellular systems are more relevant in order to determine the mechanism underlying the adverse observed effect and still display a wide field for improving their prediction capability.