Pauluhn J, Machemer L H
Institute of Toxicology, Bayer AG, Wuppertal, Germany.
Toxicol Lett. 1998 Aug;96-97:361-8. doi: 10.1016/s0378-4274(98)00094-0.
The quantification of upper respiratory tract (URT) sensory irritation is considered to be important in rodent inhalation studies, since it may be also used as an endpoint mimicking trigeminal paraesthesias observed in humans. URT sensory irritation is known to be associated with rodent-specific secondary physiological effects such as depression of body temperature and changes in heart rate. In acutely exposed rats, these endpoints have been addressed by telemetrical measurements. The analysis of the ventilation pattern during acute inhalation studies of rats exposed to the alpha-cyano-pyrethroid cyfluthrin demonstrates that concentration-dependent URT sensory irritation was associated with a hypothermic response. The no-effect levels (NO(A)EL) based on the URT sensory irritation endpoint following acute inhalation exposure for 1 h and following a repeated 4-week or 13-week inhalation exposure for 6 h/day on 5 days week were virtually identical (approximately 0.1 mg/m3 air). An additional objective was to examine whether human volunteers experience comparable signs when acutely exposed for 1 h to airborne concentrations slightly above or in the range of the NO(A)EL. In human volunteers there were no clinically significant or pyrethroid related abnormalities in vital signs, ECG's or in any clinical laboratory tests after either exposure, although transient effects related to URT (sensory) irritation were reported. In conclusion, an initial actual exposure concentration of approximately 0.1 mg cyfluthrin/m3 air appears to be in the range of the sensory irritant threshold concentration for both rats and humans. Thus, with regard to physiological afferent portal-of-entry effects, the interspecies response was consistent.
在上呼吸道（URT）感觉刺激的量化在啮齿动物吸入研究中被认为是重要的，因为它也可以用作模拟人类观察到的三叉神经感觉异常的终点。已知URT感觉刺激与啮齿动物特有的继发性生理效应有关，如体温降低和心率变化。在急性暴露的大鼠中，这些终点已通过遥测测量得到解决。对暴露于α-氰基拟除虫菊酯氟氯氰菊酯的大鼠进行急性吸入研究期间的通气模式分析表明，浓度依赖性URT感觉刺激与体温过低反应有关。基于急性吸入暴露1小时以及重复4周或13周、每周5天、每天6小时吸入暴露后的URT感觉刺激终点的无效应水平（NO(A)EL）实际上是相同的（约0.1毫克/立方米空气）。另一个目标是检查人类志愿者在急性暴露于略高于或处于NO(A)EL范围内的空气传播浓度1小时时是否会出现类似的体征。在人类志愿者中，两种暴露后，生命体征、心电图或任何临床实验室检查均未出现临床上显著的或与拟除虫菊酯相关的异常，尽管报告了与URT（感觉）刺激相关的短暂效应。总之，初始实际暴露浓度约为0.1毫克氟氯氰菊酯/立方米空气似乎在大鼠和人类的感觉刺激阈值浓度范围内。因此，就生理传入进入途径效应而言，种间反应是一致的。
