Low-Level Sarin Vapor Exposure in Rats: Effect of Exposure Concentration and Duration on Pupil Size

The probability of sarin (GB) vapor-induced miosis was estimated in rats exposed to various combinations of exposure concentration and duration. Groups of male and female rats (Sprague-Dawley) were exposed to one of a series of GB vapor concentrations for a single duration (10-240 minutes), in a who...

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Bibliographic Details
Main Authors: Mioduszewski, Robert J, Manthei, James H, Way, Ruth A, Burnett, David C, Gaviola, Bernardita P
Format: Report
Language:English
Subjects:
ACETYLCHOLINESTERASE
BLOOD
BUTYRATES
CARBOXYL RADICALS
Chemical, Biological and Radiological Warfare
CHOLINESTERASE
CONCENTRATION(COMPOSITION)
DOSAGE
DURATION
DYNAMICS
ESTERASES
EXPOSURE(GENERAL)
EYE
GB AGENT
INHALATION
LETHALITY
LINEAR REGRESSION ANALYSIS
LOW LEVEL
MIOSIS
NERVOUS SYSTEM
PATHOLOGY
PROBABILITY
RATS
RESPONSE(BIOLOGY)
SARIN
TOXIC AGENTS
TOXICITY
Toxicology
VAPORS
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Summary:The probability of sarin (GB) vapor-induced miosis was estimated in rats exposed to various combinations of exposure concentration and duration. Groups of male and female rats (Sprague-Dawley) were exposed to one of a series of GB vapor concentrations for a single duration (10-240 minutes), in a whole-body dynamic chamber. Separate effective concentrations for miosis (defined as a post-exposure pupil diameter 50% or less of the pre-exposure pupil diameter) in 50% of the exposed population (EC50) and corresponding dose-response slopes were determined, for each exposure time, by the Bliss probit method. Contrary to that predicted by Haber's rule, ECT50 values increased with exposure duration (i.e., the CT for 50% of the exposed population to show miosis was not constant over time). Linear regression analysis was used to derive a model of low-level GB vapor-induced pupil diameter changes in the rat as a function of exposure concentration and time. Female rats were more sensitive to GB vapor toxicity than male rats. Miosis was the only clinical sign noted following GB vapor exposure. Blood esterase (acetylcholinesterase, butyrylcholinesterase, and carboxylesterase) activities were not inhibited by exposure to the low-level range of GB vapor. Prepared in collaboration with GEO-Centers, Inc., Abingdon, MD.