Abstract |
Methemoglobinemia produced by exposure to the herbicide propanil (3,4-dichloropropionanilide) is thought to be mediated by toxic metabolites formed during the hepatic clearance of the parent compound. We examined the metabolism of propanil and 3,4-dichloroaniline in rat liver microsomes to identify metabolites that may be involved in propanil-induced methemoglobinemia. The major pathway of propanil metabolism in microsomal incubations was acylamidase-catalyzed hydrolysis to 3,4-dichloroaniline. The reaction did not require NADPH, and was inhibited by the acylamidase inhibitors paraoxon and sodium fluoride. Oxidized metabolites were isolated by high-performance liquid chromatography, and identified as 2'-hydroxypropanil and 6-hydroxypropanil by comparison of their mass and nuclear magnetic resonance spectra to those of synthetic standards. Major microsomal metabolites of 3,4-dichloroaniline were 6-hydroxy-3,4-dichloroaniline and N-hydroxy-3,4-dichloroaniline. Both N-hydroxy-3,4-dichloroaniline and 6-hydroxy-3,4-dichloroaniline directly oxidized hemoglobin in rat erythrocyte suspensions in a concentration-dependent manner; however, the potency of N-hydroxy-3,4-dichloroaniline was at least an order of magnitude greater than that of 6-hydroxy-3,4-dichloroaniline.
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Authors | D C McMillan, J P Freeman, J A Hinson |
Journal | Toxicology and applied pharmacology
(Toxicol Appl Pharmacol)
Vol. 103
Issue 1
Pg. 90-101
(Mar 15 1990)
ISSN: 0041-008X [Print] United States |
PMID | 2315934
(Publication Type: Journal Article)
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Chemical References |
- Anilides
- Propanil
- Methemoglobin
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Topics |
- Anilides
(metabolism)
- Animals
- Chromatography, High Pressure Liquid
- Male
- Mass Spectrometry
- Methemoglobin
(biosynthesis)
- Methemoglobinemia
(chemically induced)
- Microsomes, Liver
(metabolism)
- Propanil
(metabolism, toxicity)
- Rats
- Rats, Inbred Strains
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