US Army Edgewood Chemical and Biological Center (ECBC) , Aberdeen Proving Ground, Aberdeen, MD , USA.
Inhal Toxicol. 2014 Feb;26(3):175-84. doi: 10.3109/08958378.2013.872212.
Sexually mature male and female Gottingen minipigs were exposed to various concentrations of GB and GF vapor via whole-body inhalation exposures or to liquid GB or GF via intravenous or subcutaneous injections. Vapor inhalation exposures were for 10, 60 or 180 min. Maximum likelihood estimation was used to calculate the median effect levels for severe effects (ECT50 and ED50) and lethality (LCT50 and LD50). Ordinal regression was used to model the concentration × time profile of the agent toxicity. Contrary to that predicted by Haber's rule, LCT50 values increased as the duration of the exposures increased for both nerve agents. The toxic load exponents (n) were calculated to be 1.38 and 1.28 for GB and GF vapor exposures, respectively. LCT50 values for 10-, 60- and 180-min exposures to vapor GB in male minipigs were 73, 106 and 182 mg min/m(3), respectively. LCT50 values for 10-, 60 - and 180-min exposures to vapor GB in female minipigs were 87, 127 and 174 mg min/m(3), respectively. LCT50 values for 10-, 60- and 180-min exposures to vapor GF in male minipigs were 218, 287 and 403 mg min/m(3), respectively. LCT50 values for 10-, 60- and 180-min exposures in female minipigs were 183, 282 and 365 mg min/m(3), respectively. For GB vapor exposures, there was a tenuous gender difference which did not exist for vapor GF exposures. Surprisingly, GF was 2-3 times less potent than GB via the inhalation route of exposure regardless of exposure duration. Additionally GF was found to be less potent than GB by intravenous and subcutaneous routes.
性成熟的雄性和雌性 Gottingen 小型猪通过全身吸入暴露或静脉或皮下注射液体 GB 或 GF 来接触不同浓度的 GB 和 GF 蒸气。蒸气吸入暴露时间为 10、60 或 180 分钟。最大似然估计用于计算严重效应（ECT50 和 ED50）和致死性（LCT50 和 LD50）的中位数效应水平。有序回归用于模拟该试剂毒性的浓度-时间曲线。与哈伯定律预测的相反，对于两种神经毒剂，随着暴露时间的延长，LCT50 值增加。蒸气 GB 暴露的毒性负荷指数（n）分别为 1.38 和 1.28。雄性小型猪蒸气 GB 10、60 和 180 分钟暴露的 LCT50 值分别为 73、106 和 182mgmin/m(3)。雌性小型猪蒸气 GB 10、60 和 180 分钟暴露的 LCT50 值分别为 87、127 和 174mgmin/m(3)。雄性小型猪蒸气 GF 10、60 和 180 分钟暴露的 LCT50 值分别为 218、287 和 403mgmin/m(3)。雌性小型猪蒸气 GF 10、60 和 180 分钟暴露的 LCT50 值分别为 183、282 和 365mgmin/m(3)。对于 GB 蒸气暴露，存在微弱的性别差异，而对于 GF 蒸气暴露则不存在。令人惊讶的是，无论暴露时间如何，GF 通过吸入途径暴露的效力比 GB 低 2-3 倍。此外，GF 通过静脉和皮下途径的效力比 GB 低。
