Popcorn flavoring effects on reactivity of rat airways in vivo and in vitro.
"Popcorn workers' lung" is an obstructive pulmonary disease produced by inhalation of volatile artificial butter flavorings. In rats, inhalation of diacetyl, a major component of butter flavoring, and inhalation of a diacetyl substitute, 2,3-pentanedione, produce similar damage to airway epithelium. The effects of diacetyl and 2,3-pentanedione and mixtures of diacetyl, acetic acid, and acetoin, all components of butter flavoring, on pulmonary function and airway reactivity to methacholine (MCh) were investigated. Lung resistance (RL) and dynamic compliance (Cdyn) were negligibly changed 18 h after a 6-h inhalation exposure to diacetyl or 2,3-pentanedione (100-360 ppm). Reactivity to MCh was not markedly changed after diacetyl, but was modestly decreased after 2,3-pentanedione inhalation. Inhaled diacetyl exerted essentially no effect on reactivity to mucosally applied MCh, but 2,3-pentanedione (320 and 360 ppm) increased reactivity to MCh in the isolated, perfused trachea preparation (IPT). In IPT, diacetyl and 2,3-pentanedione (≥3 mM) applied to the serosal and mucosal surfaces of intact and epithelium-denuded tracheas initiated transient contractions followed by relaxations. Inhaled acetoin (150 ppm) exerted no effect on pulmonary function and airway reactivity in vivo; acetic acid (27 ppm) produced hyperreactivity to MCh; and exposure to diacetyl + acetoin + acetic acid (250 + 150 + 27 ppm) led to a diacetyl-like reduction in reactivity. Data suggest that the effects of 2,3-pentanedione on airway reactivity are greater than those of diacetyl, and that flavorings are airway smooth muscle relaxants and constrictors, thus indicating a complex mechanism.
Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, West Virginia 26505, USA.
Eric J
EJ
Zaccone
Janet A
JA
Thompson
Dovenia S
DS
Ponnoth
Amy M
AM
Cumpston
W Travis
WT
Goldsmith
Mark C
MC
Jackson
Michael L
ML
Kashon
David G
DG
Frazer
Ann F
AF
Hubbs
Michael J
MJ
Shimko
Jeffrey S
JS
Fedan
D019342:Acetic Acid / Q000633:toxicity; D000093:Acetoin / Q000633:toxicity; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D002478:Cells, Cultured; D045424:Complex Mixtures / Q000633:toxicity; D003931:Diacetyl / Q000633:toxicity*; D005421:Flavoring Agents / Q000633:toxicity*; D005502:Food; D019570:Inhalation Exposure; D008297:Male; D016210:Methacholine Chloride; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D010422:Pentanones / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000187:drug effects* / Q000503:physiopathology
D045424:Complex Mixtures; D005421:Flavoring Agents; D010422:Pentanones; D016210:Methacholine Chloride; D000093:Acetoin; D003931:Diacetyl; C013186:2,3-pentanedione; D019342:Acetic Acid