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2,3 pentanedione

Acetylpropionyl is used in food production facilities such as those which manufacture cookies, coffee, cereal and chocolate. It is also found in nicotine containing liquids used for vaping and flavored cigarettes.

There is substantial evidence of the pulmonary toxicity of Acetylpropionyl in animals. Rats exposed to acetylpropionyl develop both fibrosis and necrosis of the respiratory tract. Mice exposed to acetylpropionyl demonstrate more bronchial constriction in response to methacholine challenge.

Acetylpropionyl has been used as a substitute for the toxic flavoring chemical diacetyl. However, in one flavoring manufacturing facility which had substituted diacetyl for acetylpropionyl, abnormal lung function values were associated with total time spent in production areas. An investigation by NIOSH in 2009 at a facility which used buttermilk flavoring containing acetylpropionyl demonstrated that workers had higher than average reports of shortness of breath, asthma, and restrictive type spirometry defects. Another investigation by NIOSH in 2013 at a flavoring manufacturer which utilized acetylpropionyl revealed that those workers who had spent the most time working with flavoring chemicals were more likely to have abnormal lung function as detected by pulmonary function tests.

Diacetyl

Diacetyl is known to cause the lung disease bronchiolitis obliterans in those individuals exposed to it in an occupational setting.

In the year 2000 8 cases of bronchiolitis obliterans were detected in former employees of a microwave popcorn plant.  Many of these individuals had initially been misdiagnosed as having other pulmonary diseases such as COPD and asthma initially.  NIOSH investigated the worksite and suggested that artificial butter flavoring containing diacetyl was the most likely causative agent for the cases of bronchiolitis obliterans.  Follow up investigations at the plant revealed that 25% of employees had abnormal spirometry exams. The plant effectively implemented changes reducing air concentrations of diacetyl by 1 to 3 orders of magnitude in the years following.  A stabilization of respiratory symptoms was seen after this point in those who had been exposed to high levels of diacetyl. However, declines in lung function as measured by spirometry continued. Other studies also found cases of bronchiolitis obliterans in workers at 4 other microwave popcorn production facilities.  Additionally further studies have demonstrated a large increase in abnormal spirometry values in workers exposed to flavoring chemicals with a clear dose-response relationship.

Biochemical Toxicity of Diacetyl

Significant laboratory evidence points to the toxicity of diacetyl.  Diacetyl has been shown to alter the amino acid arginine which could interfere with protein structure and function.  Additionally diacetyl can bind to DNA and form guanosine adducts which can cause DNA uncoiling and cell death. In vitro studies on human cells also suggest that diacetyl alters the structure and function of the extracellular matrix and modifies epithelial cell responses to growth factors.  Human cells exposed to diacetyl also increase secretion of substance P which causes mucus hypersecretion, airway smooth muscle contraction, and edema. Studies in rats have demonstrated significant airway epithelial damage and necrosis after exposure to diacetyl.