Skip to Main Content

++

KEY POINTS

++

  • Developmental toxicology encompasses the study of pharmacokinetics, mechanisms, pathogenesis, and outcomes following exposure to agents or conditions leading to abnormal development.

  • Developmental toxicology includes teratology, or the study of structural birth defects.

  • Gametogenesis is the process of forming the haploid germ cells: the egg and the sperm.

  • Organogenesis is the period during which most bodily structures are established. This period of heightened susceptibility to malformations extends from the third to the eighth week of gestation in humans.

++

SCOPE OF PROBLEM—THE HUMAN EXPERIENCE

++

Successful pregnancy outcome in the general population occurs at a surprisingly low frequency. Estimates of adverse outcomes include postimplantation pregnancy loss, 31%; major birth defects, 2% to 3% at birth and increasing to 6% to 7% at 1 year as more manifestations are diagnosed; minor birth defects, 14%; low birth weight, 7%; infant mortality (prior to 1 year of age), 1.4%; and abnormal neurologic function, 16% to 17%. Thus, less than half of all human conceptions result in the birth of a completely normal, healthy infant. Many hundreds of chemicals are teratogens; most of them produce birth defects by an unknown mechanism. However, Table 10–1 lists chemicals, chemical classes, or conditions known to alter prenatal development in humans.

++
Table Graphic Jump Location
TABLE 10–1

Human developmental toxicants.

++

Thalidomide

++

In 1960, a large increase in newborns with rare limb malformations of amelia (absence of the limbs) or various degrees of phocomelia (reduction of the long bones of the limbs) was recorded in West Germany. Congenital heart disease; ocular, intestinal, and renal anomalies; and malformations of the external and inner ears were also involved. Thalidomide, identified as the causative agent, was used throughout much of the world as a sleep aid and to ameliorate nausea and vomiting in pregnancy. It had no apparent toxicity or addictive properties in adult humans or rodents at therapeutic exposure levels.

++

As a result of this catastrophe, regulatory agencies developed requirements for evaluating the effects of drugs on pregnancy outcomes.

++

Diethylstilbestrol

++...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.