Abstract
Monomeric acrylamide was given to beagles in daily oral doses of 15 mg/kg for 22 days and at 5 mg/kg for 60 days. The animals of the high dose group developed neurological signs consistent with peripheral neuropathy. Electrophysiological measurements on the saphenous nerve revealed abnormal nervous function at the end of the treatment period. Conduction velocity was affected to the greatest extent, followed by absolute refractory period and chronaxy. At 30 days upon cessation of treatment conduction velocity and chronaxy were restored to normal but absolute refractory period remained pathological. At that time the first morphological changes of peripheral nerves were detected. Administration of the 5-mg/kg dose resulted in some disability of gait, lengthening of the absolute refractory period and, in half of the animals, in discrete morphological changes. By contrast, after the oral administration of clioquinol up to 200 mg-kg per day for a one-year period there were no signs of functional nor structural alterations of the nervous system. The beagle dog is considered to be a species well suited to reveal neurotoxicity.
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References
R. B. Auld andS. F. Bedwell,Peripheral Neuropathy with Sympathetic Overactivity from Industrial Contact with Acrylamide, Can. med. Ass. J.96, 652–654 Mar. 18 (1967).
J. M. Barnes,Toxic Chemicals and Peripheral Neuropathy: Experimental Studies, Proc. R. Soc. Med.62, 205–208 (1969).
J. B. Cavanagh,The Significance of the ‘dying-back’ Process in Experimental and Human Neurological Disease, Int. Rev. exp. Path.3, 219 (1964).
J. B. Cavanagh,Toxic Substances and the Nervous System, Br. med. Bull.25, 268 (1969).
D. D. Mc Collister, F. Oyen andV. K. Rowe,Toxicology of Acrylamide, Toxic. appl. Pharmac.6, 172–181 (1964).
P. M. Fullerton andJ. M. Barnes,Peripheral Neuropathy in Rats Produced by Acrylamide, Br. J. ind. Med.23, 210–221, (1966).
P. M. Fullerton,Electrophysiological and Histological Observations on Peripheral Nerves in Acrylamide Poisoning in Man, J. Neurol. Neurosurg. Psychiat.32, 186–192 (1969).
T. O. Garland andM. W. H. Patterson,Six Cases of Acrylamide Poisoning, Br. med. J.4, 134–138 (1967).
D. O. Hamblin,The Toxicity of Acrylamide. A Preliminary Report, S.E.D.E.S. Paris, 195–199 (1956).
R. Hess et al.,Absence of Neurotoxicity Following Prolonged Administration of Iodochloro-8-hydroxyquinoline (Entero-Vioform ® ) to Beagle Dogs, Arzneimittelforschung23, 1566–1571 (1973).
A. P. Hopkins andR. W. Gilliatt,Acrylamide Poisoning, Br. med. J.2, 417 (1967).
A. Hopkins,The Effect of Acrylamide on the Peripheral Nervous System of the Baboon, J. Neurol. Neurosurg. Psychiat.33, 805–816 (1970).
H. Kaeser,Funktionsprüfungen peripherer Nerven bei experimentellen Polyneuritiden und bei der Wallerschen Degeneration, Dt. Z. Nervenheilk.183, 268–304 (1962).
M. L. Kaplan andS. D. Murphy,Effect of Acrylamide on Rotarod Performance and Sciatic Nerve β-Glucuronidase Activity of Rats, Toxic. appl. Pharmac.22, 259–268 (1972).
A. S. Kupermann,Effects of Acrylamide on the Central Nervous System of the Cat, J. Pharmac. exp. Ther.132, 180–192 (1958).
J. Prineas,The Pathogenesis of Dying-Back Polyneuropathies. Part II: An Ultrastructural Study of Experimental Acrylamide Intoxication in the Cat, J. neuropath. exp. Neurol.28, 598 (1969).
R. J. Leswing andW. E. Ribelin,Physiologic and Pathologic Changes in Acrylamide Neuropathy, Arch. envir. Health18, 22–29 (1969).
H. Oettel andH. Th. Hofmann,Über die biologische Wirkung von Kunststoffen, ihren Bausteinen und Zersetzungsprodukten, Arbeitsmed. Sozialmed. Arbeitshyg.4, 101–112 (1966).
M. Takahashi, T. Ohara andK. Hashimoto,Electrophysiological Study of Nerve Injuries in Workers Handling Acrylamide, Int. Arch. Arbeitsmed.28, 1–11 (1971).
J. Tateishi, S. Kuroda, A. Saito andS. Otsuki,Myelo-Optic Neuropathy Induced by Clioquinol in Animals,Lancet II, 1263 (1971).
J. Tateishi, H. Ikeda, A. Saito, S. Kuroda andS. Otsuki,Myeloneuropathy in Dogs Induced by Iodoxyquinoline, Neurology22, 702 (1972).
B. H. Wakesman, R. D. Adams andH. C. Mansmann,Experimental Study of Diphtheritic Polyneuritis in the Rabbit and Guinea-Pig, J. exp. Med.105, 591–614 (1957).
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Thomann, P., Koella, W.P., Krinke, G. et al. The assessment of peripheral neurotoxicity in dogs: comparative studies with acrylamide and clioquinol. Agents and Actions 4, 47–53 (1974). https://doi.org/10.1007/BF01965492
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DOI: https://doi.org/10.1007/BF01965492