Metabolism / Metabolites
We have developed a system for exposing cultured human bronchial/tracheal epithelial cells (NHBE) to spice vapors. NHBEs were exposed to diacetyl or 2,3-pentanedione vapors (25 or ≥ 60 ppm) for 6 hours… Analysis of the basolateral medium showed that NHBEs metabolized diacetyl and 2,3-pentanedione to acetoin and 2-hydroxy-3-pentanedione, respectively.

Toxicity Summary
Identification and Uses: 2,3-Pentanedione is a yellow liquid. It is used as a flavoring agent (butter flavoring), including in many e-cigarette brands. Human Exposure and Toxicity: Inhalation of butter flavoring by workers in the microwave popcorn industry may lead to "popcorn worker lung." Cultured human bronchial/tracheal epithelial cells (NHBEs) were exposed to diacetyl or 2,3-pentanedione vapor (25 or ≥ 60 ppm) for 6 hours, and their effects on short-circuit current and transepithelial resistance (Rt) were measured. Exposure to 25 ppm of both flavorings immediately reduced Na+ transport but did not affect Cl- transport or Na+,K+- pump activity. Concentrations of diacetyl and 2,3-pentanedione at 100–360 ppm have been reported to cause epithelial damage in vivo, while a concentration of 60 ppm has caused death of NHBEs within 0 hours of exposure. The results showed that lower concentrations of fragrance could transiently inhibit ion transport in airway epithelial cells compared to concentrations that caused changes in cell morphology in vivo or in vitro. Animal experiments: Rats were inhaled into air or different concentrations of 2,3-pentanedione (112, 241, 318, or 354 ppm) for 6 hours and sacrificed the following day. Rats inhaling 2,3-pentanedione developed necrotizing rhinitis, tracheitis, and bronchitis. To investigate delayed toxicity, other rats were inhaled at a concentration of 318 ppm (range: 317.9–318.9 ppm) of 2,3-pentanedione for 6 hours and sacrificed at 0–2 hours, 12–14 hours, or 18–20 hours post-exposure. Upper nasal respiratory tract epithelial damage involved apoptosis and necrosis and continued to progress within 12–14 hours post-exposure. Olfactory neuroepithelial damage includes the loss of olfactory neurons, in which the expression of the 2,3-pentanedione metabolic enzyme, dicarbonyl/L-xylitol reductase, is reduced relative to supporting cells. Activation of Caspase 3 is occasionally involved in the olfactory nerve bundles that form synapses in the olfactory bulb (OB). In another group of rats, after inhalation of 270 ppm 2,3-pentanedione for 6 hours and 41 minutes, real-time PCR detection revealed increased expression of IL-6 and nitric oxide synthase-2, and decreased expression of vascular endothelial growth factor A in the olfactory bulb, striatum, hippocampus, and cerebellum. Claudin-1 expression was increased in the olfactory bulb and striatum. In another experiment, male and female rats and mice were exposed to 0, 50, 100, or 200 ppm 2,3-pentanedione for 6 hours daily, 5 days a week, for up to 2 weeks. Bronchoalveolar lavage fluid (BALF) was collected after 1, 3, 5, and 10 exposures, and histopathological evaluation was performed after 12 exposures. In rat bronchoalveolar lavage fluid (BALF) exposed to 200 ppm for 5 and 10 days, the levels of MCP-1, MCP-3, CRP, FGF-9, fibrinogen, and OSM increased 2 to 9-fold. In mice, only fibrinogen levels increased after 5 days of exposure to 200 ppm. All mice and rats exposed to 200 ppm showed toxic effects on the respiratory epithelium. Notably, 2,3-pentanedione also caused intraluminal and intramural fibrotic airway lesions in rats. In a third experiment, rats exposed to 150 or 200 ppm of 2,3-pentanedione developed bronchofibrosis. In mice, concentrations up to 50% of 2,3-pentanedione did not show skin irritation. However, in mice, a concentration-dependent increase in lymphocyte proliferation was observed after exposure to 2,3-pentanedione.

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Non-human toxicity values
Oral LD50 in rats: 3000 mg/kg

[1]. Bronchial and bronchiolar fibrosis in rats exposed to 2,3-pentanedione vapors: implications for bronchiolitis obliterans in humans. Toxicol Pathol. 2012;40(3):448-465.

2,3-Pentanedione is an α-diketone formed by substituting pentane at the 2 and 3 positions with carbonyl groups. It is a flavoring agent. It is both an α-diketone and a methyl ketone. It is derived from the hydride of pentane. 2,3-Pentanedione has been reported in tobacco (Nicotiana tabacum), onions (Allium cepa), and several other organisms with relevant data. 2,3-Pentanedione is a metabolite found in or produced by the yeast Saccharomyces cerevisiae.

C5H8O2

100.12

100.052

600-14-6

2,3-Pentanedione-d5; 352431-46-0

11747

Light yellow to green yellow liquid

1.0±0.1 g/cm3

108.0±0.0 °C at 760 mmHg

-52 °C

18.9±0.0 °C

26.4±0.2 mmHg at 25°C

1.395

-0.8

0

2

2

7

94.3

0

O=C(C(C([H])([H])[H])=O)C([H])([H])C([H])([H])[H]

TZMFJUDUGYTVRY-UHFFFAOYSA-N

InChI=1S/C5H8O2/c1-3-5(7)4(2)6/h3H2,1-2H3

pentane-2,3-dione

2,3-Pentanedione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 100 mg/mL (998.80 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (24.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (24.97 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (24.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)