In vitro human skin permeation and decontamination of diisopropyl methylphosphonate (DIMP) using Dermal Decontamination Gel (DDGel) and Reactive Skin Decontamination Lotion (RSDL) at different timepoints

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

doi:10.1016/j.toxlet.2018.09.013

Cited by 14 publications

(3 citation statements)

References 16 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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“…The foam formulation was allowed to be kept on skin for 5 min to determine the decontaminating ability of foam in 5 min. Similar studies in literature have reported in vitro studies using human skin conducted for various types of decontaminating formulations such as foam, lotion, and gel. − In our studies, we applied foam in the form of solution as the developed foam formulation is a quick breaking foam that will result in solution upon application. As seen from the results, the developed foam formulation showed effective decontamination of over 75% in human skin.…”

Section: Discussionmentioning

confidence: 99%

Development and Evaluation of a Topical Foam Formulation for Decontamination of Warfare Agents

et al. 2022

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Lewisite is a highly toxic and potent chemical warfare vesicating agent capable of causing pain, inflammation, and blistering. Therapeutic strategies that safely and effectively attenuate this damage are important. Early and thorough decontamination of these agents from skin is required to prevent their percutaneous absorption. In our studies, we used phenylarsine oxide (PAO), a surrogate for arsenicals, to simulate lewisite exposure. Various parameters such as determination of extraction solvents, skin extraction efficiency, donor volume, and donor concentration were optimized for decontamination of PAO. We aimed to develop a novel, easy to apply foam formulation that can decontaminate arsenicals. We screened various foaming agents, vehicles, and chemical enhancers for the development of foam. Lead formulation foam F30 was further characterized for foam density, foam expansion, foam liquid stability, foam volume stability, and foam gas fraction. The amount of PAO delivered into human skin in 30 min of exposure was 228.57 ± 28.44 μg/sq•cm. The amount of PAO remaining in human skin after decontamination with blank foam F30 was 50.09 ± 9.71, demonstrating an overall percentage decontamination efficiency of over 75%. Furthermore, the decontamination efficacy of F30 was also tested in the porcine skin model and results indicated an even higher decontamination efficacy. These studies demonstrated that the developed foam formulation can be used for effective decontamination of chemical warfare agents.

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“…They rapidly appear in domestic swine challenged with VX, that is, time to apnea was about 1 h (Hamilton et al, 2004) and time to death about 2 h (Bjarnason et al, 2008). The timing of decontamination is crucial for effective removal of contaminating agent and its skin reservoir (Cao, Hui, Elmahdy, & Maibach, 2018).…”

Section: Introductionmentioning

confidence: 99%

Follicular pathway role in chemical warfare simulants percutaneous penetration

Elmahdy

Cao

Hui

et al. 2020

J of Applied Toxicology

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Chemical warfare (CW) exposure could be fatal to military and civilians through skin contamination. Our work and others focus on investigating stratum corneum reservoir with less regards to skin appendageal routes including hair follicles. Here, C‐14 CW simulants (CWS) with specific activity of 0.1 mCi/ml were tested on abdominal and scalp human cadaver skin using flow‐through diffusion system. Quantitative analysis of simulants in skin compartments were performed using scintillation counter. Scalp permeation of dipropylene glycol monomethyl ether (DPGME), diisopropyl methylphosphonate (DIMP) and methyl salicylate (MeS) exceed abdominal skin by 8%, 15%, and 6% (p value < 0.05) of applied dose, respectively. DPGME and DIMP (most hydrophilic) showed earlier permeation peak time (Tmax) through scalp skin at 2 and 4 h, respectively, comparing with 6 h with abdominal skin. The percentage of applied dose of DPGME and DIMP retained in human skin membrane (SC, epidermis, and viable dermis) showed no statistically significant difference between tested abdominal and scalp skin samples (p value >0.05). The percentage of applied dose of MeS in scalp showed higher partitioning in stratum corneum and viable epidermis than abdominal skin (p value <0.05). In conclusion, human scalp showed greater total skin absorption than abdominal skin. This work points to a qualitative importance of high follicular density body regions in percutaneous penetration and suggests that transfollicular pathway might have a significant role in early stage permeation of chemical warfare simulants. However, the difference noticed here between scalp and abdominal skin could be attributed to regional variability in anatomy, physiology, and barrier characteristics.

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In vitro human skin permeation and decontamination of diisopropyl methylphosphonate (DIMP) using Dermal Decontamination Gel (DDGel) and Reactive Skin Decontamination Lotion (RSDL) at different timepoints

Cited by 14 publications

References 16 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

Development and Evaluation of a Topical Foam Formulation for Decontamination of Warfare Agents

Follicular pathway role in chemical warfare simulants percutaneous penetration

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