title: In vitro percutaneous absorption of monosodium methanearsonate and disodium methanearsonate in female B6C3F1 mice.
abstract: Percutaneous absorption of monosodium [14C]methanearsonate (MSMA) and disodium [14C]methanearsonate (DSMA) was investigated in female B6C3F1 mice from a variety of exposure vehicles, including aqueous solution, solid compound, and soil. These chemicals are the sodium salts of methanearsonic acid, an in vivo metabolite of inorganic arsenic compounds, and are present in water and soil. Permeation experiments were carried out in vitro for 24 h using previously clipped dorsal skin (area = 0.64 cm2) in flow-through cells with HEPES-buffered Hanks balanced salt solution as receptor fluid. Applied doses of 10 (15.6), 100 (156), and 500 (781) micrograms (micrograms/cm2) were studied in selected vehicles, and dermal absorption was quantitated by determining the radioactivity in the receptor fluid and skin following a skin surface wash to remove unpenetrated compound. Both MSMA and DSMA exhibited similar dermal absorption 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 dibasic forms penetrated mouse skin to the same extent from aqueous vehicles. An alteration in the aqueous donor volume (20, 100, and 250 microliters) did not significantly change the total absorption of the chemicals; however, larger volumes significantly prolonged the time to reach maximal permeation rates. The major portion of the absorbed dose (53% or higher) remained in the skin for both chemicals. A constant fraction of the applied dose (12.4%) was absorbed from aqueous vehicles over the entire dosage range. Absorption of the chemicals was very low (< 0.5% of the dose) from soil. Even short-term (1 h) dermal exposure to an aqueous solution containing MSMA resulted in the penetration (0.66% of the dose) of this chemical. Thus, exposure vehicles have an important role in the in vitro dermal absorption of MSMA and DSMA in mouse skin, with aqueous solutions providing the greatest absorption.
authors.affiliation: ManTech Environmental Technology Inc., Research Triangle Park, North Carolina 27709.
authors.forename: M S
authors.initials: MS
authors.lastname: Rahman
authors.forename: M F
authors.initials: MF
authors.lastname: Hughes
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001152:Arsenicals / Q000493:pharmacokinetics*; D005260:Female; D006540:Herbicides / Q000493:pharmacokinetics*; D051379:Mice; D012869:Skin Absorption; D012996:Solutions; D013723:Teratogens / Q000493:pharmacokinetics*
chemical_list: D001152:Arsenicals; D006540:Herbicides; D012996:Solutions; D013723:Teratogens; C020300:monomethylarsonic acid