NTP researchers show butter flavoring agents cause respiratory toxicity in rats
National Toxicology Program (NTP) researchers recently demonstrated inhalation exposure to the alpha-diketone flavoring agents, 2,3-butanedione (BD), 2,3-pentanedione (PD), and 2,3-hexanedione (HD), can cause respiratory toxicity in rats. All three agents induced bronchial fibrosis after two weeks of exposure and patchy interstitial fibrosis that resulted in pulmonary function deficits that developed after a two-week recovery.
BD is a naturally occurring alpha-ketone that gives butter its flavor. BD is used as a flavoring agent in food, but it can cause obliterative bronchiolitis when inhaled, which can happen in an occupational setting. PD and HD are being used as substitutes for BD. PD is known to cause significant respiratory toxicity in rats and mice, but until recently HD had not been tested for inhalation toxicity.
NTP scientists found the small structural differences among BD, PD, and HD were sufficient to significantly alter their physical and chemical properties, as well as their reactivity and toxicity after inhalation. Alpha-diketones may exert their toxic effects by enzyme inhibition and protein crosslinking. All three agents inactivated glutathione s-transferase, but HD was significantly less reactive than BD and PD. Similarly, HD exposure resulted in less bronchial fibrosis in these studies. The authors concluded that longer chain alpha-diketones, such as HD, may reduce the likelihood of inhalation exposure and toxicity. (GK)
Citation: Morgan DL, Jokinen MP, Johnson CL, Price HC, Gwinn WM, Bousquet RW, Flake GP. 2016. Chemical reactivity and respiratory toxicity of the alpha-diketone flavoring agents: 2,3-butanedione, 2,3-pentanedione, and 2,3-hexanedione. Toxicol Pathol; doi:10.1177/0192623316638962 [Online 29 March 2016].