Low-Level Sarin (GB) Vapor Exposure in the Gottingen Minipig: Effect of Exposure Concentration and Duration on Pupil Size

摘要

One of the goals of this study was to determine the lowest sarin (GB) vapor concentration of physiological significance. During the whole body exposure to GB vapor of a living species, the first noticeable effect is constriction of the pupil (miosis). The Gottingen minipig was chosen as a model for studying the effects of GB vapor because of the anatomical and physiological similarities between humans and minipigs. The minipigs were secured in a sling during exposure and their pupil size was continuously monitored under dim-light conditions using an infrared light-sensitive video camera. High-resolution images of the eye were collected before, during, and after each exposure. The pupil area was then quantified using a custom-designed software package. Ordinal regression was used to fit various response models to the data. The effective concentrations resulting in miosis in 50% (EC (sub 50)) of the exposed subjects were determined for 3 exposure-durations (10, 60, and 180 minutes). The median effective dose (ECT (sub 50)) associated with miosis was not constant over time. The value of the toxic load exponent was essentially independent of the model used: 1.32 +/- 0.18 (95% confidence interval of 1.14 to 1.50). Since this interval did not overlap one, Haber's rule was found to be an inappropriate time dependence model for this data set.