Drugs and Poisons in Humans - A Handbook of Practical Analysis (Part 59)

Introduction:Organophosphorus pesticides (organophosphate pesticides) are being most widely used as insecticides, and thus cause poisoning cases frequently. The organophosphorus pesticides at the early stage, such as parathion and TEPP, had powerful insecticidal effects and high toxicity for both humans and beasts, and caused poisoning accidents during spraying. Although many less toxic organophosphorus pesticides were then developed, the resistance to the pesticides was acquired by insects during their repeated use, resulting in less effectiveness of the pesticides. Therefore, the development of new pesticides has been being required. Now, about 40 kinds of organophosphorus pesticides are being commercially available in Japan....
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Drugs and Poisons in Humans - A Handbook of Practical Analysis (Part 59) 7.2II.7.2 Organophosphorus pesticides by Masakatsu SakataIntroductionOrganophosphorus pesticides (organophosphate pesticides) are being most widely used asinsecticides, and thus cause poisoning cases frequently. The organophosphorus pesticides atthe early stage, such as parathion and TEPP, had powerful insecticidal effects and high toxicityfor both humans and beasts, and caused poisoning accidents during spraying. Although manyless toxic organophosphorus pesticides were then developed, the resistance to the pesticideswas acquired by insects during their repeated use, resulting in less effectiveness of the pesti-cides. Therefore, the development of new pesticides has been being required. Now, about 40kinds of organophosphorus pesticides are being commercially available in Japan. They arebeing controlled by the Poisonous and Deleterious Substances Control Law of Japan. Varioustypes of pesticides with various degrees of toxicity are available; they are classfied into poison-ous, deleterious and common substances. Even with the common substances, such as malathi-on and fenitrothion, the ingestion of their large amounts for suicidal purpose causes fatalities. The fundamental structure of organophosphorus pesticides is: The pesticides are also structurally classified according to an element bound with the phos-phorus into the phosphate type, thiono type, thiol type and dithiol type. Many of R1 and R2 aredimethoxy or diethoxy groups. To cope with resistant insects, the alkyl moieties of R1 and R2groups were replaced by unsymmetyrical propyl and ethyl groups, respectively, in some pesti-cides. As X structures, alkyl, alkoxy, alkylthio, aryl, heterocyclic, aryloxy and arylthio groupscan be mentioned. > Figure 2.1 shows the metabolic pathways of a common thiono type organophosphoruspesticide having dialkoxy groups (R1 and R2). Organophosphorus pesticides undergo both enhancement of their toxicity and detoxifica-tion at the same time in mammals. The thiono type pesticide (1) shows almost no inhibitoryaction on cholinesterase in its unchanged form; it is metabolized by cytochrome P450 (I) intothe phosphate type (2), which reveals toxicity. Therefore the phosphate type pesticide caninhibit cholinesterase without any metabolic activation. As detoxification, dealkylating reaction by enzyme II can be mentioned. The P450 andglutathion are being involved in the enzyme II; the dealkylated form thus produced does notinhibit acetylcholinesterase. The esterases III, which hydrolyze organophosphorus pesticides, as shown in > Fig. 2.1,are phosphorotriester hydrolases. There are many different enzymes responsible for such reac-tions; they are called “paraoxonase, A-esterase, phosphatase or arylesterase”. Carboxyesterase is© Springer-Verlag Berlin Heidelberg 2005536 Organophosphorus pesticides ⊡ Figure 2.1 Typical metabolic pathways for organophosphorus pesticides in mammals. related with the metabolism of malathion, which has carboxylic acid esters in its leaving groups. The metabolisms of organophosphorus pesticides are usually rapid. It is, therefore, neces- sary to analyze the metabolite(s) together with an unchanged organophosphorus pesticide to assess its poisoning correctly. As analytical instruments for organophosphorus pesticides, GC and HPLC are being used. Especially GC with detectors specific for phosphorus or sulfur is useful, because of its high sensitivity and specificity. The metabolites are usually highly polar, and thus need derivatiza- tions for GC detection. GC and GC/MS analysis Materials and preparation • Standard compounds: highly pure organophosphorus compounds can be obtained from Supelco (Bellefonte, PA, USA) and Wako Pure Chemical Industries, Ltd. (Osaka, Japan). • Standard solutions: each standard compound is dissolved in acetone to prepare 1–10 µg/ mL solutions; these solutions can be further diluted according to needs. As an internal standard (IS), an organophosphorus compound, which does not overlap the peaks of a target compound and impurities, is chosen in preliminary experiments. • Solid-phase extraction cartridges: Sep-Pak C18 cartridges (Waters, Milford, MA, USA). • Methylating reagent: Diazald® (N-methyl-N-nitroso-p-toluenesulfonamide) (Sigma-Aldrich, St. Louis, MO, USA); the distillation device attached with a 25-mL reservoir is constructed GC and GC/MS analysis 537 inside a draft; the reservoir is immersed in an ice bath. A 0.4-g ...