マウスのキノホルム長期経口投与実験 : 休薬後または間歇投与による毒性増加について

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It has been generally recognized in Japan that Subacute Myelo-Optic Neuropathy (SMON) is caused by 5-chloro-7-indo-8-quinolinol (chinoform). Several experiments on the neurotoxicities of Chinoform were done in rabbits, dogs, cats and Japanese quail, but only few reports on neurotoxicological signs in mice have been reported.We described, in the previous report, that paralysis of hind legs or gait disorder occurred in mice after the administration of Chinoform emulsified in milk.In the present paper, Chinoform was mixed with powdered diets fortified with dry milk with or without pesticides (BHC or Sumithion) and fed to mice for 16 or 25 weeks. There were no additional differences in the pesticides group as to appearance of neurological disturbances.Remarkable increase of cases with neurological disturbances and mortality were found in animals fed Chinoform biweekly, or when Chinoform administration was resumed two weeks after the administration was stopped at the end of the 15th week.Clinical signs of neurological disturbance occurred after the animals received a cumulated total dose of 40g of Chinoform/kg in continuous administration, of 24 to 28g in paused administration, and only 8 to 13g in biweekly administration.No histopathological changes in brain, spinal nerves and sciatic nerve were found in any of the animals, but by electromicroscopic observation changes in axon and myelin sheath of sciatic nerve were found.Based on our experimental findings in the difference of symptom grade caused by the mode of dosing, the record on the taking of Chinoform with or without any pause will hereafter be investigated in the epidemiological survey on SMON patients.
日本衛生学会の論文

マウスのキノホルム長期経口投与実験 : 休薬後または間歇投与による毒性増加について

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