Tolerance to the Miotic Effect of Sarin Vapor in Rats After Multiple Low-Level Exposures

Inhibition of acetylcholinesterase (AChE) by the organophosphorous compound sarin (GB) results in the accumulation of acetylcholine and excessive cholinergic stimulation. There are few data in the literature regarding the effects of multiple low-level exposures to GB and other organophosphorous compounds via relevant routes of exposure. Therefore, the present study was undertaken, and is the first, to investigate the effect of low-level repeated whole-body inhalation exposures to GB vapor on pupil size and cholinesterase activity in the eyes and blood. Male Sprague-Dawley rats were exposed to 4.0 mg/m3 of GB vapor for 1 h on each of 3 consecutive days. Pupil size and cholinesterase activities were determined at various points throughout the exposure sequence. The results demonstrate that multiple inhalation exposures to GB vapor produce a decrease in the miotic potency of GB in rats. This tolerance developed at a dose of GB that produced no overt signs of intoxication other than miosis. AChE and butyrylch...