Chronic Exposure to PM_2.5 Nitrate, Sulfate, and Ammonium Causes Respiratory System Impairments in Mice

Water-soluble inorganic (WSI) ions are major components of ambient air PM_2.5 (particulate matter of diameter ≤2.5 μm); however, their potential health effects are understudied. On C57BL/6 mice, we quantified the effect of three major PM_2.5 WSIs (NO₃^-, SO₄^2-, and NH₄⁺) on respiratory systems. Exposure scenarios include different WSI types, concentrations, animal development stages (young vs adult), and sex. The exposure effects were comprehensively assessed, with special focus on the respiratory function and tissue/cell level changes. Chronic PM_2.5 NO₃^- exposure produced significant respiratory function decline, mainly presented as airflow obstruction. The decline was more profound in young mice than in adult mice. In young mice, exposure to 22 μg/m³ PM_2.5 NO₃^- reduced FEV_0.05 (forced expiratory volume in 0.05 s) by 11.3% (p = 9.6 × 10^-3) and increased pulmonary neutrophil infiltration by 7.9% (p = 7.1 × 10^-3). Causality tests identified that neutrophil infiltration was involved in the biological mechanism underlying PM_2.5 NO₃^- toxicity. In contrast, the effects of PM_2.5 SO₄^2- were considerably weaker than NO₃^-. PM_2.5 NO₃^- exposure was 3.4 times more potent than PM_2.5 SO₄^2- in causing reduction of the peak expiratory flow. PM_2.5 NH₄⁺ exposure had no statistically significant effects on the respiratory function. In summary, this study provided strong evidence on the adverse impacts of PM_2.5 WSIs, where the impacts were most profound in young mice exposed to PM_2.5 NO₃^-. If confirmed in humans, toxicity of PM_2.5 WSI will have broad implications in environment health and policy making.