RSDL decontamination of human skin contaminated with the nerve agent VX.
Dermal exposure to low volatile organophosphorus compounds (OPC) may lead to penetration through the skin and uptake in the blood circulation. Skin decontamination of toxic OPCs, such as pesticides and chemical warfare nerve agents, might therefore be crucial for mitigating the systemic toxicity following dermal exposure. Reactive skin decontamination lotion (RSDL) has been shown to reduce toxic effects in animals dermally exposed to the nerve agent VX. In the present study, an in vitro flow-through diffusion cell was utilized to evaluate the efficacy of RSDL for decontamination of VX exposed to human epidermis. In particular, the impact of timing in the initiation of decontamination and agent dilution in water was studied. The impact of the lipophilic properties of VX in the RSDL decontamination was additionally addressed by comparing chemical degradation in RSDL and decontamination efficacy between the VX and the hydrophilic OPC triethyl phosphonoacetate (TEPA). The epidermal membrane was exposed to 20, 75 or 90% OPC diluted in deionized water and the decontamination was initiated 5, 10, 30, 60 or 120min post-exposure. Early decontamination of VX with RSDL, initiated 5-10min after skin exposure, was very effective. Delayed decontamination initiated 30-60min post-exposure was less effective but still the amount of penetrated agent was significantly reduced, while further delayed start of decontamination to 120min resulted in very low efficacy. Comparing RSDL decontamination of VX with that of TEPA showed that the decontamination efficacy at high agent concentrations was higher for VX. The degradation mechanism of VX and TEPA during decontamination was dissected by31P NMR spectroscopy of the OPCs following reactions with RSDL and its three nucleophile components. The degradation rate was clearly associated with the high pH of the specific solution investigated; i.e. increased pH resulted in a more rapid degradation. In addition, the solubility of the OPC in RSDL also influenced the degradation rate since the degradation of VX was significantly faster when the NMR analysis was performed in the organic solvent acetonitrile compared to water. In conclusion, we have applied the in vitro flow-through diffusion cell for evaluation of skin decontamination procedures of human epidermis exposed to OPCs. It was demonstrated that early decontamination is crucial for efficient mitigation of epidermal penetration of VX and that almost complete removal of the nerve agent from the skin surface is possible. Our data also indicate that the pH of RSDL together with the solubility of OPC in RSDL are of primary importance for the decontamination efficacy.
Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden. Electronic address: lina.thors@foi.se.
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Thors
Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden.
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Lindberg
Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden.
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Johansson
Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden.
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Koch
Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden.
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Koch
Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden.
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Hägglund
Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden; Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå, Sweden.
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Bucht
D000279:Administration, Cutaneous; D003666:Decontamination / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D000067397:Nerve Agents / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000633:toxicity; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012995:Solubility
D000067397:Nerve Agents; D009943:Organophosphorus Compounds; D009946:Organothiophosphorus Compounds; D010746:Phosphonoacetic Acid; C076891:triethyl phosphonoacetate; C009680:VX-agent
Agent degradation; Decontamination; Human skin; Organophosphorus compounds; RSDL