Page 315 - Industrial Ventilation Design Guidebook

5.3 TOXICITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS 27 1

Asbestos fibers

j^^^^^^^^^^^r Inflammatory cells
Mesothelium ^T~~~ —-—-__ Cytokines
i ^x'xT^-^ Reactive oxygen species
* N/^X^/^fck. Stimulation of cell
looted cytoplasmic I \\nroliferatio n
division N. ^x^
I N. Lipid peroxidation
\ \, \
Binucleate cells \ ^^ ^^

\ DNA damage
Aneuploidy X ^~~
I Cytoskeletal changes
* I T
Altered gene expression 1 Altered gene expression
^V\ - *^7?
\\ ^^^ Decreased intercellular S/
\ \ adhesion >/ /
\\ * //
\ Decreased GJIC /
\ * /
CELL TRANSFORMATION

FIGURE 5.39 Possible pathways in fiber carcinogenesis. The figure is based on review articles by
76
1992 and Kamp et al. 1992, and original publications by Marsh and Mossman 1991, Heintz et al.
1993, Kodama et al. 1993, Kinnula et al. I994b, as well as the results presented in studies II and V. The
connection between disrupted cytoplasmic division, cytoskeletal changes, and decreased intercellular
adhesion has not been studied in relation to fibers. The pathway is based on articles dealing with link-
78 80
age between cadherins, catenins, and cytoskeleton, as well as their role in cell transformation. " The
connection between decreased cell-cell adhesion and decreased GJIC has been reported by Musil et
82
8i
af. and Meyer et al., and the role of GJIC in cell transformation has been reviewed by Yamasaki, 83
(modified from Pelin). 84
a single intravenous injection. If the kinetic data obtained yield a straight line
when plotted as the logarithm of plasma concentrations versus time, the ki-
netics of the compound can be described by a one-compartment model, in
which the whole body is treated as one single space or compartment. Even
though the one-compartment model is an extreme simplification of the or-
ganism in the physiological and toxicological sense, the behavior of several
chemical compounds can be well described and understood by using this
model. Usually, only the kinetics of compounds that are rapidly distributed in
the body can be described with the one-compartment model. As described be-
low (Fig. 5.40), the theoretical concentration C 0 can then be calculated.
The rate of elimination of a chemical compound from the body is usu-
ally proportional to the amount of the chemical in the body. Elimination
processes include biotransformation, exhalation, and excretion in the
urine, bile, saliva, and sweat, and even in the hair and nails. The first-order