2-氯-1-(2',4'-二氯苯基)乙烯基二乙基磷酸酯（毒虫畏）在犬和大鼠体内的代谢

The metabolism of 2-chloro-1-(2',4'-dichlorophenyl)vinyl diethyl phosphate (Chlorfenvinphos) in the dog and rat.

作者信息

Hutson D H, Akintonwa D A, Hathway D E

出版信息

Biochem J. 1967 Jan;102(1):133-42. doi: 10.1042/bj1020133.

DOI:10.1042/bj1020133

PMID:6030274

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1270219/

Abstract

A single oral dose of [(14)C]Chlorfenvinphos to rats is quantitatively eliminated in 4 days. Rats do not show a sex difference in the elimination pattern and show only a small degree of biological variation in the total excretion data. Of the label 87.2% is excreted in the urine (67.5% in the first day after dosage), 11.2% in the faeces and 1.4% in the expired gases; less than 0.9% of (14)C is present in the gut and contents after 4 days. 2. After oral administration of [(14)C]Chlorfenvinphos to dogs, 94.0% (91.8-97.6%) of the (14)C is excreted in the urine and faeces during 4 days. Dogs do not show a sex difference in the pattern of elimination, and excretion of radioactivity in the urine is very rapid: 86.0% of (14)C during 0-24hr. 3. Chlorfenvinphos is completely metabolized in rats and dogs: unchanged Chlorfenvinphos is absent from the urine and from the carcass, when elimination is complete. In rats, 2-chloro-1-(2',4'-dichlorophenyl)vinyl ethyl hydrogen phosphate accounts for 32.3% of a dose of Chlorfenvinphos, [1-(2',4'-dichlorophenyl)ethyl beta-d-glucopyranosid]uronic acid for 41.0%, 2,4-dichloromandelic acid for 7.0%, 2,4-dichlorophenylethanediol glucuronide for 2.6% and 2,4-dichlorohippuric acid for 4.3%; in dogs, 2-chloro-1-(2',4'-dichlorophenyl)vinyl ethyl hydrogen phosphate accounts for 69.6%, [1-(2',4'-dichlorophenyl)ethyl beta-d-glucopyranosid] uronic acid for 3.6%, 2,4-dichloromandelic acid for 13.4% and 2,4-dichlorophenylethanediol glucuronide for 2.7%. 4. Dogs and rats show a species difference in the rate of excretion of (14)C in the urine, and in the proportions of the metabolites, with the exception of 2,4-dichlorophenylethanediol glucuronide, that are excreted in the urine. Alternative explanations for the latter species difference are suggested. 5. 2-Chloro-1-(2',4'-dichlorophenyl)vinyl ethyl hydrogen phosphate and 2,4-dichlorophenacyl chloride probably lie on the main metabolic pathway of Chlorfenvinphos, since, in common with that insecticide, they give rise to [1-(2',4'-dichlorophenyl)ethyl beta-d-glucopyranosid]uronic acid and 2,4-dichloromandelic acid as major metabolites in the urine. 6. The proposed scheme for the metabolism of Chlorfenvinphos represents a detoxication mechanism.

摘要

给大鼠单次口服[(14)C]毒虫畏后，4天内可定量消除。大鼠在消除模式上未表现出性别差异，且总排泄数据的生物学变异程度较小。标记物中87.2%经尿液排出（给药后第一天排出67.5%），11.2%经粪便排出，1.4%经呼出气体排出；4天后，肠道及内容物中[(14)C]的含量低于0.9%。2. 给犬口服[(14)C]毒虫畏后，4天内94.0%（91.8 - 97.6%）的(14)C经尿液和粪便排出。犬在消除模式上未表现出性别差异，且尿液中放射性物质的排泄非常迅速：0 - 24小时内排出(14)C的86.0%。3. 毒虫畏在大鼠和犬体内完全代谢：消除完成后，尿液和 carcass 中均不存在未变化的毒虫畏。在大鼠体内，2 - 氯 - 1 - (2',4'-二氯苯基)乙烯基乙基磷酸氢酯占毒虫畏剂量的32.3%，[1 - (2',4'-二氯苯基)乙基β - d - 吡喃葡萄糖苷]尿酸占41.0%，2,4 - 二氯扁桃酸占7.0%，2,4 - 二氯苯乙二醇葡萄糖醛酸占2.6%，2,4 - 二氯马尿酸占4.3%；在犬体内，2 - 氯 - 1 - (2',4'-二氯苯基)乙烯基乙基磷酸氢酯占69.6%，[1 - (2',4'-二氯苯基)乙基β - d - 吡喃葡萄糖苷]尿酸占3.6%，2,4 - 二氯扁桃酸占13.4%，2,4 - 二氯苯乙二醇葡萄糖醛酸占2.7%。4. 犬和大鼠在尿液中(14)C的排泄速率以及尿液中排泄的代谢物比例上存在物种差异，但2,4 - 二氯苯乙二醇葡萄糖醛酸除外。文中提出了关于后一种物种差异的其他解释。5. 2 - 氯 - 1 - (2',4'-二氯苯基)乙烯基乙基磷酸氢酯和2,4 - 二氯苯甲酰氯可能处于毒虫畏的主要代谢途径上，因为与该杀虫剂一样，它们在尿液中产生[1 - (2',4'-二氯苯基)乙基β - d - 吡喃葡萄糖苷]尿酸和2,4 - 二氯扁桃酸作为主要代谢物。6. 所提出的毒虫畏代谢方案代表了一种解毒机制。