Embryotoxicity

Embryotoxicity is the adverse effect of a substance on an embryo that can impair viability or development, potentially leading to miscarriage, fetal death, growth restriction, or congenital malformations. It is a component of developmental toxicity and is distinguished from general adult toxicity or postnatal toxicity. Embryotoxic effects are highly dependent on timing during gestation and the level of exposure.

Causes include chemicals, pharmaceutical agents, radiation, infectious agents, and environmental toxins. Mechanisms involve disruption of cell proliferation and differentiation, interference with signaling pathways essential for organ formation, oxidative stress and DNA damage, induction of apoptosis, and epigenetic changes. Susceptibility varies with gestational stage, species, and genetic background.

Assessment typically relies on animal studies that monitor resorption, fetal viability, growth, and malformations, as well as in vitro approaches such as embryonic stem cell tests and embryo culture models. Regulatory frameworks, including OECD developmental and reproductive toxicity guidelines, require evaluation of embryotoxic risk for drugs and chemicals, with precautionary labeling and exposure limits during pregnancy.

Classic examples of embryotoxic agents include thalidomide, isotretinoin, methotrexate, and high levels of alcohol. Risk depends on dose, timing of exposure during organogenesis, and differences between species and individuals. Understanding embryotoxicity informs risk management in drug development, environmental health, and occupational safety.