Derivation of an occupational exposure limit for diacetyl using dose‐response data from a chronic animal inhalation exposure study. Issue 5 (8th January 2019)

• Record Type: Journal Article
• Authors: Beckett, Evan M.; Cyrs, William D.; Abelmann, Anders; Monnot, Andrew D.; Gaffney, Shannon H.; Finley, Brent L.
• Is Part Of: Journal of applied toxicology. Volume 39:Issue 5(2019)
• Page Start: 688
• Page End: 701
• Publication Date: 2019-01-08
• Subjects: benchmark concentration -- diacetyl -- food flavorings -- OEL -- risk assessment; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.3757
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: Occupational exposure limits (OELs) have been previously proposed for diacetyl; however, most of these values are based on worker cohort studies that are known to have several limitations and confounders. In this analysis, an 8 hour time‐weighted average (TWA) OEL for diacetyl was derived based on data from a chronic, 2 year animal inhalation study recently released by the US National Toxicology Program. In that study, complete histopathology was conducted on male and female mice and rats exposed to 0, 12.5, 25 or 50 ppm diacetyl. Several responses in the lower respiratory tract of rats (the more sensitive species) were chosen as the critical endpoints of interest. Benchmark concentration (BMC) modeling of these endpoints was used to estimate BMC values associated with a 10% extra risk (BMC10 ) and the associated 95% lower confidence bound (BMCL10 ), which were subsequently converted to human equivalent concentrations (HECs) using a computational fluid dynamics‐physiologically based pharmacokinetic (CFD‐PBPK) model to account for interspecies dosimetry differences. A composite uncertainty factor of 8.0 was applied to the human equivalent concentration values to yield 8 hour TWA OEL values with a range of 0.16‐0.70 ppm. The recommended 8 hour TWA OEL for diacetyl vapor of 0.2 ppm, based on minimal severity of bronchiolar epithelial hyperplasia in the rat, is practical and health‐protective. Abstract : An 8 hour time‐weighted average occupational exposure limit (OEL) for diacetyl was derived utilizing data from a 2 year animal inhalation study. Several respiratory responses in rats were identified as the critical health endpoints. Benchmark concentration modeling, followed by the application of a physiologically based pharmacokinetic model and composite uncertainty factor of 8.0, the range of derived OELs was 0.16‐0.70 ppm. An OEL of 0.2 ppm, based on minimal bronchiolar epithelial hyperplasia in rats, is recommended for diacetyl.