Acute central neurotoxicity of inhaled alpha-diketone butter flavoring compounds in the rat brain

Details

• Personal Author:
  Battelli LA ; Cumpston A ; Fedan, Jeffery S. ; Frazer DG ; Goldsmith WT ; Goravanahally MP ; Hubbs, Ann F. ; Jackson MC ; Kashon ML ; Sriram K
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Food Additives Laboratories Nervous System Nervous System Disorders Occupational Health Safety
• Keywords:
  Animal-studies Central-nervous-system-disorders Food-additives Laboratory-animals Nerve-fibers Nerve-tissue Nerves Nervous-system-function Neurotoxic-effects Neurotoxicity
• ISSN:
  0300-9858
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  47
• Issue:
  6
• NIOSHTIC Number:
  nn:20037760
• Citation:
  Vet Pathol 2010 Nov; 47(6)(Suppl):57S
• CAS Registry Number:
  2,3-Pentanedione (CAS RN 600-14-6)
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  Veterinary Pathology
• Supplement:
  Suppl
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c5a311014cf16388ec9d4938b0d99d27d00646f05d7e4ca8161b5d6e2a93cfb11ea29b3672aee6cae5721118d5d3066a8d6bb27f7b39c928d5284f1c09d12451
• Download URL:
  https://stacks.cdc.gov/view/cdc/191745/cdc_191745_DS1.pdf
• File Type:
  [PDF - 283.59 KB ]