Jean Paul A, Gallavan Robert H, Kolesar Gary B, Siddiqui Waheed H, Oxley Jon A, Meeks Robert G
Dow Corning Corporation, Midland, Michigan 48686-0994, USA.
Inhal Toxicol. 2006 Jul;18(8):515-22. doi: 10.1080/08958370600686093.
The acute inhalation toxicity of 10 chlorosilanes was investigated in Fischer 344 rats using a 1-h whole-body vapor inhalation exposure and a 14-day recovery period. The median lethal concentration (LC50(1)) for each material was calculated from the nominal exposure concentrations and mortality. Experimentally derived LC50(1) values for monochlorosilanes (4257-4478 ppm) were greater than those for dichlorosilanes (1785-2092 ppm), which were greater than those for trichlorosilanes (1257-1611 ppm). Apparent was a strong structure-activity relationship (r2 = .97) between chlorine content and LC50(1) value. Estimated LC50(1) values for mono-, di-, and trichlorosilanes were determined to be 3262, 1639, and 1066 ppm, respectively, utilizing this relationship and the lower limit of the 95% prediction interval. The LC50(1) values determined in this series of studies were greater than that reported for hydrogen chloride (3124 ppm), when expressed on a chlorine equivalence basis (3570-5248 ppm), demonstrating that the acute toxicity of these chlorosilanes is similar to or less than that for hydrogen chloride. The good correlation between chlorine content and LC50(1) provides a sound basis for estimation of LC50(1) for chlorosilanes not already evaluated. The use of structure-activity relationships is consistent with the chemical industry and federal agency initiatives to reduce, refine, and/or replace the use of animals in testing without compromising the quality of health and safety assessments.
在Fischer 344大鼠中，采用1小时全身蒸汽吸入暴露和14天恢复期，研究了10种氯硅烷的急性吸入毒性。根据标称暴露浓度和死亡率计算出每种物质的半数致死浓度（LC50(1)）。实验得出的一氯硅烷（4257 - 4478 ppm）的LC50(1)值大于二氯硅烷（1785 - 2092 ppm）的LC50(1)值，而二氯硅烷的LC50(1)值又大于三氯硅烷（1257 - 1611 ppm）的LC50(1)值。氯含量与LC50(1)值之间存在明显的构效关系（r2 = 0.97）。利用这种关系和95%预测区间的下限，确定一氯、二氯和三氯硅烷的估计LC50(1)值分别为3262、1639和1066 ppm。当以氯当量为基础（3570 - 5248 ppm）表示时，本系列研究中确定的LC50(1)值大于氯化氢报告的LC50(1)值（3124 ppm），表明这些氯硅烷的急性毒性与氯化氢相似或更低。氯含量与LC50(1)之间的良好相关性为估算尚未评估的氯硅烷的LC50(1)提供了可靠依据。构效关系的使用与化学工业和联邦机构减少、完善和/或取代动物试验使用的倡议一致，同时又不影响健康和安全评估的质量。
