In vitro human skin permeation and decontamination of 2-chloroethyl ethyl sulfide (CEES) using Dermal Decontamination Gel (DDGel) and Reactive Skin Decontamination Lotion (RSDL)

Cao, Yachao; Hui, Xiaoying; Zhu, Hong; Elmahdy, Akram; Maibach, Howard I.

doi:10.1016/j.toxlet.2018.04.015

Cited by 17 publications

(5 citation statements)

References 15 publications

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“…Tape-stripping is an efficient and well-established method to evaluate the kinetics and penetration depth of multiple agents, for example, pharmaceuticals, both in vivo and in vitro [21][22][23][24] . The method has also been utilized to investigate the removal of stimulants to toxic agents by various decontamination protocols in vitro 25,26 . By repeatedly applying adhesive tape on the same skin area, certain amounts of stratum corneum (the outermost layer of epidermis) can be removed which enables the determination of agent distribution in tissue 27 .…”

Section: Introductionmentioning

confidence: 99%

Efficient agent degradation within skin is important for decontamination of percutaneously exposed VX

Thors

Wigenstam

Qvarnström

et al. 2021

Cutaneous and Ocular Toxicology

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Aim of the study: Following percutaneous exposure to the nerve agent VX, the remaining intact agent within the skin after decontamination is of great concern. Consequently, this leads to prolonged agent release to the blood circulation resulting in sustained intoxication, which may complicate the medical management. The decontamination procedure used should therefore possess the ability for agent removal both on and within the skin. The efficacy of three decontamination procedures was evaluated by measuring VX and the primary degradation product ethyl methyl phosphonic acid (EMPA) penetrated through human skin and the amount remaining within the skin. Materials and methods: Decontamination was initiated 5 min post-exposure to VX on human dermatomed skin. Experiments were conducted using an in vitro skin penetration model and the amount remaining within the skin was determined by combining the tape-stripping technique and acetylcholinesterase activity measurements. Results: In control experiments without decontamination, higher amounts of VX were recovered in the deeper layers of skin compared to EMPA, which was primarily located in the stratum corneum. Both Reactive Skin Decontamination Lotion (RSDL) and the RSDL training kit (TRSDL) significantly reduced the amount of VX within the skin and decreased the penetration through the skin. However, the degradation ability of RSDL was demonstrated to be beneficial by the reduction of intact agents remaining in the skin compared to TRSDL without agent degradation capability. Soapy water decontamination caused a "wash-in" effect of VX with decreased agent amounts within stratum corneum but increased the amount VX penetrated through the skin. Conclusion: Efficient skin decontamination of VX requires skin decontaminants reaching deeper layers of the skin, and that both absorption and degradation properties are important. In addition, the "washin" effect by using soapy water may enhance VX release to the blood circulation.

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Section: Introductionmentioning

confidence: 99%

Efficient agent degradation within skin is important for decontamination of percutaneously exposed VX

Thors

Wigenstam

Qvarnström

et al. 2021

Cutaneous and Ocular Toxicology

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“…Reactive Skin Decontamination Lotion (RSDL; Emergent BioSolutions, Gaithersburg, MD) is a US Food and Drug Administration (FDA)-approved emerging product that has been indicated for decontaminating nerve gas exposure. Published in vitro studies show that when RSDL is incubated with CS, the potency of the CS tear gas agent is substantially reduced ( Cao et al, 2018 ; Gebremedhin et al, 2020 ). However, this has not been confirmed in any preclinical or clinical studies.…”

Section: Discussionmentioning

confidence: 99%

Pharmacologic Inhibition of Transient Receptor Potential Ion Channel Ankyrin 1 Counteracts 2-Chlorobenzalmalononitrile Tear Gas Agent–Induced Cutaneous Injuries

Achanta,

Chintagari,

Balakrishna

et al. 2023

J Pharmacol Exp Ther

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Deployment of the tear gas agent 2-chlorobenzalmalononitrile (CS) for riot control has significantly increased in recent years. The effects of CS have been believed to be transient and benign. However, CS induces severe pain, blepharospasm, lachrymation, airway obstruction, and skin blisters. Frequent injuries and hospitalizations have been reported after exposure. We have identified the sensory neuronal ion channel, transient receptor potential ankyrin 1 (TRPA1), as a key CS target resulting in acute irritation and pain and also as a mediator of neurogenic inflammation. Here, we examined the effects of pharmacologic TRPA1 inhibition on CS-induced cutaneous injury. We modeled CS-induced cutaneous injury by applying 10 μ l CS agent [200 mM in dimethyl sulfoxide (DMSO)] to each side of the right ears of 8- to 9-week-old C57BL/6 male mice, whereas left ears were applied with solvent only (DMSO). The TRPA1 inhibitor HC-030031 or A-967079 was administered after CS exposure. CS exposure induced strong tissue swelling, plasma extravasation, and a dramatic increase in inflammatory cytokine levels in the mouse ear skin. We also showed that the effects of CS were not transient but caused persistent skin injuries. These injury parameters were reduced with TRPA1 inhibitor treatment. Further, we tested the pharmacologic activity of advanced TRPA1 antagonists in vitro. Our findings showed that TRPA1 is a crucial mediator of CS-induced nociception and tissue injury and that TRPA1 inhibitors are effective countermeasures that reduce key injury parameters when administered after exposure. Additional therapeutic efficacy studies with advanced TRPA1 antagonists and decontamination strategies are warranted. SIGNIFICANCE STATEMENT 2-Chlorobenzalmalononitrile (CS) tear gas agent has been deployed as a crowd dispersion chemical agent in recent times. Exposure to CS tear gas agents has been believed to cause transient acute toxic effects that are minimal at most. Here we found that CS tear gas exposure causes both acute and persistent skin injuries and that treatment with transient receptor potential ion channel ankyrin 1 (TRPA1) antagonists ameliorated skin injuries.

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“…It rapidly and completely reacts with different chemical agents (G-agents, V-agents, etc. ), producing relatively nontoxic byproducts. ,− However, this solution remains expensive. In the search for new efficient and cheap materials for skin decontamination, the ability of ceria nanoparticles (CeO 2 NPs) to degrade OPs into safer byproducts appears highly interesting.…”

Section: Introductionmentioning

confidence: 99%

Tailor-Made Synthesis of Cerium Oxide Nanoparticles for Improving the Skin Decontamination of Paraoxon

Thomas,

Briançon,

Chaput

et al. 2024

ACS Appl. Nano Mater.

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CeO 2 nanoparticles possess catalytic activity for hydrolysis of organophosphates such as paraoxon and nerve agents used in chemical warfare. Intoxication with these highly toxic compounds can occur directly through inhalation or dermal contact and lead to rapid and severe consequences including death. It is therefore necessary to have effective means of skin decontamination, and CeO 2 nanoparticles are promising. In this study, a wide range of CeO 2 nanoparticles were synthesized and their efficiency against paraoxon degradation was evaluated. Nanocubes (NC), nanorods (NR), nano-octahedra (NO), and nanopolyhedra (NPO) were studied along with nanoparticles obtained after calcination (NC*, NR*, NO*, and nanotruncated octahedra NTO*). Results show an influence of calcination, specific surface area, and crystal facets with higher activity for {111} facets compared to {100} facets. pH also impacted POX degradation rates, with higher pH accelerating the degradation. In vitro tests using the Franz cell method demonstrated the skin decontamination efficacy of the CeO 2 nanoparticles. NC* exhibited lower efficiency, possibly due to smaller surface area and limited {100} facet degradation. The most efficient nanoparticles were NR* and NO* followed by NTO* consistently with their degradation efficiency and specific surface area. Notably, NR* and NO* performed comparably to FE (Fuller's earth), the standard powder skin decontaminant on battlefield. Unlike FE that can only adsorb paraoxon, CeO 2 nanoparticles can neutralize it into safer byproducts. This study highlights the interest of CeO 2 nanoparticles and the influence of their physicochemical properties on organophosphorus compound degradation and cutaneous decontamination.

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In vitro human skin permeation and decontamination of 2-chloroethyl ethyl sulfide (CEES) using Dermal Decontamination Gel (DDGel) and Reactive Skin Decontamination Lotion (RSDL)

Cited by 17 publications

References 15 publications

Efficient agent degradation within skin is important for decontamination of percutaneously exposed VX

Efficient agent degradation within skin is important for decontamination of percutaneously exposed VX

Pharmacologic Inhibition of Transient Receptor Potential Ion Channel Ankyrin 1 Counteracts 2-Chlorobenzalmalononitrile Tear Gas Agent–Induced Cutaneous Injuries

Tailor-Made Synthesis of Cerium Oxide Nanoparticles for Improving the Skin Decontamination of Paraoxon

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