113: Insecticides: Organic Phosphorus Compounds and Carbamates

HISTORY AND EPIDEMIOLOGY

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.¹¹¹ 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 agents, initially as pesticides, and later for use in warfare (Chap. 132). During this research, Schrader’s group synthesized hundreds of compounds, including the popular pesticide parathion and the chemical weapons 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).²¹⁴ Since that time, it is estimated that more than 50,000 organic phosphorus compounds have been synthesized and screened for pesticidal activity, with dozens being produced commercially.⁴⁰

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.¹¹² 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 1877.¹¹² In the 1930s, the synthesis of aliphatic esters of carbamic acid led to the development and introduction of carbamate pesticides, marketed initially as ­fungicides. In 1953, the Union Carbide Corporation developed and marketed carbaryl, the insecticide being prepared at the plant in Bhopal, India, during the catastrophic release of methyl isocyanate in 1984 (Chap. 2).^8,193

Organic phosphorus compounds (OPs) and carbamates are the two groups of cholinesterase-inhibiting pesticides that commonly produce human toxicity. Although the term organophosphate is often used in both clinical practice and in the literature to refer to all phosphorus-containing pesticides that inhibit cholinesterase, phosphates are compounds in which the P atom is surrounded by four O atoms, and there are other derivatives of phosphoric and phosphonic acids such as phosphonates that can exhibit cholinesterase inhibition. Some chemicals, such as parathion, contain thioesters, whereas others are vinyl esters. Those cholinesterase-inhibiting (anticholinesterase) insecticides that contain phosphorus will be collectively termed organic phosphorus compounds in this chapter. Those that contain the OC=ON linkage will be termed carbamates.

Anticholinesterase pesticides are broadly grouped according to their toxicity by the World Health Organization’s Classification of Pesticides into five groups: Class Ia “Extremely hazardous,” Class Ib “Highly hazardous,” Class II “Moderately hazardous,” Class III “Slightly hazardous,” and “Active ingredients unlikely to present acute hazard in normal use” (Table 113–1). This classification is based upon comparative rat oral LD₅₀ data of the ...