RESUMEN
Water plays a key role in enhancing the permeability of human skin to many substances. To further understand its ability to potentially increase the bioavailability of soil contaminants, artificial sweat was applied to excised pig skin prior to dosing with munition-contaminated soils. Skin was mounted in chambers to allow simultaneous measurement of evaporation and penetration and to control air flow, which changed the dwell time of skin surface water within a l-h period post application of test materials. Additional variables included type of compound, aging of spiked soil samples, and carbon content of soil. To this end, the evaporation and skin penetration of C-14 labeled hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 2,6-dinitrotoluene (26DNT), and 2,4,6-trinitrotoluene (TNT) were determined from two soil types, Yolo, having 1.2% carbon, and Tinker, having 9.5% carbon. RDX soil samples aged 27 mo and 62 mo were compared to freshly spiked soils samples. Similarly, 26DNT samples aged 35-36 mo and TNT samples aged 18 mo were compared to freshly spiked samples. Approximately 10 microg/cm(2) of radiolabeled compound was applied in 10 mg/cm(2) of soil. Radiolabel recovered from the dermis and tissue culture media (receptor fluid) was summed to determine percent absorption from the soils. Radiolabel recovered from vapor traps determined evaporation. Mean skin absorption of all compounds was higher for low-carbon soil, regardless of soil age and skin surface water as affected by air flow conditions. For 26DNT, a simultaneous increase in evaporation and penetration with conditions that favored enhanced soil hydration of freshly prepared samples was consistent with a mechanism that involved water displacement of 26DNT from its binding sites. A mean penetration of 17.5 +/- 3.6% was observed for 26DNT in low-carbon soil, which approached the value previously reported for acetone vehicle (24 +/- 6%). 26DNT penetration was reduced to 0.35% under dryer conditions and to 0.08% when no sweat was applied. When soil hydration conditions were not varied from cell to cell, air flow that favored a longer water dwell time increased penetration, but not evaporation, consistent with a mechanism of enhanced skin permeability from a higher hydration state of the stratum corneum. Profiles of 26DNT penetration versus air flow conditions were exponential for freshly prepared soil samples, suggesting strong and weak binding sites; corresponding profiles of 26DNT penetration from aged samples were linear, suggesting a conversion of weak to strong binding sites. Absorption and evaporation was less than 5% for TNT and less than 1% for RDX, regardless of soil type and age. Fresh preparations of RDX in Tinker soil and aged samples of TNT in Yolo soil showed a significant decrease in skin absorption with loss of surface moisture. The penetration rate of radiolabel into the receptor fluid was highest during the 1-2 h interval after dosing with 26DNT or TNT. High-performance liquid chromatography (HPLC) analysis of 26DNT in receptor fluid at maximum flux indicated no metabolism or breakdown. For TNT, however, extensive conversion to monoamino derivatives and other metabolites was observed. Relatively little radioactivity was found in the dermis after 26DNT and TNT applications, and dermal extracts were therefore not analyzed by HPLC. RDX was not sufficiently absorbed from soils to allow HPLC analysis. This study has practical significance, as the use of water for dust control at remediation sites may have the unintended effect of increasing volatilization and subsequent absorption of soil contaminants. Soil in contact with sweaty skin may give the same result. Skin absorption of 26DNT from soil was over 50-fold higher than the value for dryer skin and over 200-fold higher than the value obtained when there was no sweat application. While the hydration effect was less dramatic for RDX and TNT, soil contaminants more closely matching the physical properties of 26DNT may be similarly affected by hydration.
Asunto(s)
Sustancias Explosivas/farmacocinética , Absorción Cutánea/efectos de los fármacos , Contaminantes del Suelo/farmacocinética , Sudor , Trinitrotolueno/farmacocinética , Animales , Disponibilidad Biológica , Isótopos de Carbono/farmacocinética , Sustancias Explosivas/química , Femenino , Humanos , Trazadores Radiactivos , Suelo , Contaminantes del Suelo/química , Soluciones/farmacocinética , Sus scrofa , Sudoración , Factores de Tiempo , Trinitrotolueno/química , VolatilizaciónRESUMEN
The percutaneous absorption potentials of (14)C-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 microg/cm(2) of radiolabeled compound was applied in 5 microl 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.