VALUE OF ED5o TESTING IN ASSESSING HAZARDS OF ACUTE POISONING BY CARBAMATES AND ORGANOPHOSPHATES BY

It is shown from the kinetics of inhibition of cholinesterase by N-methylcarbamates and organo-phosphates that the LD50 dose is likely to be a much greater multiple of the dose causing signs of poisoning in 50%-of the animals (the ED50) for the carbamates than for the organophosphates. The expected difference was demonstrated by a comparison of the LD50s and ED50s, intravenous and intramuscular, of five carbamates (2-isopropoxyphenyl N-methylcarbamate, 3-isopropylphenyl N-methylcarbamate, 6-chloro-3,4-xylyl N-methylcarbamate, 3,4,5-trimethylphenyl N-methyl-carbamate, and 3-methyl-5-isopropylphenyl N-methylcarbamate) and two organophosphorus compounds (diethyl 4-nitrophenyl phosphate and dimethyl 4-nitrophenyl phosphate). The slightest evoked tremor was chosen as the most reliable sign of poisoning from which to estimate the ED50 values. Carbamates gave much greater LD50/ED50 ratios than organophosphorus compounds. It is likely that occupational exposure to carbamates will produce incapacitating symptoms at doses well below lethal levels. Two groups of insecticides with anticholinesterase action are in widespread use-organophosphorus compounds and N-methylcarbamate esters. Ther