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Repeated small doses of a neurotoxic organophosphate

Monitoring of neurotoxic esterase in brain and spinal cord

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Abstract

The effects of small repeated oral doses of mono-2-cresyl diphenyl phosphate (MOCP, 2.5 mg/kg/day) on hen brain and spinal cord neurotoxic esterase (NTE) were measured. The enzyme levels were depressed to about 40% and 55% of normal respectively and maintained at that level for 8 weeks. No clinical and only doubtful histological signs of neuropathy were detected. Neuropathy could be precipitated by depressing the level to < 20% either with a single high dose (50 mg/kg), or by an increase of the repeated dose level to 5 mg/kg/day. There was no correlation between inhibition of NTE in the nervous tissue and the “NTE-like” activity in lymphocytes. “NTE-like” activity in spleen was consistently inhibited but to a lesser extent than that in the brain or spinal cord. Brain AChE and BuChE were not affected.

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References

  • Abou-Donia MB, Preissig S (1976) Delayed neurotoxicity from continuous low-dose oral administration of Leptophos to hens. Toxicol Appl Pharmacol 38: 595–608

    Google Scholar 

  • Barnes JM (1975) Assessing hazards from prolonged and repeated exposure to low doses of toxic substances. Br Med Bull 31: 196–200

    Google Scholar 

  • Dudek BR, Barth M, Gephart L, Huggins J, Richardson RJ (1979) Correlation of brain and lymphocyte neurotoxic esterase inhibition in the adult hen following dosing with neurotoxic compounds. Toxicol Appl Pharmacol 48: A198

    Google Scholar 

  • Ellman GL, Courtney DK, Andres V, Jr, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholin-esterase activity. Biochem Pharmacol 7: 88–95

    Google Scholar 

  • Eto M, Casida JE, Eto T (1962) Hydroxylation and cyclisation reaction involved in the metabolism of tri-o-cresyl phosphate. Biochem Pharmacol 11: 337–352

    Google Scholar 

  • Henschler D (1958) Die Trikresylphosphat-Vergiftung: Experimentelle Klärung von Problemen der Ätiologie und Pathogenese. Kllin Wochenschr 36: 663–674

    Google Scholar 

  • Hussain MA, Oloffs PC (1979) Neurotoxic effects of Leptophos in chickens and rats following chronic low-level feeding. J Environ Sci Health B14: 367–382

    Google Scholar 

  • Johnson MK (1970) Organophosphorus and other inhibitors of brain neurotoxic esterase and the development of delayed neurotoxicity in hens. Biochem J 120: 523–531

    Google Scholar 

  • Johnson MK (1974) The primary biochemical lesion leading to the delayed neurotoxic effects of some organophosphorus esters. J Neurochem 23: 785–789

    Google Scholar 

  • Johnson MK (1975) Organophosphorus esters causing delayed neurotoxic effects: mechanism of action and structure/activity relationships. Arch Toxicol 34: 259–288

    Google Scholar 

  • Johnson MK (1977) Improved assay of neurotoxic esterase for screening organophosphates for delayed neurotoxicity potential. Arch Toxicol 37: 113–115

    Google Scholar 

  • Johnson MK (1978) The anomalous behaviour of dimethyl phosphates in the biochemical test for delayed neurotoxicity. Arch Toxicol 41: 107–110

    Google Scholar 

  • Johnson MK, Barnes JM (1970) Age and the sensitivity of chicks to the delayed neurotoxic effects of some organophosphorus compounds. Biochem Pharmacol 19: 3045–3047

    Google Scholar 

  • Johnson MK, Lotti M (1980) Delayed neurotoxicity caused by chronic feeding of organophosphates requires a high point of inhibition of neurotoxic esterase. Toxicol Lett 5: 99–102

    Google Scholar 

  • Lotti M, Johnson MK (1978) Neurotoxicity of organophosphorus pesticides: predictions can be based on in vitro studies with hen and human enzymes. Arch Toxicol 41: 215–221

    Google Scholar 

  • Olajos EJ, De Caprio AP, Rosenblum I (1978) Central and peripheral neurotoxic esterase activity and dose response relationship in adult hens after acute and chronic oral administration of diisopropylfluorophosphate. Eco Toxicology Environ Safety 2: 383–399

    Google Scholar 

  • Richardson RJ, Dudek BR (1978) Occurence of neurotoxic esterase in various tissues of the hen. Toxicol Appl Pharmacol 45: 269–270

    Google Scholar 

  • Smith MI, Engel EW, Stohlman EF (1932) Further studies on the pharmacology of certain phenol esters with special reference to the relation of chemical constitution and physiologic action. Natl Inst Health Bull 160: 1–53

    Google Scholar 

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Lotti, M., Johnson, M.K. Repeated small doses of a neurotoxic organophosphate. Arch. Toxicol. 45, 263–271 (1980). https://doi.org/10.1007/BF00293807

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  • DOI: https://doi.org/10.1007/BF00293807

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