Morris J B, Wilkie W S, Shusterman D J
Toxicology Program, Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269, USA.
Toxicol Sci. 2005 Feb;83(2):380-7. doi: 10.1093/toxsci/kfi038. Epub 2004 Nov 17.
In human subjects 15-min exposure to 0.5-1.0 ppm chlorine gas causes a nasal obstructive response in the absence of a marked sensation of irritation. The current investigation was designed to assess the response of the mouse for comparative purposes. Respiratory physiological responses were measured in female C57Bl/6J mice exposed to 0.8 to 4.0 ppm chlorine gas. Chlorine was a potent sensory irritant with an RD50 of 2.3 ppm. The gas produced airway obstruction as indicated by a concentration-dependent increase in specific airways resistance (sRaw) during the 15-min exposure. At 0.8 ppm, chlorine produced only mild sensory irritation (<20% change in breathing frequency) and a 65% increase in sRaw. Pretreatment with atropine was without effect on the obstructive response, suggesting a lack of involvement of muscarinic cholinergic pathways. Pretreatment with the sensory nerve toxin, capsaicin, dramatically reduced both the sensory irritation and obstructive responses to chlorine, suggesting the involvement of sensory nerves. Studies were also performed using the surgically isolated upper respiratory tract of the anesthetized mouse. Chlorine was efficiently scrubbed from the airstream (>97%) in that site and produced an obstructive response that was of sufficient magnitude to account for the entire response observed in the intact animal. In summary, chlorine gas produces an immediate nasal obstructive response in the mouse that appears to be similar to that in the human.
在人体受试者中,暴露于0.5 - 1.0 ppm氯气15分钟会引发鼻腔阻塞反应,且无明显刺激感。本研究旨在评估小鼠的反应以便进行比较。对暴露于0.8至4.0 ppm氯气的雌性C57Bl/6J小鼠的呼吸生理反应进行了测量。氯气是一种强效的感觉刺激物,半数反应剂量(RD50)为2.3 ppm。在15分钟的暴露期间,该气体导致气道阻塞,表现为比气道阻力(sRaw)呈浓度依赖性增加。在0.8 ppm时,氯气仅产生轻微的感觉刺激(呼吸频率变化<20%),而sRaw增加了65%。用阿托品预处理对阻塞反应没有影响,这表明毒蕈碱胆碱能途径未参与其中。用感觉神经毒素辣椒素预处理可显著降低对氯气的感觉刺激和阻塞反应,这表明感觉神经参与其中。还使用麻醉小鼠的手术分离上呼吸道进行了研究。在该部位,氯气能有效地从气流中清除(>97%),并产生足以解释在完整动物中观察到的全部反应的阻塞反应。总之,氯气在小鼠中会引发即时的鼻腔阻塞反应,这似乎与人类的情况相似。