Skin decontamination of mustards and organophosphates: comparative efficiency of RSDL and Fuller's earth in domestic swine

2007 ◽  
Vol 26 (2) ◽  
pp. 135-141 ◽  
Author(s):  
L. Taysse ◽  
S. Daulon ◽  
S. Delamanche ◽  
B. Bellier ◽  
P. Breton

Research in skin decontamination and therapy of chemical warfare agents has been a difficult problem due to the simultaneous requirement of rapid action and non-aggressive behaviour. The aim of this study was to compare the performance of two decontaminating systems: the Canadian Reactive Skin Decontaminant Lotion (RSDL) and the Fuller's Earth (FE). The experiment was conducted with domestic swine, as a good model for extrapolation to human skin. RSDL and FE were tested against sulphur mustard (SM), a powerful vesicant, and VX, a potent and persistent cholinesterase inhibitor. When used 5 min after contamination, the results clearly showed that both systems were active against SM (10.1 mg/cm2) and VX (0.06 mg/cm2). The potency of the RSDL/sponge was statistically better than FE against skin injury induced by SM, observed 3 days post-exposure. RSDL was rather more efficient than FE in reducing the formation of perinuclear vacuoles and inflammation processes in the epidermis and dermis. Against a severe inhibition (67%) of plasmatic cholinesterases induced by VX poisoning, the potencies of the RSDL/sponge and FE were similar. Both systems completely prevented cholinesterase inhibition, which indirectly indicates a prevention of toxic absorption through the skin. Human & Experimental Toxicology (2007) 26, 135-141

2017 ◽  
Vol 3 (1) ◽  
pp. 5
Author(s):  
G. K. Prasad ◽  
Anshoo Gautam ◽  
G. M. Kannan ◽  
J. Acharya ◽  
A. K. Gupta ◽  
...  

<p>Present paper relates to nanomaterials based decontamination formulation made up of TiO2, MgO, and ZnO nanoparticles for the use against chemical warfare agents. This decontamination formulation was prepared by mixing 90 per cent of TiO2 nanoparticles of 5-15 nm size range, 8 per cent of MgO nanoparticles of 5-15 nm size range, and 2 per cent of ZnO nanoparticles of 20-30 nm size range. Prepared formulation exhibited 98-99 per cent of physical removal efficiency against contaminated glass, rubber, painted metal, metal surfaces. It efficiently removed chemical warfare agents from contaminated skin thus ameliorating chances of fatality which is expected due to skin penetrated chemical warfare agents. It also chemically degraded 97 per cent of sulphur mustard in 24 h, 99.9 per cent of sarin in 2 h, respectively unlike Fuller’s earth which chemically degraded only 63 per cent of sulphur mustard and 59 per cent of sarin in 24 h .</p>


2008 ◽  
Vol 27 (3) ◽  
pp. 253-261 ◽  
Author(s):  
S Bjarnason ◽  
J Mikler ◽  
I Hill ◽  
C Tenn ◽  
M Garrett ◽  
...  

An anesthetized domestic swine model was used to compare the efficacy and cross-contamination potential of selected skin decontaminant products and regimens against the chemical warfare agent, VX. Animals topically exposed to 2×, 3× or 5× LD50 VX showed typical signs of organophosphate nerve agent poisoning, including miosis, salivation, mastication, dysrhythmias, and respiratory distress prior to death. Animals were exposed to 5× LD50 VX and then decontaminated 45 min later with the reactive skin decontamination lotion (RSDL®), Fuller’s earth (FE), 0.5% hypochlorite, or soapy water. Survival was 100% when the reactive skin decontamination lotion or FE was utilized, although 50% of Fuller’s earth-decontaminated animals exhibited serious signs of VX poisoning. Decontamination of VX-treated animals with 0.5% hypochlorite was less effective but also increased survival. Soapy water was ineffective in preventing lethality. Blood cholinesterase levels were not predictive of clinical outcome in decontaminated animals. The potential of “decontaminated” VX in open wounds to cause poisoning was assessed by vigorously mixing 5× LD50 VX with the test decontaminants for 5 min and then placing the mixture onto a full-thickness skin wound. Soapy water was ineffective in preventing lethality. Although treatment with dry Fuller’s earth prevented death and all signs of organophosphate poisoning, a significant proportion of treated animals decontaminated with Fuller’s earth in aqueous suspension exhibited serious signs of organophosphate poisoning, suggesting that live agent may be desorbed from Fuller’s earth when it is exposed to a liquid environment. Animals treated with reactive skin decontamination lotion or 0.5% hypochlorite-VX mixtures showed no signs of organophosphate poisoning during the 6- h test period.


2010 ◽  
Vol 30 (6) ◽  
pp. 491-498 ◽  
Author(s):  
L. Taysse ◽  
F. Dorandeu ◽  
S. Daulon ◽  
A. Foquin ◽  
N. Perrier ◽  
...  

Using the hairless mouse screening model presented in the companion paper1 the aim of this study was to assess two skin decontaminating systems: Fuller’s earth (FE) and Reactive Skin Decontamination Lotion (RSDL) against two extremely toxic chemical warfare agents that represent a special percutaneous hazard, sulphur mustard (SM) and O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX). Five minutes after being exposed on the back to either 2 µL of neat sulphur mustard or 50 µg.kg-1 of diluted VX, mice were decontaminated. Both systems were able to reduce blisters 3 days after SM exposure. However, RSDL was found to be more efficient than FE in reducing the necrosis of the epidermis and erosion. In the case of VX exposure, RSDL, whatever the ratio of decontaminant to toxicant used (RSDL 10, 20, 50), was not able to sufficiently prevent the inhibition of plasma cholinesterases taken as a surrogate marker of exposure and toxicity. Only FE reduced significantly the ChE inhibition. Some of these observations are different from our previous results obtained in domestic swine and these changes are thus discussed in the perspective of using SKH-1 hairless mice for the initial in vivo screening of decontaminants.


2020 ◽  
Author(s):  
Clémence Maupu ◽  
Julie Enderlin ◽  
Alexandre Igert ◽  
Stéphane Auvin ◽  
Rahma Hassan-Abdi ◽  
...  

Abstract Background: Organophosphate compounds (OPs), either pesticides or chemical warfare agents are characterized by irreversible cholinesterase inhibition. In addition to severe peripheral symptoms, high doses of OPs can lead to seizures and status epilepticus (SE). Long lasting seizure activity and subsequent neurodegeneration promote neuroinflammation leading to profound pathological alterations of the brain. The aim of this study was to characterize neuroinflammatory responses at key time points after DFP-induced SE.Methods: SE was induced by diisopropylfluorophosphate (DFP) injection in male Swiss mice. Immunohistochemistry (IHC) analyses of microglial (Iba1) and astrocytic (GFAP) cell markers were studied at 1, 4, 24 h and 3 days post-SE in the hippocampus. In parallel, using RT-qPCR, microglial and astrocytic phenotype markers were quantified on isolated CD11B (microglia) and GLAST (astrocytes)-positive cells after DFP-induced SE.Results: At earlier stages (1-4 h) after SE, although IHC analysis presented no modification, an increase in pro-inflammatory (M1-like) markers and A2-specific markers was observed in CD11B and GLAST-positive isolated cells respectively. Microglial cells sequentially expressed immuno-regulatory (M2b-like) and anti-inflammatory (M2a-like) at 4 h and 24 h of SE induction. At later stages (24 h and 3 days), microglial and astrocytic activations were visible by IHC and Iba1-positive cells were increased in number in DFP animals compared to controls. Finally, at these later stages, A1-specific markers were increased in isolated astrocytes.Conclusions: Our work identified sequential microglial and astrocytic phenotype activations. Although the role of each phenotype in SE cerebral consequences requires further study, targeting specific markers at specific time point could be a beneficial strategy for OP-induced SE treatment.


Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 858 ◽  
Author(s):  
André-Guilhem Calas ◽  
Anne-Sophie Hanak ◽  
Nina Jaffré ◽  
Aurélie Nervo ◽  
José Dias ◽  
...  

(1) Background: Human exposure to organophosphorus compounds employed as pesticides or as chemical warfare agents induces deleterious effects due to cholinesterase inhibition. One therapeutic approach is the reactivation of inhibited acetylcholinesterase by oximes. While currently available oximes are unable to reach the central nervous system to reactivate cholinesterases or to display a wide spectrum of action against the variety of organophosphorus compounds, we aim to identify new reactivators without such drawbacks. (2) Methods: This study gathers an exhaustive work to assess in vitro and in vivo efficacy, and toxicity of a hybrid tetrahydroacridine pyridinaldoxime reactivator, KM297, compared to pralidoxime. (3) Results: Blood–brain barrier crossing assay carried out on a human in vitro model established that KM297 has an endothelial permeability coefficient twice that of pralidoxime. It also presents higher cytotoxicity, particularly on bone marrow-derived cells. Its strong cholinesterase inhibition potency seems to be correlated to its low protective efficacy in mice exposed to paraoxon. Ventilatory monitoring of KM297-treated mice by double-chamber plethysmography shows toxic effects at the selected therapeutic dose. This breathing assessment could help define the No Observed Adverse Effect Level (NOAEL) dose of new oximes which would have a maximum therapeutic effect without any toxic side effects.


2006 ◽  
Vol 37 (S 1) ◽  
Author(s):  
N Iwasaki ◽  
S Miyamoto ◽  
K Ishii ◽  
T Takeda ◽  
T Ohto ◽  
...  

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