TS-K784YDAttachment 8PAGEIOF5PAGESSTUDYSPONSOR:CBISTUDYTYPE:TESTITEM:STUDYNUMBER:INTRODUCTIONThestudywasperformedtoassesstheacuteoraltoxicityofthetestitemfollowingasingleoraladministrationintheWistarstrainrat(GeneralStudyPlan518-12).Thisstudywasdesignedtobecompatiblewiththeproceduresindicatedbythefollowinginternationallyacceptedguidelinesandrecommendations:•OECDGuidelinesforTestingofChemicalsNo420"AcuteOralToxicity-FixedDoseMethod"(2001)•MethodB1hisAcute Toxicity(Oral)ofCommissionRegulation(EC)No.440/2008ExperimentalStartingDate:ExperimentalCompletionDate:11June201401July2014TestitemcharacterizationdataaretheresponsibilityoftheSponsor.Allrawdatawillberetained....__________________.METHODFollowingasightingtestatadoselevelof2000mg/kg,anadditionalfourfastedfemaleanimalsweregivenasingleoraldoseoftestitematadoselevelof2000mg/kgbodyweight.Clinicalsignsandbodyweightdevelopmentweremonitoredduringthestudy.Allanimalsweresubjectedtogrossnecropsy.TS-K784YDICBIRESULTSReportAttachment8Page2IndividualclinicalobservationsandmortalitydataaregiveninTable1.IndividualbodyweightsandweeklybodyweightchangesaregiveninTable2andindividualnecropsyfindingsaregiveninTable3.Therewerenodeaths.Nosignsofsystemictoxicitywerenotedduringthestudy.Allanimalsshowedexpectedgainsinbodyweightoverthestudyperiod.Noabnormalitieswerenotedatnecropsy.CONCLUSIONTheacuteoralmedianlethaldose(LD5o)ofthetestiteminthefemaleWistarstrainratwasestimatedtobegreaterthan2000mg/kgbodyweight(GloballyHarmonizedClassificationSystem-Unclassified).ThisstudywasconductedinafacilityoperatingtoGoodLaboratoryPracticewithintheUKnationalGLPmonitoringprogramme,butthestudyreporthasnotbeenauditedbytheQAUnit.NoformalclaimofGLPcomplianceismadeforthisstudy.Thisreportisanaccuraterecordofthestudyand itsoutcome.....................A.....................................Date:APoolesStudyDirector

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**~1** Report



# TABLES

Table 1 Individual Clinical Observations and Mortality Data

Animal Effects Noted After Dosing

Dose Level Number (Hours)

mg/kg and Sex

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# 1 2 4 

# 1 2 

# 3 4



# 1-0 

# 0 0 0 0 0 0 0 0 Female

2 -0

0 0 0 0 0 0 

# 0 0 Female

2 000 2-1

Female 0 0 0 0 0 0 0 0

2

- 2

Female 0 0 

# 0 0 0 0 0 0

2-3

0 0 0 Female 0 0 0 0 0

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# 0 = No s ign s of syst e mic t oxic i ty Effects Noted During Period After Dosing

(Days )

5 

# 6 7 8 

# 9 

# 10



# 0 0 0 0 0 0

0 0 0 0 

# 0 0

0 0 0 0 0 0



# 0 0 0 

# 0 0 0



# 0 0 0 0 0 0 11 

# 12 

# 13

0 0 0

0 

# 0 0

0 0 0

0 0 0

0 0 0 Page3



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# Table2 Individual Body Weights and Body Weight Changes

Dose Level Animal Number Body Weight (g) at Day

mglkg and Sex 

# 0 7



# 1-0 Female 166 174

2 -0 Female 164 186

2000 2 -1 Female 161 180

2

- 2 Female 166 188

2-3 Female 177 194

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Body Weight Gain (g) During Week



# 14 1 

# 2



# 186 8 12

200 22 14

190 19 10

200 22 12

206 17 12 -1 

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Table3 Individual Necropsy Findings

Dose Level Animal Number Time of Death

mg / kg 

# and Sex

1-0 Female Ki1led Day I 4

2-0 Female Killed Day 14

2000 2-I Fema le Killed Day 14

2-2 Female IGlled Day 14

2-3 Female Killed Day 14 Report Page 

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Macroscopic Observations

No abnormalities d etec t e d

No abnormalities detected

No abnormalities detected

No abnorma liti es detected

No abnormalities detected I

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