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Respiratory and olfactory cytotoxicity of inhaled 2,3-pentanedione in sprague-dawley rats.

Hubbs AF; Cumpston AM; Goldsmith WT; Battelli LA; Kashon ML; Jackson MC; Frazer DG; Fedan JS; Goravanahally MP; Castranova V; Kreiss K; Willard PA; Friend S; Schwegler-Berry D; Fluharty KL; Sriram K

Am J Pathol 2012 Sep; 181(3):829-844

https://doi.org/10.1016/j.ajpath.2012.05.021

20041335

Flavorings-related lung disease is a potentially disabling disease of food industry workers associated with exposure to the a-diketone butter flavoring, diacetyl (2,3-butanedione). To investigate the hypothesis that another a-diketone flavoring, 2,3-pentanedione, would cause airway damage, rats that inhaled air, 2,3-pentanedione (112, 241, 318, or 354 ppm), or diacetyl (240 ppm) for 6 hours were sacrificed the following day. Rats inhaling 2,3-pentanedione developed necrotizing rhinitis, tracheitis, and bronchitis comparable to diacetyl-induced injury. 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. We conclude that 2,3-pentanedione is a respiratory hazard that can also alter gene expression in the brain.

Food-additives; Respiratory-system-disorders; Lung-disease; Lung-disorders; Pulmonary-system-disorders; Laboratory-animals; Animal-studies; Animals

Ann F. Hubbs, D.V.M., Ph.D., D.A.C.V.P., Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Rd, Mailstop L2015, Morgantown, WV 26505

AJPAA4

431-03-8; 600-14-6

20120901

Journal Article

ahubbs@cdc.gov

2012

B08292012

3

0002-9440

HELD

Manufacturing

The American Journal of Pathology

WV