PEDIATRICS Vol. 53 No. 5 May 1974, pp. 807-812
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Chemicals in Human Teratogenesis and Transplacental Carcinogenesis

Joseph F. Fraumeni Jr. M.D.1

1 Epidemiology Branch, National Cancer Institute, Bethesda, Maryland

It is estimated that about 2% to 3% of all congenital malformations in man can be attributed to drugs or other chemicals in the environment.1 Cancers may also result from chemical exposures prenatally, since stilbestrol therapy in pregnant women has been linked recently to the development of vaginal cancer in their daughters.2 This paper briefly reviews the current evidence in man implicating chemical agents in teratogenesis and transplacental carcinogenesis.

TERATOGENS

Generally, the chemicals that have been implicated as teratogens in man have been drugs, except for pollutants such as organic mercury and polychlorinated biphenyls. Some agents are clearly teratogenic on clinical or epidemiologic grounds, while others show only a preliminary indication of hazard. Table I lists the agents which are or may be teratogenic, according to their apparent effects on the fetus.3 The precise mechanisms for most agents remain to be clarified, but some agents seem to produce direct fetal toxicity, while others interfere with fetal metabolism. In animal models, some compounds are teratogenic by actions on the placenta or on the mother or father, but such mechanisms have not been identified in man. Table I also records the particular defects associated with each agent, in view of the tendency for teratogens to produce characteristic patterns of malformation.

Well-Documented Teratogens

Thalidomide, first identified as a teratogen in the early 1960s, is believed to be responsible for the deformities of 6,000 to 8,000 children.4 The malformations characteristically involved the extremities, face, and ether organs. Particularly striking were cases of phocomelia (seal limbs), usually a rare condition, in which hands are attached directly to the shoulders.