Bide R W, Armour S J, Yee E
Defence R&D Canada Suffield, Box 4000, Medicine Hat, Alberta, Canada T1A 8K6.
J Appl Toxicol. 2005 Sep-Oct;25(5):393-409. doi: 10.1002/jat.1074.
Estimated human inhalation toxicity values for Sarin (GB) were calculated using a new two independent (concentration, exposure time), one dependent (toxic response), non-linear dose response (toxicity) model combined with re-evaluated allometric equations relating to animal and human respiration. Historical animal studies of GB toxicity containing both exposure and fractional animal response data were used to test the new process. The final data set contained 6621 animals, 762 groups, 37 studies and 7 species. The toxicity of GB for each species was empirically related to exposure concentration (C; mg m(-3)) and exposure time (T; min) through the surface function Y = b0 + b1 Log10C + b2 Log10T or Y = b0 + b2 Log10C(n)T where Y is the Normit, b0, b1 and b2 are constants and n is the 'toxic load exponent' (Normit is PROBIT - 5). Between exposure times of 0.17 and 30 min, the average value for n in seven species was 1.35 +/- 0.15. The near parallel toxic load equations for each species and the linear relationship between minute volume/body weight ratio and the inhalation toxicity (LCt50) for GB were used to create a pseudo-human data set and then an exposure time/toxicity surface for the human. The calculated n for the human was 1.40. The pseudo-human data had much more variability at low exposure times. Raising the lower exposure limit to 1 min, did not change the LCt50 but did result in lower variability. Raising the lower value to 2 min was counterproductive. Based on the toxic load model for 1-30 min exposures, the human GB toxicities (LCt01, LCt05, LCt50 and LCt95) for 70 kg humans breathing 15 l min(-1) were estimated to be 11, 16, 36 and 83; 18, 25, 57 and 132 and 24, 34, 79 and 182 mg x min m(-3) for 2, 10 and 30 min exposures, respectively. These values are recommended for general use for the total human population. The empirical relationships employed in the calculations may not be valid for exposure times >30 min.
使用一种新的双独立（浓度、暴露时间）、单依赖（毒性反应）、非线性剂量反应（毒性）模型，并结合重新评估的与动物和人类呼吸相关的异速生长方程，计算了沙林（GB）的人体吸入毒性值。包含暴露和部分动物反应数据的GB毒性的历史动物研究被用于测试这一新方法。最终数据集包含6621只动物、762组、37项研究和7个物种。通过表面函数Y = b0 + b1 Log10C + b2 Log10T或Y = b0 + b2 Log10C(n)T，GB对每个物种的毒性与暴露浓度（C；mg m(-3)）和暴露时间（T；min）经验性相关，其中Y是正态离差，b0、b1和b2是常数，n是“毒性负荷指数”（正态离差是概率单位 - 5）。在0.17至30分钟的暴露时间之间，七个物种的n平均值为1.35 +/- 0.15。利用每个物种近乎平行的毒性负荷方程以及分钟通气量/体重比与GB吸入毒性（LCt50）之间的线性关系，创建了一个伪人体数据集，然后得到了人体的暴露时间/毒性表面。计算得出的人体n值为1.40。伪人体数据在低暴露时间时变异性更大。将较低暴露限值提高到1分钟，并未改变LCt50，但确实降低了变异性。将较低值提高到2分钟则适得其反。基于1 - 30分钟暴露的毒性负荷模型，对于体重70 kg、呼吸频率15 l min(-1)的人，GB的人体毒性（LCt01、LCt05、LCt50和LCt95）在暴露2、10和30分钟时分别估计为11、16、36和83；1十八、25、57和132以及24、34、79和182 mg x min m(-3)。这些值推荐供整个人口普遍使用。计算中采用的经验关系在暴露时间>30分钟时可能无效。
