Final Report: Effect of Ammonium Bisulfate and Carbon Black Particles Inhaled Alone and in Combination on Airway Reactivity in Actively Sensitized Brown-Norway RatsEPA Grant Number: R826778
Title: Effect of Ammonium Bisulfate and Carbon Black Particles Inhaled Alone and in Combination on Airway Reactivity in Actively Sensitized Brown-Norway Rats
Investigators: Benson, Janet M. , Barrett, Edward G. , Bice, David E. , Cheng, Yung-Sung , Powell, Quint H.
Institution: Lovelace Respiratory Research Institute
EPA Project Officer: Hunt, Sherri
Project Period: October 1, 1998 through September 30, 1999 (Extended to December 30, 2000)
Project Amount: $199,035
RFA: Health Effects of Particulate Matter and Associated Air Pollutants (1998) RFA Text | Recipients Lists
Research Category: Air , Health Effects , Particulate Matter
The purpose of this research was to determine the relationship between increases in airborne aerosol mass concentrations of three models of major components of PM10-pure ammonium bisulfate, pure carbon black (a surrogate for fine soot particles), and ammonium bisulfate-coated particles?and changes in pulmonary function and airway hyper-reactivity. Difficulties generating ultrafine pure ammonium bisulfate condensation aerosols led us to use pure ammonium sulfate (AS) aerosols instead; thus, modifying the model to include sulfate aerosols completely reduced with ammonia. Furthermore, during the study performance period, the availability of new equipment at the Institute (PALAS carbon aerosol generators and a new Buxco system for obtaining measurements of airway resistance noninvasively in awake rodents) allowed us to modify the original design. Specifically, ultrafine carbon particles were generated directly instead of isolation of a submicron size fraction from bulk carbon black. Using the Buxco system, we were able to measure a parameter of pulmonary resistance (Penh). Because we were able to measure pulmonary resistance in the rats non-invasively, other parameters of pulmonary function were not measured. Specifically, we investigated the roles of AS, carbon particles, and sulfate-coated carbon particles of relevant particle size and concentration on pulmonary function and airway reactivity in allergen-sensitized male Brown Norway (BN) rats, a rodent model for human extrinsic asthma. The experimental approach compared the potency of AS particles and carbon particles with sulfate-coated carbon particles at equivalent particle size and mass concentrations to cause increases in airway resistance in response to an allergen-specific or nonspecific inhalation challenge.
Ovalbumin-sensitized Brown Norway rats (a rodent model of allergic asthma) were exposed nose-only for 6 hours to one of three models of ambient particulate pollutantsAS, carbon, or sulfate-coated carbon particles. The particle size was 100 nm, the concentration was 500 µg/m3. Twenty-four hours later, groups of 10 animals were challenged with OA aerosol, and pulmonary resistance was measured. Forty-eight hours after particle exposure the same rats were challenged with increasing concentrations of methacholine, and resistance was measured. Seventy-two hours after particle exposure, all rats were sacrificed. Blood was collected for determination of IgE concentration. Lungs of five rats/exposure group (not having undergone airway challenge) were lavaged. Lavage fluid was evaluated for total protein, total nucleated cell counts, and differential nucleated cell counts.
Under our experimental conditions, short-term exposure to AS, carbon, or sulfate-coated carbon particles produced no (AS-exposure), or minimal (carbon or sulfate-coated carbon exposure) pulmonary inflammation measured 72 hours after exposure. Furthermore, exposure to these model ambient particles did not increase airway responsiveness to either antigen specific (OA) or nonspecific (methacholine) airway challenge in OA-sensitized BN rats. These results are consistent with earlier reports that exposure of healthy and asthmatic volunteers to sulfuric acid aerosols, carbon particles, or to sulfuric acid-coated carbon particles had minimal effects on airway responsiveness to inhaled methacholine challenge (Avol, et al., 1988, 1990; Anderson, et al., 1992).
Results of these studies support the earlier findings in humans that short-term exposure to sulfate aerosols and carbon aerosols has little effect on airway reactivity, even in asthmatics or in an animal model of allergic asthma. Our results also refute our original hypothesis that sulfate-coated carbon particles would produce greater enhancement of airway reactivity than would be elicited by inhalation of either particle type alone.