Nerve agents dermal exposure

Minimizing further absorption of the nerve agent, if exposure is dermal... 

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). 

Liquid nerve agents applied dermally cause local sweating and muscular twitching starting 3 min to 2 h after exposure. Signs last for 3 to 5 days. Following dermal exposure to a large drop clinical effects start within 30 min but with small drops a delay of up to 18 h can be seen (Sidell et al, 1997). 

Most attempts at describing CWA PK and PD have used classical kinetic models that often fit one set of animal experimental data, at lethal doses, with extrapolation to low-dose or repeated exposure scenarios having limited confidence. This is due to the inherent nonlinearity in high-dose to low-dose extrapolations. Also, the classical approach is less adept at addressing multidose and multiroute exposure scenarios, as occurs with agents like VX, where there is pulmonary absorption of agent, as well as dermal absorption. PBPK models of chemical warfare nerve agents (CWNAs) provide an analytical approach to address many of these limitations. 

Casualties are caused both by inhalation and by dermal contact. Since VX is an oily liquid with low volatility, liquid droplets on the skin do not evaporate quickly, thus facilitating effective percutaneous absorption. Clothing can release VX for about 30 min after contact with VX vapor, which can lead to the exposure of other people. In addition to inhalation and percutaneous exposure, casualties can also be caused by ocular exposure, ingestion, and injection. Although VX does not mix with water as easily as nerve agents do, it could be released into water and lead to exposures via drinking contaminated water or dermal contact with contaminated water. People can also be exposed by eating food contaminated with VX. 

Miosis may also occur as a systemic feature, although more usually it follows direct exposure. This explains why, for example, modest dermal exposure may produce systemic features but not miosis. Abdominal pain, nausea and vomiting, involuntary micturition and defecation, muscle weakness and fasciculation, tremor, restlessness, ataxia and convulsions may follow dermal exposure, inhalation or ingestion of a nerve agent. Bradycardia, tachycardia and hypertension may occur, dependent on whether muscarinic or nicotinic effects predominate. If exposure is substantial, death may occur from respiratory failure within minutes, whereas mild or moderately exposed individuals usually recover completely, although EEG abnormalities have been reported in those severely exposed to sarin in Japan (Murata etal., 1997 Sekijima et al., 1997). 

Figure 5. Theoretical representation of the toxicokinetics of a nerve agent (following dermal exposure) and pharmacokinetics of the corresponding antidote (i.m. administration). Effective concentration refers to the threshold toxic or therapeutic blood concentrations of antidote, respectively...

Recent global events have focused attention on the potential threat of international and domestie chemical terrorism as well as the possibility of chemical warfare (CW) proliferation. The need for preparedness is highlighted by the wdi-documenicd domestic terrorist u.se of an anticholinesterase compound during the Tokyo subway incident of March 1995, when commuters received toxic inhalation and dermal exposures to a nerve agent deliberately released within subway cars and stations (Liliibridge, 1995 Morita et al., 1995 Okumura el al., 1996 Sidell, 1996). 

Inhalation of nerve agent vapor inhibits blood ChE activity and produces signs and symptoms of exposure more rapidly than does dermal contact. Although there is no correlation between ChE activity and clinical effects after exposure to small amounts of vapor, both clinical effects and ChE inhibition occur within minutes. In one study,41 both the maximal inhibition of RBC-ChE activity and the appearance of signs and symptoms occurred about 1 hour after intravenous administration of small amounts of VX. After ingestion of VX, the interval was 2 to 3 hours. 

EFFECTS OF DERMAL EXPOSURE TO LIQUID NERVE AGENTS... 

Even in very small amounts, nerve agents are highly toxic if you inhale or swallow them, or if they come in contact with your skin or eyes. In general, the manifestation of toxic effects is faster if you inhale or swallow nerve agents than if they contact your skin. The initial effects also depend on the amount you are exposed to. The onset of mild to moderate effects after dermal exposure may be delayed tor as long as 18 hours. 

Veterans were also exposed to a variety of over-the-counter (for example, nonsteroidal antiinflammatory drugs [NSAIDS]) and prescription drugs (such as antibiotics), vaccines, and a prophylactic, pyridostigmine bromide (PB) for nerve agent exposure. Although many of these drugs were administered orally and not topically, their presence in the bloodstream could have a significant effect on the dermal... 

It is unknown if animals may have decreased dermal absorption compared to humans due to their protective fur or feathers. Comparing dermal exposures in humans and other species also shows differences for the various nerve agents. Mice appear to be more sensitive to dermal... 

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