van Helden Herman P M, Trap Henk C, Kuijpers Willem C, Oostdijk John P, Benschop Hendrik P, Langenberg Jan P
Department of Medical Countermeasures, TNO Prins Maurits Laboratory, PO Box 45, 2280 AA Rijswijk, The Netherlands.
J Appl Toxicol. 2004 Jan-Feb;24(1):59-68. doi: 10.1002/jat.948.
The purpose of this pilot study was to indicate, for low-level exposure of conscious guinea pigs and marmoset monkeys to sarin vapour in air, the lowest-observable-adverse-effect level (LOAEL) of sarin for miosis. This is the concentration x time (C.t) value (t = 5 h) of exposure at which miosis becomes significant. The ratio of pupil and iris diameters, measured on digital photographs taken on-line during exposure, was calculated as a measure for miosis. The exposure concentrations were in the range 7-150 microg x m(-3) and the exposure times needed to achieve significant miosis were in the range 10-300 min. Both vehicle- and pyridostigmine-pretreated animals were used in the experiments. The latter pretreatment resulted in ca. 30% inhibition of erythrocyte acetylcholinesterase in both species. In vehicle-pretreated guinea pigs and marmosets the pupil size was decreased significantly (P < 0.05) at sarin doses of 1.8 +/- 0.3 and 2.5 +/- 0.8 mg x min x m(-3), respectively. In pyridostigmine-pretreated guinea pigs and marmosets the pupil size was affected significantly (P < 0.05) at 1.8 +/- 0.5 and 3.0 +/- 0.8 mg x min x m(-3), respectively. Evidently there is no significant influence of pyridostigmine pretreatment on the LOAEL. These data were addressed in light of the recommended occupational and detection limits for sarin vapour in air. It was concluded that miosis will occur during low-level sarin exposure at levels that are not detectable by the currently fielded alarm systems, assuming that humans are as sensitive for sarin vapour in air as guinea pigs and marmosets.
本初步研究的目的是确定清醒的豚鼠和狨猴在空气中低水平接触沙林毒气时，沙林引起瞳孔缩小的最低可观察到有害作用水平（LOAEL）。这是指接触时瞳孔缩小变得明显的浓度×时间（C.t）值（t = 5小时）。通过在接触过程中在线拍摄的数码照片测量瞳孔和虹膜直径的比值，以此作为瞳孔缩小的衡量指标。接触浓度范围为7 - 150微克×立方米⁻³，实现明显瞳孔缩小所需的接触时间范围为10 - 300分钟。实验中使用了未处理动物和经吡啶斯的明预处理的动物。后一种预处理导致两种动物的红细胞乙酰胆碱酯酶均受到约30%的抑制。在未处理的豚鼠和狨猴中，当沙林剂量分别为1.8 ± 0.3和2.5 ± 0.8毫克×分钟×立方米⁻³时，瞳孔大小显著减小（P < 0.05）。在经吡啶斯的明预处理的豚鼠和狨猴中，当剂量分别为1.8 ± 0.5和3.0 ± 0.8毫克×分钟×立方米⁻³时，瞳孔大小受到显著影响（P < 0.05）。显然，吡啶斯的明预处理对最低可观察到有害作用水平没有显著影响。根据空气中沙林毒气的推荐职业接触限值和检测限值对这些数据进行了分析。得出的结论是，假设人类对空气中沙林毒气的敏感度与豚鼠和狨猴相同，那么在当前部署的警报系统无法检测到的低水平沙林接触期间，将会出现瞳孔缩小的情况。
