Teratogenesis

Birth defects are abnormal developments in embryos that are manifested either structurally or functionally. Teratogenic agents act in a narrow range of doses between no observable effect levels and levels that are lethal to the embryo. Furthermore, they are preferentially induced when the exposure occurs during a narrow time span during gestation, which corresponds to the time when organs are being formed. For humans this is

TABLE 17.2 Teratogenic Substances

Physical agents Agents causing hypoxia Infections

Dietary deficiency or excess

Hormone deficiency or excess Natural toxins Heavy metals Solvents

Pesticides Other

Hypothermia, hyperthermia, hypoxia, radiation Carbon monoxide, carbon dioxide Rubella viruses, syphilis

Vitamins A, D, and E, ascorbic acid, nicotinaminde, Zn, Mn, Mg, Co

Cortisone, insulin, androgens, estrogens Aflatoxin Bi, nicotine

Methyl mercury, lead, thallium, strontium, selenium Benzene, carbon tetrachloride, 1,1-dichloroethane, dimethyl sulfoxide, propylene glycol, xylene Insecticides, herbicides, fungicides Azo dyes, antibiotics, sulfonamides, drugs (caffeine)

approximately from day 26 to day 56 of gestation. The same dosage can cause different birth defects, depending on when during this period the dose is administered. For example, a cleft palate can be caused by exposure on one day, whereas heart defects may be caused on another.

Although teratogenesis is classified here with genotoxic effects, its causes are not well understood, and a number of other mechanisms probably also act. It seems that anything that interferes with cell division can be a teratogen. This includes agents known to block DNA expression, heavy metals such as lead and cadmium that inhibit enzymes, and even substances that simply cause a delay in cell replication.

Other forms of toxicity do not correlate well with teratogenicity. Substances that are teratogenic may not be toxic to the mother, and vice versa. Surprisingly, many mutagens are not teratogens. The sensitivity of the embryo can be decreased if the toxic substance does not easily cross the placental barrier. On the other hand, the embryo may be more sensitive than the mother to some compounds if the compounds act on cell division, since embryos undergo this process at a high rate. Both deficiencies and excesses of some vitamins, such as vitamin A, are teratogenic. Other teratogens are listed in Table 17.2.

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