Nerve agents percutaneous exposure

Typically, there is a latent period with no visible effects between the time of exposure and the sudden onset of symptoms. This latency can range from 1 minutes to 18 hours and is affected by such factors as the amount of agent involved, the amount of skin surface in contact with the agent, and the area of the body exposed (see Liquids). Moist, sweaty areas of the body are more susceptible to percutaneous penetration by solid nerve agents. 

Benton et al. (2006b, 2007) experimentally determined the LCtso and LC50 in male and female adult SD rats exposed whole body to VX vapor for 10, 60, and 240 min in a dynamic exposure chamber (Table 6.3) study protocol was similar to that for agent GB in the studies conducted by Mioduszewski et al. (2001, 2002a). Experiments testing the role of decontamination less than 24 h post-exposure provided clear evidence for percutaneous toxicity induced by whole-body vapor exposure to the persistent nerve agent VX. For severe and lethal VX vapor exposure effects, females were not more susceptible than males for the exposure durations examined. 

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. 

Exposure of skin to various solvents (e.g., acetone, alcohols, ethers, gasoline) prior to exposure to nerve agents may increase the percutaneous hazard and decreases survival time associated with agent exposure. 

Although Nerve Agents are hazardous through inhalation, skin and eye exposure, ingestion, and abraded skin (e.g., breaks in the skin or penetration of skin by debris), the primary risk posed by "V" series Nerve Agents is through percutaneous exposure. 

In the majority of animal studies which have investigated the effects of low-level exposures, it has been expedient to administer nerve agents by injection. While this is a useful starting point, more definitive studies involving inhalation or percutaneous administration may also be required to address specific questions or model particular situations. 

From a military perspective, it is not necessarily the lethality of a percutaneous threat agent that is of primary concern but its ability to cause incapacitation. On this basis, HD can be considered to be equipotent to VX (the most toxic of nerve agents). In addition, the pathological consequences of HD exposure would likely impose a substantial burden on medical resources. Thus, while HD is not generally considered to be a lethal agent, its vesicant potency combined with its relative persistence and delayed effects contribute to its reputation as king of the war gasses . 

Nerve agent VX is a persistent agent which presents both a vapor and a percutaneous threat. VX is not very volatile, so it presents much less vapor hazard than GA and GB however, it is 100 times more toxic by the percutaneous route. Therefore, if VX is aerosolized due to an explosive release, it presents a percutaneous downwind hazard. Thermal decomposition rates of VX are 1.5 hours at 200°C (392°F), 4 minutes at 250°C (482°F), and 36 seconds at 295°C (563°F). In practical terms, a toxic dose of VX is more likely to result from skin rather than respiratory exposure however, all nerve agents are sufficiently volatile to pose an inhalation hazard. At agent concentrations of 30 mg/m3 or greater, median lethal inhalation doses can be attained in a few minutes. 

It should be expected that further quantitative measurements on elimination routes of nerve agents, in combination with the wealth of available toxicokinetic data, will enable further development of physiologically-based modeling of toxicokinetics. Further model developments are needed, in particular for the respiratory and percutaneous exposure routes. Ultimately, this modeling will enable reliable interspecies extrapolation of toxicokinetic results, including extrapolation to man, which is the ultimate goal. 

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