© 1991 Oxford University Press
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Relative Acute Toxicities of Hydrogen Fluoride, Hydrogen Chloride, and Hydrogen Bromide in Nose- and Pseudo-Mouth-Breathing Rats
Pulmonary Biology and Toxicology Section, Cellular and Molecular Biology Group, MS M888, Life Science Division, Los Alamos National Laboratory Los Alamos, New Mexico 87544
Received June 7, 1990; accepted January 11, 1991
Relative Acute Toxicities of Hydrogen Fluoride, Hydrogen Chloride, and Hydrogen Bromide in Nose- and Pseudo-Mouth-Breathing Rats. Stavert, D. M., Archuleta, D. C., Behr, M. J., and Lehnert, B. E. (1991). Fundam. Appl Toxicol. 16, 636–655. Hydrogen fluoride (HF), hydrogen bromide (HBr), and hydrogen chloride (HC1) gases can be generated during the pyrolysis of a variety of materials and they may be encountered in numerous industrial settings. Although injury to the respiratory tract has been characterized following the inhalation of halide gases via the nasal route, essentially no experimental information is currently available about their injurious effects when they are inhaled during mouth breathing. In this study, we simulated mouth breathing by using a pseudo-mouth-breathing (MB) rat model in order to: (1) characterize the profiles and magnitudes of respiratory tract injury that result from the acute inhalation of relatively high mass concentrations of the above halides when the upper airway is bypassed, and (2) assess the relative toxicities of HF, HBr, and HC1 when inhaled by way of either the nasal or the oral pathways. Tracheal tubes connected to mouthpieces were inserted into temporarily anesthetized rats, i.e., mouth breathers. Awake rats were placed into whole body flow plethysmographs for pulmonary ventilation studies while they were exposed either to air or to 1300 ppm of HF, HBr, or HC1 for 30 min. Similarly pretreated rats were also exposed but without the mouthpiece, i.e., nose breathers (NB). The animals were euthanized 24 hr after exposure for histopathologic analyses of their upper and lower respiratory tracts and for lung gravimetric measurements. Tissue injury following NB exposure to the halides was confined to the nasal region, e.g., epithelial and submucosal necrosis, accumulations of inflammatory cells, exudates, and the extravasation of erythrocytes. MB exposure caused higher mortality rates and major tissue disruption in the trachea, including epithelial, submucosal, glandular, and cartilage necrosis, and accumulations of inflammatory cells and exudates. More peripheral lung damage was manifested by lung gravimetric increases and histopathologic changes primarily in the larger conducting airways. The results of this study demonstrate that the injurious response profiles to HF, HBr, and HC1 markedly differ as a function of the route by which they are inhaled. Furthermore, examinations of the magnitudes of injury caused by exposure to the halides during nose or mouth breathing in conjunction with animal ventilatory data obtained during exposure to the halides suggest that HF, HBr, and HC1 are quantitatively similar in their toxic effects in the respiratory tract.