Reproductive toxicity testing involves the study of the fertility effects of the candidate drug and its teratogenic and mutagenic toxicity. The FDA uses a 5-level descriptive scale to summarize information regarding the safety of drugs in pregnancy (Table 5–1). Teratogenesis can be defined as the induction of developmental defects in the somatic tissues of the fetus (eg, by exposure of the fetus to a chemical, infection, or radiation). Teratogenesis is studied by treating pregnant female animals of at least 2 species at selected times during early pregnancy when organogenesis is known to take place and by later examining the fetuses or neonates for abnormalities. Examples of drugs known to have teratogenic effects include thalidomide, isotretinoin, valproic acid, ethanol, glucocorticoids, warfarin, lithium, and androgens. Mutagenesis is induction of changes in the genetic material of animals of any age and therefore induction of heritable abnormalities. The Ames test, the standard in vitro test for mutagenicity, uses a special strain of salmonella bacteria that naturally depends on specific nutrients in the culture medium. Loss of this dependence as a result of exposure to the test drug signals a mutation. Many carcinogens (eg, aflatoxin, cancer chemotherapeutic drugs, and other agents that bind to DNA) have mutagenic effects and test positive in the Ames test. The dominant lethal test is an in vivo mutagenicity test carried out in mice. Male animals are exposed to the test substance before mating. Abnormalities in the results of subsequent mating (eg, loss of embryos, deformed fetuses) signal a mutation in the male's germ cells.