Grain treated with organomercurial or chlorinated hydrocarbon fungicides has been responsible for some spectacular poisonings of epidemic-sized proportions. In 1956, 1960, and again in 1971 to 1972, ethylmercuric and methylmercuric chloride-treated seed grain was consumed by rural people in Iraq, resulting in severe poisoning. In the last and most serious episode, the government of Iraq acknowledged that some 6530 individuals were hospitalized and 459 died. 2•3 An outbreak of poisoning of 100 people occurred in West Pakistan in 1961 following the ingestion of seed wheat with a mixture of phenylmercuric acetate and ethylmercuric chloride. 4 The ingestion of hexachlorobenzene, a chlorinated aromatic hydrocarbon fungicide, in treated grain was responsible for the induction of several thousand cases of acquired toxic cutaneous porphyria in southeastern Turkey between 1955 and 1959.M Large scale poisonings have been caused by the insecticides DDT,' endrin,B.9 parathion, 10 and malathion.11 Parathion was also implicated as the causative agent associated with the poisoning of orchard workers in California. 12 More recently, Kepone~* (1,la,3,3a,4,4a,5b,6-decachloro-octahydro 1,3,4-methano-2H-cyclobuta [c,d] pentalen-2-one) has been implicated in the serious poisoning of chemical workers involved in its manufacture. 13
These are only a few of the many incidents in which agricultural chemicals have been involved in widespread poisonings, but they serve to at least highlight the toxicological problems arising from these agents. It should be noted that many of these incidents were a consequence of abuse, misuse, or ignorance of the chemicals involved. The U.S. Environmental Protection Agency has estimated that each year in the U.S., some 45,000 individuals are poisoned by pesticides; some 3000 serious cases require hospitalization, and an estimated 200 deaths occur. The fatalities primarily occur among people handling pesticides: fanners, crop-dusters, and factory workers involved in the manufacture of these chemicals. 14
As long as man has been combating pests ravaging his crops, he has been interested in anything which would selectively eliminate them. Although some of the early pesticides caused minimal harm to humans on exposure, others were exceedingly dangerous and toxic; early medical literature contains many anecdotal reports of poisonings. Sulfur was used as a fumigant by the Chinese before 1000 BC and, because of its known fungicidal properties, was used in the 1800s in Europe against powdery mildew on grapes. Sulfur is still the major pesticide used in the California vineyards today. In 16th century Japan, poor quality, rendered whale oil was mixed with vinegar and sprayed on rice, this mixture preventing the development of the insects' cuticle. Mineral oils and some petroleum fractions still serve this purpose on certain crops. Inorganic salts including copper sulfate, lime sulfur (mixture of sulfur and lime), copper arsenite (Paris Green), lead arsenate, and copper sulfate mixed with lime (Bordeaux Mixture) all were found to be useful insecticides and fungicides. Extracts from tobacco leaves which contained nicotine were used as the first naturally occurring insecticides. In the late 1800s, arsenic trioxide was used as a • 'weed killer'', particularly for dandelions; in the early 1900s, sulfuric acid (10% v/v) was used as an herbicide when it was discovered that dicotyledonous weeds would absorb the acid, whereas cereal grains, etc., having a smooth, waxy monocotyledon, would not. Fortunately, these toxic agents were replaced shortly after World War II by the chlorophenoxy acid analogs.