Teratology Study Guidelines: An Overview.

Developmental toxicology is a constantly evolving research field which needs to attend to a complex underlying regulatory network. Before entering the market new substances have to be tested for toxic effects on reproduction and development in order to ensure human health and environmental safety. Traditional in vivo mammalian models represent more adequately the intricacy of human development and provide an assessment of the interaction of chemicals on the reproductive system. However, in the last years, the main goal is to reduce the use of vertebrate animals, using those only as last resort. Consequently, the interest in the development and validation of a battery of alternative tests able to cover the various aspects of the reproductive cycle has increased. Reproductive toxicity is probably the most difficult endpoint to be replaced by alternative assays, since it should provide information on mechanisms interactions essential for female and male fertility, and also knowledge on the development of a new human being during its prenatal life. This complexity explains the slow progress in implementing alternatives for reproductive toxicity safety assessments. Alternative test methods may be based on in vitro systems and non-mammalian animal models. Many biological processes have been successfully implemented using in vitro models, opening the possibility to study the interference of teratogenic compounds using these models. Their validation and implementation have lagged behind, in part because of difficulties in establishing their predictability. Nevertheless, the advance toward the process of validation is crucial for a strategy aiming to replace and reduce the use of living animals. Based on the present state of the art, it is not probable that such testing strategies will completely replace the need to assess reproductive toxicity in vivo in the near future, but they contribute to reduce the animal testing and provide important information. In this chapter the approved guidelines for standard methods and alternative methods according to their regulatory and scientific status are enumerated and described.