TOXICOKINETICS OF MONOCHLOROACETIC ACID - A WHOLE-BODY AUTORADIOGRAPHY STUDY

被引:17
作者
BHAT, HK
AHMED, AE
ANSARI, GAS
机构
[1] UNIV TEXAS,MED BRANCH,CTR CANC,DIV BIOCHEM,GALVESTON,TX 77550
[2] UNIV TEXAS,MED BRANCH,CTR CANC,PHARMACOKINET LAB,GALVESTON,TX 77550
关键词
Distribution; Monochloroacetic acid; Whole-body Autoradiography;
D O I
10.1016/0300-483X(90)90066-P
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Monochloroacetic acid (MCA) is a toxic chemical used as a herbicide and in the synthesis of various organic compounds. MCA has also been shown to be present in chlorinated drinking waters. In order to understand the mechanism of MCA toxicity, we studied the tissue distribution of [1-14C]MCA in rats, by whole-body autoradiography technique. Male Sprague-Dawley rats were given a tracer dose of [1-14C]MCA [6.8 μg/100 g (40 μCi) body weight] by tail vein and euthanized at different time intervals (5 min, 1, 4, 12, 24 and 48 h). The animals were embedded in carboxymethyl cellulose and frozen immediately. Frozen animals were sectioned and processed using whole-body autoradiographic techniques. Analysis of developed sections showed that at 5 min, there was a rapid accumulation of 14C-activity in the kidney cortex and stomach walls. The radioactivity was rapidly removed from the circulation. There was high accumulation of 14C-activity in the myocardial tissues. The liver was also loaded with MCA and/or its metabolites. After 1 h following administration of [14C]MCA, radioactivity was extensively excreted into the small intestinal lumen. The accumulation of 14C-activity in the brain, thymus, salivary glands and tongue was prominent at 1 h. After 4 h the liver and other tissues started to eliminate most of the radioactivity. Contrary to other tissues, however, the central nervous system, thymus and pancreas started to accumulate the radioactivity at later time periods. These observations suggest the accumulation of MCA and/or its metabolites into hydrophilic tissues at earlier time periods and into lipophilic tissues at later times. © 1990.
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页码:35 / 43
页数:9
相关论文
共 23 条
[1]   MONOCHLOROACETIC ACID TOXICITY IN THE MOUSE ASSOCIATED WITH BLOOD-BRAIN-BARRIER DAMAGE [J].
BERARDI, MR ;
SNYDER, R ;
WARITZ, RS ;
COOPER, KR .
FUNDAMENTAL AND APPLIED TOXICOLOGY, 1987, 9 (03) :469-479
[2]   COVALENT INTERACTION OF CHLOROACETIC AND ACETIC-ACIDS WITH CHOLESTEROL [J].
BHAT, HK ;
ANSARI, GAS .
JOURNAL OF BIOCHEMICAL TOXICOLOGY, 1989, 4 (03) :189-193
[3]  
BHAT HK, 1988, FASEB J, V2, pA373
[4]  
CHRISTIANSON M, 1961, ACTA PHARMACOL TOX, V18, P179
[5]   DIFFERENTIAL TOXICITY OF MONOCHLOROACETATE, MONOFLUOROACETATE AND MONOIODOACETATE IN RATS [J].
HAYES, FD ;
SHORT, RD ;
GIBSON, JE .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1973, 26 (01) :93-102
[6]   METABOLISM OF CHLOROETHANOL IN RAT [J].
JOHNSON, MK .
BIOCHEMICAL PHARMACOLOGY, 1967, 16 (01) :185-&
[7]  
LE POIDEVIN N., 1965, ACTA PHARM TOXICOL, V23, P98
[8]  
LIEBLER DC, 1985, CANCER RES, V45, P186
[9]  
MANN GT, 1987, FUND APPL TOXICOL, V9, P469
[10]  
NORWOOD DL, 1983, WATER CHLORINATON EN, V4, P191