Dutkiewicz T
Environ Health Perspect. 1977 Aug;19:173-6. doi: 10.1289/ehp.7719173.
Pentavalent inorganic arsenic was introduced by intravenous, intratracheal, gastrointestinal, and skin application in doses 0.1 to 4.0 mg/kg in rats. Isotopic technics were applied by use of As(74). It was found that the dynamics of arsenic distribution in the body as well as the kinetics of its elimination in urine and feces varies very substantially, depending on the mode of administration. Intravenous administration of As causes immediate appearance of arsenic in most tissues and a slow decrease of its concentrations in time. Similar situations could be observed with intratracheal dosing, because arsenic is very rapidly absorbed from the site of administration. Concentration in tissues increases more slowly after gastrointestinal resorption. Skin application causes first the accumulation of arsenic in the skin and next continuous, slow transport from the skin into the blood stream. The rate of skin resorption was 1.14-33.1 mug/cm(2)-hr for 0.01-0.2M concentrations. The red blood cell level of arsenic is very substantial and does not change with time, which indicates the accumulation of arsenic in this tissue. The elimination of arsenic occurred chiefly in urine and feces, but the urine/feces ratio changed very substantially, depending on the route of administration. The kinetics of arsenic elimination in urine was multiphasic, being three-phase in case of intravenous and intratracheal administration and two-phase after gavage and skin resorption. After intravenous administration of As, the half-times of elimination were 2.5, 10, and 690 hr, respectively. Administration of selenium salts during the slow phase increased the rate of arsenic elimination. The straight-line relations found between the absorbed dose of arsenic and its blood or urine concentrations could serve as baselines for exposure tests for humans.
以0.1至4.0毫克/千克的剂量通过静脉内、气管内、胃肠道和皮肤给药方式,将五价无机砷引入大鼠体内。通过使用砷(74)应用同位素技术。结果发现,砷在体内的分布动态以及其在尿液和粪便中的消除动力学,会因给药方式的不同而有很大差异。静脉内给予砷会使大多数组织中立即出现砷,并随着时间推移其浓度缓慢下降。气管内给药也会出现类似情况,因为砷从给药部位吸收非常迅速。胃肠道吸收后,组织中的浓度上升较慢。皮肤给药首先会使砷在皮肤中蓄积,然后持续缓慢地从皮肤转运到血流中。对于0.01 - 0.2M浓度,皮肤吸收速率为1.14 - 33.1微克/平方厘米 - 小时。红细胞中的砷含量非常高且不随时间变化,这表明砷在该组织中蓄积。砷的消除主要发生在尿液和粪便中,但尿液/粪便比值会因给药途径的不同而有很大变化。尿液中砷的消除动力学是多相的,静脉内和气管内给药情况下为三相,灌胃和皮肤吸收后为两相。静脉内给予砷后,消除半衰期分别为2.5小时、10小时和690小时。在缓慢消除阶段给予硒盐会增加砷的消除速率。所发现的砷吸收剂量与其血液或尿液浓度之间的直线关系,可作为人体暴露试验的基线。