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水螅中有机磷酸酯类神经毒剂的毒性

Organophosphate nerve agent toxicity in Hydra attenuata.

作者信息

Lum Karin T, Huebner Henry J, Li Yingchun, Phillips Timothy D, Raushel Frank M

机构信息

Department of Chemistry, P.O. Box 30012, Texas A&M University, College Station, Texas 77842-3012, USA.

出版信息

Chem Res Toxicol. 2003 Aug;16(8):953-7. doi: 10.1021/tx034047k.

Abstract

The toxicity for analogues of sarin (GB), soman (GD), and VX was evaluated using Hydra attenuata as a model organism. The organophosphate nerve agent analogue simulants used in this investigation included the following: isopropyl p-nitrophenyl methylphosphonate (for GB); pinacolyl p-nitrophenyl methylphosphonate (for GD); and diisopropyl S-(2-diisopropylaminoethyl)phosphorothioate, diethyl S-(2-diisopropylaminoethyl)phosphorothioate, and diethyl S-(2-trimethylaminoethyl)phosphorothioate (for VX). The toxicity of each organophosphate nerve agent was assessed quantitatively by measuring the minimal effective concentration within 92 h in H. attenuata. There is a positive correlation between the molecular hydrophobicity of the compound and its ability to cause toxicity. Results from this study indicate the potential for application of this assay in the field of organophosphate chemical warfare agent detection, as well as for the prediction of toxicity of structurally similar organophosphate compounds. The minimal effective concentration for two of the VX analogues was 2 orders of magnitude more toxic than the analogue for GD and 4 orders of magnitude more toxic than the analogue for GB.

摘要

以水螅为模式生物评估了沙林(GB)、梭曼(GD)和VX类似物的毒性。本研究中使用的有机磷酸酯类神经毒剂类似物模拟物包括:对硝基苯基甲基膦酸异丙酯(用于模拟GB);频哪基对硝基苯基甲基膦酸酯(用于模拟GD);以及S-(2-二异丙氨基乙基)硫代磷酸二异丙酯、S-(2-二异丙氨基乙基)硫代磷酸二乙酯和S-(2-三甲氨基乙基)硫代磷酸二乙酯(用于模拟VX)。通过测量92小时内水螅的最小有效浓度,对每种有机磷酸酯类神经毒剂的毒性进行了定量评估。化合物的分子疏水性与其毒性能力之间存在正相关。本研究结果表明该检测方法在有机磷酸酯类化学战剂检测领域以及预测结构相似有机磷酸酯类化合物毒性方面具有应用潜力。两种VX类似物的最小有效浓度的毒性比GD类似物高2个数量级,比GB类似物高4个数量级。

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