Sensitivity to teratogens

FIGURE 44-1. Embryonic development. (Reprinted, with permission, from Moore KL, The Developing Human. New York Elsevier, 1874 p 96 copyright 1974.) The horizontal bars represent potential sensitivity to teratogens. The pink areas represent the more critical times. 

Figure 6.23 Periods of peak sensitivity to teratogens in the rat. A teratogen administered at the time shown by the arrow would cause a mixture of malformations. It would particularly damage the eyes and brain but would have little or no effect on the palate. Source. Adapted from Ref. 7.

Figure 13.7 Critical periods graph including embryonic and fetal periods. Note the increased sensitivity to teratogenic events during organogenesis.

The data from the only available animal study (Prigge and Greve 1977) indicate that inhaled lead is not teratogenic. However, it impaired heme synthesis in both rat dams and fetuses. In this study, dams were exposed to 1, 3, or 10 mg lead/m3 (chemical species not provided) throughout gestation (days 1-21). Maternal and fetal ALAD were inhibited at all exposure levels in a dose-related manner, and fetal (but not maternal) hematocrit and body weight were decreased at the 10-mg/m3 lead level. These results suggest that the fetuses were more sensitive to lead-induced toxicity than were the dams. 

Most drugs and chemicals pose a threat to the developing fetus. An estimated 4 to 5% of developmental defects in humans result from prenatal exposure to drugs or environmental chemicals. This is particularly important, since women with irregular menstrual cycles may be exposed to teratogens and enter the sensitive period of organogenesis before pregnancy is suspected. 

Several published studies have demonstrated that minipig fetuses are sensitive to various known teratogens. In an early study with Pitman-Moore miniature pigs, it was found that this type of pig is sensitive to trypan blue, and a single injection on day 10 of... 

Thalidomide was not evaluated as it needs a specific MAS in our FETAX setup, but the Xenopus laevis embryo has been shown to be sensitive to the teratogenic activity of thalidomide, phocomelia being observed after metamorphosis (17). 

In the cases where only dose range-finding studies were performed and gave positive results, the routine external examination of the fetuses was supplemented with a detail fresh internal examination for rabbits, or fixed visceral and/or skeletal examinations for rats. These dose range-finding studies were thus sufficiently sensitive to detect strong teratogens. 

These drugs lower the seizure threshold and this can occasionally result in convulsions. They should be avoided if possible in patients with cardiac disease, and are contraindicated after a recent myocardial infarction. There is no specific evidence of teratogenicity but they should be avoided if possible during pregnancy. Care is required in the elderly as they are more sensitive to the adverse effects, have a lower rate of metabolism and excretion, and are more likely to have concurrent physical disease (e.g. cardiac disease). 

Effects of acute exposure to product Effects of chronic exposure to product Irritancy of the product Sensitization to the product Carcinogenicity Reproductive toxicity Teratogenicity Mutagenicity... 

DOT CLASSIFICATION EXPLOSIVE I.IA Label EXPLOSIVE I.IA SAFETY PROFILE Confirmed carcinogen with experimental carcinogenic, tumorigenic, and teratogenic data. Poison by ingestion, intraperitoneal, and intravenous routes. Moderately toxic by subcutaneous route. Experimental reproductive effects. Human mutation data reported. An explosive sensitive to heat or impact. Flammable when exposed to heat or flame can react vigorously with oxidizing materials. When heated to decomposition it emits very toxic fumes of NO. See also N-NITROSO COMPOUNDS. 

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