Teratology is the study of birth defects and teratogen refers to a substance that causes birth defects. The word "monster" was originaly a technical term for a child born with a severe birth defect, but did not in any way characterize the child's personality or other attributes. In 1816 Mary Wollstonecraft Shelley wrote the book Frankenstein and used the term "monster" to describe Dr. Frankenstein's creature. Today use of the term "monster" to describe a severe birth defect is still technically correct but avoided because of the negative connotations of the term.
Birth defects are extremely common. To start with, up to 50% of the fertilizations end in spontaneous abortions (miscarriage). Of the live births, 10 to 15% have some recognizable birth defect, although "low birth weight" is considered a defect in those statistics.
The placenta is an organ of the conceptus. You will often hear of the "blood-placental barrier," but like all the other barriers we come across, it is no barrier at all to small water-soluble molecules nor much of a barrier to lipophilic chemicals at all. The steady-state concentrations of most xenobiotics is about the same between fetal blood and maternal blood. There are exceptions, some substances are stopped or slowed by the placenta, on the other hand, some substances are concentrated in the fetus. Another important concept here regards animal testing. The arrangement of the placenta is quite different in different mammalian species, and the effect of the placental barrier on toxicity varies considerably.
A very important concept in teratogenesis is that of timing. During the period of organogenesis, which in the human lasts from day 21 to day 56, the embryo is extremely sensitive. Toxic substances administered during that time may results in severe defects. Later in the gestation, toxic substances are more likely to result in reduced birthweight. Below is from Casarett and Doull's regarding the rat. Note how a teratogenic insult in day 9 might affect the eye or brain, while one in day 12 the palate, day 15 the urogenital system.
Copyright Casarett and Doull's Toxicilogy, 4th ed.
The dilemma.
It is very difficult to test reproductive toxics in animal models. The differing
structure of the placenta relative to primates and the short gestation period
make extrapolation difficult. The easy way for pharmaceutical companies to deal
with this is to place the label "not recommended during pregnancy"
on all products. That's fine, unless a drug is needed for pregnant women. Multi-generational
testing is required in at least three species of lab animals before a drug would
be approved for pregnant women..
Milk and pesticides
Now things get worse. Lipophilic chemicals are stored in the body fat. Persistent
chemicals, such as the chlorinated pesticides, remain in the fat tissue for
years. When a woman is lactating, breast milk contains fat, and this fat provides
a method of excreting the persistent chemicals. Unfortunately, this method of
excretion for the mother is a method of exposure for the infant. For example
in a 1986 study, 19% of lactating women had DDT in the milk and 100% had the
chief metabolite of DDT, known as DDE. Their total varied between 0.2 and 4.3
ppm of milk and 1.2 and 14.7 ppm of the milk fat. These presumably have fallen,
although those numbers were developed 15 years after DDT had been banned in the
US. But DDT and DDE are only two of the hundreds of persistent chlorinated compounds
that are analyzed in human milk.
End of Submodule