Page 355 - Industrial Ventilation Design Guidebook

5.3 TOXICITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS 3 1 1

the acute form) in persons having massive bioaerosol exposure. The symptoms in-
clude fever, cough, shortness of breath, and malaise. Prolonged exposure can re-
sult in lung fibrosis. The disease is common among farmers who handle moldy
hay (the syndrome is also called farmers' lung disease). Trimellitic anhydride is an
12()
example of a reactive chemical causing a type III response.
Type IV reactions differ from the previous hypersensitivity reactions in that
they are not immunoglobulin-mediated, but mediated by T cells. It is probable
that this mechanism is also involved in the pathogenesis of extrinsic alveolar alve-
olitis, especially in the chronic form. Allergic contact dermatitis is the most com-
mon example of this allergy type. Allergic contact dermatitis is caused by
substances with low molecular weights (below 500 Da). The small molecule (e.g.,
Ni and Co), called a haptene, cannot act as an allergen alone, but needs to bind to
certain proteins (la-antigens) on the surface of Langerhans' cells. This combined
hapten and la-antigen forms the allergen. Langerhans' cells then transfer the aller-
gen to the small lymphocytes. This is carried by the lymphatic vessel to the lymph
node where it initiates the production of activated T cells (Thl lymphocytes).
When these encounter their antigens, cytokines are secreted (e.g., interferon y;
IFNy). These activate the inflammatory cells leading to visible eczema usually
within 1-4 days. T memory cells remain viable for a long time (a year or even
162 163
longer), after which the sensitivity disappears. ' The mechanisms underlying
type I-IV allergic reactions have been depicted in a simplified way in Fig. 5.50.
Over 3000 chemicals have been classified as contact allergens. Among them
are some substances (so-called "superallergens") that are so potent that they sensi-
tize most exposed persons possibly on the first contact (e.g., dinitrochloroben-
120
zene). In practice, it would be useful to be able to classify contact allergens
according to their potency. In the Nordic countries, a classification system for
skin-contact allergens resembling the criteria of IARC for the classification of car-
cinogenic substances has been proposed, but it is not yet widely accepted. How-
ever, allergenicity evaluation has become an important part of toxicity testing with
experimental animals. The guinea pig is the most commonly used animal, and the
guinea pig maximation test is probably the most sensitive method for detecting
the sensitizing potential of a compound.
Many irritative chemicals may cause non-specific hyper-responsitivity of the
airways and skin. The number of irritating chemicals is very large, several thou-
sands. The symptoms caused by exposure to irritants may resemble allergic symp-
toms. In addition, exposure to irritating substances (such as sulfur dioxide or
solvent vapors) often triggers the symptoms in individuals with allergic asthma.

5.3.4.5 Chemical Teratogenesis
A teratogen is a chemical compound that induces malformations in the fe-
tus. The term can also be defined to have a wider meaning, that a teratogen is
a compound that can permanently damage the fetus during pregnancy. In the
latter case, teratogens include compounds that induce morphological and/or
functional alterations in the fetus. Brain tissue is especially sensitive to the ef-
fects of chemical compounds, because unlike most other organs, which un-
dergo most of their organogenesic development during the first trimester of
the pregnancy, the brain continues to develop throughout the entire preg-
nancy, and even after birth, the brain continues to develop for a number of
years. 167