A study was undertaken to determine the role of S-methyl isomer formation in the toxicity of malathion and fenitrothion water-dispersible powders held in tropical storage. The S-methyl isomers of malathion and fenitrothion were synthesized, high-pressure liquid chromatography and gas-liquid chromatography methods were developed for their determination in powder formulations. Samples of malathion water-dispersible powders returned from storage in tropical countries were found to have S-methyl isomer contents as high as 3.3% and rat oral LD50 values of 500 mg/kg compared to fresh powders containing less than 0.3% of the isomer and having rat oral LD^v alues of above 2500 mg/kg. Increasing S-methyl isomer content and toxicity were also observed in malathion water-dispersible powders held at elevated temperatures in the laboratory. The rate of formation of S-methyl isomer of malathion was found to depend upon the type of "inert" ingredients in the formulation. No increase in toxicity was observed in fenitrothion powders stored at elevated temperatures although the S-methyl isomer was formed in concentrations up to 1%. By 1975 some 24 species of anopheline mosquitoes were reported to be resistant to DDT (World Health Organization, 1976). This has forced many countries to seek alternate pesticides for use in their malaria control programs. The most promising alternate compounds are malathion, fenitrothion, and propoxur. The Government of Pakistan began to use malathion, water-dispersible powder, on a large scale for malaria control in 1976. Shortly after initiation of the spraying program, many spraymen became ill and five died from pesticide intoxication (Baker et al., 1978). Chemical and toxicological analyses of samples of powders returned from the field showed that powders furnished by two companies had high S-methyl isomer content (>2.0%) and high mammalian toxicity (rat oral LDsq's <1000 mg/kg). Samples furnished by a third company had low S-methyl isomer content (<0.3%) and relatively low mammalian toxicity (rat oral LD50's >1500 mg/kg). The purpose of this study was to develop improved methods of analysis for the S-methyl isomer content of malathion and fenitrothion powders and to determine the relationship of toxicity to S-methyl isomer content. EXPERIMENTAL SECTION Reagents. The malathion, analytical standard (99.1%), technical grade, and 50% water-dispersible powder, as well as fenitrothion, analytical standard (97.5%) were obtained from the American Cyanamid Co., Princeton, NJ. Purified malathion was prepared by crystallizing the technical grade material three times from methanol at -50 °C. Fenitrothion, technical grade, and 40% water-dispersible powder
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