Stevens J T, Hall L L, Farmer J D, DiPasquale L C, Chernoff N, Durham W F
Environ Health Perspect. 1977 Aug;19:151-7. doi: 10.1289/ehp.7719151.
The distribution, excretion, and possible metabolism of (14)C- and/or (74)As-cacodylic acid, an organoarsenical herbicide, was studied in rats following a single intravenous injection, intratracheal instillation or oral gavage. Male Sherman rats were dosed at levels ranging from 200 mg/kg to 120 mug/kg. The extent and rate of lung absorption was greater than gastrointestinal absorption. Concentrations in the liver and whole blood were higher after peroral dosing than intravenous administration. Levels observed in plasma and other tissues were similar after all three routes following the absorptive phase. The percent dose found in the whole blood, red blood cells, and plasma was similar for all doses given by these routes. Less than 0.1(1/2) of the administered dose was recovered as (14)CO(2) by any route at 24 hr after administration. Twenty-four hours after intravenous, intratracheal, and peroral administration, 71, 60, and 25%, respectively, was excreted in the urine. After intravenous administration of 200 mg/kg, sufficient (14)C-cacodylic acid was recovered in bile to account for the small amount excreted in the feces. Cacodylic acid is probably not metabolized to inorganic arsenic since the disposition of (14)C and (74)As-cacodylic acid were identical.Kinetic analyses of the plasma curve for (14)C-cacodylic acid (high dose) yielded three half-times; 0.014, 0.214 and 3.42 hr with an apparent volume of distribution of 15.3 ml. Highest initial concentrations were found in the whole blood, muscle, kidney, liver and lung. Levels in all tissues decreased rapidly, but remained high in whole blood. The red blood cells were found to be the major site of body burden of cacodylic acid.
在大鼠单次静脉注射、气管内滴注或灌胃给予有机砷除草剂（14）C - 和/或（74）As - 二甲胂酸后，对其分布、排泄及可能的代谢情况进行了研究。雄性谢尔曼大鼠的给药剂量范围为200毫克/千克至120微克/千克。肺部吸收的程度和速率大于胃肠道吸收。经口给药后肝脏和全血中的浓度高于静脉给药。在吸收阶段后，所有三种给药途径后血浆和其他组织中的水平相似。通过这些途径给予的所有剂量，全血、红细胞和血浆中发现的剂量百分比相似。给药后24小时，通过任何途径回收的（14）CO₂均不到给药剂量的0.1（1/2）。静脉注射、气管内滴注和经口给药24小时后，分别有71%、60%和25%经尿液排泄。静脉注射200毫克/千克后，胆汁中回收了足够的（14）C - 二甲胂酸，可解释粪便中排泄的少量药物。二甲胂酸可能不会代谢为无机砷，因为（14）C和（74）As - 二甲胂酸的处置情况相同。对（14）C - 二甲胂酸（高剂量）血浆曲线的动力学分析得出三个半衰期；分别为0.014、0.214和3.42小时，表观分布容积为15.3毫升。全血、肌肉、肾脏、肝脏和肺中的初始浓度最高。所有组织中的水平迅速下降，但全血中仍保持较高水平。发现红细胞是二甲胂酸在体内蓄积的主要部位。
