Teratogens are those chemicals that lead to structural and/or functional birth defects. The effects of teratogenic compounds are time dependent as well as dose dependent. Time dependency is a function of the differences in development of particular organs and systems during pregnancy. The original definition of teratogens was narrow and referred to those chemicals, drugs, and diseases that led to structural and functional abnormalities observed in early life. The classic therapeutic human teratogen is thalidomide. This drug, a sedative developed in the late 1950s and early 1960s, induced serious birth defects in babies whose mothers had taken the drug during the critical period of organogenesis of the limbs (second trimester of pregnancy). The babies were born with several defects, including missing or stumped limbs (phocomelia), cleft palate and lip, and other defects. This abnormality affected over 10,000 babies worldwide and led to the testing of all new drugs (and eventually some pesticides and commodity chemicals) for teratogenic potential. Several maternal diseases, such as German measles, hypothyroidism, and syphilis, to name a few, are teratogenic.
The definition of a teratogen has been expanded as knowledge increases about the mechanism of action of additional chemicals. A broader definition of a teratogen now encompasses defects other than simply structural changes and includes the transplacental carcinogen, diethylstilbestrol.
Of great import are the retinoic acid derivatives, such as 13-cis-retinoic acid, that remain teratogenic years after a woman has taken the drug. This type of teratogen is very difficult to predict from animal studies and the scientific community must rely on mechanistic studies to assess risk.
Since the central nervous system, including the brain, completes development after birth, late pregnancy exposure to many toxicants can have serious adverse effects on the developing nervous system. Many of the heavy metals affect these systems and have been shown to be very teratogenic. The classic example is methylmercury, which induces a multitude of defects, the most devastating of which are those of the central nervous system.
Hence, teratogens are any class of xenobiotics that induce structural or functional changes in offspring when consumed by the mother during or before pregnancy.