Repeated Small Doses of a Neurotoxic Organophosphate. Monitoring of Neurotoxic Esterase in Brain and Spinal Cord

Overview

Journal Arch Toxicol

Specialty Toxicology

Date 1980 Oct 1

PMID 7447700

Citations 5

Authors

M Lotti

M K Johnson

Affiliations

Soon will be listed here.

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.

Citing Articles

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Neuropathy target esterase is required for adult vertebrate axon maintenance.

Read D, Li Y, Chao M, Cavanagh J, Glynn P J Neurosci. 2009; 29(37):11594-600.

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Poisoning by organophosphorus insecticides and sensory neuropathy.

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A benefit from mechanistic research in toxicology.

Johnson M Br J Ind Med. 1987; 44(4):217-9.

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In vivo and in vitro regional differential sensitivity of neuropathy target esterase to di-n-butyl-2,2-dichlorovinyl phosphate.

Moretto A, Lotti M, Spencer P Arch Toxicol. 1989; 63(6):469-73.

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References

Henschler D . [Tricresylphosphate poisoning; experimental clarification of problems of etiology and pathogenesis]. Klin Wochenschr. 1958; 36(14):663-74. DOI: 10.1007/BF01488746. View

Johnson M . The primary biochemical lesion leading to the delayed neurotoxic effects of some organophosphorus esters. J Neurochem. 1974; 23(4):785-9. DOI: 10.1111/j.1471-4159.1974.tb04404.x. View

Hussain M, Oloffs P . Neurotoxic effects of leptophos (PhosvelR) in chickens and rats following chronic low-level feeding. J Environ Sci Health B. 1979; 14(4):367-82. DOI: 10.1080/03601237909372135. View

Barnes J . Assessing hazards from prolonged and repeated exposure to low doses of toxic substances. Br Med Bull. 1975; 31(3):196-200. DOI: 10.1093/oxfordjournals.bmb.a071285. View

Lotti M, Johnson M . Neurotoxicity of organophosphorus pesticides: predictions can be based on in vitro studies with hen and human enzymes. Arch Toxicol. 1978; 41(3):215-21. DOI: 10.1007/BF00354093. View

Johnson M . Improved assay of neurotoxic esterase for screening organophosphates for delayed neurotoxicity potential. Arch Toxicol. 1977; 37(2):113-5. DOI: 10.1007/BF00293860. View

Johnson M . Organophosphorus esters causing delayed neurotoxic effects: mechanism of action and structure activity studies. Arch Toxicol. 1975; 34(4):259-88. DOI: 10.1007/BF00353848. View

Johnson M . The anomalous behaviour of dimethyl phosphates in the biochemical test for delayed neurotoxicity. Arch Toxicol. 1978; 41(1):107-10. DOI: 10.1007/BF00351775. View

Johnson M . Organophosphorus and other inhibitors of brain 'neurotoxic esterase' and the development of delayed neurotoxicity in hens. Biochem J. 1970; 120(3):523-31. PMC: 1179633. DOI: 10.1042/bj1200523. View

10.

Eto M, Casida J, Eto T . Hydroxylation and cyclization reactions involved in the metabolism of tri-o-cresyl phosphate. Biochem Pharmacol. 1962; 11:337-52. DOI: 10.1016/0006-2952(62)90056-4. View

11.

Johnson M, Lotti M . Delayed neurotoxicity caused by chronic feeding of organophosphates requires a high-point of inhibition of neurotoxic esterase. Toxicol Lett. 1980; 5(1):99-102. DOI: 10.1016/0378-4274(80)90155-1. View

12.

Johnson M, Barnes J . Age and the sensitivity of chicks to the delayed neurotoxic effects on some organophosphorus compounds. Biochem Pharmacol. 1970; 19(12):3045-7. DOI: 10.1016/0006-2952(70)90092-4. View

13.

Abou-Donia M, Preissig S . Delayed neurotoxicity from continous low-dose oral administration of leptophos to hens. Toxicol Appl Pharmacol. 1976; 38(3):595-608. DOI: 10.1016/0041-008x(76)90190-3. View

14.

Olajos E, DeCaprio A, ROSENBLUM I . Central and peripheral neurotoxic esterase activity and dose-response relationship in adult hens after acute and chronic oral administration of diisopropyl fluorophosphate. Ecotoxicol Environ Saf. 1978; 2(3-4):383-99. DOI: 10.1016/s0147-6513(78)80011-6. View

15.

Ellman G, COURTNEY K, ANDRES Jr V, FEATHER-STONE R . A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961; 7:88-95. DOI: 10.1016/0006-2952(61)90145-9. View