IN-VITRO PERCUTANEOUS-ABSORPTION OF DIMETHYLARSINIC ACID IN MICE

The objective of this study was to investigate the in vitro dermal abs orption of [C-14]dimethylarsinic acid. This organic arsenical is used as a herbicide and is a product of the mammalian metabolism of inorgan ic arsenic. Discs of preclipped dorsal skin were cut from adult female B6C3F, mice and mounted in flow-through diffusion cells. HEPES-buffer ed Hanks balanced salt solution was used as receptor fluid. Doses of d imethylarsinic acid included 10, 100, and 500 mu g and were applied on to the skin (0.64 cm(2)). Experiments (24 h) were conducted using soli d compound and aqueous solution (20, 100, and 250 mu l) and soil (23 m g/cm(2)) as vehicles. The epidermal surface was washed at 24 h to remo ve compound that did not penetrate. The wash contained the greatest pe rcentage of the dose in all experiments. Absorption of the compound in to 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 abso rption (10 mu g) into the skin and receptor fluid was 20 mu l water > 100 mu l water > solid > 250 mu l 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 l-octano l and buffer. Short-term (I h) exposure of dimethylarsinic acid in wat er followed by wash of the skin resulted in <1% of the dose being abso rbed. Thus, vehicles and duration of exposure have important roles on the in vitro dermal absorption of dimethylarsinic add in mouse skin.