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Acute central neurotoxicity of inhaled alpha-diketone butter flavoring compounds in the rat brain.
Hubbs-AF; Cumpston-A; Goldsmith-WT; Battelli-LA; Kashon-ML; Jackson-MC; Frazer-DG; Fedan-JS; Goravanahally-MP; Sriram-K
Vet Pathol 2010 Nov; 47(6)(Suppl):57S
Workers inhaling butter flavoring vapors have increased risk of fixed airways obstruction. Lung disease risk increases with increasing exposure to the alpha-diketone, 2,3-butanedione (diacetyl), a major component of most butter flavoring, and a chemical that also imparts the aroma and flavor of butter to many natural compounds. A related alpha-diketone, 2,3-pentanedione, is a potential substitute for 2,3-butanedione in flavorings. However, a structurally related beta-diketone, 2,4-pentanedione, causes neurotoxicity after subchronic inhalation. To investigate 2,3-pentanedione neurotoxicity, rats inhaled 2,3- pentanedione (270 ppm, 6 hr 41 min) and were sacrificed the following day. No histopathologic alterations were seen in sagittal brain sections stained with H&E or dual immunofluorescence for activated caspase-3, an indicator of apoptosis, and glucose transporter-1, a vascular marker. Apoptotic bodies and caspase-3 expressing cells occurred at similar low baseline levels in control and 2,3-pentanedione-exposed rats. In 2,3-pentanedione-exposed rats, interleukin- 6 (IL6) transcripts increased in olfactory bulb, striatum, and hippocampus. Transcripts of claudin-1, a component of blood-brain barrier, increased in olfactory bulb and striatum. Nitric oxide synthase-2 (NOS2) increased in olfactory bulb. To determine if another alpha-diketone caused similar changes, rats were exposed to air or 25, 249 or 346 ppm 2,3-butanedione (6 hr). 2,3- butanedione increased IL6 in olfactory bulb, striatum, and hippocampus at 249 or 346 ppm concentrations. NOS2 was increased in olfactory bulb, striatum, and hippocampus after 346 ppm 2,3-butanedione. Claudin-1 increased in hippocampus at 349 ppmand in olfactory bulb at 249 and 346 ppm. These findings indicate that acute 2,3-pentanedione and 2,3-butanedione exposures alter claudin-1, IL6 and NOS2 expression in brain and suggest the need for detailed neuropathologic studies after longer alpha-diketone exposures.
Food-additives; Laboratory-animals; Animal-studies; Animals; Nerves; Nerve-tissue; Nerve-fibers; Nervous-system-function; Neurotoxicity; Neurotoxic-effects; Central-nervous-system-disorders
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Page last reviewed: March 11, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division