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三氯乙烯暴露大鼠的甲酸排泄:长期研究中肾脏毒性的一种可能解释。

Formic acid excretion in rats exposed to trichloroethylene: a possible explanation for renal toxicity in long-term studies.

作者信息

Green T, Dow J, Foster J R, Hext P M

机构信息

Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.

出版信息

Toxicology. 1998 May 15;127(1-3):39-47. doi: 10.1016/s0300-483x(98)00020-1.

Abstract

Rats exposed to trichloroethylene, either by gavage or by inhalation, excreted large amounts of formic acid in urine which was accompanied by a change in urinary pH, increased excretion of ammonia, and slight increases in the excretion of calcium. Following a single 6-h exposure to 500 ppm trichloroethylene, the excretion of formic acid was comparable to that seen after a 500 mg/kg dose of formic acid itself, yet the half-life was markedly different. Formate excretion in trichloroethylene treated rats reached a maximum on day 2 and had a half-life of 4-5 days, whereas urinary excretion was complete within 24 h following a single dose of formic acid itself. Formic acid was shown not to be a metabolite of trichloroethylene. When rats were exposed to 250 or 500 ppm trichloroethylene, 6 h/day, for 28 days, the only significant effects were increased formic acid and ammonia excretion, and a change in urinary pH. There was no evidence of morphological liver or kidney damage. Long-term exposure to formic acid is known to cause kidney damage suggesting that excretion of this acid may contribute to the kidney damage seen in the long-term studies with trichloroethylene.

摘要

通过灌胃或吸入接触三氯乙烯的大鼠,尿中排出大量甲酸,同时伴有尿pH值变化、氨排泄增加以及钙排泄略有增加。单次6小时接触500 ppm三氯乙烯后,甲酸排泄量与500 mg/kg剂量的甲酸本身所观察到的排泄量相当,但半衰期明显不同。三氯乙烯处理的大鼠中甲酸排泄在第2天达到峰值,半衰期为4 - 5天,而单次给予甲酸本身后24小时内尿排泄即完成。已证明甲酸不是三氯乙烯的代谢产物。当大鼠每天6小时接触250或500 ppm三氯乙烯,持续28天时,唯一显著的影响是甲酸和氨排泄增加以及尿pH值变化。没有肝脏或肾脏形态学损伤的证据。已知长期接触甲酸会导致肾脏损伤,这表明这种酸的排泄可能是三氯乙烯长期研究中所见肾脏损伤的原因。

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