Artificial butter flavoring is a potential etiological agent of bronchiolitis obliterans (BO) in employees at microwave popcorn packaging plants;however, the specific toxic component(s),and the mechanisms of toxicity are unknown. We demonstrated that diacetyl, the major volatile component of artificial butter flavoring, caused severe the respiratory toxicity in rats and mice. Because of concerns about diacetyl toxicity, it is being replaced in some consumer products by 2,3-pentanedione (PD), a structurally-related and untested chemical. Because the toxicity of inhaled PD is unknown, studies were conducted to characterize the toxicity of inhaled PD across a range of concentrations in rodents. Male and female Wistar-Han rats and B6C3F1 mice were exposed to 0, 50, 100, or 200 ppm PD 6h/d, 5d/wk for up to 2 wk. Bronchoalveolar lavage fluid (BALF) was collected after 1, 3, 5 and 10 exposures, and histopathology was evaluated after 12 exposures. MCP-1, MCP-3, CRP, FGF-9, fibrinogen, and OSM were increased 2- to 9-fold in BALF of rats exposed for 5 and 10 days to 200 ppm. In mice, only fibrinogen was increased after 5 exposures to 200 ppm. The epithelium lining the respiratory tract was the site of toxicity in all mice and rats exposed to 200 ppm. PD also caused fibrotic airway lesions in rats with pathological features of OB. The histopathological and biological changes observed in rats raise concerns that PD inhalation may also cause OB in exposed humans.nalyzed for cytokines at various timepoints during exposure. Additional studies are underway to investigate the time course of events leading to airway fibrosis, in order to find areas for potential intervention and treatment.
