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

被引:29
作者
Green, T [1 ]
Dow, J [1 ]
Foster, JR [1 ]
Hext, PM [1 ]
机构
[1] Zeneca Cent Toxicol Lab, Macclesfield SK10 4TJ, Cheshire, England
关键词
trichloroethylene; renal toxicity; formic acid;
D O I
10.1016/S0300-483X(98)00020-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
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页码:39 / 47
页数:9
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