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Globally, anticholinesterase insecticides likely kill more people each year than acute poisoning by any other xenobiotic. An estimated 200,000 die in rural Asia where intentional self-harm is common and extremely toxic organic phosphorus insecticides are widely used in agriculture.53,84 An estimated 3000 to 6000 ventilators are constantly required in Asia alone to provide mechanical ventilation to poisoned patients.84 Banning of the most toxic organic phosphorus insecticides has resulted in a 50% decrease in total suicides in Sri Lanka, showing that governmental regulation can be effective.85 Severe occupational or unintentional poisoning also happens where such insecticides are used199 but deaths are generally less common. Anticholinesterase poisoning is less important in industrialized countries where access to toxic insecticides is controlled. However, when anticholinesterase poisoning does occur, patients often require intensive care with long hospital stays.65,155 A further threat is the terrorist use of organic phosphorus insecticides such as parathion to poison a water supply or flour used in bread baking. Such an event may result in many hundreds of casualties being treated by clinicians with limited experience of this potentially lethal toxic syndrome.


The first potent synthetic organic phosphorus anticholinesterase, tetraethylpyrophosphate (TEPP), was synthesized by Clermont in 1854. Clermont's report described the taste of the compound, a remarkable achievement because a few drops should be rapidly fatal.94 In 1932, Lange and Krueger wrote of choking and blurred vision following inhalation of dimethyl and diethyl phosphorofluoridates. This account inspired Schrader in Germany to begin investigating these xenobiotics, initially as insecticides, and later for use in warfare (Chap. 131). During this research, Schrader's group synthesized hundreds of compounds, including the popular insecticide parathion and the chemical warfare agents, sarin, soman, and tabun. Allied scientists were also motivated during the same period by the work, and independently discovered other extremely toxic compounds such as diisopropylphosphofluoridate (DFP).187 Since that time, it is estimated that more than 50,000 organic phosphorus compounds have been synthesized and screened for insecticidal activity, with dozens being produced commercially.34


The history of carbamates was first recorded by Westerners in the 19th century when they observed that the Calabar bean (Physostigma venenosum Balfour) was used in tribal cultural practice in West Africa.95 These beans were imported to Great Britain in 1840, and in 1864 Jobst and Hesse isolated an active alkaloid component they named "physostigmine." Vée and Leven (1865) claimed to have obtained physostigmine in crystallized form, and named it eserine, from ésére, the African term for the "ordeal bean". Physostigmine was first used medicinally to treat glaucoma in 1877.95 In the 1930s, the synthesis of aliphatic esters of carbamic acid led to the development and introduction of carbamate insecticides, marketed initially as fungicides. In 1953 the Union Carbide Corporation developed and first marketed carbaryl, the insecticide being prepared at the plant in Bhopal, India, during the catastrophic release of methyl isocyanate in 1984 (Chap. 2...

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