Page 370 - Industrial Ventilation Design Guidebook

5.3 TOXiCITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS 325

Biological monitoring provides integrated information on exposure via all
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routes, including dermal and oral routes. It also includes exposure that takes
place outside the workplace. These are benefits in individual risk assessment;
on the other hand, they can also be considered disadvantages in occupational
health because its aim is to provide safe working conditions for everybody, ir-
respective of individual characteristics. Biological monitoring can also be used
to ascertain effectiveness of personal protective equipment. It also has inherent
benefits for substances with long half-lives. The accumulation of substances
with very long biological half-lives, such as cadmium, is suitable for biological
monitoring because a single sample can provide valuable information pro-
vided that a steady-state situation in the body has been reached. In addition,
the variation of exposure with time will be attenuated for biological indicators
with long half-lives. Therefore, fewer biological monitoring samples are
needed for long-term exposure assessment than with conventional occupa-
tional hygiene monitoring. However, even this advantage is occasionally ne-
gated by the large individual variability typical of biological indicators.
Biological monitoring has several other limitations, in addition to those
presented above. Biological monitoring is not suitable for agents which do not
need to enter blood, such as irritating gases and many dusts. Neither is it very
useful for substances with high acute toxicity (in fact occupational hygiene
surveys are not very practical in such cases, but the working area should be
provided with some kind of continuous monitoring equipped with an auto-
matic alarm system). Another limitation is the small number of compounds
for which there are biological exposure limits or indices (BEI) compared to
those for occupational exposure limits (only ca. 10%). However, it should be
noted that biological monitoring of exposure to a certain agent is often useful
even if no BEI has been established for it. Biological monitoring is especially
beneficial for substances with significant skin penetration. Urine sampling
may well represent the most convenient means for exposure trend analysis. 196
Blood sampling may be slightly more difficult due to the analytical procedures
and unpleasantness of blood sampling. The main limitation is, however, that
biological monitoring as such does not provide any information on the causes
of exposure. New technologies have become available in which cell samples
can be collected, e.g., from the oral cavity, and possible protein or DNA ad-
ducts (reaction products between a reactive compound and proteins or DNA)
can be quantitated, e.g., with high-pressure-liquid-chromatography. Examples
of such compounds are formaldehyde and isocyanates.

5.3.5.3 Biomarkers
Extensive research is currently underway to use biological markers (biomarkers)
in exposure and risk assessment. Biomarkers include the reaction products of chemi-
cals or their metabolic products with biological macromolecules, especially with
DNA. They also involve indicators of effect, such as chromosomal damage, and indi-
cators of individual genetic susceptibility.
Formation of DNA adducts has been demonstrated for many carcinogens.
DNA bases are nucleophilic and react with electrophilic compounds. Guanine
seems to be especially reactive. Several studies have described how adduct formation
can increase with exposure. However, the individual variability is larger than with
conventional biological monitoring. Very high interindividual variation has been