Archives of Toxicology

, Volume 64, Issue 3, pp 237–241 | Cite as

Pharmacokinetics and metabolism of a single subneurotoxic oral dose of tri-o-cresyl phosphate in hens

  • Elizabeth Suwita
  • Mohamed B. Abou-Donia
Original Articles

Abstract

Hens were given a single oral dose of 50 mg (4.6 μCi)/kg [14C] tri-o-cresyl phosphate (TOCP). Four groups of three hens each were killed after 0.5, 1, 2, and 5 days. The half-life of14C in plasma was 2 days. TOCP and its metabolites in the plasma, liver, kidneys, and lungs were analyzed by high-performance liquid chromatography and liquid scintillation counting. TOCP reached its highest concentration in plasma between 0.5 and 1 day after administration. Under these experimental conditions, the disappearance of TOCP from the plasma followed monoexponential kinetics with a half-life of 2.2 days. Appreciable concentrations of saligenin cyclic-o-tolyl phosphate, the active neurotoxic metabolite, were detected in the plasma as well as in the liver, kidneys, and lungs at all time points and had half-lives of 2.06, 1.36, 1.11 and 4.44 days, respectively. The presence of this active metabolite of TOCP might contribute to the sensitivity of the hen to TOCP-induced delayed neurotoxicity. Other hydrolytic and oxidative products of TOCP were also identified in tissues.

Keywords

TOCP OPIDN 

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References

  1. Abou-Donia MB (1980) Metabolism and pharmacokinetics of a single oral dose ofO-4-bromo-2,5-dichlorophenylO-methyl phenylphosphonothioate (Leptophos) in hens. Toxicol Appl Pharmacol 55: 131–145PubMedGoogle Scholar
  2. Abou-Donia MB (1981) Organophosphorous ester-induced delayed neurotoxicity. Annu Rev Pharmacol Toxicol 21: 511–548PubMedGoogle Scholar
  3. Abou-Donia MB (1983) Toxicokinetics and metabolism of delayed neurotoxic organophosphorus esters. Neurotoxicology 4: 511–548Google Scholar
  4. Abou-Donia MB, Nomeir AA (1986) The role of pharmacokinetics and metabolism in species sensitivity to neurotoxic agents. Fundam Appl Toxicol 6: 190–207PubMedGoogle Scholar
  5. Abou-Donia MB, Kinnes CG, Abdo KM, Bjornsson TD (1983) Physiological disposition and metabolism of O-ethyl O-4- nitrophenyl phenylphosphonothioate in male cats following a single dermal administration. Drug Metab Dispos 11: 31–36PubMedGoogle Scholar
  6. Abou-Donia MB, Suwita E, Nomeier AA (1990) Absorption, distribution, and elimination of a single oral dose of [14C]tri-o-cresyl phosphate in hens. Toxicology (in press)Google Scholar
  7. Bleiberg MJ, Johnson H (1965) Effect of certain metabolically active drugs and oximes on tri-o-cresyl phosphate toxicity. Toxicol Appl Pharmacol 7: 227–235Google Scholar
  8. Buttar HS, Tyrrell DL, Taylor JD (1968) Effect of tri-o-cresyl phosphate, tri-o-cresyl thiophosphate, and 2-(o-cresyl)-4H: 1∶3∶2 benzodioxaphosphoran-2-one on pentobarbital induced sleeping time in mice. Arch Int Pharmacol 172: 373–379Google Scholar
  9. Casida JE, Eto M, Baron RL (1961) Biological activity of a tri-o-cresyl phosphate metabolite. Nature 191: 1396–1397PubMedGoogle Scholar
  10. Environmental Protection Agency (1985) Proposed guidelines for registering pesticides in the United States. Federal Register 50 (188): 39458–39465Google Scholar
  11. Eto M, Casida JE, Eto T (1962) Hydroxylation and cyclization reactions involved in the metabolism of tri-o-cresyl phosphate. Biochem Pharmacol 11: 337–352PubMedGoogle Scholar
  12. Milne MD, Schribner BN, Craford MA (1958) Non-ionic diffusion and excretion of weak acids and bases. Am J Med 24: 709–729PubMedGoogle Scholar
  13. Nomeir AA, Abou-Donia MB (1983) High performance liquid Chromatographic analysis on radial compression column of the neurotoxic tri-o-cresyl phosphate and metabolites. Anal Biochem 135: 296–303PubMedGoogle Scholar
  14. Nomeir AA, Abou-Donia MB (1984) Disposition of [14C]tri-o-cresyl phosphate and its metabolites in various tissues of the male cat following a single dermal application. Drug Metab Dispos 12: 705–711PubMedGoogle Scholar
  15. Nomeir AA, Makkawy HA, Bower JA, Abou-Donia MB (1984) Distribution and metabolism of [14C]-tri-o-cresyl phosphate (TOCP) in the male rat following oral administration. The Toxicologist 4: 90Google Scholar
  16. Nomeir AA, Abou-Donia MB (1986 a) Studies on the metabolism of the neurotoxic tri-o-cresyl phosphate. Distribution, excretion, and metabolism in male cats after a single, dermal application. Toxicology 38: 15–33PubMedGoogle Scholar
  17. Nomeir AA, Abou-Donia MB (1986 b) Studies on the metabolism of the neurotoxic tri-o-cresyl phosphate. Synthesis and identification by infrared, proton nuclear magnetic resonance, and mass spectrometry of five of its metabolites. Toxicology 38: 1–13PubMedGoogle Scholar
  18. Sharma RP, Watanabe PG (1974) Time related disposition of tri-o-tolyl phosphate (TOTP) and metabolites in chicken. Pharmacol Res Commun 6: 475–484PubMedGoogle Scholar
  19. Smith MI, Elvove E, Frazier WH (1930) The pharmacological action of certain phenol esters, with special reference to the etiology of socalled ginger paralysis. Public Health Rep 45: 2509–2524Google Scholar
  20. Sturkie PD (1976) Heart and circulation: anatomy, hemodynamics, blood pressure, blood flow, and body fluids. In: Sturkie PD (ed) Avian physiology, 3rd edn. Springer-Verlag, New York, pp 76–101Google Scholar
  21. Suwita E, Nomeir AA, Abou-Donia MB (1986) Disposition and metabolism of a single oral dose of [14C]Tri-o-cresyl phosphate (TOCP) in hens. The Toxicologist 6: 256Google Scholar
  22. Taylor JD, Buttar HS (1967) Evidence for the presence of 2-(o-cresyl) 4H-1,3,2-benzodioxaphosphoran-2-one in cat intestine following trio-cresyl phosphate administration. Toxicol Appl Pharmacol 11: 529–537PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Elizabeth Suwita
    • 1
  • Mohamed B. Abou-Donia
    • 1
  1. 1.Department of PharmacologyDuke University Medical CenterDurhamUSA

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