Kobayashi Yayoi, Negishi Takayuki, Mizumura Ayano, Watanabe Takayuki, Hirano Seishiro
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
Arch Toxicol. 2008 Aug;82(8):553-61. doi: 10.1007/s00204-007-0270-x. Epub 2007 Dec 19.
Diphenylarsinic acid (DPAA), a possible product of degradation of arsenic-containing chemical weapons, was detected in well water in Kamisu City, Ibaraki Prefecture, Japan, in 2003. Although some individuals in this area have been affected by drinking DPAA-containing water, toxicological findings on DPAA are limited. To elucidate the mechanism of its toxicity, it is necessary to determine the metabolic behavior of DPAA in the body. In this study, pregnant cynomolgus monkeys at the 50th day of pregnancy were used. The monkeys were treated daily with 1.0 mg DPAA/kg body weight using a nasogastric tube, and the distribution and excretion of arsenic were examined after the repeated administration and 198-237 days after the last administration of DPAA. Fecal excretion was higher than urinary excretion (ca. 3:2 ratio), and arsenic accumulated in the hair and erythrocytes. Distribution of DAPP to plasma and hemolyzed erythrocytes was also examined by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). Two peaks were found in the elution profile of arsenic, due to free and probably protein-bound DPAA. The protein-bound arsenic compounds were presumably trivalent diphenylarsenic compounds, since free DPAA was recovered after treatment of heat-denatured samples with hydrogen peroxide.
二苯基次胂酸（DPAA）是含砷化学武器降解的一种可能产物，2003年在日本茨城县神栖市的井水中被检测到。尽管该地区一些人因饮用含DPAA的水而受到影响，但关于DPAA的毒理学研究结果有限。为阐明其毒性机制，有必要确定DPAA在体内的代谢行为。在本研究中，使用了怀孕50天的食蟹猴。每天通过鼻饲管给猴子施用1.0毫克DPAA/千克体重，并在重复给药后以及最后一次施用DPAA后198 - 237天检查砷的分布和排泄情况。粪便排泄高于尿液排泄（约为3:2的比例），并且砷在毛发和红细胞中蓄积。还通过高效液相色谱 - 电感耦合氩等离子体质谱法（HPLC - ICP MS）检测了DAPP在血浆和溶血红细胞中的分布。在砷的洗脱图谱中发现了两个峰，分别归因于游离的以及可能与蛋白质结合的DPAA。由于用过氧化氢处理热变性样品后回收了游离的DPAA，所以与蛋白质结合的砷化合物可能是三价二苯基砷化合物。
