Comparison of sarin and cyclosarin toxicity by subcutaneous, intravenous and inhalation exposure in Gottingen minipigs

Abstract

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/m³, respectively. LCT₅₀ values for 10-, 60 - and 180-min exposures to vapor GB in female minipigs were 87, 127 and 174 mg min/m³, respectively. LCT₅₀ values for 10-, 60- and 180-min exposures to vapor GF in male minipigs were 218, 287 and 403 mg min/m³, respectively. LCT₅₀ values for 10-, 60- and 180-min exposures in female minipigs were 183, 282 and 365 mg min/m³, 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.

• Cyclosarin
• intravenous
• LCT₅₀
• LD₅₀
• nerve agents
• sarin
• subcutaneous

Acknowledgements

The authors thank Drs. Christopher Whalley, Robert Mioduszewski and Edward Jakubowski for their help in editorial review of the manuscript.