Biodegradation of α-hexachlorocyclohexane

IV. The extent of degradation of single doses in vivo
  • G. Noack
  • J. Portig
  • M. Wirsching
Article

Summary

  1. 1.

    Urine and stools were collected daily of 4 adult rats kept in single cages and injected once i.p. with α-hexachlorocyclohexane (α-HCH; dose per animal 126–150 μmoles), labelled uniformly with 14-C (10.8–14.0×106 dpm per animal).

     
  2. 2.

    In 4 weeks, 65% of the label was excreted through the kidneys and 16% by way of the intestine, with an estimated 8% being retained in depot fat.

     
  3. 3.

    GLC-analysis of the pooled urine showed it to contain very little unchanged drug, on average 0.05% of the dose. The time-course of the renal excretion of 14-C-labelled substance corresponded rather closely to the excretion of organically bound 36-Cl seen in earlier experiments with 36-Cl-labelled drug, indicating that the majority of urinary metabolites, presumably, still bear chlorine.

     
  4. 4.

    All or nearly all of the faecal 14-C was found by GLC to be accounted for by the stool's content of unchanged α-HCH.

     
  5. 5.

    Taken together, the results indicate a mean extent of α-HCH-degradation in the rat in the order of 80–85% of a dose.

     
  6. 6.

    Two rats were given 400 mg/kg of “cold” α-HCH by mouth 4 days before i.p. application of 14-C-labelled drug and were found to excrete more label through the kidneys in the first week than did the non-pretreated rats. This indicates that the drug stimulates its own degradation.

     

Key words

α-Hexachlorocyclohexane Biodegradation Renal Excretion Intestinal Excretion 

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References

  1. Albro, P. W., Thomas, R.: Intestinal absorption of hexachlorobenzene and hexachlorocyclohexane isomers in rats. Bull. enviromn. Contamin. Toxicol. 12, 289–294 (1974)Google Scholar
  2. Davidow, B., Frawley, J. P.: Tissue distribution, accumulation, and elimination of the isomers of benzene hexachloride. Proc. Soc. exp. Biol. (N. Y.) 76, 780–783 (1951)Google Scholar
  3. Freal, J. J., Chadwick, R. W.: Metabolism of hexachlorocyclohexane to chlorophenols and effect of isomer pretreatment on lindane metabolism in rat. Agric. Food Chem. 21, 424–427 (1973)Google Scholar
  4. Koransky, W., Portig, J.: Der Stoffwechsel der Hexachlorocyclohexan-Isomeren und seine Beeinflussung durch Mikrosomen aktivierende Pharmaka. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 243, 294–295 (1962)Google Scholar
  5. Koransky, W., Portig, J., Münch, G.: Resorption, Verteilung und Ausscheidung von α-und γ-Hexachlorocyclohexan. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 244, 564–575 (1963)Google Scholar
  6. Koransky, W., Portig, J., Vohland, H. W., Klempau, I.: Die Elimination von α-und γ-Hexachlorocyclohexan und ihre Beeinflussung durch Enzyme der Lebermikrosomen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 247, 49–60 (1964a)Google Scholar
  7. Koransky, W., Portig, J., Vohland, H. W., Klempau, I.: Aktivierung von Mikrosomenenzymen durch Hexachlorocyclohexan-Isomere. Ihr Einfluß auf die Scillirosidvergiftung der Ratte. Naunyn-Schmiedebergs Arcg. exp. Path. Pharmak. 247, 61–70 (1964b)Google Scholar
  8. Patterson, M. S., Greene, A. C.: Measurement of low energy beta-emitters in aqueous solution by liquid scintillation counting of emulsions. Analyt. Chem. 37, 854–857 (1965)Google Scholar
  9. Portig, J., Kraus, P., Sodomann, S., Noack, G.: Biodegradation of alpha-hexachlorocyclohexane. I. Glutathione-dependent conversion to a hydrophilic metabolite by rat liver cytosol. Naunyn-Schmiedebergs Arch. Pharmacol. 279, 185–198 (1973)Google Scholar

Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • G. Noack
    • 1
  • J. Portig
    • 1
  • M. Wirsching
    • 1
  1. 1.Institut für Toxikologie und Pharmackologie der Philipps-Universität MarburgMarburg/LahnFederal Republic of Germany

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