Page 364 - Industrial Ventilation Design Guidebook

320 CHAPTER 5 PHYSIOLOGICAL AND TOXICOLOGICAL CONSIDERATIONS

induce typical and very specific mutations in the p53 tumor suppressor gene.
One example is the aflatoxin-induced mutation in codon 249 in the p53
191
gene. In contrast, benzo(a)pyrene, present in tobacco smoke, does not bind
to this codon, but does bind to other areas of the gene, so-called hot spots. Ex-
posure to UV light also seems to induce typical and specific mutations in
thep53 gene. In addition, there are other typical mutations of the p53 gene that
seem to be associated with cancer that are induced by environmental or occu-
pational chemical carcinogens. 190
Transplacental Carcinogenesis
Transplacental carcinogenesis indicates that exposure of the mother dur-
ing pregnancy may induce cancer in the child as it grows. In animals, more
than 50 transplacental carcinogens have been found, but in humans only one
such compound has been identified, diethylstilbesterol, a synthetic estrogen
that was used to prevent spontaneous abortions. However, there is data to
suggest that several chemical compounds that are important in the occupa-
tional environment may also mediate their effect transplacentally. Such com-
pounds include polycyclic aromatic hydrocarbons, nitrosoamines, hydrazines,
and isoniazide. Thus, exposure to these compounds should be strictly con-
trolled due to the potential hazard they pose to the developing fetus. 5

5.3.5 Exposure Assessment
Workers' exposure levels can be estimated either by occupational hygiene
sampling or by biological monitoring. Since inhalation is usually the most im-
portant exposure route, occupational hygiene surveys generally include the
measurements of airborne concentrations of many impurities in workroom
air. However, dermal exposure is also important for many substances. It can
be assessed by analyzing hand-wash and patch samples. In biological monitor-
ing, the concentration of a substance or its metabolite is determined from bio-
logical samples. Urine, blood, and exhaled air are the most common biological
samples. Furthermore, molecular dosimetry, or target-dose monitoring, usu-
ally based on the analysis of DNA or protein adducts in lymphocytes or hemo-
globin adducts in erythrocytes in exposed individuals, has become popular
and holds great promise in the assessment of the association between exposure
and the effects of carcinogens.
5.3.5.1 Determination of Airborne Concentrations
Major time variation is typical for occupational inhalation exposure. It
is not unusual if a worker's daily average exposure levels varies by a factor
of ten within a single week. The concentration distribution is usually close
to lognormal (the logarithms of concentrations are distributed normally).
In fact, the distribution may be slightly skewed so that its right side is less
steep than its left. The concentration distributions can be characterized by
their geometric mean (m g) and geometric standard deviation (s g). However,
the geometric mean should never be used to describe exposure because the
exposure dose depends on the arithmetic mean. The geometric standard
deviation is typically 1.5-2.5. In industries with continuous processes, s e