手性有机磷农药的稳定性及立体选择性生物行为研究
|
摘要
我国对5种高毒有机磷农药(organophosphorus pesticides，OPs)的全面禁用将导致国内在农药使用上的巨大空缺，因此急需开发和生产既经济有效，又环境友好的可替代品。OPs在结构上有两个特点：第一，容易因亲核试剂或其他因素而发生变化，保存难度高；第二，有40％都是手性的，而手性OPs的不同旋光异构体的药效、毒性、神经系统干扰和环境归趋等均有可能不同。因此，在新OPs的开发和生态风险评价中，稳定性和手征性问题引起了广泛的关注，是农药化学和环境科学研究的共同热点，已成为一个世界性的研究课题。
本文以两种我国目前推荐使用的高毒农药的替代品——氯胺磷(CP)和蔬果磷为研究对象做了以下几个方面的研究：
(1)对CP唯一的商品化制剂——30％氯胺磷乳油(CP EC)的常温贮存过程进行监控，发现其不稳定性并解释相关机制。结果表明，氯胺磷乳油的不稳定性与其助溶剂甲醇有关，引发两个后果：一方面，大部分CP与甲醇通过亲核加成生成一个新的有机磷化合物——甲基氯胺磷(MCP)，此化合物后被证实稳定且高效；另一方面，CP分解生成甲胺磷致使制剂的毒性增加。由此，30％氯胺磷乳油的应用受到很大的限制，我们提出两条解决思路：第一是从外因出发，开发氯胺磷新剂型，使其避免过于极性的环境；第二是从内因出发，以甲基氯胺磷替代氯胺磷。
(2)鉴于环糊精在改善农药稳定性中的应用，本人制备、表征了CP/β-环糊精的包合物，并分别从环糊精对CP的稳定性和毒性效应的影响来论证此包合物作为CP新剂型活性成分的开发前景。结果表明，简单的固相研磨法可制得环糊精与CP的包合物，当CP包结于β-CD后，其热稳定性提高3．6倍，同时环糊精的包合对CP的活性和毒性均未产生明显影响。由此我们认为，与环糊精包合可能是开发氯胺磷新剂型的一条较好的途径，具有一定的应用前景。
(3)旋光纯异构体的分离和制备是研究手性农药立体特异性构效关系和环境行为的首要前提和基本保障。本文借助多糖类商品化手性柱在HPLC上拆分并制备CP、MCP和蔬果磷的旋光异构体标样。结果表明，CP和MCP的四个立体异构体在Chiralpak AD柱上均得到基线分离，结合前人的研究我们进一步发现Chiralpak AD柱对含碳、磷两个不对称中心的OPs的手性拆分具有普遍的适用性。多糖类手性固定相对蔬果磷的手性识别能力很强，Chiralpak AD、Chiralcel OD和Chiralcel OJ三根手性柱均能有效分离蔬果磷的两个对映体，其中Chiralpak AD的分离效果最好，分离度为4．14。由上，本文采用Chiralpak AD柱制备以上三种有机磷化合物的单一旋光异构体，得到的旋光异构体标样的纯度均＞98％，可用于生物学实验。
(4)在得到旋光纯异构体标样的基础上，我们进一步研究了以上三种有机磷化合物在不同毒性效应上的立体选择性。
①实验首先测定了CP外消旋体，各立体异构体(峰1～峰4)及等摩尔对映体混合物(pair 1和pair 2)的体外乙酰胆碱酯酶(AChE)抑制活性及体内大型蚤毒性，均发现了明显的立体选择性。其中，异构间对AChE的抑制活性大小为峰4＞峰3＞峰2＞峰1，差异在1．1～18．1倍之间，对大型蚤的毒性大小为峰4＞峰3＞峰2＞峰1，差异在1．1～21．4之间。进一步的酶抑制动力学研究表明不同异构体对AChE的空间取向和磷酰化性能均不相同。
②对MCP毒性的立体特异性研究开始关注农药对人体健康的影响，通过在体外模式下对人成神经细胞瘤SH-SY5Y的AChE和轴突生长的抑制的测定，分别评价了MCP对人体的急性和迟发性神经毒性的立体选择性。研究进一步结合MCP在药效上的立体选择性探讨外消旋MCP及其手性富集产品作为农药的可能性和价值。结果表明，外消旋MCP稳定、高效、急性毒性低，但有可能引发迟发性的神经中毒，因此作为农药使用有一定的限制。MCP各旋光异构体的急性毒性都很低，无明显差异，但在杀虫活性和迟发性神经毒性上则具有很明显的立体选择性。峰1、峰2、峰3、峰4的杀虫活性分别为其外消旋体的3．1、0．6、0．5和1．0倍，相应的迟发性神经毒性分别为其外消旋的＜0．7、0．7、42．9和9．5倍。由此我们得出，在MCP的四个立体异构体中，峰1是其外消旋体的最佳替代品。若以峰1替代外消旋MCP，农药用量节省2/3，同时人体遭受迟发性神经中毒的风险将下降。此外，峰1和峰3的等摩尔混合物pair 1的杀虫活性、急性毒性以及迟发性神经毒性均与峰1相当，从经济和技术上考虑，pair 1的开发价值大，应用前景佳，是CP的优良替代品。
③蔬果磷及其制剂的稳定性已有不少研究，因此我们仅关注其生物行为对映体选择性。本文评价了蔬果磷在体外AChE、丁酰胆碱酯酶(BChE)抑制，体内大型蚤毒性及细胞模式下对人体急、慢性神经毒性的对映体选择性。结果表明，蔬果磷的体外AChE抑制活性和迟发性神经毒性很低，但对体外BChE、细胞AChE的抑制活性以及对大型蚤的毒性则较高，且具有明显的对映体选择性。但总体来讲，蔬果磷在多种毒性作用上的对映体选择性均不强烈，最大差异也小于5倍，目前无手性转化的必要。另外，蔬果磷的两个对映体在多种毒性作用上都表现出明显的拮抗效应，因此由外消旋体得到的毒性数据可能会造成对其生态风险的低估，而且，随着蔬果磷在环境中的对映体选择性降解，其对环境的毒性将会增加。
综合以上，本论文有两个方面的主要成果：一方面，我们对氯胺磷制剂的贮存不稳定性给出了一个可靠而合理的解释，提出解决问题的思路并从内外因上分别给予具体尝试，为氯胺磷今后的使用提供了有效参考。另一方面，通过对氯胺磷、甲基氯胺磷和蔬果磷三个有机磷化合物的手性层面的研究，并结合其它研究者的工作，我们得到对于手性有机磷化合物的生物效应来说，立体选择性可能是个普遍现象。因此，有关手性农药的研究，只有深入到手性层面，才能反映其真实的环境行为学状况，制定出准确的环境政策、法规和标准。此外，化合物靶标药效和非靶标毒性的立体选择性的比较研究对其手性转换价值和可能性的评价也非常有效。
Since the five highly toxic organophosphorus pesticides (OPs) have been banned,the demand for pesticides in China will exceed supply in the following several years.Therefore, it is greatly expected to exploit some economically viable andenvironment-friendly alternatives. OPs have two properties in their configurations:firstly, they are susceptible to react with nucleophilic reagents or others, and thus easyto change during storage; Secondly, 40% of OPs are chiral and the biological actionssuch as activity, toxicity, neurological disruption and fate in the environment of chiralOPs are stereoselective. As a result, both the stability and chirality of the new createdOPs attract worldwide attention.
Our studies focused on chloramines phosphorus (CP) and salithion, two OPscurrently recommended to instead the highly toxic ones, and the detailed researchcontents and results are as follows:
(1) Changes in composition and toxicity of the exclusively commercialformulation of CP, i.e., 30% emulsifiable concentrates (EC) during its storage werediscovered and the corresponding mechanism was carefully investigated. The resultsshowed that the storage instability of CP EC was probably attributable to its cosolventmethanol: On the one hand, majority of the active ingredient CP was reacted withmethanol by nucleophilic addition, forming a stable and highly active neworganophosphorus compound——O,S-dimethyl-[2,2,2-trichloro-1-methoxyethyl]phosphoramidothioate (MCP); On theother hand, some CP decomposed to methamidophos, resulting in toxic potentiationof CP EC during storage. These results give us two information: first, the use of 30%CP EC is advised to be limited: second, either reformulation of CP in a lesshydrophilic environment or using MCP instead of CP may be available for resolvingthe problem.
(2) In view of cyclodextrins ability to improve the stability of pesticides,CP-β-cyclodextrin (CP-β-CD) complex was prepared and identified, and the effects ofthe encapsulated process ofβ-CD to the thermal stability, activity and toxicity of CPwere also evaluated. The results showed that the degradation rate of CP in 14-daysincubation at 54±1℃was slowed by a factor of 3.6 when it was inclusion complexed withβ-CD. Meanwhile, no significant adverse effects on the bio-efficacyof CP were caused by the encapsulation process. All these results indicate thatCP-β-CD is promising to be produced as the active ingredients of various formulationadditives of CP for its continuous application.
(3) Preparation of optical pure isomers is the prerequisite for studying thestereoselectivities of chiral pesticides in their structure-activity relationships andenvironmental behaviours. In this thesis, milligram scale amount of individual opticalisomers of CP, MCP and salithion were prepared on several polysaccharide modelchiral stationary phases (CSPs). Separation of all the four stereoisomers of CP andMCP were coincidentally accomplished on the Chiralpak AD column, with theresolutions (R_s) between either two adjacent peaks＞1.5 which suggests a baselineresolution. Addition to the previous studies, we further found that Chiralpak ADcolumn seems commonly available to separate stereoisomers of chiralorganophosphorus compounds with two chiral centres on the phosphorus and carbonatoms. The enantiomers of salithion were then successfully isolated on the ChiralpakAD, Chiralcel OD and Chiralcel OJ columns, among which the Chiralpak AD columnalso offered the highest R_s. Therefore, in our study we chose the Chiralpak ADcolumn to prepare the individual optical isomers of the above three organophosphoruscompounds. The purity was then calculated to be more than 98% for all isomersprepared for toxicity assays.
(4) Based on the successful preparation of the individual optical isomers, thestereoselectivities in various biological activities of CP, MCP. and salithion werestudied.
①The inhibition on acetylcholinesterases (AChE, in vitro) and the acuteaquatic toxicity to Daphnia magna (in vivo) tested with optically pure isomers of CPshowed its stereoselectivity. The inhibitory potentials toward AChE decreased in theorder of pk 4＞pk 3＞pk 2＞pk 1. In comparison, the acute toxicity to D. magna wasin the order of pk 3＞pk 2＞pk 1＞pk 4. The stereoselectivity was found to beisomer-dependent, with 1.1-18.1-fold differences (in vitro) and 1.1-21.4-fold differences (in vivo) among the stereoisomers. The enzyme inhibition dynamic assaysfurther indicated that both the spatial orientations and phosphorylation properties ofdifferent stereoisomers towards AChE were different.
②Studies of stereoselective toxicities of MCP became focus on human health.The acute cholinergic crisis and organophosphate-induced delayed neuropathy(OPIDN) of racemic MCP and its four stereoisomers to humans were evaluated by theinhibitory potentials to acetylcholinesterase (AChE) and axon-like outgrowth inSH-SY5Y human neuroblastoma cells, respectively. Their insecticidal activities wereadditionally measured in order to evaluate the possibility and worth of racemic MCPor its single- or enriched-enantiomer products to be a new pesticide. The resultsshowed that racemic MCP was stable, high active against insects and low acute toxictowards humans. However, the high threat to OPIDN makes its pesticidal use doubtful.The acute toxicities of the four stereoisomers to humans were all low and unselective.However, their insecticidal activities and delayed neurotoxicities were extremelydifferent. Hereinto, the relative insecticidal activities between the racemate and thestereoisomers were 3.1-, 0.6-, 0.5-, and 1.0-fold for pk1, pk2, pk 3, and pk 4,respectively. While the corresponding ratios in the delayed neurotoxicities were＜0.7,0.7, 42.9, and 9.5-times, respectively. In view of its highest activity and lowesttoxicity, pk 1 is the optimal substitute for the racemate among the four stereoisomers.It can be determined that if racemic MCP is replaced by pk 1, two-thirds of the usualpesticide amount can be saved in addition to a better prevention for humans from thedelayed neurotoxic risks. Furthermore, the insecticidal activity and the potencies ofcholinergic toxicity and neuropathic hazard of pair 1. i.e., an equimolar mixture of pk1 and pk 3, were all comparable with those of pk 1. Considering the absence of theeconomically feasible manufacturing of plants of single stereoisomers, pair 1 of MCPshows considerable worth for future applications and may be proper to instead of CP.
③Enantioselective toxicities of salithion were also evaluated. In this study, wechose five biological endpoints, including the toxicities towards AChE (in vitro),butyrylcholinesterase (BChE, in vitro) and D. Magna (in vivo), and the inhibitorypotentials against AChE and axon growth in SH-SY5Y. The restults showed that both the in vitro anti-AChE potentials and delayed neurotoxicities of the racemic salithionand its enantiomers were low, while their toxicities towards BChE, cell AChE, and D.Magna were high and selective. More concretely, the enantioselectivities of salithionin various biological behaviours were all less than a factor of five, suggesting that thechiral switch of salithion may be not necessary. Moreover, an antagonistic interactionis likely to be exist between the enantiomers of salithion during many toxic actions,which may result in an underestimation of ecological risks when using the dataderived from the racemate. It can also be predicted that the toxicity of salithion to theenvironment will increase during its enantioselective degradation.
To sum up, our work gained two achievements: First, we offered a credible andrational explanation for the instability of CP EC during storage, and this is useful for acontinuous application of CP; Second, data of the stereoselective bioassays of CP,MCP and salithion implied that stereoselectivity might be ubiquitous for thebiological actions of chiral OPs. Therefore, we suggest that only the studies whichtake the stereoselective environmental behaviors into account can offer acomprehensive assessment of the ecotoxicology risks of chiral pesticides. Moreover,comparative studies of the stereospecific toxicities against the target and non-targetorganisms are also useful to assess the worth and possibility of chiral switch ofpesticides.
本文以两种我国目前推荐使用的高毒农药的替代品——氯胺磷(CP)和蔬果磷为研究对象做了以下几个方面的研究：
(1)对CP唯一的商品化制剂——30％氯胺磷乳油(CP EC)的常温贮存过程进行监控，发现其不稳定性并解释相关机制。结果表明，氯胺磷乳油的不稳定性与其助溶剂甲醇有关，引发两个后果：一方面，大部分CP与甲醇通过亲核加成生成一个新的有机磷化合物——甲基氯胺磷(MCP)，此化合物后被证实稳定且高效；另一方面，CP分解生成甲胺磷致使制剂的毒性增加。由此，30％氯胺磷乳油的应用受到很大的限制，我们提出两条解决思路：第一是从外因出发，开发氯胺磷新剂型，使其避免过于极性的环境；第二是从内因出发，以甲基氯胺磷替代氯胺磷。
(2)鉴于环糊精在改善农药稳定性中的应用，本人制备、表征了CP/β-环糊精的包合物，并分别从环糊精对CP的稳定性和毒性效应的影响来论证此包合物作为CP新剂型活性成分的开发前景。结果表明，简单的固相研磨法可制得环糊精与CP的包合物，当CP包结于β-CD后，其热稳定性提高3．6倍，同时环糊精的包合对CP的活性和毒性均未产生明显影响。由此我们认为，与环糊精包合可能是开发氯胺磷新剂型的一条较好的途径，具有一定的应用前景。
(3)旋光纯异构体的分离和制备是研究手性农药立体特异性构效关系和环境行为的首要前提和基本保障。本文借助多糖类商品化手性柱在HPLC上拆分并制备CP、MCP和蔬果磷的旋光异构体标样。结果表明，CP和MCP的四个立体异构体在Chiralpak AD柱上均得到基线分离，结合前人的研究我们进一步发现Chiralpak AD柱对含碳、磷两个不对称中心的OPs的手性拆分具有普遍的适用性。多糖类手性固定相对蔬果磷的手性识别能力很强，Chiralpak AD、Chiralcel OD和Chiralcel OJ三根手性柱均能有效分离蔬果磷的两个对映体，其中Chiralpak AD的分离效果最好，分离度为4．14。由上，本文采用Chiralpak AD柱制备以上三种有机磷化合物的单一旋光异构体，得到的旋光异构体标样的纯度均＞98％，可用于生物学实验。
(4)在得到旋光纯异构体标样的基础上，我们进一步研究了以上三种有机磷化合物在不同毒性效应上的立体选择性。
①实验首先测定了CP外消旋体，各立体异构体(峰1～峰4)及等摩尔对映体混合物(pair 1和pair 2)的体外乙酰胆碱酯酶(AChE)抑制活性及体内大型蚤毒性，均发现了明显的立体选择性。其中，异构间对AChE的抑制活性大小为峰4＞峰3＞峰2＞峰1，差异在1．1～18．1倍之间，对大型蚤的毒性大小为峰4＞峰3＞峰2＞峰1，差异在1．1～21．4之间。进一步的酶抑制动力学研究表明不同异构体对AChE的空间取向和磷酰化性能均不相同。
②对MCP毒性的立体特异性研究开始关注农药对人体健康的影响，通过在体外模式下对人成神经细胞瘤SH-SY5Y的AChE和轴突生长的抑制的测定，分别评价了MCP对人体的急性和迟发性神经毒性的立体选择性。研究进一步结合MCP在药效上的立体选择性探讨外消旋MCP及其手性富集产品作为农药的可能性和价值。结果表明，外消旋MCP稳定、高效、急性毒性低，但有可能引发迟发性的神经中毒，因此作为农药使用有一定的限制。MCP各旋光异构体的急性毒性都很低，无明显差异，但在杀虫活性和迟发性神经毒性上则具有很明显的立体选择性。峰1、峰2、峰3、峰4的杀虫活性分别为其外消旋体的3．1、0．6、0．5和1．0倍，相应的迟发性神经毒性分别为其外消旋的＜0．7、0．7、42．9和9．5倍。由此我们得出，在MCP的四个立体异构体中，峰1是其外消旋体的最佳替代品。若以峰1替代外消旋MCP，农药用量节省2/3，同时人体遭受迟发性神经中毒的风险将下降。此外，峰1和峰3的等摩尔混合物pair 1的杀虫活性、急性毒性以及迟发性神经毒性均与峰1相当，从经济和技术上考虑，pair 1的开发价值大，应用前景佳，是CP的优良替代品。
③蔬果磷及其制剂的稳定性已有不少研究，因此我们仅关注其生物行为对映体选择性。本文评价了蔬果磷在体外AChE、丁酰胆碱酯酶(BChE)抑制，体内大型蚤毒性及细胞模式下对人体急、慢性神经毒性的对映体选择性。结果表明，蔬果磷的体外AChE抑制活性和迟发性神经毒性很低，但对体外BChE、细胞AChE的抑制活性以及对大型蚤的毒性则较高，且具有明显的对映体选择性。但总体来讲，蔬果磷在多种毒性作用上的对映体选择性均不强烈，最大差异也小于5倍，目前无手性转化的必要。另外，蔬果磷的两个对映体在多种毒性作用上都表现出明显的拮抗效应，因此由外消旋体得到的毒性数据可能会造成对其生态风险的低估，而且，随着蔬果磷在环境中的对映体选择性降解，其对环境的毒性将会增加。
综合以上，本论文有两个方面的主要成果：一方面，我们对氯胺磷制剂的贮存不稳定性给出了一个可靠而合理的解释，提出解决问题的思路并从内外因上分别给予具体尝试，为氯胺磷今后的使用提供了有效参考。另一方面，通过对氯胺磷、甲基氯胺磷和蔬果磷三个有机磷化合物的手性层面的研究，并结合其它研究者的工作，我们得到对于手性有机磷化合物的生物效应来说，立体选择性可能是个普遍现象。因此，有关手性农药的研究，只有深入到手性层面，才能反映其真实的环境行为学状况，制定出准确的环境政策、法规和标准。此外，化合物靶标药效和非靶标毒性的立体选择性的比较研究对其手性转换价值和可能性的评价也非常有效。
Since the five highly toxic organophosphorus pesticides (OPs) have been banned,the demand for pesticides in China will exceed supply in the following several years.Therefore, it is greatly expected to exploit some economically viable andenvironment-friendly alternatives. OPs have two properties in their configurations:firstly, they are susceptible to react with nucleophilic reagents or others, and thus easyto change during storage; Secondly, 40% of OPs are chiral and the biological actionssuch as activity, toxicity, neurological disruption and fate in the environment of chiralOPs are stereoselective. As a result, both the stability and chirality of the new createdOPs attract worldwide attention.
Our studies focused on chloramines phosphorus (CP) and salithion, two OPscurrently recommended to instead the highly toxic ones, and the detailed researchcontents and results are as follows:
(1) Changes in composition and toxicity of the exclusively commercialformulation of CP, i.e., 30% emulsifiable concentrates (EC) during its storage werediscovered and the corresponding mechanism was carefully investigated. The resultsshowed that the storage instability of CP EC was probably attributable to its cosolventmethanol: On the one hand, majority of the active ingredient CP was reacted withmethanol by nucleophilic addition, forming a stable and highly active neworganophosphorus compound——O,S-dimethyl-[2,2,2-trichloro-1-methoxyethyl]phosphoramidothioate (MCP); On theother hand, some CP decomposed to methamidophos, resulting in toxic potentiationof CP EC during storage. These results give us two information: first, the use of 30%CP EC is advised to be limited: second, either reformulation of CP in a lesshydrophilic environment or using MCP instead of CP may be available for resolvingthe problem.
(2) In view of cyclodextrins ability to improve the stability of pesticides,CP-β-cyclodextrin (CP-β-CD) complex was prepared and identified, and the effects ofthe encapsulated process ofβ-CD to the thermal stability, activity and toxicity of CPwere also evaluated. The results showed that the degradation rate of CP in 14-daysincubation at 54±1℃was slowed by a factor of 3.6 when it was inclusion complexed withβ-CD. Meanwhile, no significant adverse effects on the bio-efficacyof CP were caused by the encapsulation process. All these results indicate thatCP-β-CD is promising to be produced as the active ingredients of various formulationadditives of CP for its continuous application.
(3) Preparation of optical pure isomers is the prerequisite for studying thestereoselectivities of chiral pesticides in their structure-activity relationships andenvironmental behaviours. In this thesis, milligram scale amount of individual opticalisomers of CP, MCP and salithion were prepared on several polysaccharide modelchiral stationary phases (CSPs). Separation of all the four stereoisomers of CP andMCP were coincidentally accomplished on the Chiralpak AD column, with theresolutions (R_s) between either two adjacent peaks＞1.5 which suggests a baselineresolution. Addition to the previous studies, we further found that Chiralpak ADcolumn seems commonly available to separate stereoisomers of chiralorganophosphorus compounds with two chiral centres on the phosphorus and carbonatoms. The enantiomers of salithion were then successfully isolated on the ChiralpakAD, Chiralcel OD and Chiralcel OJ columns, among which the Chiralpak AD columnalso offered the highest R_s. Therefore, in our study we chose the Chiralpak ADcolumn to prepare the individual optical isomers of the above three organophosphoruscompounds. The purity was then calculated to be more than 98% for all isomersprepared for toxicity assays.
(4) Based on the successful preparation of the individual optical isomers, thestereoselectivities in various biological activities of CP, MCP. and salithion werestudied.
①The inhibition on acetylcholinesterases (AChE, in vitro) and the acuteaquatic toxicity to Daphnia magna (in vivo) tested with optically pure isomers of CPshowed its stereoselectivity. The inhibitory potentials toward AChE decreased in theorder of pk 4＞pk 3＞pk 2＞pk 1. In comparison, the acute toxicity to D. magna wasin the order of pk 3＞pk 2＞pk 1＞pk 4. The stereoselectivity was found to beisomer-dependent, with 1.1-18.1-fold differences (in vitro) and 1.1-21.4-fold differences (in vivo) among the stereoisomers. The enzyme inhibition dynamic assaysfurther indicated that both the spatial orientations and phosphorylation properties ofdifferent stereoisomers towards AChE were different.
②Studies of stereoselective toxicities of MCP became focus on human health.The acute cholinergic crisis and organophosphate-induced delayed neuropathy(OPIDN) of racemic MCP and its four stereoisomers to humans were evaluated by theinhibitory potentials to acetylcholinesterase (AChE) and axon-like outgrowth inSH-SY5Y human neuroblastoma cells, respectively. Their insecticidal activities wereadditionally measured in order to evaluate the possibility and worth of racemic MCPor its single- or enriched-enantiomer products to be a new pesticide. The resultsshowed that racemic MCP was stable, high active against insects and low acute toxictowards humans. However, the high threat to OPIDN makes its pesticidal use doubtful.The acute toxicities of the four stereoisomers to humans were all low and unselective.However, their insecticidal activities and delayed neurotoxicities were extremelydifferent. Hereinto, the relative insecticidal activities between the racemate and thestereoisomers were 3.1-, 0.6-, 0.5-, and 1.0-fold for pk1, pk2, pk 3, and pk 4,respectively. While the corresponding ratios in the delayed neurotoxicities were＜0.7,0.7, 42.9, and 9.5-times, respectively. In view of its highest activity and lowesttoxicity, pk 1 is the optimal substitute for the racemate among the four stereoisomers.It can be determined that if racemic MCP is replaced by pk 1, two-thirds of the usualpesticide amount can be saved in addition to a better prevention for humans from thedelayed neurotoxic risks. Furthermore, the insecticidal activity and the potencies ofcholinergic toxicity and neuropathic hazard of pair 1. i.e., an equimolar mixture of pk1 and pk 3, were all comparable with those of pk 1. Considering the absence of theeconomically feasible manufacturing of plants of single stereoisomers, pair 1 of MCPshows considerable worth for future applications and may be proper to instead of CP.
③Enantioselective toxicities of salithion were also evaluated. In this study, wechose five biological endpoints, including the toxicities towards AChE (in vitro),butyrylcholinesterase (BChE, in vitro) and D. Magna (in vivo), and the inhibitorypotentials against AChE and axon growth in SH-SY5Y. The restults showed that both the in vitro anti-AChE potentials and delayed neurotoxicities of the racemic salithionand its enantiomers were low, while their toxicities towards BChE, cell AChE, and D.Magna were high and selective. More concretely, the enantioselectivities of salithionin various biological behaviours were all less than a factor of five, suggesting that thechiral switch of salithion may be not necessary. Moreover, an antagonistic interactionis likely to be exist between the enantiomers of salithion during many toxic actions,which may result in an underestimation of ecological risks when using the dataderived from the racemate. It can also be predicted that the toxicity of salithion to theenvironment will increase during its enantioselective degradation.
To sum up, our work gained two achievements: First, we offered a credible andrational explanation for the instability of CP EC during storage, and this is useful for acontinuous application of CP; Second, data of the stereoselective bioassays of CP,MCP and salithion implied that stereoselectivity might be ubiquitous for thebiological actions of chiral OPs. Therefore, we suggest that only the studies whichtake the stereoselective environmental behaviors into account can offer acomprehensive assessment of the ecotoxicology risks of chiral pesticides. Moreover,comparative studies of the stereospecific toxicities against the target and non-targetorganisms are also useful to assess the worth and possibility of chiral switch ofpesticides.
引文
1. Aaron, H. S.; Michel, H. O.; Wittten, B.; Miller, J. I. The stereochemistry of asymmetric phosphorus compounds Ⅱ. Stereospecificity in the irreversible inactivation of cholinesterases by the enantiomorphs of an organophosphorus inhibitor. J. Am. Chem. Soc. 1958, 80: 456-459.
2. Abou-Donia, M. B. Organophosphorus ester-induced delayed neurotoxicity. Ann. Rev. Pharmacol. Toxicol. 1981, 21:511-548.
3. Abou-Donia, M. B. The cytoskeleton as a target for organophosphorus ester-induced delayed neurotoxicity (OPIDN). Chem. Biol. Interact. 1993, 87: 383-393.
4. Abou-Donia, M. B. Involvement of cytoskeletal proteins in the mechanisms of organophosphorus ester-induced delayed neurotoxicity. Clin. Exp. Pharmacol. Physiol. 1995, 22: 358-359.
5. Ackermann, P.; Bourgeois, F.; Drabek, J. The optical isomers of α-cyano-3-phenoxy-benzyl-3-(1,2-dibromo-2,2-dichloroethyl)-2,2-dimethylcyclo-propanecarboxylate and their insecticidal activities. Pestic. Sci. 1980, 11: 169-179.
6. Aldridge, W. N. The nature of the reaction of organophosphorus compounds and carbamates with esterase. Bull. Wld. Hlth. Org. 1971, 44: 25-30.
7. Allahyari, R.; Hollingshaus, J. G.; Lapp, R. L.; Timm, E.; Jacobson, R. A.; Fukuto, T. R. Resolution, absolute configuration, and acute and delayed neurotoxicity of the chiral isomers of O-aryl phenylphonothioate analogues related to leptophos. J. Agric. Food Chem. 1980, 28: 594-598.
8. Anigbogu, V. C.; Woldeab, H.; Garrison, A. W.; Avants, J. K. Enantioseparation of malathion, cruformate, and fensulfothion organophosphorus pesticides by mixed-mode electrokinetic capillary chromatography. Int. J. Environ. An. Ch. 2003, 83: 89-100.
9. Armstrong, D. J.; Fukuto, T. R. Synthesis, resolution and toxicological properties of the chiral isomers of O, S-dimethyl and diethyl ethylphosphonothioate. J. Agric. Food. Chem. 1987, 35: 500-506.
10. Atwood, J. L.; Lehn, J. M. Cyclodextrins. Pergamon: Oxfors, 1996, 503-513.
11. Baker, E. L.; Zack, M.; Miles, J. W.; Alderman, L.; Warren, MEW.; Dobbin, R. D.; Miller, S.; Teeters, W. R. Epidemic malathion poisoning in pakistan malaria workers. Lancet 1978, 8405: 31-34.
12. Battershill, J. M.; Edwards, P. M.; Johnson, M. K. Toxicological assessment ofisomeric pesticides: a strategy for testing of chiral organophosphorus (OP) compounds for delayed polyneuropathy in a regulatory setting. Food Chem.Toxicol. 2004, 42: 1279-1285.
13. Benshop, H. P.; Konings, C. A. G.; Genderen, V. Isolation, anticholinesterase properties,and acute toxicity in mice of the four stereoisomers of the nerve agent soman. J. Toxicol. Appl. Pharmacol. 1984, 72: 61-74.
14. Berkman, C. E.; Thompson, C. M.; Perrin, S. R. Synthesis, absolute-configuration, aned analysis of malathion, malaxon, and isomalathion enantiomers. Chem Res. Toxicol. 1993a, 6: 718-723.
15. Berkman, C. E.; Quinn, D. A.; Thompson, C. M. Kinetics of post-inhibitory reactions of AChE poisoned by chiral isomalathion: a surprising non-reactivation induced by the RP stereoisomers. Chem. Res. Toxicol. 1993b, 6: 724-731.
16. Biebel, R.; Hengstberger, K.; Polheim, D.; Viernstein, H. Improvedlight-stability of pyrethrins by complexation with gamma-cyclodextrin. Proc. Int. Symp. Controlled Release Bioact. Mater. 2000, 27: 1358-1359.
17. Buser, H. R.; Muller, M. D.; Poiger, T.; Blamer, M. E. Environmental behavior of the chiral acetamide pesticide metalaxyl: enantioselective degradation and chiral stability in soil. Environ. Sci. Technol. 2002, 36: 221-226.
18. Casida, J. E.; Sanderson, D. M. Toxic hazard from formulatingthe insecticide dimethoate in methyl "Cellosolve". Nature 1961, 189: 507-508.
19. Casida, J. E.; Sanderson, D. M. Solvent effects on toxicity, reaction of certain phosphorothionate insecticides with alcohols and potentiation by breakdown products. JAgric. Food Chem. 1963, 11: 91-96.
20. Casida, J. E.; Leader, H. Resolution and biological activity of the chiral isomers of O-(4-bromo- 2-chlorophenyl) O-ethyl S-propyl phosphorothioate (profenofos insecticide). J. Agric. Food. Chem. 1982, 30: 546-552.
21. Chin, Y. C; Dauterman, W. C. The affinity and phosphorylation constants of the optical isomers of O,O-diethyl malaoxon and the geometric isomers of phosdrin with acetylcholinesterase. Biochem. Pharmacol. 1969, 18: 359-366.
22. Connors, K. A. The stability of cyclodextrin complexes in solution. Chem. Rev. 1997,97: 1325-1357.
23. Cranmer, J. M.; Hixson, E. J. Delayed Neurotoxicity. Intox Press: Little Rock, 1984, 7-22.
24. De Wilde, V.; Vogelaers, D.; Colardyn, F. Prompt recovery from severe cholinesterase-inhibitor poisoning-emarks on classification and therapy of organophosphate poisoning. J. Molecular Med. 1990, 68: 615-618.
25. de Jong, L. P. A.; Benshop, H. P. Stereoselectivity of Pesticides. Amsterdam: Elsevier Science Publishers, 1988, 109-149.
26. Eddleston, M.; Buckley, N. A.; Eyer, P.; Dawson, A. H. Management of acute organophosphorus pesticide poisoning. Lancet 2008, 371: 597-607.
27. Eldefrawi, M. E.; Eldefrawi, A. T. Neurotransmitter receptors as targets for pesticides. J. Environ. Sci. Health B. 1983, 18: 65-88.
28. Ellington, J. J.; Evans, J. J.; Prickett, K. B.; Champion, W. L. High-performance liquid chromatographic separation of the enantiomers of organophosphorus pesticides on polysaccharide chiral stationary phases. J. Chromatogr. A 2001, 928: 145-154.
29. Eya, B. K.; Fukuto, T. R. The effect of chiral debromoleptophos oxon isomers on acute and delayed neurotoxicity and their inhibitory activity against acetylcholinesterases and neurotoxic esterase. J. Agric. Food Chem. 1985, 33: 884-888.
30. Fidalgo-Used, N.; Montes-Bayon, M.; Bianco-Gonzalez, E.; Sanz-Medel, A., SPME-enantioselective gas chromatography with ECD and ICP-MS detection for the chiral speciation of the pesticide ruelene in environmental samples. J. Anal. Atom. Spectrom. 2006a, 21: 876-883.
31. Fidalgo-Used, N.: Blanco-Gonzalez, E.; Sanz-Medel, A., Evaluation of two commercial capillary columns for the enantioselective gas chromatographic separation of organophosphorus pesticides. Talanta2006b, 70: 1057-1063.
32. Fournier, J., Pesticides stereochemistry. Actual. Chimique 2007, Suppl. 304: 21-29.
33. Fukuto, T. R.; Metcalf, R. L. Alkylphosphonic acid esters as insecticides. J. Econ. Entomol. 1959, 52: 739-743.
34. Garay, A. S. Molecular chirality of life and intrinsic chirality of matter. Nature 1918,271: 186.
35. Garc(?)a-Ruiz, C; Alvarez-Llamas, G.; Puerta, A.; Blanco, E.; Sanz-Medel, A.; Marina, M. L., Enantiomeric separation of organophosphorus pesticides by capillary electrophoresis-Application to the determination of malathion in water samples after preconcentration by off-line solid-phase extraction. Anal. Chim. Acta 2005, 543: 77-83.
36. Garrison, W., On the issue of enantioselectivity of chiral pesticides: a green chemistry opportunity. Green Chem. 2004, 6: G77-G78.
37. Garrison, A.W. Probing the enantioselectivity of chiral pesticides. Environ. Sci. Technol. 2006, 40: 16-23.
38. Garrison, A. W.; Schmitt-Kopplin, P.; Avants, J. K. Analysis of the enantiomers of chiral pesticides and other pollutants in environmental samples by capillary electrophoresis. Methods Mol. Biol. 2008, 384: 157-70.
39. Green, M. M.; Selinger, J. V. Cosmic chirality. Science 1998, 282: 880-881.
40. Grothusen, J. R.; Brown, T. M. Stereoselectivity of acetylcholinesterase, arylester hydrolase, and Chymotrypsin toward 4-nitrophenyl) alkyl (phenyl) phosphinates. Pestic. Biochem. Physiol. 1986, 26:100-112.
41. Hall, C. R.; Inch, T; D.; Inns, R. H. Differences between some biological properties of enantiomers of alkyl S-alkyl methylphosphonothiolates. J. Pharm. Pharmacol 1917, 29: 574-579.
42. Hassan, A.; Dauterman, W. C. Studies on the optically active isomers of O, O-diethyl malathion and O, O-diethyl malaoxan. Biochem. Pharmacol. 1968, 17: 1431-1438.
43. Heath, D. F.; Vandekar, M. Some spontaneous reactions of O O-dimethyl S-ethylthioethyl phosphorothiolate and related compounds in water and on storage, and their effects on the toxicological properties of the compounds. Biochem. J. 1957, 67: 187-201.
44. Hedges, A. R. Industrial applications of cyclodextrins. Chem. Rev. 1998, 98: 2035-2044.
45. Hilgetag, S.; Lehman, G. Contributions for the chemistry of the thiophosphate. VII. Optically active thiophosphate. J. prakt. Chem. 1959, 8: 224-230.
46. Hirashima A, Ishaaya I, Ueno R. et al. Effect of salithion enantiomers on the trehalase system and on the digestive protease, amylase, and invertase of Tribolium castaneum. Pestic. Biochem. Physiol. 1989, 34: 205-210.
47. Hoekstra, P. F.; Burnison, B. K.; Neheli, T.; Muir, D. C. G. Enantiomer-specific activity of o,p'-DDT with the human estrogen receptor. Toxicol. Lett. 2001, 125: 75-81.
48. Hoekstra, P. F.; Burnison, B. K.; Garrison, A. W.; Neheli, T.; Muir, D. C. G. Estrogenic activity of dicofol with the human estrogen receptor: Isomer- and enantiomer-specific implications. Chemosphere 2006, 64: 174-177..
49. Huang, L.; Lin, J. M.; Xu, L. J.; Chen, G. N. Nonaqueous and aqueous-organic media for the enantiomeric separations of neutral organophosphorus pesticides by CE. Electrophoresis 2007, 28: 2758-2764.
50. Jarman, J. L.; Jones, W. J.; Howell, L. A.; Garrison, A. W., Application of capillary electrophoresis to study the enantioselective transformation of five chiral pesticides in aerobic soil slurries. J. Agric. Food Chem. 2005, 53: 6175-6182.
51. Johnson, M. K. Organophosphorus and other inhibitors of brain "neurotoxic esterase" and the development of delayed neurotoxicity in hens. Biochem. J. 1970,720:520-531.
52. Johnson, M. K. The target for initian of delayed neurotoxicity by organophosphorus easters: biochemical studies and toxicological applications. Rev. Biochem. Toxicol 1982, 4: 141.
53. Johnson, M. K.; Vilanova, E.; Read, D. J. Anomalous biochemical responses in tests of the delayed neuropathic potential of methamidophos (O,S-dimethyl phosphorothioamidate), its resolved isomers and of some higher O-alkyl homologues. Arch. Toxicol. 1991, 65: 618-624.
54. Johnson, M. K. Symposium introduction: retrospect and prospects for neuropathy target esterase (NTE) and the delayed polyneuropathy (OPIDP) induced by some organophosphorus esters. Chem Bio/ Interact. 1993, 87:339-346.
55. Kado, M.; Yoshinaga, E. Fungicidal action of organophosphorus compounds. Residue Rev. 1969,25: 133.
56. Kamiya, M.; Nakamura, K.; Sasaki, C. Inclusion effects of cyclodextrins on photodegradation rates of parathion and paraoxon in aquatic medium. Chemosphere 1994, 28: 1961-1966.
57. Kamiya, M.; Nakamura, K. Cyclodextrin inclusion effects on photodegradation rates of organophosphorus pesticides. Environ. Int. 1995a, 21: 299-304.
58. Kamiya, M.; Nakamura, K.; Sasaki, C. Inclusion effects of p-cyclodextrins on the hydrolysis of organophosphorus pesticides. Chemosphere 1995b, 30: 653-660.
59. Katsuda, Y.; Yamamoto, S. Stabilization of pyrethroids by p-cyclodextrin. JP 51081888,1976. (CAN 85:138639)
60. Kita, K.; Nihorbashi, H. DDVP-Cyclodextrin Complexes. GB 1453801, 1976.
61. Kishimoto, D.; Oku, A.; Kurihara, N. Enantiotopic selectivity of cytochrome P_450-catalyzed oxidative demethylation of methoxychlor: Alteration of selectivity depending on isozymes and substrate concentrations. Pest. Biochem. Physiol. 1995,57:12-19.
62. Kohler, H. P. E.; Angst, W.; Giger, W.; Kanz, C; Muller, S.; Suter, M. J. F. Environmental fate of chiral pollutants-the necessity of considering stereochemistry. Chimia 1997, 57: 947-951.
63. Kurihara, N.; Miyamoto, J.; Paulson, G. D.; Zeeh, B.; Skidmore, M. W.;Hollingworth, R. M.; Kuiper, H. A. Chirality in synthetic agrochemicals: bioactivity and safety considerations, Pure Appl. Chem. 1997, 69: 2007-2025.
64. Kurihara, N.; Miyamoto, J. Chirality in agrochemicals. John Wiley & Sons: New York, 1998, 85-140.
65. Lange, W.; Krueger, B. Uber ester der monofluorphorsaure. Chem Ber 1932, 65:1598.
66. Lee, P. W.; Allahyari, R; Fukuto, T. R. Studies on the chiral isomers of fonofos and fonofos oxon: 1. Toxicity and antiesterase activities. Pestic. Biochem. Physiol. 1978a, 8: 146-157.
67. Lee, P. W.; Allahyari, R.; Fukuto, T. R. Studies on the chiral isomers of fonofos and fonofos oxon: 2. In vitro metabolism. Pestic. Biochem. Physiol. 1978b, 8:158-162.
68. Lee, P. W.; Allahyari, R.; Fukuto, T. R. Studies on the chiral isomers of fonofos and fonofos oxon: 3. Toxicity and antiesterase activities. Pestic. Biochem.Physiol. 1978c, 9: 23-28.
69. Lee, P. W.; Allahyari, R.; Fukuto, T. R. Absorption and metabolism of the chiral isomers of fonofos in the corn and cotton plant. J. Environ. Sci. Health B 1980,75: 25-29.
70. Levy, D.; Ashani, Y. Synthesis and in vitro properties of a powerful quaternary methylphosphonate inhibitor of acetylcholinesterase.A new marker in blood-brain barrier research. Biochem. Pharmacol. 1986, 35: 1079-1085.
71. Lewis, D. L.; Garrison, A. W.; Wommack, K. E.; Whittemore, A.; Steudler, P.; Melillo, J. Influence of environmental changes on degradation of chiral pollutants in soils. Nature 1999, 401: 898-901.
72. Li, Z. Y.; Zhang, Z. C; Zhou, Q. L.; Gao, R. Y.; Wang, Q. S. Fast and precise determination of phenthoate and its enantiomeric ratio in soil by the matrix solid-phase dispersion method and liquid chromatography. J. Chromatogr. A 2002, 977: 17-25.
73. Lin, K.; Zhou, S. S.; Xu, C; Liu, W. P. Enantiomeric resolution and biotoxicity of methamidophos. J. Agric. Food Chem. 2006, 54: 8134-8138.
74. Liu, W. P.; Gan, J. Y; Schlenk, D.; Jury, W. A. Enantioselectivity in environmental safety of current chiral insecticides. Proc. Natl. Acad. Sci. U.S.A. 2005a, 702:701-706.
75. Liu, W. P.; Gan, J. Y; Qin, S. J. Separation and aquatic toxicity of enantiomers of synthetic pyrethroid insecticides. Chirality 2005b, 17: S127-S133.
76. Loftsson, T.; Brewster, M. E. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization..J.Pharm. Sci. 1996, 85: 1017-1025.
77. Lotti, M., Becker, C. E.; Aminoff, M. Organophosphate polyneuropathy: pathogenesis and prevention. Neurology 1984, 34: 658.
78. Lotti, M. The pathogenesis of organophosphate polyneuropathy. Crit. Rev. Toxicol. 1992,27:465-487.
79. Lotti, M.; Moretto, A.; Capodicasa, E.; Bertolazzi, M.l Peraica, M. Scapellato, M. L. Interaction between neuropathy target esterase and its inhibitioes and the development of polyneuropathy. Toxicol. Appl. Pharmacol. 1993, 722: 165-171.
80. Loukas, Y. L.; Antoniadou-Vyza, E.; Papadaki-Valiraki, A.; Machera, K. G. γ-Cyclodextrin inclusion complex of a new organophosphorus insecticide. Determination of stability constant with HPLC. J. Agric. Food Chem. 1994, 42: 944-948.
81. Makhayeva, G. F.; Veselove, V. L; Mastryukova, T. A. Interaction of some phosphorodithioates and monothioates containing amino acids fragments with rat liver carboxylesterase. Bioorg. Khim. 1983, 9: 920-925.
82. Marrs, T. C. Organophosphate poisoning. Pharmacol. Ther. 1993, 58: 51-56.
83. Meisenheimer, J.; Lichtenstadt, L. Uber optisch-aktive Verbindungen des Phosphor. Chem. Ber., 1911, 44: 356-359.
84. Mifune, A.; Katsuda, Y.; Yoneda, T. Insecticidal and acaricidal composition and process for controlling pests. U.S. Patent 3846551, 1974.
85. Miles, J. W.; Mount, D. L.: Staiger, M. A.; Teeters, W. R. S-Methyl isomer content of stored malathion and fenitrothion water-dispersible powders and its relationship to toxicity. J Agric. Food Chem. 1979, 27: 421-425.
86. Mileson, B. E.; Chambers, J. E.; Chen, W. L.; Dettbarn, W.; Ehrich, M.; Eldefrawi, A. T.; Gaylor, D. W.; Hamernik, K.; Hodgson, E.; Karczmar, A. G; Padilla, S.; Pope, C. N.; Richardson, R. J.; Saunders, D. R.; Sheets, L. P.; Sultatos, L. G.; Wallace, K. B. Common mechanism of toxicity: A case study of organophosphorus pesticides. Toxicol. Sci. 1998, 41: 8-20.
87. Miyazaki, A.; Kawaradani, M.; Marumo, S.; Tomizawa, C. Enantiotopic demethylation of fenitrothion into partially racemised (R)p-(+)-desmethylfenitrothion by mouse liver homogenate and mice. J.Pestic. Sci. 1983,5: 115-120.
88. Miyazaki, A.; T., N.; Kawaradani, M.; Marumo, S. Resolution and biological activity of both enantiomers of methamidophos and acephate. J. Agric. Food Chem. 1988, 36: 835-837.
89. Miyazaki, A., Kawaradani, M., and Marumo, S. Analysis of an enantiomeric composition of desmethylfenitrothion, a major metabolite of achiral fenitrothion by chiral HPLC. J. Pestic. Sci. 1993, 75: 131-133.
90. Moser, H.; Ryhs, G; Sauter, H. Der Einfluss von Atropisomerie und chiralem Zentrum auf die biologische Aktivit(?)t des Metolachlor. Z. Naturforsch. 1982, 37b: 451-462.
91. Nomeir, A. A.; Dauterman, W. C. Studies on the optical isomers of EPN and EPNO. Pestic. Biochem. Physiol. 1979,10: 121-127.
92. Ohkawa, H.; Mikami, N.; Miyamoto, J. Photodecomposition of Sumithion [O,O-dimethyl 0-(3-methyl-4-nitrophenyI) phosphorothioate]. Agric. Biol. Chem. 1975,39:2265-2271.
93. Ohkawa, H.; Mikami, N.; Kasamatsu, K. Stereoselectivity in toxicity and acetylcholinesterase inhibition by the optical isomers of papthion and papoxon. Agric. Biol Chem. 1976a, 40: 1857-1862.
94. Ohkawa, H.; Mikami, N.; Miyamoto, J. Stereospecific metabolism O ethyl O 2 nitro 5 methylphenyl N isopropyl phosphoramidothioate liver microsomal mixed oxidase. J. Agric. Biol. Chem. 1976b, 40: 2125-2134.
95. Ohkawa, H.; Mikami, N.; Okuno, Y.; Miyamoto, J. Stereospecificity in toxicity of the optical isomers of EPN. Bull. Environ. Contam. Toxicol. 1977a, 75:534-540.
96. Ohkawa, H.; Mikami, N.; Miyamoto, J. Stereoselectivity in metabolism of the optical isomers of cyanofenphos (O-p-cyanophenyl O-ethyl phenylphosphonothioate) in rats and liver microsomes. J. Agric. Biol. Chem. 1977b, 41: 369-37r4.
97. Ohkawa, H. Insecticide Mode of Action. Academic Press: New York, 1982, 163-185.
98. Ooms, A. J.; Boter, H. L. Stereospecificity of hydrolytic enzymes in their reaction with optically active organophosphorus compounds. Biochem. Pharmacol. 1965, 14: 1839-1845.
99. Orgovanyi, J. H.; Otta, K.; Poppl, L.; Fenyvesi, E.; Zaray, G. Spectrophotometric and thermoanalytical study of cypermethrin/cyclodextrin complexes. Microchem.J. 2005, 79: 77-82.
100. Parker, P. E.; Brown, F. W. Organophosphate intoxication: hidden hazards. South Med.J. 1989,52: 1408-1410.
101. Perkow, W. Umsterzunge mit Alkylphosphiten. 1. Mitteil: Umlagerungen bei der Reaktion mit Chloral und Bromal. Chem, Ber. 1954, 87: 755-758.
102. Schmitt, P.; Garrison, A. W.; Freitag, D.; Kettrup, A. Application of cyclodextrin modified micellar electrokinetic chromatography to the separations of selected neutral pesticides and their enantiomers. J. Chromatogr. 1997, 792: 419-429.
103. Seiber, J. N.; Tolkmith, H.; Britton, E. C. Resolution of asymmetric organophosphoramides and their stereospecific transformations. Tetrahedron letters 1967, 34: 3333-3336.
104. Senanayake, N.; Jeyaratnam, J. Toxic polyneuropathy due to gingili oil contaminated with tricresyl phosphate affecting adolescent girl in Sri Lanka. Lancet 1981, 7:88-89.
105. Senanayake, N.; Johnson, M. K. Acute polyneuropathy after poisoning by a new organophosphate insecticide: A preliminary report. N. Engl. J. Med. 1982, 306, 155-157.
106. Senanayake, N.; Karalliedde, L. Neurotoxic effects of organophosphorus insecticides. An intermediate syndrome. N. Engl. J. Med. 1987, 316: 761-763.
107. Szejtli, J. Cyclodextrins and their inclusion complexes. Akademiai Kiad(?): Budapest, 1982, 236-255.
108. Szejtli, J. Cyclodextrins in pesticides. Slarch-Stdrke 1985, 37: 382-386.
109. Szejtli J. Cyclodextrins Technology. Kluweeer Academic Publishers: Dordrecht,1988, 86-90.
110. Szejtli, J. Introduction and general overview of cyclodextrin chemistry. Chem.Rev. 1998,98: 1743-1753.
111. Szente, L. Stable, controlled-release organophosphorous pesticides entrapped in beta-cyclodextrin I. Solid state characteristics. J. Therm. Anal. Calorim. 1998, 57:957-963.
112. Tang, S. L. Y.; Smith, R. L.; Poliakoff, M. Principles of green chemistry: Productivety. Green Chem. 2005, 7: 761-762.
113. Tolkmith, H.; Seiber, J. N.; Budde, P. B.; Mussell, D. R. Imidazole: Fungitoxic derivatives. Science 1967,158: 1462-1463.
114. Tombo, G. M. R.; Bellus, D., Chirality and Crop Protection. Angew. Chem. Int. Edit. 1991,30: 1193-1215.
115. Tsurubuchi, Y.; Kagaya, Y; Kono, Y. Suppression of tetrodotoxin-resistant voltage-gated sodium channels by enantiomers of the oxadiazine insecticide indoxacarb in rat dorsal root ganglion neurons. J. Pest. Sci. 2003, 28: 315-317.
116. Ueji, M.; Tomizawa, C. Insect toxicity and anti-acetylcholinesterase activity of chiral isomers of isofenphos and its oxon.J. Pestic. Sci. 1986,11: 447-453.
117. Ueji, M.; Tomizawa, C. Metabolism of the insecticide isofenphos in rats. J. Pestic. Sci. 1987,12: 269-275.
118. Ueji, M. Biological activity and metabolism of phosphoramidate insecticides. J.Pestic. Sci. 1988,13: 325-336.
119. Verschoyle, R. D.; Reiner, E.; Bailey, E.; Aldridge, W. N.Dimethylphosphorothioates. Reaction with malathion and effect on malathion toxicity. Arch Toxicol. 1982, 49: 293-301.
120. Wakabayashi, K.; Hizue, M.; Nozaki, H.; Nakayama, M; Kurihara, N.Enantiotopic selectivity in monodemethylation of fenitrothion by rat liver glutathione S-transferase isoenzymes and mouse liver cytosol. J. Pestic. Sci.1994, 19: 277-284.
121. Walker, B. Jr; Nidiry, J. Current concepts: organophosphate toxicity. Inhal.Toxicol. 2002, 14: 975-990.
122. Wang, Y. S.; Tal, K. T; Yen, J. H. Separation, bioactivity, and dissipation of enantiomers of the organophosphorus insecticide fenamiphos. Ecotox. Environ.Safety 2004, 57:346-353.
123. Wang, L. M.; Liu, W.; Yang, C. X.; Pan, Z. Y; Gan, J. Y; Xu, C; Zhao, M. R.;Schlenk, D. Enantioselectivity in estrogenic potential and uptake of bifenthrin. Environ. Sci. Technol. 2007, 41: 6124-6128.
124. Wang, P.; Jiang, S. R.; Liu, D. H.; Jia, G. F.; Wang, Q. X.; Wang, P.; Zhou, Z. Q. Effect of alcohols and temperature on the direct chiral resolutions of fipronil, isocarbophos and carfentrazone-ethyl. Biomed. Chromatogr. 2005, 19: 454-458.
125. Wang, P.; Jiang, S. R.; Liu, D. H.; Zhang, H. J.; Zhou, Z. Q. Enantiomeric resolution of chiral pesticides by high-performance liquid chromatography. J. Agric. Food Chem. 2006, 54:1577-1583.
126. Williams, A., Opportunities for chiral agrochemicals. Pest. Sci. 1996, 46: 3-9.
127. Wu, S. Y.; Hirashima, A.; Kuwano, E.; Eto, M. Synthesis of optically active 1,3,2-oxazaphopholidine 2-sulfides and 1,3,2-Benzodioxazaphophorin 2-sulfides. Agrie. Biol. Chem. 1987, 51: 537-547.
128. Wu, S. Y.; Hirashima, A. Synthesis and insecticidal activity of oxazaphospholidines, oxathiaphospholanes and thiazaphospholidines. J. Pestic. Sci. 1988, 13: 527-538.
129. Wu, S. Y.; Hirashima, A.; Eto, M.; Yanagi, K.; Nishioka, E.; Moriguchi, K., Synthesis of highly pure enantiomers of insecticide salithion. Agric Biol Chem 1989, 53: 157-163.
130. Wustner, D. A.; Fukuto, T. R. Stereoselectivity in cholinesterase inhibition, toxicity, and plant systemic activity by the optical isomers of O-2-butyl S-2-(ethylthio) ethyl ethylphosphonothioate. J. Agric. Food Chem. 1973, 21: 756-766.
131. Wustner D A, Fukuto T R. Affinity and phosphorylation constants for the inhibition of cholinesterases by the optical isomers of O-2-butyl S-2-(dimethylammonium)ethyl ethylphosphonothioate hydrogen oxalate. Pestic. Biochem. Physiol. 1974. 4: 365-369.
132. Xu, C.; Zhao, M. R.; Liu, W. P.; Chen, S. W.; Gan, J. Y. Enantioselectivity in zebrafish embryo toxicity of the insecticide acetofenate. Chem. Res. Toxicol. 2008, 21: 1050-1055.
133. Yamamoto, I.; Unai, T.; Suzuki, Y.; Katsuda, Y. Preparation, stabilization, and insecticidal activity of cyclodextrin-inclusion compounds of pyrethroids. Nippon Noyaku Gakkaishi 1976, 1: 41-48. (CAN 85:172714)
134. Yamamoto, I.; Katsuda, Y. β-cyclodextrin inclusion complexes of pyrethroids. Pestic. Sci. 2006, 11: 134-140.
135. Yang, Y. Pesticides and environmental health trends in China; 2007. http://www.wilsoncenter.org/topics/docs/pesticides_feb28.pdf.
136. Yen, J. H.; Tsai, C. C.; Wang, Y. S. Separation and toxicity of enantiomers of organophosphorus insecticide leptophos. Ecotox. Environ. Safety 2003, 55: 236-242.
137. Zhou, S. S.; Lin, K. D.; Yang, H. Y.; Li, L.; Liu, W. P.; Li, J. Stereoisomeric separation and toxicity of a new organophosphorus insecticide chloramidophos. Chem. Res. Toxicol. 2007, 20: 400-405.
138．毕富春，王文丽．蔬果磷稳定性研究．化学工业与工程 1996，13(3)：44-50．
139．陈万义，薛振祥，王能武．新农药研究与开发．北京：化学工业出版社，2003，1．
140．程正魁．杀螟松、乐果及水杨硫磷的热分解及其稳定化方法．精细化工中间体，1985，(1)：52-56．
141．方克美．有机磷农药中毒急救治疗进展．急症医学，2000，9(4)：283-285．
142．关里，王汉斌，赵德禄．肟类复能剂治疗急性有机磷农药中毒的研究现状．中华内科杂志，2004，43(2)：157-158．
143．郝国．磷酸三邻甲苯酯中毒迟发性神经病．第二届神经肌病学术研讨会论文汇编，1991，87．
144．华小梅，江席流．我国农药生产及对环境影响．精细与专用化学品，2000，12(2)：10-12．
145．胡林．鱼藤酮的稳定性研究及致细胞凋亡作用[博士学位论文]．广州：华南农业大学，2003．
146．蒋木庚，杨春龙，王鸣华，杨红，钱康南，刘益平，钱卫文，蒋丰．手性有机磷农药的研究与展望．世界农药2000，22(2)：16-21．
147．江藤永松．有机磷农药的有机化学与生物化学．北京：化学工业出版社，1981，185-195．
148．雷玲．鱼藤酮和Bt的光稳定性研究[硕士学位论文]．广州：华南农业大学，2004．
149．刘惠君．酰胺类除草剂的生物化学行为以及手性选择性行为研究[博士学位论文]．杭州：浙江大学，2005．
150．刘维屏．农药环境化学．北京：化工工业出版社，2006，5．
151．梁友信．劳动卫生与职业病学(第四版)．北京：人民卫生出版社，2000， 122-126．
152．马兴元，谭建华，朱平．有机磷类神经毒剂及其抗毒剂研究进展．动物医学进展2003，24(1)：37-40．
153．孟春和．有机磷农药固体剂型的稳定性．山西化工1981，(1)：47-49．
154．缪建强．中国高毒有机磷的使用和替代状况浅析．农药市场信息，2006，21(8)：18-19．
155．宁国英．急性重度有机磷农药中毒治疗方法研究[硕士学位论文]．济南：山东省医学科学院，2007．
156．童林荟．环糊精化学--基础与应用．北京：科学出版社，2001a，1．
157．童林荟．环糊精化学--基础与应用．北京：科学出版社，2001b，356-359．
158．王振君．农药缓释剂的进展．农药，1985，(3)：3-5．
159．魏方林，朱国念，程敬丽，桂文君．15％三唑磷微乳剂配方研制及其田间药效．现代农药．2004，3(4)：25-28．
160．吴霖，俞英．环糊精超分子包结物的制备与应用前景．江苏化工，2003，31(2)：32-35．
161．吴强．有机磷化合物中毒M受体及其信号传导研究．国外医学卫生学分册，2000，27(5)：472-476．
162．吴婉娥，朱绪恩，苏力宏，陈开勋，胡芝生．有机磷农药稳定剂进展．陕西化工，1997，(4)：31-34．
163．伍一军，杨琳，李薇．有机磷农药的多毒性作用．环境与职业医学，2005，22(4)：367-370．
164．小池好智，金子胜．稳定化的农药制剂．农药译丛，1984，6(2)：53-57．
165．肖和平．对提高敌敌畏稳定性途径的探讨．湖南化工，1998，28(1)：8-10．
166．徐光翠，鄢珣，张波．有机磷农药对雄性系统的损伤作用．甘肃农业大学学报，2005，40(6)：822-826．
167．续浩，陈亮．环糊精包结物的制备和研究方法．分析测试技术与仪器，2001，7(3)：143-151．
168．杨春河．新药创制、环境保护与结构调整--对我国农药工业发展的一点思考．农药，2000，39(1)：1-6．
169．叶秀林．立体化学．北京：北京大学出版社，1999，9-39．
170．张慧容，彭浩，贺红武．环糊精在农药中的研究及其应用．农药，2008，47(6)：406-411．
171．张培荣．农药储存中的稳定性分类．农资科技，1995，(5)：28-32．
172．张一宾，孙晶．国内外有机磷农药的概况及对我国有机磷农药发展的看法．农药，1999，38(7)：1-3．
173．郑荣远．有机磷持发多发性神经病的临床研究．温州医学院学报，1992，(3)：181-184．
174．周炯林．有机磷农药遗传毒性研究进展．国外医学卫生学分册，2007，34(6)：339-344．
175．周淑芳．有机磷农药的雌性生殖毒性研究进展．国外医学卫生学分册，2008，35(1)：51-55．
176．朱明钦等．有机磷农药的神经毒性作用“中间综合症”两例报告．中国工业医学杂志，1991，4(3)：54．
1. Benschop, H. P.; Konings, C. A. G.; Van Genderen, J.; De Jong, L. P. A. Isolation, anticholinesterase properties, and acute toxicity in mice of the four stereoisomers of the nerve agent soman. Toxicol. App. Pharmacol. 1984, 72: 61-74.
2. Berkman, C. E.; Quinn, D. A.; Thompson, C. M. Interaction of acetylcholinesterase with the enantiomers of malaoxon and isomalathion. Chem. Res. Toxicol. 1993, 6: 724-730.
3. Bobbitt, D. R.; Linder, S. W. Recent advances in chiral detection for high performance liquid chromatography. TrAC-Trend Anal. Chem. 2001, 20: 111-123.
4. Casida, J. E.; Leader, H. Resolution and biological activity of the chiral isomers of O-(4-bromo- 2-chlorophenyl) O-ethyl S-propyl phosphorothioate (profenofos insecticide). J. Agric. Food. Chem. 1982, 30: 546-552.
5. Doorn, J. A.; Gage, D. A.; Schall, M.; Talley, T. T.; Thompson, C. M.; Richardson, R. J. Inhibition of acetylcholinesterase by (1S, 3S)-isomalathion proceeds with loss of thiomethyl: kinetic and mass spectral evidence for an unexpected primary leaving group. Chem. Res. Toxicol. 2000, 13:1313-1320.
6. Doorn, J. A.; Talley, T. T.; Thompson, C. M.; Richardson, R. J. Probing the active sites of butyrylcholinesterase and cholesterol esterase with isomalathion: conserved stereoselective inactivation of serine hydrolases structurally related to acetylcholinesterase. Chem. Res. Toxicol. 2001, 14: 807-813.
7. Doorn, J. A.; Thompson, C. M.; Christner, R. B.; Richardson, R. J. Stereoselective inactivation of Torpedo Californica acetylcholinesterase by isomalathion, inhibitory reactions with (1R)- and (1S)-isomers proceed by different mechanisms. Chem. Res. Toxicol. 2003, 16: 958-965.
8. Ellman, G. L.; Courtney, K. D.; Andres, V.; Featherstone, R. M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961, 7: 88-95.
9. Filho, M. V. S.; Oliveira, M. M.; Salles, J. B.; Bastos, V. L. F. C.; Cassano, V. P. F.; Bastos, J. C. Methyl-paraoxon comparative inhibition kinetics for acetylcholinesterases from brain of neotropical fishes. Toxicol. Lett. 2004, 153: 247-254.
10. Gorder, G. W.; Kirino, O.; Hirashima, A.; Casida, J. E. Bioactivation of isofenphos and analogues by oxidative N-dealkylation and desulfuration. J. Agric. Food Chem. 1986, 34: 941.
11. ISO 6341. Water qualitysdetermination of the inhibition of the mobility of Daphnia magna Straus (Cladocera, Crustacca) sacute toxicity test, 1996.
12. Johnson, J. A.; Wallace, K. B. Species-related differences in the inhibition of brain acetylcholinesterase by paraoxon and malaoxon. Toxicol. Appl. Pharmacol. 1987, 88: 234-241.
13. Jianmongkol, S.; Berkman, C. E.; Thompsom, H. M.; Richardson, R. J. Relative potencies of the four stereoisomers of isomalathion for inhibition of hen brain acetylcholinesterase and neurotoxic esterase in vitro. Toxicol. Appl. Pharmacol. 1996, 139: 342-348.
14. Kitz, R.; Wilson, I. Ester of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase. J. Biol. Chem. 1962, 237: 3245-3249.
15. Konwick, B. J.; Garrison, A. W.; Avants, J. K., Fisk, A. T. Bioaccumulation, biotransformation, and metabolite formation of fipronil and chiral legacy pesticides in rainbow trout. Environ. Sci. Technol. 2006, 40: 2930-2396.
16. Lin, K. D.; Zhou, S. S.; Xu, C.; Liu, W. P. Enantiomeric resolution and biotoxicity of methamidophos. J. Agric. Food Chem. 2006, 54:8134-8138.
17. Liu, W. P.; Gan, J. Y.; Schlenk, D.; Jury, W. A. Enantioselectivity in environmental safety of current chiral insecticides. Proc. Natl. Acad. Sci. U. S. A. 2005, 102: 701-706.
18. Main, A. Affinity and phosphorylation constant for the inhibition of esterases by organophosphates. Science 1964, 144: 992-993.
19. Miyamoto, T., Kasagami, T., Asai, M., Yamamoto, I. A novel bioactivation mechanism of phosphoramidate insecticides. Pestic. Biochem. Phys. 1999, 63: 151-162.
20. Ohkawa, H.; Mikami, N.; Kasamatsu, K. Stereoselectivity in toxicity and acetylcholinesterase inhibition by the optical isomers of papthion and papoxon. Agric, Biol. Chem. 1976, 40:1857-1862.
21. Okamoto, Y., Kaida, Y. Resolution by high-performance liquid chromatography using polysaccharide carbamates and benzoates as chiral stationary phases. J. Chromatogr. A. 1994, 666:403-419.
22. Okamoto, Y.: Yashima, E. Polysaccharide derivatives for chromatographic separation of enantiomers. Angew. Chem. Int. Ed. 1998, 3 7:1020-1043.
23. Ordentlich, A.; Barak, D.; Kronman, C.; Benschop, H. P.; De Jong, L. P. A.; Ariel, N.; Barak, R..; Segall, Y.; Velan, B.; Shafferman, A. Exploring the active center of human acetylcholinesterase with stereoisomers of an organophosphorus inhibitor with two chiral centers. Biochemistry 1999, 38: 3055-3066.
24. Rodriguez, O. P.; Muth, G. W.; Berkman, C. E.; Kim, K.;Thompson, C. M. Inhibition of various cholinesterases with the enantiomers of malaoxon. Bull. Environ. Contam. Toxicol. 1997, 58: 171-176.
25. Seungmin, R.; Jing, L.; Thompson, C. M. Comparative anticholinesterase potency of chiral isoparathion methyl. Chem. Res. Toxicol. 1991, 4: 517-520.
26. Wustner, D. A.; Fukuto, T. R. Stereoselectivity in cholinesterase inhibition, toxicity, and plant systemic activity by the optical isomers of O-2-butyl S-2-(ethylthio) ethyl ethylphosphonothioate. J. Agric. Food Chem. 1973, 21: 756-761.
27. Wustner, D. A.; Fukoto, T. R. Affinity and phosphonylation constants for the inhibition of cholinesterases by the optical isomers of O-2-butyl S-2-(dimethylammonium) ethyl ethylphosphonothioate hydrogen oxalate. Pestic. Biochem. Physiol. 1974, 4: 365-376.
28. Yashima E, Okamoto Y. Chiral discrimination on polysaccharides derivatives. Bull. Chem. Soc. Jpn. 1995, 68: 3289-3307.
29. Yashima, E. Polysaccharide-based chiral stationary phases for high-performance liquid chromatographic enantioseparation. J. Chromatogr. A 2001, 906:105-125.
30．陈立仁．液相色谱手性分离．北京：科学出版社，2006，20．
31．李坚，巨修练，梁帝允，陈呈新，王一风．新杀虫剂氯胺磷．世界农药，2005，27(2)：44-46．
32．叶伟红．四种污染物质对大型蚤的毒性研究[硕士学位论文]．杭州：浙江大学，2004，20-22．
33．惠秀娟．环境毒理学．北京：化学工业出版社，2003，266-269．
1. Casida, J. E.; Sanderson, D. M. Toxic hazard from formulating the insecticide dimethoate in methyl "Cellosolve". Nature 1961, 189: 507-508.
2. Casida, J. E.; Sanderson, D. M. Solvent effects on toxicity, reaction of certain phosphorothionate insecticides with alcohols and potentiation by breakdown products. J. Agric. Food Chem. 1963, 11: 91-96.
3. Maxwell, D. M.; Brecht, K. M. Quantitative structure-activity analysis of acetylcholinesterase inhibition by oxono and thiono analogues of organophosphorus compounds. Chem. Res. Toxicol. 1992, 5: 66-71.
4. Rodbard, D.; Frazier, G. R. Statistical analysis of radioligand assay data. Methods Enzymol. 1975, 37: 3-22.
5. Tabashnik, B. E.; Cushing, N. L. Leaf residue vs. topical bioassays for assessing insecticide resistance in the diamondback moth (Plutella xylostella L.). FAO Plant Prot. Bull. 1987, 35:11-14.
6. Teichmann, H.; Schnell, M. Reaction of O, O-dimethyl phosphoramidothioate with chloral. J. Prakt. Chem. 1987, 329:871-876 (CAN 110:23978).
7．徐寿昌．有机化学．北京：高等教育出版社，1993，281-282．
1. Atwood, J. L.; Lehn, J. M. Cyclodextrins. Pergamon: Oxfors, 1996, 503-513.
2. Babcock, J. C.; Polansky, J. R.; Bowman, L. M.; Tsao, S. W.; Si, E. C. C.; Chandrasekaran, S. K. Stabilization of aminosteroids for topical ophthalmic and other applications. US 5538721, 1996.
3. Backensfeid, T.; Heil, W.; Lipp,R. Compositions of estrogen-cyclodextrin complexes. US 7163931, 2007.
4. Benesi, H. A.; Hildebrand, J. H. A spectrophotometric investigation of the interaction of iodine with aromatic hydrocarbons. J. Am.Chem. Soc. 1949, 71: 2703-2707.
5. Biocides & Pesticides Unit (BPU).Guidance on the storage stability data requirements for non-agricultural pesticide products. Pestic. News. 2004, 64: 1-15.
6. Collaborative International Pesticides Analytical Council Ltd. (CIPAC). MT46.3 Accelerated Storage Procedure. Dobrat, W.; Martin, A., Eds.; Black Bear Press Ltd.: Cambridge, 2000.
7. Connors, K. A. The stability of cyclodextrin complexes in solution. Chem. Rev. 1997, 97: 1325-1357.
8. Fava, S.; Gioia, D. D.; Marchetti, L.; Fenyvesi, E. Randomly methylated β-cyclodextrins (RAMEB) enhance the aerobic biodegradation of polychlorinated biphenyl in aged-contaminated soils. J. Inclusion Phenom. Macrocyclic Chem. 2002, 44:417-421.
9. Indirapriyadharshini. V. K.; Karunanithi, P.; Ramamurthy, P. Inclusion of resorcinol-based acridinedione dyes in cyclodextrins: fluorescence enhancement. Langmuir 2001, 17: 4056-4060.
10 Giordano, F.; Novak, C.; Moyano, J. R. Thermal analysis of cyclodextrins and their inclusion compounds. Thermochim. Acta 2001, 380:123-151.
11. Hamai, S.; Sakurai, H. 2H2O effects on the inclusional complexation of β-cyclodextrin with sodium 2-naphthalenesulfonate in capillary electrophoresis and UV spectrophotometry. J. Chromatogr. A 1998, 800: 327-332.
12. Kamiya, M.; Nakamura, K.; Sasaki, C. Inclusion effects of cyclodextrins on photodegradation rates of parathion and paraoxon in aquatic medium. Chemosphere 1994, 28:1961-1966.
13. Kamiya, M.; Nakamura, K. Cyclodextrin inclusion effects on photodegradation rates of organophosphorus pesticides. Environ. Int. 1995a, 21: 299-304.
14. Kamiya, M.; Nakamura, K.; Sasaki, C. Inclusion effects of β-cyclodextrins on the hydrolysis of organophosphorus pesticides. Chemosphere 1995b, 30: 653-660.
15. Kita, K.; Nihorbashi, H. DDVP-Cyclodextrin Complexes. GB 1453801, 1976.
16. Loftsson, T.; Brewster, M. E. Pharmaceutical applications of cyclodextrins. l. Drug solubilization and stabilization. J. Pharm. Sci-US. 1996, 85:1017-1025.
17. Loukas, Y. L.; Antoniadou-Vyza, E.; Papadaki-Valiraki, A.; Machera, K. G. γ-Cyclodextrin inclusion complex of a new organophosphorus insecticide. Determination of stability constant with HPLC. J. Agric. Food Chem. 1994, 42: 944-948.
18. Reid, B. J.; Stokes, J. D.; Jones, K. C.; Semple, K. T. Influence of hydroxypropyl-β-cyclodextrin on the extraction and biodegradation of phenanthrene in soil. Environ. Toxicol. Chem. 2004, 23: 550-556.
19. Szejtli, J. Cyclodextrins and their inclusion complexes. Akad(?)miai Kiad(?): Budapest, 1982, 236-255.
20. Szente, L. Stable, controlled-release organophosphorous pesticides entrapped in beta-cyclodextrin Ⅰ. Solid state characteristics. J. Therm. Anal. Calorim. 1998, 51: 957-963.
21. Uekama, K.; Hirayama, F.; lrie, T. Cyclodextrin drug carrier systems. Chem. Rev. 1998, 98: 2045-2076.
22. Villaverde, J.; Morillo, E.; P(?)rez-Mart(?)nez, J. I.; Gin(?)s, J. M.; Maqueda, C. Preparation and characterization of inclusion complex of norflurazon and β-cyclodextrin to improve herbicide formulations. J. Agric. Food Chem. 2004, 52: 864-869.
23. Yang, G. F.; Wang, H. B.; Yang, W. C.; Gao, D. Q.; Zhan, C. G.Bioactive permethrin/β-cyclodextrin inclusion complex. J. Phys.Chem. B 2006, 110: 7044-7048.
24. Yilmaz, V. T.; Yilmaz, V. T.; Karada(?), A.; (?)cbudak, H. Thermal decomposition of β-cyclodextrin inclusion complexes of ferrocene and their derivatives. Thermochim. Acta 1995, 261: 107-118.
25. Zhu, X. L.; Wang, H. B.; Chen, Q.; Yang, W. C.; Yang, G. F.Preparation and characterization of inclusion complex of iprodione and β-cyclodextrin to improve fungicidal activity. J. Agric. Food Chem. 2007, 55: 3535-3539.
26．童林荟．环糊精化学--基础与应用．北京：科学出版社，2001，135．
1. Abou-Donia, M. B. Organophosphorus ester-induced delayed neurotoxicity. Annu. Rev. Pharmacol. Toxicol. 1981, 21:511-548.
2. Atterwill, C. K.; Bruinink, A.; Drejer, J.; Duarte, E.; Abdulla, E. M.; Meredith, C.; Nicotera, P.; Regan, C.; Rodriguezfarre, E.; Simpson, M. G.; Smith, R.; Veronesi, B.; Vijverberg, H.; Walum, E.; Williams, D. C. In vitro neurotoxicity testing. The report and recommendations of ECVAM workshop-3. Atla-Altern. Lab. Anim. 1994, 22: 350-362.
3. Barata, C.; Baird, D. J.; Amat, F.; Soares, A. M. V. M. Comparing population responses to contaminants between laboratory and field: an approach using Daphnia magna ephippial egg banks. Funct. Ecol. 2000, 14:513-523.
4. Barata, C.; Solayan, A.; Porte, C., Role of B-esterases in assessing toxicity of organophosphorus (chlorpyrifos, malathion) and carbamate (carbofuran) pesticides to Daphnia magna. Aquat. Toxicol. 2004, 66: 125-139.
5. Berkman, C. E.; Thompson, C. M.; Perrin, S. R. Synthesis, absolute-configuration, and analysis of malathion, malaoxon, and isomalathion enantiomers. Chem. Res. Toxicol. 1993, 6:718-723.
6. Bhuyan, B. K.; Loughman, B. E.; Fraser, T. J.; Day, K. J. Comparison of different methods of determining cell viability after exposure to cytotoxic compounds. Exp. Cell Res. 1976, 97: 275-280.
7. Costa, L. G., Current issues in organophosphate toxicology. Clin. Chim. Acta 2006, 366: 1-13.
8. Ehrich, M.; Correll, L.; Veronesi, B. Acetylcholinesterase and neuropathy target esterase inhibitions in neuroblastoma cells to distinguish organophosphorus compounds causing acute and delayed neurotoxicity. Fund Appl. Toxicol. 1997, 38: 55-63.
9. EPA. Pesticide Assessment Guidelines, Subdivision F. Hazard Evaluation: Human and Domestic Animals. Addendum 10: Neurotoxicity, Series 81, 82, and 83. U.S. Environmental Protection Agency: Washington, DC, 1991.
10. Flaskos, J.; McLean, W. G.; Fowler, M. J.; Hargreaves, A. J. Tricresyl phosphate inhibits the formation of axon-like processes and disrupts neurofilaments in cultured mouse N2a and PC12 cells. Neurosci. Lett. 1998, 242: 101-104.
11. Flaskos, J.; Fowler, M. J.; Teurtrie, C.; Hargreaves, A. J. The effects of carbaryl and trichlorphon on differentiating mouse N2a neuroblastoma cells. Toxicol. Lett. 1999, 110: 79-84.
12. Guilhermino, L.; Lopes, M. C.; Carvalho, A. P.; Soares, A. M. V. M. Inhibition of acetyicholinesterase activity as effect criterion in acute tests with juvenile Daphnia Magna. Chemosphere 1996, 32: 727-738.
13. Henschler, D.; Schmuck, G.; Vanaerssen, M.; Schiffmann, D., The inhibitory effect of neuropathic organophosphate esters on neurite outgrowth in cell-cultures-a basis for screening for delayed neurotoxicity. Toxicol. in Vitro 1992, 6: 327-335.
14. Hong, M. S.; Hong, S. J.; Barhoumi, R.; Burghardt, R. C.; Donnelly, K. C.; Wild, J. R.; Venkatraj, V.; Tiffany-Castiglioni, E. Neurotoxicity induced in differentiated SK-N-SH-SY5Y human neuroblastoma cells by organophosphorus compounds. Toxicol. Appl. Pharm. 2003, 186:110-118.
15. Jianmongkol, S.; Berkman, C. E.; Thompson, C. M.; Richardson, R. J. Relative potencies of the four stereoisomers of isomalathion for inhibition of hen brain acetylcholinesterase and neurotoxic esterase in vitro. Toxicol. Appl. Pharmacol. 1996, 139: 342-348.
16. Johnson, M. K.; Read, D. J.; Benschop, H. P. Interaction of the four stereoisomers of soman (pinacolyl methylphosphonofluoridate)with acetylcholinesterase and neuropathy target esterase of hen brain. Biochem. Pharmacol. 1985, 34: 1945-1951.
17. Johnson, M. K.; Read, D. J. The influence of chirality on the delayed neuropathic potential of some organophosphorus esters: Neuropathic and prophylactic effects of some stereoisomeric esters of ethylphosphonic acid (EPN oxon and EPN) correlate with quantities of aged and unaged neuropathy target esterase in vivo. Toxicol. Appl. Pharma. 1987, 90: 103-115.
18. Johnson, M. K.; Vilanova, E.; Read, D. J. Anomalous biochemical responses in tests of the delayed neuropathic potential of methamidophos (O,S-dimethyl phosphorothioamidate), its resolved isomers and of some higher O-alkyl homologs. Arch. Toxicol. 1991, 65:618-624.
19. Li, W.; Casida, J. E., Actions of two highly potent organophosphorus neuropathy target esterase inhibitors in mammalian cell lines. Toxicol. Lett. 1997, 92: 123-130.
20. Lin, K. D.; Zhang, F.; Zhou, S. S.; Liu, W. P.; Gan, J. Y.; Pan, Z. Y. Stereoisomeric separation and toxicity of the nematicide fosthiazate. Environ. Toxicol. Chem. 2007, 26: 2399-2344.
21. Lin, K. D.; Liu, W. P.; Li, L.; Gan, J., Single and joint acute toxicity of isocarbophos, enantiomers to Daphnia magna. J. Agric. Food Chem. 2008, 56: 4273-4277.
22. Liu, W. P.; Gan, J. Y.; Schlenk, D.; Jury, W. A. Enantioselectivity in environmental safety of current chiral insecticides. Proc. Natl. Acad. Sci. U.S.A. 2005, 102: 701-706.
23. Liu W. P.; Lin, K. D.; Gan, J. Y. Separation and aquatic toxicity of enantiomers of the organophosphorus insecticide trichloronate. Chirality 2006, 18:713-716.
24. Mileson, B. E.; Chambers, J. E.; Chen, W. L.; Dettbarn, W.; Ehrich, M.; Eldefrawi, A. T.; Gaylor, D. W.; Hamernik, K.; Hodgson, E.; Karczmar, A. G.; Padilla, S.; Pope, C. N.; Richardson, R. J.; Saunders, D. R.; Sheets, L. P.; Sultatos, L. G.; Wallace, K. B. Common mechanism of toxicity: A case study of organophosphorus pesticides. Toxicol. Sci. 1998, 41: 8-20.
22. Nostrandt, A. C.; Ehrich, M. Development of a model cell-culture system in which to study early effects of neuropathy-inducing organophosphorus esters. Toxicol. Lett. 1992, 60:107-114.
23. Qian, Y.; Venkatraj, J.; Barhoumi, R.; Pal, R.; Datta, A.; Wild, J. R.; Tiffany-Castiglioni, E. Comparative non-cholinergic neurotoxic effects of paraoxon and diisopropyl fluorophosphate (DFP) on human neuroblastoma and astrocytoma cell fines. Toxicol. Appl. Pharmacol. 2007, 219:162-171.
24. Sanborn, J. R.; Fukuto, T. R.; Metcalf, R. L. Insecticidal, anticholinesterase, and hydrolytic properties of phosphoramidothioates. J. Agric. Food Chem. 1970, 18: 189-194.
25. Senanayake, N.; Johnson, M. K. Acute polyneuropathy after poisoning by a new organophosphate insecticide: A preliminary report. N. Engl. J. Med. 1982, 306: 155-157.
26. Veronesi, B., In vitro screening batteries for neurotoxicants. Neurotoxicology 1992, 13: 185-195.
27. Wang, Y. S.; Tai, K. T.; Yen, J. H. Separation, bioactivity, and dissipation of enantiomers of the organophosphorus insecticide fenamiphos. Ecotoxicol. Environ. Saf. 2004, 57: 346-353.
28. Williams, A. Opportunities for chiral agrochemicals. Pestic. Sci. 1996, 46: 3-9.
29. Yen, J. H.; Tsai, C. C.; Wang, Y. S. Separation and toxicity of enantiomers of organophosphorus insecticide leptophos. Ecotoxicol. Environ. Saf. 2003, 55: 236-242.
1. Allon, N.; Raveh, L.; Gilat, E.; Cohen, E.; Grunwald, J.; Ashani, Y. Prophylaxis against soman inhalation toxicity in guinea pigs by pretreatment alone with human serum butyrylcholinesterase. Toxicol. Sci. 1998, 43: 121-128.
2. Eto, M.; Kinoshita, Y.; Kato, T.; Oshima, Y. Saligenin Cyclic methyl phosphate and its thiono analogue: new insecticides related to the active metabolite of Tri-o-cresyl Phosphate. Nature 1963a, 200:171 - 172.
3. Eto, M.; Kinoshita, Y.; Kato, T.; Oshima, Y. Saligenin cyclic alkyl phosphates and phosphorothionates with insecticidal activity. Agric. Biol. Chem. 1963b, 27: 789-794.
4. Eto, M. Chemistry and biochemistry of salithion and related compounds. Rev. Plant Prot. Res. 1976, 9: 1-20.
5. Fossi, M. C.; Leonzio, C. Non-destructive biomarkers in vertebrates. Boca Raton: Lewis Publishers, 1994, 37-62.
6. Hirashima, A.; lshaaya, I.; Ueno, R.; Ichiyama, Y.; Wu, S. Y.; Eto, M. Biological activity of optically active salithion and salioxon. Agric. Biol. Chem. 1989a, 53: 175-178.
7. Hirashima, A.; Ishaaya, I.; Ueno, R.: Oyama, K.; Eto, M. Effect of salithion enantiomers on the trehalase system and on the digestive protease, amylase, and invertase of Tribolium castaneum. Pestic. Biochem. Physiol. 1989b, 34:205-210.
8. Hirashima, A.: Ueno, R.; Oyama, K.; Koga, H.; Eto, M. Effect of salithion enantiomers on larval growth, carbohydrases, acetylcholinesterase, adenylate cyclase activities and cyclic adenosine 3',5'-monophosphate level of Musca domestica and Tribolium castaneum. Agric. Biol. Chem. 1990, 54:1013-1022.
9. Itoh, K. Stereoselctive degradation of organophosphorus insecticide salithion in upland soils. J. Pestic. Sci. 1991a, 16: 35-40.
10. Itoh, K. Stereoselective metabolism of insecticide salithion by Agrobacterium sp. and Acinetobacter sp. isolated from soil. J. Pestic. Sci. 1991b, 16: 85-91.
11. Lin, K. D.: Zhang, F.; Zhou, S. S.; Liu, W. P.; Gan, J.: Pan, Z. Y. Stereoisomeric separation and toxicity of the nematicide fosthiazate. Environ. Toxicol. Chem. 2007, 26: 2339-2344.
12. Lin, K. D.; Liu, W. P.; Li, L.; Gan, J. Single and joint acute toxicity of isocarbophos enantiomers to Daphnia magna. J. Agric. Food Chem. 2008, 56: 4273-4277.
13. Liu, W, P.; Gan, J.; Schlenk, D,; Jury, W. A. Enantioselectivity in environmental safety of current chiral insecticides. Proc. Natl. Acad. Sci. USA 2005, 102: 701-706.
14. Liu, W. P.; Lin, K. D.; Gan, J. Separation and aquatic toxicity of enantiomers of the organophosphorus insecticide trichioronate. Chirality 2006, 18:713-716.
15. Raveh, L.; Grunwald, J.; Marcus, D.; Papier, Y.; Cohen, E.; Ashani,Y. Human butyrylcholinesterase as a general prophylactic antidote for nerve agent toxicity. In vitro and in vivo quantitative characterization. Biochem. Pharmacol. 1993, 45: 2465-2474.
16. Sternfeld, M.; Rachmilewitz, J.; Loewenstein-Lichtenstein, Y.; Andres, C.; Timberg, R.; Ben-Ar, S.; Glick, D.; Soreq, H.; Zakut, H. Normal and atypical butyrylcholinesterases in placental development, function, and malfunction. Cell Mol. Neurobiol. 1997, 17:315-332.
17. Wang, Y. S.; Tai, K. T.; Yen, J. H. Separation, bioactivity, and dissipation of enantiomers of the organophosphorus insecticide fenamiphos. Ecotox. Environ. Safe 2004, 57: 346-353.
18. Wu, S. Y.; Hirashima, A.; Kuwano, E.; Eto, M. Synthesis of optically active 1,3,2-oxazaphopholidine 2-sulfides and 1,3,2-Benzodioxazaphophorin 2-sulfides. Agric. Biol. Chem. 1987, 51: 537-547.
19. Wu, S. Y.; Hirashima, A.; Eto, M.; Yanagi, K.; Nishioka, E.; Moriguchi, K. Synthesis of highly pure enantiomers of insecticide salithion. Agric. Biol. Chem. 1989, 53: 157-163.
20. Yashima E, Okamoto Y. Chiral discrimination on polysaccharides derivatives. Bull. Chem. Soc. Jpn. 1995, 68: 3289-3307.
21．毕富春，王文丽．蔬果磷稳定性研究．化学工业与工程，1996，13(3)：44-50．
22．毕富春，陈学仁，王文丽，朱兰惠，王勇，邵瑞链，成俊然．蔬果磷对4种昆虫的杀虫活性．化学工业与工程，1997，14(4)：38-41．
23．成俊然，邵瑞链，毕富春，马治华，黄润秋．用分子内环化反应合成蔬果磷的研究．农药，1998，37(10)：15-16．
24．化学工业部农药情报中心站．国外农药品种手册(三)．沈阳：化工部农药工业科技情报站，1981，176-178．
25．谭本祝，陶贤鉴，于正英，曹修祗．蔬果磷的合成与田间药效．农药，1998，37(9)：15-16．
2. Abou-Donia, M. B. Organophosphorus ester-induced delayed neurotoxicity. Ann. Rev. Pharmacol. Toxicol. 1981, 21:511-548.
3. Abou-Donia, M. B. The cytoskeleton as a target for organophosphorus ester-induced delayed neurotoxicity (OPIDN). Chem. Biol. Interact. 1993, 87: 383-393.
4. Abou-Donia, M. B. Involvement of cytoskeletal proteins in the mechanisms of organophosphorus ester-induced delayed neurotoxicity. Clin. Exp. Pharmacol. Physiol. 1995, 22: 358-359.
5. Ackermann, P.; Bourgeois, F.; Drabek, J. The optical isomers of α-cyano-3-phenoxy-benzyl-3-(1,2-dibromo-2,2-dichloroethyl)-2,2-dimethylcyclo-propanecarboxylate and their insecticidal activities. Pestic. Sci. 1980, 11: 169-179.
6. Aldridge, W. N. The nature of the reaction of organophosphorus compounds and carbamates with esterase. Bull. Wld. Hlth. Org. 1971, 44: 25-30.
7. Allahyari, R.; Hollingshaus, J. G.; Lapp, R. L.; Timm, E.; Jacobson, R. A.; Fukuto, T. R. Resolution, absolute configuration, and acute and delayed neurotoxicity of the chiral isomers of O-aryl phenylphonothioate analogues related to leptophos. J. Agric. Food Chem. 1980, 28: 594-598.
8. Anigbogu, V. C.; Woldeab, H.; Garrison, A. W.; Avants, J. K. Enantioseparation of malathion, cruformate, and fensulfothion organophosphorus pesticides by mixed-mode electrokinetic capillary chromatography. Int. J. Environ. An. Ch. 2003, 83: 89-100.
9. Armstrong, D. J.; Fukuto, T. R. Synthesis, resolution and toxicological properties of the chiral isomers of O, S-dimethyl and diethyl ethylphosphonothioate. J. Agric. Food. Chem. 1987, 35: 500-506.
10. Atwood, J. L.; Lehn, J. M. Cyclodextrins. Pergamon: Oxfors, 1996, 503-513.
11. Baker, E. L.; Zack, M.; Miles, J. W.; Alderman, L.; Warren, MEW.; Dobbin, R. D.; Miller, S.; Teeters, W. R. Epidemic malathion poisoning in pakistan malaria workers. Lancet 1978, 8405: 31-34.
12. Battershill, J. M.; Edwards, P. M.; Johnson, M. K. Toxicological assessment ofisomeric pesticides: a strategy for testing of chiral organophosphorus (OP) compounds for delayed polyneuropathy in a regulatory setting. Food Chem.Toxicol. 2004, 42: 1279-1285.
13. Benshop, H. P.; Konings, C. A. G.; Genderen, V. Isolation, anticholinesterase properties,and acute toxicity in mice of the four stereoisomers of the nerve agent soman. J. Toxicol. Appl. Pharmacol. 1984, 72: 61-74.
14. Berkman, C. E.; Thompson, C. M.; Perrin, S. R. Synthesis, absolute-configuration, aned analysis of malathion, malaxon, and isomalathion enantiomers. Chem Res. Toxicol. 1993a, 6: 718-723.
15. Berkman, C. E.; Quinn, D. A.; Thompson, C. M. Kinetics of post-inhibitory reactions of AChE poisoned by chiral isomalathion: a surprising non-reactivation induced by the RP stereoisomers. Chem. Res. Toxicol. 1993b, 6: 724-731.
16. Biebel, R.; Hengstberger, K.; Polheim, D.; Viernstein, H. Improvedlight-stability of pyrethrins by complexation with gamma-cyclodextrin. Proc. Int. Symp. Controlled Release Bioact. Mater. 2000, 27: 1358-1359.
17. Buser, H. R.; Muller, M. D.; Poiger, T.; Blamer, M. E. Environmental behavior of the chiral acetamide pesticide metalaxyl: enantioselective degradation and chiral stability in soil. Environ. Sci. Technol. 2002, 36: 221-226.
18. Casida, J. E.; Sanderson, D. M. Toxic hazard from formulatingthe insecticide dimethoate in methyl "Cellosolve". Nature 1961, 189: 507-508.
19. Casida, J. E.; Sanderson, D. M. Solvent effects on toxicity, reaction of certain phosphorothionate insecticides with alcohols and potentiation by breakdown products. JAgric. Food Chem. 1963, 11: 91-96.
20. Casida, J. E.; Leader, H. Resolution and biological activity of the chiral isomers of O-(4-bromo- 2-chlorophenyl) O-ethyl S-propyl phosphorothioate (profenofos insecticide). J. Agric. Food. Chem. 1982, 30: 546-552.
21. Chin, Y. C; Dauterman, W. C. The affinity and phosphorylation constants of the optical isomers of O,O-diethyl malaoxon and the geometric isomers of phosdrin with acetylcholinesterase. Biochem. Pharmacol. 1969, 18: 359-366.
22. Connors, K. A. The stability of cyclodextrin complexes in solution. Chem. Rev. 1997,97: 1325-1357.
23. Cranmer, J. M.; Hixson, E. J. Delayed Neurotoxicity. Intox Press: Little Rock, 1984, 7-22.
24. De Wilde, V.; Vogelaers, D.; Colardyn, F. Prompt recovery from severe cholinesterase-inhibitor poisoning-emarks on classification and therapy of organophosphate poisoning. J. Molecular Med. 1990, 68: 615-618.
25. de Jong, L. P. A.; Benshop, H. P. Stereoselectivity of Pesticides. Amsterdam: Elsevier Science Publishers, 1988, 109-149.
26. Eddleston, M.; Buckley, N. A.; Eyer, P.; Dawson, A. H. Management of acute organophosphorus pesticide poisoning. Lancet 2008, 371: 597-607.
27. Eldefrawi, M. E.; Eldefrawi, A. T. Neurotransmitter receptors as targets for pesticides. J. Environ. Sci. Health B. 1983, 18: 65-88.
28. Ellington, J. J.; Evans, J. J.; Prickett, K. B.; Champion, W. L. High-performance liquid chromatographic separation of the enantiomers of organophosphorus pesticides on polysaccharide chiral stationary phases. J. Chromatogr. A 2001, 928: 145-154.
29. Eya, B. K.; Fukuto, T. R. The effect of chiral debromoleptophos oxon isomers on acute and delayed neurotoxicity and their inhibitory activity against acetylcholinesterases and neurotoxic esterase. J. Agric. Food Chem. 1985, 33: 884-888.
30. Fidalgo-Used, N.; Montes-Bayon, M.; Bianco-Gonzalez, E.; Sanz-Medel, A., SPME-enantioselective gas chromatography with ECD and ICP-MS detection for the chiral speciation of the pesticide ruelene in environmental samples. J. Anal. Atom. Spectrom. 2006a, 21: 876-883.
31. Fidalgo-Used, N.: Blanco-Gonzalez, E.; Sanz-Medel, A., Evaluation of two commercial capillary columns for the enantioselective gas chromatographic separation of organophosphorus pesticides. Talanta2006b, 70: 1057-1063.
32. Fournier, J., Pesticides stereochemistry. Actual. Chimique 2007, Suppl. 304: 21-29.
33. Fukuto, T. R.; Metcalf, R. L. Alkylphosphonic acid esters as insecticides. J. Econ. Entomol. 1959, 52: 739-743.
34. Garay, A. S. Molecular chirality of life and intrinsic chirality of matter. Nature 1918,271: 186.
35. Garc(?)a-Ruiz, C; Alvarez-Llamas, G.; Puerta, A.; Blanco, E.; Sanz-Medel, A.; Marina, M. L., Enantiomeric separation of organophosphorus pesticides by capillary electrophoresis-Application to the determination of malathion in water samples after preconcentration by off-line solid-phase extraction. Anal. Chim. Acta 2005, 543: 77-83.
36. Garrison, W., On the issue of enantioselectivity of chiral pesticides: a green chemistry opportunity. Green Chem. 2004, 6: G77-G78.
37. Garrison, A.W. Probing the enantioselectivity of chiral pesticides. Environ. Sci. Technol. 2006, 40: 16-23.
38. Garrison, A. W.; Schmitt-Kopplin, P.; Avants, J. K. Analysis of the enantiomers of chiral pesticides and other pollutants in environmental samples by capillary electrophoresis. Methods Mol. Biol. 2008, 384: 157-70.
39. Green, M. M.; Selinger, J. V. Cosmic chirality. Science 1998, 282: 880-881.
40. Grothusen, J. R.; Brown, T. M. Stereoselectivity of acetylcholinesterase, arylester hydrolase, and Chymotrypsin toward 4-nitrophenyl) alkyl (phenyl) phosphinates. Pestic. Biochem. Physiol. 1986, 26:100-112.
41. Hall, C. R.; Inch, T; D.; Inns, R. H. Differences between some biological properties of enantiomers of alkyl S-alkyl methylphosphonothiolates. J. Pharm. Pharmacol 1917, 29: 574-579.
42. Hassan, A.; Dauterman, W. C. Studies on the optically active isomers of O, O-diethyl malathion and O, O-diethyl malaoxan. Biochem. Pharmacol. 1968, 17: 1431-1438.
43. Heath, D. F.; Vandekar, M. Some spontaneous reactions of O O-dimethyl S-ethylthioethyl phosphorothiolate and related compounds in water and on storage, and their effects on the toxicological properties of the compounds. Biochem. J. 1957, 67: 187-201.
44. Hedges, A. R. Industrial applications of cyclodextrins. Chem. Rev. 1998, 98: 2035-2044.
45. Hilgetag, S.; Lehman, G. Contributions for the chemistry of the thiophosphate. VII. Optically active thiophosphate. J. prakt. Chem. 1959, 8: 224-230.
46. Hirashima A, Ishaaya I, Ueno R. et al. Effect of salithion enantiomers on the trehalase system and on the digestive protease, amylase, and invertase of Tribolium castaneum. Pestic. Biochem. Physiol. 1989, 34: 205-210.
47. Hoekstra, P. F.; Burnison, B. K.; Neheli, T.; Muir, D. C. G. Enantiomer-specific activity of o,p'-DDT with the human estrogen receptor. Toxicol. Lett. 2001, 125: 75-81.
48. Hoekstra, P. F.; Burnison, B. K.; Garrison, A. W.; Neheli, T.; Muir, D. C. G. Estrogenic activity of dicofol with the human estrogen receptor: Isomer- and enantiomer-specific implications. Chemosphere 2006, 64: 174-177..
49. Huang, L.; Lin, J. M.; Xu, L. J.; Chen, G. N. Nonaqueous and aqueous-organic media for the enantiomeric separations of neutral organophosphorus pesticides by CE. Electrophoresis 2007, 28: 2758-2764.
50. Jarman, J. L.; Jones, W. J.; Howell, L. A.; Garrison, A. W., Application of capillary electrophoresis to study the enantioselective transformation of five chiral pesticides in aerobic soil slurries. J. Agric. Food Chem. 2005, 53: 6175-6182.
51. Johnson, M. K. Organophosphorus and other inhibitors of brain "neurotoxic esterase" and the development of delayed neurotoxicity in hens. Biochem. J. 1970,720:520-531.
52. Johnson, M. K. The target for initian of delayed neurotoxicity by organophosphorus easters: biochemical studies and toxicological applications. Rev. Biochem. Toxicol 1982, 4: 141.
53. Johnson, M. K.; Vilanova, E.; Read, D. J. Anomalous biochemical responses in tests of the delayed neuropathic potential of methamidophos (O,S-dimethyl phosphorothioamidate), its resolved isomers and of some higher O-alkyl homologues. Arch. Toxicol. 1991, 65: 618-624.
54. Johnson, M. K. Symposium introduction: retrospect and prospects for neuropathy target esterase (NTE) and the delayed polyneuropathy (OPIDP) induced by some organophosphorus esters. Chem Bio/ Interact. 1993, 87:339-346.
55. Kado, M.; Yoshinaga, E. Fungicidal action of organophosphorus compounds. Residue Rev. 1969,25: 133.
56. Kamiya, M.; Nakamura, K.; Sasaki, C. Inclusion effects of cyclodextrins on photodegradation rates of parathion and paraoxon in aquatic medium. Chemosphere 1994, 28: 1961-1966.
57. Kamiya, M.; Nakamura, K. Cyclodextrin inclusion effects on photodegradation rates of organophosphorus pesticides. Environ. Int. 1995a, 21: 299-304.
58. Kamiya, M.; Nakamura, K.; Sasaki, C. Inclusion effects of p-cyclodextrins on the hydrolysis of organophosphorus pesticides. Chemosphere 1995b, 30: 653-660.
59. Katsuda, Y.; Yamamoto, S. Stabilization of pyrethroids by p-cyclodextrin. JP 51081888,1976. (CAN 85:138639)
60. Kita, K.; Nihorbashi, H. DDVP-Cyclodextrin Complexes. GB 1453801, 1976.
61. Kishimoto, D.; Oku, A.; Kurihara, N. Enantiotopic selectivity of cytochrome P_450-catalyzed oxidative demethylation of methoxychlor: Alteration of selectivity depending on isozymes and substrate concentrations. Pest. Biochem. Physiol. 1995,57:12-19.
62. Kohler, H. P. E.; Angst, W.; Giger, W.; Kanz, C; Muller, S.; Suter, M. J. F. Environmental fate of chiral pollutants-the necessity of considering stereochemistry. Chimia 1997, 57: 947-951.
63. Kurihara, N.; Miyamoto, J.; Paulson, G. D.; Zeeh, B.; Skidmore, M. W.;Hollingworth, R. M.; Kuiper, H. A. Chirality in synthetic agrochemicals: bioactivity and safety considerations, Pure Appl. Chem. 1997, 69: 2007-2025.
64. Kurihara, N.; Miyamoto, J. Chirality in agrochemicals. John Wiley & Sons: New York, 1998, 85-140.
65. Lange, W.; Krueger, B. Uber ester der monofluorphorsaure. Chem Ber 1932, 65:1598.
66. Lee, P. W.; Allahyari, R; Fukuto, T. R. Studies on the chiral isomers of fonofos and fonofos oxon: 1. Toxicity and antiesterase activities. Pestic. Biochem. Physiol. 1978a, 8: 146-157.
67. Lee, P. W.; Allahyari, R.; Fukuto, T. R. Studies on the chiral isomers of fonofos and fonofos oxon: 2. In vitro metabolism. Pestic. Biochem. Physiol. 1978b, 8:158-162.
68. Lee, P. W.; Allahyari, R.; Fukuto, T. R. Studies on the chiral isomers of fonofos and fonofos oxon: 3. Toxicity and antiesterase activities. Pestic. Biochem.Physiol. 1978c, 9: 23-28.
69. Lee, P. W.; Allahyari, R.; Fukuto, T. R. Absorption and metabolism of the chiral isomers of fonofos in the corn and cotton plant. J. Environ. Sci. Health B 1980,75: 25-29.
70. Levy, D.; Ashani, Y. Synthesis and in vitro properties of a powerful quaternary methylphosphonate inhibitor of acetylcholinesterase.A new marker in blood-brain barrier research. Biochem. Pharmacol. 1986, 35: 1079-1085.
71. Lewis, D. L.; Garrison, A. W.; Wommack, K. E.; Whittemore, A.; Steudler, P.; Melillo, J. Influence of environmental changes on degradation of chiral pollutants in soils. Nature 1999, 401: 898-901.
72. Li, Z. Y.; Zhang, Z. C; Zhou, Q. L.; Gao, R. Y.; Wang, Q. S. Fast and precise determination of phenthoate and its enantiomeric ratio in soil by the matrix solid-phase dispersion method and liquid chromatography. J. Chromatogr. A 2002, 977: 17-25.
73. Lin, K.; Zhou, S. S.; Xu, C; Liu, W. P. Enantiomeric resolution and biotoxicity of methamidophos. J. Agric. Food Chem. 2006, 54: 8134-8138.
74. Liu, W. P.; Gan, J. Y; Schlenk, D.; Jury, W. A. Enantioselectivity in environmental safety of current chiral insecticides. Proc. Natl. Acad. Sci. U.S.A. 2005a, 702:701-706.
75. Liu, W. P.; Gan, J. Y; Qin, S. J. Separation and aquatic toxicity of enantiomers of synthetic pyrethroid insecticides. Chirality 2005b, 17: S127-S133.
76. Loftsson, T.; Brewster, M. E. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization..J.Pharm. Sci. 1996, 85: 1017-1025.
77. Lotti, M., Becker, C. E.; Aminoff, M. Organophosphate polyneuropathy: pathogenesis and prevention. Neurology 1984, 34: 658.
78. Lotti, M. The pathogenesis of organophosphate polyneuropathy. Crit. Rev. Toxicol. 1992,27:465-487.
79. Lotti, M.; Moretto, A.; Capodicasa, E.; Bertolazzi, M.l Peraica, M. Scapellato, M. L. Interaction between neuropathy target esterase and its inhibitioes and the development of polyneuropathy. Toxicol. Appl. Pharmacol. 1993, 722: 165-171.
80. Loukas, Y. L.; Antoniadou-Vyza, E.; Papadaki-Valiraki, A.; Machera, K. G. γ-Cyclodextrin inclusion complex of a new organophosphorus insecticide. Determination of stability constant with HPLC. J. Agric. Food Chem. 1994, 42: 944-948.
81. Makhayeva, G. F.; Veselove, V. L; Mastryukova, T. A. Interaction of some phosphorodithioates and monothioates containing amino acids fragments with rat liver carboxylesterase. Bioorg. Khim. 1983, 9: 920-925.
82. Marrs, T. C. Organophosphate poisoning. Pharmacol. Ther. 1993, 58: 51-56.
83. Meisenheimer, J.; Lichtenstadt, L. Uber optisch-aktive Verbindungen des Phosphor. Chem. Ber., 1911, 44: 356-359.
84. Mifune, A.; Katsuda, Y.; Yoneda, T. Insecticidal and acaricidal composition and process for controlling pests. U.S. Patent 3846551, 1974.
85. Miles, J. W.; Mount, D. L.: Staiger, M. A.; Teeters, W. R. S-Methyl isomer content of stored malathion and fenitrothion water-dispersible powders and its relationship to toxicity. J Agric. Food Chem. 1979, 27: 421-425.
86. Mileson, B. E.; Chambers, J. E.; Chen, W. L.; Dettbarn, W.; Ehrich, M.; Eldefrawi, A. T.; Gaylor, D. W.; Hamernik, K.; Hodgson, E.; Karczmar, A. G; Padilla, S.; Pope, C. N.; Richardson, R. J.; Saunders, D. R.; Sheets, L. P.; Sultatos, L. G.; Wallace, K. B. Common mechanism of toxicity: A case study of organophosphorus pesticides. Toxicol. Sci. 1998, 41: 8-20.
87. Miyazaki, A.; Kawaradani, M.; Marumo, S.; Tomizawa, C. Enantiotopic demethylation of fenitrothion into partially racemised (R)p-(+)-desmethylfenitrothion by mouse liver homogenate and mice. J.Pestic. Sci. 1983,5: 115-120.
88. Miyazaki, A.; T., N.; Kawaradani, M.; Marumo, S. Resolution and biological activity of both enantiomers of methamidophos and acephate. J. Agric. Food Chem. 1988, 36: 835-837.
89. Miyazaki, A., Kawaradani, M., and Marumo, S. Analysis of an enantiomeric composition of desmethylfenitrothion, a major metabolite of achiral fenitrothion by chiral HPLC. J. Pestic. Sci. 1993, 75: 131-133.
90. Moser, H.; Ryhs, G; Sauter, H. Der Einfluss von Atropisomerie und chiralem Zentrum auf die biologische Aktivit(?)t des Metolachlor. Z. Naturforsch. 1982, 37b: 451-462.
91. Nomeir, A. A.; Dauterman, W. C. Studies on the optical isomers of EPN and EPNO. Pestic. Biochem. Physiol. 1979,10: 121-127.
92. Ohkawa, H.; Mikami, N.; Miyamoto, J. Photodecomposition of Sumithion [O,O-dimethyl 0-(3-methyl-4-nitrophenyI) phosphorothioate]. Agric. Biol. Chem. 1975,39:2265-2271.
93. Ohkawa, H.; Mikami, N.; Kasamatsu, K. Stereoselectivity in toxicity and acetylcholinesterase inhibition by the optical isomers of papthion and papoxon. Agric. Biol Chem. 1976a, 40: 1857-1862.
94. Ohkawa, H.; Mikami, N.; Miyamoto, J. Stereospecific metabolism O ethyl O 2 nitro 5 methylphenyl N isopropyl phosphoramidothioate liver microsomal mixed oxidase. J. Agric. Biol. Chem. 1976b, 40: 2125-2134.
95. Ohkawa, H.; Mikami, N.; Okuno, Y.; Miyamoto, J. Stereospecificity in toxicity of the optical isomers of EPN. Bull. Environ. Contam. Toxicol. 1977a, 75:534-540.
96. Ohkawa, H.; Mikami, N.; Miyamoto, J. Stereoselectivity in metabolism of the optical isomers of cyanofenphos (O-p-cyanophenyl O-ethyl phenylphosphonothioate) in rats and liver microsomes. J. Agric. Biol. Chem. 1977b, 41: 369-37r4.
97. Ohkawa, H. Insecticide Mode of Action. Academic Press: New York, 1982, 163-185.
98. Ooms, A. J.; Boter, H. L. Stereospecificity of hydrolytic enzymes in their reaction with optically active organophosphorus compounds. Biochem. Pharmacol. 1965, 14: 1839-1845.
99. Orgovanyi, J. H.; Otta, K.; Poppl, L.; Fenyvesi, E.; Zaray, G. Spectrophotometric and thermoanalytical study of cypermethrin/cyclodextrin complexes. Microchem.J. 2005, 79: 77-82.
100. Parker, P. E.; Brown, F. W. Organophosphate intoxication: hidden hazards. South Med.J. 1989,52: 1408-1410.
101. Perkow, W. Umsterzunge mit Alkylphosphiten. 1. Mitteil: Umlagerungen bei der Reaktion mit Chloral und Bromal. Chem, Ber. 1954, 87: 755-758.
102. Schmitt, P.; Garrison, A. W.; Freitag, D.; Kettrup, A. Application of cyclodextrin modified micellar electrokinetic chromatography to the separations of selected neutral pesticides and their enantiomers. J. Chromatogr. 1997, 792: 419-429.
103. Seiber, J. N.; Tolkmith, H.; Britton, E. C. Resolution of asymmetric organophosphoramides and their stereospecific transformations. Tetrahedron letters 1967, 34: 3333-3336.
104. Senanayake, N.; Jeyaratnam, J. Toxic polyneuropathy due to gingili oil contaminated with tricresyl phosphate affecting adolescent girl in Sri Lanka. Lancet 1981, 7:88-89.
105. Senanayake, N.; Johnson, M. K. Acute polyneuropathy after poisoning by a new organophosphate insecticide: A preliminary report. N. Engl. J. Med. 1982, 306, 155-157.
106. Senanayake, N.; Karalliedde, L. Neurotoxic effects of organophosphorus insecticides. An intermediate syndrome. N. Engl. J. Med. 1987, 316: 761-763.
107. Szejtli, J. Cyclodextrins and their inclusion complexes. Akademiai Kiad(?): Budapest, 1982, 236-255.
108. Szejtli, J. Cyclodextrins in pesticides. Slarch-Stdrke 1985, 37: 382-386.
109. Szejtli J. Cyclodextrins Technology. Kluweeer Academic Publishers: Dordrecht,1988, 86-90.
110. Szejtli, J. Introduction and general overview of cyclodextrin chemistry. Chem.Rev. 1998,98: 1743-1753.
111. Szente, L. Stable, controlled-release organophosphorous pesticides entrapped in beta-cyclodextrin I. Solid state characteristics. J. Therm. Anal. Calorim. 1998, 57:957-963.
112. Tang, S. L. Y.; Smith, R. L.; Poliakoff, M. Principles of green chemistry: Productivety. Green Chem. 2005, 7: 761-762.
113. Tolkmith, H.; Seiber, J. N.; Budde, P. B.; Mussell, D. R. Imidazole: Fungitoxic derivatives. Science 1967,158: 1462-1463.
114. Tombo, G. M. R.; Bellus, D., Chirality and Crop Protection. Angew. Chem. Int. Edit. 1991,30: 1193-1215.
115. Tsurubuchi, Y.; Kagaya, Y; Kono, Y. Suppression of tetrodotoxin-resistant voltage-gated sodium channels by enantiomers of the oxadiazine insecticide indoxacarb in rat dorsal root ganglion neurons. J. Pest. Sci. 2003, 28: 315-317.
116. Ueji, M.; Tomizawa, C. Insect toxicity and anti-acetylcholinesterase activity of chiral isomers of isofenphos and its oxon.J. Pestic. Sci. 1986,11: 447-453.
117. Ueji, M.; Tomizawa, C. Metabolism of the insecticide isofenphos in rats. J. Pestic. Sci. 1987,12: 269-275.
118. Ueji, M. Biological activity and metabolism of phosphoramidate insecticides. J.Pestic. Sci. 1988,13: 325-336.
119. Verschoyle, R. D.; Reiner, E.; Bailey, E.; Aldridge, W. N.Dimethylphosphorothioates. Reaction with malathion and effect on malathion toxicity. Arch Toxicol. 1982, 49: 293-301.
120. Wakabayashi, K.; Hizue, M.; Nozaki, H.; Nakayama, M; Kurihara, N.Enantiotopic selectivity in monodemethylation of fenitrothion by rat liver glutathione S-transferase isoenzymes and mouse liver cytosol. J. Pestic. Sci.1994, 19: 277-284.
121. Walker, B. Jr; Nidiry, J. Current concepts: organophosphate toxicity. Inhal.Toxicol. 2002, 14: 975-990.
122. Wang, Y. S.; Tal, K. T; Yen, J. H. Separation, bioactivity, and dissipation of enantiomers of the organophosphorus insecticide fenamiphos. Ecotox. Environ.Safety 2004, 57:346-353.
123. Wang, L. M.; Liu, W.; Yang, C. X.; Pan, Z. Y; Gan, J. Y; Xu, C; Zhao, M. R.;Schlenk, D. Enantioselectivity in estrogenic potential and uptake of bifenthrin. Environ. Sci. Technol. 2007, 41: 6124-6128.
124. Wang, P.; Jiang, S. R.; Liu, D. H.; Jia, G. F.; Wang, Q. X.; Wang, P.; Zhou, Z. Q. Effect of alcohols and temperature on the direct chiral resolutions of fipronil, isocarbophos and carfentrazone-ethyl. Biomed. Chromatogr. 2005, 19: 454-458.
125. Wang, P.; Jiang, S. R.; Liu, D. H.; Zhang, H. J.; Zhou, Z. Q. Enantiomeric resolution of chiral pesticides by high-performance liquid chromatography. J. Agric. Food Chem. 2006, 54:1577-1583.
126. Williams, A., Opportunities for chiral agrochemicals. Pest. Sci. 1996, 46: 3-9.
127. Wu, S. Y.; Hirashima, A.; Kuwano, E.; Eto, M. Synthesis of optically active 1,3,2-oxazaphopholidine 2-sulfides and 1,3,2-Benzodioxazaphophorin 2-sulfides. Agrie. Biol. Chem. 1987, 51: 537-547.
128. Wu, S. Y.; Hirashima, A. Synthesis and insecticidal activity of oxazaphospholidines, oxathiaphospholanes and thiazaphospholidines. J. Pestic. Sci. 1988, 13: 527-538.
129. Wu, S. Y.; Hirashima, A.; Eto, M.; Yanagi, K.; Nishioka, E.; Moriguchi, K., Synthesis of highly pure enantiomers of insecticide salithion. Agric Biol Chem 1989, 53: 157-163.
130. Wustner, D. A.; Fukuto, T. R. Stereoselectivity in cholinesterase inhibition, toxicity, and plant systemic activity by the optical isomers of O-2-butyl S-2-(ethylthio) ethyl ethylphosphonothioate. J. Agric. Food Chem. 1973, 21: 756-766.
131. Wustner D A, Fukuto T R. Affinity and phosphorylation constants for the inhibition of cholinesterases by the optical isomers of O-2-butyl S-2-(dimethylammonium)ethyl ethylphosphonothioate hydrogen oxalate. Pestic. Biochem. Physiol. 1974. 4: 365-369.
132. Xu, C.; Zhao, M. R.; Liu, W. P.; Chen, S. W.; Gan, J. Y. Enantioselectivity in zebrafish embryo toxicity of the insecticide acetofenate. Chem. Res. Toxicol. 2008, 21: 1050-1055.
133. Yamamoto, I.; Unai, T.; Suzuki, Y.; Katsuda, Y. Preparation, stabilization, and insecticidal activity of cyclodextrin-inclusion compounds of pyrethroids. Nippon Noyaku Gakkaishi 1976, 1: 41-48. (CAN 85:172714)
134. Yamamoto, I.; Katsuda, Y. β-cyclodextrin inclusion complexes of pyrethroids. Pestic. Sci. 2006, 11: 134-140.
135. Yang, Y. Pesticides and environmental health trends in China; 2007. http://www.wilsoncenter.org/topics/docs/pesticides_feb28.pdf.
136. Yen, J. H.; Tsai, C. C.; Wang, Y. S. Separation and toxicity of enantiomers of organophosphorus insecticide leptophos. Ecotox. Environ. Safety 2003, 55: 236-242.
137. Zhou, S. S.; Lin, K. D.; Yang, H. Y.; Li, L.; Liu, W. P.; Li, J. Stereoisomeric separation and toxicity of a new organophosphorus insecticide chloramidophos. Chem. Res. Toxicol. 2007, 20: 400-405.
138．毕富春，王文丽．蔬果磷稳定性研究．化学工业与工程 1996，13(3)：44-50．
139．陈万义，薛振祥，王能武．新农药研究与开发．北京：化学工业出版社，2003，1．
140．程正魁．杀螟松、乐果及水杨硫磷的热分解及其稳定化方法．精细化工中间体，1985，(1)：52-56．
141．方克美．有机磷农药中毒急救治疗进展．急症医学，2000，9(4)：283-285．
142．关里，王汉斌，赵德禄．肟类复能剂治疗急性有机磷农药中毒的研究现状．中华内科杂志，2004，43(2)：157-158．
143．郝国．磷酸三邻甲苯酯中毒迟发性神经病．第二届神经肌病学术研讨会论文汇编，1991，87．
144．华小梅，江席流．我国农药生产及对环境影响．精细与专用化学品，2000，12(2)：10-12．
145．胡林．鱼藤酮的稳定性研究及致细胞凋亡作用[博士学位论文]．广州：华南农业大学，2003．
146．蒋木庚，杨春龙，王鸣华，杨红，钱康南，刘益平，钱卫文，蒋丰．手性有机磷农药的研究与展望．世界农药2000，22(2)：16-21．
147．江藤永松．有机磷农药的有机化学与生物化学．北京：化学工业出版社，1981，185-195．
148．雷玲．鱼藤酮和Bt的光稳定性研究[硕士学位论文]．广州：华南农业大学，2004．
149．刘惠君．酰胺类除草剂的生物化学行为以及手性选择性行为研究[博士学位论文]．杭州：浙江大学，2005．
150．刘维屏．农药环境化学．北京：化工工业出版社，2006，5．
151．梁友信．劳动卫生与职业病学(第四版)．北京：人民卫生出版社，2000， 122-126．
152．马兴元，谭建华，朱平．有机磷类神经毒剂及其抗毒剂研究进展．动物医学进展2003，24(1)：37-40．
153．孟春和．有机磷农药固体剂型的稳定性．山西化工1981，(1)：47-49．
154．缪建强．中国高毒有机磷的使用和替代状况浅析．农药市场信息，2006，21(8)：18-19．
155．宁国英．急性重度有机磷农药中毒治疗方法研究[硕士学位论文]．济南：山东省医学科学院，2007．
156．童林荟．环糊精化学--基础与应用．北京：科学出版社，2001a，1．
157．童林荟．环糊精化学--基础与应用．北京：科学出版社，2001b，356-359．
158．王振君．农药缓释剂的进展．农药，1985，(3)：3-5．
159．魏方林，朱国念，程敬丽，桂文君．15％三唑磷微乳剂配方研制及其田间药效．现代农药．2004，3(4)：25-28．
160．吴霖，俞英．环糊精超分子包结物的制备与应用前景．江苏化工，2003，31(2)：32-35．
161．吴强．有机磷化合物中毒M受体及其信号传导研究．国外医学卫生学分册，2000，27(5)：472-476．
162．吴婉娥，朱绪恩，苏力宏，陈开勋，胡芝生．有机磷农药稳定剂进展．陕西化工，1997，(4)：31-34．
163．伍一军，杨琳，李薇．有机磷农药的多毒性作用．环境与职业医学，2005，22(4)：367-370．
164．小池好智，金子胜．稳定化的农药制剂．农药译丛，1984，6(2)：53-57．
165．肖和平．对提高敌敌畏稳定性途径的探讨．湖南化工，1998，28(1)：8-10．
166．徐光翠，鄢珣，张波．有机磷农药对雄性系统的损伤作用．甘肃农业大学学报，2005，40(6)：822-826．
167．续浩，陈亮．环糊精包结物的制备和研究方法．分析测试技术与仪器，2001，7(3)：143-151．
168．杨春河．新药创制、环境保护与结构调整--对我国农药工业发展的一点思考．农药，2000，39(1)：1-6．
169．叶秀林．立体化学．北京：北京大学出版社，1999，9-39．
170．张慧容，彭浩，贺红武．环糊精在农药中的研究及其应用．农药，2008，47(6)：406-411．
171．张培荣．农药储存中的稳定性分类．农资科技，1995，(5)：28-32．
172．张一宾，孙晶．国内外有机磷农药的概况及对我国有机磷农药发展的看法．农药，1999，38(7)：1-3．
173．郑荣远．有机磷持发多发性神经病的临床研究．温州医学院学报，1992，(3)：181-184．
174．周炯林．有机磷农药遗传毒性研究进展．国外医学卫生学分册，2007，34(6)：339-344．
175．周淑芳．有机磷农药的雌性生殖毒性研究进展．国外医学卫生学分册，2008，35(1)：51-55．
176．朱明钦等．有机磷农药的神经毒性作用“中间综合症”两例报告．中国工业医学杂志，1991，4(3)：54．
1. Benschop, H. P.; Konings, C. A. G.; Van Genderen, J.; De Jong, L. P. A. Isolation, anticholinesterase properties, and acute toxicity in mice of the four stereoisomers of the nerve agent soman. Toxicol. App. Pharmacol. 1984, 72: 61-74.
2. Berkman, C. E.; Quinn, D. A.; Thompson, C. M. Interaction of acetylcholinesterase with the enantiomers of malaoxon and isomalathion. Chem. Res. Toxicol. 1993, 6: 724-730.
3. Bobbitt, D. R.; Linder, S. W. Recent advances in chiral detection for high performance liquid chromatography. TrAC-Trend Anal. Chem. 2001, 20: 111-123.
4. Casida, J. E.; Leader, H. Resolution and biological activity of the chiral isomers of O-(4-bromo- 2-chlorophenyl) O-ethyl S-propyl phosphorothioate (profenofos insecticide). J. Agric. Food. Chem. 1982, 30: 546-552.
5. Doorn, J. A.; Gage, D. A.; Schall, M.; Talley, T. T.; Thompson, C. M.; Richardson, R. J. Inhibition of acetylcholinesterase by (1S, 3S)-isomalathion proceeds with loss of thiomethyl: kinetic and mass spectral evidence for an unexpected primary leaving group. Chem. Res. Toxicol. 2000, 13:1313-1320.
6. Doorn, J. A.; Talley, T. T.; Thompson, C. M.; Richardson, R. J. Probing the active sites of butyrylcholinesterase and cholesterol esterase with isomalathion: conserved stereoselective inactivation of serine hydrolases structurally related to acetylcholinesterase. Chem. Res. Toxicol. 2001, 14: 807-813.
7. Doorn, J. A.; Thompson, C. M.; Christner, R. B.; Richardson, R. J. Stereoselective inactivation of Torpedo Californica acetylcholinesterase by isomalathion, inhibitory reactions with (1R)- and (1S)-isomers proceed by different mechanisms. Chem. Res. Toxicol. 2003, 16: 958-965.
8. Ellman, G. L.; Courtney, K. D.; Andres, V.; Featherstone, R. M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961, 7: 88-95.
9. Filho, M. V. S.; Oliveira, M. M.; Salles, J. B.; Bastos, V. L. F. C.; Cassano, V. P. F.; Bastos, J. C. Methyl-paraoxon comparative inhibition kinetics for acetylcholinesterases from brain of neotropical fishes. Toxicol. Lett. 2004, 153: 247-254.
10. Gorder, G. W.; Kirino, O.; Hirashima, A.; Casida, J. E. Bioactivation of isofenphos and analogues by oxidative N-dealkylation and desulfuration. J. Agric. Food Chem. 1986, 34: 941.
11. ISO 6341. Water qualitysdetermination of the inhibition of the mobility of Daphnia magna Straus (Cladocera, Crustacca) sacute toxicity test, 1996.
12. Johnson, J. A.; Wallace, K. B. Species-related differences in the inhibition of brain acetylcholinesterase by paraoxon and malaoxon. Toxicol. Appl. Pharmacol. 1987, 88: 234-241.
13. Jianmongkol, S.; Berkman, C. E.; Thompsom, H. M.; Richardson, R. J. Relative potencies of the four stereoisomers of isomalathion for inhibition of hen brain acetylcholinesterase and neurotoxic esterase in vitro. Toxicol. Appl. Pharmacol. 1996, 139: 342-348.
14. Kitz, R.; Wilson, I. Ester of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase. J. Biol. Chem. 1962, 237: 3245-3249.
15. Konwick, B. J.; Garrison, A. W.; Avants, J. K., Fisk, A. T. Bioaccumulation, biotransformation, and metabolite formation of fipronil and chiral legacy pesticides in rainbow trout. Environ. Sci. Technol. 2006, 40: 2930-2396.
16. Lin, K. D.; Zhou, S. S.; Xu, C.; Liu, W. P. Enantiomeric resolution and biotoxicity of methamidophos. J. Agric. Food Chem. 2006, 54:8134-8138.
17. Liu, W. P.; Gan, J. Y.; Schlenk, D.; Jury, W. A. Enantioselectivity in environmental safety of current chiral insecticides. Proc. Natl. Acad. Sci. U. S. A. 2005, 102: 701-706.
18. Main, A. Affinity and phosphorylation constant for the inhibition of esterases by organophosphates. Science 1964, 144: 992-993.
19. Miyamoto, T., Kasagami, T., Asai, M., Yamamoto, I. A novel bioactivation mechanism of phosphoramidate insecticides. Pestic. Biochem. Phys. 1999, 63: 151-162.
20. Ohkawa, H.; Mikami, N.; Kasamatsu, K. Stereoselectivity in toxicity and acetylcholinesterase inhibition by the optical isomers of papthion and papoxon. Agric, Biol. Chem. 1976, 40:1857-1862.
21. Okamoto, Y., Kaida, Y. Resolution by high-performance liquid chromatography using polysaccharide carbamates and benzoates as chiral stationary phases. J. Chromatogr. A. 1994, 666:403-419.
22. Okamoto, Y.: Yashima, E. Polysaccharide derivatives for chromatographic separation of enantiomers. Angew. Chem. Int. Ed. 1998, 3 7:1020-1043.
23. Ordentlich, A.; Barak, D.; Kronman, C.; Benschop, H. P.; De Jong, L. P. A.; Ariel, N.; Barak, R..; Segall, Y.; Velan, B.; Shafferman, A. Exploring the active center of human acetylcholinesterase with stereoisomers of an organophosphorus inhibitor with two chiral centers. Biochemistry 1999, 38: 3055-3066.
24. Rodriguez, O. P.; Muth, G. W.; Berkman, C. E.; Kim, K.;Thompson, C. M. Inhibition of various cholinesterases with the enantiomers of malaoxon. Bull. Environ. Contam. Toxicol. 1997, 58: 171-176.
25. Seungmin, R.; Jing, L.; Thompson, C. M. Comparative anticholinesterase potency of chiral isoparathion methyl. Chem. Res. Toxicol. 1991, 4: 517-520.
26. Wustner, D. A.; Fukuto, T. R. Stereoselectivity in cholinesterase inhibition, toxicity, and plant systemic activity by the optical isomers of O-2-butyl S-2-(ethylthio) ethyl ethylphosphonothioate. J. Agric. Food Chem. 1973, 21: 756-761.
27. Wustner, D. A.; Fukoto, T. R. Affinity and phosphonylation constants for the inhibition of cholinesterases by the optical isomers of O-2-butyl S-2-(dimethylammonium) ethyl ethylphosphonothioate hydrogen oxalate. Pestic. Biochem. Physiol. 1974, 4: 365-376.
28. Yashima E, Okamoto Y. Chiral discrimination on polysaccharides derivatives. Bull. Chem. Soc. Jpn. 1995, 68: 3289-3307.
29. Yashima, E. Polysaccharide-based chiral stationary phases for high-performance liquid chromatographic enantioseparation. J. Chromatogr. A 2001, 906:105-125.
30．陈立仁．液相色谱手性分离．北京：科学出版社，2006，20．
31．李坚，巨修练，梁帝允，陈呈新，王一风．新杀虫剂氯胺磷．世界农药，2005，27(2)：44-46．
32．叶伟红．四种污染物质对大型蚤的毒性研究[硕士学位论文]．杭州：浙江大学，2004，20-22．
33．惠秀娟．环境毒理学．北京：化学工业出版社，2003，266-269．
1. Casida, J. E.; Sanderson, D. M. Toxic hazard from formulating the insecticide dimethoate in methyl "Cellosolve". Nature 1961, 189: 507-508.
2. Casida, J. E.; Sanderson, D. M. Solvent effects on toxicity, reaction of certain phosphorothionate insecticides with alcohols and potentiation by breakdown products. J. Agric. Food Chem. 1963, 11: 91-96.
3. Maxwell, D. M.; Brecht, K. M. Quantitative structure-activity analysis of acetylcholinesterase inhibition by oxono and thiono analogues of organophosphorus compounds. Chem. Res. Toxicol. 1992, 5: 66-71.
4. Rodbard, D.; Frazier, G. R. Statistical analysis of radioligand assay data. Methods Enzymol. 1975, 37: 3-22.
5. Tabashnik, B. E.; Cushing, N. L. Leaf residue vs. topical bioassays for assessing insecticide resistance in the diamondback moth (Plutella xylostella L.). FAO Plant Prot. Bull. 1987, 35:11-14.
6. Teichmann, H.; Schnell, M. Reaction of O, O-dimethyl phosphoramidothioate with chloral. J. Prakt. Chem. 1987, 329:871-876 (CAN 110:23978).
7．徐寿昌．有机化学．北京：高等教育出版社，1993，281-282．
1. Atwood, J. L.; Lehn, J. M. Cyclodextrins. Pergamon: Oxfors, 1996, 503-513.
2. Babcock, J. C.; Polansky, J. R.; Bowman, L. M.; Tsao, S. W.; Si, E. C. C.; Chandrasekaran, S. K. Stabilization of aminosteroids for topical ophthalmic and other applications. US 5538721, 1996.
3. Backensfeid, T.; Heil, W.; Lipp,R. Compositions of estrogen-cyclodextrin complexes. US 7163931, 2007.
4. Benesi, H. A.; Hildebrand, J. H. A spectrophotometric investigation of the interaction of iodine with aromatic hydrocarbons. J. Am.Chem. Soc. 1949, 71: 2703-2707.
5. Biocides & Pesticides Unit (BPU).Guidance on the storage stability data requirements for non-agricultural pesticide products. Pestic. News. 2004, 64: 1-15.
6. Collaborative International Pesticides Analytical Council Ltd. (CIPAC). MT46.3 Accelerated Storage Procedure. Dobrat, W.; Martin, A., Eds.; Black Bear Press Ltd.: Cambridge, 2000.
7. Connors, K. A. The stability of cyclodextrin complexes in solution. Chem. Rev. 1997, 97: 1325-1357.
8. Fava, S.; Gioia, D. D.; Marchetti, L.; Fenyvesi, E. Randomly methylated β-cyclodextrins (RAMEB) enhance the aerobic biodegradation of polychlorinated biphenyl in aged-contaminated soils. J. Inclusion Phenom. Macrocyclic Chem. 2002, 44:417-421.
9. Indirapriyadharshini. V. K.; Karunanithi, P.; Ramamurthy, P. Inclusion of resorcinol-based acridinedione dyes in cyclodextrins: fluorescence enhancement. Langmuir 2001, 17: 4056-4060.
10 Giordano, F.; Novak, C.; Moyano, J. R. Thermal analysis of cyclodextrins and their inclusion compounds. Thermochim. Acta 2001, 380:123-151.
11. Hamai, S.; Sakurai, H. 2H2O effects on the inclusional complexation of β-cyclodextrin with sodium 2-naphthalenesulfonate in capillary electrophoresis and UV spectrophotometry. J. Chromatogr. A 1998, 800: 327-332.
12. Kamiya, M.; Nakamura, K.; Sasaki, C. Inclusion effects of cyclodextrins on photodegradation rates of parathion and paraoxon in aquatic medium. Chemosphere 1994, 28:1961-1966.
13. Kamiya, M.; Nakamura, K. Cyclodextrin inclusion effects on photodegradation rates of organophosphorus pesticides. Environ. Int. 1995a, 21: 299-304.
14. Kamiya, M.; Nakamura, K.; Sasaki, C. Inclusion effects of β-cyclodextrins on the hydrolysis of organophosphorus pesticides. Chemosphere 1995b, 30: 653-660.
15. Kita, K.; Nihorbashi, H. DDVP-Cyclodextrin Complexes. GB 1453801, 1976.
16. Loftsson, T.; Brewster, M. E. Pharmaceutical applications of cyclodextrins. l. Drug solubilization and stabilization. J. Pharm. Sci-US. 1996, 85:1017-1025.
17. Loukas, Y. L.; Antoniadou-Vyza, E.; Papadaki-Valiraki, A.; Machera, K. G. γ-Cyclodextrin inclusion complex of a new organophosphorus insecticide. Determination of stability constant with HPLC. J. Agric. Food Chem. 1994, 42: 944-948.
18. Reid, B. J.; Stokes, J. D.; Jones, K. C.; Semple, K. T. Influence of hydroxypropyl-β-cyclodextrin on the extraction and biodegradation of phenanthrene in soil. Environ. Toxicol. Chem. 2004, 23: 550-556.
19. Szejtli, J. Cyclodextrins and their inclusion complexes. Akad(?)miai Kiad(?): Budapest, 1982, 236-255.
20. Szente, L. Stable, controlled-release organophosphorous pesticides entrapped in beta-cyclodextrin Ⅰ. Solid state characteristics. J. Therm. Anal. Calorim. 1998, 51: 957-963.
21. Uekama, K.; Hirayama, F.; lrie, T. Cyclodextrin drug carrier systems. Chem. Rev. 1998, 98: 2045-2076.
22. Villaverde, J.; Morillo, E.; P(?)rez-Mart(?)nez, J. I.; Gin(?)s, J. M.; Maqueda, C. Preparation and characterization of inclusion complex of norflurazon and β-cyclodextrin to improve herbicide formulations. J. Agric. Food Chem. 2004, 52: 864-869.
23. Yang, G. F.; Wang, H. B.; Yang, W. C.; Gao, D. Q.; Zhan, C. G.Bioactive permethrin/β-cyclodextrin inclusion complex. J. Phys.Chem. B 2006, 110: 7044-7048.
24. Yilmaz, V. T.; Yilmaz, V. T.; Karada(?), A.; (?)cbudak, H. Thermal decomposition of β-cyclodextrin inclusion complexes of ferrocene and their derivatives. Thermochim. Acta 1995, 261: 107-118.
25. Zhu, X. L.; Wang, H. B.; Chen, Q.; Yang, W. C.; Yang, G. F.Preparation and characterization of inclusion complex of iprodione and β-cyclodextrin to improve fungicidal activity. J. Agric. Food Chem. 2007, 55: 3535-3539.
26．童林荟．环糊精化学--基础与应用．北京：科学出版社，2001，135．
1. Abou-Donia, M. B. Organophosphorus ester-induced delayed neurotoxicity. Annu. Rev. Pharmacol. Toxicol. 1981, 21:511-548.
2. Atterwill, C. K.; Bruinink, A.; Drejer, J.; Duarte, E.; Abdulla, E. M.; Meredith, C.; Nicotera, P.; Regan, C.; Rodriguezfarre, E.; Simpson, M. G.; Smith, R.; Veronesi, B.; Vijverberg, H.; Walum, E.; Williams, D. C. In vitro neurotoxicity testing. The report and recommendations of ECVAM workshop-3. Atla-Altern. Lab. Anim. 1994, 22: 350-362.
3. Barata, C.; Baird, D. J.; Amat, F.; Soares, A. M. V. M. Comparing population responses to contaminants between laboratory and field: an approach using Daphnia magna ephippial egg banks. Funct. Ecol. 2000, 14:513-523.
4. Barata, C.; Solayan, A.; Porte, C., Role of B-esterases in assessing toxicity of organophosphorus (chlorpyrifos, malathion) and carbamate (carbofuran) pesticides to Daphnia magna. Aquat. Toxicol. 2004, 66: 125-139.
5. Berkman, C. E.; Thompson, C. M.; Perrin, S. R. Synthesis, absolute-configuration, and analysis of malathion, malaoxon, and isomalathion enantiomers. Chem. Res. Toxicol. 1993, 6:718-723.
6. Bhuyan, B. K.; Loughman, B. E.; Fraser, T. J.; Day, K. J. Comparison of different methods of determining cell viability after exposure to cytotoxic compounds. Exp. Cell Res. 1976, 97: 275-280.
7. Costa, L. G., Current issues in organophosphate toxicology. Clin. Chim. Acta 2006, 366: 1-13.
8. Ehrich, M.; Correll, L.; Veronesi, B. Acetylcholinesterase and neuropathy target esterase inhibitions in neuroblastoma cells to distinguish organophosphorus compounds causing acute and delayed neurotoxicity. Fund Appl. Toxicol. 1997, 38: 55-63.
9. EPA. Pesticide Assessment Guidelines, Subdivision F. Hazard Evaluation: Human and Domestic Animals. Addendum 10: Neurotoxicity, Series 81, 82, and 83. U.S. Environmental Protection Agency: Washington, DC, 1991.
10. Flaskos, J.; McLean, W. G.; Fowler, M. J.; Hargreaves, A. J. Tricresyl phosphate inhibits the formation of axon-like processes and disrupts neurofilaments in cultured mouse N2a and PC12 cells. Neurosci. Lett. 1998, 242: 101-104.
11. Flaskos, J.; Fowler, M. J.; Teurtrie, C.; Hargreaves, A. J. The effects of carbaryl and trichlorphon on differentiating mouse N2a neuroblastoma cells. Toxicol. Lett. 1999, 110: 79-84.
12. Guilhermino, L.; Lopes, M. C.; Carvalho, A. P.; Soares, A. M. V. M. Inhibition of acetyicholinesterase activity as effect criterion in acute tests with juvenile Daphnia Magna. Chemosphere 1996, 32: 727-738.
13. Henschler, D.; Schmuck, G.; Vanaerssen, M.; Schiffmann, D., The inhibitory effect of neuropathic organophosphate esters on neurite outgrowth in cell-cultures-a basis for screening for delayed neurotoxicity. Toxicol. in Vitro 1992, 6: 327-335.
14. Hong, M. S.; Hong, S. J.; Barhoumi, R.; Burghardt, R. C.; Donnelly, K. C.; Wild, J. R.; Venkatraj, V.; Tiffany-Castiglioni, E. Neurotoxicity induced in differentiated SK-N-SH-SY5Y human neuroblastoma cells by organophosphorus compounds. Toxicol. Appl. Pharm. 2003, 186:110-118.
15. Jianmongkol, S.; Berkman, C. E.; Thompson, C. M.; Richardson, R. J. Relative potencies of the four stereoisomers of isomalathion for inhibition of hen brain acetylcholinesterase and neurotoxic esterase in vitro. Toxicol. Appl. Pharmacol. 1996, 139: 342-348.
16. Johnson, M. K.; Read, D. J.; Benschop, H. P. Interaction of the four stereoisomers of soman (pinacolyl methylphosphonofluoridate)with acetylcholinesterase and neuropathy target esterase of hen brain. Biochem. Pharmacol. 1985, 34: 1945-1951.
17. Johnson, M. K.; Read, D. J. The influence of chirality on the delayed neuropathic potential of some organophosphorus esters: Neuropathic and prophylactic effects of some stereoisomeric esters of ethylphosphonic acid (EPN oxon and EPN) correlate with quantities of aged and unaged neuropathy target esterase in vivo. Toxicol. Appl. Pharma. 1987, 90: 103-115.
18. Johnson, M. K.; Vilanova, E.; Read, D. J. Anomalous biochemical responses in tests of the delayed neuropathic potential of methamidophos (O,S-dimethyl phosphorothioamidate), its resolved isomers and of some higher O-alkyl homologs. Arch. Toxicol. 1991, 65:618-624.
19. Li, W.; Casida, J. E., Actions of two highly potent organophosphorus neuropathy target esterase inhibitors in mammalian cell lines. Toxicol. Lett. 1997, 92: 123-130.
20. Lin, K. D.; Zhang, F.; Zhou, S. S.; Liu, W. P.; Gan, J. Y.; Pan, Z. Y. Stereoisomeric separation and toxicity of the nematicide fosthiazate. Environ. Toxicol. Chem. 2007, 26: 2399-2344.
21. Lin, K. D.; Liu, W. P.; Li, L.; Gan, J., Single and joint acute toxicity of isocarbophos, enantiomers to Daphnia magna. J. Agric. Food Chem. 2008, 56: 4273-4277.
22. Liu, W. P.; Gan, J. Y.; Schlenk, D.; Jury, W. A. Enantioselectivity in environmental safety of current chiral insecticides. Proc. Natl. Acad. Sci. U.S.A. 2005, 102: 701-706.
23. Liu W. P.; Lin, K. D.; Gan, J. Y. Separation and aquatic toxicity of enantiomers of the organophosphorus insecticide trichloronate. Chirality 2006, 18:713-716.
24. Mileson, B. E.; Chambers, J. E.; Chen, W. L.; Dettbarn, W.; Ehrich, M.; Eldefrawi, A. T.; Gaylor, D. W.; Hamernik, K.; Hodgson, E.; Karczmar, A. G.; Padilla, S.; Pope, C. N.; Richardson, R. J.; Saunders, D. R.; Sheets, L. P.; Sultatos, L. G.; Wallace, K. B. Common mechanism of toxicity: A case study of organophosphorus pesticides. Toxicol. Sci. 1998, 41: 8-20.
22. Nostrandt, A. C.; Ehrich, M. Development of a model cell-culture system in which to study early effects of neuropathy-inducing organophosphorus esters. Toxicol. Lett. 1992, 60:107-114.
23. Qian, Y.; Venkatraj, J.; Barhoumi, R.; Pal, R.; Datta, A.; Wild, J. R.; Tiffany-Castiglioni, E. Comparative non-cholinergic neurotoxic effects of paraoxon and diisopropyl fluorophosphate (DFP) on human neuroblastoma and astrocytoma cell fines. Toxicol. Appl. Pharmacol. 2007, 219:162-171.
24. Sanborn, J. R.; Fukuto, T. R.; Metcalf, R. L. Insecticidal, anticholinesterase, and hydrolytic properties of phosphoramidothioates. J. Agric. Food Chem. 1970, 18: 189-194.
25. Senanayake, N.; Johnson, M. K. Acute polyneuropathy after poisoning by a new organophosphate insecticide: A preliminary report. N. Engl. J. Med. 1982, 306: 155-157.
26. Veronesi, B., In vitro screening batteries for neurotoxicants. Neurotoxicology 1992, 13: 185-195.
27. Wang, Y. S.; Tai, K. T.; Yen, J. H. Separation, bioactivity, and dissipation of enantiomers of the organophosphorus insecticide fenamiphos. Ecotoxicol. Environ. Saf. 2004, 57: 346-353.
28. Williams, A. Opportunities for chiral agrochemicals. Pestic. Sci. 1996, 46: 3-9.
29. Yen, J. H.; Tsai, C. C.; Wang, Y. S. Separation and toxicity of enantiomers of organophosphorus insecticide leptophos. Ecotoxicol. Environ. Saf. 2003, 55: 236-242.
1. Allon, N.; Raveh, L.; Gilat, E.; Cohen, E.; Grunwald, J.; Ashani, Y. Prophylaxis against soman inhalation toxicity in guinea pigs by pretreatment alone with human serum butyrylcholinesterase. Toxicol. Sci. 1998, 43: 121-128.
2. Eto, M.; Kinoshita, Y.; Kato, T.; Oshima, Y. Saligenin Cyclic methyl phosphate and its thiono analogue: new insecticides related to the active metabolite of Tri-o-cresyl Phosphate. Nature 1963a, 200:171 - 172.
3. Eto, M.; Kinoshita, Y.; Kato, T.; Oshima, Y. Saligenin cyclic alkyl phosphates and phosphorothionates with insecticidal activity. Agric. Biol. Chem. 1963b, 27: 789-794.
4. Eto, M. Chemistry and biochemistry of salithion and related compounds. Rev. Plant Prot. Res. 1976, 9: 1-20.
5. Fossi, M. C.; Leonzio, C. Non-destructive biomarkers in vertebrates. Boca Raton: Lewis Publishers, 1994, 37-62.
6. Hirashima, A.; lshaaya, I.; Ueno, R.; Ichiyama, Y.; Wu, S. Y.; Eto, M. Biological activity of optically active salithion and salioxon. Agric. Biol. Chem. 1989a, 53: 175-178.
7. Hirashima, A.; Ishaaya, I.; Ueno, R.: Oyama, K.; Eto, M. Effect of salithion enantiomers on the trehalase system and on the digestive protease, amylase, and invertase of Tribolium castaneum. Pestic. Biochem. Physiol. 1989b, 34:205-210.
8. Hirashima, A.: Ueno, R.; Oyama, K.; Koga, H.; Eto, M. Effect of salithion enantiomers on larval growth, carbohydrases, acetylcholinesterase, adenylate cyclase activities and cyclic adenosine 3',5'-monophosphate level of Musca domestica and Tribolium castaneum. Agric. Biol. Chem. 1990, 54:1013-1022.
9. Itoh, K. Stereoselctive degradation of organophosphorus insecticide salithion in upland soils. J. Pestic. Sci. 1991a, 16: 35-40.
10. Itoh, K. Stereoselective metabolism of insecticide salithion by Agrobacterium sp. and Acinetobacter sp. isolated from soil. J. Pestic. Sci. 1991b, 16: 85-91.
11. Lin, K. D.: Zhang, F.; Zhou, S. S.; Liu, W. P.; Gan, J.: Pan, Z. Y. Stereoisomeric separation and toxicity of the nematicide fosthiazate. Environ. Toxicol. Chem. 2007, 26: 2339-2344.
12. Lin, K. D.; Liu, W. P.; Li, L.; Gan, J. Single and joint acute toxicity of isocarbophos enantiomers to Daphnia magna. J. Agric. Food Chem. 2008, 56: 4273-4277.
13. Liu, W, P.; Gan, J.; Schlenk, D,; Jury, W. A. Enantioselectivity in environmental safety of current chiral insecticides. Proc. Natl. Acad. Sci. USA 2005, 102: 701-706.
14. Liu, W. P.; Lin, K. D.; Gan, J. Separation and aquatic toxicity of enantiomers of the organophosphorus insecticide trichioronate. Chirality 2006, 18:713-716.
15. Raveh, L.; Grunwald, J.; Marcus, D.; Papier, Y.; Cohen, E.; Ashani,Y. Human butyrylcholinesterase as a general prophylactic antidote for nerve agent toxicity. In vitro and in vivo quantitative characterization. Biochem. Pharmacol. 1993, 45: 2465-2474.
16. Sternfeld, M.; Rachmilewitz, J.; Loewenstein-Lichtenstein, Y.; Andres, C.; Timberg, R.; Ben-Ar, S.; Glick, D.; Soreq, H.; Zakut, H. Normal and atypical butyrylcholinesterases in placental development, function, and malfunction. Cell Mol. Neurobiol. 1997, 17:315-332.
17. Wang, Y. S.; Tai, K. T.; Yen, J. H. Separation, bioactivity, and dissipation of enantiomers of the organophosphorus insecticide fenamiphos. Ecotox. Environ. Safe 2004, 57: 346-353.
18. Wu, S. Y.; Hirashima, A.; Kuwano, E.; Eto, M. Synthesis of optically active 1,3,2-oxazaphopholidine 2-sulfides and 1,3,2-Benzodioxazaphophorin 2-sulfides. Agric. Biol. Chem. 1987, 51: 537-547.
19. Wu, S. Y.; Hirashima, A.; Eto, M.; Yanagi, K.; Nishioka, E.; Moriguchi, K. Synthesis of highly pure enantiomers of insecticide salithion. Agric. Biol. Chem. 1989, 53: 157-163.
20. Yashima E, Okamoto Y. Chiral discrimination on polysaccharides derivatives. Bull. Chem. Soc. Jpn. 1995, 68: 3289-3307.
21．毕富春，王文丽．蔬果磷稳定性研究．化学工业与工程，1996，13(3)：44-50．
22．毕富春，陈学仁，王文丽，朱兰惠，王勇，邵瑞链，成俊然．蔬果磷对4种昆虫的杀虫活性．化学工业与工程，1997，14(4)：38-41．
23．成俊然，邵瑞链，毕富春，马治华，黄润秋．用分子内环化反应合成蔬果磷的研究．农药，1998，37(10)：15-16．
24．化学工业部农药情报中心站．国外农药品种手册(三)．沈阳：化工部农药工业科技情报站，1981，176-178．
25．谭本祝，陶贤鉴，于正英，曹修祗．蔬果磷的合成与田间药效．农药，1998，37(9)：15-16．