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### Working for a better future



## R **EPORT 2**  **- bromo**  **- 3,3,3**  **- trifluoropropene**  **: Toxicity Study by Inhalation**  **Administration to CD Rats for**  **13 Weeks**  **Followed by a 4**  **Week Recover** **y Period**

**HLS s tudy number:**  WAG0014 **V ersion ID:**  Final Report **Issue date:** 24 October 2013Huntingdon Life Sciences WAG0014

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# Details of Sponsor **an d**  **Te st Facilities**  **Sponsor** American Pacific Corporation 3883 Howard Hughes Parkway Suite 700 Las Vegas Nevada 89169 USA **Test facility** Huntingdon Life Sciences **Primary location** Huntingdon Research Centre Wo olley Road Alconbury Huntingdon Cambridgeshire PE28 4HS UK **Test facility** Huntingdon Life Sciences **Histology** Eye Research Centre Eye Suffolk IP23 7PX UKHuntingdon Life Sciences WAG0014

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# Ta **ble of Contents** Details of Sponsor and Test Facilities ................................................................................... 2 Compliance with Good Laboratory Practice .......................................................................... 6 Quality Assurance Statement ................................................................................................ 7 Contributing Scientists .......................................................................................................... 8 Summary .............................................................................................................................. 9 1. Introduction ................................................................................................................ 11 1.1 Objective ......................................................................................................... 11 1.2 Regulatory compliance ................................................................................... 11 1.3 Test system .................................................................................................... 11 1.4 Route of administration ................................................................................... 11 1. 5 Treatment groups and doses .......................................................................... 12 2. Experimental Procedure ............................................................................................. 13 2.1 Study schedule and structure .......................................................................... 13 2.1.1 Duration of treatment ........................................................................... 13 2.1.2 Ti me schedule ..................................................................................... 13 2.1.3 Identity of treatment groups ................................................................ . 13 2.2 Test substance ............................................................................................... 14 2.2.1 Test substance .................................................................................... 14 2.3 Animal management ....................................................................................... 15 2.3.1 Animal supply, acclimatisation and allocation ...................................... 15 2.3.2 Animal housing, diet and water supply ................................................ 15 2.3.3 Administration ..................................................................................... 16 2.4 Serial observation s ......................................................................................... 17 2.4.1 Clinical observations ........................................................................... 17 2.4.2 Detailed physical examination and arena observations ....................... 17 2.4.3 Sensory reactivity and grip strength .................................................... 18 2.4.4 Motor activity ....................................................................................... 19 2.4.5 Mortality .............................................................................................. 19 2.4.6 Bodyweight ......................................................................................... 19 2.4.7 Food consumption ............................................................................... 19 2.4.8 Ophthalmic examination ...................................................................... 19 2.4.9 Haematology, peripheral blood ............................................................ 20 2.4.10 Blood chemistry ................................................................................... 21 2.4.11 Urinalysis ............................................................................................ 21 2.5 Necropsy and Histology .................................................................................. 22 2.5.1 Method of kill ....................................................................................... 22 2.5.2 Macroscopic pathology ........................................................................ 23 2.5.3 Organ weights ..................................................................................... 23 2.5.4 Fixation ............................................................................................... 24 2.5.5 Histology ............................................................................................. 25 2.6 Pathology ........................................................................................................ 25 2.6.1 Light microscopy ................................................................................. 25 2.7 Computer systems .......................................................................................... 27 2.8 Data treatment ................................................................................................ 27 2.8.1 Definition of “We ek” ............................................................................. 28 2.8.2 Signs ................................................................................................... 28 2.8.3 Bodyweight ......................................................................................... 28Huntingdon Life Sciences WAG0014

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### 2.8.4 Ophthalmic examination ...................................................................... 28 2.8.5 Haematology ....................................................................................... 29 2.8.6 Blood chemistry ................................................................................... 29 2.8.7 Urinalysis ............................................................................................ 29 2.8.8 Organ weights ..................................................................................... 29 2.8.9 Pathology ............................................................................................ 29 2.8.10 Statistical analysis ............................................................................... 30 2.9 Quality assurance and archiving procedures .................................................. 32 2.9.1 Quality assurance ............................................................................... 32 2.9.2 Archives .............................................................................................. 32 2.10 Deviations from protocol ................................................................................. 32 3. Results ....................................................................................................................... 33 3.1 Chamber atmosphere conditions .................................................................... 33 3.2 Signs and mortality ......................................................................................... 33 3.3 Sensory reactivity and grip strength ................................................................ 34 3.4 Motor activity .................................................................................................. 34 3.5 Bodyweight ..................................................................................................... 35 3.6 Food consumption .......................................................................................... 35 3.7 Ophthalmic examination ................................................................................. 35 3.8 Haematology .................................................................................................. 35 3.9 Blood chemistry .............................................................................................. 36 3.10 Urinalysis ........................................................................................................ 36 3.11 Organ weights ................................................................................................ . 37 3.12 Macropathology .............................................................................................. 38 3.13 Histopathology ................................................................................................ 40 4. Discussion .................................................................................................................. 48 5. Conclusion ................................................................................................................. 50 6. References ................................................................................................................. 51 

# List of Figures Figure 1 Motor activity ................................................................................................ 52 Figure 2 Bodyweight .................................................................................................. 56 

# List of T **ables** Table 1 Sensory reactivity and grip strength ............................................................. 58 Table 2 Motor activity ................................................................................................ 60 Table 3 Bodyweight .................................................................................................. 64 Table 4 Haematology ................................................................................................ 70 Table 5 Blood chemistry ........................................................................................... 78 Table 6 Urinalysis ..................................................................................................... 86 Table 7 Organ weights .............................................................................................. 88 Table 8 Macropathology ........................................................................................... 96 Table 9 Histopathology ........................................................................................... 10 1Huntingdon Life Sciences WAG0014

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# List of **Ap pendices**  Appendix 1 Clinical s igns .............................................................................................. 11 9 Appendix 2 Signs associated with dosing ..................................................................... 13 9 Appendix 3 Sensory reactivity and grip strength ........................................................... 324 Appendix 4 Motor activity .............................................................................................. 332 Appendix 5 Bodyweight ................................................................................................ 348 Appendix 6 Food c onsumption ..................................................................................... 3 60 Appendix 7 Ophthalm ic examination ............................................................................. 364 Appendix 8 Haematology .............................................................................................. 366 Appendix 9 Blood chemistry ......................................................................................... 387 Appendix 10 Urinalysis ................................................................................................... 40 1 Appendix 11 Organ weights ............................................................................................ 413 Appendix 12 Macropathology and histopathology ........................................................... 425 

# List of A**nnexes** Annex 1 Certificate of analysis ................................................................................. 622 Annex 2 Aerosol technology and i nhalation a nalysis report ...................................... 624 Annex 3 Patholog y report ......................................................................................... 643 Annex 4 External pathology peer review report ........................................................ 66 1 Annex 5 GLP compliance statement s ...................................................................... 68 7HuntingdonLifeSciencesWAGOOI4CompliancewithGoodLaboratoryPractice2-bromo-3,3,3-trifluoropropene:ToxicityStudybyInhalationAdministrationtoCDRatsfor13WeeksFollowedbya4WeekRecoveryPeriodThestudydescribedinthisreport,withtheexceptionnotedbelow,wasconductedincompliancewiththefollowingGoodLaboratoryPracticestandards andIconsiderthedatageneratedtobevalid.TheUKGoodLaboratoryPracticeRegulations(StatutoryInstrument1999No.3106,asamendedbyStatutoryInstrument2004No.994).OECDPrinciplesofGoodLaboratoryPractice(asrevisedin1997),ENV/MC/CHEM(98)17.ECCommissionDirective 2004/10/ECof11February2004(Official JournalNoL50/44).TheseprinciplesofGoodLaboratoryPracticeareacceptedbytheregulatoryauthoritiesoftheUnitedStatesofAmericaandJapanonthebasisofintergovernmentalagreements.Hearttissueslidesfromallmales(mainstudyandrecovery)wereindependentlypeerreviewedbyanexternalconsultantpathologist.Thefindingsofthisreview,presentedasanexpertpathologyreport,areincludedasAnnex4ofthis reportforinformationpurposesonly.Theexpertpathologyreviewwasnotconductedinaccordance with GoodLaboratoryPracticeregulationsandwasnotsubjecttoQualityAssuranceaudit.No formalclaimofGLPcomplianceismadeforthiswork.3PaulJHrfllBSc(Hons) IDTDateStudyDirectorHuntingdonLifeSciences6HuntingdonLifeSciencesWAGOO14QualityAssuranceStatement2-bromo-3,3,3-trifluoropropene:ToxicityStudybyInhalationAdministrationtoCDRatsfor13WeeksFollowedbya4WeekRecoveryPeriodThefollowinginspectionsandauditshavebeencarriedoutinrelationtothisstudy:StudyPhaseDate(s)ofInspectionDateofReportingtoStudyDirectorandManagementProtocolAuditProtocolAmendmentNo.1StudySetUpProtocolAmendmentNo.2StudyManagementandConductPre-Terminal05Oct201205Oct201205Oct201202Nov201201Nov201201Nov201213Nov201213Nov201217Dec201217Dec201212Nov201212Nov201221Jan2013-31Jan201331Jan2013170ct2013170ct201318Oct201318Oct2013Inaddition,processbasedinspectionswereconductedofotherroutineandrepetitiveproceduresemployedonthistypeofstudyatorabout thetimethisstudywasinprogress.Similarlyaninspectionofthefacilitywherethisstudywasconductedwascarriedoutonanannualbasis.TheseinspectionswerereportedtoCompanyManagement.Th.SN\;\l-v\%LfCc/Vt)2€V20I3DilysSmith,MRQADateLeadAuditorDepartmentofQualityAssuranceHuntingdonLifeSciences13Mar201205Jul201209Jul201217Jul 201201Aug201215Mar201205Jul201210Jul201217Jul 201201Aug2012ProtocolAmendmentNo.3ProtocolAmendmentNo.4ProtocolAmendmentNo.5ProtocolAmendmentNo.6ReportAudit7Huntingdon Life Sciences WAG0014

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# Contributing Scientist **s 2-bromo-**  **3,3,3 -** **trifluoropropene: Toxicity Study by Inhalation Ad**  **ministration to CD Rats for 13 Weeks Follo wed by a 4 Week Recovery**  **Period** 

## Study management Paul J Horrell BSc (Hons) IDT Study Di rector William N Hooks MIBMS BSc (Hons) Senior Toxico lo gist 

## Aerosol technology Simo n A Moore BSc (Hons) PhD MRSC Head of Aerosol Techno lo gy 

## Inhalation analysis Caroline Finucane PhD Head of Formulat io n & Inhalat io n Analysis 

## S **ensory reactivity, grip strength and motor activity** Martin J Co llier BSc Behavioural Scient ist 

## O **phthalmic examinat ion**  Helmut Ehall MagMedVet DrMedVet MRCVS Named Veterinary

Surgeon 

## Clinical pathology John Smeraglia MSc Assoc iat e Di

r ector of Bio analysis and Clin ical Pathology 

## Pathology Kai Chiu Liu BSc MSc (Tox) PhD Senior Pathologist 

## Statistics Gareth D Thomas BS c (Hons) Head of Statist ic s and Data ManagementHuntingdon Life Sciences WAG0014

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# Summary The assess ment of lo cal

and systemic toxic potential of 2- bro mo - 3,3,3 -trifluoropropene (a fi re ext inguishing agent ), to Crl :CD (SD) rats by inhalat io n administration was assessed over a period of 13 weeks, fo llo wed by a 4 week recovery (non-dosing) period. Three groups, each comprising ten male and ten female rats received 2- bro mo -3,3,3-trifluoropropene at target exposure levels of

200 , 500 or 3000 ppm, 5 days per week (6 hour exposure) . A similarly const itut ed Control group received clean ai r only , under the same condi tions as the test groups . A further ten ma le and ten fe male rats were assigned to each of the Control and high dose groups. These animals were treated for 13 weeks, fo llo wed by a 4 w eek period wi thout treatment to assess recovery f rom any treatment related effect. During the study, clinical observat io ns , detailed physical examinat io n and arena observations, sensory reactivit y, grip strength, motor activit y, b ody weight, food consumptio n, ophthalmic examinat io n, haematology, blood chemistry, urinalysis, organ weight, macropathology and histopathology

invest igat io ns were undertaken. 

## Results The achieved aerosol concentrations were 199, 505 and 2876 ppm (100, 101 and 96% of target) for Gro ups 2 - 4 respectively. There were no deaths that were considered to be a direct result of exposure to the test material, 2 bro mo 3,3,3 trifluoropropene . Treatment - related, but transient, clinical signs, related to inhalat io n of an irritant material ( shallow breathing, piloerect io n, grinding teeth and hunched posture ) or possible CNS effects (unresponsiveness to external st imuli, underact ivit y, and partially closed eyelids ) , were evident during and after exposure atall exposure levels . Reduct io ns in grip strength and mo tor activit y were evident for animals exposed to 505 or 2876 ppm and were only partially reversible for animals previously exposed to 2876 ppm after a 4 week recovery period. Lower bodyweight gain was evident, over the 13 week treatment period , f or treated males and females exposed to 505 ppm or higher, in a dosage related manner. Total food consumption was similarly lo wer fo r treated males and females exposed to 2876 ppm. Effects on body

weight and food consumpt io n showed evidence o f recovery fo r animals previously exposed to 2876 ppm after a 4 week recovery period. Histopathological

changes related to treatment were seen in the liver (centrilobular hepatocy te hypertrophy

), pancreas (acinar cell degranulat io n), heart (chronic inflammat io n), spleen (capsular inflammat io n and/or thickening and adhesio n), thymus (invo lut io n/atrophy ), nasal turbinates (findings related to minor local irritants), larynx (ventral squamous metaplasia) and teeth (pulp cavit y necrosis). The majorit y of these findings were seen with animals at 505 and 2876 ppm. Chronic inflammation in the heart and acinar cell degranulat io n in the pancreas were evident for animals exposed to 199 ppm, however, these changes are not considered to be adverse. The slight and moderate degrees of chronic inflammat io n in the heart observed at 505 and 2876 ppm are considered adverse.Huntingdon Life Sciences WAG0014

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### Fo llo wing the 4 week recovery period, there was com

plete recovery

of test material

related histopathological changes seen in the liver, pancreas, heart, thymus, larynx and teeth and partial recovery for the findings see in the spleen (capsular inflammat io n and/or thickening) and nasal turbinates (atrophy /disorganisat io n/vacuolat io n of the olfactory epi thelium and naso lacr imal duct inflammat io n). 

## Conclusion Inhalation exposure of CD rats to atmospheres of 2 bromo 3,3,3 -trifluoropropene for 13 weeks, resulted in transient clinical signs, lower bodyweight gain, food consumpt io n, grip strength and motor activit y and histopathological changes in the liver, pancreas, he art, spleen, thymus, nasal turbinates, larynx and teeth. The majorit y of these findings were seen with animals exposed to 505 or 2876 ppm. In the heart, chronic inflammat io n was seen in males exposed to 199 ppm and both sexes exposed to 505 or 2876 ppm and was considered adverse at 505 ppm or above. The no observed adverse effect level (NOAEL) was considered to be 199 ppm.Huntingdon Life Sciences WAG0014

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# 1. **Introduction 1.1**  **Objective** The obj ect ive o f this study was to assess the lo cal

and systemic toxic potential of 2- bromo- 3,3,3 -trifluoropropene , a fire ext inguishing agent , when administered by inhalat io n (who le body) to rats for 13 weeks. Recovery from any effects seen at the highest dose was assessed during a 4 week recovery period. 

## 1.2 **Regulatory compliance** The study was designed to meet the requi rements of the fo llo wing guidelines: OECD Guideline for the Testing of Chemicals, No. 413: Subchronic Inhalat io n Toxicit y: 90 - Day

Study (Adopted: 7 September 2009). EC Di rect ive 88/302/EEC B.29 Sub - Chronic Inhalation Toxicit y Test: 90 - Day Repeated Inhalat io n Dose Study using Rodent Species. US EPA OPPTS Guideline 870.3465: 90 - day Inhalat io n Toxici ty Study, (August 1998). The study was conducted in accordance wit h the requirements of current, internat io nally recognised Good Laboratory Practice Standards, and the applicable sect io ns of the United Kingdo m Animals (Scient ific Procedures) Act 1986. 

## 1.3 **Test system** The rat was chosen as the test species because of its acceptance as a predictor of toxic change in man and the requirement for a rodent species b y regulatory agencies. The Crl:CD (SD) strain was used because of the historical control data available in this laboratory. 

## 1.4 **Route of administration** The inhalat io n route of administration was chosen to simulate the condit io ns of potential human exposure.Huntingdon Life Sciences WAG0014

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## 1.5 **T reatment groups and**  **doses** In a previous 2 - week dose range finding study ( Hunt ingdon Life Sciences Study Number: WAG0024 ) , 3 groups of rats were exposed to 2 - bromo- 3,3,3 -trifluoropropene for 6 hours per day, 5 days per week at achieved aerosol concentrations of 533, 1167 and 2980 ppm. There were no unscheduled deaths at doses up to 2980 ppm. In- life findings, consist ing of transient clinical signs, evident during and after exposure for all treated animals, and reduced body we ight gain and food consumpt io n, seen for all treated males, were not considered adverse. Histopathological

changes related to treatment were seen mainly in the nasal turbinates of rats exposed to 1167 or 2980 ppm and were consistent with a localised toxic effect of the test material . No histopathological changes were evident at 533 ppm and this was considered to be the no observed adverse effect level (NOAEL). Alt hough adverse histopathological findings were evident at 1167 ppm it was considered that these may no t progress over 13 weeks and may be readily reversible during a 4 week off - exposure recovery

period. A target high exposure level o f 3000 ppm was th us selected fo r this study, as i

t was considered that exposure for 13 weeks at this level would have adverse histopathological effects on rats which may or may not be reversible. The target i

nt ermediate exposure level of 500 ppm was selected as i t was shown to have no adverse effects after 2 weeks exposure. Since the 500 and 3000 ppm target exposure leve ls were u sed on the 2 - week study, their use on the 13 - week study would also enabl e the relat io nship of changes over time to be explored. The target low exposure level of 200 ppm was expected to have no adverse effects and would offer an acceptable worker s afet y margin .Huntingdon Life Sciences WAG0014

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# 2. **Experiment al Procedure**  **2.1 S**  **tudy schedule and structure 2.1.1**  **Duration of treatment** The test substance, 2- bro mo -3,3,3-trifluoropropene , was administered over a period of 13 consecutive weeks. The necropsy procedures were completed in 4 days fo r the ma in study and 1 day f or recovery

phase , during which time treatment continued, and serial observat io ns were recorded at appropriate intervals. The duration of treatment is reported as 13 weeks. Animals assigned to the recovery phase com

pleted a further fo ur weeks wi thout treatment. **2.1.2 Time schedule**  Study init iat io n: (Pro tocol signed by

Study Di rector) 09 March 2012 Experimental start date: (Animal arrival) 05 July 2012 Treatment commenced: 10 July 2012 Necropsy com pleted: Main Study 12 October 2012 Re covery Study 06 November 2012 Experimental co mp let io n date: (pathology

) 7 October 2013 Study com plet io n: When the Study Di rector signs the final repor t. **2.1.3 Identity of treatment groups**  The study consisted of one Control and three treated groups of rats, ident ified as fo llo ws: **Group Treatment**  **Target exposure level**  **( ppm** **) Number of animals** 

**Main study Recovery**  **Male Female**  **Male Female**  1 Control 0 10 10 10 10 2 2 - br omo - 3,3,3 - trifluoropropene 200 10 10 - - 3 2 - br omo - 3,3,3 - trifluoropropene 500 10 10 - - 4 2 - br omo - 3,3,3 - trifluoropropene 3000 10 10 10 10Huntingdon Life Sciences WAG0014

14 **Group Main study**  **Recovery**

**Cage numbers Animal numbers**  **Cage numbers Animal numbers**  **Male Female**  **Male Female**  **Male Female**  **Male Female**  1 13 - 14 5 - 6 61 - 70 21 - 30 17 - 18 9 - 10 81 - 90 4 1 - 50 2 21 - 22 11 - 12 101 - 110 51 - 60 - - - - 3 23 - 24 1 - 2 111 - 120 1 - 10 - - - - 4 3 - 4 7 - 8 11 - 20 31 - 40 15 - 16 19 - 20 71 - 80 91 - 100 

### Some serial

observations needed to be performed without the knowledge of the treatment group; therefore the animal numbering system was such that it was not easy to ident ify a treatmen t group from

the animal number. 

## 2.2 **Test substance 2.2.1**  **Test substance** Informat io n supplied by the Sponsor regarding the test substance is contained in the test substance data sheet, which is retained in study records, and the Certificate of Analysis, which is presented in Annex 1. The fo llo wing informat io n is given in summary : Ident ification: 2- bromo- 3,3,3 -trifluoropropene (stabiliz ed) Act io n: Fi

re ext inguishing agent Descript io n: Liquid at below 33  C

C le ar and may

b e colourless to light yellow t int Storage condit io ns: Atambient temperature or in a refrigerator , stored under

nitrogen (free fro m ai

r and water). Batch number: WN CC - BTP111128 Date of receipt : 02 March 2012 Quant it y received: 4 × approximately 500 kg cylinders

2 × approximately 336 kg cylinders Reassay date: 12 January 2013 Puri ty : >99.6 % including stabilisers Stabilisers: The Sponsor was responsible for the characterisat ion of the test substance and the documentation of

the methods of synt hesis, fabrication or derivat io n and stabilit y.Huntingdon Life Sciences WAG0014

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## 2.3 **Animal management 2.3.1**  **Animal supply, acclimatisat ion and allocation**  Crl :CD (SD) rats (a total

of 65 ma le and 65 fe male ) were received fro m Charles River (UK) Ltd. The rats were ordered at 42 to 49 days of age and wit hin a weight range of 180 to 210 g fo r ma les and 150 to 180 g for females . On arrival, the animals were removed fro m the transit boxes and allocated to study cages. Using the sequence of cages in the battery, one animal at a time was placed in each cage wit h the procedure being repeated until each cage held the appropriate number of animals. Each sex was allo cated separately. Each animal was assigned a number and ident ified uniquely wit hin the study by a tail tattoo. Each cage label was colour - coded according to group and was numbered uniquely wit h cage and study n umber, as well as the iden ti ty of the occupants. On Day 3 of treatment, one male was found dead , before exposure, and w as replaced wi th a spare animal of suitable weight from the same batch. The animals were allowed to acclimat ise to the condit io ns described below for atleast 5 days before treatment commenced. For those animals selected for this study, thei r age at the start of treatment was 47 to 54 days and their bodyweights were in the range o f 216 to 263 g for males and 160 to 224 g for females. The spare animals were remo ved from the study room af ter treatment commenced. **2.3.2 Animal housing, diet and water supply**  Animals were housed inside a restricted access rodent facilit y (Building Y14 , Room 011 ). The facilit y was designed and operated to minimise the entry of external biologic al and chemical agents and to minimise the transference of such agents between rooms. Before the study the room was cleaned and disinfected. Each animal room was supplied with filtered fresh air, which was passed to atmosphere and not re - circulated. The tem perature and relat ive humidit y controls were maintained wit hin the range of 19 to 23°C and 40 to 70% respectiv ely and moni tored conti

nuously. Al

though condi tions were occasionally outside the indicated ranges, these deviat io ns were minor and/or of shor t duration and were not considered to have influenced the health of the animals and/or the outcome of

the study. Artificial light ing was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours. Alarms were activat ed if there was any failure of the vent ilat io n system, or temperature limits were exceeded. A stand- by electrici ty supply was available to be automat ically brought into operation should the public supply fail. The animals were housed five of one sex per c age, unless this number was reduced by mo rtalit y or iso lat io n. The cages were made of a polycarbonate body wi th a stainless steel mesh lid. Softwood bark- free fibre was used as bedding and was sterilised by autoclaving and changed at appropriate interval s each week. Cages, food hoppers and water bottles were changed at appropriate intervals.Huntingdon Life Sciences WAG0014

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### The cages const ituting each group were blocked together by sex and the groups were dispersed in batteries so that possible environmental influences arising from thei r spat ia l distribut io n were equilibrated, as far as was pract ic able. Addit io nally, batteries of cages were rotated around the room at weekly intervals to further minimis e possible spat ial variat io ns. The animals were allowed free access to a standard rodentdiet (Rat and Mouse No. 1 Maintenance Diet), except when urine was being collected and overnight before routine blood sam

pling. This diet contained no added antibiot ic or other chemotherapeut ic or prophylact ic agent. Potable water taken fro m the public supply was f reely available via polycarbonate bottles fi tted wi th sipper tubes, except when urine was being collected. Each cage of animals was provided with an Aspen chew block and a plast ic shelter fo r environmental enrichment. The soft white untreated wood blocks were provided throughout the study and were replaced when necessary; plast ic shelters were replaced at the same time as the cages. Each batch of diet was analysed routinely by the supplier for various nutrit io nal com ponents and chemical and mi crobiological contaminants. Supplier’s analy ti cal certificates were scrutinised and approved before any b atch of diet was released for use. The qualit y of the water supply

i s governed by

regulat io ns published by the Department f

or Envi ronment, Food and R ural Affai rs. Certificates of analysis were received routinely from the water supplier and the supplier s of

the bedding and A spen chew blocks. Since the results of these various analyses did not provide evidence o f contaminat io n that might have prejudice d the study, they are not presented. No other specific contaminants that were likely to have been present in the bedding , chew blocks, diet or water were analysed, as none that may have interfered with or prejudiced the outcome of

the study was known. **2.3.3 Admi**  **nistration** Details o f administration and analysis of the test atmospheres together with the results obtained are presented in Annex 2. Each exposure system

consisted of a Glass vaporiser and a whole body exposure chamber. Different doses of 2- bro mo -3,3,3-trifluoropropene were achieved by varying the liquid feed rates of the test material in the system whilst keeping the duration of exposure constant. Group 1 was exposed to clean air only at a target concentration the same as the test groups . Groups 2, 3 and 4 were exposed to 2- bromo -3,3,3-trifluoropropene , 6 hours/day fo r 5 days each week (Monday

to Friday ) f or 13 weeks.Huntingdon Life Sciences WAG0014

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## 2.4 **Serial observations** Dated and signed records of all act ivit ies relating to the day by day running and maintenance of the study wi thin the animal unit as well as to the group observat io ns and examinat io ns outlined in this experimental procedure were recorded in the Study Day Book. In addi

tion, observat io ns relat ing to individual animals made throughout the day were recorded. All observat io ns described below were performed in cage number sequence except where otherwise indicated. **2.4.1 Clinical observations**  Animals were inspected visually at least twice daily for evidence of ill- healt h or reaction to treatment. Cages were inspected daily f or evidence of

ill - heal th amongst the occupant(s). Any deviat io n from normal was recorded at the time in respect of nature and severit y, date and time o f onset, duration and progress of the observed condit io n, as appropriate. Daily, on exposure days during Week 1 , detailed observat io ns were performed immediately before dosi

ng , during exposure and between one and two hours after complet io n of dosing and as late as possible in the working day f or all groups. From Week 2 onwards, detailed observat io ns were performe d immediately before dosing and during exposure. During the acclimat is ation period, observat io ns of the animals and their cages were recorded twice per day. In addit io n, a more detailed weekly physical examinat io n was performed on each animal to mo nit or general healt h. **2.4.2 Detailed physical examination and arena observations**  Before treatment commenced and during each week of treatment and recovery, detailed physical examinat io n and arena observations were performed on each animal. Each week , the examinat io ns were performed, bef ore dos ing during the treatment period , by an observer unaware of the experimental group to which the animal belonged. After removal

f rom the home cage, animals were assessed for physical condit io n and behaviour during handling and after being placed in a standard arena. Any deviation f

rom normal was recorded wi

th respect to the nature and, where appropriate, degree of severit y. Particular attention was paid to possible signs of neurotoxicit y, such as convulsio ns, tremor and abnormalit ies of gait or behaviour. Findings were either reported as "present" or assigned a severit y grade - slight, moderate or marked.Huntingdon Life Sciences WAG0014

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### 2.4.3 **Senso ry reactivity and grip strength**  Sensory react ivit y and gri

p strength assessments were performed (before dosing) on all main study animals and all recovery phase animals during Week 12 of treatment. In addition, grip strength was assessed in all recovery phase animals during Week 4 of recovery. Animals were tested by

an observer who was unaware of the treatment group to which each animal belo nged. Before the start of observat io ns, cage labels showing the treatment group were replaced by

l abels stating only the study, animal and cage numbers. Animals were not necessarily all tested on the same day, but the numbers of animals and the times o f testi ng were balanced across the groups on each day of testing. The fo llo wing measurements, reflexes and responses were recorded: **Approach response** A blunt probe was brought towards the animal’s head unt il itwas close to the animal’s nos e (but not touching the vibrissae). The animal’s reaction was recorded as:

1 No reaction or ignores probe 2 Normal

awareness and react io n e.g. approaches and/or sniffs probe 3 Abnormally

f earful or aggressive reaction **Touch response** The animal was stro ked gently on the nape of the neck with a blunt probe and the reaction recorded as:

1 No reaction or ignores probe 2 Normal

awareness and react io n e.g. turns towards or moves away 3 Abnormally

f earful or aggressive reaction **Auditory startle reflex** The animal’s response to a sudden loud no ise was assessed and scored as:

1 No response 2 Weak response e.g. ear twitch only 3 Normal

response e.g. obvious flinch or startle 4 Exaggerated response e.g. all feet off floor **Tail pinch response** The animal’s tail was pinched sharply wit h fo rceps approximately one third fro m the ti p and the response graded as:

1 No response 2 Weak response e.g. turns around slowly or weak vocalisat io n wi thout mo ving away 3 Normal

response e.g. j umps f

orward or turns around sharply, usually wi th vocalisat io n 4 Exaggerated response e.g. excessive vocalisat io n, body movement or aggressio nHuntingdon Life Sciences WAG0014

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### Grip strength Forelimb and hindlimb grip strength was measured using Mecmesin Force Indicators. Three trials were performed. Atany point during the observat io ns, addi tional comments were made as free text where considered appropriate. **2.4.4 M**  **otor activity** During Week 12 of

treatment (before dosing), the motor activit y of all main study

animals and all recovery phase animals was measured using a Rodent Activit y Moni toring System (Version 2.0.5), wi

th hardware supplied by

Pearson Technical

Services and software developed and maintained by Hunt ingdon Life Sciences. In addit io n, all recovery phase animals were tested during Week 4 of recovery. Animals were tested individually in clear polycarbonate cages and motor activit y was measured by counting infra- red beam breaks over ten 6 -minute intervals (one hour total). Ten beams were set at two height levels (five low and five high) to detect cage floor and rearing activit y respect ively. Animals were not necessarily all tested on the same day, but the numbers of animals and the times of testing were balanced across the groups on each day o f testing. **2.4.5 Mortality**  Debilitated animals were observed carefully and, where necessary, isolated to prevent cannibalism. Animals were killed for reasons of animal welfare where necessary. Where possible, blood samples were taken ante mortem and analysed for the characteristics specified in the haematology

and blood chemistry sect io ns below. A com plete necropsy

was performed in all cases as described below. **2.4.6 Bodyweight**  The weight of each rat was recorded one week before treatment commenced (Week -1 ), on the day that treatment commenced (Week 0), weekly throughout the treatment and recovery periods , and before necropsy. **2.4.7 Food consumption**  The weight of food supplied to each cage, that remaining and an est imate of any spilled was recorded for the week before treatment started (Week -1 , 5 days of recording only), and each week throughout the treatment and recovery periods. **2.4.8 Ophthalm**  **ic examination** Before treatment commenced, the eyes of all animals allocated to the study (including spare animals) were examined by means of a bino cular indirect ophthalmo scope . During Week 13 of treatmen t the eyes of

all animals of Groups 1 (Control) and 4 ( 2876 ppm ) were similarly examined. Prior to each examinat io n, the pupils o f each animal were dilated using tropicamide ophthalmic so lut io n (My

driacyl). The adnexae, conjunct iva, cornea, sclera, anterior chamber, ir is (pupil dilated), lens, vitreous and fundus were examined. As no treatment - related changes were observed, the examinat io n was not extended to Groups 2 and 3 during Week 13 or the recovery pha se.Huntingdon Life Sciences WAG0014

20 

### 2.4.9 **Haematology, peripheral blood** During Week 13 of

treatment (before dosing on each occasio n) and Week 4 of re covery, blood sam

ples were obtained from all animals after overnight withdrawal of food. Animals were held under light general anaesthesia induced by iso flurane and blood samples were wi thdrawn from the sublingual vein . Blood sam

ples (nominally

0.5 mL) were collected into tubes containing EDTA as ant ico agulant and examined for the fo llo wing characterist ic s using a Bayer Advia 120 haematology

analyser : Haematocrit (Hct) Haemoglobin concentration (Hb) Ery th rocy te count (RBC) Reticulocy

te count (RETA) Mean cell haemoglo bin (MCH) Mean cell haemoglo bin concentration (MCHC) Mean cell vo lume (MCV) Total whi te cell count (WBC) Different ia l WBC count Neutrophils (N) Lymphocy

tes (L) Eosinophils (E) Basop hils (B) Monocy tes (M) Large unstained cells (LUC) Platelet coun

t (Pl t) Morphology

f lags were generated by

the Advia 120 analyser. The most common mo rphological

changes, anisocy

tosis, micro/macrocy

tosis and hypo/hyperchromasia were categorised as fo llo ws :

- = no abnormalit ies detected + = slight ++ = mo derate +++ = marked Blood film (prepared for all samples) - Ro manowsky stain, examined for abnormalit ies by light microscopy, in the case of flags from the Advia 120 analyser. Confirmation or a written de scri pt io n fro m the blood f

ilm was made where appropriate. Addit io nal blood sam

ples (nominally

0.5 mL) were taken into tubes containing citrate ant ico agulant and examined in respect of: Prothrombin t ime (PT P ) - using an ACL 9000 analyser and IL PT - Fibrinoge n reagent. Act ivated partial thromboplast in time (APTT) - using an ACL 90 00 Analyser and IL APTT reagentHuntingdon Life Sciences WAG0014

21 

### 2.4.10 **Blood chemistry** Atthe same time and using the same animals as for peripheral haematology, f urther blood samples (no minally 0.7 mL) were collected int o tubes containing lit hium heparin as ant ico agulant. All

tubes were mechanically agitated for at least two minutes and the samp le subsequent ly centrifuged at 2 000 g fo r 10 minutes in order to separate the plasma. After separation, the plasma was examin ed in respect of: Using a Roche P Modular Analyser: Alkaline phosphatase (ALP) Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Total bili rubin (Bili) Urea Creatinine (Creat) Gl ucose (Gl uc) Total cho le sterol

(Chol) Triglycerides (Trig) Sodi um (Na) Potassi um (K ) Chloride (Cl) Calcium (Ca) Inorganic phosphorus (Phos) Total protein (Total Prot) Albumin (Alb) Albumin/glo bulin ratio (A/G Ratio) was calculated fro m total protein concentration and analysed albumin concentration. **2.4.11 Urinalysis**  During Week 13 of

treatment, overnight urine samples were collected fro m all animals. Animals were placed in an individual metabo lism cage wi thout f ood or water at approximately

16.00 hours; urine was collected until approximately 07.00 hours the fo llo wing day . The individual samples were examined for the fo llowing characterist ics: Appearance (App) - by visual assessment using the fo llo wing abbreviat io ns: PY Pale yellow PO Pale orange MY Medium yellow DO Dark orange DY Dark yellow Vol ume (Vol) pH - using a Radiometer PHM 92 pH meter Specific gravit y (SG) - using Atago UR- 1 digital refractometer Protein (Prot), sodium (TNAR), potassi um (T UKR) and chloride ( T CLR) - using Roche P ModularHuntingdon Life Sciences WAG0014

22 

### Gl ucose (Gl uc), ketones (Keto), bile pigments (Bili), blood pigments (UBld) by Mul ti st ix, diagnostic reagents used as qualitat ive indicators of analyte concentration. The reagent strips were interpreted using the Clinitek®500 instrument and results were categorised using the fo llo wing convent io n: NEG = negat ive TRA = trace levels 1+ = ‘small amount’ of analyte 2+ = ‘moderate amount’ of analy te 3+ = ‘large amount’ of analy te 4+ = ‘very

l arge amount’ of analy

te A microscopic examinat io n of the urine sediment was performed. An aliquot of the urine sample was centrifuged, stain ed wi th Kova stain and the result ing deposit spread on a microscope slide. The number of elements seen in nine high or low power fields (HPF or LPF) was recorded in the raw data and entered onto the database and the number seen /HPF or /LPF was derived from these data as described below . Casts/LPF (CAS) Leucocy tes ( Leuc ) Ery th rocy tes ( RBC ) Crystals ( Cryst ) Spermatozoa (Sperm

) Epi thelial cells/HPF (Epi) Abnormali

ti es (A) 

## 2.5 **Necropsy and Histology 2.5.1**  **Method of kill** Animals killed during the study and those surviving until the end o f the scheduled treatment or recovery

period were killed by

overdose of sodium

pentobarbitone so lut io n by intravenous inject io n and subsequent exsanguination. The sequence in which the animals were killed af ter com plet io n of trea

tment or recovery

was selected to allow sat isfactory int er - group com parison.Huntingdon Life Sciences WAG0014

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### 2.5.2 **Macroscopic pathology** All animals were subject to a detailed necropsy. After a review of the history of each animal, a full macroscopic examinat io n of the tissues was performed. All external features and orifices were examined visually. The cranial roof was removed to allow observat io n of the brain, pit ui tary gland and cranial nerves. After ventral mid - line incisio n, the neck and associated tissues and the thoracic, abdo minal and pelvic cavit ies and their viscera were exposed and examined in situ. Any abnormal posit io n, mo rphology

or interaction was recorded. The requisi

te organs were weighed and external and cut surfaces of the organs and tissues were examined as appropriate. Any abnormalit y in the appearance or size of any organ and tissue was recorded and the required tissue samples preserved in appropriate fixat ive. The retained tissues were checked before disposal of the carcass. **2.5.3 Organ weights**  The fo llo wing organs, taken from each animal

killed after 13 weeks of treatment or 4 weeks of recovery, were dissected free of adjacent fat and other contiguous tissue and the weights recorded: Adrenals Prostate Brain Salivary glands (submandibular/sublingual)# Epididymides Seminal vesicles Heart Spleen Kidneys Testes Liver Thymus Lungs with mainstem bronchi Thy roid wi th parathy roids* Ovaries Uterus wi th cervix P ituit ary * Weighed after partial fixation # Weighed together and reported as salivary glands 

### Bilateral organs were weighed together . Organ weights were also adjusted for terminal body weight, using the weight recorded before necropsy.Huntingdon Life Sciences WAG0014

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### 2.5.4 **Fixation** Testes were fixed in modified Davidson's fluid and eyes were fixed in Davidson's fluid. Sam ples (or the whole) of the other tissues listed below fro m all animals were preserved in 10% neutral buffered formalin: Adrenals Ovaries Ao rta - thoracic Pancreas Bone marrow smear Peyer’s patches Brain Pi tui tary Caecum Prostate Colon Rectum Duodenum Salivary glands - submandibular+ Epididymides - parotid+ Eyes - sublingual+ Femurs+ Sciat ic nerves+ Harderian glands Seminal vesicles Head# Skeletal m uscle+ Heart Skin wi th mammary glands Ileum Spinal cord Jejunum Spleen Kidneys Sternum Lachryma l glands Stomach Larynx T eeth - lo wer incisors (pair) Liver Testes Lungs Thymus Lymph nodes - mandibular Thy roid wi th parathy roids

- me senteric Tongue - tracheobronchial Trachea Nasal turbinates Urinary bladder Oesophagus Uterus and cervix Optic nerves Vagina + Only on e processed for examination # Not processed for examination 

### Sam ples o f any abnormal t is sues were also retained and processed for examinat io n. In those cases where a lesio n was not clearly delineated, cont iguous tissue was fixed with the grossly affecte d region and sect io ned as appropriate. Sam ples o f the head (including nasal cavit y, paranasal sinuses and nasopharynx) and the remaining femur, salivary gland, sciat ic nerve and skeletal muscle were not examined histologically, but are retained against any future requi rement for microscopic examinat io n.Huntingdon Life Sciences WAG0014

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### 2.5.5 **Histology** For those animals specified in the Patho lo gy sect io n, the relevant tissues were subject to histological processing. Those tissues subject to histological processing included the fo llo wing regions: Adrenals - cortex and medulla Brain - cerebellum, cerebrum and midbrain Femur wi th j oint - lo ngitudinal sect io n including articular surface, epiphysial

plate and bone marrow Heart - included auricular and ventricular regions Kidneys - included cortex, medu lla and papilla regions Liver - sect io n from two ma in lob es Lungs - sect io n from all major lobes, to include bronchi Spinal cord - transverse and lo ngitudinal sect io n at the cervical, lumbar and

thoracic levels Sternum - included bone marrow Stomach - included keratinised, glandular and antrum in sect ions Thy roid - included parathy roids in sect io n where possible Uterus - uterine body wi th cervix sect io n For bilateral organs, sections of both organs were prepared. A single section was prepared fro m each of the remaining tissues required for microscopic pathology . 

## 2.6 **Pathology 2.6.1**  **Light microscopy** Microscopic examination was performed as follows: All t issues preserved for examinat io n (as specified above) were examined for all animals o f Groups 1 (Control) and 4 (28 76 ppm ) sacrificed on com

plet io n of the scheduled treatment period and for all animals killed or dying during the study. Nasal turbinates, larynx, lungs, trachea (including bifurcation) , heart, liver, pancreas, spleen, thymu s , teeth and abnormalit ies pres erved for examinat io n were examined fo r all animals of Group 2 ( 199 ppm), Group 3 ( 505 ppm) and all recovery animals sacrificed on complet io n of the scheduled treatment period. Tissues reported at macroscopic examinat io n as being grossly abnormal were examined for Main and Recovery animals in line wi

th current practice. Findings were either reported as "present" or assigned a severit y grade. In the latter case one of the fo llo wing five grades was used - minimal, slight, moderate, marked or severe. A rev iewing pathologist undertook a peer review o f the microscopic findings.Huntingdon Life Sciences WAG0014

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### The descript io ns listed below are an attem pt to define the grades in general t erms fo r all microscopic findings reported in a study and are not specific fo r a particular tissue. They are mo re strictly applicable to so me ty pes of l esion than to others, and there may therefore be a few lesio ns fo r which these definit io ns are not completely appropriate. Thresho lds fo r the grading of l esions fo r certain tissues may vary wi th ty pe of study and also may vary, generally for all t is sues or the maj ori ty of tissues, wi

th the duration of

the study. In increasing order of degree/severit y. **Minimal** The lo west grade of a l esion which is discernible/dist inguishable from normal and is of

ten subt le and/o r invo lving a very s mall area of

the organ. **Slight** Clearly discernible/dist inguishable from normal wi th more extensive or mo re apparent changes than minimal. **Moderate** Generally invo lves a significant proportion of the affected organ or tissue. **Marked** Invo lves the majorit y of the affected organ or tissue. **Severe** Invo lves all or almo st all of an affected organ or tissue. A reviewing patho lo gist undertook a peer review of the microscopic findings. In addit io n, heart tissue slides from all males (main study and recovery

) were independently peer reviewed by an external consultant pathologist.Huntingdon Life Sciences WAG0014

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## 2.7 **Computer s ystem**  **s** The computer systems wi th version numbers that were used on this study to acquir e and quant ify data include: ClinAxys II (versio n 2.0.2) used for haematology, blood chemistry and urinalysis. Liberate Release 2 in- house system used for reporting clinical signs, dosing signs, body weights, food consumpt io n, organ weights, macropathology and histopathology, statist ics. Quasar (versio n 1. 3) and SAS (versio n 9.1.3) in- house statist ical analysis package s used for bodyweights and organ weights statistics . RAMS Rodent Activit y Moni toring System

(version 2.0) used for activit y mo nit oring. Responder - X (version 5.11) used for startle response. Sam ple Registry

System (versio n 1.0) used for Formulat io n and Inhalat io n Analysis data. StarTox (version 3.2) in- house statist ical analysis package used for gri p strength and mo tor activit y and clinical patho lo gy statist ics . Waters Empower 2, Build 2154, Feature Release 4, Servic e Pack D and used for Form ulat io n and Inhalat io n Analysis. Xybio n Path/Tox System (versio n 4.2.2) used for clinical signs, dosing signs, body weights, food consumpt io n, ophthalmic examinat io n, organ weights, macropathology

and histopathology. Xybio n Prist ima (version 6. 3 ) used for Pharmacy test substance management . 

## 2.8 **Data treatment** This report contains serial observations pertaining to all weeks of treatment and recovery com pleted, together with signs data collected during the necropsy period. The only seri al observat io ns relat ing to the acclimat isat io n period included in this report relate to the detailed physical examinat io n and arena observations, Week - 1 bodyweights, food consumpt ion and ophthalmic examinat io n. Summary statistics (e.g. means and standard deviatio ns) presented in this report were calculated from

com puter - stored individual raw data. The summary statist ic s and the individual data were stored in the computer to a certain number of decimal places, different fo r each parameter. For presentation purposes, however, they were usually

rounded to fewer places. It is, therefore, not generally possible to reproduce the presented means and standard deviat io ns exactly using the presented individual data.Huntingdon Life Sciences WAG0014

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### Throughout the report the fo llo wing abbreviat io ns are used: M Male F Female R Recovery N Number of animals/cages examined SD Standard deviat io n The death codes in the appendi ces have the fo llo wing meaning: T Scheduled kill W Killed for reasons of animal welfare **2.8.1 Definition of “Week”**  The first week of treatment started at midnight prior to treatment commencing and ended at midnight on the seventh day f ollo wing. Subsequent experimental weeks of treatment and recovery were of the same durat io n. **2.8.2 Signs**  Signs are considered in two parts: observat io ns made in associat io n wi th treatment, classified as “dosing signs” and extended changes in condit ion, classified as “clinical signs”. Both are presented for each animal that showed signs, providing detail of ty pe of sign, day or week of occurrence and information on the duration of the sign applicable. Observations during the recovery phase are recorded on a study week basis. Weeks of study relate to weeks of recovery as fo llo ws: Week of recovery Week of Study R1 14 R2 15 R3 16 R4 17 **2.8.3 Bodyweight**  Group mean we ight changes were calculated fro m the weigh t changes of individual animals surviving the specified period. **2.8.4 Ophthalm**  **ic examination** For each animal that showed findings, observations are presented in the final report. Observations were bilateral unless otherwise indicated: L Left eye R Right eyeHuntingdon Life Sciences WAG0014

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### 2.8.5 **Haematology** The abbreviat io ns used in the Appendix have the following meanings: NVR No valid resul t CTD Clotted sam ple **2.8.6 Blood chemistry**  Albumin to globulin ratio (A/G ratios ) were calculated as:

A/G Ratio = Albumin c oncentration

Total protein

– albumin concentration 

### 2.8.7 **Urinalysis** The abbreviat io ns used in the Append ix have the following meanings: TNQ Too numerous to quantify INS Insufficient sample Group means and standard deviat io ns are presented for volume, pH, sp ecific gravit y, protein and electroly

tes only . **2.8.8 Organ weights**  The abbreviat io ns used in the Append ix have the following meanings: Thy roids + Paras Thy

roids wi th parathy roids **2.8.9 Pathology**  The abbreviat io ns used in the Appendix have the following meanings: LN Lymph nodes Bifurc. Bifurcat io n C. Cord Cerv. Cervical Lum b. Lumbar Thor. Thoracic Fac. Con. Factors contribut ing S.G. Salivary

glands inc. Including Tissues which could not be examined are specified in the Appendix. The absence of a comment for a tissue scheduled for examinat io n therefore indicates that the tissue was considered to be normal. In all tabular presentations o f data the tissues specified in the protocol f or histopathological examinat io n precede other tissues.Huntingdon Life Sciences WAG0014

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### 2.8.10 **Statistical analysis**  All statistical analyses were carried out separately for males and females. All analyses were carried out using the individual animal as the basic experimental unit. The fo llo wing data ty

pes were analysed at each timepo intseparately: Gri p strength and motor activit y Body weight, using gains over appropriate study periods Blood chemistry, haematology and urinalysis Organ weights , ei

ther absol ute or adj usted for terminal bodyweight where appropriate The fo llo wing sequence of statist ical tests was used for grip strength, motor activit y, body weight, organ weight and clinical patho lo gy data: A parametric analysis was performed if Bartlett's test for variance homogeneit y ( Bartlett 1937 ) was not significant at the 1% level. The F 1 

### approximate test was applied. This test is designed to detect significant departure from mo notonici ty of means when the main test for the comparison of the means is a parametric mo notonic trend test, such as Williams’ test ( Williams 1971, 1972 ). The test statist ic compares the mean square, NMS, for the deviat io ns o f the observed means fro m the maximum

likelihood means, calculated under a constraint of monotonicit y wi th the usual error mean square, EMS. The null hypothesis is that the true means are monotonically ordered. The test statist ic is F 1 

### = NMS/EMS which can be com pared wi th standard tables o f the F distribut io n wi th 1 and EMS degrees of freedo m. If

the F 1 

### approximate test for monotonicity of dose - response was not signific ant at the 1% level, Williams' test for a monotonic trend was applied. If the F 1 

### approximate test was significant, suggesting that the dose response was not mo notone, Dunnett's test ( Dunnett 1955, 1964 ) was performed inste ad . Where there were only two groups, com

parisons were made using t- tests. A non- parametric analysis was performed if Bartlett's test was still significant at the 1% level fo llo wing both logari thmic and square - root transformat io ns. The H 1 

### approximate te st, the non- parametric equivalent of the F 1 

### test described above, was applied. This test is designed to be used when the main test for comparison o f the means is a non- parametric monotonic trend test, such as Shirley's test ( Shir ley 1977 ). The test statist ic compares the non- mo notonicit y sums of squares, NRSS, for the deviat io ns o f the observed mean ranks from the maximum likelihood mean ranks wi th the non- parametric equivalent of the error sums of squares, ERSS = N(N+1)/1 2. The test statistic is H 1 

### = NRSS/ERSS which can be co mpared to standard tables of

the χ2 - distribution wi

th 1 degree of freedo m. If

the H 1 

### approximate test for monotonicit y of dose - response was not significant at the 1% level, Shirley's test for a monotonic trend was applied. If the H 1 

### approximate test was significant, suggesting that the dose - response was not monotone, Steel's test ( Steel 1959 ) was performed instead . Where there were only two groups, com parisons were made using Wilco xon rank sum tests ( Wilcoxon 1945 ).Huntingdon Life Sciences WAG0014

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### For gri p strength, motor activit y and clinical pathology data, if 75% of the data (across all groups) were the same value, for example c, Fisher’s Exact test s ( Fisher 1973 ) were performed. Treatment groups were c om pared using pai

rwise com

parisons of each dose group against the control both for i) values <c versus values ≥c, and for ii) values ≤c versus values >c, as applicable. For organ weight data, analysis of covariance was performed using terminal body weight a s covariate (Ang ervall and Carlstrom, 1963 ) , unless non- parametric methods were applied . The treatment comparisons were made on adjusted group means in order to allow for differences in body

weight which might influence the organ weights. **Key to Tables** Significant differences between the groups compared were expressed at the 5% ( p <0.05) or 1% ( p <0.01) level. The key to the annotation used on the tables that contain statistical result s is given below. l Data were log transfo rmed f or the statist ical analysis. Du Treated groups compared to Control using Dunnett’s test. Sh Treated groups compared to Control using Shirley’s test. Wi Treated groups compared to Control using Williams’ test. Tt Group 4 co mpared with Control/Vehicle using t -te st. Wc Group 4 co mpared with Control/Vehicle using Wilcoxon rank sum test. Codes placed above adjusted means indicate that the co mpar isons were based on adjusted means . * p<0.05 ** p<0.01Huntingdon Life Sciences WAG0014

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## 2.9 **Quality assurance and archiving procedures 2.9.1**  **Quality assu**  **rance** Details o f the Qualit y Assurance inspections and audits (undertaken at Huntingdon Life Sciences) are presented on the Qualit y Assurance Statement. **2.9.2 Archives**  Fo llo wing com

plet io n of this study

all raw data, specimens and samples, except those generated or used during any Sponsor’s or supplier’s analysis, were stored in the archives o f Hunt ingdon Life Sciences. Types of sample and specimen which are unsuitable, by reason o f instabilit y, f

or long term

retention and archiving may b e disposed of after the periods stated in Hunt ingdon Life Sciences Standard Operating Procedures. A copy of the final report and all

Quali ty A ssurance inspect io n records will be retained indefinit ely . All other appropriate specimens and records will be retained fo r a minimum period of one year fro m the date of issue of the final report. At the end of this retention period the Sponsor will be contacted and advice sought on future archiving requirements. Under no circumstances will any item be discarded without the Sponsor’s knowledge . 

## 2.10 **Deviations from protocol** The fo llo wing deviat io ns from protocol occurred: Section 5.1 of the protocol stated that pre - study characterizat io n work would only be performed to “demonstrate reproducibilit y of test substance concentration”. However, addi

tional work was also carried out to confirm that the spatial distribut io n of the test material around the chamber was consistent for the high number of animals dosed in each chamber. The deviat io n fro m protocol strengthened the pre - study atmosphere charac terization work and confirmed that it satisfied the needs o f the study. Treatment related effects on the teeth of Group 4 females (brittleness and breakage) resul ted in a reduction in food consumpt io n. Consequent ly, powdered diet (standard pelleted diet, as supplied to other study rats, ground down to powder) was supplied to all Group 4 females fro m Day 64 (Cage 7) or Day

72 (Cages 8, 19 and 20) . Food consumption recording was unaffected by the supply

of the powered diet. These deviat io ns were considere d to have not affected the integri ty or validit y of

the study.Huntingdon Life Sciences WAG0014

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# 3. **Result s**  **3.1 Chamber atmosphere conditions**  Annex 2 Summary data are presented below: **Group Aerosol c**  **oncentration (ppm)**

**Target Study mean**  1 0 - 2 200 199 3 500 505 4 3000 2876 

### The achieved aerosol concentrations were 100 , 101 and 96% of the target concentration for Groups 2, 3 and 4, respectively. 

## 3.2 **Signs and mortality** Appendix 1 and Appendix 2 There were no deaths that were considered to be a direct result of exposure to the test material, 2 bromo 3,3,3 trifluoropropene. Animal 79, a ma le exposed to 2876 ppm, died in i tsho me cage prior to the start of exposures on Day 3. Animal 79 had no apparent abnormalit ies at the init ial mo rning heal th check. However, its condit io n was then seen to decline over a period of less than an hour, and it died before a necropsy

could be arranged. Macroscopic examinat io n at necropsy revealed; dark lungs, inco mp lete collapse of the lungs and slightly dark tracheobronchial lymph nodes. This decedent was renumbered 79R and replaced wit h a spare rat given the original number (79). The replacement was made prior to the start of Day 3 exposures. No data from Animal 79R is presented in this report. Animal 27, a Control fe male, was killed on welfare grounds on Day 52. At the init ial mo rning healt h check Anima l 27 was found to be underact ive, with reduced body tem perature, gasping breathing, piloerect io n, partially clos ed eyelids and pallor. The animal was subsequently sent to necropsy due to general poor clini cal condi tion . Macroscopic examinat io n at necropsy

revealed; thickened pericardium of the heart with adhesio ns and copious amounts of dark pericardial fluid, irregular surface of the liver, dark tracheobronchial lymph nodes, copious amounts of clear, sero us fluid in the thorax, and oedematous pancreas and thymus.Huntingdon Life Sciences WAG0014

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### Clinical signs seen during exposure over the 13 weeks of treatment , f or all groups exposed to the test material, included: unresponsiveness to external st imuli, underactivit y, slow and/or shallo w breathing, hunched posture (Day 1 and 94 only), grinding teeth ( at 505 ppm, Day 25 only), piloerection and partially closed eyelids (clo sed eyelids on Day 1). These signs generally reso lved quickly on cessat io n of exposure to the test article. The number and prevalence o f signs increased wit h exposure level . Abnormally

pale, whi te teeth were evident for animals from all test material groups . Animal 92, a fe male exposed to 2876 ppm was observed as having broken teeth on Day 71. A proportion of fe males exposed to 2876 ppm, teeth were reported as having br ittle teeth . Consequent ly, all females exposed to 2876 ppm received powdered diets fro m Day 64 (Cage 7) or Day

72 (Cages 8, 19, and 20). 

## 3.3 **Sensory reactivity and grip strength**  Table 1 and Appendix 3 Sensory react ivit y observat io ns for males and females were unaffected. During Week 1 2 of

treatment gri

p strength values were statist ic ally significant ly reduced fo r animals exposed to 2876 ppm (forelimbs and hindlimbs) and in males exposed to 505 ppm (hindlimbs only). Gri

p strength for animals exposed to 199 ppm and for females exposed to 505 ppm was unaffected. Forelimb grip strength values for animals previously exposed to 2876 ppm were similar to those of controls during Week 4 of recovery but hindlimb value s were still low, although to a lesser extent than during Week 1 2 of treatment. 

## 3.4 **Motor activity** Figure 1 , Table 2 and Appendix 4 High beam

and low beam

motor activi

ty scores (rearing and cage floor activit y respect ively) were consistently reduced in animals exposed to 2876 ppm throughout most of the 1 - hour recording period during Week 1 2 of treatment. High beam scores for animals exposed to 505 ppm were also reduced, as, to a lesser extent, were low beam scores for females exposed to 505 ppm, with a dose - re lat io nship being evident. Motor activit y fo r animals exposed to 199 ppm was considered to be unaffected , despi te statist ically significant reductions for both high and low beam scores at a single t imepo int(36 minutes) . Low beam scores for females previously exposed to 2876 ppm were again low compared wi th control scores during Week 4 of recovery but the differences were less marked than during Week 1 2 of

treatment. High and low beam scores for males previously exposed to 2876 ppm were lower than contro l at a few of the 6 - minute intervals (p<0.05 or 0.01) but the total act ivit y scores over the 1 - hour recording period did not attain statistical significance.Huntingdon Life Sciences WAG0014

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## 3.5 **Bodyweight** Figure 2 , Table 3 and Appendix 5 Body weight gain over the 13 weeks of treatment were statist ically significant ly lo wer f or males receiving 199, 505 or 2876 ppm (0.78X, 0.73X and 0.52X con trol respect ively) and for females receiving 505 or 2876 ppm (0.79X and 0.55X control respect ively), with evidence of a dose relat io nship. Differences fro m controls remained similar throughout the study period f or animals receiving 199 or 505 ppm . However, for animals receiving 2876 ppm, the reduction in body weight gain was mo re marked fro m Week 6 until the end of treatment. Over the 4 week recovery period , body

weight gains for males and females previously receiving 2876 ppm showed evidence of recovery and were 1.82 and 1.7 7 X control values respectively. However, gains were small for females, and overall body weights were still considerably reduced co mpared wi th control values. 

## 3.6 **Food consumption** Appendix 6 Mean food consumpt io n over the 13 weeks of treatment was statist ic ally significant ly lo wer fo r treated ma les (0.90X, 0.85X and 0.74X control , wi th ascending dose) and females exposed to 2876 ppm co mpared w ith control (0.81X control), with evidence of a dose relat io nship in males. Wit hin groups, food consumpt io n was consistent throughout the study period, wi

th similar differences fro m control

seen after 6 and 10 w eeks to those seen after 13 weeks. Over the 4 week recovery period, animals previously ex posed to 2876 ppm showed so me recovery of f ood consum

pt io n compared to treatment values, and were approximately 0.9X co ntrol

values over the recovery period. 

## 3.7 **Ophthalm ic examination**  Appendix 7 Ophthalmic examinat ion revealed no treatment - related effects. 

## 3.8 **Haematology** Table 4 and Appendix 8 Week 13 group mean total white blood cell counts were lower than control for males and females exposed to 2876 ppm (0.78 and 0.68X control respectively), statist ically significant ly so for females. This was mainly as a result of statistically significant ly lo wer lymphocy tes counts (0.68 and 0.66X con trol f or males and females exposed to 2876 ppm, respect ively). During W eek 4 of recovery, differences from control for total white b lo od cell and lymphocy te counts remained similar to Week 13 values for both sexes previously exposed to 2876 ppm .Huntingdon Life Sciences WAG0014

36 

### Eosinophil counts were statistically significant ly lo wer than control for all treated animals, wi th evidence of a dose - related response (0.26 to 0.47X and 0.27 to 0.64X control for males and females exposed to 199 and 2876 ppm respect ively). However, during Week 4 of recovery eosinophil counts showed evidence of some recovery to control

val ues. Monocy te counts were statistically significant ly higher than control for males and females exposed to 505 and 2876 ppm (1.74 and 1.84X control for males, and 2.16 and 1.68X control fo r females respect ively). However, during Week 4 of recovery monocy te counts were lower than control values for both sexes previously ex posed to 2876 ppm . Remaining differences fro m control that attained statist ic al

significance were small, inconsistent between sexes and did not show clear dose relat io nships. 

## 3.9 **Blood chemistry** Table 5 and Appendix 9 Week 13 mean al

kaline phosph atase (ALP) values for males and females exposed to 2876 ppm were statist ically significant ly higher (1.32 and 1.43x c ontrol, respectively). During W eek 4 of recovery, values for males previously exposed to 2876 ppm were unchanged. However, for females of the same group , val ues had lowered and were similar to Week 13 control values. Group mean values for aspartate amino transferase (AST) were statist ically significantly higher than control for treated ma les (2.31, 3.00 and 2.88X with ascending dose ), and f emales exposed to 505 ppm (2.72X control). There was considerable intragroup variation for this parameter. However, the group mean changes seen were outside the range of available background data . During Week 4 of recovery, values for both sexes previou sly exposed to 2876 ppm were similar to controls. Group mean values for urea were statist ically significant ly higher than control for treated females (1.18, 1.24 and 1.54X control with ascending dose), and males exposed to 505 and 2876 ppm (1.25 and 1.64X co ntrol, respectively).Group mean phosphate values were statist ically significant ly higher for treated females (1.42, 1.75 and 2 .38X con trol, wi th ascending dose) and males exposed to 2876 ppm (1.3 0X control). During Week 4 of recovery, urea val

ues f or bo th sexes previously

exposed to 2876 ppm had returned to control values. Remaining differences fro m control that attained statist ic al

significance were inconsistent between sexes and did not show clear dose relat io nships. 

## 3.10 **Urinalysis** Table 6 and Appendix 10 There were no treatment related effects on urinalysis parameters. Differences between control and test values that attained statistical significance for urinalysis parameters were often inconsistent between sexes and were related to slight differences in urine vo lume.Huntingdon Life Sciences WAG0014

37 

## 3.11 **Organ weights** Table 7 and Appendix 11 After 13 weeks of treatment, thymus weights were statist ically significant ly lo wer f or males and females exposed to 2876 ppm (0.63 and 0.54X control, respect ively). However, after 4 weeks recovery, thymus weights appeared to have fully recovered to control values. Lung and bronchi weights were slight ly elevated for males exposed to 505 or 2876 ppm (1.07 and 1.12X control respectively), with similar values after 4 weeks of treatment for males previously exp osed to 2876 ppm . Salivary gland weights were statist ically significantly lower than control values for all treated females (0.81, 0.82 and 0.84X control, with ascending dose). For males, a reduction in salivary gland weights was also evident (between 0.88 and 0.89X control for all treated males), however, these did not achieve statist ical significance. However, after 4 weeks recovery these have recovered to con trol values. Remaining differences fro m control that attained statist ic al

significance were inc onsistent between sexes and considered to be due to individual variat io n and not of any toxicological importance.Huntingdon Life Sciences WAG0014

38 

## 3.12 **Macropathology** Table 8 , Appendix 12 and Annex 3. **3.12.1 Animals killed after 13 weeks of treatment**  The macroscopic examinat io n performed after 13 weeks of treatment revealed the fo llo wing int ergroup differences of note: **Teeth** Pallor was noted in all animals exposed to 2876 ppm, the majorit y of animals exposed to 505 ppm and a few animals exposed to 199 ppm. Thickening was seen in the majorit y of femal es and one male exposed to 2876 ppm. **Summary of findings in the teeth for animals killed after 13 weeks of treatment Group/sex**  **1M 2M**  **3M 4M**  **1F 2F**  **3F 4F**  **Dose (ppm) 0**  **199 505**  **2876 0**  **199 505**  **2876** Incisor(s) pale 0 3 7 10 0 3 9 10 Incisor(s) thickened 0 0 0 1 0 0 0 8 Number of animals examined 10 10 10 10 9 10 10 10 

### Spleen Capsular thickening was observed in the majorit y of males and so me females exposed to 2876 ppm and a few animals exposed to 505 ppm. Adhesio ns were noted in so me females exposed to 505 or 2876 ppm. **Summary of findings in the spleen for animals killed after 13 weeks of treatment Group/sex**  **1M 2M**  **3M 4M**  **1F 2F**  **3F 4F**  **Dose (ppm) 0**  **199 505**  **2876 0**  **199 505**  **2876** Capsule thickened 1 1 4 8 0 1 2 5 Adhesion s 0 0 0 0 0 0 2 5 Number of animals examined 10 10 10 10 9 10 10 10 

### The nature and incidence of all the other findings were consistent with the commo nly seen background of macroscopic changes.Huntingdon Life Sciences WAG0014

39 

### 3.12.2 **Animals killed after 4 weeks of recovery** The macroscopic examinat io n performed after 4 weeks of recovery revealed the following changes in teeth and spleen. **Teeth** Pallor was noted in all animals exposed to 2876 ppm. Thickening was seen in occasional females and one male previously exposed to 28 76 ppm . **Summary of findings in the teeth for animals killed after 4 weeks of recovery Group/sex**  **1M 4M**  **1F 4F**  **Dose (ppm) 0**  **2876 0**  **2876** Incisor(s) pale 0 10 0 10 Incisor(s) thickened 0 1 0 3 Number of tissues examined 10 10 10 10 

### Spleen Cap sular thickening was observed in one male previously exposed to 2876 ppm. Adhesio ns were noted in so me males and one female previously exposed to 2876 ppm. **Summary of findings in the spleen for animals killed after 4 weeks of recovery Group/sex**  **1M 4M**  **1F 4F**  **Dose (ppm) 0**  **2876 0**  **2876** Capsular thickened 0 1 0 0 Adhesions 0 2 0 1 Number of tissues examined 10 10 10 10 

### All other findings were considered to be unrelated to treatment.Huntingdon Life Sciences WAG0014

40 

## 3.13 **Histopathology** Table 9, Appendix 12 , Annex 3 and Annex 4. **3.13.1 Anim**  **als killed after 13 weeks of treatment Treatment related findings**  Changes related to treatment with 2 - bromo- 3, 3, 3 -trifluoropropene were seen in liver, pancreas, heart, spleen, thymus, larynx, nasal turbinates and teeth. **Liver** Centrilo bular hepatocy

te hyp ertrophy

was seen in rats exposed to 2876 ppm and a female exposed to 505 ppm. **Summary of treatment related findings in the liver for animals killed after 13 weeks of treatment Group/sex**  **1M 2M**  **3M 4M**  **1F 2F**  **3F 4F**  **Dose (ppm) 0**  **199 505**  **2876 0**  **199 505**  **2876** Hepatocyte Hypertrophy, Centrilobular Minimal 0 0 0 2 0 0 1 4 Total 0 0 0 2 0 0 1 4 Number of tissues examined 10 10 10 10 9 10 10 10 

### Pancreas Increased incidence of acinar cell degranulat io n was seen in rats at all exposure levels. **Summary of treatment related findings in the pancreas for animals killed after 13 weeks of treatment Group/sex**  **1M 2M**  **3M 4M**  **1F 2F**  **3F 4F**  **Dose (ppm) 0**  **199 505**  **2876 0**  **199 505**  **2876** Acinar Cell Degranulation Minimal 0 3 2 1 0 2 3 0 Slight 0 0 3 5 1 2 2 6 Moderate 0 0 0 1 0 0 0 0 Total 0 3 5 7 1 4 5 6 Number of tissues examined 10 10 10 10 9 10 10 10Huntingdon Life Sciences WAG0014

41 

### Heart Increased incidence of chronic inflammat io n was seen in males exposed to 199 ppm and both sexes exposed to 505 or 2876 ppm . **Summary of treatment related findings in the heart for animals killed after 13 weeks of treatment Group/sex**  **1M 2M**  **3M 4M**  **1F 2F**  **3F 4F**  **Dose (ppm) 0**  **199 505**  **2876 0**  **199 505**  **2876** Inflammation, Chronic Minimal 0 4 2 1 0 0 4 7 Slight 0 0 7 3 0 0 0 2 Moderate 0 0 0 4 0 0 0 1 Total 0 4 9 8 0 0 4 10 Number of tissues examined 10 10 10 10 9 10 10 10 

### Spleen Increased incidences of capsular inflammat io n and/ or thickening were seen in rats exp osed to 505 or 2876 ppm. Adhesion was seen in females exposed to 505 or 2876 ppm. **Summary of treatment related findings in the spleen for animals killed after 13 weeks of treatment Group/sex**  **1M 2M**  **3M 4M**  **1F 2F**  **3F 4F**  **Dose (ppm) 0**  **199 505**  **2876 0**  **199 505**  **287 6**  Capsular Inflammation Minimal 0 0 1 2 0 1 0 1 Slight 0 0 1 3 0 0 1 3 Moderate 0 0 1 0 0 0 0 2 Total 0 0 3 5 0 1 1 6 Capsular Thickening Minimal 0 1 1 4 1 2 2 2 Slight 1 0 2 2 0 0 1 2 Moderate 0 0 0 0 0 0 0 4 Total 1 1 3 6 1 2 3 8 Adhesion Total 0 0 0 0 0 0 1 3 Number of tissues examined 10 10 10 10 9 10 10 10Huntingdon Life Sciences WAG0014

42 

### Thymus Invo lut io n/ atrophy

was seen in one male and five female rats exposed to 2876 ppm. **Summary of treatment related findings in the thymus for animals killed after 13 weeks of treatment**  **Group/sex 1M**  **2M 3M**  **4M 1F**  **2F 3F**  **4F Dose (ppm)**  **0 199**  **505 2876**  **0 199**  **505 2876**  Involution/Atrophy Minimal 0 0 0 0 0 0 0 2 Slight 0 0 0 0 0 0 0 1 Moderate 0 0 0 1 0 0 0 2 Total 0 0 0 1 0 0 0 5 Number of tissues examined 10 10 10 10 9 10 10 10 

### Larynx Ventral squamous metaplasia was seen in five male and two female rats exposed to 2876 ppm. **Summary of treatment related findings in the larynx for animals kille d after 13 weeks of treatment**  **Group/sex 1M**  **2M 3M**  **4M 1F**  **2F 3F**  **4F Dose (ppm)**  **0 199**  **505 2876**  **0 199**  **505 2876**  Squamous Metaplasia - Ventral Minimal 0 0 0 5 0 0 0 2 Total 0 0 0 5 0 0 0 2 Number of tissues examined 10 10 10 10 9 10 10 10 

### Nasal Turbinates In the respiratory

epi thelium, atrophy

/disorganization/vacuo lat io n, inflammat io n and inflammatory

cells in the lamina propria were seen in the rats exposed to 2876 ppm. A case of regenerat ive hyperplasia was also seen in a male at the same exposure level. In the olfactory

epi thelium, atrophy

/ disorganisat io n /vacuo lat io n, was seen in rats exposed to 505 or 2876 ppm. Inflammat io n and inflammatory cells in the lamina propria were seen in rats exposed to 2876 ppm. Respi ratory metaplasia was seen in females exposed to 2876 ppm. In the naso la crimal duct, inflammat io n was seen in females exposed to 505 ppm and both sexes exposed to 2876 ppm. Epithelial squamous metaplasia and luminal inflammatory exudates were seen in fema les exposed to 2876 ppm. Inflammatory

exudates in airways were seen in rats exposed to 2876 ppm.Huntingdon Life Sciences WAG0014

43 **Summary of treatment related findings in the nasal turbinates for animals killed after 13 weeks of treatment**  **Group/sex 1M**  **2M 3M**  **4M 1F**  **2F 3F**  **4F Dose (ppm)**  **0 1**  **99 505**  **2876 0**  **199 505**  **2876** Inc reased Vacuolation of Vomeronasal Organ Epithelium Minimal 0 0 0 1 0 0 0 0 Slight 0 0 0 2 0 0 0 0 Total 0 0 0 3 0 0 0 0 Respiratory

Epithelium Atrophy/ Disorganisation/ Vacuolation Minimal 0 1 0 1 1 1 1 1 Slight 0 0 0 4 0 0 0 6 Moderate 0 0 0 1 0 0 0 3 Total 0 1 0 6 1 1 1 10 Inflammation Minimal 0 0 0 0 0 0 0 1 Slight 0 0 0 1 0 0 0 2 Total 0 0 0 1 0 0 0 3 Inflammato

ry Cells in the Lamina Propria Minimal 0 0 0 0 0 0 0 2 Slight 0 0 0 0 0 0 0 8 Moderate 0 0 0 1 0 0 0 0 Total 0 0 0 1 0 0 0 10 Regenerative Hyperplasia Slight 0 0 0 1 0 0 0 0 Total 0 0 0 1 0 0 0 0 Olfactor y Epithelium Atrophy/ Disorganisation/ Vacuolation Minimal 1 2 5 0 0 0 2 0 Slight 0 0 3 8 1 0 3 4 Moderate 0 0 0 2 0 0 0 6 Total 1 2 8 10 1 0 5 10 Inflammation Slight 0 0 0 3 1 0 0 2 Total 0 0 0 3 1 0 0 2 Inflammato

ry Cells in the Lamina Propria Minimal 0 0 0 0 1 0 0 1 Slight 0 0 0 2 0 0 0 7 Tota l 0 0 0 2 1 0 0 8 Respiratory

Metaplasia Minimal 0 0 0 0 0 0 0 1

Slight 0 0 0 0 0 0 0 4 Total 0 0 0 0 0 0 0 5 Number of tissues examined 10 10 10 10 9 10 10 10Huntingdon Life Sciences WAG0014

44 **Summary of treatment related findings in the nasal turbinates for animals killed after 13 weeks of**  **treatment (Cont’d) Group/sex**  **1M 2M**  **3M 4M**  **1F 2F**  **3F 4F**  **Dose (ppm) 0**  **199 505**  **2876 0**  **199 505**  **2876** Nasolacrimal Duct Inflammation Minimal 1 3 1 2 2 1 1 0 Slight 4 5 3 5 0 3 5 5 Moderate 0 0 0 1 0 0 1 4 Total 5 8 4 8 2 4 7 9 Epithelial Squamous Metaplasia Minimal 0 1 0 0 1 0 0 1 Slight 1 0 0 0 1 3 2 2 Moderate 0 0 0 0 0 0 0 5 Total 1 1 0 0 2 3 2 8 Luminal Inflammatory Exudate Minimal 0 0 0 0 0 0 0 1 Slight 0 0 0 0 0 0 0 1 Moderate 0 0 0 0 0 0 0 2 Total 0 0 0 0 0 0 0 4 Inflammato

ry Exudate in Airways

Minimal 0 0 0 1 0 0 0 3 Slight 0 0 0 0 0 0 0 2 Total 0 0 0 1 0 0 0 5 Number of tissues examined 10 10 10 10 9 10 10 10 

### Teeth P ul p cavi ty necrosis was seen in females exposed to 2876 ppm. **Summary of treatment related findings in the teeth for animals killed after 13 weeks of treatment Group/sex**  **1M 2M**  **3M 4M**  **1F 2F**  **3F 4F**  **Dose (ppm) 0**  **199 505**  **2876 0**  **199 505**  **2876** Pulp Cavi ty

Necrosis Slight 0 0 0 0 0 0 0 4

Moderate 0 0 0 0 0 0 0 1 Total 0 0 0 0 0 0 0 5 Number of tissues examined 10 10 10 10 9 10 10 10Huntingdon Life Sciences WAG0014

45 

### Findings of an uncertain relationship to treatment **Teeth** Amelo blast degeneration, odontobla st degeneration and pulp cavit y increased inflammatory cell infiltration at most ly minimal level were seen in a few rats exposed to 505 or 2876 ppm. As this finding was only evident for a small number of animals and there was no clear dose relat io nship, the toxicological significance is uncertain. **Summary of findings of an uncertain relationship to treatment in the teeth after 13 weeks of treatment Group/sex**  **1M 2M**  **3M 4M**  **1F 2F**  **3F 4F**  **Dose (ppm) 0**  **199 505**  **2876 0**  **199 505**  **2876** Ameloblast Degeneration Minimal 0 0 0 1 0 0 0 2 Total 0 0 0 1 0 0 0 2 Odontoblast Degeneration Minimal 0 0 0 1 0 0 2 1 Total 0 0 0 1 0 0 2 1 Pulp Cavity Increased Inflammato

ry Cell Infiltration

Minimal 0 0 0 0 0 0 0 1 Slight 0 0 0 0 0 0 0 1 T otal 0 0 0 0 0 0 0 2 Number of tissues examined 10 10 10 10 9 10 10 10 

### Incidental findings Pyelonephri

ti s, wi th hyperplasia of both pelvic and papillary epit helium, in the kidneys and transi tional cell hyperplasia and inflammat io n in the urinary bladder were seen in two females exposed to 2876 ppm. As these findings are occasionally in rats, including controls, they are considered to be incidental and unlikely to be related to exposure to the test material. Malignant adenocarcino ma w as seen in the Harderian gland of a female exposed to 2876 ppm and benign subcapsular cell adeno ma was seen in the adrenal o f a male exposed to 2876 ppm. Both findings are considered to be incidental. All other histological changes were considered to be unrelated to treatment.Huntingdon Life Sciences WAG0014

46 

### 3.13.2 **Animals killed after 4 weeks of recovery Treatment related findings**  **Spleen** Capsular inflammat io n and/ or thickening at slight level were seen in males previously exposed to 2876 ppm. **Summary of treatment -**  **related changes in the spleen for animals killed after 4 weeks of recovery**  **Group/sex 1M**  **2M 3M**  **4M 1F**  **2F 3F**  **4F Dose (ppm)**  **0 199**  **505 2876**  **0 199**  **505 2876**  Capsular Inflammation Minimal 0 - - 2 0 - - 0 Total 0 - - 2 0 - - 0 Capsular Thickening Minimal 0 - - 0 0 - - 1 Slight 0 - - 2 0 - - 0 Total 0 - - 2 0 - - 1 Number of tissues examined 10 - - 10 10 - - 10Huntingdon Life Sciences WAG0014

47 

### Nasal Turbinates In the olfactory

epi thelium, atrophy

/ disorganisat io n/vacuo lat io n, was seen in the rats previously expo sed to 2876 ppm. In the naso la crimal duct, inflammat io n was seen in females previously exposed to 2876 ppm. **Summary of treatment -**  **related changes in the nasal turbinates for animals killed after 4 weeks of recovery**  **Group/sex 1M**  **2M 3M**  **4M 1F**  **2F 3F**  **4F Dose**  **(ppm) 0**  **199 505**  **2876 0**  **199 505**  **2876** Olfactor y Epithelium Atrophy/ Disorganisation/ Vacuolation Minimal 0 - - 2 1 - - 2 Slight 0 - - 7 0 - - 5 Total 0 - - 9 1 - - 7 Nasolacrimal Duct Inflammation Minimal 4 - - 4 5 - - 3 Slight 1 - - 2 0 - - 6 Total 5 - - 6 5 - - 9 Number of tissues examined 10 - - 10 10 - - 10 

### Incidental findings All other histological changes, including chronic inflammat io n seen in the heart of one control ma le and one male previously exposed to 2876 ppm, were consider ed to be unrelated to treatment .Huntingdon Life Sciences WAG0014

48 

# 4. **Discussion** The test article, 2- bromo- 3,3,3 -trifluoropropene, was administered to 3 groups of rats by inhalat io n administration, using a who le - body exposure syst em, f

or 6 hours a day, 5 days a week, for 13 week at achieved aerosol concentrations of 199, 505 and 2876 ppm. A control group of rats received air only at the same airflow as the high dose group. Treatment - related lower body weight gains were seen in male s exposed to 199 ppm and both sexes exposed to 505 or 2876 ppm. These reductions were exposure level related and are considered to be result of treatment and correlate to some extent with reduced food consumption seen for treated males and females exposed to 2876 ppm. There were no deaths that were considered to be a direct result of exposure to the test material, 2 bro mo 3,3,3 trifluoropropene. Clinical signs of shallow breathing, piloerect io n, grinding teeth and hunched posture, evident during and after exposure are indicat ive o f exposure to an irritant material. Whereas, the clinical signs o f unresponsiveness to external st imuli, underact ivit y, and partially clos ed eyelids, together wi

th the reduced gri

p strength and motor activit y responses seen at 505 or 2876 ppm represent potential CNS effects. The histopathological changes seen in the upper respiratory tract (larynx and nasal turbinates) of animals exposed to 2876 ppm and, to a lesser degree, animals exposed to 505 ppm, are consistent with a minor and localised i rri tant effect of the test material. They are similar , to changes seen in the two previous 2 - week dose range studies of the same test material (Hunt ingdon Life Sciences Study Numbers: WAG0013 and WAG0024 ) . In the heart, chronic inflammat io n w as seen in males exposed to 199 ppm and both sexes exposed to 505 or 2876 ppm. The heart tissue samples from all males (main study and recovery ) were independent ly peer reviewed by an external consultant pathologist and the findings agreed between the consul tant and the study

pathologist. The minimal degree observed at 199 ppm is considered unlikely to be associated with any alterat io n of heart funct io n and is considered not adverse. The slight and moderate degrees observed at 505 and 2876 ppm are considered adverse. This change may be related to the elevated al kaline phosphatase and aspartate amino transferase levels measured during Week 13 of exposures , however the toxico lo gical importance of this is unclear . Com plete recovery of

the chronic inflammat io n was seen fo llo wing the 4 week recovery period. In the spleen, capsular inflammat io n and/or thickening and adhesio n, wi th corresponding macroscopic observations, were seen in animals exposed to 2876 ppm and, to a lesser extent, animals exposed to 505 pp m. This is likely to be a toxic effect. Partial recovery was seen fo llo wing the 4 week recovery period wi

th the findings seen in 2 males previously exposed to 2876 ppm. In the thymus, invo lut io n/ atrophy, wi th a corresponding reduction in organ weight, se en in animals exposed to 2876 ppm is likely to be related to the stress of daily exposures to the test material . This effect was also seen in the reductions in body weight gain and food consumption, experienced by the animals at this exposure level .Huntingdon Life Sciences WAG0014

49 

### In the liver, minimal centrilo bular hepatocy te hy pertrophy seen in so me animals exposed to 2876 ppm and a single fe male exposed to 505 ppm , is considered to be an adapt ive change as a resul t of exposure to the test material and not an adverse effect . In the pancreas, increased incidence of acinar cell degranulat io n was seen in animals at all exposure levels. This is not considered to be a toxic response but rather a physio lo gical change and likely

to be related to the lo wer fo od consumpt io n recorded for the se animals. Clinical and macroscopic findings o f pale, thickened and/or brittle incisors were not associated wi

th histopathological

changes. However, pul

p cavi ty necrosis of the teeth, with corresponding macroscopic observat io ns, was seen in females exposed to 2876 ppm, and it is co nsidered to be a toxic effect. High levels o f fluoride have been shown to disturb development of dental enamel ( Aoba 2002 ). Increased mean lung weight and reduced mean salivary gland weight were not associated wi th any histopathological changes and are not considered to be of toxico lo gical importance. Lower values for total

whi te cell, lymphocy

te and eosinophil counts and higher values for monocy te counts , evident for all treated groups, were also not associated wi th any histopatho lo gical changes and are not considered to be of toxico lo gical importance. Fo llo wing a 4 week off

- exposure recovery

period, animals previously exposed to 2876 ppm . showed evidence of recovery wi th regard to bodyweight gain and food consumpt io n. However , o nly partial recovery was evident for grip strength and motor activit y. F or the histopathological changes, fu ll recovery was seen in the larynx, heart, thymus, liver, pancreas and teeth , but only partial recovery was evident f

or the changes in the nasal turbinates and spleen.Huntingdon Life Sciences WAG0014

50 

# 5. **Conclusion** Inhalat io n exposure of CD rats to atmospheres of 2 bromo 3,3,3 -trifluoropropene for 13 weeks, resul

ted in transient clinical sign s , lo wer bodyweight gain, food consumpt io n, grip strength and motor activit y and histopathologi cal changes in the liver, pancreas, heart, spleen, thymus, nasal turbinates, larynx and teeth. The majorit y of these findings were seen with animals exposed to 505 or 2876 ppm. In the heart, chronic inflammat io n was seen in males exposed to 199 ppm and bo th sexes exposed to 505 or 2876 ppm and was considered adverse at 505 ppm or above. The no observed adverse effect level (NOAEL) was considered to be 199 ppm.Huntingdon Life Sciences WAG0014

51 

# 6. References Angervall L and Carlström E (1963) . Theoretical criteria for the use of relative organ weights and similar ratios in biology. J Theoret Biol 4 , 254-9 Aoba T and Fejerskov O (2002). Dental fluorosis: chemistry and biology. Crit Rev Oral Biol Med 13(2) , 155-170. Bartlett MS (1937). Properties of su fficiency and statistical tests. Proceedings of the Royal Society. Series A 160 , 268-282. Dunnett CW (1955). A multiple comparison proce dure for comparing several treatments with a control. Journal of the American Statistical Association 50 , 1096-1121. Dunnett CW (1964). New tables for multip le comparisons with a control. Biometrics 20 , 482- 491. Fisher RA (1973). Statistical Methods fo r Research Workers, 14th edn., p.96. Hafner Publishing Company, New York, USA. Huntingdon Life Sciences Study Number WAG0013 2-Bromo-3,3,3-trifluoropropene : Dose Range Finding Study by Inhalation Administration to Rats for 2 Weeks Huntingdon Life Sciences Study Number: WAG0024 2-bromo-3,3,3-trifluoropropene: Dose Range Fi nding Study by Inhalati on Administration to Rats for 2 Weeks. Shirley EAC (1977). A non-parametric equivalent of Williams' test for contrasting increasing dose levels of a treatment. Biometrics 33 , 386-389. Steel RGD (1959). A multiple comparison rank sum test: treatments versus control. Biometrics 15 , 560-572. Wilcoxon F. (1945) Individual co mparisons by ranking methods. Biometrics Bulletin , 1 , 80- 83. Williams DA (1971). A test for differences between treatment means when several dose levels are compared with a zero dose control. Biometrics 27 , 103-117. Williams DA (1972). The comparison of several dose levels with a zero dose control. Biometrics , 28 , 519-531.Huntingdon Life SciencesWAG001452 FIGURE 1

Motor activity - gr oup mean scores (beam breaks) for males during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 50 5 2876 1M 2M 3M 4M

0 20 40 60 80 100 12 0 140 160

6 12 18 24 30 36 42 48 54 60Number of beam breaks

Ti me(m in utes) High beams

0 50 100 150 200 250 300

6 12 18 24 30 36 42 48 54 60Number of beam breaks

Ti me(m in utes) Low beams

0 250 500 750

1 2 3 4Beam breaks

Group

Total sc ores

0 50 0 1000 1500

1 2 3 4Beam breaks

Group

Total sc oresHuntingdon Life SciencesWAG001453 FIGURE 1 - continued

Motor activity - gr oup mean scores (beam breaks) for females during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene Exposure level (ppm) : 0 199 50 5 2876 1F 2F 3F 4F

0 20 40 60 80 100 12 0 140 160 18 0 200

6 12 18 24 30 36 42 48 54 60Number of beam breaks

Tim e (m in utes)

Hi gh beams

0 50 100 15 0 200 25 0 300

6 12 18 24 30 36 42 48 54 60Number of beam breaks

Ti me(m in utes) Low bea ms

0 25 0 50 0 75 0

1 2 3 4Beam breaks

Group

Total scores

0 500 10 00 15 00

1 2 3 4Beam breaks

Group

Total sc oresHuntingdon Life SciencesWAG001454 FIGURE 1 - continued

Motor activity - gr oup mean scores (beam breaks) for males during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluor opr opene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 50 5 2876 1M 4M

0 20 40 60 80 100 12 0 140 160

6 12 18 24 30 36 42 48 54 60Number of beam breaks

Ti me(m in utes) High beams

0 50 100 15 0 200 25 0 300 35 0

6 12 18 24 30 36 42 48 54 60Number of beam breaks

Tim e (m in utes)

Low bea ms

0 250 500 750

1 4Beam breaks

Group

Total sc ores

0 50 0 10 00 15 00

1 4Beam breaks

Group

Total scoresHuntingdon Life SciencesWAG001455 FIGURE 1 - continued

Motor activity - gr oup mean scores (beam breaks) for females during Week 4 of recovery Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropr opene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 50 5 2876 1F 4F

0 20 40 60 80 100 12 0 140 160

6 12 18 24 30 36 42 48 54 60Number of beam breaks

Ti me(m in utes) Hi gh beams

0 50 100 15 0 200 25 0 300 35 0

6 12 18 24 30 36 42 48 54 60Number of beam breaks

Tim e (m in utes)

Low beams

0 250 500 750

1 4Beam breaks

Group

Total scores

0 50 0 10 00 15 00

1 4Beam breaks

Group

Total scoresHuntingdon Life SciencesWAG001456 FIGURE 2

Bodyweight

– gr oup mean values (g)

– main study animals Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 50 5 2876Huntingdon Life SciencesWAG001457 FIGURE 2 - continued

Bodyweight

– gr oup mean values (g)

– recovery animals Group : 1 2 3 4 Compound : Control 2 - brom o - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 50 5 287658Huntingdon Life SciencesWAG0014

TABLE 1 Sensory reactivity observations and grip strength - summary of findings during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/sex: Statistical 1M 2M 3M 4M Statistical 1F 2F 3F 4F Number of animals: test (M) 20 10 10 20 test (F) 19 10 10 20 Parameter Grade Approach response (1 - 3) 1 0 0 0 0 0 1 0 2 2 20 10 10 20 19 9 10 18 Touch response (1 - 3) 1 1 1 1 0 0 1 0 1 2 19 9 9 20 19 9 10 19 Auditory startle reflex (1 - 4) 2 4 3 2 4 3 2 1 3 3 16 7 8 16 16 8 9 17 Tail pinch response (1 - 4) 2 3 0 0 0 0 0 0 0 3 17 10 10 18 19 10 10 2 0 4 0 0 0 2 0 0 0 0 Forelimb grip strength (kg) Mean Wi 1.00 1.01 0.94 0.85** Wi 0.88 0.82 0.84 0.68** SD 0.10 0.10 0.09 0.10 0.07 0.06 0.11 0.10 Hindlimb grip strength (kg) Mean Wi 0.61 0.59 0.54* 0.49** Wi 0.44 0.48 0. 43 0.36** SD 0.08 0.08 0.09 0.07 0.05 0.04 0.06 0.07 Additional observations ^ Loose faeces 0 0 0 1 0 0 0 0

^ Each animal may have more than one observation59Huntingdon Life SciencesWAG0014

TABLE 1 Sensory reactivity observations and grip strength - summary of findings during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/sex: Statistical 1M 4M Statistical 1F 4F Number of animals: test (M) 10 10 test (F) 10 10 Parameter Forelimb grip strength (kg) Mean Tt 1.12 1.07 Tt 0.87 0.86 SD 0.07 0.11 0.05 0.07 Hindlimb grip strength (kg) Mean Tt 0.67 0.57* Tt 0.52 0.48* SD 0.10 0.07 0.04 0.05

^ Each animal may have more than one observation60Huntingdon Life SciencesWAG0014

TABLE 2 Motor activity - gr oup mean scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3 ,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Number of animals Beam

level Time (minutes)

6 12 18 24 30 36 42 48 54 60 Total Statistical test: Wi Wi Wi Wi Wi Wi Wi Sh Wi Wi Wi 1M 20 High 134.9 103.9 65.9 44.9 31.9 31.5 23.9 34.5 23.4 23.9 518.4

SD 17.9 23.0 16.2 21.3 15.8 19.2 20.7 25.7 21.8 18.9 107.5 2M 10 High 139.4 97.4 74.5 49.4 43.8 34.9 26.6 17.5 27.7 19.4 530.6

SD 25.0 24.6 30.1 19.9 28.0 14.4 19.8 11.1 13 .0 19.5 151.4 3M 10 High 118.2 80.9* 57.4 38.2 31.2 16.2* 16.6 16.4 14.1 5.3* 394.5*

SD 18.4 19.1 23.3 15.8 17.4 17.1 19.1 9.4 15.4 16.4 121.8 4M 20 High 114.5* 63.0** 40.8** 28.6* 24.6 14.4** 10.9* 14.2** 8.3* 8.9** 327. 9**

SD 29.9 21.1 21.5 25.3 24.3 16.9 13.6 19.3 16.2 11.7 130.9 Statistical test: Wi Wi Wi Wi Wi Wi Sh Wi Wi Wi Wi 1M 20 Low 251.2 188.8 150.5 104.3 89.8 78.8 57.4 66.7 54.3 54.2 1095.8

SD 49.2 45.9 45.2 38.5 31.3 30.3 29.9 38.0 36.4 36.5 223.4 2M 10 Low 256.7 182.7 159.6 126.4 90.3 96.5 80.0 60.8 88.7 70.1 1211.8

SD 49.9 49.3 51.2 40.6 56.8 34.3 37.6 33.3 37.4 37.4 316.6 3M 10 Low 229.1 176.7 133.3 116.9 89.2 60.9 73.0 56.0 41.3 17.8* 994.2

SD 61 .2 36.0 34.7 47.4 38.7 39.8 74.9 38.6 36.9 26.3 270.7 4M 20 Low 209.7** 136.1** 99.3** 70.8* 57.5* 37.5** 28.0* 28.7** 22.1** 28.8* 718.3**

SD 30.5 32.1 42.0 38.7 48.7 37.8 37.1 25.0 25.8 33.7 227.261Huntingdon Life SciencesWAG0014

TABLE 2 - continued Motor activity - gr oup mean scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Number of animals Beam

level Time (minutes)

6 12 18 24 30 36 42 48 54 60 Total Statistical test: Wi Wi Wi Wi Wi Wi Sh Wi Sh Wi Wi 1F 19 High 160.5 99.5 69.4 56.6 46.5 48.2 48.0 33.8 36.5 27.1 625.9

SD 25.5 29.7 21.3 17.3 22.3 31. 7 47.7 25.4 33.7 27.3 172.8 2F 10 High 163.3 85.9 60.7 57.4 30.3 25.8* 28.3 31.4 28.3 9.9 521.3

SD 53.2 37.5 35.7 31.5 28.2 25.6 16.0 22.6 21.7 10.8 194.7 3F 10 High 151.7 93.5 61.7 41.8 36.9 25.5* 9.9* 14.9 11.4 15.9 463 .2*

SD 27.9 19.5 25.4 16.6 26.2 26.2 16.1 15.1 12.8 18.0 139.5 4F 20 High 136.8* 86.1 58.4 36.4* 24.2* 14.9** 18.7** 20.2* 18.4* 12.0* 425.8**

SD 35.5 37.6 37.4 27.3 30.5 21.2 23.9 20.4 16.4 19.6 193.6 Statistical test : Wi Wi Wi Wi Wi Wi Wi Wi Wi Wi Wi 1F 19 Low 276.2 181.7 150.6 116.5 101.8 97.3 85.1 73.9 73.7 74.4 1231.1

SD 66.5 49.2 41.5 36.5 42.1 52.9 48.8 43.1 36.2 51.1 337.0 2F 10 Low 257.2 158.6 128.4 91.5 78.1 58.8* 82.8 91.1 64.5 50.7 1061. 7

SD 52.9 45.1 44.0 46.0 51.0 47.2 39.8 34.7 37.7 46.2 329.9 3F 10 Low 249.5 174.6 145.7 96.7 92.0 58.6* 37.2* 35.9 47.5 59.4 997.1

SD 64.0 43.9 43.8 34.2 36.6 27.6 38.8 26.7 44.5 48.2 263.0 4F 20 Low 199.6* 129.8** 89 .9** 67.3** 38.6** 35.6** 41.1** 49.3* 52.3 46.1 749.5**

SD 38.2 35.4 41.6 40.2 38.4 38.9 41.0 48.5 43.1 42.4 257.562Huntingdon Life SciencesWAG0014

TABLE 2 - continued Motor activity - gr oup mean scores (beam breaks) during Week 4 of recover y Group : 1 2 3 4 C ompound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Number of animals Beam

level Time (minutes)

6 12 18 24 30 36 42 48 54 60 Total Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt 1M 10 High 112.0 73.9 54.4 43.4 28.5 14.5 19.7 11.3 10.4 13.0 381.1

SD 11.1 15.6 21.0 25.3 22.0 14.0 23.8 13.5 16.4 14.8 151.5 4M 10 High 115.5 53.7* 39.0 25.0 24.9 15.3 8.0 9.1 7.6 11 .6 309.7

SD 11.4 25.2 17.1 18.0 18.8 18.7 13.1 15.4 13.1 15.7 118.5 Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt 1M 10 Low 232.6 162.4 127.0 104.2 86.3 42.1 44.9 30.9 29.6 37.4 897.4

SD 34.0 35.3 27.4 36.5 41.1 33.0 48.0 33.2 34.3 38.4 241.6 4M 10 Low 200.3 119.1* 83.8** 67.7 60.5 50.8 33.7 36.1 32.5 35.6 720.1

SD 48.7 43.0 38.4 42.0 21.2 47.5 38.6 46.6 29.4 41.1 244.463Huntingdon Life SciencesWAG0014

TABLE 2 - continued Motor activity - gr oup mean scores (beam breaks) during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Number of animals Beam

level Time (minutes)

6 12 18 24 30 36 42 48 54 60 Total Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt Wc Tt 1F 10 High 125.9 72.6 67.6 55.5 47.0 33.7 38.0 26.9 8.9 2.7 478.8

SD 28.8 18.5 34.2 28.0 18.0 15.4 20.1 16.4 11.3 5.0 123.8 4F 10 High 135 .1 81.0 68.6 43.0 40.6 34.8 22.7 31.5 7.8 11.6 476.7

SD 22.3 20.1 46.4 30.3 21.2 20.7 23.4 27.4 10.7 16.7 175.0 Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt 1F 10 Low 260.1 168.8 160.4 139.1 130.0 104.4 112.6 89.5 41.2 17.3 1223. 4

SD 45.7 46.3 65.1 45.5 48.5 59.6 56.8 48.9 41.1 23.5 334.0 4F 10 Low 201.6* 120.3* 105.5* 88.3* 80.6* 90.6 50.0* 54.1 24.7 24.7 840.4*

SD 48.5 28.8 36.6 49.2 40.1 46.6 40.5 33.3 27.9 34.5 274.764Huntingdon Life SciencesWAG0014

TABLE 3 Request I D: 289342 Bodyweight - gr oup mean values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Week Week Week Week Week Week Week Week Week Week Week Week /Sex - 1 0 1 2 3 4 5 6 7 8 9 10 Statistical test: 1 M Mean 187 236 294 347 397 435 470 493 512 538 559 575

SD 8.9 8.7 11.3 19.9 25.4 31.3 37.3 42.0 43.2 48.8 50.5 53.3 N 20 20 20 20 20 20 20 20 20 20 20 20 2 M Mean 188 239 288 338 381 412 445 460 473 489 500 510

SD 8.5 11.7 14.3 19.1 23.9 26.4 30.6 32.4 32.7 37.4 36.9 38.9 N 10 10 10 10 10 10 10 10 10 10 10 10 3 M Mean 186 237 273 313 355 393 421 438 452 465 479 488

SD 7.9 11.3 15.5 23.4 29.6 29.9 37.4 43.8 43.9 45.4 46.4 49.1 N 10 10 10 10 10 10 10 10 10 10 10 10 4 M Mean 188 234 257 298 330 362 386 399 408 414 419 425

SD 7.0 10.8 12.8 16.7 22.6 27.1 32.4 35.5 37.0 39.1 39.3 40.5 N 20 20 20 20 20 20 20 20 20 20 20 2065Huntingdon Life SciencesWAG0014

TABLE 3 - continued Request ID: 289342 Bodyweight - gr oup mean values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Week Week Week Change As % of /Sex 11 12 13 0 - 13 Control Statistical test: Wi 1 M Mean 579 590 594 359 -

SD 57.4 60.7 61.7 64.0 N 20 20 20 20 2 M Mean 512 523 519 280** 78

SD 40.3 42.1 40.0 35.2 N 10 10 10 10 3 M Mean 494 502 497 260** 73

SD 48.4 49.0 52.1 46.4 N 10 10 10 10 4 M Mean 425 429 422 188** 52

SD 41.8 41.4 39.8 36.6 N 20 20 20 2066Huntingdon Life SciencesWAG0014

TABLE 3 - continued Request ID: 289342 Bodyweight - gr oup mean values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Week Week Week Week Week Week Week Week Week Week Week Week /Sex - 1 0 1 2 3 4 5 6 7 8 9 10 Statistical test: 1 F Mean 167 189 214 229 250 261 273 280 285 292 297 303

SD 11.5 12.8 15.0 16.2 18.6 18.6 19.2 20.5 20.2 23.2 20.1 22.1 N 20 20 20 20 20 20 20 20 20 19 19 19 2 F Mean 163 189 211 228 247 259 272 276 282 288 292 293

SD 9.2 12.2 10.4 10.9 10.9 11.0 11.8 15.7 11.5 12.3 10.6 11.1 N 10 10 10 10 10 10 10 10 10 10 10 10 3 F Mean 168 191 208 223 241 247 264 267 271 278 281 284

SD 10.8 12.6 15.3 16.5 18.5 19.5 21.0 21.0 20.2 18.9 21.8 19.3 N 10 10 10 10 10 10 10 10 10 10 10 10 4 F Mean 165 190 211 219 232 243 248 247 251 252 254 255

SD 11.5 14.2 15.5 1 7.3 15.4 20.4 20.9 19.6 22.2 21.7 24.9 26.7 N 20 20 20 20 20 20 20 20 20 20 20 2067Huntingdon Life SciencesWAG0014

TABLE 3 - continued Request ID: 289342 Bodyweight - gr oup mean values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Week Week Week Change As % of /Sex 11 12 13 0 - 13 Control Statistical test: Wi 1 F Me an 303 302 303 114 -

SD 22.3 22.5 20.5 13.2 N 19 19 19 19 2 F Mean 298 299 298 109 95

SD 12.3 8.4 15.6 16.2 N 10 10 10 10 3 F Mean 284 283 281 90** 79

SD 23.1 19.3 21.2 13.3 N 10 10 10 10 4 F Mean 260 262 253 63** 55

SD 24.2 28.2 25.7 21.1 N 20 20 20 2068Huntingdon Life SciencesWAG0014

TABLE 3 Request ID: 290312 Bodyweight - gr oup mean values (g) Gr oup : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Week Week Week Week Week Change As % of /Sex R0 R1 R2 R3 R4 R0 - R4 Control Statistical test: Tt 1 M Mean 594 602 618 629 622 34 -

SD 61.7 77.8 77.1 76.8 77.4 11.6 N 20 10 10 10 10 10 4 M Mean 422 445 464 481 483 62** 182

SD 39.8 48.7 50.1 52.5 53.0 10.5 N 20 10 10 10 10 1069Huntingdon Life SciencesWAG0014

TABLE 3 - continued Request ID: 290312 Bodyweight - gr oup mean values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -tr ifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Week Week Week Week Week Change As % of /Sex R0 R1 R2 R3 R4 R0 - R4 Control Statistical test: Wc 1 F Mean 303 310 314 31 4 312 9 -

SD 20.5 23.2 26.5 24.7 21.8 6.1 N 19 10 10 10 10 10 4 F Mean 253 265 272 271 266 16 17 7

SD 25.7 17.3 18.1 17.8 18.3 18.8 N 20 10 10 10 10 1070Huntingdon Life SciencesWAG0014

TABLE 4 Haematology - group mean values during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Gr oup Hct Hb RBC RETA MCH MCHC MCV /Sex L/L g/dL x10 12/L x10 12/L pg g/dL fL Statistical test: Wi Wi Wi Wi Wi Wi Wi 1M Mean 0.429 15.7 8.19 0.193 19.2 36.5 52.4

SD 0.0205 0.69 0.308 0.0343 0.42 0.84 0.82 N 10 10 10 10 10 10 10 2M Mean 0.44 5 16.0 8.64* 0.193 18.5** 35.9 51.5

SD 0.0335 1.16 0.617 0.0199 0.47 0.38 1.53 N 10 10 10 10 10 10 10 3M Mean 0.445 16.1 8.79** 0.188 18.3** 36.1 50.7*

SD 0.0222 0.79 0.522 0.0377 0.64 0.44 2.03 N 10 10 10 10 10 10 10 4M Mean 0.454* 16.6* 9.06** 0.206 18.3** 36.5 50.1**

SD 0.0162 0.58 0.280 0.0594 0.39 0.36 1.08 N 10 10 10 10 10 10 1071Huntingdon Life SciencesWAG0014

TABLE 4 - continued Haematology - group mean values during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - brom o - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group WBC N L E B M LUC Plt PTP APTT /Sex x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L sec sec Statistical test: lWi Wi lWi Wi Wi Wi lWi Wi lWi Wi 1M Mean 11.31 2.36 8.30 0.19 0.06 0.31 0.08 882 25.0 23.9

SD 2.623 1.196 1.882 0.066 0.033 0.138 0.025 159.7 4.21 2.98 N 10 10 10 10 10 10 10 9 10 10 2M Mean 10.63 2.92 7.05 0.09** 0.06 0.41 0.11 1017 22 .3 21.6*

SD 3.556 2.546 2.748 0.043 0.049 0.199 0.060 154.3 1.72 2.47 N 10 10 10 10 10 10 10 10 10 10 3M Mean 10.61 2.65 7.19 0.05** 0.07 0.54** 0.11 976 23.8 20.8*

SD 2.781 0.810 2.054 0.018 0.065 0.150 0.047 119.2 1.80 1.42 N 10 10 10 10 10 10 10 10 10 10 4M Mean 8.87 2.35 5.66** 0.05** 0.04 0.57** 0.20** 898 24.7 22.1*

SD 1.791 1.125 1.122 0.020 0.026 0.178 0.087 70.8 1.46 2.03 N 10 10 10 10 10 10 10 10 9 972Huntingdon Life SciencesWAG0014

TABLE 4 - continued Haematology - grou

p mean values during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Hct Hb RBC RETA MCH MCHC MCV /Sex L/L g/dL x10 12/L x10 12/L pg g/dL fL Statistical test: Wi Wi Sh lWi Wi Wi Wi 1F Mean 0.422 15.5 7.92 0.158 19.6 36.8 53.3

SD 0.0116 0.39 0.312 0.0336 0.72 0.58 1.72 N 9 9 9 9 9 9 9 2F Mean 0.412 15.2 7.93 0.166 19.1 36.8 52.0

SD 0.0179 0 .73 0.352 0.0485 0.80 0.85 1.61 N 10 10 10 10 10 10 10 3F Mean 0.427 15.6 8.20 0.176 19.0 36.5 52.0

SD 0.0200 0.73 0.325 0.0439 0.58 0.72 1.66 N 10 10 10 10 10 10 10 4F Mean 0.414 14.4** 8.05 0.329** 18.0** 34.8** 51.8

SD 0.02 44 0.88 0.906 0.1400 1.57 1.34 3.88 N 10 10 10 10 10 10 1073Huntingdon Life SciencesWAG0014

TABLE 4 - continued Haematology - group mean values during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropen e 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group WBC N L E B M LUC Plt PTP APTT /Sex x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L sec sec Statistical test: lWi Wi lWi Wi lWi Wi Wi Wi Sh Wi 1F Mean 8.54 1.68 6. 43 0.11 0.04 0.19 0.09 950 21.1 17.4

SD 3.455 1.122 2.302 0.043 0.049 0.099 0.049 139.3 0.86 1.14 N 9 9 9 9 9 9 9 9 9 9 2F Mean 7.59 0.86 6.26 0.07* 0.04 0.27 0.10 872 24.1* 19.0**

SD 1.527 0.292 1.368 0.033 0.019 0.092 0.048 94.7 0.82 1.18 N 10 10 10 10 10 10 10 10 10 10 3F Mean 7.02 1.18 5.19 0.07* 0.04 0.41** 0.13 839 23.4* 19.3**

SD 1.626 0.492 1.205 0.037 0.016 0.144 0.062 133.3 1.71 1.57 N 10 10 10 10 10 10 10 10 10 10 4F Mean 5.78* 1.07 4.24** 0.0 3** 0.03 0.32** 0.10 1070 26.4** 19.5**

SD 1.637 0.911 1.166 0.010 0.014 0.083 0.070 263.7 4.04 1.14 N 10 10 10 10 10 10 10 10 10 1074Huntingdon Life SciencesWAG0014

TABLE 4 - continued Haematology - group mean values during Week 4 of recovery Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Hct Hb RBC RETA MCH MCHC MCV /Sex L/L g/dL x10 12/L x10 12/L pg g/dL fL Statistical test: Tt Tt Tt Tt Tt Tt Tt 1M Mean 0.441 15.0 8.47 0.212 17.6 33.9 52.0

SD 0.0136 0.50 0.384 0.0446 0.51 0.33 1.75 N 10 10 10 10 10 10 10 4M Mean 0.449 15.3 8.42 0.163 * 18.1 34.0 53.3

SD 0.0186 0.63 0.314 0.0462 0.59 0.28 1.59 N 10 10 10 10 10 10 1075Huntingdon Life SciencesWAG0014

TABLE 4 - continued Haematology - group mean values during Week 4 of recovery Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group WBC N L E B M LUC Plt PTP APTT /Sex x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L sec sec Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt 1M Mean 10.77 1.75 8.39 0.14 0.10 0.28 0.12 1091 22.7 22.6

SD 2.526 0.802 2.050 0.0 47 0.063 0.094 0.053 191.5 1.71 4.17 N 10 10 10 10 10 10 10 10 10 10 4M Mean 7.78 ** 1.22 6.09 ** 0.12 0.07 0.19 * 0.09 1099 21.9 21.2

SD 1.644 0.477 1.348 0.049 0.032 0.072 0.034 136.5 1.69 2.94 N 10 10 10 10 10 10 10 10 10 1076Huntingdon Life SciencesWAG0014

TABLE 4 - continued Haematology - group mean values during Week 4 of recovery Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Hct Hb RBC RETA MCH MCHC MCV /Sex L/L g/dL x10 12/L x10 12/L pg g/dL fL Statistical test: Tt Tt Tt Tth Tt Tt Tt 1F Mean 0.417 14.4 7.60 0.129 18.9 34.4 54.9

SD 0.0104 0.37 0.270 0.0336 0.73 0.37 1.69 N 10 10 10 10 10 10 10 4F Mean 0.428 * 14.7 7.88 ** 0.132 18.6 34.4 54.3

SD 0.0095 0.37 0.136 0.0284 0.50 0.49 1.34 N 10 10 10 10 10 10 1077Huntingdon Life SciencesWAG0014

TABLE 4 - continued Haematology - group mean values during Week 4 of recovery Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3 ,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group WBC N L E B M LUC Plt PTP APTT /Sex x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L sec sec Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt 1F Mean 5.05 0.74 3.99 0.11 0.03 0.12 0.06 1006 21.7 20.9

SD 1.079 0.327 0.838 0.025 0.011 0.038 0.026 85.6 1.53 2.26 N 10 10 10 10 10 10 10 10 10 10 4F Mean 3.60 * 0.73 2.64 ** 0.09 0.02 0.09 0.04 1010 22.2 19.6

SD 1.229 0.308 0.951 0.033 0.010 0.033 0.015 107.7 1.52 2.04 N 10 10 10 10 10 10 10 10 10 1078Huntingdon Life SciencesWAG0014

TABLE 5 Blood chemistry - gr oup mean values during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropen e 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group ALP ALT AST Bili Ur ea Creat Gluc Chol Trig /Sex U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L Statistical test: Wi Wi Sh Wi lWi Wi lWi Wi Wi 1M Mean 72 31 75 2 5.11 35 8.18 1.74 0.69

SD 13.9 5.1 8.6 0.7 0.637 3.9 0.914 0.241 0.228 N 10 10 10 10 10 10 10 10 10 2M Mean 72 40* 173** 2 5.90 33 8.72 1.61 0.66

SD 10.2 9.7 117.5 0.3 0.861 3.2 1.130 0.425 0.269 N 10 10 10 10 10 10 10 10 10 3M Mean 78 39* 225** 1 6.40** 36 9.56 1.57 0.73

SD 17.7 5.5 58.6 0.5 1.061 7.3 2.539 0.519 0.174 N 10 10 10 10 10 10 10 10 10 4M Mean 95** 39* 216** 2 8.36** 34 8.01 1.03** 0.93

SD 27.3 10.7 76.3 0.3 2.022 5.1 1.207 0.342 0.419 N 10 10 10 10 10 10 10 10 1079Huntingdon Life SciencesWAG0014

TABLE 5 - continued Blood chemistry - gr oup mean values during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Na K Cl Ca Phos Total Prot Alb A/G /Sex mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio Statistical test: Wi Wi Wi Wi lWi Wi Wi Wi 1M Mean 141 4.2 102 2.44 1.89 66 34 1.11

SD 0.8 0.32 0.9 0.038 0.147 3.1 1.1 0.106 N 10 10 10 10 10 10 10 10 2M Mean 142 4.5 104** 2.43 1.93 63 34 1.19

SD 1.0 0.29 1.1 0.059 0.289 2.7 1.3 0.090 N 10 10 10 10 10 10 10 10 3M Mean 143 4.8* 105** 2.48 2.10 61** 34 1.23 **

SD 1.7 0.26 1.6 0.105 0.501 2.9 1.3 0.090 N 10 10 10 10 10 10 10 10 4M Mean 143 4.5* 108** 2.44 2.46** 60** 35 1.36**

SD 2.0 0.58 2.6 0.052 0.446 1.9 1.1 0.086 N 10 10 10 10 10 10 10 1080Huntingdon Life SciencesWAG0014

TABLE 5 - continued Blood chemistry - gr oup mean values during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group ALP ALT AST Bili Ur ea Creat Gluc Chol Trig /Sex U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L Statistical test: lWi lWi lDu Du Wi Wi lWi Wi lWi 1F Mean 42 24 68 1 6.46 41 8.40 2.13 0.51

SD 11.6 5.4 9.6 0.5 0.870 3.9 1.414 0.401 0.159 N 9 9 9 9 9 9 9 9 9 2F Mean 37 29 77 3** 7.62* 41 6.63 1.67 0.58

SD 5.4 7.8 24.0 0.5 1.114 4.4 0.884 0.229 0.204 N 10 10 10 10 10 10 10 10 10 3F Mean 44 32 185** 2 8.00** 43 7.78 1.82 0.59

SD 9.1 13.0 78.2 0.7 1.118 6.6 2.493 0.643 0.194 N 10 10 10 1 0 10 10 10 10 10 4F Mean 60** 18* 83 2 9.95** 38 5.79** 1.14** 0.87*

SD 20.0 3.6 27.1 0.5 1.461 2.9 0.871 0.411 0.465 N 10 10 10 10 10 10 10 10 1081Huntingdon Life SciencesWAG0014

TABLE 5 - continued Blood chemistry - gr oup mean values during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Na K Cl Ca Phos Total Prot Alb A/G /Sex mmol/L mmol/L mmol/L mmo l/L mmol/L g/L g/L Ratio Statistical test: Wi Wi Sh Wi Sh Wi Wi Wi 1F Mean 140 4.1 102 2.48 1.18 70 39 1.29

SD 1.4 0.41 1.3 0.079 0.215 3.9 2.3 0.175 N 9 9 9 9 9 9 9 9 2F Mean 142 3.7 104* 2.43 1.68* 66** 39 1.43

SD 1.1 0.30 2.7 0.079 0 .095 3.3 2.3 0.077 N 10 10 10 10 10 10 10 10 3F Mean 141 4.3 105** 2.44 2.07** 60** 35** 1.41

SD 0.8 0.60 1.0 0.054 0.523 2.7 1.4 0.100 N 10 10 10 10 10 10 10 10 4F Mean 140 4.2 105** 2.37** 2.81** 61** 35** 1.39

SD 2.1 0.36 3.2 0.065 0.494 2.6 2.9 0.219 N 10 10 10 10 10 10 10 1082Huntingdon Life SciencesWAG0014

TABLE 5 - continued Blood chemistry - gr oup mean values during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group ALP ALT AST Bili Ur ea Creat Gluc Chol Trig /Sex U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt 1M Mean 76 42 71 3 5.31 35 8.30 2.00 1.02

SD 14.3 11.8 18.7 1.0 0.580 6.6 0.910 0.761 0.323 N 10 10 10 10 10 10 10 10 10 4M Mean 93 * 41 76 2 5.59 36 6.81 ** 1.62 0.63 **

SD 20.5 12.3 32.5 0.7 0.573 5.8 0.863 0.266 0.242 N 10 10 10 10 10 10 10 10 1083Huntingdon Life SciencesWAG0014

TABLE 5 - continued Blood chemistry - gr oup mean values during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2 876 Group Na K Cl Ca Phos Total Prot Alb A/G /Sex mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt 1M Mean 140 4.2 100 2.50 1.75 66 34 1.07

SD 0.7 0.20 1.1 0.081 0.115 2.1 1.4 0.070 N 10 10 10 10 10 10 1 0 10 4M Mean 140 4.5 * 101 * 2.51 1.88 65 35 1.15 *

SD 0.6 0.34 0.6 0.052 0.207 2.7 1.2 0.062 N 10 10 10 10 10 10 10 1084Huntingdon Life SciencesWAG0014

TABLE 5 - continued Blood chemistry - gr oup mean values during Week 4 of recover y Group : 1 2 3 4 Comp ound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group ALP ALT AST Bili Ur ea Creat Gluc Chol Trig /Sex U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmo l/L Statistical test: Tt Tt Tt Fe Tt Tt Tt Tt Tt 1F Mean 33 49 103 2 6.28 43 6.96 2.23 0.79

SD 10.8 27.6 78.3 0.3 0.925 4.5 0.900 0.405 0.295 N 10 10 10 10 10 10 10 10 10 4F Mean 44 * 50 105 2 6.17 41 6.82 1.84 0.65

SD 7.6 16.8 38.1 0.5 0.872 2.5 0.897 0.536 0.216 N 10 10 10 10 10 10 10 10 1085Huntingdon Life SciencesWAG0014

TABLE 5 - continued Blood chemistry - gr oup mean values during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Na K Cl Ca Phos Total Prot Alb A/G /Sex mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio Statistical test: Tt lTt Tt Tt Tt Tt Tt Tt 1F Mean 139 3.7 100 2.53 1.17 71 40 1.27

SD 0.7 0.21 1.3 0.065 0.235 2.5 1.7 0.099 N 10 10 10 10 10 10 10 10 4F Mean 140 * 3.9 102 ** 2.39 ** 1.15 67 ** 38 1.32

SD 1.1 0.62 1.5 0.060 0.165 2.9 2.0 0.125 N 10 10 10 10 10 10 10 1086Huntingdon Life SciencesWAG0014

TABLE 6 Ur inalysis - group m ean values during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Vol pH SG Prot TCLR TNAR TUKR /Sex mL g/L g/L mmol mmol mmol Statistical test: Wi Wi Sh Wi Wi Wi Wi 1M Mean 5.3 7.6 1047 1.13 0.539 0.428 1.234

SD 1.61 0.76 16.6 0.200 0.2618 0.2208 0.3173 N 10 10 10 10 10 10 10 2M Mean 7.7 * 7.0 1029 ** 1.03 0.592 0.596 0.991

SD 3.06 0.28 4.5 0.580 0.2196 0.2291 0.3049 N 10 10 10 10 10 10 10 3M Mean 8.9 * 7.1 1026 ** 0.88 0.639 0.493 1.078

SD 3.00 0.61 4.7 0.277 0.2919 0.2249 0.3646 N 10 10 10 10 10 10 10 4M Mean 7.3 * 6.8 ** 1034 ** 0.79 0.676 0.608 0.820 **

SD 2.79 0.63 13.9 0.355 0.2768 0.3112 0.3166 N 10 10 10 10 10 10 1087Huntingdon Life SciencesWAG0014

TABLE 6 - continued Ur inalysis - group mean values during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Vol pH SG Prot TCLR TNAR TUKR /Sex mL g/L g/L mmol mmol mmol Statistical test: Wi Wi Sh Wi Wi Wi Wi 1F Mean 2.8 6.4 1046 0.25 0.207 0.241 0.482

SD 1.66 0.55 16.8 0.080 0.1137 0.1096 0.2468 N 9 9 9 9 9 9 9 2F Mean 4.1 6.5 1044 0.18 0.274 0.295 0.608

SD 2.07 0.31 18.5 0.101 0.1341 0.1765 0.1396 N 10 10 10 10 10 10 10 3F Mean 5.0 6.3 1032 0.14 0.375 0.368 0.549

SD 2.13 0.42 4.7 0.044 0.2009 0. 1850 0.2240 N 10 10 10 10 10 10 10 4F Mean 4.5 6.0 1036 0.20 0.500 ** 0.304 0.447

SD 2.14 0.45 13.6 0.142 0.2276 0.1870 0.2406 N 10 9 10 9 9 9 988Huntingdon Life SciencesWAG0014

TABLE 7 Request ID: 289354 Organ weights - gr oup mean unadjusted and adjusted values (g) for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Terminal

Bodywe ight Adrenals Br ain Epididymides Heart Kidneys Liver Lungs + Br onchi Pituitary Prostate Un adjusted Means Statistical test: Wi 1M Mean 601 0.056 2.114 1.522 1.805 3.375 20.357 1.761 0.014 1.246 SD 48 0.009 0.072 0.135 0.257 0.265 1.714 0.164 0.004 0.217 N 10 10 10 10 10 10 10 10 10 10 2M Mean 520** 0.046 2.084 1.355 1.675 2.923 17.348 1.655 0.011 1.052 SD 43 0.008 0.077 0.081 0.206 0.351 2.779 0.152 0.003 0.192 N 10 10 10 10 10 10 10 10 10 10 3M Me an 497** 0.047 2.035 1.292 1.518 2.781 16.310 1.644 0.012 0.886 SD 53 0.008 0.073 0.135 0.250 0.230 2.552 0.175 0.003 0.158 N 10 10 10 10 10 10 10 10 10 10 4M Mean 417** 0.043 1.940 1.178 1.416 2.376 14.211 1.506 0.011 0.832 SD 32 0.007 0.086 0.157 0.165 0.264 1.744 0.094 0.003 0.202 N 10 10 10 10 10 10 10 10 10 10 Adjusted Means Statistical test: Wi Wi Wi Wi Wi Wi Wi Wi Wi 1M Mean 0.050 2.047 1.430 1.624 2.961 16.530 1.560 0.012 1.081 2M Mean 0.045 2.076 1.344 1.654 2.873 16.883 1.630 0.011 1.033 3M Mean 0.048 2.043 1.304 1.541 2.834 16.806 1.670 0.012 0.907 4M Mean 0.050 2.005 1.269 1.595 2.786 18.007 1.705 0.013 0.99589Huntingdon Life SciencesWAG0014

TABLE 7 - continued Request ID: 289354 Organ weigh ts - gr oup mean unadjusted and adjusted values (g) for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 1 99 505 2876 Group /Sex Terminal

Bodyweight Salivary

Glands Seminal

Vesicles Spleen Testes Thy mus Thy

ro ids + Paras Un adjusted Means Statistical test: Wi 1M Mean 601 0.724 2.067 0.947 3.898 0.280 0.025 SD 48 0.073 0.191 0.099 0.268 0. 072 0.005 N 10 10 10 10 10 10 10 2M Mean 520** 0.588 1.711 0.867 3.613 0.255 0.025 SD 43 0.062 0.410 0.157 0.309 0.071 0.006 N 10 10 10 10 10 10 10 3M Mean 497** 0.580 1.452 0.890 3.644 0.220 0.025 SD 53 0.079 0.270 0.165 0.42 7 0.073 0.007 N 10 10 10 10 10 10 10 4M Mean 417** 0.516 1.279 0.695 3.238 0.111 0.023 SD 32 0.087 0.339 0.091 0.313 0.021 0.007 N 10 10 10 10 10 10 10 Adjusted Means Statistical test: Wi Wi Wi Wi lWi Wi 1M Mean 0.659 1.929 0.809 3.728 0.219 0.022 2M Mean 0.580 1.694 0.850 3.593 0.237 0.025 3M Mean 0.589 1.470 0.908 3.666 0.213 0.025 4M Mean 0.581 1.416 0.832 3.407 0.138* 0.02690Huntingdon Life SciencesWAG0014

TABLE 7 - continued Request ID: 289354 Organ weights - gr oup mean unadjusted and adjusted values (g) for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 287 6 Group /Sex Terminal

Bodyweight Adrenals Br ain Heart Kidneys Liver Lungs + Br onchi Ovaries Pituitary Salivary Glands Un adjusted Means Statistical test: Wi 1F Mean 303 0.059 1.954 1.125 1.753 9.708 1.240 0.096 0.017 0.448 SD 2 5 0.010 0.061 0.141 0.157 1.148 0.076 0.012 0.003 0.039 N 9 9 9 9 9 9 9 9 9 9 2F Mean 297 0.066 1.873 1.068 1.841 10.603 1.227 0.083 0.016 0.363 SD 14 0.007 0.083 0.070 0.164 1.100 0.095 0.016 0.003 0.035 N 10 10 10 10 10 10 10 10 10 10 3F Mean 283 0.057 1.860 0.968 1.852 9.678 1.277 0.080 0.015 0.359 SD 22 0.004 0.073 0.088 0.162 1.076 0.121 0.022 0.003 0.045 N 10 10 10 10 10 10 10 10 10 10 4F Mean 254** 0.053 1.771 1.047 1.724 9.639 1.257 0.081 0.011 0.3 54 SD 28 0.013 0.119 0.091 0.156 1.032 0.107 0.018 0.003 0.057 N 10 10 10 10 10 10 10 10 10 10 Adjusted Means Statistical test: Wi Wi Wi Wi Wi Wi Wi Wi Wi 1F Mean 0.056 1.914 1.115 1.712 9.109 1.192 0.094 0.017 0 .438 2F Mean 0.064 1.845 1.061 1.813 10.193 1.195 0.082 0.016 0.356** 3F Mean 0.057 1.861 0.969 1.853 9.699 1.279* 0.080 0.015 0.360** 4F Mean 0.058 1.833 1.063 1.788 10.567** 1.330* 0.084 0.011** 0.370**91Huntingdon Life SciencesWAG0014

TABLE 7 - continued Request ID: 289354 Organ weights - gr oup mean unadjusted and adjusted values (g) for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Terminal

Bodyweight Spleen Thy mus Thy

ro ids + Paras Uterus +

Cervix Un adjusted Means Statistical test: Wi 1F Mean 303 0.617 0.229 0.017 0.752 SD 25 0.123 0.046 0.006 0.292 N 9 9 9 9 9 2F Mean 297 0.539 0.196 0.023 0.765 SD 14 0.070 0.057 0.005 0.174 N 10 10 10 10 10 3F Mean 283 0.538 0.167 0.018 0.741 SD 22 0.096 0.048 0.004 0.247 N 10 10 10 10 10 4F Mean 254** 0.698 0.077 0.021 0.596 SD 28 0.247 0.034 0.006 0.323 N 10 10 10 10 10 Adjusted Means Statistical test: lWi Wi Wi Wi 1F Mean 0.579 0.207 0.015 0.679 2F Mean 0.517 0.181 0.022* 0.715 3F Mean 0.530 0.167 0.018* 0.743 4F Mean 0.715 0.111** 0.023** 0.70992Huntingdon Life SciencesWAG0014

T ABLE 7 - continued Request ID: 290346 Organ weights - gr oup mean unadjusted and adjusted values (g) for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3 ,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Terminal

Bodyweight Adrenals Br ain Epididymides Heart Kidneys Liver Lungs + Br onchi Pituitary Prostate Un adjusted Means Statistical test: Tt 1M Mean 623 0.0 60 2.137 1.598 1.791 3.281 20.400 1.780 0.015 1.256 SD 78 0.012 0.115 0.203 0.345 0.443 3.642 0.157 0.004 0.165 N 10 10 10 10 10 10 10 10 10 10 4M Mean 482** 0.053 1.993 1.320 1.671 2.622 16.199 1.592 0.011 1.227 SD 52 0.010 0.112 0.130 0.265 0.250 1.588 0.176 0.003 0.325 N 10 10 10 10 10 10 10 10 10 10 Adjusted Means Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt 1M Mean 0.065 2.070 1.480 1.532 3.072 18.915 1.650 0.013 1.235 4M Mean 0.048* 2.061 1.438 1.930** 2.831 17.684 1.722 0.013 1.24793Huntingdon Life SciencesWAG0014

TABLE 7 - continued Request ID: 290346 Organ weights - gr oup mean unadjusted and adjusted values (g) for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Control 2 - bromo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Terminal

Bodyweight Salivary

Glands Seminal

Vesicles Spleen Testes Thy mus Thy

ro ids + Paras Un adjusted Means Statistical test: Tt 1M Mean 623 0.778 2.023 0.904 3.842 0.230 0.028 SD 78 0.089 0.358 0.233 0.335 0.078 0.007 N 10 10 10 10 10 10 10 4M Mean 482** 0.621 1.839 0.891 3.781 0.163 0.025 SD 52 0.080 0.288 0.132 0.392 0.043 0.004 N 10 10 10 10 10 10 10 Adjusted Means Statistical test: Tt Tt Tt Tt Tt Tt 1M Mean 0.714 1.952 0.830 3.616 0.201 0.024 4M Mean 0.684 1.910 0.964 4.008 0.193 0.02894Huntingdon Life SciencesWAG0014

TABLE 7 - continued Request ID: 290346 Organ weights - gr oup mean unadjusted and adjusted values (g) for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Terminal

Bodyweight Adrenals Br ain Heart Kidneys Liver Lungs + Br onchi Ovaries Pituitary Salivary Glands Un adjusted Means Statistical test: Tt 1F Mean 312 0.065 1.911 1.066 1.858 9.347 1.242 0.092 0.017 0.440 SD 22 0.020 0.094 0.178 0.202 1.125 0.095 0.045 0.003 0.021 N 10 10 10 10 10 10 10 10 10 10 4F Mean 265** 0.059 1.812 1.133 1.751 8.429 1.222 0.170 0.014 0.439 SD 19 0.009 0.092 0.155 0.179 0.827 0.113 0.264 0.001 0.046 N 10 10 10 10 10 10 10 10 10 10 Adjusted Means Statistical test: Tt Tt Tt Tt Tt Tt lTt Tt Tt 1F Mean 0.058 1.862 0.953 1.751 8.918 1.185 0.057 0.016 0.421 4F Mean 0.066 1.860 1.246** 1.859 8.857 1.278 0.158* 0.016 0. 45995Huntingdon Life SciencesWAG0014

TABLE 7 - continued Request ID: 290346 Organ weights - gr oup mean unadjusted and adjusted values (g) for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -t rifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Terminal

Bodyweight Spleen Thy mus Thy

ro ids + Paras Uterus +

Cervix Un adjusted Means Statistical test: Tt Wc 1F Mean 312 0.549 0.155 0.021 0.8 73 SD 22 0.066 0.030 0.005 0.310 N 10 10 10 10 10 4F Mean 265** 0.566 0.178 0.024 0.681 SD 19 0.182 0.033 0.005 0.036 N 10 10 10 10 10 Adjusted Means Statistical test: lTt Tt Tt 1F Mean 0.473 0.159 0.023 4F Mean 0.631* 0.174 0.02296Huntingdon Life SciencesWAG0014

TABLE 8 Request ID: 313011 Macropathology - group distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number Examined: 10 10 10 10 9 10 10 10 Eyes Protruding 0 0 0 0 0 0 0 1 Harderian glands Swelling(s) 0 0 0 0 0 0 0 1 Kidneys Depression(s) 0 0 0 0 0 0 1 0 Pelvic dilatation 1 0 0 0 0 0 1 0 Liver Adhesions 0 0 0 0 0 0 1 1 Cyst(s) 0 0 0 0 0 0 0 1 Dark area(s) 1 0 0 0 0 0 0 0 Ln b ronc hial Small 0 0 0 1 0 0 0 0 Ln mandibular Enlarged 0 0 0 0 1 0 0 097Huntingdon Life SciencesWAG0014

TABLE 8 - continued Request ID: 313011 Macropathology - group distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number Examined: 10 10 10 10 9 10 1 0 10 Lungs + bronchi Adhesions 0 0 0 0 0 0 0 1 Dark area(s) 0 1 0 1 0 0 0 1 Pale area(s) 1 0 1 1 2 3 1 1 Petechiae 0 0 0 1 0 0 0 0 Ovaries Cyst(s) - - - - 1 0 0 0 Skin Hair loss 0 1 1 0 3 7 4 6 Scab(s) 0 0 1 1 2 0 1 0 Spleen Adhesions 0 0 0 0 0 0 2 5 Capsule thickened 1 1 4 8 0 1 2 5 Cyst(s) 0 0 0 1 0 0 1 0 Stomach Cyst(s) 0 1 0 0 0 0 0 098Huntingdon Life SciencesWAG0014

TABLE 8 - continued Request ID: 313011 Macropathology - group distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number Examined: 10 10 10 10 9 10 10 10 Teeth Incisor(s) pale 0 3 7 10 0 3 9 10 Incisor(s) thickened 0 0 0 1 0 0 0 8 General comments Situs inver sus 0 0 0 1 0 0 0 0 Paws Swelling(s) 0 0 0 0 0 1 0 099Huntingdon Life SciencesWAG0014

TABLE 8 - continued Request ID: 313012 Macropathology - group distribution of findings for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Cont ro l 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 4M 1F 4F Tissue and Finding Number Examined: 10 10 10 10 Kidneys Pelvic dilatation 0 1 0 1 Ln mandibular Enlarged 0 1 0 0 Lungs + bronchi Dark 1 0 0 0 Dark area(s) 1 1 0 0 Pale area(s) 1 0 1 0 Ovaries Periovarian sac distension - - 1 1 Pituitary Cyst(s) 0 1 0 0 Skin Hair loss 4 0 0 2100Huntingdon Life SciencesWAG0014

TABLE 8 - continued Request ID: 313012 Macropathology - group distribution of findings for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - bromo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 4M 1F 4F Tissue and Finding Number Examined: 10 10 10 10 Spleen Adhesions 0 2 0 1 Capsule thickened 0 1 0 0 Teeth Incisor(s) pale 0 10 0 10 Incisor(s) thickened 0 1 0 3 Thy mus Dark 1 0 0 0 Preputial glands Distended 1 0 - -101Huntingdon Life SciencesWAG0014

TABLE 9 Request ID: 313013 Histopathology - gr oup distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number: 10 10 10 10 9 10 10 10 Aorta Tho

racic Number Examined: 10 0 0 10 9 0 0 10 Trachea Number Examined: 10 10 10 10 9 10 10 10 Inflammation 0 0 1 0 0 2 0 1 Inflammatory Exudate in Lumen 0 0 0 0 0 0 0 1 Lungs + Bronchi Number Examined: 10 10 10 10 9 1 0 10 10 Aggregations of Alveolar Macrophages 1 1 3 3 3 3 0 3 Alveolar Congestion 0 0 0 0 0 0 1 0 Alveolar Septal Mineralisation 0 0 1 0 0 0 1 0 Alveolitis 2 0 3 4 2 1 2 5 Arterial Mural Mineralisation 5 3 3 3 3 2 0 1 Ch olesterol Clef

t Granuloma(ta) 0 0 0 0 0 2 0 0 Perivascular Inflammatory Cells 3 0 0 1 1 0 0 3 Perivascular Lymphoid Aggregates 0 0 0 0 0 0 0 1 Pleural Adhesion(s) 0 0 0 0 0 0 0 1 Pleural Fibrosis 0 1 0 0 0 0 0 0 Pleural Inflammation 0 2 0 1 0 1 0 0102Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313013 Histopathology - gr oup distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number: 10 10 10 10 9 10 10 10 Liver Number Examined: 10 10 10 10 9 10 10 10 Capsular Adhesions 0 0 0 0 0 0 1 1 Ex tramedullary Haemopoiesis 0 0 0 0 0 0 0 1 Hepatocyte Hypertrophy, Centrilobular 0 0 0 2 0 0 1 4 Hepatocyte Necrosis, Focal 0 0 1 0 0 0 0 0 Inflammation, Focal 6 3 5 3 2 1 6 1 Vascular Dilatation 0 0 0 0 0 0 0 1 Pancreas Number Examined: 10 10 10 10 9 10 10 10 Acinar Atrophy, Focal 0 0 1 0 0 1 0 1 Acinar Cell Degranulation 0 3 5 7 1 4 5 6 Arteritis/Periarteritis 0 1 0 0 0 0 0 0 Basophilic Acinar Cells, Focal 0 1 0 0 0 0 0 0 Inflammation 0 1 0 0 0 1 0 0 LN Mesenteric Number Examined: 10 0 0 10 9 0 0 10 Mastocytosis 0 0 0 0 1 0 0 0 Sinus Erythrocytosis/Erythrophagocytosis 0 0 0 1 1 0 0 0103Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313013 Histopathology - gr oup distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number: 10 10 10 10 9 10 10 10 Kidneys Number Examined: 10 0 0 10 9 0 2 10 Cortical Scarring 0 0 0 2 0 0 0 0 Cortical Tubular Basophilia 1 0 0 0 0 0 0 0 Hyp erplasia, Papillary Epithelium 0 0 0 0 0 0 0 2 Hyp erplasia , Pelvic Epithelium 0 0 0 0 0 0 0 2 Interstitial Inflammation 0 0 0 1 0 0 0 0 Mineralisation, Papilla 0 0 0 0 1 0 0 0 Pelvic Dilatation 0 0 0 0 0 0 1 0 Perivascular Lymphoid Aggregations 2 0 0 0 0 0 0 0 Pyelonephritis 0 0 0 0 0 0 0 2 Ur inary Bladder Number Examined: 10 0 0 10 9 0 0 10 Erosion 0 0 0 0 0 0 0 1 Inflammation 0 0 0 0 0 0 0 3 Refluxed Seminal Colloid Plug 0 0 0 1 0 0 0 0 Transitional Cell Hyperplasia 0 0 0 0 1 0 0 5 Heart Number Examine d: 10 10 10 10 9 10 10 10 Infiltrate, Cellular, Myocardium 3 3 3 5 2 1 2 2 Inflammation, Chronic 0 4 9 8 0 0 4 10104Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313013 Histopathology - gr oup distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number: 10 1 0 10 10 9 10 10 10 Spleen Number Examined: 10 10 10 10 9 10 10 10 Adhesion 0 0 0 0 0 0 1 3 Capsular Cyst(s) 0 0 0 1 0 0 1 0 Capsular Inflammation 0 0 3 5 0 1 1 6 Capsular Thickening 1 1 3 6 1 2 3 8 Haemosiderosis 0 0 0 0 0 0 1 0 Thy mus Number Examined: 10 10 10 10 9 10 10 10 Involution/Atrophy 0 0 0 1 0 0 0 5 Thy ro ids Number Examined: 10 0 0 10 9 0 0 10 Follicular Cell Vacuolation 4 0 0 0 0 0 0 0 Follicular Dilatation 0 0 0 1 0 0 0 0 Parathy ro ids Number Examined: 10 0 0 8 8 0 0 8 Adrenals Number Examined: 10 0 0 10 9 0 0 10 B - Subcapsular Cell Adenoma 0 0 0 1 0 0 0 0 Cortical Hypertrophy 0 0 0 1 1 0 0 0 Cortical Vacuolation 6 0 0 6 0 0 0 0 Subcapsular Ce ll Hyperplasia, Focal 0 0 0 0 1 0 0 0105Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313013 Histopathology - gr oup distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropen e 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number: 10 10 10 10 9 10 10 10 Pituitary Number Examined: 10 0 0 10 9 0 0 10 Cyst(s) 0 0 0 1 2 0 0 1 LN Mandibular Number Examined: 10 0 0 10 9 0 0 10 Paracortex - Increased Cellularity 0 0 0 0 2 0 0 0 Plasmacytosis 6 0 0 7 5 0 0 3 Sinus Erythrocytosis/Erythrophagocytosis 0 0 0 0 0 0 0 2 Sinus Histiocytosis 3 0 0 4 3 0 0 7 Salivary Glands Number Examined: 10 0 0 10 9 0 0 10 Inflammation 0 0 0 0 0 0 0 1 Tongue Number Examined: 10 0 0 10 9 0 0 10 Parotid S.G. Number Examined: 10 0 0 10 9 0 0 10 Acinar Atrophy 0 0 0 1 1 0 0 0 Mineralisation 0 0 0 0 1 0 0 0106Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313013 Histopathology - gr oup distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropr opene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number: 10 10 10 10 9 10 10 10 Stomach Number Examined: 10 1 0 10 9 0 0 10 Dilated Glands 0 0 0 1 0 0 0 1 Mucosal Erosion - Glandular Region 0 0 0 1 0 0 0 0 Non - glandular Region - Squamous Cyst(s) 0 1 0 0 0 0 0 0 Submucosal Inflammation - Glandular Region 1 0 0 0 1 0 0 0 Oesophagus Number Examined: 10 0 0 10 9 0 0 10 Duodenum Number Examined: 10 0 0 10 9 0 0 10 Ileum Number Examined: 10 0 0 10 9 0 0 10 Peyer's Patch Number Examined: 10 0 0 10 9 0 0 9 Colon Number Examined: 10 0 0 10 9 0 0 10 Jejunum Number Examined: 10 0 0 10 9 0 0 10 Caecum Number Examined: 10 0 0 10 9 0 0 10 Rectum Number Examined: 10 0 0 10 9 0 0 10 Submucosal Oedema 1 0 0 0 0 0 0 0107Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313013 Histopatholog y - gr oup distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number: 10 10 10 10 9 10 10 10 Mammary Number Examined: 10 0 0 10 9 0 0 10 Acinar Atrophy 2 0 0 4 0 0 0 0 Site Only 0 0 0 0 1 0 0 2 Skin Number Examined: 10 0 1 10 9 0 1 10 Dermal Inflammation 0 0 1 1 2 0 0 1 Epidermal Hyperplasia 0 0 1 1 2 0 0 0 Epidermal Ulceration 0 0 0 0 1 0 0 0 Scab(s) 0 0 1 1 2 0 0 0 Skeletal Muscle Number Examined: 10 0 0 10 9 0 0 10 Inflammation 0 0 0 0 1 0 0 1 Lachry mal Glands Number Examined: 10 0 0 10 9 0 0 10 Ly mphoid Aggregates 1 0 0 0 1 0 0 1 Eyes Number Examined: 10 0 0 10 9 0 0 10 Inflammation of the Sclera 0 0 0 0 0 0 0 1 Inflammatory Cells, Anterior Chamber 0 0 0 0 0 0 0 1 Iritis 0 0 0 0 0 0 0 1 Keratitis 0 0 0 0 0 0 0 1 Retinal Rosettes/Folds 1 0 0 0 0 0 0 0108Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313013 Histopathology - gr oup distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number: 10 10 10 10 9 10 10 10 Harderian Glands Number Examined: 10 0 0 10 9 0 0 10 Ly mphoid Aggregates 0 0 0 0 2 0 0 0 M - Adenocarcinoma 0 0 0 0 0 0 0 1 Sternum + Marrow Number Examined: 10 0 0 10 9 0 0 10 Marrow - Fat Replacement 0 0 0 2 0 0 0 0 Femur inc. Joint Number Examined: 10 0 0 10 9 0 0 10 Syn ovitis 1 0 0 0 0 0 0 0 Sciatic Nerve Number Examined: 10 0 0 10 9 0 0 10 Br ain Number Examined: 10 0 0 10 9 0 0 10 Spinal C. Cerv. Number Examined: 10 0 0 10 9 0 0 10 Spinal C. Thor. Number Examined: 10 0 0 10 9 0 0 10 Spinal C. Lumb. Number Examined: 10 0 0 10 9 0 0 10109Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313013 Histopathology - gr oup distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number: 10 10 10 10 9 10 10 10 Prostate Number Examined: 10 0 0 10 - - - - Abscessation 0 0 0 1 - - - - Ly mphoid Aggregates 6 0 0 1 - - - - Seminal Vesicles Number Examined: 10 0 0 10 - - - - Epididymides Number Examined: 10 0 0 10 - - - - Ly mphoid Aggregates 0 0 0 3 - - - - Testes Number Examined: 10 0 0 10 - - - - Seminiferous Tubular Atrophy 0 0 0 1 - - - - Optic nerves Number Examined: 10 0 0 10 9 0 0 10 Degenerate Fibres 0 0 0 1 0 0 0 0 Ovaries Number Examined: - - - - 9 0 0 10 Cyst(s) - - - - 1 0 0 0 Pr ominent Corpora Lutea - - - - 1 0 0 0110Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313013 Histopathology - gr oup distribution of findings for an imals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number: 10 10 10 10 9 10 10 10 Vagina Number Examined: - - - - 9 0 0 10 Dioestrus - - - - 0 0 0 1 Metoestrus - - - - 7 0 0 6 Oestrus - - - - 1 0 0 3 Pr oestrus - - - - 1 0 0 0 Uterus Number Examined: - - - - 9 0 0 10 Pol yploid Hyperplasia - - - - 1 0 0 1 Uterine cervix Number Examined: - - - - 9 0 0 10 Lary nx Number Examined: 10 10 10 10 9 10 10 10 Foreign Body Reaction - Ventral Pouch 1 0 0 0 0 0 0 0 Inflammatory Cells in Lamina Propria 5 4 4 5 3 2 5 4 Squamous Metaplasia - Ventral 0 0 0 5 0 0 0 2 Tracheal Bifurc. Number Examined: 10 10 10 10 9 10 10 10 Inflammatory Cells in Lamina Propria 1 2 0 3 1 2 2 2 Loss of Cilia at Bifurcation 0 0 0 1 0 0 0 0111Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313013 Histopathology - gr oup distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - bromo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number: 10 10 10 10 9 10 10 10 LN Bronchial Number Examined: 9 0 0 10 9 0 0 10 Decreased Cellularity - Generalised 0 0 0 1 0 0 0 0 Paracortex - Increased Cellularity 1 0 0 0 0 0 0 0 Sinus Histiocytosis 0 0 0 1 0 0 0 1112Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313013 Histopathology - gr oup distribution of findings for animals killed after 13 weeks of treat ment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number: 10 10 10 10 9 1 0 10 10 Nasal turbinates Number Examined: 10 10 10 10 9 10 10 10 Increased Vacuolation of Vomeronasal Organ Epithelium 0 0 0 3 0 0 0 0 Inflammatory Exudate in Airways 0 0 0 1 0 0 0 5 Nasolacrimal Duct - Epithelial Squamous Metaplasia 1 1 0 0 2 3 2 8 Nasolacrimal Duct - Inflammation 5 8 4 8 2 4 7 9 Nasolacrimal Duct - Luminal Inflammatory Exudate 0 0 0 0 0 0 0 4 Nasolacrimal Duct Epithelial Degeneration 2 1 0 5 0 0 0 0 Nasopharynx - Goblet Cell Hyperplasia 1 0 0 2 0 0 0 0 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation 1 2 8 10 1 0 5 10 Olfactory Epithelium - Erosion 0 0 0 0 1 0 0 0 Olfactory Epithelium - Inflammation 0 0 0 3 1 0 0 2 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria 0 0 0 2 1 0 0 8 Olfactory Epithelium - Respiratory Metaplasia 0 0 0 0 0 0 0 5 Olfactory Epithelium - Squamous Metaplasia 0 0 0 1 0 0 0 1 Periodontal Abscess 0 1 0 0 0 0 0 0 Periodontal Inflammatory Cell Infiltration 0 1 0 0 0 0 0 0 Red Blood Cells in Airways 0 2 0 0 2 0 0 0 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation 0 1 0 6 1 1 1 10 Respiratory Epithelium - Erosion 0 0 0 0 1 0 0 2 Respiratory Epithelium - Goblet Cell Hyperplasia 0 0 0 4 0 1 0 0 Respir atory Epithelium - Inflammation 0 0 0 1 0 0 0 3 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria 0 0 0 1 0 0 0 10 Respiratory Epithelium - Regenerative Hyperplasia 0 0 0 1 0 0 0 0 Respiratory Epithelium - Squamous Metaplasia 0 0 0 1 0 0 0 0113Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313013 Histopathology - gr oup distribution of findings for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluor opr opene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F Tissue and Finding Number: 10 10 10 10 9 10 10 10 Nasal turbinates (continued) Number Examined: 10 10 10 10 9 10 10 10 Squamous Epithelium - Inflammatory Cells in the Lamina Propria 0 0 0 0 0 0 0 1 Transitional Epithelium - Inflammatory Cells in the Lamina Propria 0 0 0 0 0 1 1 1 Teeth Number Examined: 10 10 10 10 9 10 10 10 Ameloblast Degenerati on 0 0 0 1 0 0 0 2 Odontoblast Degeneration 0 0 0 1 0 0 2 1 Periodontal Ligament Inflammation 0 0 0 1 0 0 0 0 Pulp Cavity Increased Inflammatory Cell Infiltration 0 0 0 0 0 0 0 2 Pulp Cavity Necrosis 0 0 0 0 0 0 0 5 Paws Number Examined: 0 0 0 0 0 1 0 0 Oedema 0 0 0 0 0 1 0 0114Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313015 Histopathology - gr oup distribution of findings for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -t rifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 4M 1F 4F Tissue and Finding Number: 10 10 10 10 Trachea Number Examined: 10 10 10 10 Inflammation 3 0 0 0 Lungs + Bronchi Number Examined: 10 10 10 10 Aggregations of Alveolar Macrophages 4 3 2 0 Alveolar Congestion 1 0 0 0 Alveolar Eosinophilic Crystals 4 3 0 0 Alveolitis 4 4 0 0 Arterial Mural Mineralisation 6 3 4 4 Perivascular Inflammatory Cells 3 1 1 1 Pleural Inflammation 0 1 0 0 Liver Number Examined: 10 10 10 10 Hepatocyte Necrosis, Focal 0 0 1 1 Hepatocyte Vacuolation, Periportal 0 0 2 0 Inflammation, Focal 4 3 5 5 Perivascular Mineralisation 0 1 0 0 Pancreas Number Examined: 10 10 10 10 Acinar Atrophy, Focal 0 1 0 1 Acinar Cell Degranulation 0 0 1 0 Inflammation 0 0 1 1115Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313015 Histopathology - gr oup distribution of findings for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 4M 1F 4F Tissue and Finding Numb er: 10 10 10 10 Kidneys Number Examined: 0 1 0 1 Pelvic Dilatation 0 0 0 1 Perivascular Lymphoid Aggregations 0 1 0 0 Heart Number Examined: 10 10 10 10 Infiltrate, Cellular, Myocardium 6 3 1 0 Inflammation, Chronic 1 1 0 0 Spleen Number Examined: 10 10 10 10 Adhesion 0 1 0 1 Capsular Inflammation 0 2 0 0 Capsular Thickening 0 2 0 1 Haemosiderosis 0 0 0 1 Thy mus Number Examined: 10 10 9 10 Pituitary Number Examined: 0 1 0 0 Cyst(s) 0 1 0 0 LN Mandibular Number Examined: 0 1 0 0 Paracortex - Increased Cellularity 0 1 0 0 Plasmacytosis 0 1 0 0116Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313015 Histopathology - gr oup distribution of findings for animals killed after 4 we eks of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 4M 1F 4F Tissue and Finding Number: 10 10 10 10 Ovaries Number Examined: - - 1 1 Cyst(s) - - 1 0 Haemorrhagic Cyst(s) - - 0 1 Lary nx Number Examined: 10 10 10 10 Haemorrhage in Lamina Propria 1 0 0 0 Inflammatory Cells in Lamina Propria 3 3 6 5 Tracheal Bifurc. Number Examined: 10 10 10 10 Inflammatory Cells in Lamina Propria 2 3 0 1117Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313015 Histopathology - gr oup distribution of findings for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 4M 1F 4F Tissue and Finding Number: 10 10 10 10 Nasal turbinates Number Examined: 10 10 10 10 Inc reased Vacuolation of Vomeronasal Organ Epithelium 0 0 1 0 Inflammatory Exudate in Airways 1 0 2 1 Nasolacrimal Duct - Epithelial Squamous Metaplasia 2 0 0 1 Nasolacrimal Duct - Inflammation 5 6 5 9 Nasolacrimal Duct - Luminal Inflammatory Exudate 0 0 0 1 Nasolacrimal Duct Epithelial Degeneration 0 1 0 0 Nasopharynx - Goblet Cell Hyperplasia 1 0 0 0 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation 0 9 1 7 Olfactory Epithelium - Erosion 0 1 0 1 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria 0 1 0 3 Olfactory Epithelium - Squamous Metaplasia 0 1 0 0 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation 1 2 1 2 Respiratory Epithelium - Erosion 0 0 0 3 Respiratory Epithelium - Goblet Cell Hyperplasia 3 4 0 3 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria 0 0 1 4 Respiratory Epithelium - Squamous Metaplasia 0 0 0 2 Transitional Epithelium - Inflammatory Cells in the Lamina Propria 2 0 1 2 T eeth Number Examined: 10 10 10 10 Ameloblast Degeneration 0 0 0 4118Huntingdon Life SciencesWAG0014

TABLE 9 - continued Request ID: 313015 Histopathology - gr oup distribution of findings for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/Sex: 1M 4M 1F 4F Tissue and Finding Number: 10 10 10 10 Preputial glands Number Examined: 1 0 - - Abscessation 1 0 - -119Huntingdon Life SciencesWAG0014

APPENDIX 1 Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 1M 81 T 18 Coat Hair loss, Head 11 - R5 82 T 18 Skin Abrasion Dry, Tail, Slight 10 - 11 85 T 18 Coat Hair loss, Forelimbs 11 - R5 Skin Abrasion Dry, Tail, Slight 5 - 7 86 T 18 Coat Hair loss, Head R4 - R5 87 T 18 Coat Hair loss, Head R4 - R5 88 T 18 Behaviour Aggressive R5 89 T 18 Coat Hair loss, Dorsal Body Surface 3 Only animals with observation s are presented120Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 2M 101 T 14 Coat Hair loss, Head 9 - 14 Skin Abrasion Dry, Head, Slight 10 Dry, Tail, Slight 6 - 7 102 T 14 Coat Hair loss, Head 10 - 14 Staining Abnormal Colour, Brown, Head 4, 8 - 9 103 T 14 Skin Encrustation, Tail 4 - 5 Staining Abnormal Colour, Brown, Dorsal Body Surface 10 - 14 104 T 14 Coat Hair loss, Head 9 - 14 Skin Abrasion Dry, He ad, Slight 10 Dry, Tail, Slight 9 106 T 14 Coat Hair loss, Dorsal Body Surface 6 - 11 109 T 14 Build Deformity Swollen Area, Nose 9 - 14 Only animals with observations are presented121Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID : 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 3M 111 T 14 Behaviour Aggressive 10 - 11 Skin Abrasion Dry, Tail, Slight 5 112 T 14 Teeth Abnormal Colour, Pale 6 - 13 Abnormal Colour, Pale, Lower Jaw 5 113 T 14 Coat Hair loss, Head 11 - 14 Skin Abrasion Dry, Tail, Slight 13 - 14 Skin Encrustation, Tail 4 - 7 114 T 14 Behaviour Aggressive 8 - 11 115 T 14 Teeth Abnormal Colour, Pale 13 - 14 117 T 14 Teeth Abnormal Colour, P ale 8 - 14 118 T 14 Behaviour Aggressive 11 Teeth Absent, Pale 10 Abnormal Colour, Pale 11 - 14 119 T 14 Staining Abnormal Colour, Brown, Head 3 Teeth Abnormal Colour, Pale 9 - 14 Only animals with observationsare presented122Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 3M 120 T 14 Staining Abnormal Colour, Brown, Dorsal Body Surface 10 - 11 Only animals with observations are presented123Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 4M 11 T 14 Behaviour Un deractive 12 - 14 Coat Piloerection 12 - 14 Staining Abnormal Colour, Brown, Forepaws 12 - 14 Abnormal Colour, Brown, Head 12 - 14 Abnormal Colour, Brown, Dorsal Body Surface 8 - 9, 12 - 14 Teeth Abnormal Colour, Pale 4, 6 - 14 Abnormal Colour, Pale, Lower Jaw 5 12 T 14 Skin Colour Abnormal Colour, Brown, Dorsal Body Surface 13 - 14 Teeth Abnormal Colour, Pale 8 - 14 13 T 14 Behaviour Un deractive 12 - 14 Teeth Abnormal Colour, Pale 6 - 14 14 T 14 Staining Abnormal Colour, Brown, Head 8 - 9 Abnormal Colour, Brown, Dorsal Body Surface 8 - 9, 11 - 12 Teeth Abnormal Colour, Pale 10 - 14 15 T 14 Teeth Abnormal Colour, Pale 9 - 14 Only animals with observations are presented124Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trif luoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 4M 16 T 14 Skin Abrasion Dry, Tail, Slight 1 0 - 14 Staining Abnormal Colour, Brown, Dorsal Body Surface 9 - 14 Teeth Abnormal Colour, Pale 6 - 14 Abnormal Colour, Pale, Lower Jaw 5 17 T 14 Skin Abrasion Dry, Tail, Slight 10 - 11 Staining Abnormal Colour, Brown, Head 3 - 9, 12 - 14 Abnormal Colour, Brown, Dorsal Body Surface 4 - 14 Teeth Abnormal Colour, Pale 6 - 14 Abnormal Colour, White 2 18 T 14 Build Deformity Kinked Tail 10 - 14 Skin Abrasion Dry, Tail, Slight 8 - 9 19 T 14 Coat P iloerection 11 Skin Abrasion Dry, Tail, Slight 13 - 14 Teeth Abnormal Colour, Pale 8 - 14 20 T 14 Staining Abnormal Colour, Brown, Dorsal Body Surface 6, 9 - 14 Teeth Abnormal Colour, Pale 8 - 14 Only animals with observati ons are presented125Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (pp m) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 4M 71 T 18 Skin Abrasion Dry, Ventral Abdomen, Slight 10 - 11 Staining Abnormal Colour, Brown, Head 10 - 11 Abnormal Colour, Dors al Body Surface 3 Abnormal Colour, Brown, Dorsal Body Surface 4 - 11 Teeth Abnormal Colour, Pale 10 - R5 72 T 18 Staining Abnormal Colour, Brown, Dorsal Body Surface 9, 11 - R1 Teeth Abnormal Colour, Pale 8 - R5 73 T 18 S taining Abnormal Colour, Brown, Dorsal Body Surface 3, 6 - 9, 11 - R2 Teeth Abnormal Colour, Pale 6 - R5 Abnormal Colour, White 2 - 4 Abnormal Colour, Pale, Lower Jaw 5 74 T 18 Staining Abnormal Colour, Brown, Dorsal Body Surface 4 - 7, 9 - R3 Teeth Abnormal Colour, Pale 4, 6 - R5 Abnormal Colour, Pale, Lower Jaw 5 75 T 18 Staining Abnormal Colour, Brown, Dorsal Body Surface 5 - R3 Teeth Abnormal Colour, Pale 8 - R5 Abnormal Colour, White 2 Only animals with observations are presented126Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoroprop ene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 4M 76 T 18 Skin Abrasion Dry, Tail, Slight 11 - 12 Staining Abnormal Colour, Brown, Head 10 Abnormal Col our, Brown, Dorsal Body Surface 9 - 10 Teeth Abnormal Colour, Pale 8 - 11 77 T 18 Staining Abnormal Colour, Brown, Dorsal Body Surface 9 - 10, 13 - R2 Teeth Abnormal Colour, Pale 10 - 11 78 T 18 Build Deformity Kinked Tail 3 - R5 Staining Abnormal Colour, Brown, Head 13 - R3 Teeth Abnormal Colour, Pale 4, 6 - R5 Abnormal Colour, Pale, Lower Jaw 5 79 T 18 Build Deformity Kinked Tail R2 - R5 Skin Abrasion Dry, Tail, Slight 11 - R1 Staining Abnormal Co lour, Brown, Head 6 - 7 Abnormal Colour, Brown, Dorsal Body Surface 6 - 7 Teeth Abnormal Colour, Pale 10 - R5 80 T 18 Staining Abnormal Colour, Brown, Head 5 - 9 Abnormal Colour, Brown, Dorsal Body Surface 10 - R2 Teeth Abnormal Colour, Pale 6 - R5 Only animals with observations are presented127Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 1F 23 T 14 Behaviour Vocalisation 6, 8 - 12 24 T 14 Behaviour Vocalisation 6 - 11, 13 - 14 26 T 14 Coat Hair loss, Forelimbs 11 - 14 Hair loss, Head 11 - 14 27 W 8 Behaviour Un deractive 8 Body temperature Reduced 8 Br eathing Gasping 8 Coat Piloerection 8 Hair loss, Dorsal Body S urface 4 - 5 Eyelids Partially Closed 8 Skin Colour Pallor 8 Reason for Dispatch General poor clinical condition 8 28 T 14 Behaviour Vocalisation 5 - 6, 8 - 12 Coat Hair loss, Head 9 - 14 Skin Abrasion Dry, Tail 9 - 10 Dry, Tail, Slight 11 - 12 Only animals with observations are presented128Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -tri fluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 1F 29 T 14 Behaviour Vocalisation 10 Coat Hair loss, Head 10 - 12 Skin Abrasion Dry, Tail, Slight 13 - 14 30 T 14 Skin Abrasion Dry, Tail, Slight 6 - 9 43 T 18 Coat Hair loss, Head R1 - R2 Teeth Abnormal Colour, White 2 - 3 44 T 18 Behaviour Vocalisation 8 - 13 48 T 18 Behavi our Aggressive R2 Vocalisation 10 - 12, R2 Teeth Abnormal Colour, Pale 4 - 8 49 T 18 Behaviour Vocalisation 6 - 8, 12, R2 - R3 50 T 18 Behaviour Vocalisation 5 - R2 Build Deformity Partially absent appendage, Tail R2 - R5 Only animals with observations are presented129Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -t rifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 2F 51 T 14 Behaviour Vocalisation 8 - 14 Coat Hair loss, Dorsal Body Surface 6 - 11 52 T 14 Build Deformity Swollen Area, Forepaw (Left) 11 - 14 Skin Encrustation, Tail 4 53 T 14 Coat Hair loss, Forelimb (Left) 10 Hair loss, Forelimbs 11 - 14 Hair loss, Dorsal Body Surface 9 - 11, 13 - 14 54 T 14 Coat Hair l oss, Dorsal Body Surface 13 - 14 55 T 14 Coat Hair loss, Forelimbs 13 - 14 Hair loss, Dorsal Body Surface 8 - 9 Teeth Abnormal Colour, Pale 6 - 11 Abnormal Colour, Pale, Lower Jaw 5 56 T 14 Behaviour Vocalisation 6 - 14 Coat Hair loss, Head 5 - 9 Teeth Abnormal Colour, White 2 57 T 14 Behaviour Vocalisation 11 - 14 Teeth Abnormal Colour, White 2 Only animals with observations are presented130Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 C linical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 2F 58 T 14 Behaviour Vocalisation 8 - 14 Build Deformity Kinked Tail 12 - 14 Coat Hair loss, Head 6 - 8, 10 - 14 Staining Abnormal Colour, Brown, Head 3 Teeth Abnormal Colour, White 2 59 T 14 Behaviour Aggressive 8 - 11 Vocalisation 5 - 14 Coat Hair loss, Head 5 - 9 Hair loss, Head 10 - 14 Skin Abrasion Dry, Tail, Slight 13 - 14 60 T 14 Coat Hair loss, Forelimb (Left) 4 Hair loss, Forelimbs 5 - 1 4 Hair loss, Hindlimbs 5 - 14 Hair loss, Head 4 - 14 Hair loss, Dorsal Body Surface 5 - 14 Only animals with observations are presented131Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Grou p : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 3F 1 T 14 Behaviour Vocalisation 5 - 14 Staining Abnormal Colour, Head 12 Abnormal Colour, Brown, Muzzle 6 2 T 14 Behaviour Vocalisation 6 - 14 Staining Abnormal Colour, Brown, Head 11 - 14 3 T 14 Behaviour Vocali sation 4, 6 - 7, 9 - 11 Skin Abrasion Dry, Tail, Slight 13 - 14 Staining Abnormal Colour, Brown, Head 6 - 7, 13 - 14 4 T 14 Teeth Abnormal Colour, Pale 10 - 11 5 T 14 Behaviour Vocalisation 4 - 6, 8 - 14 Coat Hair loss, Dorsal Body Surface 5 - 7 6 T 14 Behaviour Aggressive 10 Vocalisation 6, 10 - 14 Coat Hair loss, Head 10 - 14 Hair loss, Dorsal Body Surface 6 - 11 Staining Abnormal Colour, Brown, Head 3 Only animals with observations are pr esented132Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 3F 7 T 14 Coat Hair loss, Head 12 - 14 Hair loss, Dorsal Body Surface 8 - 14 Staining Abnormal Colour, Brown, Cervical 3 - 9 Abnormal Colour, Brown, Dorsal Body Surface 10 - 14 8 T 14 Behaviour Aggressive 11 - 14 Vocalisation 6, 8 - 14 Coat Hair loss, Dorsal Body Surface 10 - 14 Staining Abnormal Colour, Brown, Cervical 5 - 9 9 T 14 Behaviour Vocalisation 4 - 6, 8 - 12 Coat Hair loss, Head 11 - 14 Hair loss, Dorsal Body Surface 6 - 14 Staining Abnormal Colour, Brown, Cervical 8 - 9 10 T 14 Coat Hair loss, Head 10 - 14 Hair loss, Dorsal Body Surface 4 - 14 Skin Abrasion Dry, Tail, Slight 13 - 14 Skin Encrustation, Dorsal Body Surface 5 - 8 Only animals with observations are presented133Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 4F 31 T 14 Coat Hair loss, Dorsal Body Surface 8 - 11 Skin Abrasion Dry, Tail 12 - 14 Staining Abnormal Colour, Brown, Head 3 - 9 Abnormal Colour, Brown, Dorsal Body Surface 12 - 14 Teeth Abnormal Colour, Pale 4, 6 - 14 Abnormal Colour, Pale, Lower Jaw 5 32 T 14 Behaviour Un deractive 13 - 14 Coat Hair loss, Dorsal Body Surface 8 - 14 Eyelids Partially Closed 13 - 14 Muscle Reaction Reduced Body Tone, Whole Body 5 - 14 Abnormal Gait, Elevated 3 - 12 Skin Abrasion Dry, Tail, Slight 13 - 14 Skin Encrustation, Tail 5 - 7 Staining Abnormal Colour, Brown, Head 3 - 14 Teeth Abnormal Colour, Pale 9 - 14 Br ittle 10 33 T 14 Coat Hair loss, Forelimb (Left) 6 - 14 Only animals with observations are presented134Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 4F 34 T 14 Coat Hair loss, Dorsal Body Surface 9 - 14 Muscle Reaction Abnormal Gait, Elevated 10 - 12 Staining Abnormal Colour, Brown, Head 4 Teeth Abnormal Colour, Pale 13 - 14 35 T 14 Coat Hair loss, Head 6 - 14 Staining Abnormal Colour, Brown, Head 8 - 9 Teeth Abnormal Colour, Pale 8 - 14 Br ittle 11 36 T 14 Build Deformity Swollen Area, Eye (Left) 12 - 14 S kin Abrasion Dry, Tail, Slight 13 - 14 Staining Abnormal Colour, Brown, Head 8 - 9 Abnormal Colour, Brown, Dorsal Body Surface 8 - 14 Teeth Abnormal Colour, Pale 4, 6 - 14 Abnormal Colour, Pale, Lower Jaw 5 37 T 14 Behaviour U nderactive 13 - 14 Body temperature Reduced 13 - 14 Muscle Reaction Reduced Body Tone 13 - 14 Staining Abnormal Colour, Brown, Head 9 Abnormal Colour, Brown, Muzzle 13 - 14 Teeth Abnormal Colour, Pale 10 - 14 Only animals wi th observations are presented135Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 4F 38 T 14 Coat Hair loss, Head 10 - 11 Eyelids Red - Rimmed 13 - 14 Teeth Abnormal Colour, Pale 9 - 14 39 T 1 4 Behaviour Vocalisation 7 Coat Hair loss, Head 10 - 11 Teeth Abnormal Colour, Pale 9 - 14 40 T 14 Skin Abrasion Dry, Tail, Slight 4 - 9 Staining Abnormal Colour, Brown, Head 8 - 14 Teeth Abnormal Colour, Pale 9 - 14 91 T 18 Behaviour Excessive chewing 13 - 14 Un deractive 13 - 14 Coat Piloerection 13 - 14 Eyelids Partially Closed 13 - 14 Muscle Reaction Reduced Body Tone, Whole Body 13 - 14 Skin Abrasion Dry, Tail, Slight 3 Staining Abnormal C olour, Brown, Head 7 Abnormal Colour, Brown, Muzzle 13 - 14 Teeth Abnormal Colour, Pale 8 - R5 Only animals with observations are presented136Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 4F 92 T 18 Behaviour Vocalisation 10 - 11, R2 - R5 Teeth Br oken 11 - 13 Abnormal Colour, Pale 6 - R5 Br ittle 11 93 T 18 Behaviour Aggressive 10 Vocalisation 10 Build Deformity Kinked Tail 12 - R5 Coat Hair loss, Head 6 - 7 Staining Abnormal Colour, Brown, Head 5 - 9 Teeth Abnormal Colour, Pale 6 - R5 94 T 18 Behaviour Excessive chewing 11 Coat Hair loss, Head 13 - R3 Eye Dull 11 Muscle Reaction Reduced Body Tone 11 - 13 Abnormal Gait 11 Staining Abnormal Colour, Brown, Head 7, 11 Teeth Abnormal Colour, Pale 9 - R5 95 T 18 Skin Abrasion Dry, Tail, Slight 11 Staining Abnormal Colour, Brown, Head 7, 13 Teeth Abnormal Colour, Pale 9 - R5 Only animals with observations are presented137Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluor opr opene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 4F 96 T 18 Coat Hair loss, Forelimb (Right) 5 - 9 Hair loss, Head 5 - R5 Hair loss, Dorsal Body Surf ace 5 - R5 Staining Abnormal Colour, Brown, Dorsal Body Surface 13 Teeth Abnormal Colour, Pale 8 - R5 97 T 18 Coat Hair loss, Head 8 - R5 Hair loss, Dorsal Body Surface 5 - R5 Staining Abnormal Colour, Brown, Head 8 - 9 Teeth Abnormal Colour, Pale 6 - 11 Abnormal Colour, Pale, Lower Jaw 5 98 T 18 Skin Encrustation, Tail 5 Staining Abnormal Colour, Brown, Head 7 - R2 Abnormal Colour, Brown, Dorsal Body Surface 10 - 13 Teeth Abnormal Colour, Pal e 9 - R5 99 T 18 Coat Hair loss, Head 8 - R5 Hair loss, Dorsal Body Surface 6 - R3 Staining Abnormal Colour, Brown, Head 8 - 10 Teeth Abnormal Colour, Pale 6 - R5 Only animals with observations are presented138Huntingdon Life SciencesWAG0014

APPENDIX 1 - continued Request ID: 296730 Clinical signs - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Death Week of /Sex Number Code Death Category Observation Week(s) 4F 100 T 18 Coat Hair loss, Head 2 - R5 Hair loss, Dorsal Body Surface 8 - R3 Staining Abnormal Colour, Brown, Head 5 - 10 Teeth Abnormal Colour, Pale 9 - R5 Only animals with observations are presented139Huntingdon Life SciencesWAG0014

APPENDIX 2 Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3 ,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2M 101 Behaviour

Underactive 3, 15, 24 - 25, 15 - 18, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Unresponsive 18 Br eathing Slow 18 Coat Piloere ction 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88, 92 Eyelids (Left) Partially Closed 24 18, 23 - 24 Eyelids (Right) Partially Closed 24 18, 23 - 24140Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Expo sure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2M 102 Behaviour

Underactive 3, 15, 24 - 25, 15 - 18, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Unresponsive 18 Br eathing Slow 18 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88, 92 Eyelids (Left) Partially Closed 24 18, 23 - 24 Eyelids (Right) Partially Closed 24 18, 23 - 24141Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 5 05 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2M 103 Behaviour

Underactive 3, 15, 24 - 25, 15 - 18, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Unresponsive 18 Br eathing Slow 18 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35 , 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88, 92 Eyelids (Left) Partially Closed 24 18, 23 - 24 Eyelids (Right) Partially Closed 24 18, 23 - 24142Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group / Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2M 104 Behaviour

Underactive 3, 15, 24 - 25, 15 - 1 8, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Unresponsive 18 Br eathing Slow 18 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88, 92 Eyelids (Left) Partially Closed 24 18, 23 - 24 Eyelids (Right) Partially Closed 24 18, 23 - 24143Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign App roximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2M 105 Behaviour

Underactive 3, 15, 24 - 25, 15 - 18, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Unresponsive 18 Br eathing Slow 18 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88, 92 Eyelids (Left) Partially Closed 24 18, 23 - 24 Eyelids (Right) Partially Closed 24 18, 23 - 24144Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2M 106 Behaviour

Underactive 3, 15, 24 - 25, 15 - 18, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52, 94 Unresponsive 18 Br eathing Slow 18 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88, 94 43 - 44, 46, 52,

70, 88, 92 - 94 Eyelids (Left) Partially Closed 24 18, 23 - 24 Eyelids (Right) Partially Closed 24 18, 23 - 24145Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approx imately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2M 107 Behaviour

Underactive 3, 15, 24 - 25, 15 - 18, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 3 9, 42 - 43,

50 - 52, 94 Unresponsive 18 Br eathing Slow 18 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88, 94 43 - 44, 46, 52,

70, 88, 92 - 94 Eyelids (Left) Partially Closed 24 18, 23 - 24 Eyelids (Right) Partially Closed 24 18, 23 - 24146Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2M 108 Behaviour

Underactive 3, 15, 24 - 25, 15 - 18, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52, 94 Unresponsive 18 Br eathing Slow 18 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88, 94 43 - 44, 46, 52,

70, 88, 92 - 94 Eye lids (Left) Partially Closed 24 18, 23 - 24 Eyelids (Right) Partially Closed 24 18, 23 - 24147Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposur e 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2M 109 Behaviour

Underactive 3, 15, 24 - 25, 15 - 18, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52, 94 Unresponsive 18 Br eathing Slow 18 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88, 94 43 - 44, 46, 52,

70, 88, 92 - 94 Eyelids (Left) Partially Closed 24 18, 23 - 24 Eyelids (Right) Partially Closed 24 18, 23 - 24148Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - brom o - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2M 110 Behaviour

Underactive 3, 15, 24 - 25, 15 - 18, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52, 94 Unresponsive 18 Br eathing Slow 18 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88, 94 43 - 44, 46, 52,

70, 88, 92 - 94 Eyelids (Left) Partial ly Closed 24 18, 23 - 24 Eyelids (Right) Partially Closed 24 18, 23 - 24149Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropr opene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 111 Behaviour

Underactive 1 - 4, 7 - 8, 14 - 15, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -25, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53 , 56, 58 - 60, 63 - 67, 70, 72, 63 - 67, 70, 88 88 Unresponsive 1, 17 - 18, 29 - 30, 1, 15, 17 - 18, 38, 51 21, 30, 35,

38, 63 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88150Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 111 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 63, 49 - 50, 56, 63, 65, 71 - 74, 65, 71 - 74, 77 - 81, 84 - 88, 77 - 81, 84 - 88, 91 91 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88151Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 S igns associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 112 Behaviour

Underactive 1 - 4, 7 - 8, 14 - 15, 1 - 4, 7, 9, 14 - 1 8, 17 - 18, 21 -25, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 63 - 67, 70, 88 88 Unresponsive 1, 17 - 18, 29 - 30, 1, 15, 17 - 18, 38, 51 21, 30, 35,

38, 63 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88152Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposur e Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 112 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 2 5, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 63, 49 - 50, 56, 63, 65, 71 - 74, 65, 71 - 74, 77 - 81, 84 - 88, 77 - 81, 84 - 88, 91 91 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88153Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 113 Behaviour

Underactive 1 - 4, 7 - 8, 14 - 15, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -25, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 63 - 67, 70, 88 88 Unresponsive 1, 17 - 18, 29 - 30, 1, 15, 17 - 18, 38, 51 21, 30, 35,

38, 63 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

5 8, 70, 88154Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 1 13 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 63, 49 - 50, 56, 63, 65, 71 - 74, 65, 71 - 74, 77 - 81 , 84 - 88, 77 - 81, 84 - 88, 91 91 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88155Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 114 Behaviour

Underactive 1 - 4, 7 - 8, 14 - 15, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -25, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 63 - 67, 70, 88 88 Unresponsive 1, 17 - 18, 29 - 30, 1, 15, 17 - 18, 38, 51 21, 30, 35,

38, 63 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88156Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 114 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35 , 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 63, 49 - 50, 56, 63, 65, 71 - 74, 65, 71 - 74, 77 - 81, 84 - 88, 77 - 81, 84 - 88, 91 91 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88157Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 115 Behaviour

Underactive 1 - 4, 7 - 8, 14 - 15, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -25, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 63 - 67, 70, 88 88 Unresponsive 1, 17 - 18, 29 - 30, 1, 15, 17 - 18, 38, 51 21, 30, 35,

38, 63 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88158Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 115 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 63, 49 - 50, 56, 63, 65, 71 - 74, 65, 71 - 74, 77 - 81, 84 - 88, 77 - 81, 84 - 88, 9 1 91 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88159Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Grou p : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 116 Behaviour

Underactive 1 - 4, 7 - 8, 14 - 15, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -25, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 63 - 67, 70, 88 88, 92 - 93 Unresponsive 1, 17 - 18, 29 - 30, 1, 15, 17 - 18, 38, 51 21, 30, 35,

38, 63 Br eathing Shallow 23 Slow 2 8, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88, 92 - 93160Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 116 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 63, 49 - 50, 56, 63, 65, 71 - 74, 65, 71 - 74, 77 - 81, 84 - 88, 77 - 81, 84 - 88, 91 - 93 91 - 93 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 93 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 93161Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

p ossible in the working day 3M 117 Behaviour

Underactive 1 - 4, 7 - 8, 14 - 15, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -25, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 6 3 - 67, 70, 88 88, 92 - 93 Unresponsive 1, 17 - 18, 29 - 30, 1, 15, 17 - 18, 38, 51 21, 30, 35,

38, 63 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88, 92 - 93162Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trif luoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 117 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 63, 49 - 50, 56, 63, 65, 71 - 74, 65, 71 - 74, 77 - 81, 84 - 88, 77 - 81, 84 - 88, 91 - 93 91 - 93 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 93 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 93163Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Re quest ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 118 Behaviour

Underactive 1 - 4, 7 - 8, 14 - 15, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -25, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 63 - 67, 70, 88 88, 92 - 93 Unresponsive 1, 17 - 18, 29 - 30, 1, 15, 17 - 18, 38, 51 21, 30, 35,

38, 63 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88, 92 - 93164Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 118 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 63, 49 - 50, 56, 63, 65, 71 - 74, 65, 71 - 74, 77 - 81, 84 - 88, 77 - 81, 84 - 88, 91 - 93 91 - 93 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 93 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 93165Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 119 Behaviour

Underactive 1 - 4, 7 - 8, 14 - 15, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -25, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -4 6, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 63 - 67, 70, 88 88, 92 - 93 Unresponsive 1, 17 - 18, 29 - 30, 1, 15, 17 - 18, 38, 51 21, 30, 35,

38, 63 Br eathing Shallow 23 Slow 28, 32, 4 2, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88, 92 - 93166Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 119 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 4 2, 44 - 45, 42, 44 - 45, 49 - 50, 56, 63, 49 - 50, 56, 63, 65, 71 - 74, 65, 71 - 74, 77 - 81, 84 - 88, 77 - 81, 84 - 88, 91 - 93 91 - 93 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 93 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 93167Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 120 Behaviour

Underactive 1 - 4, 7 - 8, 14 - 15, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -25, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 63 - 67, 70 , 88 88, 92 - 93 Unresponsive 1, 17 - 18, 29 - 30, 1, 15, 17 - 18, 38, 51 21, 30, 35,

38, 63 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88, 92 - 93168Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3M 120 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 63, 49 - 50, 56, 63, 65, 71 - 74, 65, 71 - 74, 77 - 81, 84 - 88, 77 - 81, 84 - 88, 91 - 93 91 - 93 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 93 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 22 - 24, 28 - 29, 35, 44, 50, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 93169Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID : 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 11 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11 , 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88,

92170Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 11 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 3 2, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 - 92 84 - 87, 91 - 92 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 1 4 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Eyelids (Right) Closed 1 1171Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 11 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 - 92 91 - 92 Posture Hun ched 1 1172Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -tri fluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

compl etion of dosing all groups As late as

possible in the working day 4M 12 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 5 3, 58, 70, 88 58, 70, 88,

92173Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 12 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74 , 77 - 81, 84 - 87, 91 - 92 84 - 87, 91 - 92 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Eyelids (Right) Closed 1 1174Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual ob servations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 12 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 - 92 91 - 92 Posture Hun ched 1 1175Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 D ays Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 13 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Unresponsive 1, 10 - 11, 1 4 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88,

92176Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 13 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 - 92 84 - 87, 91 - 92 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14 , 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Eyel ids (Right) Closed 1 1177Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3, 3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 13 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 - 92 91 - 92 Posture Hun ched 1 1178Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - bromo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hoursafter

completion of dosing all groups As late as

possible in the working day 4M 14 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53 , 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 4 2 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88,

92179Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As lat e as

possible in the working day 4M 14 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74 , 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 - 92 84 - 87, 91 - 92 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Eyelids (Right) Closed 1 1180Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hour s during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 14 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 - 92 91 - 92 Posture Hun ched 1 1181Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 5 05 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 15 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Unresponsi ve 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88,

92182Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs as sociated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 15 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 - 92 84 - 87, 91 - 92 Eyelids (Left) Closed 1 1 Partially Close d 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 9 1 - 92 Eyelids (Right) Closed 1 1183Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoroprop ene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

pos sible in the working day 4M 15 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 - 92 91 - 92 Posture Hun ched 1 1184Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 16 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53 , 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88, 94 72, 77, 88,

93 - 94 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24185Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 16 Br eathing

Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 4 2, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88, 58, 70, 88, 94 92 - 94 Coat Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 4 9, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 - 94 84 - 87, 91 - 94 Eyelids (Left) Closed 1 1186Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 16 Eyelids (Left)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Eyelids (Right) Closed 1 1 Partially Clos ed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 - 94 91 - 94 Posture Hun ched 1 1187Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 17 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 8 1, 84 - 88, 91 - 94 84 - 88, 91 - 94 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88, 94 72, 77, 88,

93 - 94 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24188Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposur e 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 17 Br eathing

Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88, 58, 70, 88 , 94 92 - 94 Coat Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 - 94 84 - 87, 91 - 94 Eyelids (Left) Closed 1 1189Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 17 Eyelids (Left)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Eyelids (Right) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35 , 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 - 94 91 - 94 Posture Hun ched 1 1190Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request I D: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /S ex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 18 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4 , 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 1 1, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88, 94 72, 77, 88,

93 - 94 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24191Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3, 3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 18 Br eathing

Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88, 58, 70, 88, 94 92 - 94 Coat Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 - 94 84 - 87, 91 - 94 Eyelids (Left) Closed 1 1192Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 18 Eyelids (Left)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Eyelids (Right) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 - 94 91 - 94 Posture Hun ched 1 1193Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 19 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88, 94 72, 77, 88,

93 - 94 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24194Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 19 Br eathing

Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88, 58, 70, 88, 94 92 - 94 Coat Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 - 94 84 - 87, 91 - 94 Eyelids (Left) Closed 1 1195Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours du

ring exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 19 Eyelids (Left)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Eyelids (Right) Closed 1 1 P artially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 - 94 91 - 94 Posture Hun ched 1 1196Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

po ssible in the working day 4M 20 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81 , 70 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88, 94 72, 77, 88,

93 - 94 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24197Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours d uring exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 20 Br eathing

Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 8 8, 58, 70, 88, 94 92 - 94 Coat Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 7 4, 77 - 81, 84 - 87, 91 - 94 84 - 87, 91 - 94 Eyelids (Left) Closed 1 1198Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluor opr opene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 20 Eyelids (Left)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 4 9 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Eyelids (Right) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 - 94 91 - 94 Posture Hun ched 1 1199Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 D ays Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 71 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9 , 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88200Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 71 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1201Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposur e level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 71 Eye lids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 7 7 - 81, 84 - 88, 84 - 88, 91 91 Posture Hun ched 1 1202Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all g

roups As late as possible in the working day 4M 72 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88203Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 72 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67 , 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1204Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 h ours after

completion of dosing all groups As late as

possible in the working day 4M 72 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 91 Posture Hun ched 1 1205Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 73 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 2 5, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88206Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 73 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 5 7, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 3 9, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1207Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289 355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Ani mal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 73 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 91 Posture Hun ched 1 1208Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 74 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88 , 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eath ing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88209Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 2893 55 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 74 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 8 8, 91 Eyelids (Right) Closed 1 1210Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

po ssible in the working day 4M 74 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63 , 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 91 Posture Hun ched 1 1211Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 75 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53 , 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88212Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoroprop ene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

pos sible in the working day 4M 75 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1213Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 75 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 91 Posture Hun ched 1 1214Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group / Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 76 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88215Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observati ons Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure App roximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 76 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 3 2, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25 , 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1216Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 76 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 91 Posture Hun ched 1 1217Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As lat e as

possible in the working day 4M 77 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74 , 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 5 9 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88218Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 77 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (L eft) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 7 4, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1219Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

c ompletion of dosing all groups As late as

possible in the working day 4M 77 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 5 3, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 91 Posture Hun ched 1 1220Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during expo sure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 78 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88221Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 78 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1222Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number S ign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 78 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 91 Posture Hun ched 1 1223Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 79 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52, 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88224Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs a ssociated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Si gn Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 79 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4 , 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1225Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in th e working day 4M 79 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 91 Posture Hun ched 1 1226Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - brom o - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 80 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 60, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23, 21, 23 - 25, 25, 29 - 31, 29 - 31, 35 - 36, 35 - 36, 39, 49, 39, 43, 49, 51 - 52 , 56 - 57, 51 - 52, 56 - 57, 59 - 60, 64 - 67, 59 - 60, 64 - 67, 88 72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 18, 25, 28 -29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88227Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 80 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59 - 60, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 8 1, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 5 8 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1228Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4M 80 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58, 56, 58, 63, 63, 65 - 67, 65 - 67, 70 - 74, 70 - 74, 77 - 81, 77 - 81, 84 - 88, 84 - 88, 91 91 Posture Hun ched 1 1229Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2F 51 Behaviour

Underactive 3, 15, 24 - 25, 15 - 17, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88 Eyelids (L eft) Partially Closed 24 23 - 24 Eyelids (Right) Partially Closed 24 23 - 24230Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - brom o - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2F 52 Behaviour

Underactive 3, 15, 24 - 25, 15 - 17, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Coat Pi loerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88 Eyelids (Left) Partially Closed 24 23 - 24 Eyelids (Right) Partially Closed 24 23 - 24231Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2F 53 Behaviour

Underactive 3, 15, 24 - 25, 15 - 17, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 3 7, 88 43 - 44, 46, 52,

70, 88 Eyelids (Left) Partially Closed 24 23 - 24 Eyelids (Right) Partially Closed 24 23 - 24232Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during expo sure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2F 54 Behaviour

Underactive 3, 15, 24 - 25, 15 - 17, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39 , 50, 52 39, 42 - 43,

50 - 52 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88 Eyelids (Left) Partially Closed 24 23 - 24 Eyelids (Right) Partially Closed 24 23 - 24233Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As lat e as

possible in the working day 2F 55 Behaviour

Underactive 3, 15, 24 - 25, 15 - 17, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88 Eyelids (Left) Partially Closed 24 23 - 24 Eyelids (Right) Partially Closed 24 23 - 24234Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group / Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2F 56 Behaviour

Underactive 3, 15, 24 - 25, 15 - 17 , 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88, 92 - 93 Eyelids (Left) Partially Closed 24 23 - 24 Eyelids (Right) Partially Closed 24 23 - 24235Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exp osure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2F 57 Behaviour

Underactive 3, 15, 24 - 25, 15 - 17, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88, 92 - 93 Eyelids (Left) Partially Closed 24 23 - 24 Eyelids (Right) Partially Closed 24 23 - 24236Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trif luoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2F 58 Behaviour

Underactive 3, 15, 24 - 25, 15 - 18, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88, 92 - 93 Eyelids (Left) Partially Closed 24 18, 23 - 24 Eyelids (Right) Partially Closed 24 18, 23 - 24237Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Si gns associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Numb er Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2F 59 Behaviour

Underactive 3, 15, 24 - 25, 15 - 17, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88, 92 - 93 Eyelid s (Left) Partially Closed 24 23 - 24 Eyelids (Right) Partially Closed 24 23 - 24238Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 2F 60 Behaviour

Underactive 3, 15, 24 - 25, 15 - 17, 23 - 25, 28 - 29, 32, 35, 28 - 29, 32, 35 - 37, 39, 50, 52 39, 42 - 43,

50 - 52 Coat Piloerection 3, 8 - 9, 15, 1 - 4, 8 - 9, 15 - 17, 25, 32, 35, 22 - 23, 25, 29, 44, 52, 70, 32, 35, 37, 88 43 - 44, 46, 52,

70, 88, 92 - 93 Eyelids (Left) Partially Closed 24 23 - 24 Eyelids (Right) Partially Close d 24 23 - 24239Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene E xposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 1 Behaviour

Grinding Teeth 25 Underactive 1 - 4, 7 - 8, 14, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -24, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 64 - 67, 70, 88 88, 92 Unresponsive 1, 15, 17 - 18, 1, 17 - 18, 21, 29 - 30, 38, 51, 30, 35, 38, 64 63 - 64 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88, 92240Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 1 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 64 - 65, 49 - 50, 56, 63 - 65, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 Eyelids (Ri ght) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92241Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 2 Behaviour

Grinding Teeth 25 Underactive 1 - 4, 7 - 8, 14, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -24, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 64 - 67, 70, 88 88, 92 Unresponsive 1, 15, 17 - 18, 1, 17 - 18, 21, 29 - 30, 38, 51 , 30, 35, 38, 64 63 - 64 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88, 92242Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number S ign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 2 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21 , 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 64 - 65, 49 - 50, 56, 63 - 65, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Eyelids (Left) Partially C losed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92243Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Comp ound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 3 Behaviour

Grinding Teeth 25 Underactive 1 - 4, 7 - 8, 14, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -24, 21 - 25, 28 - 32, 28 - 32, 35 - 3 9, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 64 - 67, 70, 88 88, 92 Unresponsive 1, 15, 17 - 18, 1, 17 - 18, 21, 29 - 30, 38, 51, 30, 35, 38, 64 63 - 64 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88, 92244Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 3 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 64 - 65, 49 - 50, 56, 63 - 65, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44 , 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 4 2 - 44, 46, 50 - 53, 88 58, 70, 88,

92245Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoroprop ene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

pos sible in the working day 3F 4 Behaviour

Grinding Teeth 25 Underactive 1 - 4, 7 - 8, 14, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -24, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 6 3 - 67, 70, 72, 64 - 67, 70, 88 88, 92 Unresponsive 1, 15, 17 - 18, 1, 17 - 18, 21, 29 - 30, 38, 51, 30, 35, 38, 64 63 - 64 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88, 92246Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

poss ible in the working day 3F 4 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 64 - 65, 49 - 50, 56, 63 - 65 , 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 5 8, 70, 88,

92 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92247Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 5 Behaviour

Grinding Teet

h 25 Underactive 1 - 4, 7 - 8, 14, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -24, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 64 - 67, 70, 88 88, 92 Unresponsive 1, 15, 17 - 18, 1, 17 - 18, 21, 29 - 30, 38, 51, 30, 35, 38, 64 63 - 64 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88 46, 51 - 53,

58, 70, 88, 92248Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 5 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 64 - 65, 49 - 50, 56, 63 - 65, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 88, 91 - 92 84 - 88, 91 - 92 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 Eyelids (Right) Partially Closed 1 - 4 , 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92249Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 6 Behaviour

Grinding Teeth 25 Underactive 1 - 4, 7 - 8, 14, 1 - 4, 7, 9, 14 - 18, 17 - 18, 2 1 -24, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 64 - 67, 70, 88, 88, 92 - 94 94 Unresponsive 1, 15, 17 - 18, 1, 17 - 18, 21, 29 - 30, 38, 51, 30, 35, 38, 64 63 - 64 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88, 46, 51 - 53, 94 58, 70, 88,

92 - 94250Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 6 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 64 - 65, 49 - 50, 56, 63 - 65, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Eyelids (Left) Partially Closed 1 - 4, 7, 22 , 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 94 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24 , 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 94251Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Con trol 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 6 Posture

Hun ched 94 94252Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 7 Behaviour

Grinding Teeth 25 Underactive 1 - 4, 7 - 8, 14, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -24, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 64 - 67, 70, 88, 88, 92 - 94 94 Unresponsive 1, 15, 17 - 18, 1, 17 - 18, 21, 29 - 30, 38, 51, 30, 35, 38, 64 63 - 64 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88, 46, 51 - 53, 94 58, 70, 88,

92 - 94253Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual obs ervations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 7 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25 , 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 64 - 65, 49 - 50, 56, 63 - 65, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 2 4, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 94 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 94254Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trif luoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 7 Posture

Hun ched 94 94255Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 8 Behaviour

Grinding Teeth 25 Underactive 1 - 4, 7 - 8, 14, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -24, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 64 - 67, 70, 88, 88, 92 - 94 94 Unresponsive 1, 15, 17 - 18, 1, 17 - 18, 21, 29 - 30, 38, 51, 30, 35, 38, 64 63 - 64 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88, 46, 51 - 53, 94 58, 70, 88,

92 - 94256Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hour s during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 8 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 64 - 65, 49 - 50, 56, 63 - 65, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 94 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 94257Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3, 3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all grou

ps As late as possible in the working day 3F 8 Posture

Hun ched 94 94258Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -tri fluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

compl etion of dosing all groups As late as

possible in the working day 3F 9 Behaviour

Grinding Teeth 25 Underactive 1 - 4, 7 - 8, 14, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -24, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46 , 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 64 - 67, 70, 88, 88, 92 - 94 94 Unresponsive 1, 15, 17 - 18, 1, 17 - 18, 21, 29 - 30, 38, 51, 30, 35, 38, 64 63 - 64 Br eathing Shallow 23 Slow 28, 32, 42 , 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88, 46, 51 - 53, 94 58, 70, 88,

92 - 94259Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Contro l 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 9 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 4 2, 44 - 45, 42, 44 - 45, 49 - 50, 56, 64 - 65, 49 - 50, 56, 63 - 65, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 94 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 94260Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 9 Posture

Hun ched 94 94261Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3 ,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 10 Behaviour

Grinding Teeth 25 Underactive 1 - 4, 7 - 8, 14, 1 - 4, 7, 9, 14 - 18, 17 - 18, 21 -24, 21 - 25, 28 - 32, 28 - 32, 35 - 39, 35 - 39, 42 -46, 42, 44 - 46, 49 - 53, 56 - 60, 49 - 53, 56, 58 - 60, 63 - 67, 70, 72, 64 - 67, 70, 88, 88, 92 - 94 94 Unresponsive 1, 15, 17 - 18, 1, 17 - 18, 21, 29 - 30, 38, 51, 30, 35, 38, 64 63 - 64 Br eathing Shallow 23 Slow 28, 32, 42, 25, 28 - 29, 44, 52 - 53, 32, 36, 42 -44, 58, 70, 88, 46, 51 - 53, 94 58, 70, 88,

92 - 94262Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropr opene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completi on of dosing all groups As late as

possible in the working day 3F 10 Coat

Piloerection 1 - 4, 7 - 9, 15 - 16, 1 - 4, 7 - 9, 11, 18, 21, 23, 15 - 18, 21 - 23, 25, 30 - 31, 25, 30 - 31, 35, 37, 39, 35, 37, 39, 42, 44 - 45, 42, 44 - 45, 49 - 50, 56, 64 - 65, 49 - 50, 56, 63 - 65, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 88, 91 - 94 84 - 88, 91 - 94 Eyelids (Left) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 94 Eyelids (Right) Partially Closed 1 - 4, 7, 22, 1, 3 - 4, 7, 9, 24, 28, 32, 18, 22 - 24, 35, 44, 50, 28 - 29, 32, 35 - 36, 52 - 53, 58, 70, 42 - 44, 46, 50 - 53, 88 58, 70, 88,

92 - 94263Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 3F 10 Posture

Hun ched 94 94264Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropen e 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possibl e in the working day 4F 31 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 59, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 7 0 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59, 64 - 67, 51 - 52, 56 - 57, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88265Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 31 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1266Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all gr oups As late as

possible in the working day 4F 31 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1267Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 32 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88268Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3 ,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all group s As late as

possible in the working day 4F 32 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1269Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - indivi dual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours durin g exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 32 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1270Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 33 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 1 4 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88271Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individua l observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 33 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 3 7, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 2 2, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1272Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 33 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1273Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - brom o - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all gr oups As late as

possible in the working day 4F 34 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67 , 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88274Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 34 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 7 0 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1275Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3, 3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 34 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 4 9 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1276Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - indi vidual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 35 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88277Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

c ompletion of dosing all groups As late as

possible in the working day 4F 35 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1278Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs as sociated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 35 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 1 8, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1279Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 36 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 9 3 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88, 93 Breathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24280Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - bromo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing a ll groups As late as

possible in the working day 4F 36 Br eathing

Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88,

92 - 93 Coat Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 - 93 84 - 87, 91 - 93 Eyelids (Left) Closed 1 1281Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 36 Eyelids (Left)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 7 4, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 93 Eyelids (Right) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 93 Posture Hun ched 1282Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 37 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 93 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88, 93 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24283Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 287 6 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 37 Br eathing

Slow 22, 28 , 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88,

92 - 93 Coat Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 3 9, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 - 93 84 - 87, 91 - 93 Eyelids (Left) Closed 1 1284Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximate ly 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 37 Eyelids (Left)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 2 4 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 93 Eyelids (Right) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 93 Posture Hun ched 1285Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all gr oups As late as

possible in the working day 4F 38 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 93 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57 , 64 - 67, 88 59, 64 - 67,

72, 77, 88, 93 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24286Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 38 Br eathing

Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 7 0, 88 58, 70, 88,

92 - 93 Coat Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 - 93 84 - 87, 91 - 93 Eyelids (Left) Closed 1 1287Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion o f dosing all groups As late as

possible in the working day 4F 38 Eyelids (Left)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 93 Eyelids (Right) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 93 Posture Hun ched 1288Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 39 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 93 Unresponsive 1, 10 - 11 , 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88, 93 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24289Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 39 Br eathing

Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88,

92 - 93 Coat Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 1 1 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 - 93 84 - 87, 91 - 93 Eyelids (Left) Closed 1 1290Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 39 Eyelids (Left)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 93 Eyelids (Right) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 93 Posture Hun ched 1291Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 40 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 93 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88, 93 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24292Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 40 Br eathing

Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88,

92 - 93 Coat Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49 , 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 - 93 84 - 87, 91 - 93 Eyelids (Left) Closed 1 1293Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observati ons Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure App roximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 40 Eyelids (Left)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 3 2, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 93 Eyelids (Right) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 - 93 84 - 88, 91 - 9 3 Posture Hun ched 1294Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in th e working day 4F 91 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88295Huntingdon Life SciencesWAG0014

APPENDIX 2 - continue d Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 91 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1296Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3 ,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all group s As late as

possible in the working day 4F 91 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56 , 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1297Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hoursduring exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 92 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88298Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups A s late as

possible in the working day 4F 92 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 4 9 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1299Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individua l observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 92 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32 , 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1300Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 93 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 1 5, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9 , 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88301Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during expo sure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 93 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1302Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 93 Eyelids (R ight) Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1303Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3 ,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 94 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88304Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 94 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (L eft) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 7 4, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1305Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

c ompletion of dosing all groups As late as

possible in the working day 4F 94 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 5 3, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1306Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individ ual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 95 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31 , 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88307Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -tr ifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

comp letion of dosing all groups As late as

possible in the working day 4F 95 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60 , 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 4 2, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1308Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs assoc iated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 95 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1309Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 96 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88310Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associat ed with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Appr oximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 96 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Ri ght) Closed 1 1311Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -tri fluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 96 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1312Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3 ,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 97 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 5 7, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88313Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 97 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1314Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 97 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -4 4, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1315Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs ass ociated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 98 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88316Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exp osure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 98 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 5 7, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1317Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Gr oup /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 98 Eyelids (Right)

Partially Closed 2 - 4 , 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 P osture Hun ched 1318Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -t rifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the workin g day 4F 99 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 46, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88319Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 99 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 P artially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1320Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As lat e as

possible in the working day 4F 99 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1321Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 C ompound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours durin g exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 100 Behaviour

Underactive 1 - 4, 7 - 8, 10 - 11, 1 - 4, 7 - 11, 14 - 18, 21 -25, 14 - 18, 21 - 25, 28 - 32, 35 - 39, 28 - 32, 35 - 39, 42 - 4 6, 49 - 53, 42 - 46, 49 - 53, 56 - 60, 63 - 67, 56 - 59, 63 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Unresponsive 1, 10 - 11, 14 - 15, 1, 10 - 11, 14 - 18, 17 - 18, 21, 23 - 25, 21, 23 - 25, 29 - 31, 35 - 36, 29 - 31, 35 - 36, 39, 49, 51 - 52, 39, 43, 49, 56 - 57, 59 - 60, 51 - 52, 56 - 57, 64 - 67, 88 59, 64 - 67,

72, 77, 88 Br eathing Shallow 1 - 4, 7 - 8, 24 1 - 4, 7 - 9, 15, 17, 22 - 24 Slow 22, 28, 32, 25, 28 - 29, 35, 38, 42, 32, 35 - 38, 44, 46, 49 - 53, 42 - 44, 46, 49 - 53, 58, 70, 88 58, 70, 88322Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposure Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 100 Coat

Piloerection 1 - 4, 7 - 9, 14 - 18, 1 - 4, 7 - 9, 11, 21, 23 - 25, 14 - 18, 21 - 25, 29 - 32, 37, 39, 29 - 32, 37, 39, 45, 49, 56 - 57, 45, 49, 56 - 57, 59 - 60, 63 - 67, 59, 63 - 67, 71 - 74, 77 - 81, 71 - 74, 77 - 81, 84 - 87, 91 84 - 87, 91 Eyelids (Left) Closed 1 1 Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Eyelids (Right) Closed 1 1323Huntingdon Life SciencesWAG0014

APPENDIX 2 - continued Request ID: 289355 Signs associated with dosing - individual observations Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Days Group /Sex Animal Number Sign Approximately 2 hours during exposur e Approximately

4 hours during exposure 1 to 2 hours after

completion of dosing all groups As late as

possible in the working day 4F 100 Eyelids (Right)

Partially Closed 2 - 4, 7 - 8, 14, 2 - 4, 7, 9, 14 - 18, 22, 24 - 25, 21 - 25, 28 - 32, 28 - 32, 35, 38 - 39, 35 - 39, 42 -44, 42, 44, 46, 46, 49 - 53, 49 - 53, 56, 58 - 59, 56, 58 - 59, 63, 65 - 67, 63, 65 - 67, 70 - 74, 77 - 81, 70 - 74, 77 - 81, 84 - 88, 91 84 - 88, 91 Posture Hun ched 1324Huntingdon Life SciencesWAG0014

APPENDIX 3 Sensory reactivity

observations and grip strength - individual findings during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 5 05 2876 Group/sex: 1M Animal number: 61 62 63 64 65 66 67 68 69 70 81 82 83 84 85 86 87 88 89 90 Parameter (Grade range) Approach response (1 - 3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Touch response (1 - 3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 1 2 Auditory startle reflex (1 - 4) 3 3 3 3 2 2 3 3 3 3 3 3 3 3 3 3 3 2 3 2 Tail pinch response (1 - 4) 2 3 3 3 2 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Forelimb grip strength (kg) Trial 1 1.06 0.96 1.33 0.92 1.01 1.09 1.02 0.98 1.20 0.99 1.01 0.87 0.91 0.82 0.89 1.15 1.14 1.27 1.09 0.91 Trial 2 1.12 0.88 1.04 0.92 0.92 1.08 0.88 0.96 1.01 1.05 0.82 0.99 0.94 0.84 0.80 1.32 1.04 0.96 1.09 0.99 Trial 3 1.11 1.01 1.02 0.95 0.90 1.09 0.72 1.00 1.06 0.97 1.03 0.94 1.02 0.8 3 0.96 1.34 0.94 0.90 0.99 1.00 Mean 1.10 0.95 1.13 0.93 0.94 1.09 0.87 0.98 1.09 1.00 0.95 0.93 0.96 0.83 0.88 1.27 1.04 1.04 1.06 0.97 Hindlimb grip strength (kg) Trial 1 0.54 0.70 0.65 0.70 0.78 0.61 0.55 0.56 0.59 0.57 0.65 0.53 0.67 0.68 0.36 0.7 8 0.52 0.54 0.53 0.56 Trial 2 0.65 0.63 0.74 0.54 0.74 0.46 0.71 0.71 0.65 0.57 0.59 0.62 0.62 0.55 0.54 0.76 0.54 0.54 0.65 0.63 Trial 3 0.63 0.62 0.64 0.74 0.67 0.56 0.56 0.56 0.60 0.52 0.58 0.56 0.64 0.55 0.57 0.82 0.42 0.43 0.66 0.54 Mean 0.61 0.65 0.68 0.66 0.73 0.54 0.61 0.61 0.61 0.55 0.61 0.57 0.64 0.59 0.49 0.79 0.49 0.50 0.61 0.58 Additional observations - - - - - - - - - - - - - - - - - - - -325Huntingdon Life SciencesWAG0014

APPENDIX 3 - continued Sensory reacti vity observations and grip strength - individual findings during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/sex: 2M 3M Animal number: 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 Parameter (Grade range) Approach response (1 - 3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Touch response (1 - 3) 2 2 2 2 2 2 2 2 1 2 2 2 2 2 2 2 2 2 1 2 Auditory startle reflex (1 - 4) 2 3 3 3 3 2 3 3 2 3 3 3 3 3 3 2 3 3 2 3 Tail pinch response (1 - 4) 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Forelimb grip strength (kg) Trial 1 1.10 0.86 1.21 1.13 1.13 1.01 1.09 0.87 1.00 0.94 0.72 1.03 0.87 0.94 0.92 0.94 0.84 1.08 1.03 0.99 Trial 2 0.86 0.93 1.03 1.25 0.96 1.18 0.98 0.97 0.85 0.82 0.80 0.88 0.91 0.94 1.00 0.86 0.98 0.73 1.07 1.12 Trial 3 0.98 0.90 0.85 1.18 1.06 1.15 1.22 1.03 0.98 0.86 0. 82 0.91 0.93 0.84 1.08 0.96 0.95 0.82 1.08 1.13 Mean 0.98 0.90 1.03 1.19 1.05 1.11 1.10 0.96 0.94 0.87 0.78 0.94 0.90 0.91 1.00 0.92 0.92 0.88 1.06 1.08 Hindlimb grip strength (kg) Trial 1 0.76 0.49 0.65 0.56 0.63 0.54 0.64 0.69 0.54 0.63 0.51 0.28 0. 53 0.62 0.43 0.59 0.56 0.63 0.55 0.36 Trial 2 0.68 0.38 0.58 0.67 0.62 0.68 0.54 0.72 0.47 0.53 0.46 0.33 0.57 0.65 0.68 0.58 0.70 0.57 0.58 0.57 Trial 3 0.60 0.36 0.43 0.59 0.60 0.62 0.58 0.70 0.59 0.63 0.40 0.40 0.57 0.69 0.68 0.56 0.53 0.59 0.31 0 .59 Mean 0.68 0.41 0.55 0.61 0.62 0.61 0.59 0.70 0.53 0.60 0.46 0.34 0.56 0.65 0.60 0.58 0.60 0.60 0.48 0.51 Additional observations - - - - - - - - - - - - - - - - - - - -326Huntingdon Life SciencesWAG0014

APPENDIX 3 - continued Sensory reactivity observations and grip strength - individual findings during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/sex: 4M Animal number: 11 12 13 14 15 16 17 18 19 20 71 72 73 74 75 76 77 78 79 80 Parameter (Grade range) Approach response (1 - 3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Touch response (1 - 3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Auditory startle reflex (1 - 4) 3 3 3 3 3 3 2 3 3 2 3 2 3 3 3 3 3 3 3 2 Tail pinch response (1 - 4) 3 3 4 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 4 Forelimb grip strength (kg) Trial 1 0.73 0.85 0.70 0.82 1.07 0.7 1 0.87 0.79 0.70 0.89 0.84 1.04 0.70 0.72 0.84 0.95 0.88 1.00 0.88 1.01 Trial 2 0.68 0.80 0.70 0.68 0.96 0.63 0.96 0.82 0.75 1.12 0.73 0.99 0.76 0.89 0.89 0.94 1.00 0.96 1.00 0.85 Trial 3 0.65 0.91 0.80 0.88 0.90 0.67 0.88 0.81 0.73 0.89 0.76 0.84 0 .79 0.80 0.79 1.00 0.77 1.00 0.90 0.88 Mean 0.69 0.85 0.73 0.79 0.98 0.67 0.90 0.81 0.73 0.97 0.78 0.96 0.75 0.80 0.84 0.96 0.88 0.99 0.93 0.91 Hindlimb grip strength (kg) Trial 1 0.41 0.60 0.48 0.54 0.67 0.43 0.54 0.53 0.35 0.57 0.44 0.63 0.47 0.50 0 .46 0.38 0.48 0.48 0.48 0.49 Trial 2 0.42 0.56 0.47 0.55 0.65 0.35 0.58 0.50 0.37 0.44 0.51 0.56 0.38 0.48 0.37 0.46 0.45 0.49 0.44 0.44 Trial 3 0.44 0.52 0.49 0.44 0.63 0.32 0.54 0.55 0.39 0.51 0.40 0.56 0.44 0.48 0.52 0.51 0.41 0.56 0.45 0.54 Mean 0.42 0.56 0.48 0.51 0.65 0.37 0.55 0.53 0.37 0.51 0.45 0.58 0.43 0.49 0.45 0.45 0.45 0.51 0.46 0.49 Additional observations - - - a - - - - - - - - - - - - - - - -

a Loose faeces327Huntingdon Life SciencesWAG0014

APPENDIX 3 - continue d Sensory reactivity observations and grip strength - individual findings during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/sex: 1F Animal number: 21 22 23 24 25 26 28 29 30 41 42 43 44 45 46 47 48 49 50 Parameter (Grade range) Approach response (1 - 3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Touch response (1 - 3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Auditory startle reflex (1 - 4) 3 2 3 3 3 3 3 3 3 2 3 3 3 3 3 3 2 3 3 Tail pinch response (1 - 4) 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Forelimb grip strength (kg) Trial 1 0.93 1.02 0.92 1.08 0.92 1.04 0.79 0. 96 0.83 0.69 1.05 0.81 0.84 0.84 0.92 0.86 0.70 0.75 0.82 Trial 2 0.88 0.96 0.82 0.96 0.92 0.92 1.02 0.87 0.79 0.76 0.95 0.90 0.97 0.96 1.01 0.90 0.78 0.82 0.92 Trial 3 0.89 0.78 0.87 1.02 0.82 0.87 0.88 0.84 0.71 0.72 0.82 0.88 0.71 0.86 0.94 0.86 0.85 0.92 0.82 Mean 0.90 0.92 0.87 1.02 0.89 0.94 0.90 0.89 0.78 0.72 0.94 0.86 0.84 0.89 0.96 0.87 0.78 0.83 0.85 Hindlimb grip strength (kg) Trial 1 0.50 0.49 0.46 0.47 0.30 0.46 0.47 0.47 0.47 0.44 0.46 0.39 0.53 0.50 0.43 0.41 0.49 0.38 0.38 Tri al 2 0.54 0.43 0.57 0.45 0.36 0.50 0.52 0.39 0.42 0.44 0.46 0.49 0.50 0.40 0.57 0.42 0.45 0.42 0.36 Trial 3 0.59 0.35 0.38 0.43 0.33 0.36 0.46 0.40 0.43 0.33 0.44 0.42 0.38 0.47 0.60 0.38 0.49 0.46 0.40 Mean 0.54 0.42 0.47 0.45 0.33 0.44 0.48 0.42 0. 44 0.40 0.45 0.43 0.47 0.46 0.53 0.40 0.48 0.42 0.38 Additional observations - - - - - - - - - - - - - - - - - - -328Huntingdon Life SciencesWAG0014

APPENDIX 3 - continued Sensory reactivity observations and grip strength - individual findings during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/sex: 2F 3F Animal number: 51 52 53 54 55 56 57 58 59 60 1 2 3 4 5 6 7 8 9 10 Parameter (Grade range) Approach response (1 - 3) 2 2 2 2 2 2 2 1 2 2 2 2 2 2 2 2 2 2 2 2 Touch response (1 - 3) 2 2 2 2 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Auditory startle r eflex (1 - 4) 3 3 2 3 3 2 3 3 3 3 3 3 2 3 3 3 3 3 3 3 Tail pinch response (1 - 4) 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Forelimb grip strength (kg) Trial 1 0.81 0.81 0.79 0.72 0.74 0.74 0.88 0.96 0.94 0.83 0.98 1.08 0.76 1.19 0.82 0.87 0.69 0.81 0.86 0.79 Trial 2 0.79 0.89 0.73 0.76 0.82 0.90 0.82 0.91 0.94 0.77 0.92 0.72 0.74 1.11 0.82 0.70 0.70 0.79 0.84 0.92 Trial 3 0.80 0.84 0.82 0.77 0.77 0.74 0.82 0.97 0.81 0.74 1.01 0.70 0.73 0.92 0.94 0.78 0.75 0.66 0.84 0.83 Mean 0.80 0.85 0.78 0.75 0. 78 0.79 0.84 0.95 0.90 0.78 0.97 0.83 0.74 1.07 0.86 0.78 0.71 0.75 0.85 0.85 Hindlimb grip strength (kg) Trial 1 0.48 0.41 0.53 0.44 0.50 0.45 0.42 0.54 0.57 0.55 0.50 0.47 0.33 0.50 0.59 0.50 0.33 0.43 0.50 0.40 Trial 2 0.47 0.42 0.51 0.53 0.49 0.46 0.48 0.49 0.56 0.52 0.52 0.46 0.33 0.48 0.44 0.39 0.38 0.46 0.52 0.34 Trial 3 0.47 0.34 0.50 0.44 0.47 0.49 0.45 0.51 0.51 0.41 0.48 0.46 0.33 0.35 0.49 0.47 0.36 0.40 0.44 0.36 Mean 0.47 0.39 0.51 0.47 0.49 0.47 0.45 0.51 0.55 0.49 0.50 0.46 0.33 0.44 0.51 0.45 0.36 0.43 0.49 0.37 Additional observations - - - - - - - - - - - - - - - - - - - -329Huntingdon Life SciencesWAG0014

APPENDIX 3 - continued Sensory reactivity observations and grip strength - individual findings durin g Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/sex: 4F Animal number: 31 32 33 34 3 5 36 37 38 39 40 91 92 93 94 95 96 97 98 99 100 Parameter (Grade range) Approach response (1 - 3) 1 2 2 2 2 2 2 2 1 2 2 2 2 2 2 2 2 2 2 2 Touch response (1 - 3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 1 2 Auditory startle reflex (1 - 4) 2 3 3 3 2 3 3 3 3 3 3 3 3 3 3 3 3 3 2 3 Tail pinch response (1 - 4) 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Forelimb grip strength (kg) Trial 1 0.76 0.48 0.82 0.84 0.85 0.74 0.68 0.62 0.67 0.66 0.77 0.50 0.58 0.51 0.69 0.75 0.62 0.68 0.76 0.78 Tr ial 2 0.75 0.53 0.75 0.77 0.72 0.78 0.64 0.84 0.66 0.66 0.70 0.55 0.60 0.50 0.72 0.70 0.50 0.79 0.80 0.70 Trial 3 0.60 0.42 0.88 0.65 0.75 0.74 0.68 0.76 0.82 0.68 0.91 0.60 0.54 0.51 0.73 0.64 0.52 0.64 0.78 0.81 Mean 0.70 0.48 0.82 0.75 0.77 0.75 0 .67 0.74 0.72 0.67 0.79 0.55 0.57 0.51 0.71 0.70 0.55 0.70 0.78 0.76 Hindlimb grip strength (kg) Trial 1 0.41 0.24 0.41 0.41 0.44 0.36 0.37 0.35 0.36 0.25 0.37 0.27 0.38 0.30 0.33 0.32 0.42 0.33 0.50 0.37 Trial 2 0.33 0.29 0.43 0.48 0.40 0.42 0.31 0.4 6 0.43 0.21 0.42 0.26 0.30 0.24 0.32 0.34 0.39 0.34 0.46 0.41 Trial 3 0.35 0.24 0.45 0.48 0.41 0.36 0.32 0.42 0.33 0.22 0.34 0.32 0.33 0.28 0.39 0.39 0.28 0.34 0.50 0.46 Mean 0.36 0.26 0.43 0.46 0.42 0.38 0.33 0.41 0.37 0.23 0.38 0.28 0.34 0.27 0.35 0.35 0.36 0.34 0.49 0.41 Additional observations - - - - - - - - - - - - - - - - - - - -330Huntingdon Life SciencesWAG0014

APPENDIX 3 - continued Sensory reactivity observations and grip strength - individual findings during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/sex: 1M 4M Animal number: 81 82 83 84 85 86 87 88 89 90 71 72 73 74 75 76 77 78 79 80 Parameter Forelimb grip strength (kg) Trial 1 1.10 1.08 1.20 1.26 1.08 1.26 0.99 1.20 1.28 1.19 1.02 1.00 1.06 0.89 1.22 0.90 1.10 1.37 1.04 1.06 Trial 2 1.16 1.10 1.10 1.09 1.28 1.40 1.17 0.97 1.14 1.10 0.84 0.94 1.17 1.28 1.01 1.20 1.02 1.20 0.92 1.14 Trial 3 1.13 0.99 0.86 1.09 1.08 1.19 1.10 1.00 1.09 0.96 1.06 1.14 1.21 0.93 1.10 0.85 1.21 1.34 0.81 0.97 Mean 1.13 1.06 1.05 1.15 1.15 1.28 1.09 1.06 1.17 1.08 0.97 1.03 1.15 1.03 1.11 0.98 1.11 1.30 0.92 1.06 Hindlimb grip strength (kg) Trial 1 0.68 0.66 0.60 0.79 0.69 0.70 0.50 0.68 0.80 0.68 0.64 0.73 0.57 0.51 0.62 0.64 0.53 0.60 0.42 0.50 Trial 2 0.79 0.48 0.78 0.69 0.60 0.73 0.50 0.66 0.85 0.70 0.58 0.60 0.63 0.49 0.51 0. 65 0.60 0.60 0.42 0.59 Trial 3 0.63 0.43 0.66 0.70 0.69 0.76 0.46 0.67 0.77 0.71 0.54 0.61 0.68 0.51 0.54 0.58 0.58 0.58 0.46 0.56 Mean 0.70 0.52 0.68 0.73 0.66 0.73 0.49 0.67 0.81 0.70 0.59 0.65 0.63 0.50 0.56 0.62 0.57 0.59 0.43 0.55 Additional ob servations - - - - - - - - - - - - - - - - - - - -331Huntingdon Life SciencesWAG0014

APPENDIX 3 - continued Sensory reactivity observations and grip strength - individual findings during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group/sex: 1F 4F Animal number: 41 42 43 44 45 46 47 48 49 50 91 92 93 94 95 96 97 98 99 10 0 Parameter Forelimb grip strength (kg) Trial 1 0.88 0.88 0.76 0.82 0.89 0.99 1.03 0.84 0.94 1.09 0.98 0.83 0.89 0.86 1.02 0.99 0.74 0.80 1.02 0.87 Trial 2 0.78 0.82 0.89 0.78 0.90 0.88 0.84 0.81 0.87 0.84 0.85 0.85 0.70 0.79 0. 84 0.76 0.73 0.75 1.01 1.00 Trial 3 0.90 0.66 0.84 0.99 0.83 0.90 0.84 0.76 0.97 0.84 1.01 0.88 0.73 0.84 0.97 0.79 0.80 0.81 0.78 0.83 Mean 0.85 0.79 0.83 0.86 0.87 0.92 0.90 0.80 0.93 0.92 0.95 0.85 0.77 0.83 0.94 0.85 0.76 0.79 0.94 0.90 Hindlimb grip strength (kg) Trial 1 0.60 0.44 0.56 0.54 0.52 0.64 0.54 0.54 0.54 0.43 0.52 0.43 0.38 0.42 0.54 0.50 0.49 0.46 0.65 0.54 Trial 2 0.53 0.59 0.55 0.50 0.52 0.62 0.55 0.56 0.46 0.40 0.47 0.40 0.48 0.48 0.42 0.44 0.45 0.48 0.47 0.52 Trial 3 0.49 0 .48 0.59 0.47 0.46 0.50 0.56 0.50 0.47 0.49 0.46 0.31 0.51 0.53 0.44 0.39 0.50 0.56 0.49 0.53 Mean 0.54 0.50 0.57 0.50 0.50 0.59 0.55 0.53 0.49 0.44 0.48 0.38 0.46 0.48 0.47 0.44 0.48 0.50 0.54 0.53 Additional observations - - - - - - - - - - - - - - - - - - - -332Huntingdon Life SciencesWAG0014

APPENDIX 4 Motor activity - individual scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 1M 61 High 111 120 61 36 50 19 23 42 8 31 501

62 163 108 65 48 32 6 2 0 14 4 442 63 136 108 72 47 55 60 20 36 36 26 596 64 148 113 83 41 25 49 24 14 2 0 499 65 110 132 54 62 19 37 22 0 0 43 479 66 140 76 28 8 9 3 0 0 0 0 264 67 123 105 88 83 66 41 65 84 44 20 719 68 148 107 44 74 22 12 23 5 22 0 457 6 9 106 96 76 54 1 0 14 40 26 0 413 70 144 144 65 28 45 35 0 0 0 0 461 81 142 91 48 34 32 18 0 18 50 36 469 82 117 88 84 41 23 23 22 53 4 42 497 83 125 102 69 74 20 42 77 66 66 47 688 84 113 63 63 19 27 15 45 48 27 42 462 85 125 80 68 13 4 5 42 32 62 18 18 503 86 140 56 63 49 30 27 34 36 26 22 483 87 156 130 52 80 46 30 39 34 41 22 630 88 167 115 62 38 32 53 7 49 0 48 571 89 147 118 97 37 21 64 13 69 69 57 692 90 136 125 76 32 37 53 16 34 14 19 542333Huntingdon Life SciencesWAG0014

APPENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 1M 61 Low 221 170 138 83 87 78 84 106 37 97 1101

62 319 286 228 193 104 98 29 0 87 41 1385 63 314 182 201 86 32 115 67 93 42 85 1217 64 210 178 141 161 112 100 72 64 47 5 1090 65 207 112 107 59 85 70 101 23 2 79 845 66 237 158 161 33 96 19 17 0 16 9 746 67 247 275 218 152 98 91 62 84 60 81 1368 68 241 153 112 105 98 67 44 108 38 11 977 69 204 151 95 98 23 19 77 102 85 3 857 70 290 219 166 88 110 54 9 0 2 0 938 81 252 178 142 85 66 66 4 45 118 137 1093 82 143 127 85 77 54 45 78 54 31 40 734 83 237 206 101 86 120 106 94 59 125 76 1210 84 218 172 125 84 71 55 41 66 68 84 984 85 262 256 193 125 130 94 70 105 52 70 1357 86 325 195 143 106 132 88 77 111 87 60 1324 87 271 197 157 106 102 84 105 83 86 48 1239 88 210 145 100 100 53 80 38 42 0 38 806 89 277 194 231 91 95 135 39 86 35 66 1249 90 338 222 165 168 128 111 39 103 68 54 1396334Huntingdon Life SciencesWAG0014

APPENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 2M 101 High 150 94 87 57 35 36 31 6 28 17 541

102 134 73 55 37 50 19 19 13 35 17 452 103 128 85 48 41 24 46 17 6 16 13 424 104 145 120 120 63 39 50 26 24 43 26 656 105 110 90 70 52 55 39 5 29 34 0 484 106 129 70 29 6 1 23 16 17 19 0 310 107 139 100 78 80 84 35 66 26 38 26 672 108 174 102 57 50 76 51 18 36 0 4 568 109 103 86 77 43 7 7 11 2 26 24 386 110 182 154 124 65 67 43 57 16 38 67 813 101 Low 198 149 138 135 147 113 118 56 138 94 1286 102 287 177 199 170 133 124 79 69 91 62 1391 103 235 173 126 134 41 105 99 23 72 51 1059 104 263 133 122 104 112 75 81 19 1 14 71 1094 105 232 152 116 127 90 83 63 91 69 142 1165 106 216 171 118 44 13 91 16 47 52 15 783 107 341 305 282 187 177 155 151 125 152 80 1955 108 326 207 167 122 111 118 43 71 30 17 1212 109 200 153 152 91 8 32 82 28 83 88 917 110 269 2 07 176 150 71 69 68 79 86 81 1256335Huntingdon Life SciencesWAG0014

APPENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 3M 111 High 121 83 51 25 26 16 1 19 0 0 342

112 144 82 77 51 51 61 62 28 45 52 653 113 102 101 51 42 20 16 29 21 26 0 408 114 108 49 17 18 0 0 0 21 6 0 219 115 130 70 29 28 55 9 2 4 0 0 327 116 140 102 68 63 16 12 16 19 26 0 462 117 86 50 47 15 24 0 0 8 25 0 255 118 113 86 69 48 43 18 25 2 8 0 412 119 132 94 69 46 31 11 15 13 0 0 411 120 106 92 96 46 46 19 16 29 5 1 456 111 Low 224 125 92 69 84 98 32 34 0 0 758 112 377 230 136 96 126 102 74 135 62 74 1412 113 186 192 122 143 128 70 111 79 106 5 1142 114 172 151 96 79 0 0 17 71 27 0 613 115 273 215 118 204 116 31 27 2 5 7 998 116 196 154 172 105 64 49 70 47 28 0 885 117 206 137 106 48 65 0 6 29 90 0 687 118 207 160 147 146 98 71 73 26 54 12 994 119 261 191 141 162 113 80 54 46 0 24 1072 120 189 212 203 117 9 8 108 266 91 41 56 1381336Huntingdon Life SciencesWAG0014

APPENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3, 3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 4M 11 High 75 14 0 0 20 6 0 0 0 29 144

12 152 74 44 30 65 9 32 14 0 0 420 1 3 58 60 25 25 0 0 0 6 36 30 240 14 92 34 12 7 19 0 12 0 0 0 176 15 86 59 28 45 4 0 0 0 0 15 237 16 79 52 53 37 33 26 18 0 0 2 300 17 123 61 17 17 11 24 34 6 0 0 293 18 115 66 36 60 43 51 25 41 57 22 516 19 150 60 33 0 0 25 2 0 0 5 275 20 85 58 21 3 34 4 0 5 0 0 210 71 125 75 42 47 38 19 0 3 0 0 349 72 143 55 26 5 0 0 0 0 0 0 229 73 114 65 63 60 29 0 0 13 1 0 345 74 139 54 45 16 1 8 7 25 4 6 305 75 98 76 67 41 24 25 0 23 6 0 360 76 97 71 67 40 64 43 32 76 22 28 540 7 7 145 70 58 21 4 0 0 29 35 2 364 78 112 57 32 0 7 0 0 0 0 0 208 79 165 128 80 97 83 45 27 10 4 28 667 80 136 71 67 21 12 2 28 32 0 10 379337Huntingdon Life SciencesWAG0014

APPENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 4M 11 Low 159 86 0 1 73 40 6 0 26 110 501

12 225 111 120 111 83 77 78 16 17 8 846 13 156 128 84 58 1 8 6 41 76 75 633 14 224 106 70 24 78 10 74 2 1 14 603 15 238 109 66 52 24 3 0 1 1 61 555 16 235 147 113 101 88 32 7 0 0 9 732 17 193 102 75 37 46 30 52 18 0 2 555 18 162 114 68 61 53 59 48 33 49 51 698 19 197 122 84 63 2 90 7 0 0 16 581 20 176 131 81 51 73 19 0 25 2 0 558 71 251 119 123 91 75 64 0 12 0 4 739 72 200 133 79 68 0 0 0 2 3 0 0 503 73 179 170 127 117 84 10 0 53 20 20 780 74 223 170 94 77 2 16 21 39 12 5 659 75 206 185 114 106 65 41 1 48 43 0 809 76 234 186 160 104 78 85 43 54 66 60 1070 77 216 148 120 51 41 3 3 58 61 15 716 78 228 98 92 18 12 0 0 14 0 0 46 2 79 252 186 211 163 215 141 102 44 19 89 1422 80 239 171 105 62 56 22 111 93 49 36 944338Huntingdon Life SciencesWAG0014

APPENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 1F 21 High 177 139 101 80 28 34 0 0 64 0 623

22 180 127 75 73 56 51 34 29 45 67 737 23 156 85 47 28 20 7 18 31 24 1 417 24 123 109 62 65 38 66 5 63 34 50 615 25 155 129 93 71 89 102 200 20 144 0 1003 26 146 51 31 38 27 28 30 47 18 7 423 28 131 79 5 4 47 37 33 38 41 9 24 493 29 155 122 54 70 59 16 79 38 3 0 596 30 151 130 94 72 42 90 21 10 31 103 744 41 193 82 62 66 45 31 68 0 1 0 548 42 144 69 59 35 32 42 23 9 31 0 444 43 177 117 75 57 33 35 12 9 23 22 560 44 174 84 76 72 102 57 59 71 68 40 803 45 160 110 93 43 48 10 13 2 7 29 515 46 124 55 40 32 32 26 35 29 19 34 426 47 174 136 100 67 34 60 28 40 60 34 733 48 223 101 60 72 72 126 71 58 34 37 854 49 176 117 91 57 64 71 123 80 66 20 865 50 130 48 51 30 25 30 55 66 12 46 493339Huntingdon Life SciencesWAG0014

APPENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 1F 21 Low 332 220 228 132 57 139 40 19 50 131 1348

22 243 181 187 121 103 99 58 55 88 115 12 50 23 271 164 167 127 45 35 53 90 113 26 1091 24 208 135 117 68 41 100 21 43 67 77 877 25 194 128 123 75 100 104 44 15 52 7 842 26 309 163 117 137 90 104 152 97 79 31 1279 28 279 279 203 181 149 174 106 108 81 163 1723 29 236 128 142 89 1 03 31 92 90 26 12 949 30 154 106 90 79 33 64 93 20 36 71 746 41 313 174 152 100 89 35 82 8 1 18 972 42 192 114 112 124 76 89 33 47 51 6 844 43 352 231 121 156 159 130 37 73 87 101 1447 44 319 194 146 121 91 127 70 119 91 101 1379 45 285 2 34 190 121 90 43 43 47 64 40 1157 46 238 143 132 75 111 52 113 76 61 142 1143 47 392 201 182 191 172 172 118 124 113 125 1790 48 376 209 127 111 151 216 202 164 133 130 1819 49 329 257 225 142 165 88 158 114 146 44 1668 50 225 191 100 63 110 46 102 95 61 73 1066340Huntingdon Life SciencesWAG0014

APPENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3 ,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 2F 51 High 155 54 26 24 4 0 23 35 20 0 341

52 178 133 83 78 45 65 41 44 2 22 6 91 53 128 46 26 0 0 0 48 23 13 2 286 54 156 118 63 57 38 44 48 29 27 27 607 55 155 122 99 106 85 12 39 84 54 6 762 56 157 84 29 75 28 34 31 3 23 0 464 57 138 96 66 87 13 5 5 43 9 7 469 58 304 122 131 64 63 61 20 25 50 10 850 59 156 31 28 38 0 0 4 14 68 25 364 60 106 53 56 45 27 37 24 14 17 0 379 51 Low 277 159 117 63 47 1 53 98 49 9 873 52 284 200 205 125 119 105 134 112 5 17 1306 53 155 103 58 0 0 3 73 28 46 9 475 54 309 252 160 152 114 90 129 126 88 105 15 25 55 223 130 143 89 77 22 40 80 35 38 877 56 293 156 95 117 113 99 94 136 45 18 1166 57 201 143 98 93 61 16 22 76 61 35 806 58 326 188 179 142 151 104 118 105 139 44 1496 59 269 149 103 49 0 34 54 107 80 88 933 60 235 106 126 85 99 114 1 11 43 97 144 1160341Huntingdon Life SciencesWAG0014

APPENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -tr ifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 3F 1 High 153 88 33 41 14 18 1 13 6 0 367

2 167 75 60 81 84 12 1 23 18 27 548 3 112 86 36 46 39 45 0 11 0 10 385 4 192 106 99 36 59 27 28 45 17 8 617 5 128 82 76 42 10 12 0 0 14 29 393 6 121 84 75 41 52 30 20 0 0 0 423 7 127 85 29 36 0 4 3 21 0 0 305 8 183 108 73 23 22 0 0 0 0 0 409 9 163 81 43 21 32 17 0 5 20 36 418 10 171 140 93 51 57 90 46 31 39 49 767 1 Low 294 179 203 157 71 74 16 69 53 0 1116 2 223 151 146 136 140 88 79 57 106 66 1192 3 170 127 47 48 54 21 1 0 0 13 481 4 227 154 144 102 116 51 97 56 90 50 1087 5 197 150 167 77 78 37 1 34 67 102 910 6 323 212 127 113 117 79 82 4 4 70 1131 7 173 145 120 68 30 26 20 60 0 60 702 8 279 200 187 61 68 50 11 0 0 0 856 9 361 275 178 110 116 54 0 28 107 156 1385 10 248 153 138 95 130 106 65 51 48 77 1111342Huntingdon Life SciencesWAG0014

APP ENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 4F 31 High 122 80 70 61 0 0 0 0 0 0 333

32 209 82 64 82 42 0 41 39 14 0 573 33 139 79 51 0 0 0 40 19 14 0 342 34 183 99 89 48 101 23 39 0 0 14 596 35 151 91 51 20 10 0 3 41 0 9 376 36 98 58 20 0 0 0 0 0 0 0 176 37 93 53 14 26 4 8 1 11 44 13 267 38 141 117 72 49 11 0 0 0 0 0 390 39 109 34 0 0 0 0 0 0 6 36 185 40 205 204 153 80 34 27 12 24 28 37 804 91 101 55 44 25 2 12 0 0 11 18 268 92 148 81 0 0 0 56 0 0 0 0 285 93 127 78 39 13 32 4 15 37 43 8 396 94 87 38 70 16 0 0 0 21 15 0 247 95 108 78 53 60 22 1 2 0 25 0 349 96 123 80 100 56 44 17 41 45 23 0 529 97 155 100 93 63 92 44 53 65 36 2 0 721 98 176 140 96 65 50 70 81 44 29 79 830 99 144 71 30 31 0 0 6 37 34 6 359 100 116 103 58 32 40 35 40 20 45 0 489343Huntingdon Life SciencesWAG0014

APPENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 12 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 4F 31 Low 257 152 85 79 0 0 0 0 0 0 573

32 199 126 74 97 38 0 55 56 66 64 775 33 208 160 122 7 0 1 136 64 98 108 904 34 181 100 89 60 70 72 25 1 5 22 625 35 272 144 96 57 115 0 59 74 0 55 872 36 187 112 70 41 0 0 0 0 0 0 410 37 248 154 110 126 49 29 77 129 98 71 1091 38 174 106 79 99 19 0 0 0 10 0 487 39 216 111 7 0 1 4 2 1 39 113 494 40 255 232 187 105 57 87 129 69 106 99 1326 91 192 131 95 139 10 53 6 4 47 101 778 92 199 65 0 0 0 74 0 0 0 0 338 93 160 124 93 53 56 26 40 105 71 60 788 94 154 96 48 28 0 0 2 27 31 0 386 95 144 124 121 98 57 14 37 148 80 26 849 96 225 161 110 108 68 107 61 79 98 0 1017 97 193 101 137 82 127 93 82 106 39 29 989 98 132 101 69 47 40 68 34 33 25 75 624 99 209 161 110 54 7 2 40 83 112 94 872 100 187 135 96 66 57 81 36 7 121 5 791344Huntingdon Life SciencesWAG0014

APPENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 4 of recovery Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 1M 81 High 101 65 40 25 19 6 0 0 0 15 271

82 106 73 30 28 14 0 0 0 0 0 251 83 104 84 38 63 21 28 31 29 13 8 419 84 136 91 87 83 84 45 74 40 52 46 738 85 111 80 30 43 23 6 13 9 0 0 315 86 105 61 46 33 29 6 0 16 5 4 305 87 119 62 73 39 39 20 23 9 21 19 424 88 124 65 52 13 13 15 0 6 0 10 298 89 110 104 78 85 36 18 40 4 13 28 516 90 104 54 70 22 7 1 16 0 0 0 274 81 Low 242 130 134 87 36 17 2 4 6 86 744 82 184 124 66 74 65 8 25 10 0 0 556 83 249 153 163 147 99 95 131 58 100 81 1276 84 1 78 181 126 112 63 65 66 106 59 43 999 85 263 210 132 91 85 10 11 33 1 0 836 86 229 166 140 109 117 18 0 38 32 12 861 87 197 128 114 122 161 21 24 2 48 33 850 88 259 125 103 31 37 69 0 2 0 12 638 89 266 207 149 159 133 85 98 46 50 100 1293 90 259 200 143 110 67 33 92 10 0 7 921345Huntingdon Life SciencesWAG0014

APPENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 4 of recovery Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoroprop ene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 4M 71 High 116 33 24 22 14 4 0 0 0 0 213

72 102 54 34 0 0 1 0 0 0 0 191 73 136 64 49 36 9 38 8 0 0 0 340 74 111 39 38 23 27 43 17 10 40 28 376 75 117 70 19 43 44 15 2 41 2 0 353 76 122 86 65 27 40 5 12 1 0 46 404 77 123 43 38 11 25 2 0 0 6 17 265 78 96 20 25 26 6 1 0 0 0 0 174 79 122 97 69 59 60 4 4 41 34 21 7 554 80 110 31 29 3 24 0 0 5 7 18 227 71 Low 152 78 68 101 74 15 1 5 12 26 532 72 183 127 148 12 26 16 5 10 5 6 538 73 177 134 87 65 56 131 45 4 41 4 744 74 188 86 70 138 61 91 120 37 75 58 924 75 147 121 25 99 5 6 36 22 54 24 0 584 76 225 123 45 46 80 21 42 16 10 55 663 77 213 184 120 42 69 20 0 4 29 122 803 78 175 77 69 39 23 11 0 0 0 0 394 79 314 191 130 111 77 128 72 140 87 9 1259 80 229 70 76 24 83 39 30 91 42 76 760346Huntingdon Life SciencesWAG0014

APPENDIX 4 - continued Motor activity - individual scores (beam breaks) during Week 4 of recovery Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 1F 41 High 79 59 53 47 23 29 62 7 0 0 359

42 118 49 20 39 56 17 23 11 0 0 333 43 148 91 96 119 58 17 23 53 0 5 610 44 151 96 88 63 73 42 59 34 2 0 608 45 131 51 60 54 39 34 22 30 22 16 459 46 121 70 28 34 19 37 58 13 4 3 387 47 148 85 129 56 51 49 40 53 27 2 640 48 141 97 98 84 54 61 17 26 0 0 578 49 149 70 54 27 65 39 61 15 9 0 489 50 73 58 50 32 32 12 15 27 2 5 1 325 41 Low 206 159 163 117 121 125 158 50 9 2 1110 42 246 125 95 145 119 36 48 42 1 0 857 43 226 126 116 102 151 31 61 95 53 2 963 44 240 137 130 146 81 97 100 77 8 9 1025 45 268 143 178 129 141 125 96 68 73 61 1282 46 2 55 155 57 84 48 75 134 46 8 35 897 47 347 212 223 236 146 139 229 143 94 10 1779 48 303 236 202 153 214 126 91 58 0 0 1383 49 303 250 280 184 183 232 155 127 58 1 1773 50 207 145 160 95 96 58 54 189 108 53 1165347Huntingdon Life SciencesWAG0014

APPENDIX 4 - c ontinued Motor activity - individual scores (beam breaks) during Week 4 of recovery Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Beam

level Time (minutes) number 6 12 18 24 30 36 42 48 54 60 Total 4F 91 High 111 72 36 7 29 7 0 9 1 0 272

92 137 63 12 26 0 0 0 0 0 0 238 93 155 94 55 24 34 27 44 32 0 0 465 94 146 82 66 18 76 32 67 36 0 0 523 95 112 80 40 33 28 34 18 0 0 0 345 96 163 119 115 108 63 54 44 29 24 36 755 97 126 58 59 55 54 48 36 56 18 32 542 98 139 73 69 45 38 28 4 88 26 10 520 99 100 62 57 37 34 55 7 18 8 0 378 100 162 107 177 77 50 63 7 47 1 38 729 91 Low 154 110 117 24 62 102 0 26 3 0 598 92 174 96 27 57 0 0 5 0 0 0 359 93 245 163 141 61 110 76 85 65 4 4 954 94 187 89 89 58 68 97 58 70 0 2 718 95 176 108 109 97 66 65 60 1 0 0 682 96 168 135 137 166 145 99 111 65 45 7 0 1141 97 205 127 97 64 101 133 96 76 51 74 1024 98 162 79 71 69 72 49 5 74 68 8 657 99 236 135 119 174 63 168 60 66 60 10 1091 100 309 161 148 113 119 117 20 98 16 79 1180348Huntingdon Life SciencesWAG0014

APPENDIX 5 Request ID: 289239 Bodyweights - indivi dual values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Week Week Week Week Week Week Week Week Week Week Week Week /Sex Number - 1 0 1 2 3 4 5 6 7 8 9 10 1 M 61 185 227 296 339 389 432 473 508 530 563 591 606

62 194 248 308 354 404 450 489 513 513 543 564 578 63 197 240 30 0 367 432 477 504 530 533 554 588 603 64 189 238 296 354 416 455 501 529 553 587 606 629 65 180 223 272 326 370 403 446 468 490 511 538 550 66 181 236 301 366 426 469 531 568 585 625 642 663 67 191 237 284 323 375 415 455 469 494 516 524 548 68 189 246 302 348 394 425 450 466 481 492 516 536 69 187 237 296 345 392 426 466 489 505 534 560 582 70 191 242 297 345 390 430 469 485 500 522 545 564 81 187 232 289 340 387 425 447 477 501 525 549 559 82 188 239 296 352 393 425 463 479 499 538 561 586 83 178 228 294 344 400 446 472 495 514 538 551 574 84 211 258 318 377 421 451 472 483 493 520 536 546 85 175 227 295 350 406 462 501 525 549 587 616 633 86 182 224 282 325 372 407 444 472 500 534 553 566 87 193 231 279 326 365 386 408 434 451 466 485 493 88 177 229 292 360 402 445 4 76 493 520 537 562 565 89 173 234 312 394 456 502 549 585 612 642 659 675 90 197 239 281 313 348 368 388 400 414 429 439 445349Huntingdon Life SciencesWAG0014

APPENDIX 5 - continued Request ID: 289239 Bodyweights - individual values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Week Week Week Week Week Week Week /Sex Number 11 12 13 /R0 R1 R2 R3 R4 1 M 61 617 631 627

62 562 577 578 63 611 623 628 64 645 656 653 65 557 569 576 66 674 688 690 67 552 5 64 576 68 537 533 535 69 578 587 592 70 561 559 552 81 564 579 584 605 622 629 629 82 574 585 579 586 609 620 607 83 567 589 603 609 632 646 649 84 543 567 586 5 96 620 624 624 85 643 656 660 684 703 721 702 86 570 575 590 610 614 633 629 87 509 507 509 525 543 557 555 88 571 578 588 596 607 613 607 89 697 719 730 746 759 763 754 90 443 453 450 459 475 484 466350Huntingdon Life SciencesWAG0014

APPENDIX 5 - continued Request ID: 289239 Bodyweights - individual values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Expo sure level (ppm) : 0 199 505 2876 Group Animal Week Week Week Week Week Week Week Week Week Week Week Week /Sex Number - 1 0 1 2 3 4 5 6 7 8 9 10 2 M 101 190 243 290 341 383 426 474 496 5 11 528 546 561

102 180 223 271 321 355 390 419 433 440 450 465 462 103 197 247 299 356 405 443 481 501 516 538 547 558 104 186 231 283 322 369 395 425 438 457 479 494 510 105 186 233 283 352 400 427 461 482 492 511 518 522 106 178 235 291 336 387 412 444 461 479 497 503 520 107 193 249 292 341 381 416 438 445 457 466 483 490 108 204 263 319 374 423 456 488 498 499 519 525 535 109 183 232 273 313 346 372 394 409 414 419 427 438 110 180 230 275 321 362 388 424 437 461 477 495 506 3 M 111 187 241 296 338 382 425 461 495 500 525 541 565

112 196 240 258 292 328 364 386 402 412 427 444 448 113 185 230 271 303 350 397 429 444 475 487 509 525 114 191 233 259 293 337 367 403 416 442 442 448 467 115 184 242 279 317 354 392 419 423 435 444 468 469 116 179 232 264 291 333 368 396 410 430 440 450 452 117 175 222 258 296 331 385 385 399 403 416 422 430 118 187 240 280 328 359 379 403 418 423 438 453 461 119 175 225 266 315 352 392 422 442 458 475 488 501 120 199 262 301 361 426 461 505 534 546 556 566 569351Huntingdon Life SciencesWAG0014

APPENDIX 5 - continued Request ID: 289239 Bodyweights - individual values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3, 3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Week Week Week /Sex Number 11 12 13 2 M 101 567 576 572

102 461 468 472 103 565 580 574 104 520 530 516 10 5 516 522 520 106 524 539 540 107 492 499 501 108 537 544 540 109 442 449 449 110 499 521 508 3 M 111 568 576 578

112 458 465 455 113 528 542 533 114 479 490 492 115 472 474 472 116 454 467 464 117 432 442 433 118 464 465 460 119 510 517 497 120 570 578 584352Huntingdon Life SciencesWAG0014

APPENDIX 5 - continued Request ID: 289239 Bodyweights - individual values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Week Week Week Week Week Week Week Week Week Week Week Week /Sex Number - 1 0 1 2 3 4 5 6 7 8 9 10 4 M 11 194 243 259 293 325 353 380 400 408 423 425 433

12 190 235 244 307 360 395 415 426 437 440 441 450 13 192 244 280 326 368 406 436 448 446 448 456 457 14 199 251 264 308 345 375 397 416 433 446 450 465 15 185 229 254 303 342 372 398 411 420 433 447 452 16 186 236 247 292 324 359 378 387 393 397 393 386 17 189 231 256 289 318 349 377 376 388 395 411 417 18 201 2 45 267 306 342 365 388 402 417 421 431 433 19 188 224 253 287 305 331 341 354 374 365 372 371 20 179 216 245 293 325 358 390 399 411 421 432 439 71 181 226 254 292 321 358 381 398 406 417 427 433 72 182 232 263 310 346 394 432 450 465 472 474 486 73 188 232 260 288 309 343 362 367 371 382 382 385 74 181 224 253 295 329 359 387 407 411 421 428 433 75 195 258 290 337 368 406 443 454 465 466 465 470 76 176 233 251 306 341 368 404 438 454 462 467 476 77 195 243 273 307 342 377 393 393 400 404 402 406 78 186 237 242 281 313 347 374 385 396 394 398 402 79 178 217 239 261 284 305 319 32 6 323 323 330 338 80 187 227 254 280 297 313 328 338 348 347 349 362353Huntingdon Life SciencesWAG0014

APPENDIX 5 - continued Request ID: 289239 Bodyweights - individual values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Week Week Week Week Week Week Week /Sex Number 11 12 13 /R0 R1 R2 R3 R4 4 M 11 431 400 397

12 457 462 434 13 460 464 450 14 465 469 464 15 461 463 454 16 394 385 366 17 420 433 425 18 437 444 434 19 369 380 377 20 446 458 427 71 393 416 410 446 470 489 487 72 486 483 488 512 538 559 560 73 380 391 386 401 420 436 434 74 442 445 447 468 491 504 495 75 470 480 476 505 517 534 549 76 468 4 72 470 487 504 527 533 77 406 412 406 441 459 467 469 78 412 414 414 439 457 475 479 79 337 343 348 375 389 398 409 80 361 364 368 381 399 416 419354Huntingdon Life SciencesWAG0014

APPENDIX 5 - continued Request ID: 289239 Bodyweights - individual values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Week Week Week Week Week Week Week Week Week Week Week Week /Sex Number - 1 0 1 2 3 4 5 6 7 8 9 10 1 F 21 168 186 216 230 258 268 282 289 289 304 310 318

22 150 169 187 216 229 240 251 253 258 264 270 276 23 162 179 213 225 234 241 253 263 270 267 273 281 24 164 194 213 235 245 265 286 285 280 298 308 311 25 162 179 207 213 240 244 258 261 262 266 280 281 26 182 206 234 255 272 283 301 30 9 305 320 328 329 27 176 197 226 228 251 271 280 289 305 28 178 202 223 250 276 295 294 301 309 324 325 332 29 163 188 210 224 242 252 256 270 274 277 288 293 30 157 169 207 225 233 252 262 263 284 288 298 299 41 151 177 205 223 249 245 264 268 276 279 286 290 42 187 209 233 256 278 279 307 309 302 323 319 325 43 167 193 217 225 256 257 263 282 295 294 293 306 44 179 217 249 258 28 6 302 303 313 329 337 329 348 45 158 183 199 218 228 243 254 251 273 281 282 283 46 175 198 221 229 266 273 292 295 296 305 309 315 47 180 191 222 241 258 264 282 296 300 311 311 321 48 161 179 198 213 233 249 262 269 261 265 278 289 49 172 187 204 216 234 247 263 280 277 276 288 292 50 146 184 192 198 225 242 246 247 252 267 268 266355Huntingdon Life SciencesWAG0014

APPENDIX 5 - continued Request ID: 28 9239 Bodyweights - individual values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Week Week Week Week We ek Week Week /Sex Number 11 12 13 /R0 R1 R2 R3 R4 1 F 21 312 325 316

22 275 273 275 23 279 272 281 24 308 319 320 25 278 273 280 26 319 323 326 27 28 332 331 333 29 299 290 293 30 309 313 308 41 290 289 292 303 304 304 306 42 315 323 327 325 323 322 330 43 309 304 298 306 313 310 298 44 353 342 332 349 369 363 349 45 285 287 281 285 296 294 293 46 318 314 319 324 332 333 324 47 329 319 321 334 334 337 336 48 290 286 290 300 295 295 306 49 291 287 296 304 301 297 300 50 266 273 273 272 275 283 279356Huntingdon Life SciencesWAG0014

APPENDIX 5 - continued Request ID: 289239 Bodyweights - individual values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene Exposure level (ppm) : 0 199 505 2876 Group Animal Week Week Week Week Week Week Week Week Week Week Week Week /Sex Number - 1 0 1 2 3 4 5 6 7 8 9 10 2 F 51 172 199 219 227 263 266 2 72 268 281 292 294 293

52 162 194 211 224 251 267 286 290 288 296 290 295 53 157 184 205 228 251 254 269 268 281 281 291 293 54 171 192 202 224 229 247 265 246 262 265 282 288 55 157 189 212 226 241 253 271 287 281 294 287 293 56 169 188 215 230 248 252 279 276 292 292 306 299 57 164 192 212 234 252 264 264 278 278 288 288 289 58 152 166 197 212 237 252 257 272 288 288 294 289 59 180 21 1 233 254 259 282 294 304 304 308 312 318 60 151 177 203 219 235 249 259 268 271 272 276 274 3 F 1 169 189 215 224 253 263 282 278 289 287 291 300

2 171 201 215 246 261 263 291 290 287 293 296 298 3 158 176 184 197 211 212 226 227 230 240 233 238 4 180 197 222 233 258 261 275 286 283 286 299 298 5 176 200 223 240 250 266 280 280 290 291 292 289 6 178 205 225 232 257 263 272 288 287 300 307 299 7 157 177 189 208 222 227 241 247 250 257 265 283 8 170 191 202 223 227 243 262 261 267 281 281 287 9 147 170 191 200 221 226 243 249 258 262 266 266 10 174 204 216 2 30 248 247 271 269 274 283 276 281357Huntingdon Life SciencesWAG0014

APPENDIX 5 - continued Request ID: 289239 Bodyweights - individual values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Week Week Week /Sex Number 11 12 13 2 F 51 302 305 294

52 299 297 286 53 299 302 301 54 282 288 282 55 295 300 286 56 315 309 323 57 295 298 299 58 294 293 299 59 320 311 326 60 281 286 283 3 F 1 308 297 292

2 301 295 294 3 234 243 236 4 293 302 294 5 299 297 299 6 308 301 298 7 266 263 254 8 281 278 283 9 270 272 271 10 282 283 289358Huntingdon Life SciencesWAG0014

APPENDIX 5 - continued Request ID: 289239 Bodyweights - individual values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Week Week Week Week Week Week Week Week Week Week Week Week /Sex Number - 1 0 1 2 3 4 5 6 7 8 9 10 4 F 31 147 172 192 200 209 216 217 216 224 221 216 216

32 159 182 185 196 212 218 219 215 210 210 189 211 33 162 186 228 234 245 261 273 273 275 275 284 294 34 163 190 209 208 232 247 244 262 261 257 258 264 35 163 192 213 221 230 249 255 259 256 253 257 233 36 178 200 241 241 261 255 284 265 273 286 283 294 37 171 197 214 225 235 260 255 258 261 265 273 271 38 171 194 211 217 236 243 245 251 247 249 256 250 39 166 190 219 228 245 271 265 272 287 279 284 289 40 157 189 215 220 229 247 240 234 241 250 251 260 91 177 201 216 225 246 279 263 267 265 269 270 275 92 144 160 184 190 199 201 205 209 2 09 210 216 201 93 176 195 219 228 229 244 255 244 250 261 253 259 94 175 191 212 224 228 233 237 236 233 233 242 238 95 176 211 222 248 247 259 270 259 280 270 273 278 96 168 194 213 220 232 236 243 244 248 252 251 248 97 155 179 198 194 215 221 222 228 231 235 240 238 98 148 167 193 194 217 222 235 239 233 238 241 246 99 188 224 239 248 249 265 273 270 267 269 274 277 100 166 195 206 2 20 235 234 256 248 262 256 260 254359Huntingdon Life SciencesWAG0014

APPENDIX 5 - continued Request ID: 289239 Bodyweights - individual values (g) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Week Week Week Week Week Week Week /Sex Number 11 12 13 /R0 R1 R2 R3 R4 4 F 31 217 217 211

32 218 207 207 33 291 312 294 34 259 269 271 35 254 255 257 36 284 291 272 37 273 277 256 38 261 260 253 39 287 286 279 40 264 263 265 91 279 2 87 220 266 279 284 283 92 214 216 209 232 236 239 240 93 269 260 251 267 279 275 263 94 231 240 237 248 260 262 256 95 285 303 284 285 292 288 297 96 256 257 253 269 273 271 261 97 247 247 251 260 265 263 253 98 249 246 249 256 263 257 254 99 284 282 286 292 302 303 291 100 270 267 265 273 275 274 264360Huntingdon Life SciencesWAG0014

APPENDIX 6 Request ID: 289244 Food consumption - individual values (g/animal/week) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Cage Week Week Week Week Week Week Week Week Week Week Week Week /Sex Number - 1 1 2 3 4 5 6 7 8 9 10 11 1M 13 132 206 204 211 207 220 214 208 214 224 222 207 14 137 204 201 211 207 222 213 209 215 225 218 202 17 136 218 218 224 223 218 217 208 227 229 225 206 18 133 208 215 213 203 211 207 208 211 211 2 04 196 2M 21 134 190 197 191 191 204 199 193 191 192 189 187 22 140 196 196 196 194 200 195 187 190 188 182 179 3M 23 136 166 168 177 186 193 192 192 189 192 188 184 24 143 175 184 184 188 193 191 186 183 175 174 173 4M 3 135 137 180 174 177 189 177 170 169 158 156 159

4 130 134 171 161 163 168 165 161 154 144 143 144 15 132 148 178 164 178 185 180 174 167 154 154 140 16 135 130 161 149 159 169 164 156 151 141 146 141361Huntingdon Life SciencesWAG0014

APPENDIX 6 - continued Request ID: 289244 Food consumption - individual values (g/animal/week) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2 876 Group Cage Week Week Week Week Week Week /Sex Number 12 13 R1 R2 R3 R4 1M 13 212 195 14 191 186 17 218 218 237 236 228 199 18 199 206 207 212 202 181 2M 21 184 169 22 179 163 3M 23 184 160 24 171 145 4M 3 138 128

4 144 120 15 154 157 195 186 193 177 16 141 150 193 179 182 170362Huntingdon Life SciencesWAG0014

APPENDIX 6 - continued Request ID: 289244 Food consumption - individual values (g/animal/week) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Cage Week Week Week Week Week Week Week Week Week Week Week Week /Sex Number - 1 1 2 3 4 5 6 7 8 9 10 11 1F 5 89 130 123 127 127 139 124 127 133 134 127 127

6 92 139 127 135 137 143 130 135 134 138 138 137 9 103 144 135 152 143 154 150 151 152 143 146 139 10 97 136 130 142 140 153 147 146 147 146 141 138 2F 11 99 132 1 28 126 132 133 133 132 135 125 127 122 12 97 127 129 134 138 142 147 145 141 137 134 131 3F 1 102 127 125 131 132 137 136 134 128 126 123 124

2 95 120 116 121 127 138 135 138 134 133 136 130 4F 7 92 111 109 110 118 114 1 06 105 111 94 94 92

8 100 118 117 116 124 117 116 118 119 111 116 117 19 98 119 117 112 113 117 109 112 111 108 108 105 20 103 120 119 120 113 124 115 117 115 115 113 115363Huntingdon Life SciencesWAG0014

APPENDIX 6 - continued Request ID: 289244 Food consumptio

n - individual values (g/animal/week) Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Cage Week Week Week Week Week Week /Sex Number 12 13 R1 R2 R3 R4 1F 5 127 122

6 130 126 9 134 142 155 150 147 130 10 140 148 152 143 148 137 2F 11 123 115 12 128 125 3F 1 117 111

2 126 125 4F 7 97 88

8 108 85 19 108 85 147 126 122 112 20 114 108 153 139 131 113364Huntingdon Life SciencesWAG0014

APPENDIX 7 Ophthalmic examination - individual observations before commencement of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3 ,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group and sex Structure Observation 1M 2M 3M 4M 1F 2F 3F 4F Animal number/site Cornea Scratch, faint 86L Superficial opacity, faint 63, 8 4 101, 104, 109 113,

119, 120 15, 19,

72 26, 30, 42, 45 57 1, 2, 3,

4, 6 93 Iris Iritis, slight 101R Lens Anterior subcapsular opacity, faint, lateral 62L Anterior suture line opacity, faint 37R Nuclear opac ity, faint 118L 13 8R Nuclear opacity, slight 34 Persistent hyaloid artery 101, 102, 104, 114,

116R 18, 76,

78 28L, 44L, 49 6 36L, 38L, 95 Posterior subcapsular opacity, slight 44L Posterior subcapsular opacity, moderate 57R Vitreous Haemorrhage, slight 116R 44L 38L Fundus Optic disc coloboma, slight 10R 38L Number of animals examined : 20 10 10 20 20 10 10 20365Huntingdon Life SciencesWAG0014

APPENDIX 7 - continued Ophthalmic examination - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group and sex Structure Observation 1M 4M 1F 4F Animal number/site Conjunctiva Conjunctivitis, faint 94R Cornea Superficial opacity, faint 63, 84L 15L, 17L, 19 26, 30,

42 93 Superficial opacity, slight 76L Lens Anterior subcapsular opacity, faint, lateral 62L Anterior suture line opacity, faint 37R Nuclear opacity, faint 13 Nuclear opacity, slight 34 Persistent hyaloid artery 18, 76, 78 28L, 44L, 49 38L, 95 Posterior subcapsular opacity, slight 44L Vitreous Haemorrhag e, slight 44L 38L Fundus Optic disc coloboma, slight 38L Number of animals examined : 20 20 19 20366Huntingdon Life SciencesWAG0014

APPENDIX 8 Haematology - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3 ,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Hct Hb RBC RETA MCH MCHC MCV /Sex Number L/L g/dL x10 12/L x10 12/L pg g/dL fL 1M 61 0.433 15.7 8.23 0.192 1 9.0 36.2 52.6

62 0.418 15.0 7.98 0.211 18.7 35.8 52.3 63 0.468 16.9 8.72 0.184 19.4 36.2 53.7 64 0.438 16.0 8.37 0.228 19.1 36.5 52.3 65 0.444 16.1 8.58 0.158 18.8 36.2 51.8 66 0.398 14.5 7.76 0.255 18.7 36.5 51.4 67 0.421 15.0 8.00 0.213 18.8 35.7 52.6 68 0.418 15.8 8.06 0.175 19.7 37.9 51.8 69 0.409 15.6 7.88 0.178 19.8 38.2 51.8 70 0.445 16.1 8.27 0.139 19.5 36.2 53.9 2M 101 0.430 15.3 8.27 0.206 18.5 35.6 52.0

102 0.406 14.7 8.06 0.184 18.2 36.2 50.4 103 0.424 15.5 8.15 0.219 19.0 36.6 52.0 104 0.475 17.0 8.97 0.177 18.9 35.7 53.0 105 0.432 15.6 8.69 0.175 18.0 36.1 49.7 106 0.480 17.1 9.50 0.234 18.0 35.7 50.5 107 0.418 15.1 8.42 0.187 17.9 36.1 49.7 108 0.459 16.2 8.40 0.186 19.3 35.3 54.6 109 0.418 14.9 8.1 2 0.186 18.4 35.6 51.5 110 0.508 18.3 9.86 0.177 18.6 36.1 51.5367Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -t rifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal WBC N L E B M LUC /Sex Number x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L 1M 61 9.63 1.42 7.69 0.15 0.03 0.25 0.08

62 12.71 3.64 8.26 0. 22 0.07 0.40 0.12 63 13.04 1.24 11.37 0.13 0.08 0.17 0.06 64 7.25 1.35 5.52 0.12 0.02 0.19 0.05 65 8.48 1.56 6.44 0.17 0.02 0.23 0.06 66 14.98 4.41 9.48 0.35 0.09 0.55 0.11 67 14.83 3.11 10.93 0.18 0.12 0.38 0.10 68 11.96 3.53 7.58 0.21 0.04 0. 51 0.08 69 9.62 2.14 6.96 0.16 0.05 0.20 0.11 70 10.58 1.24 8.81 0.16 0.07 0.24 0.07 2M 101 10.12 0.91 8.67 0.07 0.05 0.31 0.11

102 7.63 1.99 5.10 0.07 0.02 0.37 0.07 103 17.69 3.44 13.20 0.15 0.17 0.58 0.15 104 8.93 2.73 5.51 0.10 0.0 3 0.47 0.09 105 11.72 1.63 9.59 0.06 0.07 0.30 0.08 106 12.26 3.87 7.31 0.17 0.10 0.66 0.14 107 7.59 1.44 5.72 0.09 0.02 0.27 0.05 108 7.20 1.99 4.83 0.08 0.01 0.21 0.07 109 8.04 1.52 6.22 0.02 0.03 0.19 0.06 110 15.13 9.67 4.32 0.08 0.05 0.77 0.25368Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure leve l (ppm) : 0 199 505 2876 Group Animal Plt PTP APTT Aniso - Micro - Macro - Hypo - Hyper - /Sex Number x10 9 /L sec sec cy to sis cy

to sis cy

to sis chromasia chromasia 1M 61 949 30.2 27.7 - - - - -

62 972 25.7 22.2 - - - - - 63 974 22.7 20.9 - - - - - 64 493 25.7 26.5 - - - - - 65 782 21.3 25.0 - - - - - 66 914 22.0 21.1 - - - - - 67 NVR 22.0 23.4 - - - - - 68 933 34.2 29.1 - - - - - 69 912 22.1 22.3 - - - - - 70 1013 23.9 21.1 - - - - - 2M 101 1123 19.5 19.3 - - - - -

102 962 23.4 24.2 - - - - - 103 983 23.8 20.8 - - - - - 104 1212 21.0 21.0 - - - - - 105 878 21.6 20.2 - - - - - 106 1224 22.5 20.2 - - - - - 107 822 25.3 27.4 - - - - - 108 907 21.5 20.7 - - - - - 109 1184 20.9 19.8 - - - - - 110 873 23.5 22. 2 - - - - -369Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Hct Hb RBC RETA MCH MCHC MCV /Sex Number L/L g/dL x10 12/L x10 12/L pg g/dL fL 3M 111 0.438 15.9 9.11 0.225 17.4 36.2 48.1

112 0.429 15.9 8.78 0.151 18.1 37.0 48.9 113 0.481 17.1 9.23 0.139 18.5 35.5 52.1 114 0.467 16.8 9.58 0.179 17.5 36.0 48.7 115 0.444 16.1 8.47 0.171 19.0 36.2 52.4 116 0.470 17.3 9.36 0.174 18.5 36.7 50.3 117 0.428 15.5 8.76 0.260 17.7 36.2 48.8 118 0.443 16.0 8.31 0.159 19.2 36.0 53.4 119 0.407 14.6 7.95 0.201 18 .4 35.9 51.2 120 0.447 15.9 8.38 0.218 19.0 35.7 53.3 4M 11 0.437 16.1 8.68 0.093 18.5 36.8 50.3

12 0.432 15.9 8.72 0.255 18.3 36.9 49.6 13 0.455 16.6 9.34 0.207 17.8 36.5 48.8 14 0.469 16.9 8.95 0.227 18.9 36.0 52.4 15 0.484 17.6 9.60 0.234 18.3 36.3 50.4 16 0.462 16.9 9.17 0.236 18.5 36.7 50.3 17 0.438 15.9 9.05 0.191 17.6 36.3 48.4 18 0.447 16.1 8.92 0.261 18.1 36.1 50.1 19 0.463 17.2 9.21 0.107 18.6 37.1 50.3 20 0.453 16.6 8.97 0.244 18.5 36.7 50.5370Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Gr oup Animal WBC N L E B M LUC /Sex Number x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L 3M 111 12.74 3.18 8.64 0.04 0.04 0.70 0.14

112 7.21 1.48 5.13 0.04 0.02 0.45 0.08 113 12.36 3.69 7.66 0.06 0.10 0.70 0.14 114 10.20 2.01 7.44 0.05 0 .07 0.52 0.11 115 12.63 3.82 7.67 0.09 0.09 0.78 0.18 116 10.68 2.59 7.42 0.04 0.06 0.50 0.08 117 9.37 2.32 6.34 0.05 0.05 0.53 0.08 118 7.00 1.58 5.02 0.04 0.03 0.27 0.05 119 8.24 2.82 4.85 0.03 0.02 0.44 0.08 120 15.71 2.98 11.68 0.07 0.24 0. 55 0.19 4M 11 7.35 0.51 6.48 0.03 0.02 0.24 0.07

12 6.56 2.02 3.59 0.05 0.07 0.55 0.28 13 8.97 2.98 4.89 0.04 0.06 0.77 0.23 14 11.66 3.29 7.45 0.05 0.09 0.67 0.10 15 9.77 2.63 6.33 0.03 0.04 0.58 0.15 16 8.40 2.15 5.52 0.05 0.02 0.50 0.17 17 8.61 1.36 6.35 0.08 0.02 0.42 0.37 18 6.79 1.64 4.45 0.04 0.02 0.41 0.23 19 11.70 4.59 6.05 0.08 0.07 0.73 0.18 20 8.87 2.34 5.51 0.02 0.03 0.79 0.18371Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Plt PTP APTT Aniso - Micro - Macro - Hypo - Hyper - /Sex Number x10 9 /L sec sec cy to sis cy

to sis cy

to sis chromasia chromasia 3M 111 1134 21.7 19.2 - - - - -

112 1014 24.5 20.3 - - - - - 113 919 22.4 21.5 - - - - - 114 1059 25.6 18.5 - - - - - 115 1059 21.8 19.3 - - - - - 116 910 22.6 21.2 - - - - - 117 1041 26.6 22.3 - - - - - 118 755 25.0 22.0 - - - - - 119 1044 22.6 22.6 - - - - - 120 826 25.5 21.2 - - - - - 4M 11 821 23.8 22.1 - - - - -

12 945 25.6 19.6 - - - - - 13 1004 26.1 25.6 - - - - - 14 792 22.4 23.2 - - - - - 15 970 24.3 20.9 - - - - - 16 886 CTD CTD - - - - - 17 936 24.0 19.2 - - - - - 18 890 24.5 23.9 - - - - - 19 922 27.4 22.2 - - - - - 20 814 24.2 21.9 - - - - -372Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Hct Hb RBC RETA MCH MCHC MCV /Sex Number L/L g/dL x10 12/L x10 12/L pg g/dL fL 1F 21 0.407 14.8 7.78 0.200 19.1 36.4 52.3

22 0.406 15.4 7.75 0.099 19.9 37.9 52.3 23 0.431 15.5 8.06 0.156 19.3 36.0 53.5 24 0.417 15.5 7.75 0.203 20.0 37.1 53.8 25 0.436 15.9 7.88 0.144 20.1 36.4 55.3 2 6 0.422 15.3 8.38 0.187 18.3 36.4 50.3 28 0.416 15.5 7.45 0.146 20.8 37.3 55.8 29 0.423 15.5 7.82 0.134 19.8 36.7 54.1 30 0.438 16.2 8.41 0.156 19.3 37.0 52.1 2F 51 0.436 15.8 8.15 0.210 19.3 36.2 53.4

52 0.393 14.1 7.82 0.169 18.1 36.0 50.2 53 0.422 15.5 7.85 0.135 19.7 36.7 53.8 54 0.409 15.7 7.82 0.129 20.0 38.3 52.3 55 0.388 13.9 7.60 0.207 18.2 35.7 51.1 56 0.406 14.8 8.04 0.131 18.5 36.5 50.6 57 0.441 16.1 8.40 0.185 19.2 36.5 52.5 58 0.422 15.6 8.53 0.090 18.3 37.1 49.5 59 0.395 15.1 7.52 0.150 20.0 38.1 52.6 60 0.409 15.1 7.52 0.253 20.1 36.9 54.3373Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoroprop ene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal WBC N L E B M LUC /Sex Number x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L 1F 21 8.05 2.42 5.25 0.10 0.02 0.19 0.06

22 4.98 0.34 4.41 0.08 0.01 0.07 0.06 23 8.75 2.01 6.23 0.13 0.03 0.29 0.05 24 4.38 0.69 3.48 0.06 0.02 0.10 0.03 25 6.43 0.55 5.59 0.07 0.02 0.14 0.06 26 10.07 2.22 7.42 0.08 0.03 0.19 0.15 28 12.72 2.78 9.12 0.12 0.17 0.39 0.15 29 14.69 3.39 10 .74 0.12 0.06 0.22 0.15 30 6.77 0.71 5.61 0.20 0.04 0.14 0.06 2F 51 7.42 0.84 5.86 0.14 0.08 0.41 0.10

52 6.85 0.96 5.57 0.03 0.02 0.25 0.03 53 6.80 0.76 5.73 0.04 0.02 0.17 0.08 54 7.41 0.39 6.60 0.06 0.03 0.16 0.17 55 11.14 1.09 9.57 0.04 0.05 0.28 0.10 56 9.03 1.50 6.88 0.07 0.03 0.44 0.09 57 8.15 0.71 6.90 0.05 0.04 0.25 0.19 58 5.94 0.93 4.61 0.08 0.04 0.22 0.07 59 6.63 0.70 5.48 0.10 0.02 0.25 0.07 60 6.53 0.75 5.41 0.05 0.02 0.23 0.08374Huntingdon Life SciencesWAG0014

APPENDIX 8 - continue d Haematology - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Plt PTP APTT Aniso - Micro - Macro - Hypo - Hyper - /Sex Number x10 9 /L sec sec cy to sis cy

to sis cy

to sis chromasia chromasia 1F 21 1236 21.5 18.8 - - - - -

22 843 21.2 16.4 - - - - - 23 1023 20.8 17.6 - - - - - 24 853 20.6 19.0 - - - - - 25 7 97 20.8 18.3 - - - - - 26 871 22.2 15.9 - - - - - 28 960 22.0 16.9 - - - - - 29 896 21.2 17.2 - - - - - 30 1071 19.3 16.2 - - - - - 2F 51 747 25.6 19.9 - - - - -

52 853 24.0 17.8 - - - - - 53 932 23.9 21.5 - - - - - 54 985 23.8 18 .1 - - - - - 55 997 23.9 19.4 - - - - - 56 798 24.6 18.1 - - - - - 57 758 24.4 18.8 - - - - - 58 822 24.0 19.6 - - - - - 59 849 24.7 19.4 - - - - - 60 978 22.4 17.7 - - - - -375Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual obs ervations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Hct Hb RBC RETA MCH MCHC MCV /Sex Number L/L g/dL x10 12/L x10 12/L pg g/dL fL 3F 1 0.426 15.5 7.97 0.212 19.4 36.3 53.4

2 0.418 14.7 7.96 0.136 18.5 35.3 52.5 3 0.465 16.5 8.89 0.255 18.6 35.6 52.3 4 0.397 14.4 8.03 0.201 18.0 36.4 49.5 5 0.416 15.7 8.43 0.137 18.7 37.8 49.4 6 0.435 16.2 8.31 0.137 19.5 37.2 52.3 7 0.412 15.1 8.17 0.226 18.5 36.8 50.4 8 0.411 15.0 7.72 0.147 19.4 36.5 53.2 9 0.439 16.0 8.13 0.156 19.6 36.4 54.0 10 0.446 16.4 8.38 0.148 19.6 36.8 53.2 4F 31 0.425 15.2 8.04 0.376 18.9 35.7 52.9

32 0.370 13.1 6.03 0.627 21.7 35.4 61.3 33 0.407 15.2 8.44 0.230 18.0 37.4 48.2 34 0.433 15.7 8.50 0.210 18.4 36.2 50.9 35 0.387 13.5 7.30 0.462 18.5 34.9 53.0 36 0.415 14.0 7.85 0.323 17.9 33.9 52.8 37 0.397 13.5 8.07 0.336 16.8 34.1 49.2 38 0.436 14.6 8.45 0.362 17.3 33.5 51.6 39 0.424 14.2 8.35 0.192 17.0 33.4 50.8 40 0.450 15.1 9.50 0.175 15.9 33.7 47.3376Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal WBC N L E B M LUC /Sex Number x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L 3F 1 6.82 1.24 4.93 0.02 0.06 0.43 0.14

2 10.50 1.54 7.88 0.13 0.03 0.70 0.20 3 5.24 1.17 3.52 0.07 0.05 0.36 0.07 4 7.11 1.19 5.10 0.08 0.02 0.47 0.25 5 6.49 0.67 5.34 0.08 0.04 0.29 0.07 6 8.03 1.79 5.44 0.05 0.04 0.56 0.15 7 4.38 0.31 3.80 0.03 0.02 0.18 0.05 8 7.07 1.35 5.15 0.06 0.03 0.37 0.11 9 7.08 1.84 4.69 0.08 0.01 0.34 0.10 10 7.47 0.74 6.03 0.13 0.05 0.41 0.12 4F 31 5.86 1.37 4.00 0.02 0.01 0.38 0.07

32 6.09 1.00 4.71 0.02 0.02 0.21 0.13 33 4.49 0.61 3.40 0.03 0.02 0.38 0.05 34 5.41 0.67 4.22 0.03 0.04 0.37 0.08 35 4.03 1.19 2.56 0.02 0.01 0.19 0.06 36 8.76 3.39 4.77 0.02 0.02 0.33 0.24 37 3.30 0.31 2.66 0.01 0.01 0.25 0.06 38 7.56 0.33 6.48 0.04 0.05 0.44 0.22 39 6.73 1.40 4.86 0.02 0.03 0.35 0.08 40 5.59 0.46 4.73 0.04 0.04 0.27 0.05377Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3 ,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Plt PTP APTT Aniso - Micro - Macro - Hypo - Hyper - /Sex Number x10 9 /L sec sec cy to sis cy

to sis cy

to sis chromasia chromasia 3F 1 784 25.4 18.0 - - - - -

2 1064 20.5 16.9 - - - - - 3 601 24.0 21.3 - - - - - 4 709 22.8 21.2 - - - - - 5 853 23.9 19.5 - - - - - 6 940 22.2 20.0 - - - - - 7 788 26.3 17.4 - - - - - 8 944 24.2 20.1 - - - - - 9 919 22.7 18.3 - - - - - 10 790 22.0 20.5 - - - - - 4F 31 1369 2 5.7 20.6 - - - - -

32 1052 31.1 19.4 + - - - - 33 1033 28.9 20.1 - - - - - 34 683 25.7 20.0 - - - - - 35 803 27.1 18.6 - - - - - 36 1496 28.1 18.4 - - - - - 37 1203 27.4 17.9 - - - - - 38 785 24.0 21.4 - - - - - 39 1248 29.8 20.3 - - - - - 40 1032 16.6 18.5 - - - - -378Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene Exposure level (ppm) : 0 199 505 2876 Group Animal Hct Hb RBC RETA MCH MCHC MCV /Sex Number L/L g/dL x10 12/L x10 12/L pg g/dL fL 1M 81 0.424 14.7 8.72 0.291 16.8 34.6 48.6

82 0.450 15.3 9.05 0.183 16.9 33.9 49.7 83 0.453 15.3 8. 65 0.233 17.7 33.8 52.3 84 0.439 15.0 8.21 0.167 18.2 34.1 53.5 85 0.460 15.7 8.77 0.180 17.9 34.1 52.5 86 0.428 14.3 8.26 0.257 17.3 33.4 51.9 87 0.424 14.3 7.99 0.182 17.9 33.7 53.1 88 0.448 15.1 8.63 0.197 17.5 33.8 51.9 89 0.428 14.4 7.83 0 .260 18.3 33.6 54.6 90 0.451 15.4 8.63 0.169 17.8 34.1 52.2 4M 71 0.446 15.4 8.34 0.181 18.5 34.5 53.5

72 0.451 15.2 8.24 0.156 18.4 33.7 54.8 73 0.434 14.8 8.11 0.177 18.3 34.1 53.5 74 0.471 15.9 8.69 0.144 18.3 33.8 54.2 75 0.432 14. 7 7.89 0.263 18.7 34.1 54.7 76 0.444 15.0 8.21 0.156 18.3 33.9 54.1 77 0.490 16.7 8.92 0.116 18.7 34.1 54.9 78 0.451 15.3 8.65 0.123 17.7 33.9 52.1 79 0.438 14.7 8.61 0.111 17.0 33.5 50.8 80 0.433 14.8 8.54 0.204 17.3 34.1 50.7379Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal WBC N L E B M LUC /Sex Number x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L 1M 81 11.41 3.12 7.50 0.18 0.03 0.46 0.13

82 12.28 2.98 8.66 0.16 0.12 0.23 0.15 83 9.17 0.97 7.65 0.16 0.06 0.29 0.05 84 8.99 1.40 7.12 0.12 0. 06 0.24 0.06 85 9.31 1.49 7.20 0.16 0.10 0.25 0.10 86 16.80 2.11 13.52 0.24 0.26 0.43 0.24 87 9.63 0.73 8.40 0.08 0.11 0.21 0.11 88 10.74 1.23 8.99 0.12 0.11 0.17 0.13 89 11.55 2.02 8.95 0.10 0.10 0.24 0.14 90 7.84 1.45 5.86 0.11 0.06 0.25 0.11 4M 71 9.21 1.18 7.55 0.09 0.05 0.19 0.15

72 6.73 0.87 5.44 0.10 0.05 0.20 0.07 73 6.36 1.14 4.80 0.14 0.04 0.16 0.09 74 9.49 1.63 7.34 0.13 0.10 0.20 0.08 75 9.98 1.65 7.87 0.18 0.07 0.14 0.07 76 6.24 0.96 4.95 0.08 0.07 0.10 0.07 7 7 5.10 0.99 3.74 0.14 0.03 0.16 0.05 78 7.69 0.83 6.19 0.13 0.06 0.34 0.14 79 7.86 0.72 6.85 0.04 0.07 0.12 0.06 80 9.13 2.24 6.16 0.21 0.14 0.27 0.11380Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 4 of reco ver y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Plt PTP APTT Aniso - Micro - Macro - Hypo - Hyper - /Sex Number x10 9 /L sec sec cy to sis cy

to sis cy

to sis chromasia chromasia 1M 81 1080 21.2 17.6 + - - - -

82 1067 23.3 24.8 + - - - - 83 1117 20.4 18.6 - - - - - 84 621 23.1 23.6 - - - - - 85 1011 20.5 27.3 - - - - - 86 1301 23.6 20.3 - - - - - 87 1305 2 4.2 22.8 - - - - - 88 1180 22.9 19.6 - - - - - 89 1149 21.6 20.6 - - - - - 90 1077 25.7 30.9 - - - - - 4M 71 1227 17.7 13.9 - - - - -

72 1109 20.9 22.3 - - - - - 73 1079 22.1 24.0 - - - - - 74 1173 21.7 23.5 - - - - - 75 1221 22.5 22.3 - - - - - 76 914 23.1 18.7 - - - - - 77 866 22.0 21.5 - - - - - 78 1250 23.5 22.7 - - - - - 79 1168 23.5 21.4 - - - - - 80 979 21.5 21.6 - - - - -381Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Hct Hb RBC RETA MCH MCHC MCV /Sex Number L/L g/dL x10 12/L x10 12/L pg g/dL fL 1F 41 0.409 14.4 7.21 0.108 19.9 35.1 56.8

42 0.418 14.5 7.68 0.082 18.9 34.6 54.4 43 0.420 14.2 7.97 0.189 17.9 33.9 52.8 44 0.401 13.7 7.61 0.152 17.9 34.1 52.7 45 0.426 14.5 7.50 0.172 19.4 34.1 56.8 46 0.438 15.1 8.00 0.100 18.9 34.5 54.7 47 0.410 14.2 7.29 0.123 19.4 34.6 56.2 48 0.412 14.1 7.80 0.136 18.1 34.2 52.8 49 0.423 14.6 7.57 0.105 19.3 34.5 55.9 50 0.415 14.4 7.37 0.127 19.6 34.8 56.3 4F 91 0.435 15.1 7.82 0.129 19.3 34.6 55.7

92 0. 406 14.0 7.74 0.112 18.1 34.4 52.4 93 0.427 14.5 8.00 0.149 18.1 34.0 53.4 94 0.432 14.6 8.05 0.139 18.2 33.9 53.6 95 0.421 14.8 7.81 0.073 19.0 35.3 53.9 96 0.422 14.3 7.94 0.104 18.0 33.8 53.1 97 0.430 14.7 7.85 0.142 18.7 34.1 54.8 98 0.440 15.0 7.84 0.168 19.1 34.1 56.1 99 0.433 15.2 8.09 0.155 18.7 35.0 53.5 100 0.431 14.8 7.67 0.150 19.2 34.3 56.2382Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 4 of recover y Group : 1 2 3 4 Compound : Contro l 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal WBC N L E B M LUC /Sex Number x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L 1F 41 4.93 0.46 4.20 0.08 0.04 0.10 0.05

42 5.77 0.85 4.47 0.13 0.05 0.15 0.12 43 5.58 0.54 4.75 0.11 0.03 0.08 0.06 44 3.78 0.46 3.12 0.08 0.01 0.08 0.03 45 4.19 0.54 3.35 0.10 0.03 0.13 0.03 46 5.87 0.96 4.66 0.07 0.03 0.09 0.06 47 5.72 0.65 4.70 0.14 0.03 0 .14 0.06 48 6.90 1.55 4.91 0.14 0.02 0.19 0.08 49 4.00 0.71 2.96 0.11 0.03 0.13 0.05 50 3.76 0.72 2.79 0.10 0.03 0.07 0.05 4F 91 3.43 0.48 2.69 0.05 0.01 0.15 0.04

92 6.58 1.41 4.87 0.09 0.02 0.13 0.07 93 2.32 0.70 1.37 0.16 0.01 0.06 0.02 94 2.98 0.58 2.17 0.11 0.02 0.06 0.04 95 3.78 0.78 2.78 0.06 0.04 0.08 0.05 96 2.36 0.44 1.78 0.06 0.01 0.04 0.03 97 3.66 0.54 2.89 0.08 0.02 0.08 0.04 98 4.33 0.92 3.17 0.10 0.03 0.07 0.05 99 3.66 0.98 2.44 0.08 0.03 0.08 0.04 100 2.85 0.44 2.21 0.06 0.02 0.10 0.02383Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluor opr opene Exposure level (ppm) : 0 199 505 2876 Group Animal Plt PTP APTT Aniso - Micro - Macro - Hypo - Hyper - /Sex Number x10 9 /L sec sec cy to sis cy

to sis cy

to sis chromasia chromasia 1F 41 913 22.9 25.2 - - - - -

42 952 22.9 21.3 - - - - - 4 3 1155 22.8 22.3 - - - - - 44 1021 22.8 19.3 - - - - - 45 997 22.3 20.6 - - - - - 46 1072 18.2 23.0 - - - - - 47 1003 22.1 20.7 - - - - - 48 956 20.0 17.1 - - - - - 49 1104 22.0 19.9 - - - - - 50 882 21.4 19.2 - - - - - 4F 91 1054 20.5 16.6 - - - - -

92 961 21.7 23.2 - - - - - 93 1036 22.9 21.2 - - - - - 94 1222 23.0 20.4 - - - - - 95 897 24.3 19.1 - - - - - 96 904 22.8 20.2 - - - - - 97 916 23.9 20.2 - - - - - 98 1014 21.3 16.7 - - - - - 99 1144 21.7 20.3 - - - - - 100 949 19.4 18.1 - - - - -384Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations sporadic sample Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Hct Hb RBC RETA MCH MCHC MCV /Sex Number L/L g/dL x10 12/L x10 12/L pg g/dL fL 1F 27 0.527 17.4 8.78 0.377 19.8 32.9 60.0385Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations sporadic sample Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal WBC N L E B M LUC /Sex Number x10 9 /L x10 9 /L x 10 9 /L x10 9 /L x10 9 /L x10 9 /L x10 9 /L 1F 27 4.80 2.97 1.43 0.01 0.02 0.33 0.03386Huntingdon Life SciencesWAG0014

APPENDIX 8 - continued Haematology - individual observations sporadic sample Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Plt PTP APTT Aniso - Micro - Macro - Hypo - Hyper - /Sex Number x10 9 /L sec sec cy to sis cy

to sis cy

to sis chromasia chromasia 1F 27 1339 25.5 18.3 + - - - -387Huntingdon Life SciencesWAG0014

APPENDIX 9 Blood chemistry - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal ALP ALT AST Bili Ur ea Creat Gluc Chol Trig /Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L 1M 61 74 33 82 2 4.93 40 6.69 1.77 0.85

62 99 38 94 1 5.92 29 7.45 1.62 0.44 63 89 23 71 2 5.16 29 8.68 1.81 1.07 64 59 26 74 2 4.49 34 8.74 1.70 0.84 65 76 37 71 1 5.61 37 10.03 1.81 0.66 66 61 24 73 3 4.97 40 8.66 1.65 0.88 67 70 31 63 2 4.79 32 7.57 1.65 0.44 68 55 32 81 1 6.24 36 7.79 1.60 0.59 69 75 34 72 1 4.21 35 8.11 2. 35 0.73 70 62 31 70 2 4.76 36 8.04 1.44 0.37 2M 101 88 29 94 2 5.49 37 7.15 2.32 0.82

102 63 44 74 2 6.34 29 8.37 1.55 0.47 103 66 38 136 2 5.84 35 8.77 1.11 0.42 104 84 41 250 2 4.71 28 8.53 1.89 1.24 105 78 27 85 2 5.55 31 7.54 1.6 0 0.63 106 78 39 216 2 5.06 36 7.80 2.07 0.75 107 77 48 105 1 6.55 33 10.11 1.07 0.53 108 61 41 118 2 6.25 33 9.21 1.29 0.31 109 58 32 188 2 7.73 37 10.82 1.29 0.86 110 69 60 462 2 5.49 34 8.92 1.90 0.58388Huntingdon Life SciencesWAG0014

APPENDIX 9 - continued Blood chemistry - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal N a K Cl Ca Phos Total Prot Alb A/G /Sex Number mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio 1M 61 142 3.8 100 2.47 1.78 67 36 1.16

62 142 4.1 102 2.44 1.92 70 34 0.94 63 142 4.6 102 2.44 2.09 62 33 1.14 64 143 4.2 103 2.44 2.12 61 34 1.26 65 141 4.5 102 2.40 1.83 63 34 1.17 66 140 4.6 101 2.42 2.05 64 34 1.13 67 141 4.5 103 2.43 1.76 66 33 1.00 68 141 3.7 102 2.36 1.81 69 35 1.03 69 141 4.1 102 2.46 1.74 69 35 1.03 70 141 4.2 101 2.50 1.77 65 36 1.24 2M 101 142 4.4 104 2.43 2.02 62 35 1.30

102 141 4.3 104 2.44 1.78 65 34 1.10 103 141 4.4 103 2.39 1.98 62 33 1.14 104 144 4.0 105 2.46 1.95 60 34 1.31 105 141 4.2 104 2.38 2.15 63 34 1.17 106 142 5.0 105 2.54 1.67 67 37 1.23 107 142 4.8 105 2.33 1.50 63 3 5 1.25 108 143 4.5 106 2.41 1.61 61 34 1.26 109 143 4.6 104 2.44 2.41 61 32 1.10 110 142 4.6 102 2.49 2.22 68 35 1.06389Huntingdon Life SciencesWAG0014

APPENDIX 9 - continued Blood chemistry - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal ALP ALT AST Bili Ur ea Creat Gluc Chol Trig /Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmo l/L mmol/L mmol/L 3M 111 57 39 191 1 5.84 34 7.45 2.55 0.53

112 98 44 191 1 7.09 33 8.87 1.08 1.06 113 100 48 310 2 6.85 50 10.83 1.76 0.63 114 83 38 175 2 7.82 36 10.31 1.16 0.65 115 79 42 257 2 7.39 34 12.56 2.38 0.82 116 65 31 190 1 5.93 31 7.03 1.47 0.76 117 80 40 129 1 7.07 28 7.79 1.17 0.45 118 101 31 245 1 4.18 34 6.83 1.16 0.77 119 63 41 266 1 5.76 34 9.38 1.49 0.77 120 55 34 298 2 6.02 49 14.55 1.45 0.86 4M 11 64 30 68 2 8.55 29 6.71 1.19 0.45

12 119 45 323 2 7.14 34 8.18 1.31 0.96 13 111 38 209 2 11.93 36 9.30 0.43 1.39 14 62 25 188 2 5.76 31 9.75 1.53 0.85 15 92 39 248 2 7.42 34 9.85 1.08 0.58 16 135 40 267 2 11.12 31 7.43 0.62 1.70 17 83 37 137 2 6.22 35 7.28 1.15 0.54 18 74 33 189 1 9.55 47 7.65 1.27 0.95 19 81 65 301 2 8.62 31 7.33 1.00 0.57 20 133 37 234 2 7.26 31 6.65 0.72 1.29390Huntingdon Life SciencesWAG0014

APPENDIX 9 - continued Blood chemistry - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Na K Cl Ca Phos Total Prot Alb A/G /Sex Number mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio 3M 111 141 4.6 103 2.49 1.43 68 36 1.13

112 141 4.9 107 2.30 1.46 61 33 1.18 113 144 5.0 105 2.42 1.87 61 32 1.10 114 141 4.8 104 2.53 2.12 61 35 1.35 115 141 5.1 104 2.44 1.90 59 33 1.27 116 144 4.4 106 2.49 2.49 61 34 1.26 117 141 4.5 105 2.35 1.99 59 33 1.27 118 144 4.6 108 2.51 2.39 57 33 1.38 119 144 4.8 105 2.55 2.25 59 32 1.19 120 145 5.2 107 2.67 3.12 62 34 1.21 4M 11 145 3.7 111 2.34 1.61 57 33 1.38

12 139 4.7 107 2.47 1.99 59 34 1.36 13 143 4.0 105 2.38 2.90 60 35 1.40 14 143 4.9 109 2.46 2.10 61 34 1.26 15 140 5.5 106 2.53 2.30 64 36 1.29 16 145 5.0 112 2.44 2.85 59 36 1.57 17 144 4.4 107 2.47 2.87 60 34 1.31 18 142 5.0 109 2.46 2.66 58 33 1.32 19 143 4.3 106 2.43 2.83 60 35 1.40 20 142 3.9 104 2.42 2.53 61 35 1.35391Huntingdon Life SciencesWAG0014

APPENDIX 9 - continued Blood chemistry - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Expo sure level (ppm) : 0 199 505 2876 Group Animal ALP ALT AST Bili Ur ea Creat Gluc Chol Trig /Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L 1F 21 30 21 65 2 6.07 47 6.59 2.47 0.46

22 35 20 63 1 5.75 38 8.14 2.16 0.71 23 37 29 77 2 6.88 45 5.76 2.20 0.49 24 38 20 54 2 5.59 42 8.34 1.94 0.42 25 30 28 57 1 5.36 36 8.93 2.46 0.51 26 67 19 77 2 7.87 44 8.96 1.94 0.29 28 42 35 83 1 6.45 38 9.04 2.77 0.43 29 45 22 69 1 7.58 40 9.97 1.71 0.82 30 50 24 66 1 6.59 37 9.8 9 1.50 0.50 2F 51 40 23 141 3 6.41 42 7.65 1.64 0.37

52 40 30 72 2 6.28 43 6.60 1.63 1.04 53 35 34 51 3 8.38 32 6.71 1.68 0.45 54 33 24 77 3 7.79 45 5.87 1.65 0.52 55 33 23 77 2 7.17 41 6.19 1.47 0.60 56 42 25 63 3 7.66 42 7.31 1.70 0.35 57 39 31 67 2 9.64 45 5.50 1.40 0.62 58 26 48 78 3 8.89 46 6.97 1.60 0.69 59 33 23 76 2 7.56 39 5.48 1.64 0.69 60 44 28 67 2 6.44 36 8.06 2.26 0.44392Huntingdon Life SciencesWAG0014

APPENDIX 9 - continued Blood chemistry - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Na K Cl Ca Phos Total Prot Alb A/G /Sex Number mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio 1F 21 141 3.7 103 2.61 1.33 76 42 1.24

22 142 4.1 104 2.50 1.00 69 40 1.38 23 141 3.4 101 2.53 1.56 66 37 1.28 24 142 3.7 102 2.44 1.46 66 38 1.36 25 140 4.1 102 2.58 1.17 70 41 1.41 26 141 4 .4 103 2.42 1.02 75 41 1.21 28 139 4.4 101 2.43 1.01 68 37 1.19 29 138 4.7 100 2.37 1.10 71 35 0.97 30 139 4.1 101 2.47 1.00 65 40 1.60 2F 51 142 3.9 105 2.43 1.69 69 40 1.38

52 141 4.0 104 2.41 1.67 65 40 1.60 53 141 4.2 104 2.55 1.5 8 71 42 1.45 54 140 3.5 101 2.34 1.67 66 39 1.44 55 143 3.9 110 2.37 1.73 62 36 1.38 56 142 3.6 105 2.42 1.82 63 37 1.42 57 141 3.5 103 2.48 1.79 63 37 1.42 58 143 3.3 100 2.57 1.69 70 42 1.50 59 143 3.5 106 2.37 1.70 64 37 1.37 60 141 3.4 10 4 2.37 1.49 63 36 1.33393Huntingdon Life SciencesWAG0014

APPENDIX 9 - continued Blood chemistry - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluor opr opene Exposure level (ppm) : 0 199 505 2876 Group Animal ALP ALT AST Bili Ur ea Creat Gluc Chol Trig /Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L 3F 1 58 25 217 2 8.32 40 9.77 1.18 0.53

2 49 21 191 2 6.01 49 12.85 2.09 0.54 3 32 64 274 3 9.14 52 4.25 1.36 0.32 4 32 20 104 2 8.84 43 9.70 1.51 0.55 5 41 32 93 1 7.95 32 6.48 2.95 0.44 6 43 38 328 1 8.10 39 8.18 1.92 0.71 7 44 22 85 3 6.46 37 5.52 0.78 0.84 8 42 36 174 2 7.47 50 6.30 1.73 0.61 9 58 34 204 2 8.15 48 7.97 2.34 0.94 10 39 28 177 2 9.58 39 6.82 2.35 0.40 4F 31 76 17 80 1 10.10 41 4.97 1.52 1.29

32 78 16 57 1 9.28 37 5.56 1.04 0.76 33 40 25 129 2 12.52 38 6.76 0.79 0.89 34 49 18 98 2 8.07 34 6.54 0.75 1.65 35 89 19 58 2 9. 09 40 4.79 1.10 0.44 36 81 16 80 2 8.87 35 6.23 1.93 0.45 37 64 15 58 2 12.00 42 4.90 0.72 0.97 38 45 13 69 1 9.32 37 6.13 1.62 1.43 39 40 22 127 2 9.09 36 7.09 0.92 0.33 40 36 15 69 2 11.11 42 4.89 1.03 0.45394Huntingdon Life SciencesWAG0014

APPENDIX 9 - continue d Blood chemistry - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Ani mal Na K Cl Ca Phos Total Prot Alb A/G /Sex Number mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio 3F 1 142 4.0 107 2.44 2.07 58 34 1.42

2 142 5.2 104 2.54 2.37 59 33 1.27 3 141 5.5 106 2.47 3.06 58 34 1.42 4 141 4.0 104 2.44 2.16 59 35 1.46 5 140 3.8 105 2.49 1.44 63 36 1.33 6 142 4.2 106 2.40 1.46 64 36 1.29 7 141 4.0 106 2.37 1.74 60 37 1.61 8 143 4.2 105 2.38 2.71 57 34 1.48 9 141 4.0 105 2.48 1.80 64 37 1.37 10 141 3.7 106 2.41 1.93 58 34 1.42 4F 31 141 4.8 1 09 2.36 3.11 61 33 1.18

32 145 4.3 110 2.26 3.60 58 31 1.15 33 138 4.0 99 2.31 2.18 60 37 1.61 34 141 3.8 103 2.42 2.89 65 39 1.50 35 140 4.2 106 2.40 3.07 57 33 1.38 36 137 4.3 104 2.37 2.27 64 33 1.06 37 141 3.8 106 2.30 3.37 59 34 1.36 38 140 4.3 105 2.47 2.83 63 38 1.52 39 139 4.8 108 2.43 2.26 62 36 1.38 40 140 3.9 104 2.34 2.49 61 39 1.77395Huntingdon Life SciencesWAG0014

APPENDIX 9 - continued Blood chemistry - individual observations during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal ALP ALT AST Bili Ur ea Creat Gluc Chol Trig /Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L 1M 81 89 45 66 2 5.33 28 9.17 1.85 1.36

82 64 38 61 2 4.60 31 7.77 1.21 1.14 83 59 36 55 2 5.30 31 8.57 3.15 0.99 84 62 36 65 2 4.46 29 8.62 1.46 0.96 85 57 23 55 2 5.32 44 9.53 1.50 1.73 86 94 56 81 4 5.10 29 9.01 2.39 0.81 87 80 49 71 2 6.17 43 8.23 1.54 0.85 88 78 61 119 4 6.19 43 6.54 2.92 0.71 89 81 28 64 4 4.99 40 8.29 2.87 0.93 90 94 44 76 2 5.68 33 7.24 1.14 0.67 4M 71 87 33 53 2 5.75 31 6.51 2.11 0.98

72 84 31 52 1 4.79 32 7.97 1.71 0.91 73 60 39 78 2 5.78 35 5.73 1.37 0.42 74 102 25 64 2 5.41 47 6.21 1.67 0.56 75 84 56 162 3 6.71 45 8.13 1.91 0.60 76 118 63 74 2 5.78 36 5.82 1.53 0.23 77 75 41 65 2 4.91 32 6.12 1.36 0.37 78 80 29 57 1 5.36 32 6.96 1.37 0.73 79 113 38 65 2 6.13 31 7.40 1.3 5 0.76 80 123 50 92 3 5.24 37 7.22 1.79 0.78396Huntingdon Life SciencesWAG0014

APPENDIX 9 - continued Blood chemistry - individual observations during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Na K Cl Ca Phos Total Prot Alb A/G /Sex Number mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio 1M 81 140 4.1 100 2.50 1.72 68 35 1.06

82 140 3.9 99 2.51 1 .94 66 35 1.13 83 139 4.1 98 2.56 1.69 67 34 1.03 84 140 4.2 102 2.43 1.74 64 33 1.06 85 140 4.0 100 2.37 1.56 63 34 1.17 86 139 4.4 99 2.62 1.79 67 35 1.09 87 139 4.5 99 2.46 1.64 67 32 0.91 88 141 4.5 100 2.61 1.92 67 35 1.09 89 140 4.2 100 2.49 1.76 63 32 1.03 90 139 4.3 101 2.43 1.73 69 36 1.09 4M 71 141 4.3 100 2.55 2.02 69 37 1.16

72 139 4.4 101 2.54 2.26 64 34 1.13 73 140 4.0 101 2.48 1.64 65 35 1.17 74 140 4.4 101 2.47 1.98 65 35 1.17 75 140 4.3 101 2.52 1.81 65 3 5 1.17 76 140 4.3 101 2.41 1.64 63 33 1.10 77 140 5.0 100 2.49 1.72 63 35 1.25 78 140 4.5 100 2.58 2.12 63 33 1.10 79 140 4.9 102 2.51 1.79 64 35 1.21 80 139 5.0 101 2.57 1.86 71 36 1.03397Huntingdon Life SciencesWAG0014

APPENDIX 9 - continued Blood chemistry - individual observations during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal ALP ALT AST Bili Ur ea Creat Gluc Chol Trig /Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L 1F 41 22 41 64 2 7.62 51 7.48 2.66 0.63

42 26 120 312 2 6.34 35 8.31 2.17 0.69 43 46 63 152 2 5.29 41 6.82 1.90 0.42 44 28 33 75 2 5.57 46 6.31 1.61 0.76 45 24 26 58 2 4.97 40 7.30 2.21 0.49 46 25 53 77 2 6.31 46 8.13 2.14 0.92 47 41 33 58 2 7.29 46 7.10 2.47 1.39 48 38 34 71 3 7.19 43 5.60 2.26 0.70 49 23 33 83 2 6.72 45 6.77 1.86 1.16 50 52 49 79 2 5.47 40 5.79 3.00 0.78 4F 91 56 29 60 2 5.86 40 7.40 1.76 0.77

92 46 69 151 2 6.72 38 8.49 2.31 1.15 93 31 69 162 2 6.26 41 7.26 2.74 0.54 94 49 64 141 1 5.91 44 6.64 2.51 0.61 95 38 45 97 2 8.10 39 5.41 1.26 0.39 96 39 32 59 2 5.23 40 7.45 1.58 0.68 97 50 65 104 1 6.50 44 6.39 1.09 0.46 98 51 35 82 2 5.78 40 6.98 1.49 0.72 99 44 57 126 2 4.96 46 5.77 1.76 0.47 100 38 32 70 1 6.36 41 6.39 1.92 0.66398Huntingdon Life SciencesWAG0014

APPENDIX 9 - continued Blood chemistry - individual observations during Week 4 of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Na K Cl Ca Phos Total Prot Alb A/G /Sex Number mmol/L mmol/L mmol/L mmol/L mmo l/L g/L g/L Ratio 1F 41 139 3.9 99 2.62 1.18 75 41 1.21

42 138 3.8 99 2.54 1.32 68 38 1.27 43 139 3.8 99 2.40 1.04 67 38 1.31 44 140 3.6 102 2.56 1.10 73 39 1.15 45 139 3.8 101 2.57 0.94 73 42 1.35 46 139 3.9 100 2.54 1.31 71 39 1.22 47 139 3.3 100 2.59 1.08 72 43 1.48 48 139 3.9 100 2.45 1.47 70 39 1.26 49 138 3.5 98 2.52 1.51 73 39 1.15 50 140 3.5 102 2.53 0.76 71 40 1.29 4F 91 140 3.4 101 2.44 1.16 68 36 1.13

92 139 3.4 101 2.49 1.30 72 41 1.32 93 140 4.0 102 2.42 1.07 70 40 1.33 94 140 3.7 102 2.44 1.15 69 38 1.23 95 138 3.8 99 2.32 1.47 62 35 1.30 96 142 3.5 103 2.33 0.97 68 40 1.43 97 141 3.6 103 2.31 1.13 64 38 1.46 98 139 5.4 104 2.35 1.27 68 36 1.13 99 140 4.5 104 2.40 0.93 67 40 1.48 100 1 40 3.6 102 2.41 1.02 66 38 1.36399Huntingdon Life SciencesWAG0014

APPENDIX 9 - continued Blood chemistry - individual observations sporadic sample Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene Exposure level (ppm) : 0 199 505 2876 Group Animal ALP ALT AST Bili Ur ea Creat Gluc Chol Trig /Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L 1F 27 86 27 196 1 11.51 24 16.14 2.01 1.75400Huntingdon Life SciencesWAG0014

APPENDIX 9 - c ontinued Blood chemistry - individual observations sporadic sample Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal N a K Cl Ca Phos Total Prot Alb A/G /Sex Number mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio 1F 27 132 5.5 92 2.60 2.16 53 31 1.41401Huntingdon Life SciencesWAG0014

APPENDIX 10 Ur inalysis - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal App Vol pH SG Gluc Keto Bili UBld /Sex Number mL g/L 1M 61 MY 6.4 7 .3 1044 NEG 1+ NEG NEG

62 MY 6.2 7.1 1042 NEG 2+ NEG NEG 63 MY 4.0 8.2 1047 NEG 2+ NEG NEG 64 PY 7.2 7.0 1036 NEG TRA NEG NEG 65 MY 7.2 8.0 1035 NEG 1+ NEG NEG 66 MY 6.2 7.2 1038 NEG 1+ NEG TRA 67 MY 4.4 7.7 1078 NEG 1+ 1+ NEG 68 PY 3.8 8.6 1 027 NEG 1+ NEG NEG 69 MY 5.0 8.5 1046 NEG 2+ NEG NEG 70 MY 2.4 6.2 1074 NEG 1+ 1+ NEG 2M 101 MY 6.2 7.3 1032 NEG 1+ NEG NEG

102 MY 4.4 6.7 1033 NEG 1+ NEG NEG 103 MY 7.0 7.3 1033 NEG 1+ NEG NEG 104 MY 5.0 6.5 1034 NEG 1+ NEG 2+ 105 PY 8.4 7.1 1025 NEG 1+ NEG TRA 106 MY 9.5 7.2 1028 NEG 1+ NEG TRA 107 MY 9.2 7.3 1031 NEG 1+ NEG NEG 108 PY 6.4 6.9 1025 NEG TRA NEG NEG 109 MY 6.2 7.1 1029 NEG 2+ NEG TRA 110 PY 15.0 6.8 1020 NEG 2+ NEG TRA402Huntingdon Life SciencesWAG0014

APPENDIX 10 - continued Ur inalysis - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal CA S A Leuc RBC Cryst Sperm Epi /Sex Number /LPF 1M 61 0 0 0 0 TNQ 7 0

62 0 0 0 0 1 7 0 63 0 0 0 0 TNQ TNQ 0 64 0 0 0 0 12 0 0 65 0 0 0 0 1 0 0 66 0 0 0 0 9 0 0 67 0 0 0 0 23 0 0 68 0 0 0 0 5 0 0 69 0 0 0 0 4 2 0 70 0 0 0 0 3 0 0 2M 101 0 0 0 0 13 22 0

102 0 0 0 0 1 0 0 103 0 0 0 0 5 0 0 104 0 0 0 0 2 TNQ 0 105 0 0 0 0 16 0 0 106 0 0 0 0 6 0 0 107 0 0 0 0 13 TNQ 0 108 0 0 0 0 9 11 0 109 0 0 0 0 TNQ 0 0 110 0 0 0 0 2 TNQ 0403Huntingdon Life SciencesWAG0014

APPENDIX 1 0 - continued Ur inalysis - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Gr oup Animal Prot TCLR TNAR TUKR /Sex Number g/L mmol mmol mmol 1M 61 1.18 0.736 0.608 1.501

62 1.36 0.360 0.279 1.324 63 1.46 0.388 0.452 0.944 64 0.93 0.864 0.727 1.429 65 0.94 0.850 0.576 1.447 66 1.03 0.397 0.298 1.392 67 1.22 0.810 0.642 1.404 68 0.82 0.217 0.125 0.665 69 1.18 0.580 0.480 1.475 70 1.19 0.190 0.089 0.761 2M 101 0.80 0.564 0.434 0.998

102 1.28 0.317 0.374 0.629 103 0.82 0.546 0.490 1.215 104 0.87 0.520 0.395 0.915 105 0.63 0.613 0.706 0.903 106 0.75 0.589 0.589 1.216 107 1.19 1.040 0.975 1.481 108 0.76 0.371 0.461 0.483 109 2.57 0.471 0.533 0.822 110 0.67 0.885 1.005 1.245404Huntingdon Life SciencesWAG0014

APPENDIX 10 - continued Ur inalysis - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal App Vol pH SG Gluc Keto Bili UBld /Sex Number mL g/L 3M 111 PY 8.8 7.0 1029 NEG 1+ NEG NEG

112 MY 6.0 6.5 1033 NEG 2+ NEG TRA 113 PY 10.0 7.2 1026 NEG 1+ NEG 3+ 114 PY 11.0 7.7 1021 NEG 1+ NEG NEG 115 PO 7.4 6.3 1032 NEG 1+ NEG TRA 116 PY 8.2 8.3 1023 NEG 1+ NEG TRA 117 PY 9.8 7.0 1025 NEG 1+ NEG TRA 118 PY 4.8 6.6 1029 NEG TRA NEG 1+ 119 PY 15.5 6.8 1022 NEG 1+ NEG 2+ 120 MY 7.2 7.5 1019 NEG 1+ NEG 2+ 4M 11 PY 6.0 6.6 1022 NEG TRA NEG NEG

12 PY 10.5 6.3 1030 NEG 1+ NEG 2+ 13 MY 10.5 6.3 1032 NEG 3+ NEG TRA 14 PO 7.0 6.5 1031 NEG 1+ 1+ NEG 15 MY 8.4 6.5 1030 NEG 3+ NEG 1+ 16 DO 2.6 7.2 1050 NEG 3+ NEG 1+ 17 MY 4.8 8.2 1062 NEG 1+ NEG TRA 18 PY 8.2 6.9 1023 NEG 1+ NEG NEG 19 MY 4.6 7.1 1044 NEG 3+ 1+ NEG 20 PY 10.5 6.0 1017 NEG 3+ NEG 1+405Huntingdon Life SciencesWAG0014

APPENDIX 10 - continued Ur inalysis - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal CAS A Leuc RBC Cryst Sperm Epi /Sex Number /LPF 3M 111 0 0 0 0 1 0 0

112 0 0 0 0 2 0 0 113 0 0 0 0 4 TNQ 0 114 0 0 0 0 0 3 0 115 0 0 0 0 5 9 0 116 0 0 0 0 1 0 0 117 0 0 0 0 0 2 0 118 0 0 0 0 0 0 0 119 0 0 0 0 0 1 0 120 0 0 0 0 TNQ TNQ 0 4M 11 0 0 0 0 2 0 0

12 0 0 0 0 2 0 0 13 0 0 0 0 1 0 0 14 0 0 0 0 1 0 0 15 0 0 0 0 1 11 0 16 0 0 0 0 3 2 0 17 0 0 0 0 0 0 0 18 0 0 0 0 1 0 0 19 0 0 0 0 TNQ 0 0 20 0 0 0 0 0 0 0406Huntingdon Life SciencesWAG0014

APPENDIX 10 - continued Ur inalysis - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Pr ot TCLR TNAR TUKR /Sex Number g/L mmol mmol mmol 3M 111 0.99 0.554 0.607 1.008

112 0.88 0.228 0.138 0.873 113 1.14 0.630 0.450 1.360 114 0.65 1.078 0.737 1.293 115 1.32 0.400 0.215 1.006 116 0.60 0.771 0.648 0.816 117 0.70 0.706 0.578 0.779 118 0.51 0.475 0.427 0.593 119 0.83 1.132 0.822 1.860 120 1.22 0.418 0.310 1.195 4M 11 0.14 0.660 0.444 0.585

12 0.48 0.725 0.977 0.662 13 0.63 1.166 1.061 1.229 14 1.15 0.658 0.427 0.903 15 1.24 0.748 0.798 0.895 16 1.15 0.25 5 0.226 0.475 17 0.65 0.389 0.202 0.542 18 0.56 0.804 0.746 0.754 19 1.01 0.391 0.373 0.683 20 0.88 0.966 0.830 1.470407Huntingdon Life SciencesWAG0014

APPENDIX 10 - continued Ur inalysis - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal App Vol pH SG Gluc Keto Bili UBld /Sex Number mL g/L 1F 21 PY 1.8 7.6 1040 NEG NEG NEG NEG

22 PY 1.4 6.0 1049 NEG TRA NEG NEG 23 MY 1.8 5.7 1064 NEG TRA NEG NEG 24 PY 1.4 6.5 1030 NEG NEG NEG NEG 25 MY 1.4 5.9 1076 NEG 1+ 1+ NEG 26 MY 3.0 6.3 1058 NEG TRA NEG NEG 28 PY 5.6 6.5 1029 NEG NEG NEG NEG 29 PY 3.6 6.4 1034 NEG NEG NEG NEG 30 PY 5.2 6.6 1033 NEG NEG NEG NEG 2F 51 PY 5.6 7.0 1026 NEG TRA NEG NEG

52 MY 2.8 6.3 1046 NEG TRA NEG NEG 53 PY 7.6 6.6 1026 NEG NEG NEG NEG 54 MY 2.2 6.7 1068 NEG 1+ 1+ NEG 55 PY 7.0 6.5 1030 NEG TRA NEG NEG 56 MY 1. 6 6.3 1072 NEG 1+ 1+ NEG 57 PY 4.8 6.8 1028 NEG TRA NEG NEG 58 MY 3.2 6.0 1043 NEG NEG NEG NEG 59 MY 2.4 6.2 1066 NEG TRA 1+ NEG 60 MY 4.2 6.3 1033 NEG TRA NEG NEG408Huntingdon Life SciencesWAG0014

APPENDIX 10 - continued Ur inalysis - individual observations durin g Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal CAS A Leuc RBC Cryst Sperm Epi /Sex Number /LPF 1F 21 0 0 0 0 1 0 0

22 INS INS INS INS INS INS INS 23 0 0 0 0 0 0 0 24 INS INS INS INS INS INS INS 25 INS INS INS INS INS INS INS 26 0 0 0 0 0 0 0 28 0 0 0 0 0 0 0 29 0 0 0 0 0 0 0 30 0 0 0 0 0 0 0 2F 51 0 0 0 0 1 0 0

52 0 0 0 0 0 0 0 53 0 0 0 0 1 0 0 54 0 0 0 0 TNQ 0 0 55 0 0 0 0 0 0 0 56 INS INS INS INS INS INS INS 57 0 0 0 0 7 0 0 58 0 0 0 0 1 0 0 59 0 0 0 0 2 0 0 60 0 0 0 0 1 0 0409Huntingdon Life SciencesWAG0014

APPENDIX 10 - continued Ur inalysis - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Prot TCLR TNAR TUKR /Sex Number g/L mmol mmol mmol 1F 21 0.18 0.085 0.205 0.391

22 0.28 0.176 0.165 0.240 23 0.32 0.191 0.148 0.327 24 0.18 0.034 0.070 0.190 25 0.40 0.217 0.217 0.391 26 0.27 0.177 0.333 0.726 28 0.21 0.414 0.414 0.728 29 0.22 0.313 0.349 0.43 6 30 0.15 0.255 0.265 0.907 2F 51 0.09 0.213 0.347 0.596

52 0.24 0.188 0.151 0.500 53 0.10 0.471 0.372 0.840 54 0.17 0.163 0.156 0.712 55 0.09 0.315 0.686 0.725 56 0.40 0.230 0.184 0.325 57 0.09 0.456 0.451 0.586 58 0.26 0.429 0.291 0.630 59 0.22 0.108 0.185 0.544 60 0.15 0.168 0.122 0.617410Huntingdon Life SciencesWAG0014

APPENDIX 10 - continued Ur inalysis - individual observations during Week 13 of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal App Vol pH SG Gluc Keto Bili UBld /Sex Number mL g/L 3F 1 PY 6.6 6.0 1030 NEG 1+ NEG TRA

2 PY 1.2 5.9 1032 NEG TRA NEG NEG 3 PY 4.8 6.9 10 32 NEG 2+ NEG NEG 4 PY 7.8 5.8 1024 NEG 1+ NEG NEG 5 PY 7.6 6.8 1025 NEG TRA NEG NEG 6 MY 3.6 6.0 1039 NEG 1+ NEG TRA 7 MY 4.8 6.5 1035 NEG 1+ NEG NEG 8 MY 2.6 6.7 1036 NEG 1+ NEG NEG 9 MY 6.2 5.9 1033 NEG 1+ NEG TRA 10 MY 4.6 6.5 1034 NEG 1+ NEG NEG 4F 31 PY 5.8 5.8 1021 NEG 2+ NEG NEG

32 PY 0.6 INS 1050 NEG 2+ NEG NEG 33 PY 6.8 5.5 1032 NEG 2+ NEG NEG 34 MY 5.4 6.9 1029 NEG 2+ NEG NEG 35 DY 2.4 6.4 1044 NEG 3+ NEG NEG 36 MY 7.0 6.0 1030 NEG 2+ NEG NEG 37 PY 4.8 6.1 10 26 NEG 2+ NEG TRA 38 PY 6.0 5.7 1027 NEG 2+ NEG NEG 39 MY 2.2 5.8 1066 NEG 3+ NEG NEG 40 MY 4.2 5.5 1034 NEG 3+ NEG NEG411Huntingdon Life SciencesWAG0014

APPENDIX 10 - continued Ur inalysis - individual observations during Week 13 of treatment Group : 1 2 3 4 Comp ound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal CAS A Leuc RBC Cryst Sperm Epi /Sex Number /LPF 3F 1 0 0 0 0 0 0 0

2 INS INS INS INS INS INS INS 3 0 0 0 0 0 0 0 4 0 0 0 0 0 0 0 5 0 0 0 0 1 0 0 6 0 0 0 0 0 0 0 7 0 0 0 0 2 0 0 8 0 0 0 0 0 0 0 9 0 0 0 0 0 0 0 10 0 0 0 0 1 0 0 4F 31 0 0 0 0 0 0 0

32 INS INS INS INS INS INS INS 33 0 0 0 0 0 0 0 34 0 0 0 0 0 0 0 35 0 0 0 0 0 0 0 36 0 0 0 0 0 0 0 37 0 0 0 0 0 0 0 38 0 0 0 0 0 0 0 39 0 0 0 0 TNQ 0 0 40 0 0 0 0 0 0 0412Huntingdon Life SciencesWAG0014

APPENDIX 10 - continued Ur inalysis - individual observations during Week 13 of treatment Group : 1 2 3 4 C ompound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group Animal Prot TCLR TNAR TUKR /Sex Number g/L mmol mmol mmol 3F 1 0.11 0.680 0.601 0.832

2 0.20 0.065 0.096 0.110 3 0.11 0.278 0.413 0.545 4 0.10 0.577 0.484 0.527 5 0.10 0.426 0.494 0.688 6 0.23 0.076 0.083 0.641 7 0.15 0.437 0.307 0.521 8 0.15 0.286 0.208 0.309 9 0.13 0.415 0.453 0.843 10 0.16 0.511 0.543 0.474 4F 31 0 .55 0.319 0.168 0.328

32 INS INS INS INS 33 0.10 0.707 0.435 0.887 34 0.11 0.594 0.416 0.413 35 0.17 0.382 0.146 0.383 36 0.16 0.903 0.686 0.784 37 0.09 0.384 0.216 0.192 38 0.17 0.552 0.336 0.495 39 0.27 0.130 0.081 0.216 40 0.18 0.525 0 .256 0.321413Huntingdon Life SciencesWAG0014

APPENDIX 11 Request ID: 289241 Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Number Terminal Bodyweight Adrenals Br ain Epididymides Heart Kidneys Liver Lungs + Br onchi Pituitary Prostate 1M 61 631 0.052 2.159 1.812 2.085 3.556 21.287 1. 764 0.011 1.212 62 580 0.055 2.101 1.533 1.984 3.469 20.036 1.921 0.019 1.225 63 627 0.061 2.256 1.637 1.883 3.462 21.249 1.851 0.013 1.143 64 649 0.072 2.197 1.394 2.037 3.766 21.404 1.778 0.022 1.470 65 574 0.062 2.110 1.483 2.168 3.483 20.323 1. 530 0.013 1.048 66 691 0.059 2.102 1.395 1.680 3.509 23.517 1.988 0.013 1.358 67 575 0.045 2.086 1.584 1.587 3.336 17.945 1.909 0.012 1.203 68 533 0.049 2.045 1.423 1.457 2.859 18.173 1.527 0.012 1.145 69 596 0.041 2.019 1.392 1.649 3.019 20.920 1. 746 0.011 0.947 70 555 0.065 2.059 1.565 1.518 3.288 18.717 1.596 0.014 1.704 2M 101 574 0.044 2.085 1.312 1.574 3.499 21.994 1.877 0.015 1.306 102 463 0.043 2.166 1.440 1.611 2.760 18.184 1.669 0.012 0.819 103 585 0.066 2.052 1.358 1.6 09 3.515 21.784 1.801 0.012 1.241 104 519 0.049 2.099 1.361 1.543 2.967 17.557 1.537 0.017 1.099 105 521 0.052 2.112 1.394 1.555 2.759 15.705 1.652 0.014 1.012 106 537 0.045 1.985 1.283 1.741 2.754 16.189 1.470 0.008 1.361 107 500 0.037 2.071 1.297 1.510 2.552 13.760 1.474 0.008 0.920 108 543 0.040 2.210 1.463 2.164 3.087 18.005 1.835 0.011 0.923 109 449 0.048 2.108 1.208 1.893 2.512 14.650 1.513 0.008 1.000 110 508 0.039 1.947 1.438 1.557 2.830 15.648 1.720 0.010 0.845414Huntingdon Life SciencesWAG0014

APPENDIX 11 - continued Request ID: 289241 Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -tri fluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Number Salivary

Glands Seminal

Vesicles Spleen Testes Thy mus Thy

ro ids + Paras 1M 61 0.784 2.002 1.036 3.824 0.276 0.032 62 0.753 2.098 0.981 4.197 0.272 0.021 63 0.791 1 .715 0.908 4.290 0.258 0.018 64 0.759 2.177 0.833 3.691 0.284 0.031 65 0.769 1.804 0.956 3.572 0.323 0.031 66 0.793 2.003 1.099 3.849 0.438 0.023 67 0.579 2.332 0.978 4.124 0.326 0.026 68 0.653 2.143 0.760 4.017 0.228 0.021 69 0.701 2.241 0.914 3.476 0.175 0.029 70 0.657 2.157 1.008 3.943 0.221 0.021 2M 101 0.600 1.879 0.876 3.375 0.304 0.019 102 0.499 2.245 0.828 3.407 0.248 0.029 103 0.605 1.079 1.086 3.771 0.412 0.031 104 0.623 2.124 0.726 3.204 0.258 0.026 105 0.564 1.666 0.916 3.748 0.171 0.029 106 0.503 1.943 0.726 3.497 0.282 0.023 107 0.657 1.413 0.689 3.324 0.184 0.016 108 0.692 1.914 1.072 4.210 0.185 0.026 109 0.541 1.050 0.706 3.911 0.266 0.018 110 0.594 1.794 1.045 3.685 0.240 0.033415Huntingdon Life SciencesWAG0014

APP ENDIX 11 - continued Request ID: 289241 Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Number Terminal Bodyweight Adrenals Br ain Epididymides Heart Kidneys Liver Lungs + Br onchi Pituitary Prostate 3M 111 578 0.051 2.098 1.528 1.664 2.939 19.625 1.665 0.014 0. 833 112 460 0.036 1.920 1.160 1.322 2.756 14.903 1.394 0.011 0.999 113 537 0.056 2.021 1.403 1.991 2.897 18.137 1.965 0.015 1.037 114 493 0.055 1.981 1.370 1.492 2.536 15.675 1.620 0.015 1.068 115 472 0.051 2.063 1.422 1.597 3.012 17.853 1.454 0.01 3 0.984 116 457 0.038 2.004 1.168 1.152 2.767 13.777 1.561 0.009 0.739 117 429 0.041 2.012 1.121 1.278 2.311 13.829 1.558 0.007 0.789 118 457 0.041 2.096 1.243 1.383 2.677 13.232 1.641 0.009 0.694 119 499 0.059 1.981 1.303 1.527 2.837 15.636 1.696 0.014 0.665 120 585 0.039 2.170 1.202 1.770 3.077 20.438 1.881 0.011 1.054 4M 11 380 0.038 1.887 1.006 1.279 2.169 12.431 1.485 0.013 0.552

12 428 0.049 2.008 1.370 1.299 2.357 14.366 1.548 0.013 0.861 13 446 0.056 2.036 1.277 1.589 2.9 30 17.110 1.705 0.010 0.919 14 450 0.039 2.049 1.221 1.324 2.582 15.179 1.500 0.012 1.106 15 451 0.042 1.952 1.210 1.293 2.348 15.185 1.500 0.016 0.842 16 362 0.042 1.754 0.945 1.440 2.132 11.720 1.431 0.008 0.610 17 419 0.039 1.926 1.363 1.600 2.3 49 12.868 1.446 0.007 1.172 18 421 0.042 1.967 1.015 1.355 2.594 15.614 1.476 0.008 0.643 19 380 0.034 1.915 1.069 1.257 2.040 12.474 1.368 0.008 0.758 20 433 0.055 1.904 1.308 1.727 2.255 15.165 1.598 0.012 0.862416Huntingdon Life SciencesWAG0014

APPENDIX 11 - continued Request ID: 289241 Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Number Salivary

Glands Seminal

Vesicles Spleen Testes Thy mus Thy

ro ids + Paras 3M 111 0.586 1.291 1.052 4.302 0.320 0.032 112 0.547 1.199 0.684 2.980 0.302 0.016 113 0.557 1.856 0.715 4.015 0.185 0.017 114 0.636 1.471 1.080 4.082 0.210 0.035 115 0.575 1.672 0.977 3.884 0.126 0.023 116 0.666 1.557 0.840 3.211 0.167 0.030 117 0.453 1.048 0.654 3.423 0.130 0.018 118 0.500 1.134 0.840 3.464 0.246 0.019 119 0.557 1.611 0.988 3.75 3 0.201 0.026 120 0.724 1.686 1.068 3.330 0.315 0.031 4M 11 0.399 1.293 0.761 2.808 0.139 0.024

12 0.539 1.347 0.811 3.645 0.100 0.016 13 0.483 1.267 0.764 3.363 0.110 0.038 14 0.516 1.829 0.623 2.919 0.128 0.019 15 0.445 1.247 0.688 3. 455 0.121 0.023 16 0.612 0.582 0.532 2.892 0.097 0.028 17 0.607 1.486 0.621 3.656 0.091 0.012 18 0.409 1.122 0.788 3.118 0.114 0.029 19 0.503 1.016 0.623 3.096 0.135 0.019 20 0.651 1.602 0.736 3.428 0.074 0.022417Huntingdon Life SciencesWAG0014

APPENDIX 11 - continued Request ID: 289241 Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Number Terminal Bodyweight Adrenals Br ain Heart Kidneys Liver Lungs + Br onchi Ovaries Pituitary Salivary Glands 1F 21 316 0.070 2.098 1.067 1.805 10.947 1.293 0.091 0.017 0.474 22 271 0.046 1.984 0.913 1.798 8.691 1.129 0.103 0.020 0.384 23 271 0.073 1.896 1.171 1.730 10.024 1.257 0.093 0.020 0.432 24 318 0.062 1.946 1.204 1.657 9.619 1.339 0.100 0.019 0.473 25 277 0.061 1.921 1.062 2.123 9.143 1.172 0.111 0.020 0.475 26 326 0.0 41 1.960 1.342 1.647 11.007 1.292 0.079 0.013 0.454 28 337 0.062 1.934 1.027 1.750 11.205 1.314 0.108 0.017 0.503 29 300 0.059 1.900 1.034 1.581 8.513 1.207 0.099 0.014 0.395 30 307 0.058 1.947 1.309 1.688 8.228 1.157 0.078 0.015 0.444 2F 51 293 0.063 1.845 1.081 1.989 8.800 1.219 0.089 0.020 0.366 52 287 0.053 2.049 1.194 1.698 9.442 1.124 0.060 0.021 0.346 53 297 0.064 1.887 1.045 1.700 10.402 1.171 0.104 0.016 0.321 54 278 0.065 1.810 0.992 2.016 9.912 1.322 0.075 0.017 0.430 55 285 0.065 1.896 1.087 1.796 11.760 1.082 0.072 0.018 0.412 56 315 0.065 1.956 0.956 1.924 10.121 1.272 0.104 0.016 0.364 57 296 0.076 1.865 1.137 1.783 11.572 1.341 0.096 0.015 0.364 58 306 0.064 1.855 1.023 1.926 10.830 1.243 0.062 0.013 0.316 59 320 0.080 1.810 1.110 2.039 12.382 1.354 0.096 0.012 0.364 60 288 0.064 1.754 1.055 1.541 10.809 1.145 0.073 0.015 0.352418Huntingdon Life SciencesWAG0014

APPENDIX 11 - continued Request ID: 289241 Organ weights - individual absolute values (g) for animals kill ed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Number Spleen Thy mus Thy

ro ids + Paras Uterus +

Cervix 1F 21 0.638 0.168 0.023 1.319 22 0.502 0.172 0.021 0.585 23 0.623 0.251 0.015 0.636 24 0.600 0.273 0.025 1.189 25 0.558 0.208 0.008 0.703 26 0.718 0.271 0.020 0.515 28 0.852 0.293 0.018 0.659 29 0.637 0.199 0.009 0. 555 30 0.422 0.230 0.014 0.606 2F 51 0.628 0.190 0.025 0.693 52 0.490 0.129 0.016 0.730 53 0.432 0.168 0.017 1.125 54 0.423 0.136 0.020 0.779 55 0.608 0.227 0.027 0.665 56 0.591 0.287 0.027 0.835 57 0.563 0.265 0.024 0.690 58 0.539 0.250 0.025 0.484 59 0.554 0.148 0.019 0.949 60 0.564 0.165 0.030 0.702419Huntingdon Life SciencesWAG0014

APPENDIX 11 - continued Request ID: 289241 Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Number Terminal Bodyweight Adrenals Br ain Heart Kidneys Liver Lungs + Br onchi Ovaries Pituitary Salivary Glands 3F 1 294 0.059 1.857 1.049 1.979 10.039 1.493 0.096 0.017 0.327

2 297 0.057 1.836 1.013 2.032 10.858 1.263 0.049 0.018 0.348 3 233 0.056 1.761 0.825 1.600 7.227 1.129 0.071 0.015 0.399 4 298 0.051 1.936 1.026 2.046 9.512 1.331 0.078 0.015 0.338 5 294 0.059 1.897 1.025 1.987 10.084 1.324 0.071 0.017 0.294 6 304 0.064 1.921 1.016 1.878 10.960 1.230 0.061 0.019 0.443 7 257 0.058 1.931 0.871 1.761 8.849 1.104 0.130 0.013 0.339 8 291 0.060 1.813 1.067 1.695 9.265 1.183 0.075 0.012 0.406 9 271 0.054 1.733 0.925 1.870 9.936 1.313 0.083 0.011 0.328 10 291 0.050 1.916 0.864 1.667 10.050 1.405 0.088 0.010 0.373 4F 31 211 0.034 1.575 1.062 1.595 7.823 1.060 0.042 0.009 0.360 32 205 0.032 1.585 1.191 1 .585 9.220 1.155 0.071 0.009 0.301 33 293 0.071 1.884 1.009 2.053 11.395 1.316 0.085 0.019 0.416 34 269 0.050 1.797 0.997 1.612 9.251 1.143 0.084 0.014 0.334 35 259 0.055 1.808 0.983 1.779 9.967 1.307 0.103 0.011 0.380 36 265 0.047 1.757 1.124 1.74 4 8.992 1.301 0.108 0.010 0.362 37 249 0.062 1.759 1.191 1.788 9.805 1.284 0.074 0.011 0.237 38 247 0.056 1.729 0.997 1.561 8.927 1.429 0.075 0.010 0.344 39 282 0.064 1.921 0.965 1.653 10.898 1.305 0.090 0.010 0.440 40 262 0.060 1.897 0.949 1.874 1 0.108 1.266 0.076 0.011 0.362420Huntingdon Life SciencesWAG0014

APPENDIX 11 - continued Request ID: 289241 Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoroprop ene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Number Spleen Thy mus Thy

ro ids + Paras Uterus +

Cervix 3F 1 0.548 0.208 0.022 0.595

2 0.596 0.225 0.024 0.654 3 0.368 0. 131 0.019 0.534 4 0.542 0.185 0.012 0.519 5 0.684 0.162 0.021 0.897 6 0.625 0.243 0.022 1.020 7 0.452 0.138 0.011 0.641 8 0.619 0.153 0.016 0.875 9 0.471 0.085 0.019 1.211 10 0.478 0.138 0.018 0.460 4F 31 0.509 0.047 0.009 0.705 32 0.814 0.015 0.016 0.232 33 0.558 0.115 0.027 1.449 34 0.378 0.116 0.025 0.463 35 1.268 0.109 0.022 0.549 36 0.881 0.087 0.021 0.481 37 0.707 0.049 0.022 0.434 38 0.610 0.079 0.026 0.584 39 0.586 0.100 0.017 0.506 40 0.673 0.056 0.020 0.558421Huntingdon Life SciencesWAG0014

APPENDIX 11 - continued Request ID: 289499 Organ weights - individual absolute values (g) for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Number Terminal Bodyweight Adrenals Br ain Epididymides Heart Kidneys Liver Lungs + Br onchi Pituitary Prostate 1M 81 632 0.061 2.082 1.437 1.678 3.883 25.4 93 1.985 0.011 1.071 82 609 0.078 2.214 1.501 2.164 3.192 17.177 1.893 0.013 1.577 83 647 0.073 2.215 1.818 1.717 3.641 24.667 1.722 0.018 1.375 84 625 0.054 2.062 1.664 1.728 3.448 19.070 1.890 0.012 1.160 85 706 0.035 2.167 1.775 2.176 2.759 16.9 07 1.752 0.014 1.398 86 629 0.058 2.335 1.663 1.687 3.757 22.550 1.811 0.016 1.316 87 555 0.071 2.140 1.394 1.607 3.044 21.133 1.674 0.017 1.296 88 608 0.055 1.993 1.403 1.488 2.870 21.126 1.708 0.015 1.074 89 755 0.055 2.209 1.945 2.387 3.589 22.0 09 1.921 0.025 1.127 90 465 0.062 1.954 1.377 1.274 2.633 13.874 1.444 0.012 1.164 4M 71 490 0.054 2.006 1.326 1.804 2.906 16.147 1.690 0.011 1.401 72 559 0.048 2.056 1.331 2.254 2.953 17.961 1.867 0.012 1.217 73 433 0.063 1.964 1.230 1 .573 2.305 14.771 1.487 0.007 0.959 74 491 0.053 2.082 1.394 1.472 2.655 14.370 1.586 0.013 1.474 75 544 0.052 1.986 1.168 1.852 2.606 18.998 1.571 0.017 0.832 76 532 0.039 2.032 1.634 1.699 2.925 18.133 1.887 0.011 1.357 77 466 0.042 1.998 1.284 1 .331 2.645 15.519 1.523 0.009 1.910 78 476 0.065 2.168 1.220 1.752 2.502 15.193 1.522 0.005 1.064 79 408 0.045 1.756 1.359 1.529 2.241 15.582 1.340 0.010 0.884 80 422 0.069 1.887 1.253 1.443 2.481 15.314 1.444 0.010 1.170422Huntingdon Life SciencesWAG0014

APPENDIX 11 - continued Request ID: 289499 Organ weights - individual absolute values (g) for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Group /Sex Animal Number Salivary

Glands Seminal

Vesicles Spleen Testes Thy mus Thy

ro ids + Paras 1M 81 0.765 2.454 0.749 3.681 0.180 0.030 82 0.819 1.649 0.872 3.928 0.253 0.022 83 0.822 2.249 1. 040 4.244 0.386 0.024 84 0.759 1.966 0.980 3.928 0.164 0.033 85 0.862 1.398 0.723 4.106 0.247 0.033 86 0.839 2.531 1.280 4.090 0.139 0.020 87 0.754 1.966 0.796 3.635 0.237 0.032 88 0.716 1.952 0.867 3.342 0.182 0.023 89 0.870 2.275 1.220 4.160 0.332 0.040 90 0.570 1.791 0.511 3.309 0.184 0.019 4M 71 0.542 2.084 0.921 3.718 0.214 0.024 72 0.650 1.837 0.939 3.924 0.161 0.030 73 0.640 1.815 0.756 3.570 0.071 0.021 74 0.588 1.878 0.777 3.981 0.155 0.026 75 0.728 2.058 0.680 3.400 0.235 0.027 76 0.655 2.053 0.980 4.771 0.147 0.020 77 0.631 2.028 0.871 3.713 0.168 0.024 78 0.673 1.167 0.941 3.584 0.169 0.030 79 0.664 1.938 1.152 3.686 0.160 0.021 80 0.441 1.529 0.889 3.466 0.155 0.028423Huntingdon Life SciencesWAG0014

APPENDIX 11 - continued Request ID: 289499 Organ weights - individual absolute values (g) for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposur e level (ppm) : 0 199 505 2876 Group /Sex Animal Number Terminal Bodyweight Adrenals Br ain Heart Kidneys Liver Lungs + Br onchi Ovaries Pituitary Salivary Glands 1F 41 306 0.057 1.854 1.054 1.655 8.641 1.145 0.073 0.013 0.467 42 329 0.061 1.953 1.305 1.872 8.009 1.323 0.072 0.016 0.460 43 301 0.063 1.900 1.035 1.981 8.588 1.171 0.088 0.014 0.448 44 350 0.114 2.090 1.420 2.319 11.281 1.424 0.219 0.020 0.449 45 293 0.055 1.833 0.981 1.730 8.651 1.240 0.078 0.017 0.411 46 325 0.051 1.8 56 0.916 1.983 9.267 1.189 0.073 0.022 0.451 47 335 0.047 1.803 1.148 1.718 10.058 1.147 0.064 0.017 0.420 48 303 0.054 2.026 0.933 1.656 8.240 1.237 0.080 0.016 0.458 49 301 0.087 1.957 1.011 1.884 10.860 1.352 0.091 0.021 0.416 50 280 0.060 1.835 0.852 1.782 9.870 1.192 0.084 0.014 0.422 4F 91 281 0.075 1.772 1.320 1.726 9.451 1.231 0.104 0.013 0.418 92 237 0.054 1.758 1.115 1.571 7.935 1.102 0.040 0.012 0.408 93 261 0.050 1.834 1.007 1.925 7.942 1.242 0.062 0.015 0.414 94 253 0.049 1.936 1.426 1.608 7.161 1.300 0.084 0.013 0.499 95 298 0.069 1.918 1.258 1.729 8.820 1.407 0.125 0.015 0.493 96 261 0.052 1.720 1.105 1.820 8.246 1.114 0.070 0.016 0.397 97 251 0.056 1.682 1.030 1.462 7.461 1.057 0.118 0.014 0.390 98 253 0.06 3 1.725 1.039 1.741 9.227 1.357 0.080 0.016 0.420 99 289 0.052 1.895 1.102 1.863 8.494 1.240 0.917 0.015 0.515 100 263 0.064 1.878 0.927 2.070 9.552 1.167 0.099 0.015 0.442424Huntingdon Life SciencesWAG0014

APPENDIX 11 - continued Request ID: 289499 Organ weight s - individual absolute values (g) for animals killed after 4 weeks of recover y Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Grou p /Sex Animal Number Spleen Thy mus Thy

ro ids + Paras Uterus +

Cervix 1F 41 0.449 0.121 0.017 1.220 42 0.593 0.205 0.018 0.582 43 0.548 0.103 0.020 0.780 44 0.691 0.170 0.019 0.824 45 0.487 0.159 0.021 0.522 46 0.570 0.161 0.024 1.051 47 0.500 0.141 0.033 0.670 48 0.553 0.143 0.024 1.387 49 0.564 0.160 0.021 1.151 50 0.535 0.186 0.017 0.541 4F 91 0.487 0.198 0.016 0.679 92 0.443 0.231 0.032 0.754 93 0.531 0.156 0.025 0.667 94 0.497 0.136 0.023 0.636 95 0.651 0.146 0.0 16 0.662 96 0.513 0.199 0.026 0.689 97 0.463 0.149 0.027 0.647 98 0.529 0.218 0.024 0.661 99 1.058 0.165 0.022 0.683 100 0.489 0.185 0.025 0.729425Huntingdon Life SciencesWAG0014

APPENDIX 12 Request ID: 313014 Macropathology and histopathology - individual fin dings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 61 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status : Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 630.6 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Kidneys Kidneys Pelvic dilatation, Left, Slight No significant lesions Lungs + Bronchi Arterial Mural Mineralisation, Minimal Thy ro ids Follicular Cell Vacuolation, Bilat eral, Slight The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileu m, Jejunum, LN Bronchial, LN Mandibular, LN Mesenteric, Lachrymal Glands, Larynx, Liver, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Pancreas, Pa rathy ro ids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesi cles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Testes, Thymus, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder426Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 62 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 580.0 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Kidneys Cortical Tubular Basophilia, Focal, Slight LN Mandibular Plasmacytosis, Moderate Liver Inflammation, Focal, Minimal Lungs + Bronchi Lungs + Bronchi Pale area(s), Left, Punctate, One, subpleural. Arterial Mural Mineralisation, Minimal Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileu m, Jejunum, LN Bronchial, LN Mesenteric, Lachrymal Glan ds, Larynx, Mammary, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rect um, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spl een, Sternum + Marrow, Stomach, Teeth, Testes, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder427Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Con trol 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 63 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 626.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Adrenals Cortical Vacuolation, Bilateral, Minimal LN Mandibular Plasmacytosis, Slight Sinus Histiocytosis, Slight Lachry mal Glands Lymphoid Aggregates, Focal, Minimal Liver Inflammation, Focal, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal Aggregations of Alveolar Macrophages, Minimal428Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 63 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final pha se sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 626.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Nasolacrimal Duct - Inflammation, Slight Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight Nasolacrimal Duct Epithelial Degeneration, Slig ht Prostate Lymphoid Aggregates, Focal, Minimal Spleen Spleen Capsule thickened Capsular Thickening, Slight Thy ro ids Follicular Cell Vacuolation, Bilateral, Slight The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum , Kidneys, LN Bronchial, LN Mesenteric, Larynx, Mammary, Oesoph agus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Teeth, Testes , Thy mus, To ngue, Trachea, Tracheal Bifurc., Urinary Bladder429Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 64 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 648.8 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** LN Mandibular Sinus Histiocytosis, Minimal Lungs + Bronchi Alveolitis, Minimal Mammary Acinar Atrophy, Slight Nasal turbinates Nasolacrimal Duct - Inflammation, Slight Nasopharynx - Goblet Cell Hyperplasia, Slight Prostate Lymphoid Aggregates, Focal, Slight The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididy mides, Ey

es, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, Kidneys, LN Br onchial, LN Mesenteric, Lachrymal Glands, Larynx, Liver, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands , Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Testes, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder430Huntingdon Life SciencesWAG0014

APPENDIX 12 - continue d Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Anima l Number: 65 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 574.3 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Adrenals Cortical Vacuolation, Bilateral, Minimal Eyes Retinal Ro settes/Folds, Unilateral, Minimal Femur inc. Joint Syn ovitis, Minimal LN Mandibular Plasmacytosis, Slight Lungs + Bronchi Alveolitis, Minimal Per ivascular Inflammatory Cells, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Nasolacrimal Duct - Inflammation, Slight431Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 65 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 574.3 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Prostate Lymphoid Aggregates, Focal, Minimal The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididy mides, Harderian Glands, Heart, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Lachrymal Glands, Liver, Mammary, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Sal ivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Testes, Thymus, Thy ro ids, To ngue, Trachea, Tracheal Bifurc., Urinary Bladder432Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 31301 4 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 66 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 690.8 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Adrenals Cortical Vacuolation, Bilateral, Minimal Heart Infiltrate, Cellular, Myocar dium, Minimal LN Mandibular Plasmacytosis, Moderate Lungs + Bronchi Arterial Mural Mineralisation, Minimal Per ivascular Inflammatory Cells, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slig ht Prostate Lymphoid Aggregates, Focal, Minimal Stomach Submucosal Inflammation - Glandular Region, Minimal433Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 66 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase s acrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 690.8 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Thy ro ids Follicular Cell Vacuolation, Bilateral, Slight The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Lachrymal Glands, Liver, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G ., Peyer's Pa tch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Tho r., Spleen, Sternum + Marrow, Teeth, Testes, Thymus, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder434Huntingdon Life SciencesWAG0014

AP PENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 67 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 575.1 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLO GY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Kidneys Per ivascular Lymphoid Aggregations, Focal, Minimal LN Bronchial Par acortex - Increased Cellularity, Slight LN Mandibular Plasmacytosis, Marked Liver Inflammation, Focal, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Fore ign Body Reaction - Ventral Pouch, Focal, Slight The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, LN Mesenteric, Lachry mal Glands, Lungs + Bronchi, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, Sem inal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Testes, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder435Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 68 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 532.8 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Adrenals Cortical Vacuolation, Bilateral, Minimal LN Mandibular Sinus Histiocytosis, Minimal Liver Liver Dark area(s), Media

n lobe, One, subcapsular, 2mm. Inflammation, Focal, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal Prostate Lymphoid Aggregates, Focal, Moderate The following examined tissues had no gross obs ervations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum , Kidneys, LN Bronchial, LN Mesenteric, Lachrymal Glands, Larynx, Mammary, Nasa l turbinates, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Tho r., Spleen, Sternum + Ma rrow, Stomach, Teeth, Testes, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder436Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3, 3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 69 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 595.8 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Adrenals Cortical Vacuolation, Bilateral, Slight Heart Infiltrate, Cellular, Myocardium, Minimal LN Bronchial Tissue missing LN Mandibular Plasmacytosis, Slight Liver Inflammation, Focal, Minimal Lungs + Bronchi Per ivascular Inflammatory Cells, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Nasolacrimal Duct - Inflammation, Slight437Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 69 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 595.8 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal Thy ro ids Follicular Cell Vacuolation, Bilateral, Slight The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Mesenteric, Lachrymal Glands, Mammary, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Testes, Thymus, Tongue, Trachea, Urinary Bladder438Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual f indings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 70 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 555.4 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Adrenals Cortical Vacuolation, Slight Heart Infiltrate, Cellular, Myocardium, Minimal Kidneys Per ivascular Lymphoid Aggr egations, Focal, Minimal Liver Inflammation, Focal, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Mammary Acinar Atrophy, Slight Nasal turbinates Nasolacrimal Duct - Inflammation , Minimal Nasolacrimal Duct Epithelial Degeneration, Slight439Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3 ,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 70 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 555.4 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Prostate Lymphoid Aggregates, Focal, Slight Rectum Submucosal Oedema, Slight The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides , Ey es, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Bronchial, LN Mandibular, LN Mesenteric, Lachrymal Glands, Lungs + Bronchi, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Salivary Glands, Sciatic Ne

rve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Testes, Thy mus, Thy ro ids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder440Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID : 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 8 1 Sex: Male Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 632.0 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Infiltrate, Cellular, Myocardium, Minimal Liver Inflammation, Focal, Minimal Lungs + Bronchi Lungs + Bronchi Dark area(s), A few, subpleural, up to 3mm. Arterial Mural Mineralisation, Slight Aggregations of Alveolar Macrophages, Slight Alveolitis, Slight Skin Hair loss, Cranial region Tracheal Bifurc. Inf lammatory Cells in Lamina Propria, Minimal Trachea Inflammation, Slight The following examined tissues had no gross observations and no findings microscopically: Larynx, Nasal turbinates, Pancreas, Spleen, Teeth, Thymus441Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 82 Sex: Male Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 609.1 g PATHOLOGY OBSERVATIONS MACROPATHOL OGY HISTOPATHO LOGY Heart Infiltrate, Cellular, Myocardium, Minimal Lungs + Bronchi Alveolar Eosinophilic Crystals, Slight Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal Nasolacrimal Duct - Inflammation, Slight Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight Inflammatory Exudate in Airways, Minimal Preputial glands Preputial glands Distended Abscessation, Moderate The following examined tissues had no gross observations and no findings microscopically: Larynx, Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.442Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 83 Sex: Male Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweigh t: 646.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Heart Infiltrate, Cellular, Myocardium, Minimal Lungs + Bronchi Per ivascular Inflammatory Cells, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Minimal The following examined tissues had no gross observations and no findings microscopically: Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.443Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macr opathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 84 Sex: Male Do se Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 624.6 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Heart Inflammation, Chronic, Moderate Lungs + Bronchi Arterial Mural Mineralisation, Minimal Alveolitis, Minimal Alveolar Eosinophilic Crystals, Minimal Nasal turbinates Respiratory Epithelium - Goblet Cell Hyperplasia, Slight The following examined tissues had no gross observations and no findings micro scopically: Larynx, Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.444Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -tr ifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 85 Sex: Male Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Deat h: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 705.5 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Infilt

rate, Cellular, Myocardium, Minimal Liver Inflammation, Focal, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal Nasal turbinates Respiratory Epithelium - Goblet Cell Hyperplasia, Slight Nasolacrimal Duct - Inflammation, Minimal Nasopharynx - Goblet Cell Hyperplasia, Slight Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Slight Skin Hair loss, Forelimb(s), diffuse. Tracheal B ifurc. Inflammatory Cells in Lamina Propria, Minimal445Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -tr ifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 85 Sex: Male Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup : 1 Terminal Bodyweight: 705.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Trachea Infl ammatio

n, Slight The following examined tissues had no gross observations and no findings microscopically: Larynx, Pancreas, Spleen, Teeth, Thymus446Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - indivi dual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 86 Sex: Male Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 628.7 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lungs + Bronchi Per ivascular Inflammatory Cells, Minimal Nasal turbinates Nasolacrimal Duct - Inflammation, Minimal Skin Hair loss, Side(s) of face Trachea Inflammation, Slight The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Liver, Pancreas, Spleen, Teeth, Thymus, Tracheal Bifurc.447Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 87 Sex: Male D ose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 554.6 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Liver Inflammation, Focal, Minimal Lungs + Bronchi Lungs + Bronchi Pale area(s), A few, subpleural, up to 1mm Arterial Mural Mineralisation , Minimal Aggregations of Alveolar Macrophages, Minimal Alveolar Congestion, Moderate Lary nx Inflammatory Cells in Lamina Propria, Slight Skin Hair loss, Side(s) of face The following examined tis sues had no gross observations and no findings microscopically: Heart, Nasal turbinates, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.448Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual f indings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 88 Sex: Male Dose Group: 1 Phase: Recover y Sacrifice Statu s: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 607.9 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Liver Inflammation, Focal, Slight Lungs + Bronchi Arterial Mural Mineralisation, Minimal Aggregations of Alveolar Macrophages, Minimal Nasal turbinates Respiratory Epithelium - Goblet Cell Hyperplasia, Slight Thy mus Thy mus Dark, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Pancreas, Spleen, Teeth, Trachea, Tracheal Bifurc.449Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -tr ifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 89 Sex: Male Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 754.8 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Infiltrate, Cellular, Myocardium, Minimal Lungs + Bronchi Lungs + Bronchi Dark, Patchy Aggregations of Alveolar Macrophages, Minimal Alveolitis, Slight Per ivascular Inflammatory Cells, Slight Alveolar Eosinophilic Crystals, Moderate Lary nx Inflammatory Cells in Lamina Propria, Slight Haemorrhage in Lamina Propria, Slight Nasal turbinates Nasolacrimal Duct - Inflammation, Minimal Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight The following examined tissues had no gross observations and no findings microscopically: Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.450Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 90 Sex: Male Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 465.4 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Heart Infiltrate, Cellular, Myocardium, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal Alveolitis, Minimal Alveolar Eosinophilic Crystals, Minimal Nasal turbinates Nasolacrimal Duct - Inflammation, Minimal The following examined tissues had no gross observations and no findings microscopically: Larynx, Liver, Pancreas, Spleen, Teeth, Thy mus, Trachea, Tracheal Bifurc.451Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trif luoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 101 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 573.8 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Nasolacrimal Duct - Inflammation, Minimal Skin Hair loss, Side(s) of face, Left, diffuse. The following examined tissues had no gross observations and no findings microscopically: Heart, Liver, Lungs + Bronchi, Pa nc reas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.452Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 102 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 462.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Liver Inflammation, Focal, Minimal Nasal turbinates Nasolacrimal Duct - Inflammation, Slight Red Blood Cells in Airways, Slight Pancreas Acinar Cell Degranulation, Minimal Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal Teeth Teeth Incisor(s) pale, Lower No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Lungs + Bronchi, Spleen, Thymus, Trachea453Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 103 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 585.3 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lungs + Bronchi Pleural Inflammation, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Nasolacrimal Duct - Inflammation, Slight Stomach Stomach Cyst(s), Pale, One, forestomach, 2mm. Non - glandular Region - Squamous Cyst(s), Focal, Slight The following examined tissues had no gross observations a nd no findings microscopically: Heart, Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.454Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Contr ol 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 104 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 518.6 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY H eart Inflammation, Chronic, Minimal Infiltrate, Cellular, Myocardium, Minimal Lungs + Bronchi Aggregations of Alveolar Macrophages, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal Pancreas Basophilic Acinar Cells, Focal, Minimal Teeth Teeth Incisor(s) pale, Lower, Patchy No significant lesions The fo llowing examined tissues had no gross observations and no findings microscopically: Liver, Spleen, Thymus, Trachea, Tracheal Bifurc.455Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 105 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phas e sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 521.2 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Liver Inflammation, Focal, Minimal Lungs + Bronchi Pleural Fibrosis, Slight Pleural Inflammation, Slight Nasal turbinates Nasolacrimal Duct - Inflammation, Minimal Spleen Spleen Capsule thickened, a few areas. Capsular Thickening, Minimal The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Pancreas, Teeth, Thymus, Trachea, Tracheal Bifurc .456Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 106 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 536.9 g PATHOLOGY OBSERVATIONS MA CROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Lungs + Bronchi Arterial Mural Mineralisation, Min imal Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal Nasolacrimal Duct - Inflammation, Slight Nasola crimal Duct - Epithelial Squamous Metaplasia, Minimal Nasolacrimal Duct Epithelial Degeneration, Slight Pancreas Arteritis/Periarteritis, Slight The following examined tissues had no gross observations and no findings micr oscopically: Heart, Larynx, Liver, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.457Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trif luoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 107 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Deat h: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 499.5 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lungs + Bronchi Arterial Mural Mineralisation, Minimal Nasal turbinates Nasolacrimal Duct - Inflammation, Minimal Teeth Teeth Incisor(s) pale, Lower, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Liver, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.458Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 108 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 542.7 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HIST OPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Heart Inflammation, Chronic, Minimal Infiltrate, Cellular, Myocardium, Minimal Nasal turbinates Nasolacrimal Duct - Inflammation, Slight Per iodontal Abscess, Slight Per iodontal Inflammatory Cell Infiltration, Slight Pancreas Acinar Cell Degranulation, Minimal The following examined tissues had no gross observations and no findings microscopically: Laryn x, Liver, Lungs + Bronchi, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.459Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 109 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of D eath: 14 Subgroup: 1 Terminal Bodyweight: 449.1 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Heart Inflammation, Chronic, Minimal Liver Inflammation, Focal, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal Nasal turbinates Nasolacrimal Duct - Inflammation, Slig ht Pancreas Inflammation, Minimal Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal The following examined tissues had no gross observations and no findings microscopically: Larynx, Spleen, Teeth , Thy mus, Trachea460Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 110 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 508.2 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Minimal Infiltrate, Cellular, Myocardium, Mini mal Lungs + Bronchi Lungs + Bronchi Dark area(s), Right, caudal lobe, One, subpleural, 2mm. No significant lesions Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Red Blood Cells in Airways, Slight Pancreas Acinar Cell Degranulation, Minimal The following examined tissues had no gross observations and no findings microscopically: Liver, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.461Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 28 76 Animal Number: 111 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 577.6 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Heart Inflammation, Chronic, Minimal Lungs + Bronchi A rterial Mural Mineralisation, Minimal Alveolitis, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal The following examined tissues had no gross observations and no findings microscopically: Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.462Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 112 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status : Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 459.7 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Slight Lungs + Bronchi Lungs + Bronchi Pale area(s), Right, caudal lobe, Punctate, One, subpleural. Arterial Mural Mineralisation, Slight Nasal turbin ates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Trachea Inflammation, Slight The following examined tissues had no gross observations and no findings microscopically: Larynx, Liver, Pancrea s, Spleen, Teeth, Thymus, Tracheal Bifurc.463Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - brom o - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 113 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 537.0 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Slight Liver Inf lammation, Focal, Minimal Skin Skin Hair loss, Side(s) of face, diffuse. Scab(s), Slight Scab(s), Tail, One, 5mm. Epidermal Hyperplasia, Slight Dermal Inflammation, Minimal The following examined ti ssues had no gross observations and no findings microscopically: Larynx, Lungs + Bronchi, Nasal turbinates, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.464Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopatho logy - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 114 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 493.4 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Slight Infiltrate, Cellular, Myocardium, Minimal Liver Inflammation, Focal, Minimal Lungs + Bronchi Alveolar Sep tal Mineralisation, Focal, Minimal Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Teeth Teeth Incisor(s) pale, Lower, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Larynx, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.465Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 115 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrific e Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 471.7 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HI STOPATHOLOGY Heart Inflammation, Chronic, Slight Liver Hepatocyte Necrosis, Focal, Moderate Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal Pancreas Acinar Atrophy, Focal, Slight Spleen Spleen Capsule thickened, Anterior pole Capsular Thickening, Minimal Teeth Teeth Incisor(s) pale, Lower No significant lesions The following examined tissues had no gross observations and no findings microscopically: Larynx, Lungs + Bronchi, Thymus, Trachea, Tracheal Bifurc.466Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 116 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 457.2 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Minimal Infiltrate, Cellular, Myocardium, Minimal Liver Inflammation, Focal, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal Aggregations of Alveolar Macrophages, Minimal Alveolitis, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Pancreas Acinar Cell Degranulation, Slight Teeth Teeth Incisor(s) pale, Lower No significant lesions467Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (pp m) : 0 199 505 2876 Animal Number: 116 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 457.2 g PATHOLOGY OBSERVATIONS MACRO PATHOLOGY HIST OPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopi cally : Nasal turbinates, Spleen, Thymus, Trachea, Tracheal Bifurc.468Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 117 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 428.6 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal Nasolacrimal Duct - Inflammation, Slight Pancreas Acinar Cell Degranulation, Minimal Spleen Spleen Capsule thickened, Diffuse. Capsular Inflammation, Focal, Minimal Capsular Thickening, Slight Teeth Teeth Incisor(s) pale, Lower, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, La ry nx, Liver, Lungs + Bronchi, Thymus, Trachea, Tracheal Bifurc.469Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -tr ifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 118 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgr oup: 1 Terminal Bodyweight: 457.2 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Slight Infiltrate, Cellular, Myocardium, Minimal Liver Inflammation, Focal, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Slight Pancreas Acinar Cell Degranulation, Slight Spleen Spleen Capsule thickened, Anterior pole, a few areas, up to 3mm. Capsular Inflammation, Focal, Slight470Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 118 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 457.2 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTO PATHOLOGY continued from previous page... Teeth Teeth Incisor(s) pale, Lower No significant lesions The f ollowing examined tissues had no gross observations and no findings microscopically: Lungs + Bronchi, Thymus, Trachea, Tracheal Bifurc.471Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Gr oup : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 119 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 498.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Slight Lungs + Bronchi Aggregations of Alveolar Macrophages, Minimal Alveolitis, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal Nasolacrimal Duct - Inflammation, Minimal Pancreas Acinar Cell Degranulation, Slight Spleen Spleen Capsule thickened, patchy, diffuse. Capsular Inflammation, Focal, Moderate Capsular Thickening, Slight472Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - brom o - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 119 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 498.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from pr evious page... Teeth Teeth Incisor(s) pale, Lower No significant lesions The following examined tissues had no gross observations and no findings microscopically: Liver, Thymus, Trachea, Tracheal Bifurc.473Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 50 5 2876 Animal Number: 120 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 585.1 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Slight Liver Inflammation, Focal, Minimal Lungs + Bronchi Aggregations of Alveolar Macrophages, Minimal Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal Nasolacrimal Duct - Inflammation, Slight Pancreas Acinar Cell Degranulation, Mini mal Teeth Teeth Incisor(s) pale, Lower No significant lesions The following examined tissues had no gross observations and no findings microscopically: Larynx, Spleen, Thymus, Trachea, Tracheal Bifurc.474Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2 876 Animal Number: 11 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 379.6 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Adrenals B - Subcapsular Cell Adenoma Heart Infiltrate, Cellular, Myocardium, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal LN Mesenteric Sinus Erythrocytosis/Erythrophagocytosis, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Squamous Metaplasia - Ventral, Minimal475Huntingdon Life SciencesWAG0014

APP ENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 1 99 505 2876 Animal Number: 11 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 379.6 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Increased Vacuolation of Vomeronasal Organ Epithelium, Slight Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight Respiratory Epithelium - Goblet Cell Hyperplasia, Minimal Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - In flammation, Slight Nasolacrimal Duct Epithelial Degeneration, Slight Pancreas Acinar Cell Degranulation, Slight Prostate Abscessation, Focal, Minimal Sternum + Marrow Marrow - Fat Replacement, Slig ht476Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 11 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 379.6 g PATHOLOGY OBSERVATIONS MA CROPATHOLOGY HISTOPATHOLOGY continued from previous page... Spleen Spleen Capsule thickened Capsular Inflammation, Focal, Slight Capsular Thickening, Minimal Thy ro ids Follicular Dilatation, Bilateral, Minimal Teeth Teeth Incisor(s) pale No significant lesions The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mandibular, Lachrymal Glands, Liver, Mammary, Oesophagus, Optic nerves, Parat hy ro ids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Stomach, Testes, Thy mus, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder477Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 12 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 428.0 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HIS TOPATHOLOGY Adrenals Cortical Vacuolation, Bilateral, Slight Heart Inflammation, Chronic, Moderate Lungs + Bronchi Aggregations of Alveolar Macrophages, Minimal Alveolitis, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Mammary Acinar Atrophy, Moderate478Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 12 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 428.0 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Increased Vacuolation of Vomeronasal Organ Epithelium, Slight Respiratory Epi thelium - Goblet Cell Hyperplasia, Minimal Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Moderate Pancreas Acinar Cell Degranulation, Moderate Pituitary Cyst(s), Focal, Minimal Prostate Lymphoid Aggregates, Focal, Minimal Teeth Teeth Incisor(s) pale Ameloblast Degeneration, Minimal Odontoblast Degeneration, Minimal479Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - in dividual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 12 Sex: Male Dose Group: 4 Phase: Treatment Sacr ifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 428.0 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mandibular, LN Mesenteric, Lachrymal Glands, Liver, Oesophagus, Optic nerves, Parathyroids, Parotid S.G., Peyer's Patch, Rect um, Salivary

Glands, Sciatic Nerve, Seminal Vesicles, Skel etal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Testes, Thymus, Thy ro ids, To ngue, Trachea, Tracheal Bifurc., Urinary Bladder480Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and hist opathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 13 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 445.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Adrenals Cortical Vacuolation, Bilateral, Minimal Heart Inflammation, Chronic, Moderate Infiltrate, Cellular, Myocardium, Minimal LN Mandibular Plasmacytosis, Slight Sinus Histiocytosis, Slight Lungs + Bronchi Lungs + Bronchi Dark area(s), A few, subpleural, up to 1mm. Aggregations of Alveolar Macrophages, Minimal Alveolitis, Slight Pe rivascular Inflammatory Cells, Slight Lary nx Squamous Metaplasia - Ventral, Minimal481Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3 ,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 13 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day o f Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 445.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previ ous page... Nasal turbinates Increased Vacuolation of Vomeronasal Organ Epithelium, Minimal Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Slight Nasolacrimal Duct Epithelial Degeneration, Slight Spleen Spleen Capsule thickened Capsular Inflammation, Focal, Minimal Capsular Thickening, Minimal Stomach Dilated Glands, Minimal Teeth Teeth Incisor(s) pale No significant lesions482Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 13 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death : 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 445.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued f

rom previous page... The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kid neys, LN Bronchial, LN Mesenteric, Lachrymal Glands, Liver, Mammary, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Testes, Thymus, Thy ro ids, To ngue, Trachea, Tracheal Bifurc., Urinary Bladder483Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 14 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase s acrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 449.6 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Adrenals Cortical Vacuolation, Bilateral, Slight Epididymides Lymphoid Aggregates, Focal, Minimal Heart Inflammation, Chronic, Minimal LN Mandibular Sinus Histiocytosis, Sli ght Lungs + Bronchi Arterial Mural Mineralisation, Minimal Aggregations of Alveolar Macrophages, Minimal Alveolitis, Minimal Lary nx Squamous Metaplasia - Ventral, Minimal484Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 14 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 449.6 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Slight Nasolacrimal Duct Epithelial Degeneration, Slight Optic nerves Degenerate Fibres, Unilateral, Minimal Pancreas Acinar Cell Degranulation, Minimal Spleen Spleen Capsule thickened, a few areas. Capsular Inflammation, Focal, Minimal Capsular Thickening, Minimal Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal485Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Expo sure level (ppm) : 0 199 505 2876 Animal Number: 14 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 449.6 g PATHOLOGY OBSER

VATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Teeth Teeth Incisor(s) pale No significant lesions The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Lachrymal Glands, Liver, Mammary, Oesophagus, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, S ciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach , Testes, Thymus, Thyroids, Tongue, Trachea, Urinary Bladder486Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 15 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 451.4 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Adrenals Cortical Vacuolation, Bilateral, Minimal Cortical Hypertrophy, Focal, Minimal Heart Inflammation, Chronic, Slight Infiltrate, Cellular, Myocardium, Minimal LN Mandibular Plasmacytosis, Slight Sinus Histiocytosis, Minimal Liver Hepatocyte Hypertrophy, Centrilobular, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight487Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 15 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 451.4 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HIS TOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inf

lammation, Slight Nasopharynx - Goblet Cell Hyperplasia, Minimal Sternum + Marrow Marrow - Fat Replacement, Slight Spleen Spleen Capsule thickened Capsular Thickening, Minimal Teeth Teeth Incisor(s) pale No significant lesions488Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 15 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 451.4 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gros s observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Lachrymal Glands, Lungs + Bronchi, Mammary, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Tho r., Stomach, Testes, Thymus, Thy ro ids, To ngue, Trachea, Tracheal Bifurc., Urinary Bladder489Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -t rifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 16 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgr oup: 1 Terminal Bodyweight: 362.3 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Adrenals Cortical Vacuolation, Bilateral , Minimal Epididymides Lymphoid Aggregates, Focal, Minimal Heart Inflammation, Chronic, Moderate Kidneys Cortical Scarring, Focal, Minimal LN Bronchial Sinus Histiocytosis, Slight LN Mandibular Plasmacytosis, Slight Sinus Histiocytosis, Slight Liver Inflammation, Focal, Minimal Hepatocyte Hypertrophy, Centrilobular, Minimal490Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology an d histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 16 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 362.3 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Lungs + Bronchi Arterial Mural Mineralisation, Minimal Mammary Acinar Atrophy, Moderate491Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 16 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 362.3 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate Respiratory Epithelium - Goblet Cell Hyperplasia, Minimal Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Moderate Respiratory Epithelium - Squamous Metaplasia, Slight Respiratory Epithelium - Inflammation, Slight Respiratory Epithelium - Regenerative Hyperplasia, Slight Olfactory Epithelium - Inflammation, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Moderate Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Nasolacrimal Duct - Inflammation, Moderate Nasolacrimal Duct Epithelial Degeneration, Slight492Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Grou p : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 16 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phas e sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 362.3 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Pancreas Acinar Cell Degranulation, Slight Skin Skin Scab(s), Tail, Two, distal, up to 4mm. Scab(s), Marked Epidermal Hyperplasia, Moderate Dermal Inflammation, Slight Stomach Mucosal Erosion - Glandular Region, Focal, Slight Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal Teeth Teeth Incisor(s) pale Per iodontal Ligament Inflammation, Minimal Incisor(s) thickened Thy mus Involution/Atrophy, Moderate493Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 16 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 362.3 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previou s page... General Comments Situs inversus The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Mesenteric, Lachrymal Glands, Larynx, Oesophagus, Optic nerves, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spina l C. Thor., Spleen, Sternum + Marrow, Testes, Thyroids, Tongue, Trachea, Urinary Bladder494Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluor opr opene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 17 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 418.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Adrenals Cortica l Vacuolation, Bilateral, Minimal Heart Infiltrate, Cellular, Myocardium, Minimal Kidneys Interstitial Inflammation, Unilateral, Minimal LN Mandibular Plasmacytosis, Slight Lungs + Bronchi Lungs + Bronchi Pale area(s), Left, Punctate, One, subpleural. Alveolitis, Minimal Pleural Inflammation, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight495Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropatho logy and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 17 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 418.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Goblet Cell Hyperplasia, Minimal Olfactory Epithelium - Squamous Metaplasia, Focal , Slight Olfactory Epithelium - Inflammation, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Minimal Inflammatory Exudate in Airways, Minimal Spleen Spleen Capsule thickened, Anterior pole, an area, 3mm. No significant lesions Tracheal Bifurc. Loss of Cilia at Bifurcation, Minimal Teeth Teeth Incisor(s) pale, Lower No significant lesions496Huntingdon Life SciencesWAG0014

APP ENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 1 99 505 2876 Animal Number: 17 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 418.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Br on chial, LN Mesenteric, Lachry mal Glands, Liver, Mammary, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer 's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Testes, Thy mus, Thy ro ids, Tongue, Trachea, Urinary Bladder497Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 18 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 421.1 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPAT HOLOGY Heart Inflammation, Chronic, Slight Infiltrate, Cellular, Myocardium, Minimal LN Bronchial LN Br onchial Small Decreased Cellularity - Generalised, Slight LN Mandibular Plasmacytosis, Slight Lary nx Squamous Metaplasia - Ventral, Minimal Mammary Acinar Atrophy, Marked498Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2 876 Animal Number: 18 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 421.1 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Minimal Pancreas Acinar Cell Degranulation, Slight Spleen Spleen Capsule thickened Capsular Inflammation, Focal, Slight Capsular Thickening, Slight Teeth Teeth Incisor(s) pale, Patchy No significant lesions499Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 18 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase s acrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 421.1 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Mesenteric, Lachry mal Glands, Liver, Lungs + Bronchi, Oesophagus, Optic nerves, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Pro state, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Mus cle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Testes, Thymus, Thy ro ids, To ngue, Trachea, Tracheal Bifurc., Urinary Bladder500Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 19 Sex: Male Dose Group: 4 Phase: Treatment Sacri fice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 379.9 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Epididymides Lymphoid Aggregates, Focal, Minimal Heart Inflammation, Chronic, Slight LN Mandibular Plasmacytosis, Slight Liver Inflammation, Focal, Min imal Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Slight Pancreas Acinar Cell Degranulation, Slight Parathy ro ids Both mis sing501Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 19 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 379.9 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Parotid S.G. Acinar Atrophy, Focal, Slight Spleen Spleen Capsule thickened No significant lesions Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal Teeth Teeth Incisor(s) pale No significant lesions The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Lachry mal Glands, Lary

nx, Lungs + Bronchi, Mammary, Oesophagus, Optic nerves, Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Testes , Thy mus, Thy ro ids, Tongue, Trachea, Urinary Bladder502Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 20 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 432.6 g PAT HOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Moderate Kidneys Cortical Scarring, Focal, Minimal LN Mandibular Plasmacytosis, Slight Liver Inflammation, Focal, Minimal Lungs + Bronchi Lungs + Bronchi Petechiae, Left, A few No significant lesions Lary nx Inflammatory Ce lls in Lamina Propria, Slight Squamous Metaplasia - Ventral, Minimal Mammary Acinar Atrophy, Slight503Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 20 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Dat e of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 432.6 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPAT HOLOGY continued from previous page... Nasal turbinates Olfactory Epithelium - Inflammation, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Nasolacrimal Duct Epithelial Degeneration, Minimal Nasopharynx - Goblet Cell Hyperplasia, Slight Pancreas Acinar Cell Degranulation, Slight Parathy ro ids Both missing504Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 28 76 Animal Number: 20 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 432.6 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Spleen Spleen Capsule thickened, Patchy Capsular Inflammation, Focal, Slight Cyst(s), Anterior pole, Clear fluid, One, 3mm. Capsular Thickening, Slight Capsular Cyst(s), Focal, Slight Testes Seminiferous Tubular Atrophy, Unilateral, Minimal Teeth Teeth Incisor(s) pale, Lower No significant lesions Ur inary Bladder Refluxed Seminal Colloid Plug, Present The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Bronchial, LN Mesenteric, Lachrymal Glands, Oesophagus, Optic nerves, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Gl ands, Sciatic Nerve, Seminal Vesicles, S keletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc.505Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 71 Sex: Male Dose Group: 4 Phase: Recover y Sacrifice Status: Fi nal phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 489.5 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Kidneys Kidneys Pelvic dilatation Per ivascular Lymphoid Aggregations, Focal, Minimal Lungs + Bronchi Alveolitis, Minimal Alveolar Eosinophilic Crystals, Slight Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Respiratory Epithelium - Goblet Cell Hyperplasia, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflamm ation, Slight Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, Liver, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.506Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposur e level (ppm) : 0 199 505 2876 Animal Number: 72 Sex: Male Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 558.7 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Minimal Liver Inflammation, Focal, Minimal Lung s + Bronchi Aggregations of Alveolar Macrophages, Minimal Alveolitis, Minimal Pleural Inflammation, Focal, Minimal Nasal turbinates Respiratory Epithelium - Goblet Cell Hyperplasia, Slight Nasolacrimal Duct - Inflammation, Minimal Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal Teeth Teeth Incisor(s) pale, Patchy No significant lesions507Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathol ogy and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 72 Sex: Male Dose Grou p: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 558.7 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Larynx, Pancreas, Spleen, Thymus, Trachea508Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 73 Sex: Male Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 432.7 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLO GY Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Slight Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Liver, Lungs + Bronchi, Pancreas , Spleen, Thymus, Trachea, Tracheal Bifurc.509Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 74 Sex: Male Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodywei ght: 491.4 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Nasal turbinates Respiratory Epithelium - Goblet Cell Hyperplas ia, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Minimal Nasolacrimal Duct Epithelial Degeneration, Slight Teeth Teeth Incisor(s) pale, Patchy No significant lesions Incisor(s) thickened The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Liver, Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.510Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (pp m) : 0 199 505 2876 Animal Number: 75 Sex: Male Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 544.4 g PATHOLOGY OBSERVATIONS MACROPAT HOLOGY HISTOPATHOLOGY Heart Infiltrate, Cellular, Myocardium, Minimal Lungs + Bronchi Lungs + Bronchi Dark area(s), A few, subpleural, 2mm. Per ivascular Inflammatory Cells, Minimal Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal Pituitary Pituitary Cyst(s), Clear, One, 2mm. Cyst(s), Moderate Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Larynx, Liver, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.511Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 76 Sex: Male Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 532.3 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTO PATHOLOGY Heart Infiltrate, Cellular, Myocardium, Minimal Liver Per ivascular Mineralisation, Slight Lungs + Bronchi Aggregations of Alveolar Macrophages, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Minimal Spleen Spleen Adhesions, Slight, to omental fat. Capsular Inflammation, Focal, Minimal Capsule thickened, Anterior pole Capsular Thickening, Slight512Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 76 Sex: Male Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 532.3 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Pancreas, Thymus, Trachea513Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopatholo gy - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 77 Sex: Male Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 466.2 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Infiltrate, Cellular, Myocardium, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal Alveolitis, Slight Alveolar Eosinophilic Crystal s, Slight Lary nx Inflammatory Cells in Lamina Propria, Slight514Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 77 Sex: Male Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 466.2 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Goblet Cell Hyperplasia, Slight Olfactory Epithelium - Squamous Metaplasia, Minimal Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal Nasolacrimal Duct - Inflammation, Minimal Pancreas Acinar Atrophy, Focal, Slight Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Liver, Spleen, Thymus, Trachea515Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropatholo gy and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 78 Sex: Male Dose Group : 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 476.2 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Liver Inflammation, Focal, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal Aggregations of Alveolar Macrophages, Slight Nas al turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.516Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 79 Sex: Male Dose Group: 4 Phase: Recover y Sa crifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 407.7 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lungs + Bronchi Arterial Mural Mineralisation, Minimal Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal Olfactory Epithelium - A

trophy /Disorganisation/Vacuolation, Minimal Spleen Spleen Adhesions, Anterior pole, to left abdominal wall. Capsular Inflammation, Focal, Minimal Capsular Thickening, Slight Adhesion, Present Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Liver, Pancreas, Thymus, Trachea, Tracheal Bifurc.517Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 80 Sex: Male Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 422.2 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY LN Mandibular LN Mandibular Enlarged, Left, One, 12mm. Plasmacytosis, Moderate Par acortex - Increased Cellularity, Moderate Liver Inflammation, Focal, Minimal Lungs + Bronchi Alveolitis, Minimal Alveolar Eosinophilic Crystals, Minimal Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Olfactory Epithelium - Erosion, Focal, Moderate Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, Lary

nx, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.518Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -tr ifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 21 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 316.4 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Kidneys Min eralisation, Papilla, Unilateral, Minimal LN Mandibular Plasmacytosis, Moderate Sinus Histiocytosis, Slight Lary nx Inflammatory Cells in Lamina Propria, Moderate519Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 21 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 316.4 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Erosion, Focal, Slight Olfactory Epithelium - Inflammation, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal Olfactory Epithelium - Erosion, Focal, Slight Nasol acrimal Duct - Inflammation, Minimal Nasolacrimal Duct - Epithelial Squamous Metaplasia, Minimal Parotid S.G. Acinar Atrophy, Focal, Slight Min eralisation, Focal, Minimal Uterus Polyploid Hyperplasia, F ocal, Slight520Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Expo sure level (ppm) : 0 199 505 2876 Animal Number: 21 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 316.4 g

PATHOLOGY OBS ERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Vagina Oestrus, Present The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, LN Br onchial, LN Mesenteric, Lachry mal Glands, Liver, Lungs + Br onchi, Mammary, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teet h, Thy mus, Thy ro ids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix521Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropr opene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 22 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 9 3 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 271.4 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPI C FINDINGS RECORDED*** Adrenals Subcapsular Cell Hyperplasia, Focal, Unilateral, Slight Lungs + Bronchi Arterial Mural Mineralisation, Minimal Aggregations of Alveolar Macrophages, Minimal LN Mesenteric Mastocytosis, Slight Ovaries Pr ominent Corpora Lutea, Present Pituitary Cyst(s), Focal, Minimal Vagina Metoestrus, Present522Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathol ogy - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 22 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 271.4 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc . Joint, Harderian Glands, Heart, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mandibular, Lachry mal Glands, Lary

nx, Liver, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., P ey er's Patch, Rectum, Salivary Glands, Scia

tic Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth , Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus523Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number : 23 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 271.0 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Heart Infiltrate, Cellular, Myocardium, Minimal LN Mandibular Plasmacyt osis, Slight Sinus Histiocytosis, Slight Lungs + Bronchi Arterial Mural Mineralisation, Minimal Aggregations of Alveolar Macrophages, Minimal Alveolitis, Minimal Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal Red Blood Cells in Airways, Slight Skeletal Muscle Inflammation, Minimal524Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 23 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice S tatus: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 271.0 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Vagina Metoestrus, Present The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Lachry mal Glands, Lary

nx, Liver, Mammary, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Parotid S.G., Peyer's Pa tch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Thy mus, Thy ro ids, To ngue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus525Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 24 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 317.9 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Liver Inflammation, Focal, Minimal Lungs + Bronchi Arteri al Mural Mineralisation, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Mammary Site Only, Present Nasal turbinates Nasolacrimal Duct - Inflammation, Minimal Nasolacrimal Duct - Epithe lial Squamous Metaplasia, Slight Red Blood Cells in Airways, Slight Pituitary Cyst(s), Focal, Minimal Vagina Pr oestrus, Present526Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 24 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 317.9 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mandibular, LN Mesenteric, Lachrymal Glands, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Rectum, Salivary Glands, Sciatic Nerve, S keletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Thymus, Thyr oids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus527Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 25 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 276.7 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY LN Mandibular Sinus Histiocytosis, Moderate Lungs + Bronchi Lungs + Bronchi Pale area(s), Left, Punctate, One, subpleural. No sign ificant lesions LN Mesenteric Sinus Erythrocytosis/Erythrophagocytosis, Minimal Ur inary Bladder Transitional Cell Hyperplasia, Slight Vagina Metoestrus, Present The following examined tissues had no gr oss observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, Ki dneys, LN Bronchial, Lachrymal Glands, Larynx, Liver, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Thymus, Thy ro ids, To ngue, Trachea, Tracheal Bifurc., Uterine cervix, Uterus528Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoroprop ene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 26 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 We ek of Death: 14 Subgroup: 1 Terminal Bodyweight: 326.3 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY LN Mandibular Plasmacyt osis, Moderate Lungs + Bronchi Lungs + Bronchi Pale area(s), A few, subpleural, up to 1mm. No significant lesions Skin Skin Scab(s), Side(s) of face, Punctate, A few Scab(s), Slight Hair loss, Side(s) of face Epidermal Hyperplasia, Slight Dermal Inflammation, Minimal Epidermal Ulceration, Focal, Moderate Vagina Metoestrus, Present The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, Ki dneys, LN Bronchial, LN Mesenteric, Lachrymal Glands, Larynx, Liver, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Thymus, Thyr oids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus529Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 27 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Killed for welfare reasons Date of Death: 30 - Aug - 12 Day of Death: 52 Week of Death: 8 Subgroup: 1 Terminal Bodyweight: 291.1 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Adrenals Sinusoida l Dilatation/Congestion, Unilateral, Moderate Caecum Submucosal Oedema, Moderate Fac con to death Per icarditis, Present Heart Heart Adhesion(s), to pericardium. Infiltrate, Cellular, Myocardium, Minimal Pericardial fluid, Dark, copious. Per icarditis, Marked Pericardium thickened Adhesion, Present Per icardial Haemorrhage, Marked Per icardial Fibrosis, Marked Kidneys Pelvic Dilatation , Unilateral, Slight530Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 27 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Killed for welfare reasons Date of Death: 30 - Aug - 12 Day of Death: 52 Week of Death: 8 Subgroup: 1 Terminal Bodyweight: 291.1 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... LN Bronchial LN Bronchial Dark Sinus Erythrocy to sis/Ery throphagocy

tosis, Slight Liver Liver Irregular surface Inflammation, Focal, Slight Hepatocyte Necrosis, Focal, Minimal Lungs + Bronchi Per ivascular Haemorrhage, Focal, Slight Pleural Fibrosis, Slight LN Mesenteric Sinus Erythrocytosis/Erythrophagocytosis, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal531Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 27 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Killed for welfare reasons Date of Death: 30 - Aug - 12 Day of Death: 52 Week of Death: 8 Subgroup: 1 Terminal Bodyweight: 291.1 g

PATHOLOGY O BSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Pancreas Pancreas Oedematous Oedema, Slight Sp leen Capsular Thickening, Minimal Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Slight Thorax Contained fluid, Clear, serous, copious. Thy mus Thy mus Oedematous Involution/Atrophy, Moderate Oedema, Moderate The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Mandibular, Lac hry mal Glands, Mammary, Oesophagus, Optic nerves, Ovaries, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Teeth, Thy ro ids, Tongue, Trachea, Urinary Bladder, Uterine cervix, Uterus, Vagina532Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 28 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week o f Death: 14 Subgroup: 1 Terminal Bodyweight: 336.8 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY LN Mandibular Plasmacyt osis, Slight Par acortex - Increased Cellularity, Slight Lungs + Bronchi Aggregations of Alveolar Macrophages, Slight Lary nx Inflammatory Cells in Lamina Propria, Slight Ovaries Ovaries Cyst(s), Left, Clear fluid, One, 2mm. Cyst(s), Focal, Slight Skin Skin Hair loss, Side(s) of face, diffuse. No significant lesions Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Slight Vagina Metoestru s, Present533Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 28 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 336.8 g

PATHOLOGY OBSER

VATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findin gs microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, Ki dneys, LN Bronchial, LN Mesenteric, Lachrymal Glands, Liver, Mammary, Nasal turbinates, Oesophagus, Op tic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Thy mus, Thy ro ids, Tongue, Trac

hea, Urinary

Bladder, Uterine cervix, Uterus534Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 29 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bo dyweight: 299.9 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Adrenals Cortical Hypertrophy, Bilateral, Slight Harderian Glands Lymphoid Aggregates, Focal, Minimal Heart Infiltrate, Cellular, Myocardium, Minimal LN Mandibular LN Mandibular Enlarged, Right, One, 15mm. Plasmacytosis, Moderate Par acortex - Increa sed Cellularity, Slight Lachry mal Glands Lymphoid Aggregates, Focal, Minimal Liver Inflammation, Focal, Minimal Pancreas Acinar Cell Degranulation, Slight535Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Ma cropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 29 Sex: Femal e Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 299.9 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Parathy ro ids Both missing Skin Skin Scab(s), Side(s) of face, Left, A few, up to 2mm. Scab(s), Moderate Hair loss, Side(s) of face, Left Epidermal Hyperplasia, Slight Dermal Inflammation, Minimal Stomach Submucosal Inflammation - Glandular Region, Slight Vagina Metoestrus, Present The following examined tissues had no gross observations and no findings microscopically: Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Larynx, Lungs + Bronchi, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Ovaries, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Teeth, Thymus, Thyroids, Tongue, Trach ea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus536Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -tr ifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 30 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 306.6 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Harderian Glands Lymphoid Aggregates, Focal, Minimal Lungs + Bronchi Alveolitis, Minimal Per ivascular Inflammatory Cells, Minimal Spleen Capsular Thickening, Minimal Vagina Metoestrus, Pr esent The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Heart, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mandibular , LN Mesenteric, Lachrymal Glands, Larynx, Liver, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyr oids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Teeth, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus537Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 41 Sex: Female Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 306.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Lary nx Inflammatory Cells in Lamina Propria, Slight The following examined tissues had no gross observations and no findings microscopically: Heart, Liver, Lungs + Bronchi, Nasal turbinates, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.538Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : C ontrol 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 42 Sex: Female Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 328.6 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Liver Inflammation, Focal, Minimal Hepatocyte Vacuolation, Periportal, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal Nasal turbinates Nasolacrimal Duct - Inflammation, Minimal The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.539Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 43 Sex: Female Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 301.0 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal Nasolacrimal Duct - Inflammation, Minimal The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Liver, Lungs + Bronchi, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.540Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropen e 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 44 Sex: Female Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 350.4 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Infiltrate, Cellular, Myocardium, Minimal Liver Inflammation, Focal, Minimal Hepatocyte Vacuolation, Periportal, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal Lary nx Inflammatory Cells in Lamina Pr opr ia, Slight Nasal turbinates Inflammatory Exudate in Airways, Minimal Ovaries Ovaries Periovarian sac distension, Left, Clear, Minimal, 7mm. Cyst(s), Unilateral, Slight The following examined tissues had no gr oss observations and no findings microscopically: Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.541Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : C ontrol 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 45 Sex: Female Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 293.3 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Lungs + Bronchi Arterial Mural Mineralisation, Minimal Per ivascular Inflammatory Cells, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Slight Pancreas Inflammation, Minimal The following examined tissues had no gross observations and no findings microscopically: Heart, Liver, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.542Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 46 Sex: Female Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Termin al Bodyweight: 325.3 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Liver Inflammation, Focal, Slight Hepatocyte Necrosis, Focal, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal Nasal turbinates Nasolacrimal Duct - Inflammation, Minimal Inflammatory Exudat e in Airways, Minimal Thy mus Tissue missing The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Pancreas, Spleen, Teeth, Trachea, Tracheal Bifurc.543Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 47 Sex: Female Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 335.1 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Liver Inflammation, Focal, Minimal The following examined tissues had n o gross observations and no findings microscopically: Heart, Larynx, Lungs + Bronchi, Nasal turbinates, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.544Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 48 Sex: Female Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 302.5 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Liver Inflammation, Focal, Slight Lungs + Bronchi Lungs + Bronchi Pale area(s), A few, subpleural, up to 2mm. Aggregations of Alveolar Macrophages, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Increased Vacuolation of Vomeronasal Organ Epithelium, Slight Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight The followin g examined tissues had no gross observations and no findings microscopically: Heart, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.545Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 49 Sex: Female Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 301.0 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Lungs + Bronchi Aggregations of Alveolar Macrophages, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Nasolacrimal Duct - Inflammation, Minimal Pancreas Acinar Cell Degranulation, Minimal The following examined tissues had no gross observations and no findings microscopically: Heart, Liver, Spleen, Teeth, Thymus, Trac hea, Tracheal Bifurc.546Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoroprop ene Exposure level (ppm) : 0 199 505 2876 Animal Number: 50 Sex: Female Dose Group: 1 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 279.7 g

PATHOL OGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY ***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED*** Lary nx Inflammatory Cells in La mina Propria, Slight Nasal turbinates Nasolacrimal Duct - Inflammation, Minimal The following examined tissues had no gross observations and no findings microscopically: Heart, Liver, Lungs + Bronchi, Pancreas, Spleen, Teeth , Thy mus, Trachea, Tracheal Bifurc.547Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 51 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 293.4 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lungs + Bronchi Lungs + Bronchi Pale area(s), Right, caudal lobe, Punctate, A few, subpleural. Arterial Mural Mineralisation, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal The following examined tissue s had no gross observations and no findings microscopically: Heart, Liver, Nasal turbinates, Pancreas, Spleen, Teeth, Thymus, Trachea548Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Grou p : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 52 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final ph ase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 286.7 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Infiltrate, Cellular, Myocardium, Minimal Lungs + Bronchi Ch olesterol Cleft Granuloma(ta), Minimal Nasal turbinates Respiratory Epithelium - Goblet Cell Hyperplasia, Slight P aws Paws Swelling(s), Left fore, One, 3x2mm. Oedema, Slight Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal The following examined tissues had no gross observations and no findings microscopically: Larynx, Liver, Pancreas, Spleen, Teeth, Thymus, Trachea549Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -tri fluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 53 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgr oup: 1 Terminal Bodyweight: 296.7 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lungs + Bronchi Alveolitis, Minimal Pleural Inflammation, Minimal Nasal turbinates Nasolacrimal Duct - Inflammation, Minimal Skin Hair loss, Forelimb(s), Slight The following examined tissues had no gross observations and no findings microscopical ly : Heart, Larynx, Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.550Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -tri fluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 54 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of De ath: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 278.0 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lungs + Bronchi Aggregations of Alveolar Macrophages, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal Skin Hair loss, Sc apular region(s), diffuse. Spleen Capsular Thickening, Minimal The following examined tissues had no gross observations and no findings microscopically: Heart, Liver, Pancreas, Teeth, Thymus, Trachea, Tracheal Bifurc.551Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 55 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 284.9 g

PATHOLOGY OBSERVATIONS MACROPAT HOLOGY HISTOPATHOLOGY Skin Hair loss, Forelimb(s), Right, diffuse. Spleen Spleen Capsule thickened, Anterior pole, a f ew areas, diffuse. Capsular Inflammation, Focal, Minimal Capsular Thickening, Minimal Teeth Teeth Incisor(s) pale, Lower No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Liver, Lungs + Bronchi, Nasal turbinates, Pancreas, Thymus, Trachea, Tracheal Bifurc.552Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 56 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sac rifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 315.1 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lungs + Bronchi Lungs + Bronchi Pale area(s), Right, caudal lobe, Punctate, A few, subpleural. Aggregations of Alveolar Macrophages, Minimal Nasal turbinates Nasolacrimal Duct - Inflammation, Slight Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight Pancreas Inflammation, Minimal Teeth Teeth Incisor(s) pale, Lower, Patchy No significant lesions The following examined tissues had no gross obs ervations and no findings microscopically: Heart, Larynx, Liver, Spleen, Thymus, Trachea, Tracheal Bifurc.553Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Con trol 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 57 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 296.1 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Liver Inflammation, Focal, Minimal Nasal turbinates Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight Pancreas Acinar Cell Degranulation, Minimal Acinar Atrophy, Focal, Minimal Skin Hair loss, Dorsal surface, diffuse. Trachea Inflammation, Slight The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Lungs + Bronchi, Spleen, Teeth, Thymus, Tracheal Bifurc.554Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 58 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 306.3 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lungs + Bronchi Aggregations of Alveolar Macrophages, Minimal Nasal turbinates Nasolacrimal Duct - Inflammation, Slight Pancreas Acinar Cell Degranulation, Minimal Skin Hair loss, Side(s) of face, diffuse. Teeth Teeth Incisor(s) pale, Lower No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Liver, Spleen, Thymus, Trachea, Tracheal Bifurc.555Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 59 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 320.4 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lungs + Bronchi Arterial Mural Mineralisation, Minimal Nasal turbinates Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Minimal Pancreas Acinar Cell Degranulation, Slight Skin Hair loss, Side(s) of face, diffuse. Trachea Inflammation, Slight The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Liver, Spleen, Te eth, Thymus, Tracheal Bifurc.556Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 60 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 287.9 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lungs + Bronchi Lungs + Bronchi Pale area(s), A few, subpleaural, up to 1mm. Ch olesterol Cleft Granuloma(ta), Focal, Minimal Nasal turbinates Nasolacrimal Duct - Inflammation, Slight Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight Pancreas Acinar Cell Degranulation, Sl ight Skin Hair loss, dorsal region and limbs, diffuse. The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Liver, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.557Huntingdon Life SciencesWAG0014

APP ENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 1 99 505 2876 Animal Number: 1 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 293.8 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLO GY Heart Inflammation, Chronic, Minimal Nasal turbinates Respiratory Epithelium - Atrophy/Disorganis ation/Vacuolation, Minimal Nasolacrimal Duct - Inflammation, Minimal Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Larynx, Liver, Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.558Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -tri fluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 2 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 296.8 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Infi ltrate, Cellular, Myocardium, Minimal Liver Inflammation, Focal, Minimal Lungs + Bronchi Lungs + Bronchi Pale area(s), Punctate, Multiple, subpleural. Alveolitis, Minimal Nasal turbinates Olfactory Epit

helium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Slight Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight Pancreas Acinar Cell Degranulation, Slight559Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 2 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 296.8 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Spleen Spleen Cyst(s), Clear fluid, A few, capsular, up to 2mm. Capsular Inflammation, Fo cal, Slight Capsule thickened, a few areas. Capsular Thickening, Slight Adhesions, Anterior pole, to left retroperitoneal adipose tissue. Capsular Cyst(s), Focal, Slight Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Larynx, Thymus, Trachea, Tracheal Bifurc.560Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopat hology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 3 Sex: Female Dose Group: 3 Phase: Tr eatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 232.9 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Minimal Liver Inflammation, Focal, Minimal Lungs + Bronchi Alveolitis, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Nasolacrimal Duct - Inflammation, Slight Pancreas Acinar Cell Degranulation, Slight Skin Skin Scab(s), Tail, Two, up to 4mm. No significant lesions Teeth Te eth Incisor(s) pale, Patchy No significant lesions561Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3, 3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 3 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 S ubgroup: 1 Terminal Bodyweight: 232.9 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Spleen, Thymus, Trachea, Tracheal Bifurc.562Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 4 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 297.7 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Minimal Liver Inflammation, Focal, Minimal Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Slight Pancreas Acinar Cell Degranulation, Minimal Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Larynx, Lungs + Bronchi, Spleen, Thymus, Trachea563Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 5 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 294.1 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Liver Liver Adhesions, Posterior caudate lobe, to stomach. Capsular Adhesions, Present Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganis ation/Vacuolation, Minimal Nasolacrimal Duct - Inflammation, Moderate Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight Spleen Spleen Adhesions, to stomach, posterior caudate liver lobe and omental adipose tissue . Capsular Thickening, Minimal Adhesion, Present Teeth Teeth Incisor(s) pale, Lower No significant lesions564Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 5 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Fina l phase sacrifice Date of Death: 10 - Oct - 12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 294.1 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Heart, Lungs + Bronchi, Pancreas, Thymus, Trachea, Tracheal Bifurc.565Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 6 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 303.6 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Liver Inflammation, Focal, Minimal Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Pancreas Acinar Cell Degranulation, Minimal Teeth Teeth Incisor(s) pale, Patchy Odontoblast Degeneration, Minimal The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Lungs + Bronchi, Spleen, Thymus, Trachea, Tracheal Bifurc.566Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoroprop ene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 7 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 257.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Nasolacrimal Duct - Inflammation, Slight Skin Hair loss, Thoracic region, Dorsal Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal Teeth Teeth Incisor(s) pale, Lower No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, Liver, Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea567Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 8 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 290.7 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Infiltrate, Cellular, Myocardium, Minimal Kidneys Kidneys Pelvic dilatation, Right Pelvic Dilatati on, Unilateral, Moderate Liver Inflammation, Focal, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Minimal Skin Hair loss, Side(s) of face, extending to lateral cervical regions, diffuse. Teeth Teeth Incisor(s) pale, Lower, Patchy No significant lesions568Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histop athology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 8 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 290.7 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.569Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposur e level (ppm) : 0 199 505 2876 Animal Number: 9 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 270.9 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Minimal Lungs + Bronchi Alveolar Septal Mineralis atio n, Minimal Alveolar Congestion, Slight Lary nx Inflammatory Cells in Lamina Propria, Slight Skin Hair loss, Side(s) of face, diffuse. Spleen Spleen Capsule thickened Capsular Thickening, Minimal Teeth Teeth Incisor(s) pale, Lower, Patchy Odontoblast Degeneration, Minimal The following examined tissues had no gross observations and no findings microscopically: Liver, Nasal turbinates, Pancreas, Thymus, Tr achea, Tracheal Bifurc.570Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene Exposure level (ppm) : 0 199 505 2876 Animal Number: 10 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 291.4 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Kidneys Kidneys Depression(s), Right, One, 2mm. No significant lesions Liver Inflammation, Focal, Minimal Hepatocyte Hypertrophy, Centrilobular, Minimal Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal Nasolacrimal Duct - Inflammation, Slig ht Pancreas Acinar Cell Degranulation, Minimal Skin Hair loss, Thoracic region, Dorsal, extending to cranial region. Spleen Haemosiderosis, Slight571Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathol ogy and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 10 Sex: Female Dose Gr oup: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 12 - Oct - 12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 291.4 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Lungs + Bronchi, Teeth, Thymu s, Trachea, Tracheal Bifurc.572Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene Exposure level (ppm) : 0 199 505 2876 Animal Number: 31 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 211.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Slight Kidneys Pyel onephritis , Bilateral, Moderate Hyperplasia, Papillary Epithelium, Bilateral, Moderate Hyperplasia, Pelvic Epithelium, Bilateral, Slight LN Mandibular Plasmacytosis, Slight Sinus Histiocytosis, Slight573Huntingdon Life SciencesWAG0014

APPENDIX 1 2 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 31 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 211.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Moderate Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Nasolacrimal Duct - Inflammation, Moderate Nasolacrimal Duct - Epithelial Squamous Metaplasia, Moderate Inflammatory Exudate in Airways, Minimal Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Slight574Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (pp m) : 0 199 505 2876 Animal Number: 31 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 211.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HIS TOPATHOLOGY continued from previous page... Pancreas Acinar Cell Degranulation, Slight Skin Skin Hair lo ss, Tho

racic regio

n, Patchy, diffuse. No significant lesions Skeletal Muscle Inflammation, Slight Spleen Spleen Capsule thickened, multiple areas, diffuse. Capsular Thickening, Minimal Stomach Dilated Glands, Minimal Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Minimal Teeth Teeth Incisor(s) pale Pulp Cavity Necrosis, Unilateral, Moderate Incisor(s) thickened575Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 31 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 211.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Thy mus Involution/Atrophy, Minimal Ur inary Bladder Transitional Cell Hyperplasia, Moderate Inflammation, Moderate Erosion, Moderate Uterus Polyploid Hyperplasia, Focal, Slight Vagina Oestrus, Present The following examined tissues had no gross observations and no findings microscopically : Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Bronch ial, LN Mesenteric, Lachrymal Glands, Larynx, Liver, Lungs + Bronchi, Mammary, Oesophagus, Optic nerves, Ovaries, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Thyroids, Tongue, Trachea, Uterin e cervix576Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 32 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 205.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Slight Liver Liver Adhesions, between all lobes. Extramedullary Haemopoiesis, Slight Capsul ar Adhesions, Present Lungs + Bronchi Lungs + Bronchi Adhesions, between right cranial and middle lobes. Arterial Mural Mineralisation, Minimal Aggregations of Alveolar Macrophages, Slight Alveolitis, Slight Per ivascular Inflammatory Cells, Slight Pleural Adhesion(s), Slight Mammary Site Only, Present577Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 C ompound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 32 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 205.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HIST OPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Respiratory Epith elium - Erosion, Focal, Minimal Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Moderate Olfactory Epithelium - Respiratory Metaplasia, Slight Nasolacrimal Duct - Inflammation, Moderate Nasolacrimal Duct - Epithelial Squamous Metaplasia, Moderate Nasolacrimal Duct - Luminal Inflammatory Exudate, Moderate Inflammatory Exudate in Airways, Minimal578Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 32 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 205.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Skin Skin Hair loss, Thoracic region, Patchy, diffuse. No significant lesions Spleen Spleen Capsule thickened Capsular Inflammation, Focal, Slight Adhesions, to omental and left mesovarian adipose tissue. Capsular Thickening, Moderate Teeth Teeth Incisor(s) pale Pulp Cavity Necrosis, Unilateral, Slight Incisor(s) thickened Thy mus Involution/Atrophy, Moderate Vagina Metoestrus, Present The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femu r inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mandibular, LN Mesenteric, Lachrymal Glands, Larynx, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thyroids, Tongue, Tr achea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus579Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 33 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 293.1 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Moderate Lungs + Bronchi Lungs + Bronchi Dark area(s), A few, subpleural, up to 2mm. Alveolitis, Minimal Pale area(s), Right, middle lobe, Punctate, A few, subpleural. Per ivascular Inflammatory Cells, Minimal Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight Respiratory Epithelium - Inflammat ory Cells in the Lamina Propria, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Moderate Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Nasolacrimal Duct - Inflammation, Slight580Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (pp m) : 0 199 505 2876 Animal Number: 33 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 293.1 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HIS TOPATHOLOGY continued from previous page... Skin Skin Hair loss, Forelimb(s), Left, diffuse. No significant lesi ons Teeth Teeth Incisor(s) pale Pulp Cavity Increased Inflammatory Cell Infiltration, Minimal Vagina Oestrus, Present The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mandibular, LN Mesenteric, Lachrymal Glands, Larynx, Liver, Mammary, Oesophagus, Optic nerves, Ovaries, Panc reas, Parathy

ro ids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Thymus, Thy ro ids, To ngue, Trachea, Tracheal Bifurc., Ur inary Bladder, Uterine cervix, Uterus581Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3 ,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 34 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodywei ght: 268.6 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Minimal LN Mandibular Sinus Histiocytosis, Slight Sinus Erythrocytosis/Erythrophagocytosis, Minimal Lachry mal Glands Lymphoid Aggregates, Focal, Minimal Liver Liver Cyst(s), Median lobe, Clear fluid, Two, subcapsular,, up to 3mm. Vascular Dilatation, Slight Lary nx Inflammatory Cells in Lamina Propria, Slight Mammary Site Only, Present582Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 34 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 268.6 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Moderate Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Nasolacrimal Duct - Inflammation, Slight Nasolacrimal Duct - Epithelial Squamous Metaplasia, Minimal Parathy ro ids Both missing Pituitary Cyst(s), Focal, Minimal583Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 34 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - O ct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 268.6 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued fr om previous page... Skin Skin Hair loss, Cervical region, diffuse. No significant lesions Teeth Teeth Incisor(s) pale No significant lesions Incisor(s) thickened Ur inary Bladder Transitional Cell Hyperplasia, Slight Inflammation, Slight Vagina Metoestrus, Present The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon , Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Lungs + Bronchi, Oesophagus, Optic nerves, Ovaries, Pancreas, Parotid S.G., Peyer's Patch, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifur c., Uterine cervix, Uterus584Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individ ual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 35 Sex: Female Dose Group: 4 Phase: Treatment Sacrifi ce Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 258.7 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Minimal LN Mandibular Sinus Histiocytosis, Slight Lungs + Bronchi Alveolitis, Minimal Per ivascular Inflammatory Cells, Minimal585Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 35 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 258.7 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, S light Nasolacrimal Duct - Inflammation, Slight Nasolacrimal Duct - Epithelial Squamous Metaplasia, Moderate Nasolacrimal Duct - Luminal Inflammatory Exudate, Minimal Skin Skin Hair loss, Scapular region(s), Lef t, diffuse. No significant lesions586Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - brom o - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 35 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Body weight: 258.7 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Spleen Spleen Adhesions, to omental, left mesovarian and left retroperitoneal adipose tissue. Capsular Inflammation, Focal, Moderate Capsular Thickening, Moderate Adhesion, Present Teeth Teeth Incisor(s) pale Ameloblast Degeneration, M inimal Incisor(s) thickened Odontoblast Degeneration, Minimal Pulp Cavity Necrosis, Unilateral, Slight Ur inary Bladder Transitional Cell Hyperplasia, Slight Vagina Oestrus, Present587Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 50 5 2876 Animal Number: 35 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 09 - Oct - 12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 258.7 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Lachry mal Glands, Lary

nx, Liver, Mammary, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroid s, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thymus, Thy ro ids, To ngue, Trachea, Tracheal Bifurc., Uterine cervix, Uterus588Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 36 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 265.1 g

PATHOLOGY OBSERVATIONS MACRO PATHOLOGY HIST OPATHOLOGY Eyes Eyes Pr otruding, Left Keratitis, Unilateral, Moderate Inflammatory Cells, Anterior Chamber, Unilateral, Slight Iritis, Unilateral, Moderate Inflammation of the Sclera, Unilateral, Moderate Harderian Glands Harderian Glands Swelling(s), Left, One, 6mm. Cut surface: purulent exudate. M - Adenocarcinoma Heart Inflammation, Chronic, Minimal LN Bronchial Sinus Histiocytosis, Slight LN Mandibular Plasmacytosis, Slight Sinus Histiocytosis, Slight589Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 36 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 265.1 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Liver Hepatocyte Hypertrophy, Centrilobular, Minimal Lungs + Bronchi Alveolitis, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Squamous Metaplasia - Ventral, Minimal590Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3, 3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 36 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 265.1 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from pr evious page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Respiratory Epithelium - Erosion, Slight Olfactory Epithelium - Squamous Metaplasia, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Moderate Nasolacrimal Duct - Epithelial Squamous Metaplasia, S light Nasolacrimal Duct - Luminal Inflammatory Exudate, Moderate Inflammatory Exudate in Airways, Minimal Squamous Epithelium - Inflammatory Cells in the Lamina Propria, Slight591Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 3130 14 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 36 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 265.1 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Pancreas Acinar Cell Degranulation, Slight Spleen Spleen Capsule thickened Capsular Inflammation , Focal, Moderate Adhesions, to omental and left mesovarian adipose tissue. Capsular Thickening, Moderate Adhesion, Present Teeth Teeth Incisor(s) pale Ameloblast Degeneration, Minimal Incisor(s) thickened Pulp Cavity Necrosis, Unilateral, Slight Vagina Metoestrus, Present The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Femur inc. Joint, Ileum, Jejunum, Kidneys, LN Mesenteric, Lachrymal Glands, Mammary, Oesophagus, Optic nerves, Ovaries, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C . Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus592Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - indivi dual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 37 Sex: Female Dose Group: 4 Phase: Treatment Sacrif ice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 249.4 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Minimal Infiltrate, Cellular, Myocardium, Minimal LN Mandibular Sinus Histiocytosis, Slight Lary nx Inflammatory Cells in Lam ina Propria, Slight Squamous Metaplasia - Ventral, Minimal593Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3, 3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 37 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 1 4 Subgroup: 1 Terminal Bodyweight: 249.4 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Respiratory Epithelium - Inflammation, Slight Olfactory Epithel ium - Inflammation, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Moderate Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Olfactory Epithelium - Respiratory Metaplasia, Slight Nasolacrimal Duct - Inflammation, Moderate Nasolacrimal Duct - Epithelial Squamous Metaplasia, Moderate Nasolacrimal Duct - Luminal Inflammatory Exudate, Slight594Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropatholo gy and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 37 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 249.4 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Pancreas Acinar Cell Degranulation, Slight Parathy ro ids Both missing Salivary Glands Inflammation, Sligh t Spleen Spleen Capsule thickened, Patchy Capsular Inflammation, Focal, Slight Adhesions, to left mesovarian adipose tissue. Capsular Thickening, Moderate Adhesion, Present Teeth Teeth Incisor (s) pale No significant lesions Thy mus Involution/Atrophy, Moderate Vagina Metoestrus, Present595Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 37 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacr ifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 249.4 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Lachry mal Glands, Liver, Lungs + Bronchi, Mammary, Oesophagus, Optic nerves, Ovaries, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus596Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 38 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 246.8 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HIS TOPATHOLOGY Heart Inflammation, Chronic, Minimal Infiltrate, Cellular, Myocardium, Minimal Kidneys Pyel onephritis, Bilateral, Slight Hyperplasia, Papillary Epithelium, Bilateral, Moderate Hyperplasia, Pelvic Epithelium, Bilateral, Moderate LN Mandibular Sinus Histiocytosis, Slight Liver Inflammation, Focal, Slight Hepatocyte Hypertrophy, Centrilobular, Minimal Lungs + Bronchi Aggregations of Alveolar Macrophages, Minimal597Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 38 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 246.8 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Respiratory Epithelium - Inflammation, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuol ation, Slight Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Olfactory Epithelium - Respiratory Metaplasia, Slight Nasolacrimal Duct - Inflammation, Slight Nasolacrimal Duct - Epithelial Squamous Metaplasia, Moderate Inflammatory Exudate in Airways, Slight598Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 38 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 246.8 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Pa ncreas Acinar Cell Degranulation, Slight Peyer's Patch Tissue missing Skin Skin Hair loss, Side(s) of face No significant lesions Spleen Capsular Inflammation, Focal, Minimal Capsula r Thickening, Slight Teeth Teeth Incisor(s) pale, Patchy Pulp Cavity Increased Inflammatory Cell Infiltration, Slight Incisor(s) thickened Thy mus Involution/Atrophy, Minimal599Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Requ est ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Numb er: 38 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 246.8 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Ur inary Bladder Transitional Cell Hyperplasia, Moderate Inflammation, Slight Vagina Metoestrus, Present The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Bronch ial, LN Mesenteric, Lachrymal Glands, Larynx, Mammary, Oesophagus, Optic nerves, Ovaries, Parathyroids, Parotid S.G., Pituitary, Rectum, Salivary Glands, S ciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, S tomach, Thyroids, Tongue, Trachea, Tracheal Bifurc., Uterine cervix, Uterus600Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 39 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of De ath: 14 Subgroup: 1 Terminal Bodyweight: 281.8 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic , Minimal LN Mandibular Plasmacytosis, Slight Sinus Histiocytosis, Slight Sinus Erythrocytosis/Erythrophagocytosis, Minimal Liver Hepatocyte Hypertrophy, Centrilobular, Minimal Lungs + Bronchi Aggregations of Alveolar Macrophages, Slight Alveolitis, Moderate Per ivascular Lymphoid Aggregates, Moderate601Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 39 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase s acrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 281.8 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Olfact ory Epithelium - Inflammation, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Moderate Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Olfactory Epithelium - Respiratory Metaplasi a, Slight Nasolacrimal Duct - Inflammation, Slight Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight Inflammatory Exudate in Airways, Slight602Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 39 Sex: Female Dose Group: 4 Pha se: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 281.8 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Pancreas Acinar Cell Degranulation, Slight Acinar Atrophy, Focal, Slight Spleen Capsular Thickening, Minimal Teeth Teeth Incisor(s) pale Pulp Cavity Necrosis, Unilateral, Slight Incisor(s) thickened Ur inary Bladder Transitional Cell Hyperplasia, Slight Vagina Metoestrus, Present The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Lachry mal Glands, Lary

nx, Mammary, Oesophagus, Optic nerves, Ovaries, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Uterine cervix, Uterus603Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropr opene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 40 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 262.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Heart Inflammation, Chronic, Minimal Li ver Hepatocyte Hypertrophy, Centrilobular, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight604Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 40 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 262.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HIS TOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal Respiratory Epi thelium - Inflammation, Minimal Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal Olfactory Epithelium - Respiratory Metaplasia, Minimal Pancreas Acinar Cell Degranulation, Slight Skin Dermal Inflammation, Minimal605Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Contro l 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 40 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 262.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued f

rom previous page... Spleen Spleen Capsule thickened Capsular Inflammation, Focal, Slight Adhesions, to left mesovarian and retroperitoneal adipose tissue. Capsular Thickening, Slight Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Moderate Trachea Inflammatory Exudate in Lumen, Slight Inflammation, Moderate Teeth Teeth Incisor(s) pale No significant lesions Incisor(s) thickened Thy mus Involution/Atrophy, Slight Vagina Dioestrus, Present606Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 40 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice Date of Death: 11 - Oct - 12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 262.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mandibula r, LN Mesenteric, Lachrymal Glands, Lungs + Bronchi, Mammary, Oesophagus, Optic nerves, Ovaries, Parathyroids, Parotid S.G., Pey er's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor ., Sternum + Marrow, Stomach, Thyroids, Tongue, Ur inary Bladder, Uterine cervix, Uterus607Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropr opene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 91 Sex: Female Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 280.6 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lungs + Bronchi A rterial Mural Mineralisation, Minimal Nasal turbinates Respiratory Epithelium - Goblet Cell Hyperplasia, Slight Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Respiratory Epithelium - Erosion , Slight Nasolacrimal Duct - Inflammation, Slight Nasolacrimal Duct - Luminal Inflammatory Exudate, Slight Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gr oss observations and no findings microscopically: Heart, Larynx, Liver, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.608Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 92 Sex: Female Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifi ce Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 237.1 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HI STOPATHOLOGY Liver Hepatocyte Necrosis, Focal, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight609Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 31301 4 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 92 Sex: Female Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 237.1 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight Respiratory Epithelium - Erosion, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Olfactory Epithelium - Erosion, Minimal Nasolacrimal Duct - Inflammation, Minimal Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight Teeth Teeth Incisor(s) pale, Patchy Ameloblast Degeneration, Minimal Incisor(s) thickened The following examined tissues had no gross observations and no findings microscopically: Heart, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.610Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 93 Sex: Female Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 260.9 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPAT HOLOGY Liver Inflammation, Focal, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Nasolacrimal Duct - Inflammation, Slight Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Slight Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, Lungs + Bronchi, Pancreas, Spleen, Thy mus, Trachea, Tracheal Bifurc.611Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 94 Sex: Female Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 25 3.0 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Kidneys Kidneys Pelvic dilatation, Right Pelvic Dilatation, Unil ateral, Slight Liver Inflammation, Focal, Slight Lungs + Bronchi Per ivascular Inflammatory Cells, Minimal Nasal turbinates Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal Nasolacrimal Duct - Inflammation, Slight Pancreas Acinar Atrophy, Focal, Slight612Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopatho logy - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 94 Sex: Female Dose Group: 4 Phase: Rec over y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 253.0 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Teeth Teeth Incisor(s) pale, Patchy No significant lesions Incisor(s) thickened The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Spleen, Thymus, Trachea, Tracheal Bifurc.613Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 95 Sex: Female Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 298.2 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Nasal turbin ates Respiratory Epithelium - Goblet Cell Hyperplasia, Slight Respiratory Epithelium - Squamous Metaplasia, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammati on, Slight Inflammatory Exudate in Airways, Slight Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Slight Teeth Teeth Incisor(s) pale, Patchy No significant lesions Incisor(s) thickene d The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Liver, Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.614Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 96 Sex: Female D ose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 260.6 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lungs + Bronchi Arterial Mural Mineralisation, Minimal Nasal turbinates Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Minimal Nasolacrimal Duct - Inflammation, Slight Pancreas Inflammation, Minimal Skin Hair loss, Side(s) of face Teeth Teeth Incisor(s) pale, Patchy Ameloblast Degeneration, Minimal The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Liver, Spleen, Thymus, Trachea, Tracheal Bifurc.615Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 97 Sex: Female Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 251.0 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Liver Inflammation, Focal, Minimal Lungs + Bronchi Arterial Mural Mineralisation, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Respirat ory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal Respiratory Epithelium - Erosion, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Minimal Skin Hair loss, Side(s) of face, Left616Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 97 Sex: Female Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bo dyweight: 251.0 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Teeth Teeth Incisor(s) pale, Patchy Ameloblast Degeneration, Minimal The following examined tissues had no gross observations and no findings microscopically: Heart, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.617Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 3 13014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 98 S ex: Female Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 253.0 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Liver Inflammation, Focal, Minimal Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal Nasolacrimal Duct - Inflam mation, Minimal Spleen Haemosiderosis, Slight Tracheal Bifurc. Inflammatory Cells in Lamina Propria, Slight618Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 98 Sex: Female Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 253.0 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... Teeth Teeth Incisor(s) pale, Patchy Ameloblast Degeneration, Minimal The following examined tissues had no gross observations and no findings microscopically: Heart, Lu ngs + Bronchi, Pancreas, Thymus, Trachea619Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 99 Sex: Female Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 289.0 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Liver Inflammation, Focal, Minimal Nasal turbinates Respiratory Epithelium - Goblet Cell Hyperplasia, Slight Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight Olfactory Epithelium - Atr ophy/Disorganisation/Vacuolation, Slight Nasolacrimal Duct - Inflammation, Slight Ovaries Ovaries Periovarian sac distension, Right, Dark fluid, 15mm. Haemorrhagic Cyst(s), Unilateral, Moderate Spleen Spleen Adhesions, to adipose tissue. Capsular Thickening, Minimal Adhesion, Present Teeth Teeth Incisor(s) pale, Patchy No significant lesions620Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathology and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3 ,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 99 Sex: Female Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 289.0 g PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY continued from previous page... The following examined tissues had no gross observations and no findings microscopically: Heart, Larynx, Lungs + Bronchi, Pancreas, Thymus, Trachea, Tracheal Bifurc.621Huntingdon Life SciencesWAG0014

APPENDIX 12 - continued Request ID: 313014 Macropathol ogy and histopathology - individual findings Group : 1 2 3 4 Compound : Control 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene 2 - br omo - 3,3,3 -trifluoropropene Exposure level (ppm) : 0 199 505 2876 Animal Number: 100 Sex: Female Dose Group: 4 Phase: Recover y Sacrifice Status: Final phase sacrifice Date of Death: 06 -Nov- 12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 262.9 g

PATHOLOGY OBSERVATIONS MACROPATHOLOGY HISTOPATHOLOGY Lary nx Inflammatory Cells in Lamina Propria, Slight Nasal turbinates Respiratory Epithelium - Squamous Metaplasia, Slight Olfactory Epithel ium - Inflammatory Cells in the Lamina Propria, Slight Teeth Teeth Incisor(s) pale, Patchy No significant lesions The following examined tissues had no gross observations and no findings microscopically: Heart, Liver, Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.Huntingdon Life Sciences WAG0014

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### Annex **1 Certificate of Analysis** Huntingdon Life Sciences WAG0014

623Huntingdon Life Sciences WAG0014

624 

### Annex **2 Aerosol Technology and Inhalation Analysis report** Huntingdon Life Sciences WAG0014

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### Working for a better future



## Aerosol Technology Report

HLS study number: WAG0014 Author A Grasiewicz Version ID:  )LQDO Issue date: 2FWREHUHuntingdon Life Sciences WAG0014

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# Table of Contents Signature Page ................................................................................................................ ....... 3 1. Pre-study Atmosphere Characterization ......................................................................... 4 2. Test Article Handling and Processing for Inhalation Generation ..................................... 4 3. Exposure System ............................................................................................................ 4 4. Administration ................................................................................................................. 5 5. Atmosphere Analysis ...................................................................................................... 5 

### 5.1 Vapour Concent ration ................................................................................... 5 5.2 Flow diagram of the analytical met hod for the analysis of 2-bromo-3,3,3- trifluoropropene in test at mosphere sa mples .......................................................... 5 5.3 Nominal Concent ration .................................................................................. 6 5.4 Chamber Tem perature .................................................................................. 6 5.5 Chamber Humi dity ........................................................................................ 6 6. Data and Calculations ..................................................................................................... 6 7. Results and Discussion ................................................................................................... 6 

### 7.1 Aerosol Concent rations ................................................................................. 6 7.2 Chamber Tem perature .................................................................................. 7 7.3 Chamber Humi dity ........................................................................................ 7 

# List of Tables Table 1 Chamber atmosphere concentration of 2-bromo-3,3,3-trifluoropropene – dail y means and individual exposure values – Group 2........................................... 8 Table 2 Chamber atmosphere concentration of 2-bromo-3,3,3-trifluoropropene – daily means and individual exposure values – Group 3......................................... 10 Table 3 Chamber atmosphere concentration of 2-bromo-3,3,3-trifluoropropene – daily means and individual exposure values – Group 4......................................... 12 Table 4 Chamber Temperature - daily mean values .................................................. 14 Table 5 Chamber Humidity - daily mean values ......................................................... 16 

# List of Figures Figure 1 Schematic of Inhalation Exposure System .................................................... 18HuntingdonLifeSciencesWAGOOI4SignaturePageAerosolTechnologyReport%‘eOr7E2i2AntonyGrasiewiczMIATSeniorAerosolTechnologistDateHuntingdonLife SciencesPage3627Huntingdon Life Sciences WAG0014

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# 1. Pre-study Atmosphere Characterization Inhalation exposure system characteri zed including determinations of: Achieved vapour concentration Spatial distribution around the chamber 

# 2. Test Article Handling and Processing for Inhalation Generation As supplied, 2-Bromo-3,3,3-trifluoro-1-propene was easily vapourised using warmed air through a sintered glass vapouriser. 

# 3. Exposure System A schematic of the exposure system is presented in Figure 1. Components of the exposure system: Directed flow Whole body exposure chamber: 0.75 m3 

### chamber of stainless stee l and glass construction Animal Restraint: Wire mesh modular caging Aerosol Generator: Sintered glass vaporiser for Groups 2 to4 all in a water bath set at 40°C Syringe driver, polypropylene syringe for Group 2 Liquid reservoir and feed rate used toalter concentration Groups 3 and 4 Test groups - 30 L/min Diluent Airflow: From in-house compressed air system – breathing quality Group 1 - 149 L/min Group 2 to 4 - 119 L/min Extract Airflow: Drawn by a fan extract system Drawn from base of exposure system Controlled by a gate clamp situated at the rear of the chamber Airflow Monitoring: In-line flowmeters monitored continuously for generation and diluent airflows Chamber pressure differential monitored by Magnahelic set at -1 to -5 mm H 2 

### O to ensure a slight negative pressure within the chamber ~ 150 L/min.Huntingdon Life Sciences WAG0014

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# 4. Administration Animals exposed for 6 hours per day, 5 days a week for 13 consecutive weeks. Exposure system operational parame ters monitored continuously Airflows documented initially and monitored during exposure 

# 5. Atmosphere Analysis 5.1 Vapour Concentration Vapour samples collected as follows: Sample frequency – minimum of 3 samples/group/exposure Sample location – representative animal level Sample position remained constant Sample analysis Infra-red spectrophotometer 

## 5.2 Flow diagram of the analytical method for the analysis of 2-bromo-3,3,3-trifluoropropene in test atmosphere samples Sample Assay Test atmosphere sample (Gas bag or chamber) ↓ Sample directly using the IR spectrophotometer ↓ Perform a single measurement on the IR spectrophotometer Calibration Prepare a set of calibration standards by direct addition of a suitable volume of test item directly into gas bags containing a suitable volume of air ↓ Prepare a set of calibration standards for analysis at nominal concentrations of 146, 388, 1167, 2042, 2918 and 3880 ppm ↓ Measure the response of each calibration standard using the IR spectrophotometer for calibration IR conditions Instrument: MIRAN SapphIRe model 205B Path length: Short (0.5m) Wavelength: 10.699 μm The IR spectrophotometer was calibrated using external standards. Absorbance measurements acquired by the IR spectrophotometer were us ed to calculate analysed concentration (ppm) using a 2 nd order fit subjected to least squares regression analysis. Standards were shared with another concurrent and related study.Huntingdon Life Sciences WAG0014

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## 5.3 Nominal Concentration A mean daily nominal concentration was calculated for all test groups from the mass of test article used over the exposure period and the airflow through the exposure chamber. The ideal gas equation was used with the molecular weight of the test article and the measured chamber conditions to compute the volume of va pour produced from the mass of test article used. This data is not reporte d but retained in the raw data. 

## 5.4 Chamber Temperature Monitored using a liquid in glass thermometer. 

## 5.5 Chamber Humidity Monitored using wet and dry liquid in glass thermometers, with humidity calculated using proprietary tables. 

# 6. Data and Calculations To minimize the cumulative errors from repeated rounding of numbers, data in this report has been calculated continuously using unrounded numbers and only rounded for printing. Consequently, presented data may include rounding errors in the last significant figure. All data not presented in thisreport is retained in the st udy data files and archives. 

# 7. Results and Discussion 7.1 Aerosol Concentrations Individual exposure concentrations and daily means are presented in Table 1 to 3 and summarized below:

Group Concentration (ppm) Target Mean 2 200 199 3 500 505 4 3000 2876 

### All groups were close to target. Additional samples were taken for confirmation of atypical results and after minor generation rate adjustments. All samples collected for Group 1 were negative for the presence of test article. This information is not tabulated but is retained in the study data files.Huntingdon Life Sciences WAG0014

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## 7.2 Chamber Temperature The chamber temperature was monitored continuously for all groups and recorded at 30 minute intervals. Daily means are presented in Table 4 and were within expected parameters for this type of exposure system. 

## 7.3 Chamber Humidity The chamber humidity was derived from wet and dry bulb thermometers for all groups. These temperatures were recorded at 30 minute intervals and the subsequent humidity determined from propriatory tables. Daily means are presented in Table 5 and were within expected parameters for this type of exposure system.Huntingdon Life Sciences WAG0014

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### Table 1 Chamber atmosphere concentration of 2-bromo-3,3,3-trifluoropropene – daily means and individual exposure values – Group 2 Chamber concentration (ppm) Week/ Exposure Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Daily mean 1.1 190 188 190 189 1.2 190 188 188 189 1.3 231 192 198 207 1.4 223 188 194 202 1.5 188 196 200 195 2.1 189 195 189 191 2.2 191 214 191 199 2.3 63 92 115 147 147 178 124 2.4 166 92 187 174 155 2.5 201 206 212 206 3.1 115 203 212 177 3.2 189 1 206 1 208 1 3.3 86 176 195 187 161 3.4 199 180 203 194 3.5 201 206 206 204 4.1 183 192 194 190 4.2 188 190 190 189 4.3 181 194 196 190 4.4 186 192 196 191 4.5 181 192 194 189 5.1 190 192 192 191 5.2 192 192 192 192 5.3 190 195 197 194 5.4 188 195 195 193 5.5 190 190 197 192 6.1 192 194 180 189 6.2 202 209 207 206 6.3 213 215 213 214 6.4 205 211 217 211 6.5 202 215 219 212 7.1 211 217 219 216 7.2 215 215 221 217 7.3 191 197 209 199 7.4 189 201 203 198 7.5 188 192 194 191 8.1 197 199 203 200 8.2 202 204 212 206 8.3 202 206 204 204 8.4 204 210 212 209 8.5 206 208 204 206 9.1 205 220 216 214 9.2 207 212 216 212 9.3 203 210 218 210 9.4 216 216 220 217 9.5 205 220 225 217Huntingdon Life Sciences WAG0014

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### Table 1 Chamber atmosphere concentration of 2-bromo-3,3,3-trifluoropropene – daily means and individual exposure values – Group 2 (continued) Chamber concentration (ppm) Week/ Exposure Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Daily mean 10.1 203 207 210 207 10.2 175 193 201 190 10.3 212 214 222 216 10.4 185 193 210 196 10.5 212 218 220 217 11.1 193 200 195 196 11.2 204 202 208 205 11.3 232 185 230 216 11.4 202 210 204 205 11.5 195 202 202 200 12.1 205 195 201 200 12.2 264 187 203 218 12.3 201 205 207 204 12.4 199 205 203 202 12.5 199 205 209 204 13.1 258 202 193 218 13.2 189 184 197 190 13.3 184 189 193 189 13.4 189 189 193 190 13.5 193 193 193 193 14.1 192 196 196 195 14.2 188 194 196 193 14.3 192 196 196 195 Mean 199 2

sd 15.7 CV (%) 7.9 1 For exposures 3.2 the samples have been excluded due to standard check bag failures. The samples and test article usage are within expected tolerances. 2 Overall mean from occasions 1.1 to 13.5 sd Standard deviation CV (%) Coefficient of variation (sd × 100/mean)Huntingdon Life Sciences WAG0014

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### Table 2 Chamber atmosphere concentration of 2-bromo-3,3,3-trifluoropropene – daily means and individual exposure values – Group 3 Chamber concentration (ppm) Week/ Exposure Sample 1 Sample 2 Sample 3 Sample4 Sample 5 Sample 6 Sample 7 Daily mean 1.1 553 749 519 677 625 1.2 132 697 287 708 456 1.3 485 465 439 463 1.4 459 503 441 468 1.5 509 513 467 496 2.1 464 443 469 459 2.2 389 486 1 438 2.3 308 299 786 571 499 471 839 539 2.4 417 551 456 475 2.5 346 299 735 630 503 3.1 394 456 469 440 3.2 490 2566 2516 2 3.3 458 486 490 478 3.4 503 392 564 486 3.5 407 687 531 467 523 4.1 462 522 518 501 4.2 495 409 608 362 469 4.3 329 453 453 412 4.4 475 469 608 517 4.5 460 489 531 493 5.1 549 505 539 531 5.2 489 354 503 539 471 5.3 483 451 489 474 5.4 517 567 580 555 5.5 430 517 535 537 505 6.1 453 453 578 495 6.2 476 566 615 552 6.3 498 459 541 499 6.4 512 516 549 526 6.5 613 615 642 599 586 541 506 586 7.1 111 548 409 475 437 810 756 507 7.2 347 488 453 429 7.3 465 455 518 479 7.4 536 494 500 510 7.5 537 513 499 516 8.1 537 510 522 523 8.2 511 466 501 493 8.3 451 507 619 557 534 8.4 491 852 575 509 607 8.5 501 466 523 497 9.1 540 500 487 509 9.2 743 511 481 571 577 9.3 716 593 558 520 597 9.4 476 476 450 467 9.5 453 452 505 470Huntingdon Life Sciences WAG0014

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### Table 2 Chamber atmosphere concentration of 2-bromo-3,3,3-trifluoropropene – daily means and individual exposure values – Group 3 (continued) Chamber concentration (ppm) Week/ Exposure Sample 1 Sample 2 Sample 3 Sample4 Sample 5 Sample 6 Sample 7 Daily mean 10.1 511 484 463 486 10.2 488 469 465 474 10.3 482 559 534 525 10.4 488 488 534 503 10.5 633 528 648 824 593 645 11.1 520 551 461 511 11.2 540 538 527 535 11.3 452 505 514 490 11.4 468 472 479 473 11.5 470 509 479 486 12.1 542 497 501 513 12.2 515 474 524 504 12.3 478 466 495 480 12.4 542 478 505 508 12.5 476 495 433 468 13.1 552 469 485 502 13.2 449 396 507 451 13.3 516 668 443 542 13.4 569 523 460 517 13.5 518 608 561 562 14.1 395 655 574 541 14.2 534 534 510 526 14.3 427 554 514 498 Mean 505 3

sd 45.0 CV (%) 8.9 1 Electrical fault with analyser no sample taken. 2 For exposures 3.2 the samples have been excluded due to standard check bag failures. The samples and test article usage are within expected tolerances. 3 Overall mean from occasions 1.1 to 13.5 sd Standard deviation CV (%) Coefficient of variation (sd × 100/mean)Huntingdon Life Sciences WAG0014

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### Table 3 Chamber atmosphere concentration of 2-bromo-3,3,3-trifluoropropene – daily means and individual exposure values – Group 4 Chamber concentration (ppm) Week/ Exposure Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Daily mean 1.1 2854 2716 2902 2824 1.2 2726 2838 2392 2652 1.3 2490 2621 2713 2608 1.4 2379 2147 2414 2313 1.5 2364 2110 1788 2087 2.1 2265 2240 2253 2253 2.2 702 2104 1992 1 1599 2.3 3175 3332 3191 3092 2817 3121 2.4 2860 2584 2362 2602 2.5 1990 2293 3007 2430 3.1 3095 2975 3356 3142 3.2 2697 2 2944 2 2707 2 3.3 2046 2224 2771 2278 2330 3.4 2586 386 3 3148 3228 2987 3.5 2871 3856 3268 1575 2864 2887 4.1 3274 3030 3111 3138 4.2 3030 3415 3518 3184 3287 4.3 2426 3316 3297 3013 4.4 3297 3027 3349 3224 4.5 2845 3200 3168 3071 5.1 3043 2858 3095 2999 5.2 3422 3016 1707 2994 2888 2805 5.3 2301 3087 2745 2711 5.4 2977 3696 2734 3136 5.5 2615 2745 3040 2874 2819 6.1 2711 2795 3377 2961 6.2 2766 3262 2401 3341 2943 6.3 2908 2751 3256 2972 6.4 3224 3243 3181 3216 6.5 2483 3181 2714 2546 3458 2876 7.1 719 2939 2550 3526 3387 2958 2680 7.2 2345 2435 3136 2917 2708 7.3 2476 2936 2721 2606 2684 2685 7.4 2338 2710 2826 2625 7.5 2734 2990 2721 2815 8.1 2731 2809 3023 2854 8.2 2717 3088 2880 2895 8.3 2638 2707 3287 2877 8.4 3214 3106 2955 3092 8.5 4103 3168 2717 2702 3173 9.1 3217 2953 2783 2984 9.2 3209 2796 2791 2932 9.3 2877 3179 2806 2954 9.4 3017 2882 2838 2912 9.5 2895 2778 3030 2901Huntingdon Life Sciences WAG0014

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### Table 3 Chamber atmosphere concentration of 2-bromo-3,3,3-trifluoropropene – daily means and individual exposure values – Group 4 (continued) Chamber concentration (ppm) Week/ Exposure Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Daily mean 10.1 2138 2974 3216 2816 2786 10.2 2983 3108 3111 3067 10.3 3276 2706 3162 3048 10.4 2716 3097 3602 2430 2961 10.5 4242 2824 2631 2805 3126 11.1 3236 3016 2790 3014 11.2 2809 2793 2683 2762 11.3 3211 2899 2753 2954 11.4 2822 2936 2925 2894 11.5 3043 3076 2848 2989 12.1 2761 2700 2929 2797 12.2 3472 3163 2758 3131 12.3 2996 2964 2755 2905 12.4 3447 3608 3006 3354 12.5 3048 3334 3160 3181 13.1 3412 3096 2750 3086 13.2 2750 2807 3111 2889 13.3 2818 1932 2986 2579 13.4 2912 2929 3134 2992 13.5 3427 3415 3448 3430 14.1 3328 3229 3247 3268 14.2 3707 3107 3219 2911 3236 14.3 2864 3014 2814 2897 Mean 2876 4

sd 304 CV (%) 10.6 1 Electrical fault with analyser no sample taken. 2 For exposures 3.2 the samples have been excluded due to standard check bag failures. The samples and test article usage are within expected tolerances. 3 Value omitted from daily mean due to sample taken when pressure vessel was empty, vessel refilled and sample repeated. 4 Overall mean from occasions 1.1 to 13.5 sd Standard deviation CV (%) Coefficient of variation (sd × 100/mean)Huntingdon Life Sciences WAG0014

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### Table 4 Chamber Temperature - daily mean values Exposure Week/Day Chamber Temperature (°C) Group 1 Group 2 Group 3 Group 4 1.1 23.8 22.1 22.1 22.9 1.2 23.8 22.8 22.7 23.0 1.3 24.7 22.5 22.3 23.0 1.4 24.5 22.2 22.0 22.4 1.5 24.7 22.9 22.5 23.2 2.1 24.6 22.6 22.5 22.9 2.2 24.4 22.5 22.2 22.7 2.3 25.9 23.9 23.0 23.8 2.4 24.8 23.9 23.0 23.6 2.5 26.0 23.7 23.2 24.3 3.1 24.7 23.4 22.7 24.2 3.2 24.1 22.5 21.9 24.3 3.3 24.9 22.8 21.8 23.7 3.4 25.3 22.9 22.8 23.4 3.5 25.0 23.8 23.6 24.2 4.1 25.4 24.0 23.2 24.4 4.2 24.8 24.3 23.3 24.3 4.3 25.1 24.5 23.3 24.2 4.4 24.8 24.2 23.4 25.0 4.5 25.6 24.8 23.8 24.2 5.1 25.2 24.3 23.7 24.4 5.2 25.3 24.6 23.9 24.8 5.3 25.5 24.8 23.6 25.0 5.4 25.9 24.5 23.9 24.4 5.5 25.5 24.9 23.8 24.7 6.1 25.5 24.3 23.4 25.4 6.2 25.7 23.8 23.0 24.8 6.3 25.4 23.8 22.9 25.3 6.4 25.3 24.3 22.9 24.6 6.5 26.2 23.8 22.4 24.6 7.1 25.7 22.7 22.8 24.9 7.2 25.8 22.6 23.4 25.0 7.3 26.2 23.8 23.2 24.0 7.4 25.8 23.6 23.4 23.8 7.5 25.6 24.1 24.3 25.3 8.1 26.1 24.3 23.8 25.8 8.2 25.8 23.8 23.7 24.9 8.3 25.8 23.8 23.3 24.5 8.4 26.5 24.7 23.8 25.0 8.5 26.6 24.7 23.0 24.3 9.1 25.9 24.0 23.3 24.9 9.2 25.5 23.7 23.9 24.4 9.3 25.6 24.0 22.3 25.1 9.4 24.7 22.3 22.6 24.2 9.5 25.6 22.9 21.6 23.6 10.1 24.2 21.7 22.8 23.9 10.2 25.0 23.8 22.5 23.8 10.3 24.9 23.1 22.8 23.6 10.4 23.9 22.9 22.6 23.0 10.5 25.3 23.0 22.1 23.8Huntingdon Life Sciences WAG0014

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### Table 4 Chamber Temperature - daily mean values- (Continued) Exposure Week/Day Chamber Temperature (°C) Group 1 Group 2 Group 3 Group 4 11.1 24.3 23.0 22.3 23.6 11.2 24.8 23.5 23.0 24.2 11.3 24.9 23.1 22.9 23.5 11.4 24.9 23.0 22.7 23.8 11.5 24.8 22.8 22.3 23.0 12.1 24.9 23.4 22.7 24.4 12.2 24.9 23.1 22.8 24.0 12.3 24.9 22.9 22.8 24.1 12.4 24.9 23.1 22.8 24.0 12.5 25.1 23.1 22.7 24.1 13.1 24.3 22.4 21.6 23.2 13.2 22.8 20.9 20.8 21.6 13.3 22.7 19.5 20.8 22.3 13.4 22.9 21.0 20.9 22.1 13.5 23.7 21.8 21.2 22.2 14.1 21.0 20.9 20.5 20.9 14.2 20.9 20.2 20.0 20.7 14.3 20.6 20.0 20.0 20.5 Mean 24.9 23.2 22.7 23.9

sd 1.19 1.17 0.94 1.10 CV (%) 4.8 5.1 4.2 4.6 sd Standard deviation CV (%) Coefficient of variation (sd × 100/mean)Huntingdon Life Sciences WAG0014

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### Table 5 Chamber Humidity - daily mean values Exposure Week/Day Chamber Humidity (%) Group 1 Group 2 Group 3 Group 4 1.1 31.1 27.2 32.8 36.8 1.2 29.1 22.9 22.8 38.6 1.3 25.0 26.2 25.7 37.2 1.4 26.8 26.5 34.8 42.7 1.5 25.2 21.7 24.2 37.0 2.1 28.0 35.9 28.5 38.5 2.2 29.6 34.3 30.6 39.0 2.3 30.9 49.6 32.9 47.2 2.4 52.0 51.2 29.9 51.2 2.5 30.2 37.5 40.2 39.2 3.1 72.5 46.2 48.6 60.2 3.2 50.9 48.0 40.2 53.1 3.3 34.5 50.1 48.9 78.0 3.4 35.8 36.5 51.2 68.1 3.5 49.9 31.6 41.6 51.6 4.1 28.3 37.1 47.8 53.1 4.2 44.2 29.1 38.1 64.4 4.3 35.8 30.8 47.9 50.9 4.4 41.5 36.5 44.0 54.9 4.5 34.5 30.7 44.6 57.0 5.1 39.7 35.2 47.7 49.9 5.2 36.7 38.5 44.8 49.8 5.3 34.8 38.0 49.4 48.2 5.4 39.0 35.0 44.4 57.7 5.5 33.5 32.0 41.6 50.2 6.1 33.0 39.0 42.9 50.7 6.2 31.5 36.8 49.2 53.8 6.3 34.0 39.6 38.3 41.8 6.4 40.8 38.3 42.4 47.8 6.5 35.2 43.5 41.2 56.5 7.1 29.8 51.4 60.1 44.7 7.2 29.5 51.6 53.8 45.5 7.3 28.7 41.3 46.3 63.8 7.4 32.1 43.8 50.0 61.0 7.5 29.2 32.2 43.6 47.8 8.1 25.9 29.0 38.5 48.4 8.2 29.8 37.0 38.1 49.3 8.3 27.3 32.6 41.1 55.5 8.4 31.3 30.2 40.6 48.4 8.5 33.0 33.0 44.1 54.7 9.1 29.0 38.4 44.4 47.2 9.2 32.1 32.5 50.1 58.9 9.3 32.6 29.2 40.3 44.5 9.4 30.2 27.8 39.6 42.6 9.5 29.4 26.8 34.9 49.2 10.1 24.8 49.5 37.5 41.2 10.2 20.4 32.7 36.8 38.9 10.3 21.9 18.3 33.1 45.4 10.4 21.9 21.1 27.8 54.0 10.5 18.5 21.2 33.8 47.6Huntingdon Life Sciences WAG0014

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### Table 5 Chamber Humidity - daily mean values- (Continued) Exposure Week/Day Chamber Humidity (%) Group 1 Group 2 Group 3 Group 4 11.1 20.8 21.2 35.1 40.8 11.2 20.3 22.0 31.8 34.5 11.3 18.7 22.2 33.8 39.8 11.4 23.1 19.6 31.0 38.1 11.5 14.5 21.2 32.3 49.9 12.1 20.9 24.2 32.4 39.3 12.2 22.2 19.9 31.2 42.1 12.3 23.5 23.0 33.5 43.7 12.4 22.8 21.4 32.8 42.7 12.5 20.0 25.3 30.7 49.4 13.1 20.9 24.0 28.6 49.7 13.2 21.5 25.0 30.7 49.5 13.3 26.0 20.7 30.5 47.5 13.4 23.2 21.1 31.8 47.8 13.5 16.5 21.3 30.1 49.5 14.1 22.2 23.7 28.1 46.5 14.2 20.6 25.8 30.2 43.8 14.3 22.5 21.2 35.1 50.5 Mean 29.9 31.9 38.3 48.5

sd 9.49 9.28 7.99 8.08 CV (%) 31.8 29 .1 20.8 16.7 sd Standard deviation CV (%) Coefficient of variation (sd × 100/mean)Huntingdon Life Sciences WAG0014

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### Figure 1 Schematic of Inhalation Exposure System

D A B

F C E

F

H I

J K Front view Side view

L Generation Trolley

G M N P Q O



### Key A Whole body chamber J Water bath B Test material delivery tu bing K Generation flowmeters C Elutriator L Control valves D Secondary generation trolley M Balance for more accurate weighing E Magnahelics N Harvard Syringe driver F Pressure Vessels O Sampling port G Load cells P Extract plenum inside chamber H Air-line coil Q Drain for washing down I Sintered glass vaporiser Closed during exposureHuntingdon Life Sciences WAG0014

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### Annex **3 Pathology report** Huntingdon Life Sciences WAG0014

Page 1 of 17 

### Working for a better futur e



## PATHOLOGY REPORT 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period

HLS study number: WAG0014 Version ID: Final 2 Report Issue date: 07 October 2013Huntingdon Life Sciences WAG0014

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# Table of Contents Signature Page ................................................................................................................ ....... 2 1. Introduction .................................................................................................................. .. 4 1.1 Objective ............................................................................................................ 4 2. Results ....................................................................................................................... .... 4 2.1 Decedents .......................................................................................................... 4 2.2 Macroscopic Pathology ...................................................................................... 4 2.2.1 Animals killed after 13 weeks of treatment ............................................. 4 2.2.2 Animals killed after 4 weeks of recovery ................................................ 5 2.3 Microscopic Pathology ....................................................................................... 6 2.3.1 Animals killed after 13 weeks of treatment ............................................. 6 2.3.2 Animals killed after 4 weeks of recovery .............................................. 13 3. Discussion .................................................................................................................... 14 4. Conclusion ................................................................................................................... 16 5. References ................................................................................................................... 17



### .Huntingdon Life Sciences WAG0014

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# 1. Introduction 1.1 Objective Assessment of local and systemic toxic potential in a 13 week inhalation study in CD Rats with assessment of reversibility, progression, ordelayed appearance of any observed effects over both a 4 week recovery (non-dosing) period.

Group Treatment Achieved Exposure level (ppm) Number of animals Main study Recovery Phase Male Female Male Female 1 Control 0 10 10 10 10 2 2-bromo-3,3,3-trifluoropropene 199 10 10 - - 3 2-bromo-3,3,3-trifluoropropene 505 10 10 - - 4 2-bromo-3,3,3-trifluoropropene 2876 10 10 10 10 

# 2. Results 2.1 Decedents One female control animal (No. 27) was killedon Day 52, due to poor clinical condition. Irregular surface of the liver; oedematous pancreas and thymus; thickened pericardium, adhesion to pericardium and peri cardial fluid with the heart; dark bronchial lymph node and fluid filled thorax were seen at necropsy. Following microscopic examination, significant findings were seen in the lung (perivascular h aemorrhage and pleural fibrosis); heart (marked pericarditis, adhesion, marked pericardial haemorrhage and marked pericardial fibrosis) and the thymus (moderate atrophy). The factor contributory to death is pericarditis. 

## 2.2 Macroscopic Pathology 2.2.1 Animals killed after 13 weeks of treatment The macroscopic examination performed after 13 weeks of treatment revealed the following intergroup differences of note:Huntingdon Life Sciences WAG0014

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### Teeth Pallor was noted in all animals exposed to 2876 ppm, the majority of animals exposed to 505 ppm and a few animals exposed to 199 ppm. Thickening was seen in the majority of females and one male exposed to 2876 ppm.

Summary of findings in the teeth for anim als killed after 13 weeks of treatment Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Incisor(s) pale 0 3 7 10 0 3 9 10 Incisor(s) thickened 0 0 0 1 0 0 0 8 Number of animals examined 10 10 10 10 9 10 10 10 

### Spleen Capsular thickening was observed in the majority of males and some females exposed to 2876 ppm and a few animals exposed to 505 ppm. Adhesions were noted in some females exposed to 505 or 2876 ppm.

Summary of findings in the spleen for animals killed after 13 weeks of treatment Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Capsule thickened 1 1 4 8 0 1 2 5 Adhesions 0 0 0 0 0 0 2 5 Number of animals examined 10 10 10 10 9 10 10 10 

### The nature and incidence of all the other findi ngs were consistent with the commonly seen background of macroscopic changes. 2.2.2 Animals killed a fter 4 weeks of recovery The macroscopic examination performed after 4 weeks of recovery revealed the following changes in teeth and spleen.Huntingdon Life Sciences WAG0014

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### Teeth Pallor was noted in all animals exposed to 2876 ppm. Thickening was seen in occasional females and one male previously exposed to 2876 ppm.

Summary of findings in the teeth for an imals killed after 4 weeks of recovery Group/sex 1M 4M 1F 4F Dose (ppm) 0 2876 0 2876 Incisor(s) pale 0 10 0 10 Incisor(s) thickened 0 1 0 3 Number of tissues examined 10 10 10 10 

### Spleen Capsular thickening was observed in one male previously exposed to 2876 ppm. Adhesions were noted in some males and one female previously exposed to 2876 ppm.

Summary of findings in the spleen for animals killed after 4 weeks of recovery Group/sex 1M 4M 1F 4F Dose (ppm) 0 2876 0 2876 Capsular thickened 0 1 0 0 Adhesions 0 2 0 1 Number of tissues examined 10 10 10 10 

### All other findings were consideredto be unrelated to treatment. 

## 2.3 Microscopic Pathology 2.3.1 Animals killed after 13 weeks of treatment Treatment related findings Changes related to treatment with 2-bromo- 3, 3, 3-trifluoropropene were seen in liver, pancreas, heart, spleen, thymus, larynx, nasal turbinates and teeth.Huntingdon Life Sciences WAG0014

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### Liver Centrilobular hepatocyte hypertrophy was seenin rats exposed to 2876 ppm and a female exposed to 505 ppm.

Summary of treatment related findings in the liver for animals killed after 13 weeks of treatment Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Hepatocyte Hypertrophy, Centrilobular Minimal 0 0 0 2 0 0 1 4 Total 0 0 0 2 0 0 1 4 Number of tissues examined 10 10 10 10 9 10 10 10 

### Pancreas Increased incidence of acinar cell degranulation was seen in rats at all exposure levels.

Summary of treatment related findings in the pancrea s for animals killed after 13 weeks of treatment Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Acinar Cell Degranulation Minimal 0 3 2 1 0 2 3 0 Slight 0 0 3 5 1 2 2 6 Moderate 0 0 0 1 0 0 0 0 Total 0 3 5 7 1 4 5 6 Number of tissues examined 10 10 10 10 9 10 10 10 

### Heart Increased incidence of chroni c inflammation was seen in males exposed to 199 ppm and both sexes exposed to 505 or 2876 ppm.

Summary of treatment related findings in the heart for animals killed after 13 weeks of treatment Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Inflammation, Chronic Minimal 0 4 2 1 0 0 4 7 Slight 0 0 7 3 0 0 0 2 Moderate 0 0 0 4 0 0 0 1 Total 0 4 9 8 0 0 4 10 Number of tissues examined 10 10 10 10 9 10 10 10Huntingdon Life Sciences WAG0014

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### Spleen Increased incidences of capsular inflammation and/ or thickening were seen in rats exposed to 505 or 2876 ppm. Adhesion was seen in females exposed to 505 or 2876 ppm.

Summary of treatment related findings in the spleenfor animals killed after 13 weeks of treatment Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Capsular Inflammation Minimal 0 0 1 2 0 1 0 1 Slight 0 0 1 3 0 0 1 3 Moderate 0 0 1 0 0 0 0 2 Total 0 0 3 5 0 1 1 6 Capsular Thickening Minimal 0 1 1 4 1 2 2 2 Slight 1 0 2 2 0 0 1 2 Moderate 0 0 0 0 0 0 0 4 Total 1 1 3 6 1 2 3 8 Adhesion Total 0 0 0 0 0 0 1 3 Number of tissues examined 10 10 10 10 9 10 10 10 

### Thymus Involution/ atrophy was seen inone male and five femalerats exposed to 2876 ppm.

Summary of treatment related findings in the thymusfor animals killed after 13 weeks of treatment Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Involution/Atrophy Minimal 0 0 0 0 0 0 0 2 Slight 0 0 0 0 0 0 0 1 Moderate 0 0 0 1 0 0 0 2 Total 0 0 0 1 0 0 0 5 Number of tissues examined 10 10 10 10 9 10 10 10Huntingdon Life Sciences WAG0014

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### Larynx Ventral squamous metaplasia was seen in fi ve male and two female rats exposed to 2876 ppm.

Summary of treatment related findings in the larynxfor animals killed after 13 weeks of treatment Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Squamous Metaplasia - Ventral Minimal 0 0 0 5 0 0 0 2 Total 0 0 0 5 0 0 0 2 Number of tissues examined 10 10 10 10 9 10 10 10 

### Nasal Turbinates In the respiratory epithelium, atrophy/disorganization/vacuolation, inflammation and inflammatory cells in the lamina propria were seen in the rats exposed to 2876 ppm. A case of regenerative hyperplasia was also seen in a male at the same exposure level. In the olfactory epithelium, atrophy/ disorganisation /vacuolation, was seen in rats exposed to 505 or 2876 ppm. Inflammation and inflammatory cells in the lamina propria were seen in rats exposed to 2876 ppm. Respiratory metaplasiawas seen in females exposed to 2876 ppm. In the nasolacrimal duct, inflammation was s een in females exposed to 505 ppm and both sexes exposed to 2876 ppm. Epithelial squamous metaplasia and luminal inflammatory exudates were seen in females exposed to 2876 ppm. Inflammatory exudates in airways wereseen in rats exposed to 2876 ppm.Huntingdon Life Sciences WAG0014

Page 10 Summary of treatment related findings in the nasal turbinates for animals killed after 13 weeks of treatment Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Increased Vacuolation of Vomeronasal Organ Epithelium Minimal 0 0 0 1 0 0 0 0 Slight 0 0 0 2 0 0 0 0 Total 0 0 0 3 0 0 0 0 Respiratory Epithelium Atrophy/ Disorganisation/ Vacuolation Minimal 0 1 0 1 1 1 1 1 Slight 0 0 0 4 0 0 0 6 Moderate 0 0 0 1 0 0 0 3 Total 0 1 0 6 1 1 1 10 Inflammation Minimal 0 0 0 0 0 0 0 1 Slight 0 0 0 1 0 0 0 2 Total 0 0 0 1 0 0 0 3 Inflammatory Cells in the Lamina Propria Minimal 0 0 0 0 0 0 0 2 Slight 0 0 0 0 0 0 0 8 Moderate 0 0 0 1 0 0 0 0 Total 0 0 0 1 0 0 0 10 Regenerative Hyperplasia Slight 0 0 0 1 0 0 0 0 Total 0 0 0 1 0 0 0 0 Olfactory Epithelium Atrophy/ Disorganisation/ Vacuolation Minimal 1 2 5 0 0 0 2 0 Slight 0 0 3 8 1 0 3 4 Moderate 0 0 0 2 0 0 0 6 Total 1 2 8 10 1 0 5 10 Inflammation Slight 0 0 0 3 1 0 0 2 Total 0 0 0 3 1 0 0 2 Inflammatory Cells in the Lamina Propria Minimal 0 0 0 0 1 0 0 1 Slight 0 0 0 2 0 0 0 7 Total 0 0 0 2 1 0 0 8 Respiratory Metaplasia Minimal 0 0 0 0 0 0 0 1 Slight 0 0 0 0 0 0 0 4 Total 0 0 0 0 0 0 0 5 Number of tissues examined 10 10 10 10 9 10 10 10Huntingdon Life Sciences WAG0014

Page 11 Summary of treatment related findings in the nasal turbinates for animals killed after 13 weeks of treatment (Cont’d) Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Nasolacrimal Duct Inflammation Minimal 1 3 1 2 2 1 1 0 Slight 4 5 3 5 0 3 5 5 Moderate 0 0 0 1 0 0 1 4 Total 5 8 4 8 2 4 7 9 Epithelial Squamous Metaplasia Minimal 0 1 0 0 1 0 0 1 Slight 1 0 0 0 1 3 2 2 Moderate 0 0 0 0 0 0 0 5 Total 1 1 0 0 2 3 2 8 Luminal Inflammatory Exudate Minimal 0 0 0 0 0 0 0 1 Slight 0 0 0 0 0 0 0 1 Moderate 0 0 0 0 0 0 0 2 Total 0 0 0 0 0 0 0 4 Inflammatory Exudate in Airways Minimal 0 0 0 1 0 0 0 3 Slight 0 0 0 0 0 0 0 2 Total 0 0 0 1 0 0 0 5 Number of tissues examined 10 10 10 10 9 10 10 10 

### Teeth Pulp cavity necrosis was seen in females exposed to 2876 ppm.

Summary of treatment related findings in the teeth for animals killed after 13 weeks of treatment Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Pulp Cavity Necrosis Slight 0 0 0 0 0 0 0 4 Moderate 0 0 0 0 0 0 0 1 Total 0 0 0 0 0 0 0 5 Number of tissues examined 10 10 10 10 9 10 10 10Huntingdon Life Sciences WAG0014

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### Findings of an uncertain relationship to treatment Teeth Ameloblast degeneration, odontoblast degenerati on and pulp cavity increased inflammatory cell infiltration at mostlyminimal level were seen in a few rats exposed to 505 or 2876 ppm. As this finding was only evident for a small nu mber of animals and there was no clear dose relationship, the toxicologicalsignificance is uncertain.

Summary of findings of an uncertain relationship to treatment in the teeth after 13 weeks of treatment Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Ameloblast Degeneration Minimal 0 0 0 1 0 0 0 2 Total 0 0 0 1 0 0 0 2 Odontoblast Degeneration Minimal 0 0 0 1 0 0 2 1 Total 0 0 0 1 0 0 2 1 Pulp Cavity Increased Inflammatory Cell Infiltration Minimal 0 0 0 0 0 0 0 1 Slight 0 0 0 0 0 0 0 1 Total 0 0 0 0 0 0 0 2 Number of tissues examined 10 10 10 10 9 10 10 10 

### Incidental findings Pyelonephritis, with hyperplasia of both pelvic and papillary epithelium, in the kidneys and transitional cell hyperplasia and inflammation in the urinary bladder were seen in two females exposed to 2876 ppm. As these findingsare occasionally in rats, including controls, they are considered to be incidental and unlikely to be related to exposure to the test material. Malignant adenocarcinoma was seen in the Harderian gland of a female exposed to 2876 ppm and benign subcapsular cell adenoma was seen in the adrenal of a male exposed to 2876 ppm. Both findings are considered to be incidental. All other histological changes were cons idered to be unrelated to treatment.Huntingdon Life Sciences WAG0014

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### 2.3.2 Animals killed a fter 4 weeks of recovery Treatment related findings Spleen Capsular inflammation and/ or thickening at slight level wereseen in males previously exposed to 2876 ppm.

Summary of treatment-related chan ges in the spleen for animals killed after 4 weeks of recovery Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Capsular Inflammation Minimal 0 - - 2 0 - - 0 Total 0 - - 2 0 - - 0 Capsular Thickening Minimal 0 - - 0 0 - - 1 Slight 0 - - 2 0 - - 0 Total 0 - - 2 0 - - 1 Number of tissues examined 10 - - 10 10 - - 10 

### Nasal Turbinates In the olfactory epithelium, atrophy/ disorganisation/vacuol ation, was seen in the rats previously exposed to 2876 ppm. In the nasolacrimal duct, inflammation was seen in females previously exposed to 2876 ppm.

Summary of treatment-related chan ges in the nasal turbinates for animals killed after 4 weeks of recovery Group/sex 1M 2M 3M 4M 1F 2F 3F 4F Dose (ppm) 0 199 505 2876 0 199 505 2876 Olfactory Epithelium Atrophy/ Disorganisation/ Vacuolation Minimal 0 - - 2 1 - - 2 Slight 0 - - 7 0 - - 5 Total 0 - - 9 1 - - 7 Nasolacrimal Duct Inflammation Minimal 4 - - 4 5 - - 3 Slight 1 - - 2 0 - - 6 Total 5 - - 6 5 - - 9 Number of tissues examined 10 - - 10 10 - - 10Huntingdon Life Sciences WAG0014

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### Incidental findings All other histological changes, including chro nic inflammation seen in the heart of one control male and one male previously exposed to 2876 ppm, were considered to be unrelated to treatment. 

# 3. Discussion Minor localised toxic effects were seen in the upper respiratory tract (larynx and nasal turbinates) of animals exposedto 2876 ppm and, to a lesser degree, animals exposed to 505 ppm. Similar changes were seenin the two previous 2-week dose range studies of the same test material ( Huntingdon Life Sciences Study Numbers: WAG0013 andWAG0024) . Following a 4 week recovery period, full recoverywas seen for the larynx finding and partial recovery for the nasal turbinate findings. In the heart, chronic inflammation was seenin males exposed to 199 ppm and both sexes exposed to 505 or 2876 ppm. The minimal degree observed at 199 ppm is considered unlikely to be associated with any alteration of heart function and is cons idered not adverse. The slight and moderate degrees observed at 505 and 2876 ppm are considered adverse. This change may be related to the elevated alkali ne phosphatase and aspartate amino transferase levels measured during Week 13 of exposures. Complete recovery was seen following the 4 week recovery period. In the spleen, capsular infl ammation and/or thickening and adhesion, with corresponding macroscopic observations, were seen in animal s exposed to 2876 ppm and, to a lesser extent, animals exposed to 505 ppm. This is likely to be a toxic effect. Partial recovery was seen following the 4 week recovery period with the fi ndings seen in 2 males previously exposed to 2876 ppm. In the thymus, involution/atrophy, with corresponding reduction in organ weight, was seen in animals exposed to 2876 ppm. This is likely to be related to stress, as indicated by the effect on the body weight and food consumption, experiencedby the animals, in the presence of the test material, at this exposure level. Co mplete recovery was seen following the 4 week recovery period. In the liver, centrilobular hepatocyte hypertrophy at minimal level was seen in animals exposed to 2876 ppm and also a female exposed to 505 ppm. This is considered to be an adaptive change as a result of exposure to the test material. Complete recovery was seen following the 4 week recovery period. In the pancreas, increased incidence of acinar cell degranulation was seen in animals at all exposure levels. This is not considered to be a toxic response but rather a physiological change and likely to be related to the reduced food consumption recorded for these animals. Complete recovery was seen follo wing the 4 week recovery period.Huntingdon Life Sciences WAG0014

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### In the teeth, pulp cavity necrosis, with corres ponding macroscopic observations, was seen in females exposed to 2876 ppm, and it is considered to be a toxic effect. Full recovery was seen following the 4 week recovery period. There were no histopathological changes to account for the pale and/or thickene d incisors seen macroscopically. There were no histopathological changes seen in the study to account for the increased lung weight or the reduced saliv ary gland weight recorded for the treated animals.Huntingdon Life Sciences WAG0014

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# 4. Conclusion Following exposure of CD rats to atmospheres of 2-bromo-3,3,3-trifluoropropene for 13 weeks, test substance related findings were seen in the liver (centrilobular hepatocyte hypertrophy), pancreas (acinar cell degranulation), heart (chronic inflammation), spleen (capsular inflammation and/or thickening and adhesion), thymus (involution/atrophy), nasal turbinates (findings related to minor local irritants), larynx (ventral squamous metaplasia) and teeth (pulp cavity necrosis). The majority of these findings were seen with animals at 505 and 2876 ppm. Chronic inflammation in the he art and acinar cell de granulation in the pancreas were evident for animals exposed to 199 ppm, however, these changes are not considered to be adverse. Following the 4 week recovery peri od, there was complete recoveryof test material related histopathological changes seen in the liver, pancreas, heart, thymus, larynx and teeth and partial recovery for the findings see in the sp leen (capsular inflammation and/or thickening) and nasal turbinates (atrophy/disorganisation/vacuolation of the olfactory epithelium and nasolacrimal duct inflammation).Huntingdon Life Sciences WAG0014

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# 5. References Huntingdon Life Sciences Study Number: WAG0013 2-bromo-3,3,3-trifluoropropene: Dose Range Fi nding Study by Inhalati on Administration to Rats for 2 Weeks Huntingdon Life Sciences Study Number: WAG0024 2-bromo-3,3,3-trifluoropropene: Dose Range Fi nding Study by Inhalati on Administration to Rats for 2 WeeksHuntingdon Life Sciences WAG0014

661 

### Annex **4 Externa**  **l pathology peer review report**N o v a Pa t h o l o gy, P C



### Histopathology Review of the Heart in Male Rats: 2-bromo-3,3,3-trifluoropropene : Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period Nova Pathology Study Number: 13-025 Test Facility Study Number: WAG0014 Submitted By: Michael J Tomlinson, D.V.M, Ph.D. Diplomate, ACVP Nova Pathology, PC 1015 Railroad Ave., Suite 103 Bellingham, WA 98225, USA Sponsor: American Pacific Corporation 3883 Howard Hughes Parkway, Suite 700 Las Vegas, NV 89169, USA Test Facility: Huntingdon Life Sciences Eye, Suffolk

1P23 7PX EnglandHistopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period Test Facility Study Number: WAG0014 Table of Contents 1 Quality Assurance 3 2 Signature Page 3 3 Summary of Histologic Findings 4 4 Introduction 5 4.1 Experimental Design 5 4.2 Evaluation Procedure 5 4.3 Diagnostic Terms 6 5 Results / Discussion 6 6 Conclusions 9 In-Text Tables 1 Summary of Experimental Design 5 2 Summary of Selected Histologic Findings in the Heart: Main Study 7 3 Summary of Selected Histologic Findings in the Heart: Recovery 8 Data Tables 1 Summary of Histologic Findings: Main Study 10 2 Summary of Histologic Findings: Recovery 12 3 Individual Animal Data 14 4 Tabulated Summary of Study Pathologist and Reviewing Pathologist Findings 23Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period Test Facility Study Number: WAG0014 3 Summary of Test Article-Related Histologic Findings The objective of this independent histopathology review was to more completely characterize the test article-related histologic findings in the heart of male rats in all groups in study WAG0014, Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period, conducted by Huntingdon Life Sciences, Eye, Suffolk, 1P23 7PX, England. The findings attributed to the test article by the reviewing pathologist are: 2-bromo-3,3,3-trifluoropropene 199 ppm 1. Minimal chronic inflammation in the heart in 4 of 10 males in the main study. 2-bromo-3,3,3-trifluoropropene 505 ppm 1. Minimal to slight chronic inflammation in the heart in 9 of 10 males in the main study . 2-bromo-3,3,3-trifluoropropene 2,876 ppm 1. Minimal to moderate chronic inflammation in the heart in 8 of 10 males in the main study.Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period Test Facility Study Number: WAG0014 4 Introduction The objective of this independent histopathology review was to more completely characterize the test article-related histologic findings in the heart of male rats in all groups in study WAG0014, Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period, conducted by Huntingdon LifeSciences, Eye, Suffolk, 1P23 7PX, England. 4.1 Experimental Design This was a 13 week repeat exposure inhalation toxi city study in Crl:CD (SD) rats followed by a 4 week recovery period. The animals received cleanair (control) or 2-bromo-3,3,3-trifluoropropene 6 hours/day, for 5 days each week for 13 weeks. The study included 10 rats per sex per group per scheduled sacrifice as outlined in the Summary of Experimental Design. In-Text Table 1: Summary of Experimental Design Group Dose (ppm) 2-bromo-3,3,3-trifluoropropene Number of Animals Main Study Recovery Male Female Male Female 1 0 10 10 10 10 2 199 10 10 - - 3 505 10 10 - - 4 2,876 10 10 10 10 4.2 Evaluation Procedure This review was conducted at N ova Pathology, 1015 Railroad Ave., Suite 103, Bellingham, WA 98225, USA on April 14 and 15, 2013. While this review was not a peer-review (no interaction between study pathologist and reviewing pathologist), the reviewing pathologist followed as appropriate the guidelines set forth in the recommendations for peer review published by the Society of Toxicologic Pathology (Morton, D, et al , Toxicologic Pathology , 38: 1118-1127, 2010). Slides containing hematoxylin and eosin (H&E) stained sections of heart from all malerats in this study were evaluated by light microscopy. Initially the slides from control and highdose males were reviewed in order to identify baseline findings in controls and possible test article-related findings in high-dose animals in th e main study. The slides from mid and low dose main study groups and control and high-dose recovery groups were then evaluated. The reviewing pathologist entered the histologic findings into a validated data management program (Graham StarToxTM version 3.0.0). The findings of the reviewing pathologist are presented in the data tables (1, 2 and 3). The relationship of observed histologic findings to the test article, 2- bromo-3,3,3-trifluoropropene, was determined from the incidence and severity of those findings. An increase in either incidence or severity with increasing exposure to the test article relative to the control group indicated that finding to be related to the test article. No statistical evaluation of the data from this review was performed due to the nature of histopathology data and the low number of animals in each group. Major differences between the study pathologist and the reviewing pathologist included absence of a diagnosis for a non-proliferative or proliferative lesion which was present or the presence of a diagnosis for a non-proliferative or proliferative lesion which was not present. Minor differences between the study pathologist and the reviewing pathologist included a difference of one severity grade or a difference of a severity grade of minimal and not present.Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period Test Facility Study Number: WAG0014 4.3 Diagnostic Terms The following diagnostic terms are defined to aid in the interpretation and discussion of the data. Other diagnostic terms used were considered to be self-explanatory. Inflammation, Chronic: Myocardial infiltrates of macrophages with fewer lymphocytes, interstitial fibroplasia/fibrosis and capillary di latation, most often observed in the apex, interventricular septum and free wall of the left ventricle. Infiltrate, Cellular, Myocardium: Focal aggregates of infiltrating lymphocytes with fewer macrophages in the myocardium; most often but not exclusively found in the free wall of the left and right ventricles (equivalent to cardiomyopathy). Hemorrhage: Extravascular blood within the myo cardium; associated with foci of inflammation or cellular infiltrates. The scheme for severity scoring of histologic findings used in the WAG0014 pathology report was maintained for consistency. Minimal: The lowest grade of a lesion which is discernible/distinguishable from normal and is often subtle and/or involves a very small area of the organ. Slight: Clearly discernible/distinguishable from normal with more extensive or more apparent changes than minimal. Moderate: Generally involves a significant portion of the affected organ or tissue. Marked: Involves the majority of the affected organ or tissue. Severe: Involves all or almost all of an affected organ or tissue. 5 Results / Discussion The histologic findings in the heart recorded bythe reviewing pathologist are presented in the following data tables. Table 1: Summary of Histologic Findings, Main study Table 2: Summary of Histologic Findings, Recovery Table 3: Individual Animal Data Table 4: Tabulated Summary of Study Pathologist and Reviewing Pathologist Findings The histologic findings recorded were assigned semi-quantitative severity scores based on the following scheme; minimal = 1, slight = 2, moderate = 3, marked = 4 and severe = 5 . The study pathologist identified myocardial inflammatory cell infiltration/fibrosis as a test articlerelated histologic finding in males at 199, 505 and at 2,876 ppm. The reviewing pathologist identified this finding as described by the study pathoogist but recognized a second finding identified as cellular infiltrate, myocardium, which was distinct both morphologically and in distribution from chronic inflammation. After review of all male hearts from main study and recovery males, it was unclear to the reviewing pathologist whether or not the diagnostic termHistopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period Test Facility Study Number: WAG0014 used by the study pathologist, myocardial inflammatory cell infiltration/fibrosis study pathologist included the finding of myocardial cellular infiltrates identified by the reviewing pathologist. Main Study The only histologic finding in the heart that was attributed to the test article in main study animals by the reviewing pathologist was chronic inflammation in Groups 2, 3 and 4. The incidence and incidence by severity of this finding are presented in the following table. In-Text Table 2: Summary of Selected Histologic Findings in the Heart: Main Study Finding Incidence / Incidence by Severity Group 1 2 3 4 Within Normal Limits Incidence 6/10 6/10 1/10 1/10 Inflammation, Chronic Incidence 0/10 4/10 9/10 8/10 minimal 0/10 4/10 3/10 1/10

slight 0/10 0/10 6/10 4/10 moderate 0/10 0/10 0/10 3/10 Infiltrate, Myocardium Cellular Incidence 4/10 2/10 2/10 4/10 minimal 4/10 2/10 2/10 4/10 Incidence = Number Affected / Number Evaluated In the main study, based on the data summarize d above, chronic inflammation in the myocardium was considered to be related to the test artic le in males at 199, 505 and at 2,876 ppm. This finding was regionally diffuse and most common in the apex and interventricular septum when of minimal severity and but was also present in the ventricular free walls at slight or moderate severity. Chronic inflammation was present in 4 of 10, 9 of 10 and 8 of 10 rats exposed to the test article at 199, 505 or 2,876 ppm, respectively. The severity of this finding was generally similar, minimal to moderate, in animals exposed at 505 or 2, 876 ppm but was of minimal severity in the 4 affected animals exposed at 199 ppm. Chroni c inflammation of minimal severity consisted predominantly of cellular infiltrates and capillary dilatation with fibroplasia/fibrosis being a minor part of the finding, even at slight or moderate severity. Cellular infiltrates in the myocardium were focal and most often in the free wall of the left and right ventricles. This finding occurred in all do se groups, was of minimal severity in all affected animals and did not have a dose-related incidence. Sometimes referred to as cardiomyopathy, this is a common finding in naïve male rats (Chanut, F. et al, Toxicologic Pathology , 00: 1-11, 2013, online). Based on its incidence and severity in this study, this finding was considered to be incidental and unrelated to the test article. Hemorrhage in one control rat was considered incidental. Recovery After the 4 week recovery period, both the incidence and severity of chronic inflammation in the myocardium were reduced relative to the main study high-dose group. The incidence and incidence by severity of this finding are presented in the following table.Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period Test Facility Study Number: WAG0014 In-Text Table 3: Summary of Summary of Selected Histologic Findings in the Heart: Recovery Finding Incidence / Incidence by Severity Group 1 4 Within Normal Limits Incidence 3/10 6/10 Inflammation, Chronic Incidence 1/10 1/10 minimal 0/10 1/10

slight 1/10 0/10 Infiltrate, Myocardium Cellular Incidence 6/10 3/10 minimal 6/10 3/10 Incidence = Number Affected / Number Evaluated After a 4 week recovery period, chronic inflammation was minimal in 1 of 10 high-dose animals. Chronic inflammation was also present in 1 of 10 control animals after the recovery period. The chronic inflammation in the affected control animal occurred in the apex and interventricular septum. Similar to the distribution within the heart, the morphologic features of this finding were also similar to those in the groups exposed to the test article though the interventricular septum contained a large focal infiltrate of mainly lymphocytes and was associated with hemorrhage. Based on the similarity of the inci dence and morphology of chronic inflammation in the affected control and high-dose recovery animals, this finding was considered to have resolved after the 4 week recovery period. Minimal cellular infiltrates in the myocardium were present in 6 of 10 control rats and in 3 of 10 high-dose rats and were considered to be incidental and unrelated to the test article. Hemorrhage in one control rat was considered incidental. Comparison of Study Pathologist and Reviewing Pathologist Findings This histopathology review was limited to sections of the heart of male rats from Study WAG0014. The findings of the study pathologist and the reviewing pathologist are compared in data Table 4 : Tabulated Summary of Study Path ologist and Reviewing Pathologist Findings. Myocardial inflammatory cell infiltration/fibrosis was the only histologic finding in the heart that was attributed to the test article by the study pathologist. The reviewing pathologist identified chronic inflammation in the myocardium as a test article-related finding. The reviewing pathologist also identified a second finding, myocardial cellular infiltrates (sometimes referred to as cardiomyopathy), which was not a test article-related finding. The study pathologist did not record the presence of cellular infiltrates, of cardiomyopathy or of another equivalent term. It was unclear to the reviewing pathologist whether the study pathologist considered cellular infiltrates to be part of the finding of myocardialinflammatory cell infiltration/fibrosis or were considered incidental and were not recorded. The study pathologist (myocardial inflammatorycell infiltration/fibrosis) and the reviewing pathologist (chronic inflammation) both identifie d equivalent test article-related histologic findings in the heart of male rats at exposures of 199, 505 and 2,876 ppm of 2-bromo-3,3,3- trifluoropropene at the end of the exposure peri od and both pathologists considered these findings to have resolved after a 4 week recovery period. For these reasons, the study pathologist and the reviewing pathologist were in general agreement.Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period Test Facility Study Number: WAG0014 6 Conclusions In this independent expert review , sections of heart from all main study and recovery male rats in this study were examined by light microscopy. The only histologic finding in the heart that was attributed to 2-bromo-3,3,3-trifluoropropene w as chronic inflammation in the myocardium. This finding was related to 2-bromo-3,3,3-trifluoropropene in males at 199, 505 and 2,876 ppm in main study animals. This finding was considered to have resolved after a 4 week recovery period.Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period Test Facility Study Number: WAG0014



### Data Table 1 Summary of Histologic Findings: Main StudyTable Number: 1 Summary of Histologic Findings: Main Study Study Number: WAG0014 Hintingdon Life Sciences Eye, Suffolk, 1P23 7PX, England Organs Group: Group 1 Group 2 Group 3 Group 4

Diagnoses Sacrifice: MS MS MS MS

Modifiers Sex: M M M M Total Animals Selected: [10] [10] [10] [10] Heart (10) (10) (10) (10)

Within Normal Limits 6 6 1 1 Hemorrhage 1 0 0 0

minimal 1 0 0 0 Infiltrate, Cellular, Myocardium 4 2 2 4

minimal 4 2 2 4 Inflammation, Chronic 0 4 9 8

minimal 0 4 3 1 slight 0 0 6 4 moderate 0 0 0 3

Group 1=Control Group 2=2-bromo-3,3,3-trifluoropropene, 199 ppm Group 3=2-bromo-3,3,3-trifluoropropene, 505 ppm Group 4=2-bromo-3,3,3-trifluoropropene, 2,876 ppmHistopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period Test Facility Study Number: WAG0014



### Data Table 2 Summary of Histologic Findings: RecoveryTable Number: 2 Summary of Histologic Findings: Recovery Study Number: WAG0014 Hintingdon Life Sciences Eye, Suffolk, 1P23 7PX, England Organs Group: Group 1 Group 4

Diagnoses Sacrifice: RE RE

Modifiers Sex: M M Total Animals Selected: [10] [10] Heart (10) (10)

Within Normal Limits 3 6 Hemorrhage 1 0

minimal 1 0 Infiltrate, Cellular, Myocardium 6 3

minimal 6 3 Inflammation, Chronic 1 1

minimal 0 1 slight 1 0

Group 1=Control Group 4=2-bromo-3,3,3-trifluoropropene, 2,876 ppm Page: 2Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period Test Facility Study Number: WAG0014



### Data Table 3 Individual Animal DataTable Number: 3 Individual Animal Data Study Number: WAG0014 Hintingdon Life Sciences Eye, Suffolk, 1P23 7PX, England Gp: ( 1) Control Animal Number: 61 Species: Rat Sex: Male

Microscopic Results

Heart Within Normal Limits Gp: ( 1) Control Animal Number: 62 Species: Rat Sex: Male

Microscopic Results

Heart Within Normal Limits Gp: ( 1) Control Animal Number: 63 Species: Rat Sex: Male

Microscopic Results

Heart Within Normal Limits Gp: ( 1) Control Animal Number: 64 Species: Rat Sex: Male

Microscopic Results

Heart Within Normal Limits Gp: ( 1) Control Animal Number: 65 Species: Rat Sex: Male

Microscopic Results

Heart Within Normal Limits Gp: ( 1) Control Animal Number: 66 Species: Rat Sex: Male

Microscopic Results

Heart Infiltrate, Cellular, Myocardium , apex , focal , minimal Gp: ( 1) Control Animal Number: 67 Species: Rat Sex: Male

Microscopic Results

Heart Within Normal Limits Gp: ( 1) Control Animal Number: 68 Species: Rat Sex: Male

Microscopic Results

Heart Infiltrate, Cellular, Myocardium , atrium , focal , minimal Gp: ( 1) Control Animal Number: 69 Species: Rat Sex: Male

Microscopic Results

Heart Hemorrhage , focal , apex , minimal Infiltrate, Cellular, Myocardium , apex , left ventricle , right ventricle , minimalTable Number: 3 Individual Animal Data Study Number: WAG0014 Hintingdon Life Sciences Eye, Suffolk, 1P23 7PX, England Gp: ( 1) Control Animal Number: 70 Species: Rat Sex: Male

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, left ventricle, focal, minimal Gp: ( 1) Control Animal Number: 81 Species: Rat Sex: Male

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, focal, minimal Gp: ( 1) Control Animal Number: 82 Species: Rat Sex: Male

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, apex, minimal Gp: ( 1) Control Animal Number: 83 Species: Rat Sex: Male

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, left ventricle, focal, minimal Gp: ( 1) Control Animal Number: 84 Species: Rat Sex: Male

Microscopic Results

Heart Hemorrhage, myocardium, interventricular septum, minimal Inflammation, Chronic, apex, interventricular septum, slight One large focus in the IVS is associated with the hemorrhage. Gp: ( 1) Control Animal Number: 85 Species: Rat Sex: Male

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, left ventricle, right ventricle, minimal Gp: ( 1) Control Animal Number: 86 Species: Rat Sex: Male

Microscopic Results

Heart Within Normal Limits Gp: ( 1) Control Animal Number: 87 Species: Rat Sex: Male

Microscopic Results

Heart Within Normal LimitsTable Number: 3 Individual Animal Data Study Number: WAG0014 Hintingdon Life Sciences Eye, Suffolk, 1P23 7PX, England Gp: ( 1) Control Animal Number: 88 Species: Rat Sex: Male

Microscopic Results

Heart Within Normal Limits Gp: ( 1) Control Animal Number: 89 Species: Rat Sex: Male

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, apex, left ventricle, minimal Gp: ( 1) Control Animal Number: 90 Species: Rat Sex: Male

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, right ventricle, minimal Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 101 Species: Rat Sex: Male Microscopic Results

Heart Within Normal Limits Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 102 Species: Rat Sex: Male Microscopic Results

Heart Within Normal Limits Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 103 Species: Rat Sex: Male Microscopic Results

Heart Within Normal Limits Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 104 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, minimal Infiltrate, Cellular, Myocardium, interventricular septum, focal, minimal Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 105 Species: Rat Sex: Male Microscopic Results

Heart Within Normal LimitsTable Number: 3 Individual Animal Data Study Number: WAG0014 Hintingdon Life Sciences Eye, Suffolk, 1P23 7PX, England Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 106 Species: Rat Sex: Male Microscopic Results

Heart Within Normal Limits Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 107 Species: Rat Sex: Male Microscopic Results

Heart Within Normal Limits Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 108 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, minimal Infiltrate, Cellular, Myocardium, focal, minimal Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 109 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, minimal Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 110 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, minimal Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 111 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, interventricular septum, focal, minimal Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 112 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, right ventricle, slightTable Number: 3 Individual Animal Data Study Number: WAG0014 Hintingdon Life Sciences Eye, Suffolk, 1P23 7PX, England Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 113 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, minimal Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 114 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, left ventricle, slight Infiltrate, Cellular, Myocardium, right ventricle, focal, minimal Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 115 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, left ventricle, interventricular septum, slight Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 116 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, left ventricle, minimal Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 117 Species: Rat Sex: Male Microscopic Results

Heart Within Normal Limits Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 118 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, left ventricle, slight Infiltrate, Cellular, Myocardium, right ventricle, focal, minimal Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 119 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, left ventricle, interventricular septum, atrium, slightTable Number: 3 Individual Animal Data Study Number: WAG0014 Hintingdon Life Sciences Eye, Suffolk, 1P23 7PX, England Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 120 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, left ventricle, interventricular septum, slight Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 11 Species: Rat Sex: Male Microscopic Results

Heart Infiltrate, Cellular, Myocardium, left ventricle, focal, minimal Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 12 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, right ventricle, left ventricle, interventricular septum, moderate Infiltrates of macrophages and fewer lymphocytes, interstitial fibroplasia /fibrosis and capillary dilatation. Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 13 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, right ventricle, left ventricle, interventricular septum, moderate Infiltrate, Cellular, Myocardium, focal, left ventricle, minimal Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 14 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, left ventricle, interventricular septum, minimal Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 15 Species: Rat Sex: Male Microscopic Results

Heart Infiltrate, Cellular, Myocardium, right ventricle, focal, minimal Inflammation, Chronic, apex, interventricular septum, left ventricle, slight Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 16 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, left ventricle, interventricular septum, slightTable Number: 3 Individual Animal Data Study Number: WAG0014 Hintingdon Life Sciences Eye, Suffolk, 1P23 7PX, England Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 17 Species: Rat Sex: Male Microscopic Results

Heart Within Normal Limits Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 18 Species: Rat Sex: Male Microscopic Results

Heart Infiltrate, Cellular, Myocardium, left ventricle, focal, minimal Inflammation, Chronic, apex, left ventricle, interventricular septum, moderate Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 19 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, left ventricle, interventricular septum, slight Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 20 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, left ventricle, right ventricle, interventricular septum, slight Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 71 Species: Rat Sex: Male Microscopic Results

Heart Within Normal Limits Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 72 Species: Rat Sex: Male Microscopic Results

Heart Inflammation, Chronic, apex, minimal Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 73 Species: Rat Sex: Male Microscopic Results

Heart Within Normal LimitsTable Number: 3 Individual Animal Data Study Number: WAG0014 Hintingdon Life Sciences Eye, Suffolk, 1P23 7PX, England Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 74 Species: Rat Sex: Male Microscopic Results

Heart Within Normal Limits Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 75 Species: Rat Sex: Male Microscopic Results

Heart Infiltrate, Cellular, Myocardium, right ventricle, focal, minimal Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 76 Species: Rat Sex: Male Microscopic Results

Heart Infiltrate, Cellular, Myocardium, apex, focal, minimal Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 77 Species: Rat Sex: Male Microscopic Results

Heart Infiltrate, Cellular, Myocardium, right ventricle, left ventricle, minimal Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 78 Species: Rat Sex: Male Microscopic Results

Heart Within Normal Limits Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 79 Species: Rat Sex: Male Microscopic Results

Heart Within Normal Limits Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 80 Species: Rat Sex: Male Microscopic Results

Heart Within Normal LimitsHistopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period Test Facility Study Number: WAG0014



### Data Table 4 Tabulated Summary of Study Pathologist and Reviewing Pathologist FindingsHistopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13Weeks Followed by a 4 Week Recovery PeriodTest Facility Study Number: WAG0014Main Study, Group 1Pathologist ObservationAnimal NumberIncidence61 62 63 64 65 66 67 68 69 70Study Myocardial Inflammatory Cell Infiltration / Fibrosis - - - - - 1 - - 1 - 2/10ReviewingInflammation, Chronic- - - - - - - - - - 0/10Infiltrate, Cellular, Myocardium- - - - - 1 - 1 1 1 4/10Main Study, Group 2Pathologist ObservationAnimal NumberIncidence101 102 103 104 105 106 107 108 109 110Study Myocardial Inflammatory Cell Infiltration / Fibrosis - - - 2 - - - 1 1 2 4/10ReviewingInflammation, Chronic- - - 1 - - - 1 1 1 4/10Infiltrate, Cellular, Myocardium - - - 1 - - - 1 - - 2/10Main Study, Group 3Pathologist ObservationAnimal NumberIncidence111 112 113 114 115 116 117 118 119 120Study Myocardial Inflammatory Cell Infiltration / Fibrosis 1 2 2 3 2 2 - 2 2 2 9/10ReviewingInflammation, Chronic1 2 1 2 2 1 - 2 2 2 9/10Infiltrate, Cellular, Myocardium - - - 1 - - - 1 - - 2/10Main Study, Group 4Pathologist ObservationAnimal NumberIncidence11 12 13 14 15 16 17 18 19 20Study Myocardial Inflammatory Cell Infiltration / Fibrosis - 3 3 1 2 3 1 2 2 3 9/10ReviewingInflammation, Chronic- 3 3 1 2 2 - 3 2 2 8/10Infiltrate, Cellular, Myocardium 1 - 1 - 1 - - 1 - - 4/10- = Not Present, 1 = minimal, 2 = slight, 3 = moderate; Incidence = number affected / number evaluated

685Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Administration to CD Rats for 13Weeks Followed by a 4 Week Recovery PeriodTest Facility Study Number: WAG0014Recovery, Group 1Pathologist ObservationAnimal NumberIncidence81 82 83 84 85 86 87 88 89 90Study Myocardial Inflammatory Cell Infiltration / Fibrosis 1 1 - 3 2 - - - 1 1 6/10ReviewingInflammation, Chronic- - - 2 - - - - - - 1/10Infiltrate, Cellular, Myocardium 1 1 1 - 1 - - - 1 1 6/10Recovery, Group 4Pathologist ObservationAnimal NumberIncidence71 72 73 74 75 76 77 78 79 80Study Myocardial Inflammatory Cell Infiltration / Fibrosis - 1 - - - - 1 - - - 2/10ReviewingInflammation, Chronic- 1 - - - - - - - - 1/10Infiltrate, Cellular, Myocardium - - - - 1 1 1 - - - 3/10- = Not Present, 1 = minimal, 2 = slight, 3 = moderate; Incidence = number affected / number evaluated

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### Annex 5 GLP compliance statementsHuntingdon Life Sciences WAG0014

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### EYE RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2011Huntingdon Life Sciences WAG0014

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### EYE RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2012Huntingdon Life Sciences WAG0014

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### HUNTINGDON RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2011Huntingdon Life Sciences WAG0014

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### HUNTINGDON RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2012