Test methods for respiratory sensitization

Abstract

The increasing awareness of the potential of chemicals capable of inducing allergic respiratory hypersensitivity has resulted in attempts to develop test models that can be used to evaluate this endpoint (Botham et al., 1988; Griffiths-Johnson and Karol, 1991; Thorne and Karol, 1988; Karol et al., 1985, 1989; Karol and Thorne, 1988; Karol, 1988). To date, practically all such models have relied upon the use of the guinea pig, a species known to be sensitive for agents inducing bronchoconstriction and in which respiratory fonction and respiratory hypersensitivity can be measured readily. 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. Respiratory hypersensitivity is characterized by a specific allergic hyperresponsiveness as well as increased non-specific airway hyperresponsiveness. Both responses may be clinically indistinguishable. Experimental and clinical studies have intimated that there is reason to suspect that acute exposure to brief high-level concentrations of asthmagenic chemicals and the development of increased airway hyperresponsiveness are associated.