Inhalation Dosimetry of Diacetyl and Butyric Acid, Two Components of Butter Flavoring Vapors
Inhalation Dosimetry of Diacetyl and Butyric Acid, Two Components of Butter Flavoring Vapors
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DOI：
10.1093/toxsci/kfn222
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发表时间：
2009-03-01
影响因子：
3.8
通讯作者：
Hubbs, Ann F.
中科院分区：
文献类型：
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作者：
Morris, John B.;Hubbs, Ann F.
职业接触黄油调味蒸气 (BFV) 与严重的肺损伤有关。当前研究的目标是表征 BFV 的两种成分二乙酰和丁酸的吸入剂量模式，并开发一种混合计算流体动力学-生理学药代动力学模型 (CFD-PBPK) 来描述这些模式。在等速流动条件下测量麻醉雄性 Sprague-Dawley 大鼠上呼吸道单独和组合的二乙酰和丁酸蒸气的摄取，并使用摄取数据来验证 CFD-PBPK 模型。在 100-400 毫升/分钟的流量下，二乙酰蒸气（100 或 300 ppm）从气流中被净化，效率为 76-36%。丁酸 (30 ppm) 的洗涤效率 > 90%。同时接触丁酸会导致二乙酰摄取量小幅但显着减少（36% vs. 31%，p < 0.05）。二乙酰在体外鼻组织中代谢，可能是通过二乙酰还原酶（一种已知可被丁酸抑制的酶）代谢的。 CFD-PBPK 模型密切描述了二乙酰的摄取；丁酸对二乙酰摄取的减少可以通过抑制二乙酰还原酶来解释。通过该模型推断人类表明，与大鼠相比，吸入的二乙酰在人类中可能更大程度地渗透到肺内气道。因此，根据剂量关系，大鼠的肺外气道损伤可以预测人类的肺内气道损伤。丁酸可以通过抑制其代谢和/或改变其吸入剂量模式来调节二乙酰毒性。
Occupational exposure to butter flavoring vapors (BFV) is associated with significant pulmonary injury. The goal of the current study was to characterize inhalation dosimetric patterns of diacetyl and butyric acid, two components of BFV, and to develop a hybrid computational fluid dynamic-physiologically based pharmacokinetic model (CFD-PBPK) to describe these patterns. Uptake of diacetyl and butyric acid vapors, alone and in combination, was measured in the upper respiratory tract of anesthetized male Sprague-Dawley rats under constant velocity flow conditions and the uptake data were used to validate the CFD-PBPK model. Diacetyl vapor (100 or 300 ppm) was scrubbed from the airstream with 76-36% efficiency at flows of 100-400 ml/min. Butryic acid (30 ppm) was scrubbed with > 90% efficiency. Concurrent exposure to butyric acid resulted in a small but significant reduction of diacetyl uptake (36 vs. 31%, p < 0.05). Diacetyl was metabolized in nasal tissues in vitro, likely by diacetyl reductase, an enzyme known to be inhibited by butyric acid. The CFD-PBPK model closely described diacetyl uptake; the reduction in diacetyl uptake by butyric acid could be explained by inhibition of diacetyl reductase. Extrapolation to the human via the model suggested that inspired diacetyl may penetrate to the intrapulmonary airways to a greater degree in the human than in the rat. Thus, based on dosimetric relationships, extrapulmonary airway injury in the rat may be predictive of intrapulmonary airway injury in humans. Butyric acid may modulate diacetyl toxicity by inhibiting its metabolism and/or altering its inhalation dosimetric patterns.