Page 307 - Industrial Ventilation Design Guidebook

5.3 TOXICITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS 263

of urinary elimination of ethylenethiourea (Fig. 5.336). Figure 5.33<z shows that
the urinary elimination of ethylenethiourea has several elimination phases due
to the distribution of the compound in different body compartments.

5.33 Kinetics of Chemical Compounds
The kinetic properties of chemical compounds include their absorption arid distri-
bution in the body, their biotransformation to more soluble forms through meta-
bolic processes in the liver and other metabolic organs, and the excretion of the
metabolites in the urine, the bile, the exhaled air, and in the saliva. An important
issue in toxicokinetics deals with the formation of reactive toxic intermediates
during phase I metabolic reactions (see Section 5.3.3).
5.3.3.1 Absorption
As stated earlier, inhalation is the main route of absorption for occupa-
tional exposure to chemicals. Absorption of gaseous substances depends on
solubility in blood and tissues (as presented in Sections 2.3.3-2.3.5), blood
flow, and pulmonary ventilation. Particle size has an important influence on
the absorption of aerosols (see Sections 2.3.7 and 3.1,1).
Absorption via the skin depends on the lipid- and water-solubility of the
compound, its polarity, and the molecular size. Dermal absorption is also
52 54 65 67
markedly affected by the size of the exposed skin area. ' ' '
Chemicals have to pass through either the skin or mucous membranes lining
the respiratory airways and gastrointestinal tract to enter the circulation and
reach their site of action. This process is called absorption. Different mechanisms
of entry into the body also greatly affect the absorption of a compound. Passive
57
diffusion is the most important transfer mechanism. According to Pick's law,
diffusion velocity v depends on the diffusion constant (D), the surface area of the
membrane (A), concentration difference across the membrane (Ac), and thickness
of the membrane (L)

The diffusion constant depends on the lipid solubility, molecular weight, and
structure of the substance. Lipid-soluble compounds with a molecular weight less
than about 500 diffuse readily through the membranes. Polar compounds are
poorly absorbed. However, active transport systems play a major role in the ab-
sorption of a number of amino acids, sugars, ions, and other nutrients. The blood-
brain barrier, a functional structure that protects the central nervous system (CNS)
against foreign substances, prevents the entry of most compounds in to the CNS.
In fact, only lipid-soluble compounds, and polar compounds which have an active
transport mechanism, can readily enter the CNS. Examples of such polar com-
pounds include amino acids and sugars. Active transport also plays an important
role in the testicles, which are protected by a testicular-blood barrier which has a.
57 68
role similar to the blood-brain barrier. ' Figure 5.34^ shows how mevinphos, a
greenhouse organophosphorus insecticide which mainly gains access to the body
via the skin, is absorbed. Figure 534b shows that exposure through lungs was neg-
ligible, because there was an excellent correlation between mevinphos on the foli-
age, the source of the compound, and mevinphos level on the skin. 54