Value of ED50 testing in assessing hazards of acute poisoning by carbamates and organophosphates

Abstract

It is shown from the kinetics of inhibition of cholinesterase by N-methylcarbamates and organophosphates 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-methylcarbamate, 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.