Page 327 - Industrial Ventilation Design Guidebook

5.3 TOXICITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS 283

is an essential energy source of the cells. Cellular energy metabolism can be pre-
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vented by inducing anoxia, for example, by exposure to carbon monoxide.
Carbon monoxide reacts with hemoglobin and forms carboxyhemoglobin,
which is unable to bind oxygen. Nitrite-induced oxidation of heme iron causes
formation of methemoglobin from hemoglobin. An increased amount of methe-
moglobin also prevents oxidation of cells and tissues because methemoglobin
does not bind oxygen. However, the treatment of methemoglobinemia is much
easier than the treatment of CO-induced carboxyhemoglobinemia. In fact, in-
duction of slight methemoglobinemia with nitrite can be used as an antidote in
cyanide poisonings, because the ferric (trivalent iron) form present in methemo-
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globin acts as a sink by binding free cyanide.
Cyanide, hydrogen sulfide, and azides prevent cells and tissues from utiliz-
ing oxygen by binding to cytochrome oxidase and thereby preventing mito-
chondria! energy production. The release of hydrogen cyanide may take place
if cyanides make contact with acids, and, for example, sewage workers may be
exposed to hydrogen sulfide if anaerobic conditions occur. Formation of hy-
drogen sulfide also takes place in many industries. This gas is insidious be-
cause its very unpleasant odor virtually disappears at high concentrations. 109
The inhibition of ATP formation can also take place through other mecha-
nisms. Dinitrophenol (a herbicide) blocks the citric acid cycle by uncoupling it
from mitochondrial oxidative metabolism. Fluoro-aceticacid, in turn, blocks
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the citric acid cycle by inhibiting several key enzymes in the cycle. '" '
Depletion of ATP in the cells prevents maintenance of the membrane po-
tential, inhibits the functioning of ion pumps, and attenuates cellular signal
transduction (e.g., formation of second messengers such as inositol phos-
phates or cyclic AMP). A marked ATP depletion ultimately impairs the activ-
ity of the cell and leads to cell death.

Disturbances in Cellular Calcium Metabolism
As stated above, calcium is an extremely important cellular ion for several
cellular functions. The concentration of calcium in human extracellular fluid
is about 2.5 mM, while the intracellular concentration is only 100-200 nM
depending on the cell type. Thus, there is 10 000-20 000 fold concentration
difference between the cell interior and exterior that has to be maintained by
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cellular pumping mechanisms. This requires a large amount of energy. ' '
The behavior of calcium in the cells can be considered as a metabolic pro-
cess. There is uptake, distribution, and excretion of calcium in the cells. The
uptake of calcium occurs via activation of calcium channels. The end result is
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elevation of intracellular calcium levels and subsequent activation. ' ' Be-
cause calcium is a powerful cell-activating ion, increased calcium levels in the
cell have to be controlled carefully. There are a number of calcium pumps that
are responsible for pumping of calcium out of the cells. This again requires a
large amount of energy. 115

Nitric Oxide
Nitric oxide (NO) is a gaseous cellular messenger that transmits informa-
tion between cells and within cells. In spite of its physiological role, NO is also a
reactive species which is capable of reacting with biological molecules, and