Nerve agents oral effects

The human intravenous bolus dose of oximes in nerve agent treatment ranges between 250 and 500 mg ". Side effects of oxime treatment in humans were monitored in 750 volunteers, and the main adverse effects reported were changes in blood pressure, pulse rate, dizziness, nausea and blurred vision . Oral administration of oximes produces gastrointestinal distress. ... 

The major gap in the available information on GA is the lack of either a subchronic or a chronic oral toxicity study from which to derive the RfD. The absence of oral data could be addressed by conducting a subchronic oral toxicity study that assesses anti-ChE activity in red blood cells (RBCs) and plasma in one or preferably two species. If further research reveals that significant toxic effects can be induced by any of the nerve agents at doses below those that cause significant ChE inhibition, additional studies should be conducted to reassess the safety of the recommended RfD for GA. 

The potency of nerve agents can also be expressed in terms of the dose necessary to produce 50% inhibition of cholinesterase (ChEso). In humans, RBC-CI1E50 values for GB are 0.003 mg/kg and 0.01 mg/kg, respectively, for i.v. and oral doses (Grob and Harvey, 1958). The relative effectiveness of nerve agents in inhibiting cholinesterase is closely correlated with their acute toxicity (see Appendix A). 

Nerve agents can be absorbed by any route (ocular, oral, inhalation, dermal) (RTECS, 2008 HSDB, 2008). Onset of signs and duration of effects depend on the form of nerve gas (vapor, hquid) and the route of exposure. With a vapor exposure and inhalation, local signs of nasal discharge and respiratory noise begin within one to several minutes and signs can last for a few hours (mild exposure) up to 1 to 2 days (severe exposure) (Pfaff, 1998). Inhalation of a large amount of the vapor will result in sudden loss of consciousness, apnea, flaccid paralysis, and seizures within seconds to 2 to 3 min (Sidell et al, 1997). Peak effects are seen within 20 to 30 min and death is usually due to respiratory failure (Berkenstadt et al, 1991). 

There are only a few reports in the open literature on the effect of oximes in nerve agent-exposed humans. Pralidoxime chloride was very effective in reactivating erythrocyte AChE in individuals exposed to sublethal intravenous or oral VX while this oxime was substantially less effective in humans exposed to IV sarin (Sidell and Groff, 1974). Accidental sarin exposure by inhalation resulted in an initial progressive deterioration (coma, apnea) of the patient despite atropine and 2-PAM treatmentand substantial recovery of erythrocyte AChE activity (Sidell, 1974). It took several hours until the patient s condition improved. Sidell also reported an accidental oral soman exposure. A lethal dose of diluted soman splashed into and around the mouth of an individual, resulting in coma, bronchoconstriction and respiratory depression, which was successfully treated with repeated atropine injections. 2-PAM (2 g IV) had no effect on inhibited erythrocyte AChE. 

---