Toxicological Evaluation of the Anticholinesterase Agents

  • Kenneth P. Dubois
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 15)


The toxicology of the anticholinesterase (anti-ChE) agents has received a great deal of attention during the last twenty years. The intense interest exhibited in this aspect of their biological actions has been stimulated by consideration of their potential value as chemical warfare agents and to a greater extent in recent years by their established value and widespread use as agricultural insecticides. The latter practical application of these compounds has prompted investigation of their toxicity to various laboratory animals as a means of evaluating the possible human health hazards to those engaged in the manufacture and use of these compounds and the consumption of food upon which they have been used. The anti-ChE agents have limited medicinal uses. By far the most important use of these agents at the present time, from the standpoint of both the quantities involved and benefits derived, is for the eradication of destructive insects. High toxicity to insects is thus an essential requirement for anti-ChE agents.


Organophosphorus Compound Chemical Warfare Agent Organophosphorus Insecticide Mammalian Toxicity Carbamic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Augustinsson, K. B.: Mintacol (diethyl p-nitrophenyl phosphate). Svensk farm. T. 57, 261 to 267 (1953).PubMedGoogle Scholar
  2. Aldridge, W. N.: The differentiation of true and pseudocholinesterase by organophosphorus compounds. Biochem. J. 53, 62–67 (1953).PubMedGoogle Scholar
  3. Aldridge, W. N., and J. M. Barnes: Some problems in assessing the toxicity of the “organophosphorus” insecticides towards mammals. Nature (Lond.) 169, 345–352 (1952).CrossRefGoogle Scholar
  4. Bagdon, R. E., and K. P. DuBois: Pharmacologic effects of Chlorthion, Malathion and tetrapropyl dithionopyrophosphate in mammals. Arch. int. Pharmacodyn. 103, 192–199 (1955).Google Scholar
  5. Barnes, J. M., and F. A. Denz: The reaction of rats to diets containing octamethyl pyrophosphoramide (Schradan) and 0,0-diethyl-S-ethylmercaptoethanol thiophosphate (“Systox”). Brit. J. industr. Med. 11, 11–19 (1954).PubMedGoogle Scholar
  6. Bidstrup, P. L., J. A. Bonnell and A. G. Beckett: Paralysis following poisoning by a new organic phosphorus insecticide (Mipafox). Brit. med. J. 1, 1068–1072 (1953).PubMedCrossRefGoogle Scholar
  7. Bombinski, T. J., and K. P. Dubois: Toxicity and mechanism of action of Di-Syston. A.M. A. Arch. industr. Hlth 17, 192–199 (1958).Google Scholar
  8. Brauer, R. W.: Inhibition of the cholinesterase activity of human blood plasma and erythrocyte stromata by alkylated phosphorus compounds. J. Pharmacol. exp. Ther. 92, 162–172 (1948).PubMedGoogle Scholar
  9. Bruce, R. B., J. W. Howard and J. R. Elsea: Toxicity of 0,0-diethyl 0-(2-isopropyl6-methyl-4-pyrimidyl phosphorothioate (Diazinon). J. Agric. food Chem. 3, 1017–1021 (1955).CrossRefGoogle Scholar
  10. Burgen, A. S. V., C. A. Keele and D. Slome: Pharmacological actions of tetraethylpyro-phosphate and hexaethyltetraphosphate. J. Pharmacol. exp. Ther. 96, 396–409 (1949).PubMedGoogle Scholar
  11. Casida, J. E.: Metabolism of organophosphorus insecticides in relation their antiesterase activity, stability, and residual properties. J. Agric. food Chem. 4, 772–785 (1956).CrossRefGoogle Scholar
  12. Casida, J. E., T. C. Allen and M. A. Stahmann: Mammalian conversion of octamethyl pyrophosphoramide to a toxic phosphoramide-N-oxide. J. biol. Chem. 210, 607–616 (1954).PubMedGoogle Scholar
  13. Cook, J. W., J. R. Blake and M. W. Wu Llams: The enzymic hydrolysis of Malathion and its inhibition by EPN and other organic phosphorus compounds. J. Ass. Off. Agric. Chem. 40, 664 665 (1957).Google Scholar
  14. Davies, D. R.: Cholinesterases and the mode of action of some anticholinesterases. J. Pharmacol. 6, 1–26 (1954).CrossRefGoogle Scholar
  15. Davison, A. N.: The conversion of Schradan (OMPA) and Parathion into inhibitors of cholinesterase by mammalian liver. Biochem. J. 61, 203–209 (1955).PubMedGoogle Scholar
  16. Deichmann, W. B., and K. Lampe: Dipterex: Its pharmacologic action and an appraisal of the hazard associated with its use. Univ. Miami School med. Bull. 9, 7–12 (1955).Google Scholar
  17. Deichmann, W. B., W. Pugliese and J. Cassidy: Effects of dimethyl and diethyl paranitrophenyl thio- phosphate on experimental animals. A. M. A. Arch. industr. Hyg. 5, 44–51 (1952).Google Scholar
  18. Deichmann, W. B., and R. Rakoczy: Toxicity and mechanism of action of Systox. A. M. A. Arch. industr. 111th 11, 324–331 (1955).Google Scholar
  19. Diggle, W. M., and J. C. Gage: Cholinesterase inhibition in vivo by 0,0-diethyl 0-p-nitrophenyl thiophosphate (Parathion, E 605). Biochem. J. 49, 491–494 (1951).PubMedGoogle Scholar
  20. Distefano, V., L. Hurwitz, W. F. Neuman and H. C. Hodge: Coramine (Nikethamide) as adjuvant to atropine in treatment of poisoning by EPN (ethyl p-nitrophenyl thionobenzenephosphonate). Proc. Soc. exp. Biol. (N. Y.) 78, 712–713 (1951).CrossRefGoogle Scholar
  21. Doull, J., and K. P. Dubois: Toxicity and anticholinesterase action of tetra-n-propyl dithionopyrophosphate. J. Pharmacol. exp. Ther. 106, 382 (1952).Google Scholar
  22. DuBois, K. P.: Potentiation of the toxicity of organophosphorus compounds. Advances in Pest Control Research, Vol. 4. In press. New York: Interscience Publishers 1961.Google Scholar
  23. DuBois, K. P., and K. W. Cochran: Inhibition of cholinesterase by dimethylamino fluorophosphate. Fed. Proc. 10, 292 (1951).Google Scholar
  24. DuBois, K. P., and J. M. CooN: Toxicology of organic phosphorus-containing insecticides to mammals. Arch. industr. Hyg. 6, 9–13 (1952).Google Scholar
  25. DuBois, K. P., and G. J. Cotter: Studies on the toxicity and mechanism of action of Dipterex. A. M. A. Arch. industr. Hlth 11, 53–60 (1955).Google Scholar
  26. DuBois, K. P. J. DoULL and J. M. COON: Toxicity and mechanism of action of p-nitro-phenyl-diethylthionophosphate (E 605). Fed. Proc. 7, 216 (1948).PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1963

Authors and Affiliations

  • Kenneth P. Dubois

There are no affiliations available

Personalised recommendations