The thalidomide epidemic dispelled the complacent belief that the placenta is an impenetrable barrier protecting the foetus against all toxicants within a mother’s blood. In subsequent decades, knowledge of the risks accompanying exposure to developmental toxicants increased substantially. According to long-standing observations, substances that harm the unborn typically produce a combination of three toxic outcomes, namely, growth retardation, embryolethality and congenital abnormalities. Study of affected offspring revealed the influence of the precise timing of toxicant administration, with ‘windows of prenatal susceptibility’ identified for many developmental toxicants. While knowledge of the molecular basis for prenatal toxicity in animals has advanced significantly, extending these findings to humans is rarely straightforward. This chapter explores basic principles that apply during study of chemically induced birth defects, with particular focus on the mechanisms underlying the prenatal toxicity of drugs such as thalidomide and valproate as well as workplace toxicants such as cadmium and organic solvents.
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