EFFECTS OF INHALED SULFURIC ACID AEROSOLS ON PULMONARY IMMUNOCOMPETENCE: A COMPARATIVE STUDY IN HUMANS AND ANIMALS

Abstract

There is increasing concern regarding the potential health effects associated with the inhalation of ambient acid aerosols. Laboratory studies with animals have demonstrated that inhalation exposure to sulfuric acid (H2SO4) can alter airway responsiveness, cause cell damage leading to alveolitis and edema, produce hypertrophy/hyperplasia of epithelial secretory cells in the tracheobronchial tree, and alter nonspecific and specific immune defense mechanisms. While the adverse effects of inhaled H SO upon pulmonary 2 4 immunocompetence in animals appear relatively clear, data concerning effects on host defense in exposed humans are inconclusive and appear to contrast with those observed in animal models. Despite the fact that extrapolation between different species is of major importance in inhalation toxicology, baseline comparative data between species are lacking, which often results in the questionable validity of extrapolation modeling. This interlaboratory study was designed to compare the effects produced by a single inhalation exposure (3 h) of H2SO4 at 1 mg/m3 in human subjects with those in a similarly exposed animal model in order to provide a basis for extrapolation to human health effects. Bronchoalveolar lavage of rabbits and human volunteers was performed after exposure and the recovered macrophages (M) used to assess effects upon macrophage attachment; uptake and intracellular killing of Staphylococcus aureus; modulation of Fc receptor (Fc R) expression; phagocytosis of opsonized latex particles; and resting and stimulated production of superoxide (O2-) and hydrogen peroxide (H2 O2) . Effects upon bronchopul monary lavage fluid and lavaged cell profiles were also evaluated in this study. Similarities with respect to effects upon cell attachment, lavaged cell numbers and M viability, total lavageable protein, polymorphonuclear cell infiltration, O2- and H2 O2 production, Fc R expression, and the percentage of phagocytically active cells were observed between rabbits and humans in response to H2 SO4 exposure. Alternatively, while the capacity to phagocytose latex particles was significantly increased in rabbit cells, phagocytic capacity was reduced by 28% in human M. Acid exposure significantly reduced the ex vivo uptake and killing of ingested S. aureus by rabbit cells, but the data were inconclusive for humans. This investigation represents the first attempt to directly compare, using similar assay protocols and experimental methods, the immunotoxic effects of inhaled H2 SO4 in an animal model with those in exposed human volunteers. Although making interspecies comparisons between humans and rabbits is complicated and needs to be approached with caution due to differences in such things as breathing rates, metabolism, and deposition, results of this study provide a database for future immunotoxicological studies and support the applicability of rabbits as a model to predict H2 SO4-induced alterations in human pulmonary immunocompetence.