Cutaneous challenge with chemical warfare agents in the SKH-1 hairless mouse. (I) Development of a model for screening studies in skin decontamination and protection

2010 ◽  
Vol 30 (6) ◽  
pp. 470-490 ◽  
Author(s):  
F. Dorandeu ◽  
L. Taysse ◽  
I. Boudry ◽  
A. Foquin ◽  
F. Hérodin ◽  
...  

Exposure to lethal chemical warfare agents (CWAs) is no longer only a military issue due to the terrorist threat. Among the CWAs of concern are the organophosphorus nerve agent O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX) and the vesicant sulfur mustard (SM). Although efficient means of decontamination are available, most of them lose their efficacy when decontamination is delayed after exposure of the bare skin. Alternatively, CWA skin penetration can be prevented by topical skin protectants. Active research in skin protection and decontamination is thus paramount. In vivo screening of decontaminants or skin protectants is usually time consuming and may be expensive depending on the animal species used. We were thus looking for a suitable, scientifically sound and cost-effective model, which is easy to handle. The euthymic hairless mouse Crl: SKH-1 (hr/hr) BR is widely used in some skin studies and has previously been described to be suitable for some experiments involving SM or SM analogs. To evaluate the response of this species, we studied the consequences of exposing male anaesthetized SKH-1 mice to either liquid VX or to SM, the latter being used in liquid form or as saturated vapours. Long-term effects of SM burn were also evaluated. The model was then used in the companion paper (Taysse et al.1).

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.


2011 ◽  
Vol 356-360 ◽  
pp. 2610-2615
Author(s):  
Lian Yuan Wang ◽  
Meng Meng Ma ◽  
Xiao Chun Hu ◽  
Guo Min Zuo ◽  
Hai Yan Zhu ◽  
...  

Oxidation of chemical warfare agents (CWAs) such as Sulfur Oxidation of chemical warfare agents (CWAs) such as Sulfur Mustard (HD) and Soman (GD) and their simulants 2-chloroethyl ethyl sulfide (2-CEES) and dimethyl methylphosphonate (DMMP) in supercritical water were studied by a batch reactor. Results showed that HD, GD and their simulants 2-CEES and DMMP could be effectively destroyed into their corresponding mineral compounds by supercritical water oxidation (SCWO). The mineral ratio was a function of reaction temperature, reaction time and oxidant concentration. But reaction temperature seemed to have more important effect on the mineral ratio than other two factors. Sulfur compounds 2-CEES and HD could easily be mineralized under 475°C and the inorganic products were mainly SO32- and SO42- , while complete oxidation of organic phosphorus reactants GD and DMMP needed a high temperature of >600°C. And under relatively low temperature, DMMP tended to form a white organic phosphorus polymer with P-C and P-O-P bonds. Results also indicated that P-F bond was more easily broken than P-C bond.


2000 ◽  
Vol 628 ◽  
Author(s):  
Stephen T. Hobson ◽  
Erich K. Lehnert ◽  
Ernest H. Braue

ABSTRACTIn 1994, the U. S. Army initiated a research effort towards an effective material that acts both as a protective barrier and as an active destructive matrix against chemical warfare agents (CWA). We report results on our preparation and evaluation of Reactive Topical Skin Protectants (rTSP's). These creams are composite materials consisting of a base material (TSP) and a reactive moiety. Using an established base of perfluorinated-polyether and perfluoropolyethylene solids we incorporated over 60 reactive components. Classes tested include organic polymers, organic/inorganic hybrid materials, polyoxometallates (POM's), enzymes, inorganic oxides, metal alloys and small molecules. We characterized these materials by light microscopy and FTIR. We determined the efficacy of these materials against both sulfur mustard (HD) and a representative nerve agent, soman (GD), using a penetration cell model coupled to a continuous air monitor and also by in vivo testing. Composite materials with optimum reactive compounds exhibit a 94% reduction of GD vapor break-through after 20 hours (from 9458 ng to 581 ng) and a 3.6 fold increase (from 162 min to 588 min) in the time 1000 ng of GD liquid penetrates through the material. Similar composite materials show a 99% reduction in HD vapor break-through after 20 hours (from 4040 ng to 16 ng), a 2.3 fold increase (from 524 min to >1200 min) in the time 1000 ng of HD vapor penetrates through the material, and an elimination of erythema versus control in an HD vapor challenge. These results indicate that an rTSP that protects against sulfur mustard and nerve agents is within reach.


2019 ◽  
Vol 19 (12) ◽  
pp. 970-979 ◽  
Author(s):  
J. Bajgar ◽  
J. Kassa ◽  
T. Kucera ◽  
K. Musilek ◽  
D. Jun ◽  
...  

Nerve agents belong to the most dangerous chemical warfare agents and can be/were misused by terrorists. Effective prophylaxis and treatment is necessary to diminish their effect. General principles of prophylaxis are summarized (protection against acetylcholinesterase inhibition, detoxification, treatment “in advance” and use of different drugs). They are based on the knowledge of mechanism of action of nerve agents. Among different examinations, it is necessary to test prophylactic effectivity in vivo and compare the results with protection in vitro. Chemical and biological approaches to the development of new prophylactics would be applied simultaneously during this research. Though the number of possible prophylactics is relatively high, the only four drugs were introduced into military medical practice. At present, pyridostigmine seems to be common prophylactic antidote; prophylactics panpal (tablets with pyridostigmine, trihexyphenidyl and benactyzine), transant (transdermal patch containing HI-6) are other means introduced into different armies as prophylactics. Scavenger commercionally available is Protexia®. Future development will be focused on scavengers, and on other drugs either reversible cholinesterase inhibitors (e.g., huperzine A, gallantamine, physostigmine, acridine derivatives) or other compounds.


2009 ◽  
Author(s):  
Carol A. Brevett ◽  
Christopher V. Giannaras ◽  
Erin L. Maloney ◽  
Joseph P. Myers ◽  
Robert G. Nickol ◽  
...  

2010 ◽  
Author(s):  
Carol A. Brevett ◽  
John J. Pence ◽  
Robert G. Nickol ◽  
Erin L. Maloney ◽  
Joseph P. Myers ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
pp. 40-54
Author(s):  
Anshoo Gautam ◽  
Gangavarapu K. Prasad ◽  
Deeksha Singh ◽  
Rajagopalan Vijayaraghavan

Background: This study addresses the efficacy of nanomaterials based formulation developed for personal decontamination application against chemical warfare agents and used in Personal Decontamination Kit (PDK). It has the potential to decontaminate the skin of an individual, protective equipment, and small arms contaminated with chemical warfare agents. As this formulation has been developed for personal decontamination, risk of nanomaterial toxicity would always be there while sprinkling or applying to the affected area. It may get into the body through various routes specifically through the inhalation route. Aim: The aim of this study was to evaluate in vivo decontamination efficiency of the formulation and acute inhalation, intratracheal, intranasal, oral, dermal, and intraperitoneal toxicity of the formulation. Materials and Methods: 14 days survival was recorded for the evaluation of decontamination efficiency of this formulation. Various endpoints were considered while assessing the toxicity of Nanomaterial Decontamination Formulation which include Organ Body Weight Index (OBWI), serum biochemical parameters, and respiratory variables like tidal volume, respiratory rate, time of inspiration, time of expiration, etc. LD50 of the formulation were also determined for various routes. As skin is the primary organ to come in contact with the decontaminant, its primary skin irritation response has also been determined in this study. Results and Conclusion: It was found that there is no gross acute toxicity observed at different doses. Though there were some changes in the initial respiratory pattern, they were all later recovered. The preliminary histological evaluation did not show any adverse effect on various organs after exposure with NDF.


2017 ◽  
Vol 89 (10) ◽  
pp. 1491-1503 ◽  
Author(s):  
Igor V. Rybalchenko ◽  
Igor A. Rodin ◽  
Timur M. Baygildiev ◽  
Andrey N. Stavrianidi ◽  
Arcady V. Braun ◽  
...  

AbstractIn this paper a summary of the author’s approaches for investigation of the mass spectral behavior of some chemical warfare agents (CWAs), their degradation products and metabolites, as well as the results of development of analytical methods for confirmation of nerve and blister agents application are presented. Hydrolysis and oxidation metabolites of nerve agents, sulfur mustard and lewisite were used as biomarkers of the exposure. Sensitive analytical methods have been developed for their detection, based mainly on tandem mass spectrometry coupled with liquid chromatography. Several techniques for fast screening of CWAs degradation products based on capillary electrophoresis were also proposed. Some of developed approaches were successfully applied in the frame of the proficiency testing system of the Organization for the Prohibition of Chemical Weapons.


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