Acute airway effects of diacetyl in mice

Occupational exposures to the butter flavouring agent diacetyl (2,3-butanedione) have caused lung inflammation and severe airflow limitation due to bronchiolitis obliterans. Diacetyl is naturally present in butter, beer, white wine, etc., and its pleasant odour is easily recognized by consumers. However, this pleasant odour may induce a false sense of safety when higher airborne concentrations are encountered in industrial use. In this study, the acute warning properties, in terms of sensory irritation, that could be useful to prevent workers from exposures to a high concentration were first investigated in a mouse bioassay. Then at higher exposure concentrations, the possibility of airflow limitation and pulmonary irritation were studied with the same mouse bioassay. Diacetyl induces concentration-dependent irritation in all parts of the respiratory tract during a 2-h exposure period. The no-observed-effect levels for each effect in the mice were above 100 ppm and initiation of sensory irritation in humans was estimated to occur above 20 ppm. No acute warning signal from the airways is expected at diacetyl levels that have caused bronchiolitis obliterans and other toxic effects. The sensory irritation effect, which occurred rapidly upon initiation of exposure, faded rapidly. Furthermore, high-level diacetyl exposures decreased the sensory irritation warning signal in mice upon repeated exposure, which suggests that the compound is especially insidious.