National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100, Copenhagen Ø, Denmark.
Regul Toxicol Pharmacol. 2018 Nov;99:89-97. doi: 10.1016/j.yrtph.2018.09.012. Epub 2018 Sep 14.
In mice, inhalation of formic, acetic, propionic and butyric acid caused a rapid decrease in the respiratory rate, which decreased to a stable level during the remaining part of the 30 min exposure period; this was due to sensory irritation. The concentration decreasing the respiratory rate (RD) by 50% (RD50) was 438, 308, 386 and 285 ppm, respectively, which allowed an adequate prediction of the Threshold Limit Values. In mice inhaling through a tracheal cannula, bypassing the trigeminal nerves, caused a slower decrease in respiratory rate due to pulmonary irritation. In the low concentration range, the pulmonary irritation response was less pronounced than the sensory irritation response. As the response in the normal (non-cannulated) mice was not influenced by pulmonary irritation, sensory irritation is the key effect, presumably due to the scrubbing effect of the upper airways, preventing access to the lungs. The activated receptors were in a non-lipophilic (hydrophilic) environment, from where the receptors may be activated by means of liberated protons. At the RD0, formic acid may, at least partly, activates ASIC, TRPV1 and TRPA1 receptors, whereas acetic, propionic and butyric acid may activate ASIC and TRPA1 receptors, based on the estimated pH in the mucus layer.
在小鼠中，吸入甲酸、乙酸、丙酸和丁酸会导致呼吸频率迅速下降，在 30 分钟暴露期的剩余时间内，呼吸频率降至稳定水平；这是由于感觉刺激。分别使呼吸率降低 50%（RD50）的浓度为 438、308、386 和 285 ppm，这足以充分预测阈限值。在通过气管套管吸入的小鼠中，绕过三叉神经会导致呼吸率下降更缓慢，这是由于肺部刺激。在低浓度范围内，肺部刺激反应不如感觉刺激反应明显。由于正常（未插管）小鼠的反应不受肺部刺激影响，因此感觉刺激是关键效应，可能是由于上呼吸道的擦洗作用，防止了进入肺部的通道。被激活的受体处于非脂溶性（亲水性）环境中，受体可能通过释放的质子被激活。在 RD0 时，甲酸可能至少部分激活 ASIC、TRPV1 和 TRPA1 受体，而乙酸、丙酸和丁酸可能通过估计的粘液层中的 pH 值激活 ASIC 和 TRPA1 受体。
