Comparative Toxicity of Simulated Smog Atmospheres in Healthy and Allergic Mice
Citation:
McGee, M., L. Copeland, Todd Krantz, C. King, J. Krug, C. Wood, Ian Gilmour, AND S. Gavett. Comparative Toxicity of Simulated Smog Atmospheres in Healthy and Allergic Mice. Society of Toxicology, New Orleans, LA, March 13 - 17, 2016.
Impact/Purpose:
This research supports efforts in ACE NMP-1 (ACE207) to assess the health effects of complex multi-pollutant mixtures in animal models of disease. Results show that 2 different smog mixtures (different ozone, nitrogen dioxide, and particulate matter profiles0 did not elicit significant changes in lung mechanics or inflammatory endpoints in a mouse model of allergic asthma. Future studies will be conducted to determine if any smog constituents can prime the model responses.
Description:
Effects of complex regional multipollutant mixtures on disease expression in susceptible populations are dependent on multiple exposure and susceptibility factors. Differing profiles of ozone (O3), nitrogen dioxide (NO2), and particulate matter (PM), which are key components of smog, and other hazardous pollutants may develop as a result of regional-specific geographic and urban environment characteristics. We investigated the pulmonary effects of two smog mixtures with different compositions in a mouse model of allergic airway disease to determine which source profile had the greatest impact on pulmonary endpoints. A hydrocarbon mixture was combined with NO gas in the presence of UV light in a controlled setting. Simulated smog atmosphere 1 (SSA-1) consisted of concentrations of 1070 µg/m3 secondary organic aerosol (SOA), 0.104 ppm O3, and 0.252 ppm NO2. SSA-2 consisted of a starting concentration of 53 µg/m3 SOA, 0.376 ppm O3, and 0.617 ppm NO2. An increased aerosol concentration was noted in the exposure chamber. Healthy and house dust mite (HDM)-sensitized (allergic) female BALB/cJ mice were exposed 4 hr/day for 1 or 5 days to either smog mixture or clean air. Two days after HDM challenge, airway mechanics were tested in anesthetized ventilated mice. Following methacholine aerosol challenge, increased airway resistance and elastance and a decrease in lung compliance were consistently observed in air- and smog-exposed HDM-allergic groups compared with non-allergic groups. Neither SSA study produced significant changes in lung injury markers (bronchoalveolar lavage protein, lactate dehydrogenase). Further analyses will be conducted to investigate effects of allergic challenge or smog exposure on nasal and lung histopathology. Generation of simulated smog atmospheres in a photochemical reaction chamber allows precise control of atmospheric chemistry for real-time exposures, but to date few significant changes in health endpoints have been observed in the mouse allergy model. (This abstract does not represent U.S. EPA policy.)