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The Oximes and Organophosphate Poisoning

The Oximes and Organophosphate Poisoning Abstract Since the insects began fighting back in 1947,1 the war against them has demanded an increasingly diversified armamentarium, and the organic phosphate insecticides have played an important part in the battle. Unfortunately, this group of compounds, an outgrowth of wartime investigation of the chemically related nerve gases, are poisonous to man as well as to insects. For toxicologic purposes, they may be roughly divided into the highly toxic group, exemplified by parathion (O,O-diethyl-O-p-nitrophenyl thiophosphate) and TEPP (tetraethyl pyrophosphate), and those with less toxicity, such as malathion (O,O-dimethyl dithiophosphate of diethyl mercaptosuccinate). The former group is used primarily for agricultural insect control, whereas the latter compound has been approved for household use as well. The incidence of human poisoning by organic phosphorus insecticides appears to be increasing in frequency. In 1957 in California3 there were 229 cases of occupational disease ascribed to organic phosphate insecticides, including one References 1. Busvine, J. R.: Symposium on Insecticides and Public Health: Recent Trends; (A) The Problem of Insecticide Resistance , Roy. Soc. Health 79:505, 1959.Crossref 2. Grob, D.: The Manifestations and Treatment of Poisoning Due to Nerve Gas and Other Organic Phosphate Anticholinesterase Compounds , A.M.A. Arch. Intern. Med. 98:221, 1956.Crossref 3. Kleinman, G. D.; West, I., and Augustine, M. A.: Occupational Disease in California Attributed to Pesticides and Agricultural Chemicals , Arch. Environ. Health 1:118, 1960.Crossref 4. Wislicki, L.: Personal communication to the authors. 5. Toivonen, T.; Ohela, K., and Kaipainen, W. J.: Parathion Poisoning. Increasing Frequency in Finland, Lancet 2:175, 1959.Crossref 6. Namba, T., and Hiraki, K.: PAM (Pyridine-2-Aldoxime Methiodide) Therapy for Alkylphosphate Poisoning , J.A.M.A. 166:1834, 1958.Crossref 7. Kanagaratnam, K.; Boon, W. H., and Hoh, T. K.: Parathion Poisoning from Contaminated Barley , Lancet 1:538, 1960.Crossref 8. Wolfe, H. R.; Elliott, J. W., and Durham, W. F.: The Trend of DDT and Parathion Residues on Apples Grown in Central Washington , J. Econ. Entomol. 52:1053, 1959. 9. Stevens Point [Wis.] Daily Journal, July 25, 1960. 10. Florida State Board of Health, Broward County Health Department: Personal communication to the authors. 11. DuBois, K. P.; Doull, J.; Salerno, P. R., and Coon, J. M.: Studies on the Toxicity and Mechanism of Action of p-Nitrophenyl Diethyl Thiono phosphate (Parathion) , J. Pharmacol. Exp. Ther. 95:79, 1949. 12. Grob, D., and Johns, R. J.: Use of Oximes in the Treatment of Intoxication by Anticholinesterase Compounds in Normal Subjects , Amer. J. Med. 24:497, 1958.Crossref 13. Mattison, A. M., and Sedlak, V. A.: Ether-Extractable Urinary Phosphates in Man and Rats Derived from Malathion and Similar Compounds , Agric. Food Chem. 8:107, 1960.Crossref 14. Elliott, J. W.; Walker, R. C.; Penick, A. E., and Durham, W. F.: A Sensitive Procedure for Urinary p-Nitrophenol Determination as a Measure of Exposure to Parathion , J. Agric. Food Chem. 8:111, 1960.Crossref 15. Durham, W. F.: Personal communication to the authors. 16. Namba, T.: Personal communication to the authors. 17. Nachmansohn, D., and Feld, E. A.: Studies on Cholinesterase: IV. On the Mechanism of Diisopropyl Fluorophosphate Action in Vivo , J. Biol. Chem. 171:715, 1947. 18. Jones, H. W.; Meyer, B. J., and Karel, L.: The Relationship of Cholinesterase Inhibiting Activity to the Toxicity of Some Organic Phosphorus Compounds , J. Pharmacol. Exp. Ther. 94:215, 1948. 19. Naess, K.: The Specificity of Diisoproypylfluorophosphate , Acta. Pharmacol. (Kbh.) 12:154, 1956.Crossref 20. Murtha, E. F.; McNamara, B. F.; Edberg, L. J.; Bergner, A. D., and Wills, J. H.: Studies on the Pharmacology of Tetraethylpyrophosphate , J. Pharmacol. Exp. Ther. 115:291, 1955. 21. Groblewski, G. E.; McNamara, B. P., and Wills, J. H.: Stimulation of Denervated Muscle by DVP and Related Compounds , J. Pharmacol. Exp. Ther. 118:116, 1956. 22. Myers, D. K.; Mendel, B.; Gersmann, H. R., and Ketelaar, J. A. A.: Oxidation of Thiophosphate Insecticides in the Rat , Nature 170:805, 1952.Crossref 23. Davison, A. N.: The Conversion of Schraden (OMPA) and Parathion into Inhibitors of Cholinesterase by Mammalian Liver , Biochem. J. 61:203, 1955. 24. Wilson, I. B.: Anticholinesterase: XI. Reversibility of the Inhibition by Tetraethyl Pyrophosphate , J. Biol. Chem. 190:111, 1951. 25. Wilson, I. B.: Acetylcholinesterase: XIII. Reactivation of Alkylphosphate-Inhibited Enzyme , J. Biol. Chem. 199:113, 1952. 26. Wilson, I. B., and Ginsberg, S.: A Powerful Reactivator of Aklylphosphate-Inhibited Acetylcholinesterase , Biochim. Biophys. Acta 18:168, 1955.Crossref 27. Kewitz, H., and Wilson, I. B.: A Specific Antidote Against Lethal Alkyl-Phosphate Intoxication , Arch. Biochem. Biophys. 60:261, 1956.Crossref 28. Askew, B. M.; Davies, D. R.; Green, A. T., and Holmes, R.: The Nature of the Toxicity of the 2-Oxo-Oximes , Brit. J. Pharmacol. 11:424, 1956. 29. Hobbiger, F.; O'Sullivan, D. G., and Sadler, P. W.: New Potent Reactivators of Acetylcholinesterase Inhibited by Tetraethyl Pyrophosphate , Nature 182:1498, 1958.Crossref 30. Grob, D., and Johns, R. J.: Use of Oximes in the Treatment of Intoxication by Anticholinesterase Compounds in Patients with Myasthenia Gravis , Amer. J. Med. 24:512, 1958.Crossref 31. Rosen, F. S.: Parathion , New Engl. J. Med. 262:1243, 1960.Crossref 32. Hayes, W. J. (Communicable Disease Center): Personal communication to the authors. 33. Quinby, G. E., and Clappison, G. B.: Biochemical Studies of a Near-Fatal Case of Parathion Poisoning Treated with PAM and Atropine Sulfate, to be published. 34. Namba, T., et al.: The Effectiveness of Pyridine-2-Aldoxime Methiodide (PAM) Against Parathion Poisoning in Thirty-Nine Human Cases , Naiki No Ryoiki 6:86, 1958 (translation by personal communication). 35. Wilson, I. B.; Ginsberg, S., and Quan, E.: Molecular Complementariness as Basis for Reactivation of Alkylphosphate-Inhibited Enzyme , Arch. Biochem. 77:286, 1958.Crossref 36. Poziomek, E. J.; Hackley, B. E., and Steinberg, G. M.: Pyridinium Aldoximes , J. Organic Chem. 23:714, 1958.Crossref 37. Askew, B. M.: Oximes and Hydroxamic Acids as Antidotes in Anticholinesterase Poisoning , Brit. J. Pharmacol. 11:417, 1956. 38. Wills, J. H.: Recent Studies of Organic Phosphate Poisoning , Fed. Proc. 18:1020, 1959. 39. Funckes, A. J.: Treatment of Severe Parathion Poisoning with 2-Pyridine Aldoxime Methiodide , Arch. Environ. Health 1:404, 1960.Crossref 40. Kewitz, H.; Wilson, I. B., and Nachmansohn, D.: A Specific Antidote Against Lethal Alkylphosphate Intoxication: II. Antidotal Properties , Arch. Biochem. Biophys. 64:456, 1956.Crossref 41. Hobbiger, F.: Protection Against the Lethal Effects of Organo-Phosphates by Pyridine-2-Aldoxime Methiodide , Brit. J. Pharmacol. 12:438, 1957. 42. Brown, R. V.; Kunkel, R. M.; Somers, L. M., and Wills, J. H.: Pyridine-2-Aldoxime Methiodide in the Treatment of Sarin and Tabun Poisoning, with Notes on Its Pharmacology , J. Pharmacol. 120:276, 1957. 43. O'Leary, J. F.; Harrison, B.; Groblewski, G., and Wills, J. H.: The Effect of 2-Formyl-1-Methylpyridinium Iodide Oxime (2-PAM) on Reactivation of Tissue Cholinesterase Following Poisoning by a Certain Phosphate Anticholinesterase , Fed. Proc. 18:430, 1959. 44. Kewitz, H., and Nachmansohn, D.: A Specific Antidote Against Lethal Alkylphosphate Intoxication: IV. Effect in Brain , Arch. Biochem. Biophys. 66:271, 1957. 45. Wilson, I. B.: Designing of a New Drug with Antidotal Properties Against the Nerve Gas Sarin , Biochim. Biophys. Acta 27:196, 1958.Crossref 46. Hobbiger, F.: Effect of Nicotinhydroxamic Acid Methiodide on Human Plasma Cholinesterase Inhibited by Organophosphates Containing a Di-alkylphosphate Group , Brit. J. Pharmacol. 10:356, 1955. 47. Hobbiger, F.: Chemical Reactivation of Phosphorylated Human and Bovine True Cholinesterase , Brit. J. Pharmacol. 11:295, 1956. 48. Blaber, R. C., and Creasey, N. H.: The Recovery of Brain and Erythrocyte Cholinesterase Activity Following Organo-Phosphate Poisoning , Biochem. J. 71:7P, 1959. 49. Namba, T., et al.: PAM (Pyridine-2-Aldoxime Methiodide) as a Prophylactic for Parathion Poisoning , Naiki No Ryoiki 6:442, 1958 (translated by personal communication). 50. Namba, T., et al.: Toxicity of PAM (Pyridine-2-Aldoxime Methiodide) , Naiki No Ryoiki 6:437, 1958 (translated by personal communication). 51. Lehman, R. A. (Campbell Pharmaceuticals, Inc.): Personal communication to the authors. 52. Witter, R. F. (Communicable Disease Center): Personal communication to the authors. 53. Wilson, I. B., and Ginsberg, S.: Reactivation of Alkylphosphate-Inhibited Anticholinesterase by Bis-Quaternary Derivatives of 2-PAM and 4-PAM , Biochem. Pharmacol. 1:200, 1959.Crossref 54. Hobbiger, F., and Sadler, P. W.: Protection by Oximes of Bis-Pyridimum Ion Against Lethal Diisopropyl Phosphonofluoridate Poisoning , Nature 182:1672, 1958.Crossref 55. Fleisher, J. H.; Michel, H. O.; Yates, L., and Harrison, C. S.: 1,1'-Trimethylene Bis-(4-Formylpyridinium Bromide) Dioxime (TMB-4) and 2-Pyridine Aldoxime Methiodide (2-PAM) as Adjuvants to Atropine in the Treatment of Anticholinesterase Poisoning , J. Pharmacol. 129: 31, 1960. 56. Combes, M. A., and Read, W. T.: Organic Phosphate Ester Poisoning: A New Specific Antidote, presented at the 71st Annual Meeting of the American Pediatric Society, Atlantic City, N.J., May 2-3, 1961. 57. Wilson, I. B.; Hatch, M. A., and Ginsberg, S.: Carbamylation of Acetylcholinesterase , J. Biol. Chem. 235:2312, 1960. 58. Wilson, I. B.; Harrison, M. A., and Ginsberg, S.: Carbamyl Derivatives of Acetylcholinesterase , J. Biol. Chem. 236:1498, 1961. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Diseases of Children American Medical Association

The Oximes and Organophosphate Poisoning

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American Medical Association
Copyright
Copyright © 1962 American Medical Association. All Rights Reserved.
ISSN
0002-922X
DOI
10.1001/archpedi.1962.02080020191015
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Abstract

Abstract Since the insects began fighting back in 1947,1 the war against them has demanded an increasingly diversified armamentarium, and the organic phosphate insecticides have played an important part in the battle. Unfortunately, this group of compounds, an outgrowth of wartime investigation of the chemically related nerve gases, are poisonous to man as well as to insects. For toxicologic purposes, they may be roughly divided into the highly toxic group, exemplified by parathion (O,O-diethyl-O-p-nitrophenyl thiophosphate) and TEPP (tetraethyl pyrophosphate), and those with less toxicity, such as malathion (O,O-dimethyl dithiophosphate of diethyl mercaptosuccinate). The former group is used primarily for agricultural insect control, whereas the latter compound has been approved for household use as well. The incidence of human poisoning by organic phosphorus insecticides appears to be increasing in frequency. In 1957 in California3 there were 229 cases of occupational disease ascribed to organic phosphate insecticides, including one References 1. Busvine, J. R.: Symposium on Insecticides and Public Health: Recent Trends; (A) The Problem of Insecticide Resistance , Roy. Soc. Health 79:505, 1959.Crossref 2. Grob, D.: The Manifestations and Treatment of Poisoning Due to Nerve Gas and Other Organic Phosphate Anticholinesterase Compounds , A.M.A. Arch. Intern. Med. 98:221, 1956.Crossref 3. Kleinman, G. D.; West, I., and Augustine, M. A.: Occupational Disease in California Attributed to Pesticides and Agricultural Chemicals , Arch. Environ. Health 1:118, 1960.Crossref 4. Wislicki, L.: Personal communication to the authors. 5. Toivonen, T.; Ohela, K., and Kaipainen, W. J.: Parathion Poisoning. Increasing Frequency in Finland, Lancet 2:175, 1959.Crossref 6. Namba, T., and Hiraki, K.: PAM (Pyridine-2-Aldoxime Methiodide) Therapy for Alkylphosphate Poisoning , J.A.M.A. 166:1834, 1958.Crossref 7. Kanagaratnam, K.; Boon, W. H., and Hoh, T. K.: Parathion Poisoning from Contaminated Barley , Lancet 1:538, 1960.Crossref 8. Wolfe, H. R.; Elliott, J. W., and Durham, W. F.: The Trend of DDT and Parathion Residues on Apples Grown in Central Washington , J. Econ. Entomol. 52:1053, 1959. 9. Stevens Point [Wis.] Daily Journal, July 25, 1960. 10. Florida State Board of Health, Broward County Health Department: Personal communication to the authors. 11. DuBois, K. P.; Doull, J.; Salerno, P. R., and Coon, J. M.: Studies on the Toxicity and Mechanism of Action of p-Nitrophenyl Diethyl Thiono phosphate (Parathion) , J. Pharmacol. Exp. Ther. 95:79, 1949. 12. Grob, D., and Johns, R. J.: Use of Oximes in the Treatment of Intoxication by Anticholinesterase Compounds in Normal Subjects , Amer. J. Med. 24:497, 1958.Crossref 13. Mattison, A. M., and Sedlak, V. A.: Ether-Extractable Urinary Phosphates in Man and Rats Derived from Malathion and Similar Compounds , Agric. Food Chem. 8:107, 1960.Crossref 14. Elliott, J. W.; Walker, R. C.; Penick, A. E., and Durham, W. F.: A Sensitive Procedure for Urinary p-Nitrophenol Determination as a Measure of Exposure to Parathion , J. Agric. Food Chem. 8:111, 1960.Crossref 15. Durham, W. F.: Personal communication to the authors. 16. Namba, T.: Personal communication to the authors. 17. Nachmansohn, D., and Feld, E. A.: Studies on Cholinesterase: IV. On the Mechanism of Diisopropyl Fluorophosphate Action in Vivo , J. Biol. Chem. 171:715, 1947. 18. Jones, H. W.; Meyer, B. J., and Karel, L.: The Relationship of Cholinesterase Inhibiting Activity to the Toxicity of Some Organic Phosphorus Compounds , J. Pharmacol. Exp. Ther. 94:215, 1948. 19. Naess, K.: The Specificity of Diisoproypylfluorophosphate , Acta. Pharmacol. (Kbh.) 12:154, 1956.Crossref 20. Murtha, E. F.; McNamara, B. F.; Edberg, L. J.; Bergner, A. D., and Wills, J. H.: Studies on the Pharmacology of Tetraethylpyrophosphate , J. Pharmacol. Exp. Ther. 115:291, 1955. 21. Groblewski, G. E.; McNamara, B. P., and Wills, J. H.: Stimulation of Denervated Muscle by DVP and Related Compounds , J. Pharmacol. Exp. Ther. 118:116, 1956. 22. Myers, D. K.; Mendel, B.; Gersmann, H. R., and Ketelaar, J. A. A.: Oxidation of Thiophosphate Insecticides in the Rat , Nature 170:805, 1952.Crossref 23. Davison, A. N.: The Conversion of Schraden (OMPA) and Parathion into Inhibitors of Cholinesterase by Mammalian Liver , Biochem. J. 61:203, 1955. 24. Wilson, I. B.: Anticholinesterase: XI. Reversibility of the Inhibition by Tetraethyl Pyrophosphate , J. Biol. Chem. 190:111, 1951. 25. Wilson, I. B.: Acetylcholinesterase: XIII. Reactivation of Alkylphosphate-Inhibited Enzyme , J. Biol. Chem. 199:113, 1952. 26. Wilson, I. B., and Ginsberg, S.: A Powerful Reactivator of Aklylphosphate-Inhibited Acetylcholinesterase , Biochim. Biophys. Acta 18:168, 1955.Crossref 27. Kewitz, H., and Wilson, I. B.: A Specific Antidote Against Lethal Alkyl-Phosphate Intoxication , Arch. Biochem. Biophys. 60:261, 1956.Crossref 28. Askew, B. M.; Davies, D. R.; Green, A. T., and Holmes, R.: The Nature of the Toxicity of the 2-Oxo-Oximes , Brit. J. Pharmacol. 11:424, 1956. 29. Hobbiger, F.; O'Sullivan, D. G., and Sadler, P. W.: New Potent Reactivators of Acetylcholinesterase Inhibited by Tetraethyl Pyrophosphate , Nature 182:1498, 1958.Crossref 30. Grob, D., and Johns, R. J.: Use of Oximes in the Treatment of Intoxication by Anticholinesterase Compounds in Patients with Myasthenia Gravis , Amer. J. Med. 24:512, 1958.Crossref 31. Rosen, F. S.: Parathion , New Engl. J. Med. 262:1243, 1960.Crossref 32. Hayes, W. J. (Communicable Disease Center): Personal communication to the authors. 33. Quinby, G. E., and Clappison, G. B.: Biochemical Studies of a Near-Fatal Case of Parathion Poisoning Treated with PAM and Atropine Sulfate, to be published. 34. Namba, T., et al.: The Effectiveness of Pyridine-2-Aldoxime Methiodide (PAM) Against Parathion Poisoning in Thirty-Nine Human Cases , Naiki No Ryoiki 6:86, 1958 (translation by personal communication). 35. Wilson, I. B.; Ginsberg, S., and Quan, E.: Molecular Complementariness as Basis for Reactivation of Alkylphosphate-Inhibited Enzyme , Arch. Biochem. 77:286, 1958.Crossref 36. Poziomek, E. J.; Hackley, B. E., and Steinberg, G. M.: Pyridinium Aldoximes , J. Organic Chem. 23:714, 1958.Crossref 37. Askew, B. M.: Oximes and Hydroxamic Acids as Antidotes in Anticholinesterase Poisoning , Brit. J. Pharmacol. 11:417, 1956. 38. Wills, J. H.: Recent Studies of Organic Phosphate Poisoning , Fed. Proc. 18:1020, 1959. 39. Funckes, A. J.: Treatment of Severe Parathion Poisoning with 2-Pyridine Aldoxime Methiodide , Arch. Environ. Health 1:404, 1960.Crossref 40. Kewitz, H.; Wilson, I. B., and Nachmansohn, D.: A Specific Antidote Against Lethal Alkylphosphate Intoxication: II. Antidotal Properties , Arch. Biochem. Biophys. 64:456, 1956.Crossref 41. Hobbiger, F.: Protection Against the Lethal Effects of Organo-Phosphates by Pyridine-2-Aldoxime Methiodide , Brit. J. Pharmacol. 12:438, 1957. 42. Brown, R. V.; Kunkel, R. M.; Somers, L. M., and Wills, J. H.: Pyridine-2-Aldoxime Methiodide in the Treatment of Sarin and Tabun Poisoning, with Notes on Its Pharmacology , J. Pharmacol. 120:276, 1957. 43. O'Leary, J. F.; Harrison, B.; Groblewski, G., and Wills, J. H.: The Effect of 2-Formyl-1-Methylpyridinium Iodide Oxime (2-PAM) on Reactivation of Tissue Cholinesterase Following Poisoning by a Certain Phosphate Anticholinesterase , Fed. Proc. 18:430, 1959. 44. Kewitz, H., and Nachmansohn, D.: A Specific Antidote Against Lethal Alkylphosphate Intoxication: IV. Effect in Brain , Arch. Biochem. Biophys. 66:271, 1957. 45. Wilson, I. B.: Designing of a New Drug with Antidotal Properties Against the Nerve Gas Sarin , Biochim. Biophys. Acta 27:196, 1958.Crossref 46. Hobbiger, F.: Effect of Nicotinhydroxamic Acid Methiodide on Human Plasma Cholinesterase Inhibited by Organophosphates Containing a Di-alkylphosphate Group , Brit. J. Pharmacol. 10:356, 1955. 47. Hobbiger, F.: Chemical Reactivation of Phosphorylated Human and Bovine True Cholinesterase , Brit. J. Pharmacol. 11:295, 1956. 48. Blaber, R. C., and Creasey, N. H.: The Recovery of Brain and Erythrocyte Cholinesterase Activity Following Organo-Phosphate Poisoning , Biochem. J. 71:7P, 1959. 49. Namba, T., et al.: PAM (Pyridine-2-Aldoxime Methiodide) as a Prophylactic for Parathion Poisoning , Naiki No Ryoiki 6:442, 1958 (translated by personal communication). 50. Namba, T., et al.: Toxicity of PAM (Pyridine-2-Aldoxime Methiodide) , Naiki No Ryoiki 6:437, 1958 (translated by personal communication). 51. Lehman, R. A. (Campbell Pharmaceuticals, Inc.): Personal communication to the authors. 52. Witter, R. F. (Communicable Disease Center): Personal communication to the authors. 53. Wilson, I. B., and Ginsberg, S.: Reactivation of Alkylphosphate-Inhibited Anticholinesterase by Bis-Quaternary Derivatives of 2-PAM and 4-PAM , Biochem. Pharmacol. 1:200, 1959.Crossref 54. Hobbiger, F., and Sadler, P. W.: Protection by Oximes of Bis-Pyridimum Ion Against Lethal Diisopropyl Phosphonofluoridate Poisoning , Nature 182:1672, 1958.Crossref 55. Fleisher, J. H.; Michel, H. O.; Yates, L., and Harrison, C. S.: 1,1'-Trimethylene Bis-(4-Formylpyridinium Bromide) Dioxime (TMB-4) and 2-Pyridine Aldoxime Methiodide (2-PAM) as Adjuvants to Atropine in the Treatment of Anticholinesterase Poisoning , J. Pharmacol. 129: 31, 1960. 56. Combes, M. A., and Read, W. T.: Organic Phosphate Ester Poisoning: A New Specific Antidote, presented at the 71st Annual Meeting of the American Pediatric Society, Atlantic City, N.J., May 2-3, 1961. 57. Wilson, I. B.; Hatch, M. A., and Ginsberg, S.: Carbamylation of Acetylcholinesterase , J. Biol. Chem. 235:2312, 1960. 58. Wilson, I. B.; Harrison, M. A., and Ginsberg, S.: Carbamyl Derivatives of Acetylcholinesterase , J. Biol. Chem. 236:1498, 1961.

Journal

American Journal of Diseases of ChildrenAmerican Medical Association

Published: Feb 1, 1962

References