Low volatile organophosphorous
nerve agents such as
VX, will most likely enter the body via the skin. The pharmacokinetics of drugs such as
oximes,
atropine and
diazepam, are not aligned with the variable and persistent toxicokinetics of the agent. Repeated administration of these drugs showed to improve treatment efficacy compared to a single injection treatment. Because of the effectiveness of continuous treatment, it was investigated to what extent a subchronic pretreatment with
carbamate (
pyridostigmine or
physostigmine combined with either
procyclidine or
scopolamine) would protect against percutaneous
VX exposure. Inclusion of
scopolamine in the pretreatment prevented
seizures in all animals, but none of the pretreatments affected survival time or the onset time of
cholinergic signs. These results indicate that percutaneous
poisoning with
VX requires additional conventional treatment in addition to the current pretreatment regimen. Decontamination of
VX-exposed skin is one of the most important countermeasures to mitigate the effects of the exposure. To evaluate the window of opportunity for decontamination, the fielded skin decontaminant Reactive Skin Decontaminant Lotion (RSDL) was tested at different times in hairless guinea pigs percutaneously challenged with 4× LD50
VX in IPA. The results showed that RSDL decontamination at 15 min after exposure could not prevent progressive blood
cholinesterase inhibition and therefore would still require additional treatment. A similar decontamination regimen with RSDL at 90 min showed that it still might effectively increase the time window of opportunity for treatment. In conclusion, the delay in absorption presents a window of opportunity for decontamination and treatment. The continuous release of
VX from the skin presents a significant challenge for efficacious
therapy, which should ideally consist of thorough decontamination and continuous treatment.