AAAR 37th Annual Conference October 14 - October 18, 2019 Oregon Convention Center Portland, Oregon, USA
Abstract View
Characterization and Performance Evaluation of a Nose-only Inhalation (NOI) Exposure System for a 90-Day Repeated-Dose NNK Inhalation Toxicity Study
Shu-Chieh Hu, Yunan Tang, Seonggi Min, Hyun-Ki Kang, Dong-Jin Yang, Mallikarjuna Basavarajappa, Estatira Sepehr, Raul Trbojevich, Matthew Bryant, JINGHAI YI, Susan Chemerynski, Steven Yee, Hans Rosenfeldt, R. Philip Yeager, Paul Howard, NCTR-FDA
Abstract Number: 848 Working Group: Health-Related Aerosols
Abstract Human exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific nitrosamine classified as a carcinogen, occurs through the use of combusted or smokeless tobacco products, or exposure to environmental tobacco smoke. However, studies of inhaled NNK are limited. To properly perform a 90-day inhalation toxicology study, aerosols in NOI chamber must have (1) a steady mass concentration maintained at a desired level for the entire exposure period, (2) a stable size distribution with a mass-median-aerodynamic-diameter (MMAD) < 2 µm and a geometric-standard-deviation (GSD) of 1 to 3, (3) a spatially-uniform distribution, and (4) a repeatable concentration. To date, no method has been reported on generating respirable NNK aerosols with a stable and repeatable concentration. Six NOI exposure systems were characterized in a 90-day NNK inhalation toxicology study. Each system consisted of (1) an aerosol generation system, (2) a 50-port NOI exposure chamber, and (3) a test atmosphere control and monitor system. NNK aerosols, generated from NNK formulation (NNK dissolved in propylene glycol and water) with a nebulizer, were delivered into the NOI exposure system at 50 LPM. Particle size distribution was measured using a cascade impactor. NNK concentration was determined by gravimetric collection of aerosols into filter and analyzed by an ultra-high-performance-liquid-chromatography. The air pressure, temperature, relative humidity, and oxygen concentration were monitored and controlled continuously. The NNK aerosols delivered to the NOI exposure systems had (1) a steady concentration at 0.0066, 0.026 and 0.257 mg/L during a 1-hour exposure, (2) a stable size distribution with a MMAD of 1.21~1.77 µm and a GSD of 1.55~2.0, (3) a spatially uniform distribution with a spatial variation < 3%, and (4) a repeatable concentration with a relative-standard-deviation < 5.0%. The six nose-only inhalation exposure systems reliably and repeatedly created well-controlled test atmospheres that can be used to evaluate the health impact of NNK inhalation exposures.