抗球虫化合物——阿德呋啉的毒理学研究-toxicological study on anticoccidial compound adefuraline.docx

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2018-05-29 发布于上海
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抗球虫化合物——阿德呋啉的毒理学研究-toxicological study on anticoccidial compound adefuraline.docx

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抗球虫化合物——阿德呋啉的毒理学研究-toxicological study on anticoccidial compound adefuraline

AbstractAdprin,aanti-coccidiosiscompound,hasnotenteredclinical.Untilthisresport,researchesontoxicityofAdprinlackedarelativesystematiconeinourcountry.InordertoevaluatethesafetyofAdprin,somesystematictoxicologicalexperimentswerecarriedoutbytheprinciplesandmethodsoftoxicologywhichwerebasedonAdprin’sphysico-chemicalpropertiesandclinicalcharacteristics.Inthetest,theKunMingmiceandhylinechickenweretakenasexperimentanimalsandthetoxicityofAdprinwasstudiedbyintragastricadministration.FirstlytheLD50forAdpinwasdeterminedintheacutetoxictestandthenthe30daccumulativetoxicitytest,micronucleustest,spermabnormalitytestwereperformedonmice.AcutetoxicandsubacutetoxictestofAdprinwerealsocarriedoutonchicken,thetargetanimal.Acutetoxictestresultsshowedthat:medianlethaldose(LD50)ofAdprininmiceis43.76mg/kgandits95%confidenceintervalrangeis35.73~53.58mg/kg.AccordingtotheWHOrecommengedclassificationofacutetoxicityonexogenouschemicalcompounds(5level)itindicatedthatAdprinishigh-poisonoussubstanceonmice.Accumulationoftoxicitytestresultsshowedthat:StoragecoefficientofAdprininmiceis3.76,theaccumulativedoseis164.54mg/kgwhichrevealedamodereatecapacityofaccumulativetoxicityonmiceaccordingtoaccumulativegradingstandards.Andaccumulationtoxicitycausedmicegrowthinhibition.PCEmicrocleustestinBoneMarrowcellsonmiceisnegativeandthereisnosignificantdefferencecomparedwithnegativecontrol.SoAdprinisnochromosomeclastogenandnospindletoxiceffectonmice.SpermabnormalitytestonthemalemicereproductioncellsisnegativewhichshowedthatAdprinwasnon-mutagenicactivityongermcell.Acutetoxicitytestresultsshowedthat:medianlethaldose(LD50)ofAdprininhylinechickenis108.44mg/kgandits95%confidenceintervalrangeis95.17~123.56mg/kg.AccordingtotheWHOrecommendedclassificationofacutetoxicityonexogenouschemicalcompounds(5level)itindicatedthatAdprinismid-poisonoussubstanceonchicken.Thelivermaybethemajortargetorganofacutetoxitityonchicken.Subactutetoxicitytestresultsshowedthatmicehasnon-subactuetoxicitywithAdprinatdoseof1/80～1/20LD50for30dadministr