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Ultrastructural changes in the airways of rats inhaling butter flavoring vapors.

Hubbs AF; Mercer RR; Battelli L; Friend S; Schwegler-Berry D; Castranova V; Kreiss K; Kullman G; Frazer D; Goldsmith WT; Jones WG
Toxicologist 2002 Mar; 66(1-S):194
A cluster of eight cases of fixed airway obstruction occurred in former workers in a microwave popcorn plant. As part of a request to NIOSH to find the cause, extensive medical and environmental measurements were made at the plant. High levels of organic gases and decreased pulmonary function among workers were associated with butter flavoring in use at the plant but other exposures existed. To assess the biological effects of the flavoring, we exposed rats by inhalation for 6 hours to butter flavoring vapors. Qualitative GC-MS analysis yielded a variety of organic gases including diacetyl and acetoin. Average diacetyl concentration in the exposure chamber was about 350 ppm. By transmission electron microscopy (TEM), the principal finding in the mainstem bronchus of exposed rats was airway epithelial necrosis. Unusual features of the epithelial alterations included rarefaction of basilar cytoplasm and relative preservation of cilia. Denuded basement membrane was frequently observed although a thin fragment of basilar cytoplasm of respiratory epithelium remained attached in some foci. Damage in the mainstem bronchus extended beneath the basement membrane into the lamina propria where edematous changes were characterized by disorganization and separation of collagen fibers and fibrils. Necrotizing changes were less frequent in smaller airways. By scanning electron microscopy (SEM), ulceration of bronchiolar epithelium tended to be localized at bronchiolar bifurcations. No evidence of alveolar injury was evident in TEM or SEM sections. These findings document that artificial butter flavoring, while considered safe to consume at concentrations present in food, produces vapors capable of inducing severe airway injury in laboratory animals when inhaled at high concentrations similar to peak exposures in the workplace.
Environmental-health-monitoring; Worker-health; Animal-studies; Inhalation-studies; Respiratory-function-tests; Respiratory-irritants; Food-additives; Food-processing; Food-processing-workers; Laboratory-animals
Publication Date
Document Type
Fiscal Year
NIOSH Division
Priority Area
Work Environment and Workforce: Mixed Exposures
Source Name
The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee
Page last reviewed: March 3, 2021
Content source: National Institute for Occupational Safety and Health Education and Information Division