Toxicology of Industrial Compounds

method- ological approaches. In toxicology, the guinea-pig has been used
for decades in order to evaluate the skin sensitizing properties of chemicals
and proteins and has also been able to reproduce immediate-onset
pulmonary hypersensitivity responses following inhalation of chemical
haptens, their protein-conjugates or antigens. This animal model has
therefore been used to disclose principles governing both the development
of pulmonary hypersensitivity and airway hyperreactivity. Due to the
guinea-pig’s abundant amount of smooth bronchial musculature, it is used
as a physiologic elicitation model that reproduces bronchospasm upon
challenge to specific or nonspecific stimuli. Other animal models designed
to display many of the chronic features of hypersensitivity lung diseases
characteristic of occupational asthma focus more on the induction of
airway inflammation, the basic prerequisite for airway hyperreactivity. It
should be noted, however, that the induction of asthma in the rat model,
for example, commonly requires more aggressive protocols and more
elaborate techniques to classify responses when compared with the guineapig
elicitation model (vide infra).
The guinea-pig model
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To date, practically all such models have relied upon the use of the guineapig,
a species known to be sensitive for agents inducing
bronchoconstriction and in which respiratory function and respiratory
hypersensitivity can be measured readily. In addition, guinea-pigs are easy
to handle, relatively inexpensive, and produce consistent
bronchoconstrictive reactions. The models have utilized various modes of
hapten or antigen administration and methods for detecting sensitization,
It has been shown that guinea-pigs sensitized by inhalation exposure to
either a free or a protein-bound chemical can be induced to exhibit changes
in respiratory patterns following inhalation challenge with the same
chemical in the free or in the form of its hapten-protein conjugate. In the
guinea-pig no adjuvant is needed for successful lung sensitization. More
recently it has been found that changes in sensitive respiratory parameters
can also be provoked in dermally sensitized guinea-pigs by inhalation
challenge with the free chemical or the hapten-protein conjugate (Botham et
al., 1988; Pauluhn and Eben, 1991; Hayes et al., 1992). In attempting to
derive an animal model that permits the identification of asthmagenic lowmolecularweight
chemicals without the presence of overriding effects
caused by toxic (irritant) airway inflammation the intradermal route of
induction appears to be preferable. This route of induction also minimizes
the risk of potential confounding effects attributable to irritant-induced
nonspecific reactive airways dysfunction as a result of previous inhalation
exposures (Briatico-Vangosa et al., 1993).