In vitro percutaneous absorption of dimethylarsinic acid in mice

The objective of this study was to investigate the in vitro dermal absorption of [14C]dimethylarsinic acid. This organic arsenical is used as a herbicide and is a product of the mammalian metabolism of inorganic arsenic. Discs of preclipped dorsal skin were cut from adult female B6C3F1 mice and mounted in flow-through diffusion cells. HEPES-buffered Hanks balanced salt solution was used as receptor fluid. Doses of dimethylarsinic acid included 10, 100, and 500 micrograms and were applied onto the skin (0.64 cm2). Experiments (24 h) were conducted using solid compound and aqueous solution (20, 100, and 250 microliters) and soil (23 mg/cm2) as vehicles. The epidermal surface was washed at 24 h to remove compound that did not penetrate. The wash contained the greatest percentage of the dose in all experiments. Absorption of the compound into the skin and receptor fluid was observed and ranged from < 1 to 40% of the dose in experiments with the three exposure scenarios. The rank order of the various exposure conditions of dimethylarsinic acid absorption (10 micrograms) into the skin and receptor fluid was 20 microliters water > 100 microliters water > solid > 250 microliters water > soil. No dose or pH effects on absorption of dimethylarsinic acid was observed. There was also no pH effect on the partitioning of dimethylarsinic acid between 1-octanol and buffer. Short-term (1 h) exposure of dimethylarsinic acid in water followed by wash of the skin resulted in < 1% of the dose being absorbed. Thus, vehicles and duration of exposure have important roles on the in vitro dermal absorption of dimethylarsinic acid in mouse skin.