Percutaneous Absorption of Explosives and Related Compounds: An Empirical Model of Bioavailability of Organic Nitro Compounds from Soil

Abstract

The percutaneous absorption potentials of 14C-labeled 2,4,6-trinitrotoluene (TNT), trinitrobenzene, 2,4-dinitrotoluene (2,4-DNT), 2,6-dinitrotoluene (2,6-DNT), 2-amino-4,6-dinitrotoluene, 4-amino-2,6-dinitrotoluene, 2,4-diamino-6-nitrotoluene, 2,6-diamino-4-nitrotoluene, N-methyl- N,2,4,6-tetranitrobenzamine, hexahydro-1,3,5-trinitro-1,3,5-triazine, octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine, and 2,2-thiobis(ethanol) were determined from two soil types, Yolo having 1.9% carbon and Tinker having 9.5% carbon. TNT skin absorption from another low-carbon soil (Umatilla) was also determined. Approximately 10 μg/cm 2 of radiolabeled compound was applied in 5 μl of acetone or 10 mg/cm 2 of soil to excised pigskin mounted in skin penetration–evaporation chambers. Absorption from acetone served as a control. Radiolabel recovered from the dermis and tissue culture media (receptor fluid) was summed to determine the percentage of absorption from the soils. For each compound, percentage absorptions of radiolabel were highest from acetone solution and lowest from Tinker soil, with the results from Yolo soil being intermediate. Skin absorptions of TNT from Yolo and Umatilla soils were similar. For TNT in all vehicles, the penetration rate of radiolabel into the receptor fluid was highest during the 1- to 2-h interval after dosing. HPLC analysis of TNT radiolabel in receptor fluid at maximum flux indicated extensive conversion to monoamino derivatives and other metabolites. For 2,4-DNT and 2,6-DNT applications in Yolo soil, percentage absorptions approached those obtained from acetone applications. After 2,4-DNT and 2,6-DNT applications (acetone and soils), HPLC analysis of radiolabel in receptor fluid during the period of maximum flux revealed no significant metabolites. Skin absorption of the nitro compounds from soils was found to correlate with the compound's water solubility and vapor pressure. These findings formed the basis of an empirical model to predict skin bioavailability.