Evolution of the percutaneous penetration and distribution of uranyl nitrate as a function of skin-barrier integrity: anin vitroassessment

Abstract

As recommended by OECD Guidelines, percutaneous penetration studies consider intact skin, but rarely injured skin. Recent years have witnessed a growing concern for these two types of dermal exposure in the industry, particularly in the nuclear industry. The aim of this study was to show that a method based on an in vitro device can be used to realistically assess how skin-barrier alterations caused by occupational accidents can modify the percutaneous penetration and distribution of radionuclides, particularly uranium. Wounds encountered in the nuclear industry (i.e., nitric acid burns and abrasion) were simulated on hairless rat skin. Skin-barrier alterations were characterized by means of a histological study and by measuring transepidermal water loss (TEWL) and skin thickness. The percutaneous penetration of uranyl nitrate through intact or injured skin biopsies was then measured in vitro. The maximum uranium flux values obtained for intact skin, skin abrasion with stratum corneum removal, and skin exposed to 2 N HNO(3), 5 N HNO(3), and 14 N HNO(3) were, respectively, 0.6 +/- 0.02, 1.2 +/- 0.03, 1.2 +/- 0.04, 42.0 +/- 1.0, and 174.0 +/- 8.7 ng.cm(-2).h(-1). These results demonstrated that the percutaneous absorption of uranium increased with the increased impairment of the stratum corneum. TEWL, combined with maximum uranium flux values measured in vitro, yielded a good prediction of the percutaneous penetration of uranium through injured skin, previously observed in vivo. To conclude, this in vitro assay provides a conservative estimate of the percutaneous diffusion of uranium through intact or injured skin, making it a good alternative method for toxicological studies and risk assessments.

Percutaneous absorption in diseased skin: an overview

“…Petitot et al . () studied percutaneous penetration of uranyl nirate through chemically burned rat skin. They found no significant difference in uranium concentration between 10 n NaOH burned skin and intact skin.…”

“…They presumed the effect was due to a conformational collapse of the protein in this layer and a consequent increase in porosity from the damaged ductal epithelium of the exocrine glands. Petitot et al (2007Petitot et al ( , 2010 studied percutaneous penetration of uranyl nirate through chemically burned rat skin. They found no significant difference in uranium concentration between 10 N NaOH burned skin and intact skin.…”

Synergistic cytotoxicity and DNA strand breaks in cells and plasmid DNA exposed to uranyl acetate and ultraviolet radiation

“…In spite of the lack of attention paid to skin as a route or target organ for uranium exposure in epidemiological studies, the dermal uptake of uranium is well established. Animal studies have shown that uranium passes through both intact and injured skin to reach other target organs (de Rey et al, 1983;López et al, 2000;Petitot et al, 2010;Spagnul et al, 2011). Monitoring of Gulf War veterans with uranium-containing shrapnel embedded in their skin has determined that the shrapnel dissolves and the uranium migrates to systemic organs and is excreted in urine (Leggett and Pellmar, 2003;McDiarmid et al, 2000).…”

Human Health and Environmental Uranium

“…Other uranium compounds (uranium tetrachloride or tetrafluoride, uranium trioxide) are absorbed through the skin of mice, rats, and guinea pigs at a rate of 0.1% of dermally applied uranium, a relatively low absorption rate (Orcutt, 1949). Also other studies show that soluble uranium compounds can be absorbed through the skin (Petitot et al, 2007(Petitot et al, , 2010, however, the concentrations of uranium applied to the skin were extremely high, and it is unlikely that humans would typically experience such exposures.…”