Cassee F R, Arts J H, Groten J P, Feron V J
Toxicology Division, TNO Nutrition and Food Research Institute, Zeist, The Netherlands.
Arch Toxicol. 1996;70(6):329-37. doi: 10.1007/s002040050282.
Sensory irritation of formaldehyde (FRM), acrolein (ACR) and acetaldehyde (ACE) as measured by the decrease in breathing frequency (DBF) was studied in male Wistar rats using nose-only exposure. Groups of four rats were exposed to each of the single compounds separately or to mixtures of FRM, ACR and/or ACE. Exposure concentrations of the mixtures were chosen in such a way that summation of the effects of each chemical would be expected not to exceed 80% reduction of the breathing frequency. FRM, ACR and ACE appeared to act as sensory irritants as defined by Alarie (1966, 1973). With FRM and ACR desensitization occurred, whereas with ACE the breathing frequency gradually decreased with increasing exposure time (up to 30 min). For mixtures, the observed DBF was more pronounced than the DBF for each compound separately, but was less than the sum of the DBFs for the single compounds. A model for three compounds competing for the same receptor was applied to predict the DBF of mixtures of FRM, ACE and ACR. The results also showed that with mixtures no desensitization occurred; in fact, the breathing frequency further decreased in the last 15 min of exposure. These observations were similar to those found for ACE alone, and might have been caused by effects on the upper respiratory tract. The results of the present study allow the conclusion that sensory irritation in rats exposed to mixtures of irritant aldehydes is more pronounced than that caused by each of the aldehydes separately, and that the DBF as a result of exposure to a mixture could well be predicted using a model for competitive agonism, thus providing evidence that the combined effect of these aldehydes is basically a result of competition for a common receptor (trigeminal nerve).
采用仅经鼻暴露的方式，在雄性Wistar大鼠中研究了通过呼吸频率降低（DBF）来衡量的甲醛（FRM）、丙烯醛（ACR）和乙醛（ACE）的感觉刺激作用。将四只大鼠分为一组，分别暴露于每种单一化合物或FRM、ACR和/或ACE的混合物中。混合物的暴露浓度选择为使得每种化学物质的效应总和预计不会超过呼吸频率降低80%。FRM、ACR和ACE似乎如Alarie（1966年、1973年）所定义的那样起感觉刺激物的作用。对于FRM和ACR发生了脱敏现象，而对于ACE，呼吸频率随着暴露时间增加（长达30分钟）而逐渐降低。对于混合物，观察到的DBF比每种单一化合物的DBF更明显，但小于单一化合物DBF的总和。应用一种三种化合物竞争同一受体的模型来预测FRM、ACE和ACR混合物的DBF。结果还表明，对于混合物没有发生脱敏现象；实际上，在暴露的最后15分钟呼吸频率进一步降低。这些观察结果与单独观察到的ACE的结果相似，可能是由对上呼吸道的影响引起的。本研究结果可以得出结论，暴露于刺激性醛混合物的大鼠中的感觉刺激比每种醛单独引起的更明显，并且使用竞争性激动模型可以很好地预测暴露于混合物导致的DBF，从而提供证据表明这些醛的联合作用基本上是竞争共同受体（三叉神经）的结果。
