IN-VITRO PERCUTANEOUS-ABSORPTION OF MONOSODIUM METHANEARSONATE AND DISODIUM METHANEARSONATE IN FEMALE B6C3F1 MICE

Percutaneous absorption of monosodium [C-14]methanearsonate (MSMA) and disodium [C-14]methanearsonate (DSMA) was investigated in female B6C3 F1 mice from a variety of exposure vehicles, including aqueous solutio n, solid compound, and soil. These chemicals are the sodium salts of m ethanearsonic acid, an in vivo metabolite of inorganic arsenic compoun ds, and are present in water and soil. Permeation experiments were car ried out in vitro for 24 h using previously clipped dorsal skin (area = 0.64 cm2) in flow-through cells with HEPES-buffered Hanks balanced s alt solution as receptor fluid. Applied doses of 10 (15.6), 100 (156), and 500 (781) mug (mug/cm2) were studied in selected vehicles, and de rmal absorption was quantitated by determining the radioactivity in th e receptor fluid and skin following a skin surface wash to remove unpe netrated compound. Both MSMA and DSMA exhibited similar dermal absorpt ion from different vehicles, and the rank order was aqueous solution > solid compound > soil. The degree of ionization of the compounds did not appear to affect their skin absorption, as both monobasic and diba sic forms penetrated mouse skin to the same extent from aqueous vehicl es. An alteration in the aqueous donor volume (20, 100, and 250 mul) d id not significantly change the total absorption of the chemicals; how ever, larger volumes significantly prolonged the time to reach maximal permeation rates. The major portion of the absorbed dose (53% or high er) remained in the skin for both chemicals. A constant fraction of th e applied dose (12.4%) was absorbed from aqueous vehicles over the ent ire dosage range. Absorption of the chemicals was very low (<0.5% of t he dose) from soil. Even short-term (1 h) dermal exposure to an aqueou s solution containing MSMA resulted in the penetration (0.66% of the d ose) of this chemical. Thus, exposure vehicles have an important role in the vitro dermal absorption of MSMA and DSMA in mouse skin, with aq ueous solutions providing the greatest absorption.