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5.3 TOXICITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS 275

system that may become saturated follows zero-order kinetics. As the concentra-
tion of a chemical compound decreases to below the concentration at which the
enzyme becomes saturated, it changes to first-order kinetics.
From a practical point of view, saturation of elimination has important
consequences. If the metabolism becomes saturated, the duration of the ac-
tion of the compound is prolonged. In such a case, correct timing for collec-
tion of biological monitoring samples also becomes difficult to assess,
Furthermore, saturation of metabolism may also have qualitative effects. For
example, it has been argued (but not yet proved} that arsenic compounds
cause cancer at high doses at which methylation of inorganic arsenic be-
comes saturated. 68

Physiologically Based Toxicokinetic Models
Physiologically based toxicokinetic models are nowadays used increasingly
for toxicological risk assessment. These models are based on human physiol-
ogy, and thus take into consideration the actual toxicokinetic processes more
accurately than the one- or two-compartment models. In these models, all of
the relevant information regarding absorption, distribution, biotransformation,
and elimination of a compound is utilized. The principles of physiologically
based pharmaco/ toxicokinetic models are depicted in Fig. 5.41a and b. The

FIGURE 5.41 (continued]