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小鼠体内二甲基胂酸的体外经皮吸收

In vitro percutaneous absorption of dimethylarsinic acid in mice.

作者信息

Hughes M F, Mitchell C T, Edwards B C, Rahman M S

机构信息

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

出版信息

J Toxicol Environ Health. 1995 Jul;45(3):279-90. doi: 10.1080/15287399509531996.

DOI:10.1080/15287399509531996
PMID:7609003
Abstract

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.

摘要

本研究的目的是调查[14C]二甲基胂酸的体外皮肤吸收情况。这种有机砷化物用作除草剂,是无机砷在哺乳动物体内的代谢产物。从成年雌性B6C3F1小鼠身上切下预先修剪过的背部皮肤圆盘,并安装在流通扩散池中。用HEPES缓冲的汉克斯平衡盐溶液作为接收液。二甲基胂酸的剂量包括10、100和500微克,并施用于皮肤(0.64平方厘米)。实验(24小时)使用固体化合物、水溶液(20、100和250微升)和土壤(23毫克/平方厘米)作为载体进行。在24小时时清洗表皮表面以去除未渗透的化合物。在所有实验中,清洗液中所含剂量的百分比最高。观察到化合物被皮肤和接收液吸收,在三种暴露情况下的实验中,吸收量占剂量的比例为<1%至40%。二甲基胂酸(10微克)被皮肤和接收液吸收的各种暴露条件的吸收顺序为:20微升水>100微升水>固体>250微升水>土壤。未观察到剂量或pH值对二甲基胂酸吸收的影响。二甲基胂酸在1-辛醇和缓冲液之间的分配也没有pH值影响。二甲基胂酸在水中短期(1小时)暴露后清洗皮肤,导致吸收的剂量<1%。因此,载体和暴露持续时间对小鼠皮肤中二甲基胂酸的体外皮肤吸收具有重要作用。

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