- Developmental toxicology encompasses the study of pharmacokinetics, mechanisms, pathogenesis, and outcome 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.
Successful pregnancy outcome in the general population occurs at a surprisingly low frequency. Estimates of adverse outcomes include postimplantation pregnancy loss, 31 percent; major birth defects, 2 to 3 percent at birth and increasing to 6 to 7 percent at 1 year as more manifestations are diagnosed; minor birth defects, 14 percent; low birth weight, 7 percent; infant mortality (prior to 1 year of age), 1.4 percent; and abnormal neurologic function, 16 to 17 percent. 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 10–1 Human developmental toxicants. ||Download (.pdf)
Table 10–1 Human developmental toxicants.
- Atomic fallout
- Herpes simplex virus I and II
- Parvovirus B-19 (erythema infectiosum)
- Rubella virus
- Varicella virus
- Venezuelan equine encephalitis virus
Maternal trauma and metabolic imbalances
- Amniocentesis, early
- Chorionic villus sampling (before day 60)
- Folic acid deficiency
- Rheumatic disease and congenital heart block
- Sjogren's syndrome
- Virilizing tumors
Drugs and chemicals
- Androgenic hormones
- Angiotensin converting enzyme inhibitors: captopril, enalapril
- Angiotensin receptor antagonists: sartans
- Anticonvulsants: diphenylhydantoin, trimethadione, valproic acid, carbamazepine
- Carbon monoxide
- Ethylene oxide
- Folate antagonists: aminopterin, methotrexate
- Mercury, organic
- Methylene blue
- Quinine (high dose)
- Retinoids: accutane, isotretinoin, etretinate, acitretin
- Tobacco smoke
- Vitamin A (high dose)
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 animals at therapeutic exposure levels.
As a result of this catastrophe, regulatory agencies developed requirements for evaluating the effects of drugs on pregnancy outcomes.
Diethylstilbestrol (DES) is a synthetic nonsteroidal estrogen ...