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.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ALDRIDGE W. N. [The inhibition of erythrocyte cholinesterase by tri-esters of phosphoric acid. III. The nature of the inhibitory process]. Biochem J. 1953 Jun;54(3):442–448. doi: 10.1042/bj0540442. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GOLDBERG M. E., JOHNSON H. E., KNAAK J. B., SMYTH H. F., Jr PSYCHOPHARMACOLOGICAL EFFECTS OF REVERSIBLE CHOLINESTERASE INHIBITION INDUCED BY N-METHYL 3-ISOPROPYL PHENYL CARBAMATE (COMPOUND 10854). J Pharmacol Exp Ther. 1963 Aug;141:244–252. [PubMed] [Google Scholar]
- Thompson W. R. USE OF MOVING AVERAGES AND INTERPOLATION TO ESTIMATE MEDIAN-EFFECTIVE DOSE: I. Fundamental Formulas, Estimation of Error, and Relation to Other Methods. Bacteriol Rev. 1947 Jun;11(2):115–145. [PMC free article] [PubMed] [Google Scholar]
- WILSON I. B., HARRISON M. A., GINSBURG S. Carbamyl derivatives of acetylcholinesterase. J Biol Chem. 1961 May;236:1498–1500. [PubMed] [Google Scholar]
- WILSON I. B., HATCH M. A., GINSBURG S. Carbamylation of acetvlcholinesterase. J Biol Chem. 1960 Aug;235:2312–2315. [PubMed] [Google Scholar]
