title: Necrosis of nasal and airway epithelium in rats inhaling vapors of artificial butter flavoring.
abstract: As the result of a high prevalence of fixed airways obstruction in workers at a microwave popcorn manufacturing plant, we examined the hypothesis that vapors of butter flavoring used in the manufacture of microwave popcorn and other foods can produce airway injury in rats. Rats were exposed to vapors liberated from heated butter flavoring. Rats were exposed for 6 h by inhalation and were necropsied 1 day after exposure. The exposure was found by GC-MS analysis to be a complex mixture of various organic gases with the major peaks consisting of diacetyl (2,3-butanedione), acetic acid, acetoin (3-hydroxy-2-butanone), butyric acid, acetoin dimers, 2-nonanone, and delta-alkyl lactones. Diacetyl was used as a marker of exposure concentration. In the lung, butter flavoring vapors containing 285-371 ppm diacetyl caused multifocal, necrotizing bronchitis, which was most consistently present in the mainstem bronchus. Alveoli were unaffected. Butter flavoring vapors containing 203-371 ppm diacetyl caused necrosuppurative rhinitis, which affected all four levels of the nose. Within the posterior two nasal levels (T3 and T4), necrosis and inflammation was principally localized to the nasopharyngeal duct. Control rats were unaffected. Therefore, concentrations of butter flavoring vapors that can occur during the manufacture of foods are associated with epithelial injury in the nasal passages and pulmonary airways of rats.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health1, Centers for Disease Control and Prevention, 1095 Willowdale Road, Morgantown, West Virginia 26505, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Hubbs
authors.forename: L A
authors.initials: LA
authors.lastname: Battelli
authors.forename: W T
authors.initials: WT
authors.lastname: Goldsmith
authors.forename: D W
authors.initials: DW
authors.lastname: Porter
authors.forename: D
authors.initials: D
authors.lastname: Frazer
authors.forename: S
authors.initials: S
authors.lastname: Friend
authors.forename: D
authors.initials: D
authors.lastname: Schwegler-Berry
authors.forename: R R
authors.initials: RR
authors.lastname: Mercer
authors.forename: J S
authors.initials: JS
authors.lastname: Reynolds
authors.forename: A
authors.initials: A
authors.lastname: Grote
authors.forename: V
authors.initials: V
authors.lastname: Castranova
authors.forename: G
authors.initials: G
authors.lastname: Kullman
authors.forename: J S
authors.initials: JS
authors.lastname: Fedan
authors.forename: J
authors.initials: J
authors.lastname: Dowdy
authors.forename: W G
authors.initials: WG
authors.lastname: Jones
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D003931:Diacetyl / Q000633:toxicity*; D005421:Flavoring Agents / Q000633:toxicity*; D006651:Histocytochemistry; D019570:Inhalation Exposure; D008297:Male; D008854:Microscopy, Electron; D017817:Nasal Lavage Fluid / Q000166:cytology; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms
chemical_list: D005421:Flavoring Agents; D003931:Diacetyl