Effects of arsenic trioxide inhalation exposure on pulmonary antibacterial defenses in mice

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Abstract
The effects of single and multiple (5 and 20) 3‐h inhalation exposures to aerosols of arsenic trioxide on the pulmonary defense system of mice were investigated. Arsenic trioxide mist was generated from an aqueous solution and dried to produce paniculate aerosols of 0.4 μm mass median aerodynamic diameter. Aerosol mass concentration ranged from 125 to 1000 μg As/m 3 . Effects of the exposures were evaluated by determination of changes in susceptibility to experimentally induced streptococcal aerosol infection and in pulmonary bactericidal activity to 35S‐labeled Klebsiella pneumoniae. Significant increases in mortality due to the infectious challenge and decreases in bactericidal activity were seen after single 3‐h exposures to 270, 500, and 940 μg As/m 3 . Similarly, 5 or 20 multiple 3‐h exposures to 500 μg As/m 3 produced consistently significant increases in mortality and decreases in pulmonary bactericidal activity. At 125 or 250 μg As/m 3 , a decrease in bactericidal activity was seen only after 20 exposures to 250 μg/m 3 . Results from earlier studies with an arsenic‐containing copper smelter dust were compared to these data. The possibility of the development of adaptation during multiple exposures to arsenic trioxide is also considered.