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INTRODUCTION

Globally and historically, pesticide poisoning has killed approximately 150,000 people each year, with anticholinesterase compounds responsible for about two-thirds of these deaths. Most deaths occur in rural Asia where intentional self-harm is common and where highly toxic organic phosphorus (OP) insecticides are still widely used in agriculture and available in households at times of stress.67,104 Severe occupational or unintentional poisoning also happens where these highly toxic insecticides are used,241 but deaths are generally less common.

Anticholinesterase poisoning is uncommon in industrialized countries where access to toxic pesticides is more controlled and a far smaller proportion of the population works in agriculture. However, when anticholinesterase poisoning does occur, patients often require intensive care with long hospital stays.85,117,199 A further threat is the terrorist use of OP insecticides such as parathion to poison a water supply or flour used in bread baking. Food-borne poisoning occurs regularly in rural Asia;57,180 such poisoning occurring in industrialized countries would result in hundreds of casualties being treated by clinicians with little experience of this frequently lethal toxic syndrome.

HISTORY AND EPIDEMIOLOGY

The first potent synthetic organic phosphorus (OP) anticholinesterase, ­tetraethylpyrophosphate (TEPP), was synthesized by Clermont in 1854. In 1932, Lange and Krueger wrote of choking and blurred vision following ­inhalation of dimethyl and diethyl phosphorofluoridates. Their account inspired Schrader in Germany to begin investigating these compounds, initially as pesticides, and later as warfare agents (Chap. 126). During this research, Schrader’s group synthesized hundreds of compounds, including the pesticide parathion and the chemical weapons sarin, soman, and tabun.115 Since that time, it is estimated that more than 50,000 OP compounds have been synthesized and screened for pesticidal activity, with ­dozens being produced commercially.39

Carbamates were first identified by Western scientists in the 19th century when the use of the Calabar bean (Physostigma venenosum) was recognized in tribal cultural practice in West Africa.114 In 1864, Jobst and Hesse isolated an active alkaloid component they named physostigmine, which was used medicinally to treat glaucoma in 1877.114 The synthesis of aliphatic esters of carbamic acid in the 1930s led to the development of carbamate pesticides, marketed initially as fungicides. In 1953 the Union Carbide Corporation first marketed carbaryl, the insecticide being prepared at the plant in Bhopal during the catastrophic release of methyl isocyanate in 1984 (Chap. 2).7

Although the term organophosphate is often used in both clinical practice and literature to refer to all phosphorus-containing pesticides that inhibit cholinesterase, phosphates are compounds in which the phosphorus atom is surrounded by 4 oxygen atoms, which is not the case for most OP compounds. Some chemicals, such as parathion, contain thioesters, whereas others are vinyl esters. Those cholinesterase-inhibiting (anticholinesterase) insecticides that contain phosphorus are collectively termed organic phosphorus compounds in this chapter. Those that ...

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