April 6, 2023

Studies Examine Inhalation Toxicity of Flavoring Compounds

A technical report published in March by the National Toxicology Program details a series of studies to evaluate the inhalation toxicity of acetoin and 2,3-pentanedione, which NTP describes as highly volatile components of artificial butter flavoring. Occupational exposures to 2,3-pentanedione and other substances used in artificial butter flavoring have been linked to decreased lung function and to the severe, irreversible lung disease obliterative bronchiolitis. Other health effects of occupational exposure to 2,3-pentanedione include irritation of the skin, eyes, and respiratory tract. According to NTP, both acetoin and 2,3-pentanedione are used as ingredients in synthetic flavoring formulations for food additives. 2,3-Pentanedione is used in some cases as a substitute for the flavoring compound diacetyl due to concerns about diacetyl’s respiratory toxicity. But 2,3-pentanedione is structurally similar to diacetyl, and “has been shown to exhibit potency similar to [diacetyl] regarding airway toxicity following acute inhalation (whole-body) exposure,” the NTP report explains.

Researchers conducted studies to evaluate the two‑week inhalation toxicity of acetoin and the three‑month inhalation toxicity of acetoin and 2,3‑pentanedione as administered to Wistar Han rats and B6C3F1/N mice. The rats and mice were exposed to the acetoin and 2,3‑pentanedione vapors via whole-body inhalation. No significant adverse effects related to exposure occurred among the rats and mice exposed to acetoin for two weeks or three months as part of this inhalation study. But researchers identified significant adverse effects—primarily in the respiratory tract but also in the eyes—in the rats and mice exposed to 2,3‑pentanedione for three months.

“The [no-observed-effect level (NOEL)] of 2,3-pentanedione for this study overall was 12.5 ppm on the basis of adverse respiratory tract effects in rats and mice,” NTP’s report concludes. “These 3-month inhalation exposure data, including NOELs for adverse respiratory tract effects, can inform regulatory agencies to help mitigate exposure risks to 2,3-pentanedione vapors in the workplace.”

NTP’s full report can be found on the program’s website. Additional information about NTP’s research on the components of artificial butter flavorings is also available.

Related: A NIOSH topic page on flavorings-related lung disease provides information about agency research and investigations focused on the microwave popcorn and flavorings manufacturing industries. In 2016, NIOSH researchers raised concerns that workers at coffee processing facilities are also at risk for lung disease caused by occupational exposure to diacetyl and 2,3-pentanedione, which are naturally produced and released when coffee beans are roasted and when coffee is ground.