Teratogenicity
The potential of a substance to cause birth defects when administered during pregnancy. Teratogenicity studies in animals assess structural abnormalities in offspring. GnRH agonists and antagonists, for example, carry pregnancy contraindications due to their effects on reproductive hormones.
Technical Context
Teratogenicity assessment uses animal models: typically rats (representing rodents) and rabbits (representing non-rodents, particularly sensitive to some teratogens). Dosing during the organogenesis window (days 6-17 in rats, days 6-18 in rabbits) identifies structural malformations. Endpoints include: external malformations (limb defects, neural tube defects), visceral abnormalities (cardiac, urogenital), skeletal abnormalities (vertebral, rib, sternal), and developmental variations (delayed ossification). For peptide drugs, teratogenic risk may relate to: direct embryotoxicity, disruption of growth factor signalling essential for development, or hormonal effects that alter the uterine environment. The thalidomide tragedy established the requirement for thorough reproductive toxicity testing before drugs are used in women of childbearing potential. Modern developmental toxicity testing follows ICH S5(R3) guidelines.