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Abstract The in vitro percutaneous penetration of the nerve agent VX through pig skin was measured in the absence and presence of water or artificial sweat to determine the impact such conditions might have on penetration rates. Experiments were performed with Franz-type glass diffusion cells containing dermatomed pig skin as a surrogate for human skin. The receptor fluid used was 50% aqueous ethanol. 14C labelled VX was applied to the skin surface under infinite or finite dosing conditions with regular receptor fluid sampling up to 24 h. Penetration from aqueous solutions of VX showed the maximal steady state penetration rate (Jss) was from the 50% (v:v) solution (366 ± 149 μg·cm−2·h−1), this being ~2.2 fold greater than Jss measured for neat VX (169 ± 89 μg·cm−2·h−1). Application of neat VX to water-wetted skin was also found to result in an increased penetration rate, compared to dry skin, shortly after contamination. These studies have shown that, in vitro , aqueous solutions of VX in contact with the skin can result in increased penetration rates when compared to neat VX applied to dry skin. Highlights • Measurement of VX percutaneous penetration in presence of water or artificial sweat • VX in 50% aqueous solution had increased penetration compared to neat VX. • The penetration rate of VX may be increased shortly after it contaminates wet skin. • Presence of water may alter VX diffusion by changing the permeability coefficient. [ABSTRACT FROM AUTHOR]

Diffusion cells are used to determine the penetration of chemicals through skin in vitro . The cells have a limited surface area defined by the edge of the donor chamber. Should the penetrant spread rapidly to this containment limit the penetration rate can be accurately quantified. For the hazard assessment of small droplets of toxic chemicals, such as cholinesterase inhibitors, limiting skin surface spread in vitro could lead to underestimation of percutaneous penetration and hence underestimation of systemic toxicity in vivo . The current study investigated the dependency of the percutaneous penetration of undiluted radiolabelled nerve agents (VX and soman (GD), 10 μl) on skin surface spread (pig and guinea pig) using Franz-type glass diffusion cells with an area available for diffusion of either 2.54 cm 2 or 14.87 cm 2 . Both VX and GD spread to the edge of the 2.54 cm 2 cells, but, not the 14.87 cm 2 cells over the study duration. Amounts of VX and GD penetrating pig and guinea pig skin in the 2.54 cm 2 cells were less than in the 14.87 cm 2 cells (except for GD under unoccluded conditions); however, penetration rates expressed per unit area were similar. Artificial limitation of skin surface spread in vitro does not impact percutaneous penetration in vitro as long as penetration is expressed in terms of mass per unit area. [ABSTRACT FROM AUTHOR]

Abstract: The physico-chemical properties of VX make the skin the most likely route of absorption into the human body. The development of effective medical countermeasures against such percutaneous threat agents relies on the use of appropriate animal models, as the inherent toxicity of nerve agents precludes the use of human volunteers. Previous studies have characterised the mechanism of nerve agent toxicity in rodent models, however, it is generally accepted that one of the most appropriate animal models for human skin absorption is the domestic pig. The purpose of the present study was to measure and compare the skin absorption kinetics of VX in vitro using pig, human and guinea pig skin to highlight any potential species differences in skin permeability. When undiluted VX was applied directly to the skin, the permeability of guinea pig skin was approximately 7-fold greater than human skin. There was no significant difference in the permeability of pig and human skin. When VX diluted with isopropyl alcohol was applied to the skin, the permeability of guinea pig skin was approximately 4-fold greater than human skin. There was no significant difference in the permeability of pig and human skin. From this data it may be inferred that dermatomed, abdominal pig skin is an appropriate model for the human skin absorption of VX. [Copyright &y& Elsevier]

The purpose of this study was to investigate the relationship between transepidermal water loss and skin permeability to tritiated water (3 H2 O) and the lipophilic penetrant sulfur mustard in vitro . No correlation was found between basal transepidermal water loss rates and the permeability of human epidermal membranes to 3 H2 O (p = 0.72) or sulfur mustard (p = 0.74). Similarly, there was no correlation between transepidermal water loss rates and the 3 H2 O permeability of full-thickness pig skin (p = 0.68). There was no correlation between transepidermal water loss rate and 3 H2 O permeability following up to 15 tape strips (p = 0.64) or up to four needle-stick punctures (p = 0.13). These data indicate that transepidermal water loss cannot be unconditionally ascribed to be a measure of skin barrier function. It is clear that further work should be conducted to interpret the significance of measuring transepidermal water loss by evaporimetry. [ABSTRACT FROM AUTHOR]

Carfentanil is a synthetic opioid restricted to veterinary use due to its potency. Public health concerns have been raised as to the potential of carfentanil to exhibit toxicity after absorption via the percutaneous route following unintentional contamination. The current study measured the penetration of free base carfentanil through human, pig and rat skin using in vitro static diffusion cells. The human penetration rates were compared against literature toxicology values and indicated that, dependent on the contamination density, contamination area and residence time, skin decontamination and medical countermeasures may be required to ameliorate toxicity. The pig and rat skin penetration data will form the basis of future work to develop relevant in silico and in vivo models to further elucidate likely toxic effects and the medical strategies to mitigate against them. • Rat skin was more permeable to free base carfentanil than pig or human skin. • Transient exposure to low contamination densities unlikely to lead to toxicity. • There is the potential for prolonged penetration of carfentanil via the dermal route. • Effective mitigation strategies may be required for high dose, long residence times. [ABSTRACT FROM AUTHOR]