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大鼠体内二正辛基二氯化锡的吸收、组织分布及排泄

The absorption, tissue distribution and excretion of di-n-octyltin dichloride in rats.

作者信息

Penninks A H, Hilgers L, Seinen W

出版信息

Toxicology. 1987 Apr;44(1):107-20. doi: 10.1016/0300-483x(87)90050-3.

Abstract

In this study the absorption, tissue distribution and excretion of 14C-labeled di-n-octyltin dichloride ([14C]DOTC) in rats were investigated after oral and intravenous (i.v.) administration. Although after i.v. administration with 1.2 mg [14C]DOTC/kg body weight the tissue radioactivity was about 3-4 times higher than after oral administration with 6.3 mg [14C]DOTC/kg body weight, the relative tissue accumulation was found to be the same after the oral and i.v. dosage. The highest amount of radioactivity was found in liver and kidney, and to a lesser degree in adrenal, pituitary and thyroid glands. The lowest activity was recovered from blood and brain. No selective accumulation was observed in thymus, although it has been reported that thymus atrophy is the most sensitive parameter of DOTC toxicity in rats. For all tissues a time dependent decrease in radioactivity was found, except for kidney. The excretion of radioactivity in feces and urine was determined after a single i.v. or oral dose of 1.2 and 2 mg [14C]DOTC, respectively. After i.v. administration most of the radioactivity was excreted in the feces which was characterized by a biphasic excretion pattern. In orally treated rats more than 80% of the radioactivity was already excreted in the feces during the first day after administration. This indicated that only a small part of the DOTC was absorbed, which was calculated to be approximately 20% of the dose. Similar half-life values of 8.3 and 8.9 days were obtained from the fecal excretion of radioactivity after the i.v. and oral administration, respectively. The urinary excretion of radioactivity appeared to be independent of the body burden, since the daily amount of radioactivity excreted in urine was nearly the same independent of the route of administration as well as the time after administration.

摘要

在本研究中,对大鼠经口和静脉注射给予14C标记的二正辛基二氯化锡([14C]DOTC)后,研究了其吸收、组织分布和排泄情况。尽管静脉注射1.2mg[14C]DOTC/kg体重后组织放射性比经口给予6.3mg[14C]DOTC/kg体重后高约3 - 4倍,但经口和静脉给药后相对组织蓄积情况相同。在肝脏和肾脏中发现放射性含量最高,在肾上腺、垂体和甲状腺中含量较低。从血液和大脑中回收的放射性最低。尽管有报道称胸腺萎缩是大鼠DOTC毒性最敏感的参数,但在胸腺中未观察到选择性蓄积。除肾脏外,所有组织中的放射性均随时间下降。分别经静脉或口服给予1.2mg和2mg[14C]DOTC单次剂量后,测定了粪便和尿液中的放射性排泄情况。静脉注射后,大部分放射性经粪便排泄,其排泄模式呈双相。经口处理的大鼠在给药后的第一天内,超过80%的放射性已随粪便排泄。这表明只有一小部分DOTC被吸收,经计算约为剂量的20%。静脉注射和口服给药后,从粪便放射性排泄中分别获得了相似的半衰期值,分别为8.3天和8.9天。放射性的尿液排泄似乎与体内负荷无关,因为无论给药途径和给药后时间如何,每日经尿液排泄的放射性量几乎相同。

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