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雌性B6C3F1小鼠体内甲胂酸钠和甲胂酸二钠的体外经皮吸收

In vitro percutaneous absorption of monosodium methanearsonate and disodium methanearsonate in female B6C3F1 mice.

作者信息

Rahman M S, Hughes M F

机构信息

ManTech Environmental Technology Inc., Research Triangle Park, North Carolina 27709.

出版信息

J Toxicol Environ Health. 1994 Apr;41(4):421-33. doi: 10.1080/15287399409531854.

DOI:10.1080/15287399409531854
PMID:8145283
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.

摘要

在雌性B6C3F1小鼠中,研究了[14C]甲基胂酸单钠(MSMA)和[14C]甲基胂酸二钠(DSMA)通过多种暴露载体的经皮吸收情况,这些载体包括水溶液、固体化合物和土壤。这些化学物质是甲基胂酸的钠盐,是无机砷化合物的体内代谢产物,存在于水和土壤中。使用先前剪毛的背部皮肤(面积 = 0.64 cm2),在流通池中以HEPES缓冲的汉克斯平衡盐溶液作为接收液进行了24小时的体外渗透实验。在选定的载体中研究了10(15.6)、100(156)和500(781)微克(微克/平方厘米)的给药剂量,并通过测定皮肤表面冲洗以去除未渗透化合物后接收液和皮肤中的放射性来定量皮肤吸收。MSMA和DSMA从不同载体表现出相似的皮肤吸收,顺序为水溶液>固体化合物>土壤。化合物的电离程度似乎不影响它们的皮肤吸收,因为一元和二元形式从水性载体中穿透小鼠皮肤的程度相同。水性供体体积(20、100和250微升)的改变并没有显著改变化学物质的总吸收;然而,较大体积显著延长了达到最大渗透速率的时间。两种化学物质吸收剂量的主要部分(53%或更高)保留在皮肤中。在整个剂量范围内,从水性载体中吸收的给药剂量的恒定比例(12.4%)。化学物质从土壤中的吸收非常低(<剂量的0.5%)。即使短期(1小时)皮肤暴露于含有MSMA的水溶液也会导致该化学物质的渗透(剂量的0.66%)。因此,暴露载体在小鼠皮肤中MSMA和DSMA的体外皮肤吸收中起重要作用,并提供最大吸收。

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