IDENTIFICATION AND USE: 2,3-Pentanedione is a yellow liquid. It is used as flavoring agent (butter flavoring) including many e-cigarette brands.
HUMAN EXPOSURE AND TOXICITY: Inhalation of butter flavoring by workers in the microwave popcorn industry may result in "popcorn workers" lung." Cultured human bronchial/tracheal epithelial cells (NHBEs) were exposed for 6 hours to diacetyl or 2,3-pentanedione vapors (25 or >/= 60 ppm) and the effects on short circuit current and transepithelial resistance (Rt) were measured. Immediately after exposure to 25 ppm both flavorings reduced Na+ transport, without affecting Cl- transport or Na+,K+-pump activity. Concentrations (100-360 ppm) of diacetyl and 2,3-pentanedione reported to give rise in vivo to epithelial damage, and 60 ppm, caused death of NHBEs 0 hours post-exposure. The results indicate that ion transport is inhibited transiently in airway epithelial cells by lower concentrations of the flavorings than those that result in morphological changes of the cells in vivo or in vitro.
ANIMAL STUDIES: Rats that inhaled air, 2,3-pentanedione (112, 241, 318, or 354 ppm) for 6 hours were sacrificed the following day. Rats inhaling 2,3-pentanedione developed necrotizing rhinitis, tracheitis, and bronchitis. To investigate delayed toxicity, additional rats inhaled 318 (range, 317.9-318.9) ppm 2,3-pentanedione for 6 hours and were sacrificed 0 to 2, 12 to 14, or 18 to 20 hours after exposure. Respiratory epithelial injury in the upper nose involved both apoptosis and necrosis, which progressed through 12 to 14 hours after exposure. Olfactory neuroepithelial injury included loss of olfactory neurons that showed reduced expression of the 2,3-pentanedione-metabolizing enzyme, dicarbonyl/L-xylulose reductase, relative to sustentacular cells. Caspase 3 activation occasionally involved olfactory nerve bundles that synapse in the olfactory bulb (OB). An additional group of rats inhaling 270 ppm 2,3-pentanedione for 6 hours 41 minutes showed increased expression of IL-6 and nitric oxide synthase-2 and decreased expression of vascular endothelial growth factor A in the OB, striatum, hippocampus, and cerebellum using real-time PCR. Claudin-1 expression increased in the OB and striatum. In other experiment, male and female rats and mice were exposed to 0, 50, 100, or 200 ppm 2,3-pentanedione 6 hr/d, 5 d/wk for up to 2 weeks. 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. Significantly, 2,3-pentanedione also caused both intraluminal and intramural fibrotic airway lesions in rats. In third experiment, rats exposed to 150 or 200 ppm 2,3-pentanedione developed bronchial fibrosis. In mice, 2,3-pentanedione was not a dermal irritant when tested at concentrations up to 50%. However, concentration-dependent increases in lymphocyte proliferation were observed following exposure to 2,3-pentanedione in mice. |