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5,3 TOXICITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS 267

volume of distribution in practice, it provides valuable information on the char-
acteristics of the compound, that can be used in a number of pharmaco/toxico-
62 68
kinetic models. '
Special Considerations
Chemical compounds may also be distributed to the placenta and through
the placenta to the fetus and thereby cause exposure of the offspring. Even
though the placenta! wall consists of several layers, it is a biological mem-
brane, and the same principles apply to the placenta as to any other biological
membrane, i.e., penetration depends on lipid-solubility and ionization of
chemical compounds. However, the concentrations of lipid-soluble com-
pounds increase slowly in the fetus, because it is a separate body compart-
ment, and redistribution with this compartment is a time-consuming process.
However, an equilibrium will be reached between the mother and the fetus
during long-term exposure. This is the main reason chemical exposure during
pregnancy is strictly controlled in most developed countries.
5.3.3.3 Biotransformation
The purpose of metabolism or biotransformation of xenobiotics (foreign
compounds) is to transform them into a water-soluble form so that they can
be excreted either in the urine or in the bile. These processes are catalyzed by a
number of enzymes. Biotransformation reactions are divided into phase I and
phase II reactions: in phase I reactions, functional groups, such as the hy-
droxyl group, are linked to the xenobiotic (Fig. 5.37). This is why phase I re-
actions are also called functionalization reactions. In phase II, the functional
group is conjugated with one of several chemical compounds in the body, e.g.,
glucuronic acid, glutathione, sulfates, glycine, or methionine. Most xenobiot-
ics undergo both phase I and phase II reactions, but some compounds undergo
only one of the phases. It is noteworthy that rarely will all of the absorbed

FIGURE 5.37 Janus faces of the biotransformation of xenobiotics. On one hand metabolism leads
to inactivation and elimination of xenobiotics, but on the other hand many metabolites are reactive and
may cause deleterious effects by binding to DNA, proteins, and other macromoiecules.