Long-Term Effects of Subclinical Exposures to Sarin

摘要

The purpose of this study was to determine if exposure to levels of sarin causing no overt clinical symptoms would cause adverse health effects that could persist after the exposure had ended. Inhalation exposures of male Fischer 344 rats to 0, 0.2 or 0.4 mg/ml of sarin for 1 hour/day for 1, 5 or 10 days under normal and heat-stressed conditions were completed and observations made at 1 day and 1 month after the exposures. Observations for which there was no effect of sarin included body weight, respiration rate and minute volume during exposure, body temperature and activity during the 30-day recovery period, apoptosis and histopathology in the brain. Brain mRNA for IL-1Beta, TNF-alpha, and IL-6 was increased in a dose-dependent manner. The immune system was depressed as noted by a dose-dependent suppression of the response of splenic lymphocytes to the mitogen, Concanavalin A. M1 cholinergic receptor site densities, unchanged at 1 day after repeated exposures, were decreased in a dose-dependent manner in the frontal cortex, olfactory tubercle, anterior olfactory nucleus and hippocampus at 30 days after exposure. M3 receptor sites were not affected by sarin exposure alone, but in the presence of heat stress, there was an upregulation of the sites in the frontal cortex, olfactory tubercle, anterior nucleus and striatum. These effects persisted at 30 days. Although red blood cell acetylcholine esterase (AChE) was only slightly inhibited by the 1-day exposure, there were 30% and 60% inhibitions at the low and high dose, respectively, after repeated exposures. Total or broad regional sections of the brain showed no inhibition of AChE; however, autoradiographic histochemical staining for AChE indicated sarin exposure alone reduced AChE in the cerebral cortex, striatum and olfactory bulb. Sarin exposure under heat- stress reduced AChE staining in the hippocampus.