Absorption of ¹⁴C-Cyclotrimethylenetrinitramine (RDX) from Soils through Excised Human Skin

ABSTRACT

Cyclotrimethylenetrinitramine (RDX), a compound used widely in bursting-type munitions, is a concern for the U.S. Department of Defense because it has been detected in soil and groundwater at military installations. Dermal absorption of ¹⁴C-RDX from acetone solutions and from two different soils was studied using excised human skin (from surgery) in flow-through diffusion cells. RDX in acetone (10 μL) or in soils (10 mg) was applied to the epidermal surface of the skin (0.64 cm²) and allowed to transverse the skin and become dissolved in a reservoir of receptor fluid that was maintained in contact with the dermal surface. The reservoir was of the flow-through type and receptor fluid was pumped at a rate of 1.5 mL/h. Receptor fluid was collected every 6 h for 24 h. Because the bioavailability of a chemical from soils depends on soil composition, dermal absorption of ¹⁴C-RDX from both a low-carbon (1.9%) and a high-carbon (9.5%) soil was assessed. At the conclusion of the experiment, the RDX remaining on the skin was washed with soap and water using cotton swabs, and the radioactivity present in washings was determined. The stratum corneum was removed from the deeper epidermis and radioactivity found in that layer was not considered in calculations of dermal absorption. The dermal absorption of RDX was relatively low. Only about 5.7 ± 1.9% of the RDX that had been applied in acetone was found in the skin (epidermis and dermis) (3.2 ± 1.9) and receptor fluid (2.5 ± 1.8) combined (over the full 24-h duration of the study). The levels of RDX found in the skin layers were stratum corneum 2.1%, epidermis 0.83%, and dermis 0.45%. The total recovery of applied dose (receptor fluid, skin, and washings) was about 80%. The extent of RDX absorption from soil was even lower than from acetone. Approximately 2.6 ± 1.1% of the RDX applied in the low-carbon soil and 1.4 ± 0.41% applied in the high-carbon soil was found in receptor fluid and skin in 24 h. The total recovery of the applied dose (receptor fluid, skin, and washings) was about 87% for the low-carbon soil and 94% for the high-carbon soil. Thus, the dermal absorption of RDX from soils was reduced considerably when compared with absorption from acetone and absorption was lower in the high-carbon soil than in the low-carbon soil.

KEYWORDS:

• Absorption
• Bioavailability
• Dermal
• Human
• RDX
• Skin
• In Vitro
• Soils

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of Army, Department of Defense, or U.S. Government.

This work was presented in part at the 42nd Annual Meeting of Society of Toxicology, March 9–13, 2003, Salt Lake City, UT. We would like to thank Dr. W. Reifenrath for kindly providing soil samples and critical review of the manuscript. We also want to thank Dr. R. Bronaugh, Dr. J. Yourick, and Ms. M. Kraeling of USFDA, Laurel, MD, for their help and guidance.