Bronchiolitis Obliterans Syndrome in Chemical Workers Producing Diacetyl for Food Flavorings

Rooy, F G B G J van; Rooyackers, J.M.; Prokop, Mathias; Houba, Remko; Smit, Lidwien A M; Heederik, Dick

doi:10.1164/rccm.200611-1620oc

Cited by 144 publications

(83 citation statements)

References 18 publications

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“…Similar findings were observed by Lockey et al 25 Three cases of clinical bronchiolitis obliterans were also diagnosed in a diacetyl facility in the Netherlands. 26 Finally, a cross-sectional analysis of medical surveillance data from 16 companies confirmed the risk of lung disease among workers at companies using diacetyl. 27 AP is chemically and structurally almost identical to DA, has a similar buttery, creamy flavor, and has been used as a DA substitute in many flavoring manufacturing facilities.…”

Section: Toxicity Of Da and Apmentioning

confidence: 92%

Evaluation of Electronic Cigarette Liquids and Aerosol for the Presence of Selected Inhalation Toxins

Farsalinos

Kistler

Gillman

et al. 2014

Nicotine &Amp; Tobacco Research

272

217

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Introduction: The purpose of this study was to evaluate sweet-flavored electronic cigarette (EC) liquids for the presence of diacetyl (DA) and acetyl propionyl (AP), which are chemicals approved for food use but are associated with respiratory disease when inhaled. Methods: In total, 159 samples were purchased from 36 manufacturers and retailers in 7 countries. Additionally, 3 liquids were prepared by dissolving a concentrated flavor sample of known DA and AP levels at 5%, 10%, and 20% concentration in a mixture of propylene glycol and glycerol. Aerosol produced by an EC was analyzed to determine the concentration of DA and AP. Results: DA and AP were found in 74.2% of the samples, with more samples containing DA. Similar concentrations were found in liquid and aerosol for both chemicals. The median daily exposure levels were 56 μg/day (IQR: 26-278 μg/day) for DA and 91 μg/day (IQR: 20-432 μg/day) for AP. They were slightly lower than the strict NIOSH-defined safety limits for occupational exposure and 100 and 10 times lower compared with smoking respectively; however, 47.3% of DA and 41.5% of AP-containing samples exposed consumers to levels higher than the safety limits. Conclusions: DA and AP were found in a large proportion of sweet-flavored EC liquids, with many of them exposing users to higher than safety levels. Their presence in EC liquids represents an avoidable risk. Proper measures should be taken by EC liquid manufacturers and flavoring suppliers to eliminate these hazards from the products without necessarily limiting the availability of sweet flavors.

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Section: Toxicity Of Da and Apmentioning

confidence: 92%

Evaluation of Electronic Cigarette Liquids and Aerosol for the Presence of Selected Inhalation Toxins

Farsalinos

Kistler

Gillman

et al. 2014

Nicotine &Amp; Tobacco Research

272

217

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“…In particular, acetic acid and acetoin are abundant in butter flavoring vapor mixtures and also were found along with diacetyl in the less complex exposure in a flavoring manufacturing workplace with affected workers (van Rooy et al, 2007(van Rooy et al, , 2009. It is critical to understand whether acetic acid and acetoin, as frequent adjunct agents, might mitigate or exacerbate the effects of diacetyl inhaled concomitantly.…”

Section: Effects Of Mixed Inhalation Exposure To Diacetyl Acetic Acimentioning

confidence: 99%

“…The primary component in butter flavoring mixture that is thought to be toxic to the lungs of workers is diacetyl (2,3-butanedione; C 4 H 6 O 2 ) (Hubbs et al, 2008;van Rooy et al, 2007). Diacetyl is a low-molecular-weight, four-carbon α-diketone largely responsible for the taste of butter (Harber et al, 2006;Hubbs et al, 2008).…”

mentioning

confidence: 99%

“…Other volatile components in flavoring mixtures, alone or in combination with diacetyl, may exert pulmonary toxicity. In particular, acetoin and acetic acid are present in vapor mixtures associated with popcorn workers' lung (Boylstein et al, 2006;Kreiss et al, 2002;van Rooy et al, 2007van Rooy et al, , 2009). …”

mentioning

confidence: 99%

“…The potential role of the epithelium in the development of these responses was investigated. Finally, other flavorings, such as acetic acid and acetoin, are often present in abundant amounts in the vapors of butter flavorings and also were reported in a flavoring manufacturing workplace with affected workers (Boylstein et al, 2006;van Rooy et al, 2007van Rooy et al, , 2009). They are not currently regarded as being key compounds in the development of toxicity in humans.…”

mentioning

confidence: 99%

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Popcorn Flavoring Effects on Reactivity of Rat Airways in Vivo and in Vitro

Zaccone

Thompson

Ponnoth

et al. 2013

Journal of Toxicology and Environmental Health, Part A

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Abstract"Popcorn workers' lung" is an obstructive pulmonary disease produced by inhalation of volatile artificial butter flavorings. In rats, inhalation of diacetyl, a major component of butter flavoring, and inhalation of a diacetyl substitute, 2,3-pentanedione, produce similar damage to airway epithelium. The effects of diacetyl and 2,3-pentanedione and mixtures of diacetyl, acetic acid, and acetoin, all components of butter flavoring, on pulmonary function and airway reactivity to methacholine (MCh) were investigated. Lung resistance (R L ) and dynamic compliance (C dyn ) were negligibly changed 18 h after a 6-h inhalation exposure to diacetyl or 2,3-pentanedione (100-360 ppm). Reactivity to MCh was not markedly changed after diacetyl, but was modestly decreased after 2,3-pentanedione inhalation. Inhaled diacetyl exerted essentially no effect on reactivity to mucosally applied MCh, but 2,3-pentanedione (320 and 360 ppm) increased reactivity to MCh in the isolated, perfused trachea preparation (IPT). In IPT, diacetyl and 2,3-pentanedione (≥3 mM) applied to the serosal and mucosal surfaces of intact and epithelium-denuded tracheas initiated transient contractions followed by relaxations. Inhaled acetoin (150 ppm) exerted no effect on pulmonary function and airway reactivity in vivo; acetic acid (27 ppm) produced hyperreactivity to MCh; and exposure to diacetyl + acetoin + acetic acid (250 + 150 + 27 ppm) led to a diacetyl-like reduction in reactivity. Data suggest that the effects of 2,3-pentanedione on airway reactivity are greater than those of diacetyl, and that flavorings are airway smooth muscle relaxants and constrictors, thus indicating a complex mechanism.Employees at microwave popcorn manufacturing factories have developed "popcorn workers' lung" (Department

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Ketones of Four or Five Carbons

O’Donoghue

2023

Patty's Toxicology

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Several billion pounds of ketones are produced annually for industrial use in the United States and worldwide. Those with the highest production volumes include acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, 4‐hydroxy‐4‐methyl‐2‐pentanone, isophorone, mesityl oxide, and acetophenone. Common methods used to manufacture ketones include aliphatic hydrocarbon oxidation, alcohol dehydration with subsequent oxidation, dehydrogenation of phenol, alkyl aromatic hydrocarbon oxidation, and condensation reactions. Ketones are commonly used in industry as solvents, extractants, chemical intermediates, and, to a lesser extent, flavor and fragrance ingredients. Although a common effect of excessive ketone exposure is CNS depression some ketones have pulmonary effects that are well below levels that cause acute CNS effects. For example, ketones such as diacetyl and chemically similar chemicals used for flavoring foods, coffee, and e‐cigarettes provide opportunities for widespread exposure and very debilitating pulmonary disease including bronchiolitis obliterans.

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Bronchiolitis Obliterans Syndrome in Chemical Workers Producing Diacetyl for Food Flavorings

Abstract: Exposure to an agent during diacetyl production appears to be responsible for causing bronchiolitis obliterans syndrome in chemical process operators, consistent with the suspected role of diacetyl in downstream food production.

Cited by 144 publications

References 18 publications

Evaluation of Electronic Cigarette Liquids and Aerosol for the Presence of Selected Inhalation Toxins

Evaluation of Electronic Cigarette Liquids and Aerosol for the Presence of Selected Inhalation Toxins

Popcorn Flavoring Effects on Reactivity of Rat Airways in Vivo and in Vitro

Ketones of Four or Five Carbons

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