Estimating Lethal and Severe Toxic Effects in Minipigs Following 10, 60, and 180 Minutes of Whole-Body GB Vapor Exposure

摘要

Sexually mature male and female Gottingen minipigs were exposed to various concentrations of GB vapor via whole-body inhalation for 10, 60, or 180 min. Signs of nerve agent exposure were classified as lethal, severe, or moderate. Maximum likelihood estimation was used to calculate the median effect levels: lethal (LCT50) and severe (ECT50) for each gender-duration combination. Ordinal regression was used to model the product of concentration and time profile of the agent toxicity. Contrary to the values predicted by Haber's rule, LCT50 and ECT50 values increased as the duration of the exposures increased. The values for LCT50 (with 95% confidence limits) for 10-, 60-, and 180-min exposures in male minipigs were 72.5 (57.3-91.6), 105.7 (85.6-130.6), and 182.3 (145.2-228.9) mg.min/m3, respectively. The LCT50 values (with 95% confidence limits) for 10-, 60-, and 180-min exposures in female minipigs were 86.9 (69.2- 109.2), 127.1 (100.7-160.4), and 174.3 (134.7-225.5) mg.min/m3, respectively. The data were best fit using a probit slope of 15.7 and toxic load exponent of 1.38 (95% confidence limits of 1.25-1.51). Although males were significantly (p = 0.01) more sensitive than females to the lethal effects of GB vapor, the ratios of lethal to severe concentrations were higher in female minipigs (99% ANOVA confidence), indicating that there is less difference between severely toxic and lethal dosages in the female as compared to male pigs.