Diacetyl and 2,3-pentanedione exposure of human cultured airway epithelial cells: Ion transport effects and metabolism of butter flavoring agents

Inhalation of butter flavoring by workers in the microwave popcorn industry may result in “popcorn workers' lung.” In previous in vivo studies rats exposed for 6h to vapor from the flavoring agents, diacetyl and 2,3-pentanedione, acquired flavoring concentration-dependent damage of the upper airway epithelium and airway hyporeactivity to inhaled methacholine. Because ion transport is essential for lung fluid balance, we hypothesized that alterations in ion transport may be an early manifestation of butter flavoring-induced toxicity. We developed a system to expose cultured human bronchial/tracheal epithelial cells (NHBEs) to flavoring vapors. NHBEs were exposed for 6h to diacetyl or 2,3-pentanedione vapors (25 or ≥60ppm) and the effects on short circuit current and transepithelial resistance (Rt) were measured. Immediately after exposure to 25ppm both flavorings reduced Na+ transport, without affecting Cl− transport or Na+,K+-pump activity. Rt was unaffected. Na+ transport recovered 18h after exposure. Concentrations (100–360ppm) of diacetyl and 2,3-pentanedione reported earlier to give rise in vivo to epithelial damage, and 60ppm, caused death of NHBEs 0h post-exposure. Analysis of the basolateral medium indicated that NHBEs metabolize diacetyl and 2,3-pentanedione to acetoin and 2-hydroxy-3-pentanone, respectively. The results indicate that ion transport is inhibited transiently in airway epithelial cells by lower concentrations of the flavorings than those that result in morphological changes of the cells in vivo or in vitro. •Butter flavoring vapor effects on human cultured airway epithelium were studied.•Na transport was reduced by a 6-h exposure to 25ppm diacetyl and 2,3-pentanedione.•Na transport recovered 18h after exposure.•>60ppm transepithelial voltage and resistance were abolished; cells were damaged.•Cells metabolized diacetyl and 2,3-pentanedione into acetoin and 2-OH-3-pentanone.