IDENTIFICATION OF VOLATILE METABOLITES OF INHALED NORMAL-HEPTANE IN RAT URINE

被引:20
作者
BAHIMA, J [1 ]
CERT, A [1 ]
MENENDEZGALLEGO, M [1 ]
机构
[1] INST NACL SEGURIDAD & HIGIENE TRABAJO, CTR INVEST & ASISTENCIA TECN, SEVILLA, SPAIN
关键词
D O I
10.1016/0041-008X(84)90351-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
For many years petroleum solvents had been considered relatively nontoxic. Polyneuropathy resulting from industrial exposure to the solvents n-hexane and 2-hexanone is now recognized. Experimental studies in animals have shown that peripheral neuropathies can be attributed to 2,5-hexanedione, which is the probable ultimate neurotoxic metabolite on the common metabolic pathway of n-hexane and 2-hexanone. Recently, this metabolite was identified in human urine following exposure to n-hexane. A study was conducted to obtain information about the metabolic pathway of n-heptane and its potential neurotoxicity. Female Wistar rats were exposed to 2000 ppm n-heptane inhalation for 12 wk. Metabolites in urine were identified by gas chromatography-mass spectrometry. Urinary metabolites were quantified following 6 h n-heptane exposures. n-Heptane metabolites were 1-, 2-, 3- and 4-heptanols, 2- and 3-heptanones, 2,5- and 2,6-heptanediols, 5-hydroxy-2-heptanone, 6-hydroxy-2-heptanone, 6-hydroxy-3-heptanone, 2,5- and 2,6-heptanediones and .gamma.-valerolactone. The amount of urinary metabolites increased greatly after the 2nd exposure day, achieving a steady-state concentration on subsequent exposure days over the 12 wk of exposure. n-Heptane was metabolized mainly by hydroxylation at .omega..sbd.1 C atom and to a lesser extent at the .omega..sbd.2 C atom. 2-Heptanol, 6-hydroxy-2-heptanone and 3-heptanol were the major metabolites and were excreted as sulfate and glucuronides. 2,5-Heptanedione, which was a neurotoxin agent, was the metabolite found in least amounts (2.4 .+-. 2 .mu.g/rat) in the urine. No clinical evidence of neurotoxicity was observed after n-heptane exposure. Apparently, the lack of neurotoxicity was due to a low production of 2,5-heptanedione, the toxic metabolite.
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页码:473 / 482
页数:10
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