Archives of Toxicology

, Volume 53, Issue 4, pp 297–316 | Cite as

Intoxication with four synthetic pyrethroids fails to show any correlation between neuromuscular dysfunction and neurobiochemical abnormalities in rats

  • G. P. Rose
  • A. J. Dewar


The neurological effects of four synthetic pyrethroids resmethrin, permethrin, cypermethrin, and deltamethrin have been investigated in the rat to establish whether there is a correlation between the clinical-functional status of the animal and peripheral nerve damage as measured biochemically. Neuromuscular dysfunction was assessed by means of the inclined plane test and peripheral nerve damage by reference to β-glucuronidase and β-galactosidase activity increases in nerve tissue homogenates from treated and control animals. A transient functional impairment was found in animals treated with any one of the four pyrethroids tested and in all cases this was maximal at the end of the 7 day subacute dosing regimen. Significant increases in β-glucuronidase and β-galactosidase were found 3–4 weeks after the start of dosing in the distal portion of the sciatic/posterior tibial nerves from permethrin, cypermethrin, and deltamethrin treated animal; but no changes were found in remesthrin-dosed animals. It is concluded therefore, that there is no direct correlation between the time-course of the neuromuscular dysfunction and the neurobiochemical changes. This suggests that these pyrethroids have at least two distinct actions — a short-term pharmacological effect and at near-lethal dose levels a more chronic neurotoxic effect that results in sparse axonal nerve damage.

Key words

Pyrethroids Neuromuscular dysfunction Inclined plane test Peripheral nerve damage Neurochemical correlates β-Glucuronidase β-Galactosidase Sciatic/posterior tibial nerve 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Brodie ME, Aldridge WN (1982) Elevated cerebellar cyclic GMP levels during deltamethrin-induced motor syndrome. Neurobehav Toxicol Teratol 4: 109–113PubMedGoogle Scholar
  2. Carlton M (1977) Some effects of cismethrin on the rabbit nervous system. Pestic Sci 8: 700–712CrossRefGoogle Scholar
  3. Cavanagh JB, Chen CK (1971) The effect of methylmercury dicyandianide on the peripheral nerves and spinal cord of rats. Acta Neuropath (Berl) 19: 208–215CrossRefGoogle Scholar
  4. Dewar AJ (1981) Neurotoxicity testing with particular reference to biochemical methods. In: Gorrod J (ed) Testing for Toxicity. Taylor Francis Ltd., London, pp 119–217Google Scholar
  5. Dewar AJ, Moffett BJ (1979) Biochemical methods for detecting neurotoxicity — short review. Pharmacol Ther 5: 545–562CrossRefGoogle Scholar
  6. Dewar AJ, Moffett BJ, Rose GP (1979) A biochemical approach to neurotoxicity testing. Abstract D9-5-R22, XI International Congress of Biochemistry, July 8–13, Toronto, p 550Google Scholar
  7. Dewar AJ, Barron G, Reading HW (1975) The effect of retinol and acetylsalicyclic acid on the release of lysosomal enzymes from the rat retina in vitro. Exp Eye Res 20: 63–72CrossRefGoogle Scholar
  8. Fehling C, Abdulla M, Brun A, Dictor H, Schutz A, Skerfving S (1975) Methylmercury poisoning in the rat: A combined neurological, chemical and histopathological study. Toxicol Appl Pharmacol 33: 27–37CrossRefGoogle Scholar
  9. Fishman WH, Springer B, Brunetti P (1948) Application of an improved glucuronidase method to the study of human blood β-glucuronidase. J Biol Chem 173: 449–456PubMedGoogle Scholar
  10. Griffin JW, Prince DL, Kuethe OD, Goldberg AM (1980) Neurotoxicity of misonidazole in rats. I. Neuropathology. Neurotoxicology 1: 653–666Google Scholar
  11. Hollinger DM, Rossiter RJ (1952) Chemical studies of peripheral nerve during Wallerian degeneration. 5. β-glucuronidase. Biochem J 62: 659–663CrossRefGoogle Scholar
  12. Lock EA Berry PN (1981) Biochemical changes in the rat cerebellum following cypermethrin administration. Toxicol Appl Pharmacol 59: 508–514CrossRefGoogle Scholar
  13. Lotti M, Johnson MK (1978) Neurotoxicity of organophosphorus pesticides: Predictions can be based on in vitro studies with hend and human enzymes. Arch Toxicol 41: 215–221CrossRefGoogle Scholar
  14. McCaman RE, Robbins E (1959) Quantitative biochemical studies of Wallerian degeneration in the peripheral and central nervous systems. II. Twelve enzymes. J Neurochem 5: 21–42Google Scholar
  15. Narahashi T (1971) Mode of action of pyrethroids. Bull Wld Health Org 44: 337–345Google Scholar
  16. Ray DE (1980) An EEG investigation of decamethrin-induced choreathetosis in the rat. Exp Brain Res 38: 221–227CrossRefGoogle Scholar
  17. Rose GP, Dewar AJ, Stratford IJ (1980) A biochemical method for assessing the neurotoxic effects of misonidazole in the rat. Br J Cancer 42: 890–899CrossRefGoogle Scholar
  18. Rose GP, Dewar AJ, Stratford IJ (1982) A biochemical neurotoxicity study relating to the neurotoxic potential of metronidazole and nitrofurantoin with misonidazole. Int J Radiat Oncol Biol Phys 8: 781–785CrossRefGoogle Scholar
  19. Schaumburg MH, Wisniewski P, Spencer PS (1974) Ultra-structural studies of the dying-back process, I: Peripheral nerve terminal and axon degeneration in systemic acrylamide intoxication. J Neuropath Exp Neurol 33: 260–284CrossRefGoogle Scholar
  20. Schaumburg HH, Spencer PS (1976) Degeneration in central and peripheral nervous systems produced by pure n-hexane in an experimental study. Brain 99: 183–197CrossRefGoogle Scholar
  21. Van den Bercken J, Akkermans LMA, van der Zalm JM (1973) DDT-like action of allethrin in the sensory nervous system of Xenopus laevis. Eur J Pharmacol 21: 95–106CrossRefGoogle Scholar
  22. Verschoyle RD, Barnes JM (1972) Toxicity of natural and synthetic pyrethrins to rats. Pestic Biochem Physiol 2: 308–311CrossRefGoogle Scholar
  23. Verschoyle RD, Aldridge WN (1980) Structure-activity relationships of some pyrethroids in rats. Arch Toxicol 45: 325–329CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • G. P. Rose
    • 1
  • A. J. Dewar
    • 1
  1. 1.Shell Research Limited, Sittingbourne Research CentreSittingbourneEngland

Personalised recommendations