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

7.2

© Springer-Verlag Berlin Heidelberg 2005

II.7.2 Organophosphorus

pesticides

by Masakatsu Sakata

Introduction

Organophosphorus pesticides ( organophosphate pesticides) are being most widely used as

insecticides, and thus cause poisoning cases frequently. Th e organophosphorus pesticides at

the early stage, such as parathion and TEPP, had powerful insecticidal eff ects 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 eff ectiveness of the pesti￾cides. Th erefore, the development of new pesticides has been being required. Now, about 40

kinds of organophosphorus pesticides are being commercially available in Japan. Th ey are

being controlled by the Poisonous and Deleterious Substances Control Law of Japan. Various

types of pesticides with various degrees of toxicity are available; they are classfi ed 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.

Th e fundamental structure of organophosphorus pesticides is:

Th e pesticides are also structurally classifi ed 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 are

dimethoxy or diethoxy groups. To cope with resistant insects, the alkyl moieties of R1 and R2

groups were replaced by unsymmetyrical propyl and ethyl groups, respectively, in some pesti￾cides. As X structures, alkyl, alkoxy, alkylthio, aryl, heterocyclic, aryloxy and arylthio groups

can be mentioned.

> Figure 2.1 shows the metabolic pathways of a common thiono type organophosphorus

pesticide having dialkoxy groups (R1 and R2).

Organophosphorus pesticides undergo both enhancement of their toxicity and detoxifi ca￾tion at the same time in mammals. Th e thiono type pesticide (1) shows almost no inhibitory

action on cholinesterase in its unchanged form; it is metabolized by cytochrome P450 (I) into

the phosphate type (2), which reveals toxicity. Th erefore the phosphate type pesticide can

inhibit cholinesterase without any metabolic activation.

As detoxifi cation, dealkylating reaction by enzyme II can be mentioned. Th e P450 and

glutathion are being involved in the enzyme II; the dealkylated form thus produced does not

inhibit acetylcholinesterase.

Th e esterases III, which hydrolyze organophosphorus pesticides, as shown in > Fig. 2.1,

are phosphorotriester hydrolases. Th ere are many diff erent enzymes responsible for such reac￾tions; they are called “ paraoxonase, A-esterase, phosphatase or arylesterase”. Carboxyesterase is