Evolution of the percutaneous penetration and distribution of uranyl nitrate as a function of skin-barrier integrity: an in vitro assessment

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 HNO₃, 5 N HNO₃, and 14 N HNO₃ 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.

Keywords::

• Uranium
• in vitro percutaneous penetration
• injured skin
• rat
• risk assessment
• kidneys
• bones

Acknowledgments

The authors would like to thank Dr. P. Laloi, PhD and Dr. I. Dublineau, PhD for the useful discussions they had with them during the writing of this article.

Declaration of interest

This study was partly supported by grants from AREVA. The authors declare that there are no conflicts of interest.