Respiratory hypersensitivity in guinea pigs sensitized to 1,6-hexamethylene diisocyanate (HDI): comparison of results obtained with the monomer and homopolymers of HDI.

This study used guinea pigs that were sensitized to the biuret or isocyanurate type homopolymers of 1,6 hexamethylene diisocyanate (HDI). Induction was either by intradermal injection or repeated inhalation exposures. For comparison, groups of guinea pigs were sensitized to monomeric HDI. Naive animals served as negative controls. Two and three weeks following induction, animals were challenged by inhalation with the hapten and homologous protein conjugate of the hapten, respectively. Assessments were based on changes in respiratory rate, serum IgG(1)-antibody titer, and influx of eosinophilic granulocytes in airways. Guinea pigs induced and challenged with the HDI-monomer did not display appreciable changes in respiratory rate, whilst the re-challenge with the HDI-protein conjugate caused unequivocal changes in respiratory patterns, including a marked bronchial influx of eosinophilic granulocytes. In contrast, animals induced and challenged with either the free or conjugated aerosols of HDI-homopolymers failed to elicit specific physiological or morphological pulmonary responses. IgG(1) antibodies were observed in all groups receiving monomeric HDI or HDI-homopolymers. Based on the comparative assessment of antibody titers following intradermal injections, it appeared that monomeric HDI was more potent to induce specific IgG(1) antibodies than the homopolymers of HDI. In summary, with respect to induction of allergy and asthma, the data presented here suggest that the homopolymeric forms of HDI appear to be less potent asthmagens, if any, than monomeric HDI.

Respiratory hypersensitivity to trimellitic anhydride in Brown Norway rats: a comparison of endpoints.

A rat bioassay has been developed to provide an objective approach for the identification and classification of respiratory allergy using trimellitic anhydride (TMA), which is a known respiratory tract irritant and asthmagen. Particular emphasis was placed on the study of route-of-induction-dependent effects and their progression upon inhalation challenge with TMA (approximately 23 mg m(-3) for a duration of 30 min), which included analysis of specific and non-specific airway hyperreactivity and pulmonary inflammation initiated and sustained by immunological processes. Refinement of the bioassay focused on procedures to probe changes occurring upon challenge with TMA or methacholine aerosols using physiological, biochemical and immunological procedures. Following challenge with TMA, the rats sensitized to TMA showed marked changes in peak inspiratory and expiratory air flows and respiratory minute volume. In these animals, a sustained pulmonary inflammation occurred, characterized by specific endpoints determined in bronchoalveolar lavage (lactate dehydrogenase, protein, nitrite, eosinophil peroxidase, myeloperoxidase). When compared with the naive controls, lung weights were increased significantly, as were the weights of lung-associated lymph nodes following inhalation induction and auricular lymph nodes following topical induction. The extent of changes observed was equal or more pronounced in animals sensitized epicutaneously (day 0:150 microl vehicle/50% TMA on each flank, day 7; booster administration to the skin of the dorsum of both ears using half the concentration and volume used on day 0) when compared with rats sensitized by 5 x 3 h day(-1) inhalation exposures (low dose: 25 mg TMA m(-3), high dose: 120 mg TMA m(-3)). In summary, the findings support the conclusion that the Brown Norway rat model is suitable for identifying TMA as an agent that causes both an immediate-type change of breathing patterns and a delayed-type sustained pulmonary inflammatory response. However, it remains unresolved whether the marked effects observed in the topically sensitized rats are more related to a route-of-induction or dose-dependent phenomenon.