In vitro permeation of potassium hexachloroplatinate through full thickness human abdominal skin

Abstract

Background: During the processing and refining of platinum (Pt), workers are exposed to respiratory sensitizing platinum salts. The most toxic of these platinum salts are tetra- and hexachloroplatinate, especially when attached to potassium. Although multiple researches have associated the respiratory exposure route with the development of respiratory sensitization to platinum salts, the notion of an additional dermal route of exposure was suggested. This notion was suggested due to active dermal exposure to these platinum salts in many instances and the high sensitization occurrence during low levels of respiratory exposure. Dermal exposure has previously been associated with the development of respiratory sensitization in animal studies Subsequent in vitro studies investigated the permeation of potassium tetrachloroplatinate through intact abdominal skin and substantiated the plausibility of the dermal route of exposure contributing to platinum absorption. However, the more toxic sensitizer, potassium hexachloroplatinate has not been investigated regarding its permeation profile. Aims and objections: In vitro laboratory experiments were conducted to investigate the permeation profile of potassium hexachloroplatinate (K₂PtCl₆) through full thickness human abdominal skin. The research objectives were to quantify the permeation of potassium hexachloroplatinate by utilizing the static Franz diffusion cell method, to calculate the percentage of platinum retained in the skin, and lastly, to evaluate the effect of exposure duration on the permeation of platinum at 8-, 12- and 24-hour intervals. Methods: Intact abdominal skin from Caucasian female donors, aged between 41 and 48, were obtained after abdominoplasty procedures following ethics approval and informed consent. Utilizing the Franz diffusion compartment methodology, the permeation of 0.3 mg/mL K₂PtCl₆ was quantified at time intervals of 2-, 4-, 6-, 8-, 10-, 12-, 14-, and 24-hours after the onset of the experiment. After the 24-hour extraction, the skin was digested and analyzed by Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES), quantifying the penetrated platinum mass inside the skin. Whereas the permeated platinum mass in the receptor solution was quantified by the means of Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Blank cells not containing the platinum salt, were used for quality control purposes. Results: Platinum permeation, increasing with the continued duration of exposure, occurred through the intact full thickness female Caucasian abdominal skin. The influence of time on permeation was significantly indicated by the 68 % increase in dermal absorption between 8 and 12 hours, and 62 % increase between 12 and 24 hours. The dose percentage of platinum mass contained in the skin after 24-hours was calculated as 3.11 ± 0.25 % (8848.03 ± 699.02 ng). Flux and lag time were calculated as 0.32 ± 0.05 ng/cm²/h and 2.26 ± 0.31 hours, respectively. Conclusion: With the results all aims and objectives were achieved. Results indicating a considerable platinum reservoir forming in the skin together with the short lag time implicated that continuous real-world permeation may occur adding to the body burden of platinum even after removal from the source of exposure. The presence of detectable levels of platinum mass in the receptor fluid at the 2-hour interval further suggested that even short periods of exposure to potassium hexachloroplatinate presents a risk of permeation into the body. Significant increase in mean permeation between 8 and 12 hours was substantial as extended work shifts are commonly implemented. Furthermore, exposure circumstances such as the so called ‘take-home’ effect and the layering of new deposition onto previous deposition on the skin, emphasize the importance of proper decontamination protocols. Indications were made towards a shorter lag time and heightened cumulative mass parameter when utilizing potassium hexachloroplatinate compared to other PGM research. Recommendations were made based on the real-world implications of the results in occupational settings to be applied by future PGM permeation investigations.