title: Chemical Reactivity and Respiratory Toxicity of the α-Diketone Flavoring Agents: 2,3-Butanedione, 2,3-Pentanedione, and 2,3-Hexanedione.
abstract: Occupational exposure to 2,3-butanedione (BD) vapors has been associated with severe respiratory disease leading to the use of potentially toxic substitutes. We compared the reactivity and respiratory toxicity of BD with that of two structurally related substitutes, 2,3-pentanedione (PD) and 2,3-hexanedione (HD). Chemical reactivity of the diketones with an arginine substrate decreased with increasing chain length (BD > PD > HD). Animals were evaluated the morning after a 2-week exposure to 0, 100, 150, or 200 ppm BD, PD, or HD (postexposure) or 2 weeks later (recovery). Bronchial fibrosis was observed in 5/5 BD and 5/5 PD rats at 200 ppm and in 4/6 BD and 6/6 PD rats at 150 ppm in the postexposure groups. Following recovery, bronchial fibrosis was observed in all surviving rats exposed to 200 ppm BD (5/5) or PD (3/3) and in 2/10 BD and 7/9 PD rats exposed to 150 ppm. Bronchial fibrosis was observed only in 2/12 HD-exposed rats in the 200 ppm postexposure group. Patchy interstitial fibrosis affected lungs of recovery groups exposed to 200 ppm PD (3/3) or BD (1/5) and to 150 ppm PD (4/9) or BD (7/10) and correlated with pulmonary function deficits. BD and PD were more reactive and produced more bronchial fibrosis than HD.
authors.affiliation: National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA morgan3@niehs.nih.gov.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Morgan
authors.affiliation: Integrated Laboratory Systems, Morrisville, North Carolina, USA.
authors.forename: Micheal P
authors.initials: MP
authors.lastname: Jokinen
authors.affiliation: Charles River Laboratories, Inc., Durham, North Carolina, USA.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Johnson
authors.affiliation: Alion Science and Technology, Research Triangle Park, North Carolina, USA.
authors.forename: Herman C
authors.initials: HC
authors.lastname: Price
authors.affiliation: National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Gwinn
authors.affiliation: Alion Science and Technology, Research Triangle Park, North Carolina, USA.
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Bousquet
authors.affiliation: National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Gordon P
authors.initials: GP
authors.lastname: Flake
mesh_terms: D000818:Animals; D003931:Diacetyl / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005421:Flavoring Agents / Q000008:administration & dosage / Q000633:toxicity*; D006588:Hexanones / Q000008:administration & dosage / Q000633:toxicity; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D010422:Pentanones / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats
chemical_list: D005421:Flavoring Agents; D006588:Hexanones; D010422:Pentanones; C043231:2,3-hexanedione; D003931:Diacetyl; C013186:2,3-pentanedione
keywords: 2,3-butanedione (diacetyl); 2,3-hexanedione (acetyl butyryl); 2,3-pentanedione (acetyl propionyl); fibrosis; flavoring agents; obliterative bronchiolitis; pulmonary function