Hau K M, Connell D W, Richardson B J
Health and Safety Office, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
Toxicol Sci. 1999 Jan;47(1):93-8. doi: 10.1093/toxsci/47.1.93.
A model was developed for describing the triggering of nasal pungency in humans, based on the partition of volatile organic compounds (VOCs) between the air phase and the biophase. Two partition parameters are used in the model: the water-air partition coefficient and the octanol-water partition coefficient. The model was validated using data from the literature, principally on alcohols, acetates and ketones. The model suggests that all test compounds, regardless of their chemical functional groups, bind to a common receptor site within the hydrophobic interior of the bilayer membrane of the trigeminal nerve endings. There is probably only a slight, non-specific interaction between the VOC molecule and the receptor molecule, whereas this type of non-specific interaction for the detection of odor is much stronger. In practical terms, the suggestion that all VOCs share a common irritation receptor site implies that nasal-pungency thresholds of individual VOCs may be additive. Quantitative structure-activity relationships (QSARs) for nasal-pungency thresholds were also developed from the model, which can be used to predict nasal-pungency thresholds of common VOCs. Although the present model does not offer additional precision over that of M.H. Abraham et al., 1996, Fundam. Appl. Toxicol. 31, 71-76, it requires fewer descriptors and offers a physiological basis to the QSAR. Another advantage of the present model is that it also provides a basis for comparison between the olfactory process and nasal pungency.
基于挥发性有机化合物（VOCs）在气相和生物相之间的分配，开发了一种用于描述人类鼻腔刺激性触发的模型。该模型使用了两个分配参数：水-气分配系数和正辛醇-水分配系数。该模型利用文献数据进行了验证，主要涉及醇类、醋酸酯类和酮类。该模型表明，所有测试化合物，无论其化学官能团如何，都与三叉神经末梢双层膜疏水内部的一个共同受体位点结合。VOC分子与受体分子之间可能只有轻微的非特异性相互作用，而这种用于检测气味的非特异性相互作用要强得多。实际上，所有VOCs共享一个共同刺激受体位点的这一观点意味着单个VOCs的鼻腔刺激性阈值可能是可加的。还从该模型中开发了鼻腔刺激性阈值的定量构效关系（QSARs），可用于预测常见VOCs的鼻腔刺激性阈值。尽管当前模型相比M.H. Abraham等人1996年发表在《基础与应用毒理学》第31卷第71 - 76页上的模型并没有提供更高的精度，但它所需的描述符更少，并为QSAR提供了生理基础。当前模型的另一个优点是，它还为嗅觉过程和鼻腔刺激性之间的比较提供了基础。
