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### Working for a better futur e



## REPORT HFO-1234yf: A 28-Day Inhalation (Whole-Body Exposures) Toxicity Study in Minipigs

HLS study number: 13-6434 Sponsor reference number: Version ID: Final Issue date: 20 January 2014Sponsor reference number: Huntingdon Life Sciences: 13-6434

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# Table of Contents Statement of Compliance..............................................................................................................6 Signature Page ................................................................................................................. ............7 Quality Assurance Statement .................................................................................................... ...8 Details of Sponsor, Test Facility and Test Sites ...........................................................................9 Contributing Scientists ........................................................................................................ ........10 Summary........................................................................................................................ .............11 1. Introduction ................................................................................................................... .....12 1.1 Objective ................................................................................................................12 1.2 Regulatory compliance...........................................................................................12 1.2.1 Test guidelines ...........................................................................................12 1.2.2 Good laboratory practices ..........................................................................12 1.2.3 Animal welfare act compliance ...................................................................12 1.3 Test system ............................................................................................................12 1.4 Route, duration and frequency of administration....................................................13 1.5 Exposure level........................................................................................................13 1.6 Number of animals .................................................................................................13 1.7 Use of restraint device............................................................................................14 2. Experimental Procedure.....................................................................................................15 2.1 Study schedule and structure.................................................................................15 2.1.1 Study dates.................................................................................................15 2.1.2 Experimental outline ...................................................................................16 2.2 Test substance.......................................................................................................16 2.2.1 Test substance ...........................................................................................16 2.3 Test substance administration................................................................................17 2.4 Animal management ..............................................................................................18 2.4.1 Animals, allocation and identification..........................................................18 2.4.2 Husbandry ..................................................................................................19 2.5 Experiment al evaluations .......................................................................................21 2.5.1 Daily observations (in-pen)......................................................................... 21 2.5.2 Dosing observations (in-chamber)..............................................................21 2.5.3 Signs...........................................................................................................21 2.5.4 Body weight ................................................................................................22 2.5.5 Food consumption ......................................................................................22 2.5.6 Clinical pathology .......................................................................................22 2.6 Postmortem ............................................................................................................24 2.6.1 Method of euthanasia .................................................................................24 2.6.2 Scheduled necropsy ...................................................................................24 2.6.3 Macroscopic examinations .........................................................................24 2.6.4 Organ weights ............................................................................................24 2.6.5 Tissues preserved and examined histopathologically ................................24 2.6.6 Preservatives..............................................................................................25 2.6.7 Processing..................................................................................................26 2.7 Computer systems .................................................................................................27 2.8 Data treatment........................................................................................................27Sponsor reference number: Huntingdon Life Sciences: 13-6434

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### 2.8.1 Serial observations .....................................................................................28 2.8.2 Terminal procedures...................................................................................29 2.8.3 Statistical analysis ......................................................................................29 2.9 Data storage...........................................................................................................31 2.10 Protocol deviations .................................................................................................31 3. Results and Di scussion......................................................................................................33 3.1 Exposure results.....................................................................................................33 3.2 Mortality..................................................................................................................33 3.3 Clinical observations ..............................................................................................33 3.4 Body weights ..........................................................................................................33 3.5 Food consumption..................................................................................................34 3.6 Clinical pathology ...................................................................................................34 3.6.1 Hematology ................................................................................................34 3.6.2 Clinical chemistry........................................................................................34 3.7 Organ weights ........................................................................................................34 3.8 Pathology ...............................................................................................................35 3.8.1 Mortality and macroscopic findings ............................................................35 3.8.2 Microscopic evaluation ...............................................................................35 4. Conclusion ..................................................................................................................... ....37 5. References..................................................................................................................... ....38Sponsor reference number: Huntingdon Life Sciences: 13-6434

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# List of Tables Table 1 Daily observations - group distribution of observations.......................................40 Table 2 Dose observations - group distribution of observations.....................................102 Table 3 Clinical signs - group distribution of observations .............................................124 Table 4 Body weights - group mean values ...................................................................127 Table 5 Body weight change – group mean values........................................................129 Table 6 Visual food consumption – group distribution of observations ..........................131 Table 7 Hematology – group mean values.....................................................................133 Table 8 Clinical chemistry – group mean values............................................................149 Table 9 Organ weights – group mean absolute values ..................................................165 Table 10 Organ weights – group mean values relative (%) to body weight .....................167 Table 11 Organ weights – group mean values relative (%) to brain weight .....................169 Table 12 Macropathology – group distribution of findings................................................171 

# List of Appendices Appendix 1 Daily observations – individual observations.....................................................173 Appendix 2 Dose observations – individual observations ....................................................184 Appendix 3 Clinical signs – individual observations .............................................................190 Appendix 4 Body weights – individual values.......................................................................198 Appendix 5 Body weight change - individual values ............................................................202 Appendix 6 Visual food consumption - individual observations............................................206 Appendix 7 Hematology - individual values..........................................................................220 Appendix 8 Clinical chemistry - individual values.................................................................244 Appendix 9 Organ weights - individual values......................................................................268 Appendix 10 Macropathology – individual findings.................................................................276Sponsor reference number: Huntingdon Life Sciences: 13-6434

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# List of Annexes Annex 1 Certificates of analysis ......................................................................................284 Annex 2 Aerosol technology report .................................................................................295 Annex 3 Clinical pathology report....................................................................................314 Annex 4 Anatomic pathology report – organ weights ......................................................316 Annex 5 Anatomic pathology report – macroscopic and histopathology .........................318Sponsor reference number: Huntingdon Life Sciences: 13-6434

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# Details of Sponsor, Test Facility and Test Sites

Sponsor

Test facility Huntingdon Life Sciences PO Box 2360 Mettlers Road East Millstone, New Jersey 08875-2360 Test site Ani Lytics, Inc. [Serum biomarker] 200 Girard Street Suite 200 Gaithersburg, Maryland 20877-3490 Test site University of Würzburg [Urine metabolite Versbacher Straße 9 analysis] 97078 Würzburg Germany Test site HSRL Inc. [Anatomic pathology] 5930 Main St. Mount Jackson, VA 22842Sponsor reference number: Huntingdon Life Sciences: 13-6434

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# Contributing Scientists Senior Vice President, Safety Assessment Vice President, Bioanalytical and Translational Sciences Vice President, Toxicology Operations Director, Pathology Director, Quality Assurance Study Director Veterinarian Inhalation Toxicology Large Animal Toxicology Pharmacy Clinical Pathology and Sample Logistics Necropsy, Fetal Pathology and Histology Principal Investigator, Aerosol Technologist Principal Investigator, Clinical Pathologist Principal Investigator, Organ Weight Evaluations Principal Investigator, Microscopic Pathologist HSRL Inc. Mount Jackson, Virginia Principal Investigator, Serum Biomarker Analysis Ani Lytics, Inc. Gaithersburg, Maryland Principal Investigator, Urine Metabolite Analysis University of Würzburg, Germany Peer Review Pathologist Experimental Pathology Laboratories Sterling, VirginiaSponsor reference number: Huntingdon Life Sciences: 13-6434

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# Summary HFO-1234yf: A 28-Day Inhalation (Whole -Body Exposures) Toxicity Study in Minipigs Göttingen minipigs (8/sex/group) were exposed by whole-body inhalation to HFO-1234yf at target concentrations of 0, 5,00 0 or 10,000 ppm (daily for 6 hour s per day) for up to 28 days. Animal No. 2148 was euthanized before the initia tion of exposures on Day 1, and was replaced by Animal No. 2153, who was exposed for 27 days. At the end of the treatment period, all surviving animals were euthanized and necropsied. Parameters evaluated during the study were: viability, clinical observations, body weights, f ood consumption, or clinical pathology (pretest and Days 21 and 28), organ weights, macrosc opic observations and microscopic pathology. Mean target and achieved expos ure results were as follows: Group Treatment Target Exposure Levels Actual Exposure Levels (ppm) (mg/L) (ppm) 1 Air 0 0 0 2 HFO-1234yf 5,000 26 5145 3 HFO-1234yf 10,000 50 10200 No HFO-1234yf gas was detected in Group 1 sample s. Mean atmosphere concentrations were 3.8% and 2.0% above target for Group 2 males a nd females, respectively, and 2.0% above target for Group 3. At Day 29, there were no HFO-1234yf-related microscopic findings involving the heart (left ventricle, right ventricle and se ptum) and skeletal muscle (rec tus femoris, psoas and soleus muscles as well as the diaphragm). Theref ore, there was no microscopic evidence of cardiotoxicity or skeletal muscle toxicity follo wing whole-body inhalation of the test substance at up to 10,000 ppm for 28 days in male and female Gottingen minipigs. The results of this study demonstrate that minipigs respond very di fferently to HFO-1234yf inhalation exposure as compared to rabbits. Under the condition of this study, the No-O bserved-Adverse-Effect-Level (NOAEL) for inhalation toxicity was determin ed to be the actual achieved exposure level of 10,200 ppm.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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# 1. Introduction 1.1 Objective The purpose of this study was to assess the card iotoxicity and skeletal muscle toxicity of HFO-1234yf when administered via whole-body inhalation to minipigs for 28 days. 

## 1.2 Regulatory compliance 1.2.1 Test guidelines This study is designed in accord ance with OECD Guidelines fo r Testing of Chemicals No. 412 "Subacute Inhalation Toxicity: 28 Days", Adop ted 7 September 2009 (e xcept this study was conducted in minipigs and onl y for selected parameters). 1.2.2 Good laboratory practices This study was conducted in compliance with the following Good Laboratory Practices: Organization for Economic Cooperation and De velopment (OECD) Principles of Good Laboratory Practices ENV/MC/CHEM/( 98)17 with the following exception: The urine metabolites analysis will not be conduc ted in compliance with the referenced GLPs because the Sponsor-subcontracted laboratory is not GLP-compliant. 1.2.3 Animal welfare act compliance This study complied with all appropriate parts of the Animal Welfare Act Regulations: 9 CFR Parts 1 and 2 Final Rules, Federal Register, Volume 54, No. 168, August 31, 1989, pp. 36112- 36163 effective October 30, 1989 and 9 CFR Part 3 Animal Welfare Standards; Final Rule, Federal Register, Volume 56, No. 32, February 15, 1991, pp. 6426-6505 effective March 18, 1991. 

## 1.3 Test system The minipig is accepted by regulat ory authorities (including the Eu ropean Chemicals Agency) as a non-rodent surrogate for humans in the detection of toxic effects. Cardiotoxicity and skeletal muscle toxicity were the prin cipal endpoints of interest for this study and the minipig is considered to be a sensitive and representative model for human responses. In prior testing via inhalation exposures with this test substance, pregnant and non-pr egnant female rabbits and male rabbits were found to be more sensitive to the test substance when compared to pregnant and non-pregnant female rats and male rats. This st udy was designed to determine whether there is a repeated exposures (4 weeks instead of the prior te sted 2 weeks) sensitivity in minipigs with this test substance since the minipig is a more appr opriate large animal model for safety evaluation for this test substance.

.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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## 1.4 Route, duration and frequency of administration The inhalation route is a potential route of human exposure to this test substance. The duration and frequency of the exposures in this study were intended to insure adequate repeat-exposure toxicity characterization for the test substance in minipigs, as compared to prior data in rabbits. In prior rabbit testing (HLS study 11-6387), cardiotoxicity and skeletal muscle toxicity were seen after 1-2 weeks of exposures. Similar effects were not observed in rabbits following acute exposure, indicating that repeated exposure was needed to produce th ese effects. However, in a pilot minipig study (HLS study 13-6432), cardiotoxicity and skeletal muscle toxicity were not seen after 2 weeks of exposure. This study confirmed that minipigs responded similar to rats as compared to rabbits. 

## 1.5 Exposure level A prior 28-days inhalation study (HLS 11-6387) in male and non-pregnant fe male rabbits resulted in unscheduled deaths/sacrifices at 4500 ppm (1 female) and 5500 ppm (1 male, 1 female). Clinical signs prior to euthanasia included d ecreased activity, ano-genital staining decreased fecal volume and unformed stool. Exposure to HFO-1234yf was associated with microscopic findings in the heart and skeletal muscle at ≥ 1000 ppm with males more frequently affected than females. The NOEL (No-Observed-Effect-Level ) based on anatomic pathology findings was 500 ppm in males and 1000 ppm in females. No mortality or toxicity was seen in male and female minipigs (HLS 13-6432) from up to 2 weeks of exposures up to a 10,000 ppm level of the test substance. Based on the data in rabbit and minipig toxicity studies discussed previously, a high exposure level of 10,000 ppm was selected for this study. Since several animals di d not have a cause of death determined, it is not certain that the lethality was due to the cardiac lesions. As such, there was a need to evaluate the different endpoint(s) us ing this high concentration (for example – the effects may have been due to a saturation of a me tabolic pathway). If only lower exposure levels were used, this (or a similar) finding might ha ve been missed. A lower exposure level of 5,000 ppm was also selected to provide a range of possible test substance effects. The potential effects in minipigs following inhalation of 5,000 and 10,000 ppm HFO-1234yf for following 28 days had not been previously investigated. 

## 1.6 Number of animals The number of animals in this study was consider ed the minimum necessary for statistical and scientific reasons. The purpose of this study was to monitor for toxicity of the test substance and to compare the data to the 28-day rabbit inhala tion toxicity study 11-6387 to help determine the appropriate animal model for use in human risk assessment. The number of animals/sex/group (8) for this 28 days toxicity evaluation was considered the minimum number that would account for the following: (1) The expected variability among animals as noted during the 14-day preliminary study 13-6432 in minipigs.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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### (2) To provide an adequately robust data set considering the expected subtlety of the possible cardiotoxic and skeletal muscle effects as noted in the 28-day rabbit study 11-6387. In the 14-day preliminary study 13-6432 in minipigs, elevations in selected biomarkers and histological effects were observed in some animals in all exposure groups, including pretest and controls. The exposure durati on for this study was twice as long and sufficient animals were needed to discriminate test substance-related effects, if any, from background variations. Due to the potential for subtle effects, it was important in this definitive study that sufficient animals were evaluated to produce robust results and conclusions. (3) The historical control database for minipi gs exposed via whole- body inhalation exposure is very limited (only one study: the 14-day preliminary minipig i nhalation study 13-6432) at this laboratory. The proposed group sizes were thus necessary to better define the normal range of variability for the parameters evaluated under this exposure study in this species. (4) A robust study design such as proposed for this study provided an enhanced degree of confidence in the results to best protec t the potentially exposed human population. Two test substance-treated groups receiving lo w and high exposure levels and a negative air control group were considered the minimum numb er of groups necessary to provide a range of effects and allow for extrapol ation of results to humans. 

## 1.7 Use of restraint device Animals were restrained by a technician in a V-trough for the clinical pathology bleeding since bleeding the animals without this restraint was impractical. Formal habituation to the v-trough for purposes of blood collection was not necessary because the animals were handled frequently before they were bled. Animals were restrained in the whole-body inhalation exposure chambers (each chamber was considered a restraint device because of its lim ited floor space of ~10 square-feet for 4 pigs) during the daily exposures since exposing the animal s without this restrain t was impractical (for example to expose the animals in their pens would require impractical quantities of test substance in the room air and would create a heal th hazard for the technical staff). Also, the exposures method simulated the exposures method for the prior rabbit and minipig inhalation studies. Animals were habituated to the inha lation exposure chambers for purposes of minimizing stress during exposures (to include ~1 hour on the 1 st 

### day, ~1 hour on the 2 nd 

### day preceding the 2 nd 

### day of pretest blood colle ction (bleeding done within 1 hour after removal from the chamber and before the pm feeding) in preparation for this study.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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# 2. Experimental Procedure 2.1 Study schedule and structure 2.1.1 Study dates Study initiation: 6 September 2013 (Date Study Director signed the Protocol) Experimental start date: 17 September 2013 (Date of first data collection) Animal receipt: 17 September 2013 Dosing initiation: males 2 October 2013 females 3 October 2013 Dosing termination: males 29 October 2013 females 30 October 2013 Necropsy: males 30 October 2013 females 31 October 2013 Experimental completion date: 17 January 2014 (Date of last data collection) Study completion: 20 January 2014 (Dat e Study Director signed the Final Report)Sponsor reference number: Huntingdon Life Sciences: 13-6434

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### 2.1.2 Experimental outline The test substance was administered via w hole-body inhalation to minipigs for up to 28 consecutive days. Animal No. 2148 was euthanized before the initiation of exposures on Day 1, this animal was replaced by Animal No. 2153 who was exposed for only 27 days. The study consisted of 1 control and 2 tr eated groups identified as follows: Target Exposure Levels Number of animals Group Treatment (ppm) (mg/L) Male Female 1 Control 0 0 8 8 2 b HFO-1234yf 5,000 26 8 8 3 HFO-1234yf 10,000 50 8 8

a Exposures were 6 hours per day for 7 days per week for up to 28 days. Exposure levels are expressed as ppm (part per million of test substance in air) and equiva lent mg/L (mg of test substance per Liter of air) of test substance. Exposure results are reported as in terms of PPM. Animals in Group 1 were similarly exposed to air only. 

## 2.2 Test substance 2.2.1 Test substance Information supplied by the Sponsor regarding th e test substance is contained in the study records. Certificates of Analys is for each lot number of test substance are presented in Annex 1. The following information is given in summary: Test substance: HFO-1234yf (2,3,3,3 – Tetrafluoropropene) MW: 114 grams/mole CAS No.: 754-12-1 Test Substance Category: Industrial chemical used as a possible refrigerant Manufacturer/Supplier:

Description: Liquid (compressed gas) Storage conditions: Room temperatureSponsor reference number: Huntingdon Life Sciences: 13-6434

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### Lot numbers: 050714C 051181C 053912C 058794C 058876C 060571C 060648C 060668C 061520C 062669C Purity: 99.99% Date received: 13 September 2013 Expiration date: 26 August 2014 Documentation of the identity, strength, purity, composition, stability, and method of synthesis, fabrication, and/or derivation of each batch of the test substan ce and the maintenance of these records were the responsibility of the Sponsor. A sample from each lot of test substance is stor ed in the Archives of the Testing Facility under conditions specified for te st substance storage. The unused portion of the test substance and any em pty test substance contai ners will be returned to the Sponsor following issue of the final report of the final study with this test substance. The test substance was used as supplied. Detailed records of test substance usag e were maintained in the study raw data. 

## 2.3 Test substance administration Route Inhalation – whole-body. Controls (Group 1) Air only.Training for dosing (wholebody) The animals were acclimated to the method of restraint for two 1 hour sessions during the pretest period. Duration of daily exposure 6 hours. Details of administration and analys is of the test atmospheres together with the results obtained are presented in Annex 2
.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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## 2.4 Animal management 2.4.1 Animals, allocation and identification Animals Strain/Species Göttinge n Minipig (juvenile) Supplier Marshall BioResources North Rose, New York 14516 Number of animals Received Placed on test Total: 52 48 Males: 26 24 Females: 26 24 Pretest period The pretest period wa s approximately 2 weeks. Pretest procedures were not performed until animals had been allowed to stabilize for approximately 1 week. Prior to exposure initiation, all animals were examined by the staff veterinarian to ascertain suitability for study. The staff veterinarian examined the general health of each animal and determined the need for medical treatment or prophylaxis. Age of at start of treatment Approximately 3 to 4 months Males: 6.0 kg to 8.9 kg Weight range at the start of treatment Females: 6.3 kg to 9.7 kg Veterinary procedures Veterinary care Animals were monitored by the technical staff for any conditions requiring possible veterinary care and treated as necessary. Miscellaneous, non-test subs tance-related veterinarian evaluations and treatments (as necessary) for individual animals were reviewed by the study director and are documented in the study file. Allocation and identification Allocation More animals than require d for the study were purchased and stabilized. Animals considered su itable for study were allocated to the control, treated or spar e animal groups upon arrival. Animal No. 2148 was euthanized before the initiation ofSponsor reference number: Huntingdon Life Sciences: 13-6434

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### exposures on Day 1 and this animal was replaced by Animal No. 2153. Information as to th e disposition of all animals not utilized in the study is ma intained in the study file. Identification of animals Each animal bore an ear tag identification applied by the Supplier. Following allocation to the study, the assigned number was applied (marked on a hind limb and the head with permanent marker pen). The animal number plus the study number comprised the unique animal number for each animal. Each animal’s pen was provide d with a card, color-coded for exposure level identification and bearing the study number and animal number information. 2.4.2 Husbandry Facilities management/animal husbandry Currently acceptable practices of good animal husbandry were followed e.g., Guide for the Care and Use of Laboratory Animals ; National Academies Press, 2011. Huntingdon Life Sciences, East Millstone, New Jersey is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC). Environmental control Light/dark cycle A twelve hour light/dar k cycle was provided and controlled via an automatic timer. Temperature and relative humidity The temperature was monitored and maintained within the range of 22 to 27 °C. The relative humidity was monitored and maintained within the range of 30 to 70%. Although conditions were occasionally outside the indicated ranges, these deviations were mi nor and/or of short duration and were not considered to have influenced the health of the animals and/or the outcome of the study. Air changes Ten to fifteen (10 to 15) fresh air changes per hour are considered the acceptable sta ndard. Air changes were periodically monitored by plan t maintenance and the records were reviewed by the veterinarian. Animal housing and environmental enrichmentHousing during nonexposure periods Pens by sex and exposure group. Number of animals per pen Up to 4 of the same sex per pen. The number of animals in a penSponsor reference number: Huntingdon Life Sciences: 13-6434

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### was reduced due to mortality. Housing during exposure periods Group housed in chamber (~10 square-feet for up to 4 pigs). Animals were single-housed in the chamber due to injury and resumed group-housing following appr oval by the veterinarian as detailed below. Beginning on Day 15, Animal No. 1148 was singled-housed in the chamber due to injury to its penis. On Day 13, Animal No. 1145 was singled-housed in the chamber due to injury to its tail. For the entire study, Animal No. 2153 was singled-housed in the chamber because this animal was not previously housed with other animals in the group. Environmental enrichment Animals were exercised in accordance with the Animal Welfare Standards; Final Rule (9 CFR Part 3), following the Testing Facility’s Standard Operating Procedures. Feed Diet Certified Miniswine Diet, No. 7037 Harlan Teklad, Madison, Wisconsin Diet during exposure periods None. Availability Minipigs were fed 2 times daily with the approximate total amount of 250 grams per day. Feed was presented at approximately the same times each day including approximately one-half of the feed before exposures and approximately one-half of the feed after exposures on the days of exposures. On Days 21 and 28 when clinical pathology sample collections were scheduled after the exposures, the animals were fed approximately one-half of the feed before exposures and approximately one-half of the feed after the blood and urine collections. On occasion, diets were supplemented with pieces of fruit and with “treats” (such as small amounts of fruit juice, or other acceptable food). Analysis Analysis of each feed lot used during this study was performed by the manufacturer. Results were provided to the Testing Facility and are maintained on file at the Testing Facility. There were no known contaminants in the feed that were expected toSponsor reference number: Huntingdon Life Sciences: 13-6434

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### interfere with the results of this study. Water Supply Potable water from the public supply (New Jersey-American Water Company, Cherry Hill, New Jersey) via an automated watering system. Availability Without restriction (e xcept during the periods of urine collection). Water during exposure periods None. Analysis Water analyses are conducted by New Jersey-American Water Company, Cherry Hill, New Jersey (Raritan-Millstone Plant) to ensure that water meets sta ndards specified under the EPA Federal Safe Drinking Water Act Re gulations (40 CFR Part 141). In addition, water samples ar e collected biannually from representative rooms in the Te sting Facility; chemical and microbiological water analyses are conducted on these samples by a subcontract laboratory. Resu lts of all water analyses are maintained on file at the Testi ng Facility. There were no known contaminants in the water which were expected to interfere with the results of this study. 

## 2.5 Experimental evaluations 2.5.1 Daily observations (in-pen) Animals were observed in their pens twice daily for mortality and genera l condition. During the treatment period animals were obser ved twice daily for signs of toxi c or pharmacologic effects. Animals in extremely poor health or in a possi ble moribund condition were identified for further monitoring and possible euthanasia. 2.5.2 Dosing observations (in-chamber) Animals were monitored continuously duri ng each exposure period and observations individually recorded at leas t twice, approximately 2 hours and 4 hours into the exposure. 2.5.3 Signs Animals were removed from their pens and exam ined twice pretest and weekly during the study period. Examinations included observations of ge neral condition, skin and fur, eyes, nose, oral cavity, abdomen and external genitalia as well as evaluations of respiration.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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### 2.5.4 Body weight Animals were removed from their pens and weig hed 3 times pretest, weekly during treatment and terminally (after fasting). Terminal, fa sted body weights were obtained just prior to necropsy. 2.5.5 Food consumption A visual estimate of the amount of food consumed per day was ma de for each minipig (after the PM feeding interval) starting during the 2 nd 

### week after animal rece ipt and continuing throughout the treatment period, except when animal s are fasted for terminal sacrifice. 2.5.6 Clinical pathology Blood obtained via the vena cava from unanesthetized animals was used to analyze hematology, and clinical chemistry parameters for up to 8 an imals/sex/group twice pret est and after exposures on Days 21 and 28 (within 1 hour after removal from the exposure chamber and before PM feeding). Animals were fasted for at least 7 hours (including during the 6 hours of exposure on exposure days) prior to each scheduled blood colle ction interval. The animals were held or placed into a v-trough for each sampling. The be havior of all animals during blood collection was recorded in the raw data including any unusual or excessive struggling. Hematology Blood samples (approximately 2 mL) were collected into tubes containing K 2 

### EDTA anticoagulant and analyzed for the following using a Siemens ADVIA 120 Hematology Analyzer: Hemoglobin concentration (HGB) Hematocrit (HCT) Erythrocyte count (RBC) Platelet count (PLT) Mean corpuscular volume (MCV) Mean corpuscular hemoglobin (MCH) Mean corpuscular hemoglobin concentration (MCHC) Red cell distribution width (RDW) Total leukocyte count (WBC) Reticulocyte count (RETIC) Differential leukocyte count Neutrophils (ANEU) Lymphocytes (ALYM) Eosinophils (AEOS) Basophils (ABASO) Monocytes (AMONO) Large unstained cells (ALUC)Sponsor reference number: Huntingdon Life Sciences: 13-6434

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### A peripheral blood smear was prepared for each anim al at each blood collection interval and was available for confirmation of automated results an d/or other evaluations deemed necessary by the Clinical Pathologist. Clinical chemistry Blood samples (approximately 3 mL) were collected into tubes with no anticoagulant, allowed to clot and centrifuged to obtain serum then split in to 2 aliquots. An approximately 400 μL aliquot of serum was designated for clinical chemis try analysis by the Testing Facility. An approximately 800 μL aliquot of serum was desi gnated for cardiac biomarker analysis, stored frozen at – 80 °C ± 10 °C and shipped on dry ic e to Ani Lytics, Inc., Gaithersburg, Maryland for analysis. Blood samples (approximately 2 mL) were collected into tubes containing K 3 

### EDTA anticoagulant and centrifuged to obtain plasma. One aliquot of plasma (approximately 800 μL) was stored frozen at – 80 °C ± 10 °C for possibl e future evaluations after the issue of the final report. Clinical chemistry blood samples were collecte d from Animal No. 2147 prior to sacrifice for welfare reasons. Tests performed by the Testing Facility Samples were analyzed for the following us ing a Siemens ADVIA 1800 Chemistry Analyzer: Aspartate aminotransferase (AST) ( Kinetic - Modified Bergmeyer 

### ) Alanine aminotransferase (ALT) ( Kinetic - Modified Bergmeyer 

### ) Creatine kinase-Total (CK) ( UV, NAC-activated Kinetic 

### ) Tests performed by Ani Lytics, Inc.: Serum cardiac biomarker samples were frozen and stored at – 80 °C ± 10 °C until shipped on dry ice. Creatine kinase-Total (CK) ( UV, NAC-activated Kinetic 

### ) creatine kinase-MB (CK(MB)) ( electrophoretic isoenzyme separation 

### ) creatine kinase-MM (CK(MM)) ( electrophoretic isoenzyme separation 

### ) myoglobin (MYOGLOBI) (ELISA) cardiac troponin I (TPI) (ELISA) Serum samples for possible future evaluations were stored frozen at – 80 °C ± 10 °C until the Sponsor determines the final dispositi on after the issue of the final report. Urinalysis Urine obtained via an up to 15-hour overnight coll ection period will be analyzed for up to 8 animals/sex/group once pretest and after expos ures on Days 21 and 28. Animals were transferred to cages, fasted and water-deprived during the collection periods.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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### Urine was collected into ice-ch illed containers overnight (app roximately 13 to 15 hours) from urine pans beneath each individually-housed animal ’s cage. Urine samples were processed (total volume measured), split into 2 samples (prima ry and backup, approximately 10 mL each) and frozen in dry ice/alcohol and stored at –20 °C ± 10 °C. The primary samples were shipped on dry ice to Paragon Global Services Ltd., Alconbur y Cambridgeshire, UK for further shipment to University of Würzburg, Germany for urine meta bolites analysis. The urine metabolites data will be communicated to the Study Director and main tained in the study data but not presented in the report. The backup samples will remain fr ozen until the Sponsor determines the final disposition after the issue of the final report. 

## 2.6 Postmortem 2.6.1 Method of euthanasia Animals sacrificed for welfare reasons or at the scheduled sacrifice interval were sedated with telazol and xylazine followed by intravenous over dose of administration of sodium pentobarbital and then exsanguination. 2.6.2 Scheduled necropsy Necropsy was performed on up to 8 animals/sex/group after animals had been treated for up to 28 days. Animals were fasted overnight prior to necropsy. Necropsy schedules were established in order to assure that approximately equal num bers of males and females from each group were examined at similar times of the day throughout the necropsy period. A pathologist was present during the scheduled necropsy examinations. 2.6.3 Macroscopic examinations Complete macroscopic examinations were performed on all animals including the unscheduled decedent. The macroscopic examination included examination of the external surface and all orifices; the external surfaces of the brain and spin al cord; the organs and tissues of the cranial, thoracic, abdominal and pelvic cavities and ne ck; and the remainder of the carcass for the presence of macroscopic morphologic abnormalities. 2.6.4 Organ weights Organs indicated in Text Table 2.6.5-1 were weighed for all anim als at the scheduled sacrifice interval. Prior to weighing, the organs were car efully dissected and prop erly trimmed to remove adipose and other contiguous tissu es in a uniform manner. Organs were weighed as soon as possible after dissection in orde r to avoid drying. Paired or gans were weighed together. 2.6.5 Tissues preserved and examined histopathologically The tissues listed in Text Table 2.6.5-1 were obtained from all animals and preserved. In addition, slides of the indicated tissues were prepared and shipped to the pathologist and examined microscopically. Any abnormalities not noted during macroscopic examinations which were seen during histol ogy processing were recorded.Sponsor reference number: Huntingdon Life Sciences: 13-6434

25 Text Table 2.6.5-1: Tissues weighed, preserved and examined microscopically

ORGAN NAME WEIGHED PRESERVED EXAMINED MICROSCOPICALLY brain (medulla, pons, cerebrum and cerebellum) X X heart (left and right vent ricles and septum) X X X kidneys X X liver X X lungs (with mainstem bronchi) X X skeletal muscle (diaphragm and bilateral

psoas and bilateral rectus femoris and soleus) X X tissues with macroscopic findings including tissue masses X a Qualitative examination (no differential count). 

### 2.6.6 Preservatives All tissues were preserved in 10% neutral buffered formalin (NBF). Lungs were infused with 10% NBF prior to their immersion into a larger volume of the same fixative. The rectus femoris was removed in its entirety from each hind leg, laid flat on a stiff card and stapled at either end of the card to maintain it s position during fixation. A thin longitudinal slice of rectus femoris was removed and flash frozen for possible future analysis. Each psoas muscle was removed in its entirety and stapled to a stiff card (no psoas muscle was frozen). The calf muscle that gives rise to the calcaneal tendon (including both heads of the gastrocnemius muscle and the underlying soleus muscle) was removed from both hind legs. Each muscle mass was collected by cutting th e common calcaneal tendon, reflecting it toward the femorotibial joint and cutting the muscles at their origin on the distal femur (gastrocnemius) and head of the fibula (soleus). The soleus wa s not separated from the gastrocnemius. The muscles were stapled to a stiff card (no soleus muscle was frozen). The diaphragm was sampled on the left side of the body from the thoracic wall to the esophageal hiatus and stapled to a card to maintain its position during immersion fixation (no diaphragm was frozen). Tissues for possible future analysis (hearts and rectus femoris ) were archived. The Sponsor will determine the disposition of these materials (i.e . archival, shipment or disposal of samples). To best remove and preserve the hearts to reduce as much as possible any artifacts in the tissues: 1. The animal was sedated in the study room and euthanized in the necropsy lab. 2. The heart was quickly removed from the animal, weighed and the 4 chambers were flushed with chilled saline usi ng a perfusion pump in order to cool the heart rapidly.Sponsor reference number: Huntingdon Life Sciences: 13-6434

26 

### 3. When the hearts stop beating, the left and righ t ventricles were finely dissected for best fixation. A longitudinal incision was made pa rallel to the two main bundles of papillary muscles in the left ventricle and the largest papillary muscle bundle in the right ventricle. The purpose of these incisions was to allow mo re rapid fixation of the papillary muscles. The incisions were made adjacent to the muscle bundles to facilitate formalin penetration but not so close that they inte rfere with accurate trimming. 4. A thin longitudinal slice of left ventricula r free wall was made from both margins of the opening incision in the left vent ricle. The slice from the left margin was flash frozen with liquid nitrogen and stored for possible future analysis. 5. The slice from the right marg in was sampled for electron mi croscopy and preserved in modified Karnovsky’s fixative for possible fu ture analysis. Care was taken to avoid damaging the papillary muscles near the opening incisions since these area s were sampled for histopathology. 6. After removing tissue for freezing and electron microscopy, the hearts were placed into chilled formalin for the durati on of the necropsy and transferre d to the bucket of formalin at the conclusion of the necropsy. 2.6.7 Processing Tissues (heart and muscle) were processed, sectioned at approximately 5 microns, and examined microscopically for all animals. A total of eight (8) longitudina l sections were sampled from the heart, 2 from the right ventricular free wall, 2 from the interventricular septum and 4 from the left ventricular free wall. The exact position of these secti ons was indicated in a trimming gui de in the study file. Sections were processed in large cassettes with the top su rface of the tissue sample marked with surgical ink to ensure proper positioning at embedding. The rectus femoris was sampled at the midbody and toward s either end (but away from the stapled areas) for a total of 3 sample areas. At each area, both a cross section and a longitudinal section of the muscle tissue were taken. A cro ss section and a longitudina l section were made in the middle of the psoas muscle (1 sample area). A cross section and a longitudinal section were made in the middle of the soleus muscle (1 sa mple area). A cross section and a longitudinal section were made from a repres entative area of the diaphragm. Each block was serial sectioned to prepare 2 duplicate sets of slides. One set of the duplicate slides fo r the hearts and muscles were shipped to the pathologist at HSRL. The slides were then transferred to th e Peer Review Pathologis t. The histopathology report including the peer review statement is presented in Annex 5
. The other set of the duplicate slides for hear ts were shipped to for an informal peer review (no report was required). All slides were returned to the Testing Facility upon completion of examination.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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## 2.7 Computer systems The computer systems with version numbers that were used on this study to acquire and quantify data include: System Version Use AmegaView Environmental Monitoring System 3 Monitoring of environmental conditions within the pharmacy ClinAxys II 1.1.5.1.2 Acquisition, processing and reporting of clinical pathology data from a variety of instruments Liberate Reporting System 2.2 Generation of report tables in MS Word formats for data collected using the Xybion Path/Tox System and ClinAxys II Liberate Reporting System - Global 1 Generation of report tables in MS Word formats for data collected using the Xybion Pristima ® 

### System Microsoft Word and/or Excel Additional formatting of report tables. Quasar 1.4 Statistical analysis of data REES Scientific Environmental Monitoring System WIN 1.5 Monitor and record temperature, humidity and/or light intensity readings of applicable rooms as well as the temperature readings of applicable refrigerators a nd/or freezers Xybion Pristima ® 

### System 6.2 Documentation of receipt and tracking of substances received by Pharmacy; dire ct online capture of inlife and postmortem evaluations PathData ® 

### Systems (HSRL only) V6.2c2 Direct online capture of microscopic pathology data and for the generation of report tables for the microscopic pathology data.


## 2.8 Data treatment Individual animal data presented in this repo rt may be rounded. Unrounded individual animal data were used to calculate the reported mean an d standard deviation valu es. Therefore, use of the reported individual values to reproduce mean s, standard deviations and/or to perform any subsequent calculations may produce minor disc repancies between the calculated values and those presented in this report.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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### Group means and standard deviatio ns for calculated data points (i.e. body weight change) were derived from individual animal/cage values. The data collection system used for collecting the in-life and post-life data divides the study into phases. The start of each phase begins with Day 1/Week 1. The phases presented in this report are: Pre-Treatment: Begins the day the animals arrive. Phase days/weeks are labeled P1, P2, P3, etc. During this phase, animals are not being dosed and they have not been assigned their permanent identification numbers. Treatment: Begins for each animal when it receives its first administration of test/control substance as sp ecified in the protocol. The following abbreviations are used in this report: M Male(s) F Female(s) ~ approximately Conc concentration Lpm Liters per minute mg/L milligrams of test substance per Liter of air ppm parts per million HLS Huntingdon Life Sciences MW molecular weight The death codes used have the following meanings: S1 Scheduled Euthanasia 1 WE Euthanized for welfare reasons 2.8.1 Serial observations Clinical observations Clinical observations are presented for each animal that showed signs, providing detail of the type of sign, day or week of occurrence and in formation on the duration of the sign applicable. AM Morning (pre-exposure) Observation PM Afternoon (post-exposure) Observation US PM Unscheduled Afternoon (post-exposure) Observation 2 Hours 2 Hours into Exposure 4 Hours 4 Hours into Exposure US1 1 st 

### Unscheduled Observation US2 2 nd 

### Unscheduled ObservationSponsor reference number: Huntingdon Life Sciences: 13-6434

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### Hematology The following abbreviations were used: NS No specimen Sample condition (SC) was describe d using the followi ng abbreviations: CLSE Severe platelet clumping noted CLSL Slight platelet clumping noted NCLP No clumping Blood chemistry CK values below the analytical limit (<7800) are excluded from calculations. The following abbreviation was used: NS No specimen Sample condition (SC) was describe d using the followi ng abbreviations: SHI Slightly hemolyzed Absolute blood creatine kinase-M B (CK(MB)) was calculated as: creatine kinase-total x (creatine kinase-MB ÷ 100) Absolute blood creatine kinase-M M (CK(MM)) was calculated as: creatine kinase-total x (creatine kinase-MM ÷ 100) 2.8.2 Terminal procedures Organ weights Organ weights were presented as absolute, rela tive to terminal body we ight using the weight recorded on the day of necropsy and relative to brain weight. 2.8.3 Statistical analysis All statistical analyses were carried out separately for males and females. For all other parameters, the analyses were carried out using the individual animal as the basic experimental unit.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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### The following data types were analyzed at each timepoint separately: body weight body weight change from interval to interval cumulative body weight change from baseline hematology clinical chemistry organ weights The parameters to analyze were identified as continuous, discrete or binary. Test-substance treated groups were then compared to the control using the following procedures. Continuous Parameters For comparisons involving more than two groups , if Bartlett's test for variance homogeneity ( Bartlett, 1937 ) was not significant at the 1% level, then parametric methods were applied. If the F1 approximate test for monotonicity (described below) of dose-response was not significant at the 1% level, Williams' test ( Williams’, 1971, 1972 ) for a monotonic trend was applied. If the F1 test was significant, sugge sting that the dose-response was not monotone, Dunnett's test ( Dunnett, 1955, 1964 ) was performed instead. If Ba rtlett's test was signifi cant at the 1% level, then logarithmic and square-root transformations were tried. If Bartlett's test was still significant, then non-parametric methods were applie d to mean ranks. If the H1 approximate test for monotonicity (described below) was not signif icant at the 1% level, Shirley's test for a monotonic trend ( Shirley, 1977 ) was applied. If th e H1 test was significant, then Steel's test ( Steel, 1959 ) was performed instead. ( Bartlett, 1937 ) The F1 test is designed to dete ct significant departure from m onotonicity of an ordered set of means. The test statistic compares the mean squa re, NMS, for the deviations of the absolute or adjusted means from the maximum likelihood means, calculated under a constraint of monotonicity, with the usual error mean square, EM S. The null hypothesis is that the true means are monotonically ordered. The test statistic is F1 = NMS/EMS which can be compared with standard tables of the F-distribution with 1 and error degrees of freedom. The H1 test is the non-parametric equivalent of the F1 test. Th e test statistic compares the nonmonotonicity sums of squares, NRSS, for the de viations of the mean ranks from the maximum likelihood mean ranks, with the non-parametric eq uivalent of the error sums of squares, ERSS=N(N+1)/12. The test statistic is H1 = NRSS/ERSS which can be compared to standard tables of the χ 2-distribution with 1 degree of freedom. Discrete Parameters For comparisons involving more than two groups, if the Jonckheere-Terpstra test ( Jonckheere, 1954 ) was significant at the 5% level, then the direction of the trend was established and onetailed step-down testing in this direction was perf ormed. If the Jonckheere-Terpstra test was not significant at the 5% level, then the Kruskal- Wallis test ( Kruskal and Wallis, 1952, 1953 ) was applied. If the Kruskal-Wallis test was significa nt at the 5% level, the test-substance treatedSponsor reference number: Huntingdon Life Sciences: 13-6434

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### groups were compared to the control using exact Wilcoxon rank sum tests ( Wilcoxon, 1945 ), otherwise, no further comparisons were made. Binary Parameters For comparisons involving more than two groups, if the Cochran-Armitage test ( Armitage, 1955 ) was significant at the 5% level, then the dir ection of the trend was es tablished and one-tailed step-down testing in this dire ction was performed. If the Cochran-Armitage test was not significant at the 5% level, then the χ 2 test ( Armitage, et. al. , 2002 ) was applied. If the χ 2 test was significant at the 5% level, the test-substance treated groups were compared to the control using Fisher’s Exact tests ( F isher, 1973 ), otherwise, no further comparisons were made. Statistical annotation Significant differences between control and treated groups were expressed at the 5% (p<0.05) or 1% (p<0.01) level. The key to annotations used on the tables that contai n statistical results is given below. Av Groups compared during the pretreatme nt period using Analysis of variance. Wi Treated groups compared with Control using Williams’ test. * p<0.05 ** p<0.01 

## 2.9 Data storage All raw data, preserved specimens, and retained sa mples, as well as the original study protocol and the original final report will be maintain ed in the Archives of the Testing Facility upon completion of the study. All slides were return ed to the Testing Facility following microscopic examination and peer review. The Sponsor will determine the final disposition of these materials. Electronic raw data generated at th e Testing Facility are maintained on the computer system on which the data applicati on resides or archived off-line. Biological samples collected for clinical pathology will be stored for up to 6 months after completion of assays and then discarded. All documentation, samples and data pertaining to the portions of the study performed by Principal Investigators will be maintained by the Test Sites’ according to their SOPs. 

## 2.10 Protocol deviations The following protocol deviations occurred duri ng the study but were no t considered to have compromised the validity or integrity of the study: 

## 1. During the 1st interval of pretest clinical pa thology blood collection, animals were fasted for more than 7 hours prior to blood colle ction (fasted at 1002, blood collection at 1716 to 1823 and fed at 2016).Sponsor reference number: Huntingdon Life Sciences: 13-6434

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## 2. During the 2 nd 

### interval of pretest c linical pathology blood co llection, Group 1 male animals were not fasted for at least 7 hours prior to blood collection but were fasted for 6 hours, 11 minutes to 6 hours, 45 minutes. 

## 3. On Days 2 to 5 of the pretest period, due to scheduling error, visual food consumption was measured and recorded although the pr otocol required food consumption to be estimated starting the 2 nd 

### week after animal receipt. The data recorded on these days was removed from Pristima (but is available for revi ew in the audit trail) and is not reported. 

## 4. On Day 9 of the pretest period, documentati on indicating the behavi or of all animals during clinical pathology blood collection wa s not recorded; therefore it cannot be confirmed that the protocol requirement was met. 

## 5. For animal identification, the supplier ear tags were not removed and the Testing Facility’s animal number was not applied by ta ttoo; the Testing Facility’s animal number was applied by permanent marker pen. 

## 6. On Day 14, Animal No. 1148 was given an expo sure holiday because of health concerns. 

## 7. On Days 16 and 17, Animal No. 1148 was exposed for 353 and 268, respectively, instead of the required duration of 360 minutes (6 hours). The exposures were terminated early for this animal because he was able to bypass the single-restraint compartment in the chamber and join the group-housed animals in the chamber. 

## 8. Beginning on Day 15, Animal No. 1148 was sing led-housed in the cham ber due to injury to its penis. 

## 9. On Days 18, 19 and 20, the chamber housing Animal No. 1148 had an average temperature of 19.1 °C to 19.6 °C; however, th e protocol required a temperature range of 20 °C to 27 °C. 

## 10. Due to oversight, Animal Nos. 1145, 1146, 2145 and 3145 were sedated and euthanized in the animal room rather then transferred to the necropsy lab for sedation and euthanasia. 

## 11. Documentation was not recorded for Animal Nos. 1145, 1146, 1147, 2145, 2146, 3145, 3146 and 3147 to indicate that after removing tissue for freezing and electron microscopy, the hearts were placed into chilled formalin for the duration of the necropsy; therefore, it cannot be confirmed that the pr otocol requirement was met. 

## 12. The protocol did not require that CK-BB be analysed by the Subcontractor however this parameter was analysed by the Subcontractor and included with their raw data transfer to HLS. This data was not included in the HL S report but was reviewed by the HLS clinical pathologist and not considered to re flect any treatment -related effects.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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# 3. Results and Discussion 3.1 Exposure results ( Annex 2 ) Mean target and achieved expos ure results were as follows: Group Treatment Target Exposure Levels Actual Exposure Levels (ppm) (mg/L) (ppm) 1 Air 0 0 0 2 HFO-1234yf 5,000 26 5145 3 HFO-1234yf 10,000 50 10200 No HFO-1234yf gas was detected in Group 1 sample s. Mean atmosphere concentrations were 3.8% and 2.0% above target for Group 2 males a nd females, respectively, and 2.0% above target for Group 3. The mean nominal concentration of 19100 ppm wa s 7% less than the overall combined IR measured concentration of 20600 ppm for Group 2. The mean nominal concentration of 39200 ppm was 4% less than the overall combined IR measured concentration of 40800 ppm for Group 3. This was considered a reasonable experimental difference as seen previously at this laboratory. 

## 3.2 Mortality There were no test substance-related unscheduled deaths or sacrifices. A Group 2 male animal #2147 was euthanized on Day 16 due to a severely prolapsed rectum. All other animals survived until their scheduled sacrifices. 

## 3.3 Clinical observations ( Table 1 , Table 2 , Table 3 , Appe ndix 1 , Appendix 2 and Appendix 3 ) There were no test substance-related clinical signs. 

## 3.4 Body weights ( Table 4 , Table 5 , Appendix 4 and Appendix 5 ) When compared to control animals, there were no test substance-related effects on body weights.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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## 3.5 Food consumption ( Table 6 and Appendix 6 ) When compared to control animals, there we re no test substance-related effects on food consumption. 

## 3.6 Clinical pathology 3.6.1 Hematology ( Table 7 , Appendix 7 and Annex 3 ) There were no test substance-related effects. All differences from controls or Pretest were not considered to be test substance-related because they were small in magnitude, not dose-relate d and/or consistent with normal biological variability. 3.6.2 Clinical chemistry ( Table 8 , Appendix 8 and Annex 3 ) There were no test substance-related effects. Minimal increases in total creatine kinase and CK-MM isoenzyme noted in 3/8 females on Study Day 21 at 10,000 ppm HFO-1234yf were not considered to be test substance-related because they were transient and values were within normal biological variability. 

## 3.7 Organ weights ( Table 9 , Table 10 , Table 11 , Appendix 9 and Annex 4 ) HFO-1234yf-related, marginal to slightly higher mean absolute and relative liver weights (compared to body and brain weights) were noted at exposure levels ≥ 5,000 ppm in females: Text Table 3.7-1: Test substance-related organ weight differences (approximate % difference in mean values relative to controls) at Terminal Sacrifice in Females

Sex Exposure Level Females HFO-1234yf ppm 0 5,000 10,000 No. examined 8 8 8 Liver Absolute (g) 224 253 272 a 

### Absolute % NA 12.9 21.6 a 

### vs body weight % NA 17.7 a 

### 22.1 a 

### vs brain weight % NA 18.3 32.8 a
a Statistically significant difference be tween mean values for test subs tance-treated and control groups. NA = not applicable: vs = versusSponsor reference number: Huntingdon Life Sciences: 13-6434

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### Potential morphologic correlates for differences in liver weight were not identified since histopathologic evaluation of the liver was not mandated by the protocol. Statistically significant differen ce in heart weight to body weight ratio in the 10,000 ppm group males was considered spurious because of th e lack of histopathologic findings and the discordance between absolute weights and weights relative to body and brai n weights. All other differences in organ weights were considered in cidental and due to norma l biological variability. 

## 3.8 Pathology 3.8.1 Mortality and macroscopic findings ( Table 12 , Appendix 10 and Annex 5 ) Group 2 male Animal 2147 was euthanized for welfare reasons on Day 16. At necropsy for this animal, the Testing Facility documented a prolapse of the rectum; the presence of clear, gelatinous material in the colon; and a single thrombus in the left ventricle as well as a single thrombus in the right ventricle. There was no evidence to suggest that these findings were associated with exposure to the test substance. At Day 29, there were a few sporadic macroscopic findings reported by the Testing Facility but there were no incidence patterns/trends for these findings to suggest a relationship to test substance exposure. Macroscopic findings reported included the fo llowing: Group 1 male Animal 1145 with diffuse red, dark areas of the right cr anial lung lobe; Group 1 female Animal 1652 with a few, clear, 10-19 mm cysts involving the caudal pole of the right kidney; Group 2 female Animal 2648 with a few, 10-19 mm, red, dark areas involving the cardiac region of the gastric mucosa; Group 2 female Animal 2649 with many 2-9 mm dark ar eas involving all lung lobes; Group 2 female Animal 2651 with bilateral dark mandibular lymph nodes; Group 3 male Animal 3148 with increased pericardial fluid; Group 3 male Animal 3151 with many small ( ≤ 1 mm), red, dark areas involving all lung lobes; Group 3 ma le Animal 3152 with focal adhesion of the pericardium to the left ventricle and many small ( ≤ 1 mm), red, dark areas involving the mucosa of the lower rectum; Group 3 female Animal 3646 with many 2-9 mm dark areas involving all lung lobes; Group 3 female Animal 3648 with bilateral dark mandibular lymph nodes; and Group 3 female Animal 3651 with many small ( ≤ 1 mm), red, dark areas involving all lung lobes as well as a few, 10-19 mm, red, dark areas i nvolving the cardiac region of the gastric mucosa and one, raised, 2-9 mm dark area of the gastric mucosa of the pylorus. 3.8.2 Microscopic evaluation ( Annex 5 ) There were no HFO-1234yf-related mi croscopic findings involving the heart (left ventricle, right ventricle, and septum) and skeletal muscle (rectus femoris, psoas, and soleus muscles as well as the diaphragm).Sponsor reference number: Huntingdon Life Sciences: 13-6434

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### Microscopic observations involving the heart were of sporadic incidence and primarily limited to cellular infiltration (mononuclear or mixed cell) involving the epicardium, myocardium, and/or endocardium. These observations were of mi nimal, insignificant intensity and showed no predilection as to anatomic site. An additiona l irrelevant finding included the single occurrence of focal pigmented macrophages within the epicardium in a single cardiac specimen. For skeletal muscle, microscopic observations included sporadic mononuclear cell infiltration, neutrophil infiltration, histiocytic infiltration, cy toplasmic basophilia of m yofibers, and myofiber degeneration involving the rectus femoris, soleus, psoas, and/or diaphragmatic muscle. These findings were of limited intensity as they predominantly occurred with minimal degree. A single animal, Group 2 female 2647, had minimal to mo derate myofiber atrophy involving the rectus femoris (right and left), soleus (right and left ), and psoas (right and left) muscles that was accompanied by slight myofiber mi neralization of the left psoa s muscle. As these atrophic changes were only observed in a single female at the low dose exposure level, they were deemed to be unrelated to HFO-1234yf. The aforementioned cardiac and skeletal muscle changes were incidental and many were those that can be observed in the age of Gottingen minipigs used in this study ( McInnes, 2012; Svendson et. al. , 1998 ). The microscopic observations s howed no consistent patterns/trends involving incidence or intensity to suggest a relationship to test substance exposure.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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# 4. Conclusion Daily inhalation administration of HFO-1234yf to minipigs for 28 days and up to a target exposure level of 10,000 ppm (actual achieved expos ure level of 10,200 ppm) was not associated with cardiotoxicity or skeletal muscle toxicity. The results of this study demonstrate that minipigs respond very differently to HFO-1234yf i nhalation exposure as compared to rabbits. Under the condition of this study, the No-O bserved-Adverse-Effect-Level (NOAEL) for inhalation toxicity was determin ed to be the actual achieved exposure level of 10,200 ppm.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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# 5. References Armitage, P. 1955. Tests for linear tre nds in proportions and frequencies. Biometrics (Sept.): 375-386. Armitage, P., Berry, G. and Matthews, J.N.S. 2002. Statistical Methods in Medical Research

. 4th edition, p.227. UK: Blackwell Science. Bartlett, M.S. 1937. Properties of su fficiency and statistical tests. Proceedings of the Royal Society, Series A , 160: 268-282. Dunnett, C.W. 1955. A multiple comparison proce dure for comparing several treatments with a control. Journal of the American Statistical Association 50: 1096-1121. Dunnett, C.W. 1964. New tables for multiple comparisons with a control. Biometrics 20-3: 482- 491. Fisher, R.A. 1973. Statistical Methods fo r Research Workers . 14 th 

### edition. New York: Hafner Publishing Company. Jonckheere, A.R. 1954. A distribution-free k-sample test ag ainst ordered alternatives. Biometrics 41: 133-145. Kruskal, W.H. and Wallis, W.A. 1952. Use of Ranks in One-Criterion Variance Analysis. Journal of the American Statistical Association 47: 583-621. Kruskal, W.H. and Wallis, W.A. 1953. Errata for Kruskal-Wallis (1952). Journal of the American Statistical Association 48: 907-911. McInnes, E.F. 2012. Background Lesions in Laboratory Animals: A Color Atlas. Edinburgh: Saunders Elsevier. Shirley, E.A.C. 1977. A non-parametric equivalent of Williams’ test for contrasting increasing dose levels of a treatment. Biometrics 33: 386-389. Steel, R.G.D. 1959. A multiple comparison rank sum test: treatments versus control. Biometrics 15: 560-572. Svendson O., Skydsgaard M., Aarup V. and Klastrup S. 1998. Spontaneously Occurring Microscopic Lesions in Selected Organs of the Gottingen Minipig. Scand. J. Lab. Anim. Sci. Suppl. 1 . Vol 25. Wilcoxon, F. 1945. Individual comparisons by ranking methods. Biometrics Bulletin 1: 80-83.Sponsor reference number: Huntingdon Life Sciences: 13-6434

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### Williams, D.A. 1971. A test for differences between treatment means when several dose levels are compared with a zero dose control. Biometrics 27: 103-117. Williams, D.A. 1972. The comparison of severa l dose levels with a zero dose control. Biometrics 28: 519-531.Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1M P1 Normal W ithin normal limits 0 4 0

Skin abrasion Dry , Ears 0 2 0 Dry , Ventral Surface 0 3 0 P2 Normal Within normal limits 4 4 0 Skin abrasion Dry , Ears 2 2 0 Dry , Ventral Surface 3 3 0 P3 Normal Wit hin normal limits 4 4 0 Skin abrasion Dry , Ears 2 2 0 Dry , Ventral Surface 3 3 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1M P4 Normal Within normal limits 4 4 0

Skin abrasion Dry , Ears 2 2 0 Dry , Ventral Surface 3 3 0 P5 Normal Within no rmal limits 8 8 0 P6 Normal Within normal limits 8 8 0 P7 Normal Within normal limits 8 8 0 P8 Normal Within normal limits 8 8 0 P9 Normal Within normal limits 8 8 0 P10 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1M P11 Normal Within normal limits 8 7 0

Skin Br uise, HindLimb

- Right

- Slight 0 1 0 P12 Normal Within normal limits 7 7 0 Skin Br uise, Hindlimb

- Right 1 1 0 P13 Normal Within normal limits 8 8 0 P14 Norm al Within normal limits 8 8 0 P15 Normal Within normal limits 8 8 0 1 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1M 2 Normal Within normal limits 8 8 0

3 Normal Within normal limits 8 7 0 Skin Scab, Hindlimb

- Right 0 1 0 4 Normal Within normal limits 7 7 0 Skin Scab, Hindlimb

- Right 1 1 0 5 Normal Within normal limits 7 7 0 Skin Scab, Hindlimb

- Right 1 1 0 6 Normal Within normal limits 7 7 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) D aily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1M 6 Skin Scab, Hindlimb

- Right 1 1 0

Skin abrasion Dry , Head 0 1 0 7 Normal Within normal limits 7 7 0 Skin Scab, Ears 1 1 0 Scab, Hindlimb

- Right 1 1 0 8 Normal Within normal limits 7 7 0 Skin Scab, Ears 1 1 0 Scab, Hindlimb

- Right 1 0 0 9 Normal Within normal limits 7 7 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1M 9 Skin Scab, Ears 1 1 0 10 Normal Within normal limits 7 7 0 Skin Scab, Ears 1 1 0 11 Normal Within normal limits 7 7 0 Sk in Scab, Ears 1 1 0 12 Normal Within normal limits 7 7 0 Skin Scab, Ears 1 1 0 13 Normal Within normal limits 7 6 0 Discharge Viscous, Red, Penis 0 1 1 Skin Scab, Ears 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Dai ly observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1M 13 Skin Scab, Tail 0 1 0 Ulceration, Tail 1 0 0 14 Normal Within normal limits 6 7 0 Discharge Viscous, Red, Penis 1 0 0 Skin Scab, Ears 1 1 0 Scab, Tail 1 1 0 15 Normal Within normal limits 7 7 0 Skin Scab, Ears 1 1 0 Scab, Tail 1 1 0 16 Normal Within normal limits 5 7 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1M 16 Discharge Aqueous, Red, Penis 1 0 0

Exudate Red Exudate In Cage 1 0 0 Skin Scab, Ears 1 0 0 Scab, Tail 1 0 0 Skin abrasion Dry , Tail 1 1 0 17 Normal Within normal limits 6 6 0 Skin Scab, Ears 1 1 0 Scab, Tail 1 1 0 Skin abrasion Dry , Tail 1 1 0 18 Normal Within normal limits 5 5 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Dai ly observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1M 18 Skin Scab, Ears 1 1 0 Scab, Head 1 1 0 Skin abrasion Dry , Tail 1 1 0 19 Normal Within normal limits 6 6 0 Skin Scab, Head 1 1 0 Skin abrasion Dry , Tail 1 1 0 20 Normal Within normal limits 6 6 0 Skin Scab, Hindlimb

- Right 1 1 0 Skin abrasion Dry , Tail 1 1 0 21 Normal Within normal limits 6 7 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (p pm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1M 21 Skin Scab, Hindlimb

- Right 1 0 0

Skin abrasion Dry , Ear
- Left 1 1 0 22 Normal Within normal limits 7 7 0 Skin abrasion Dry , Ear
- Left 1 1 0 23 Normal Within normal limits 7 7 0 Skin abrasion Dry , Ear
- Left 1 1 0 24 Normal Within normal limits 8 8 0 25 Normal Within normal limits 8 8 0 26 Normal Wit hin normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observa tion AM PM US PM 1M 27 Normal Within normal limits 8 8 0 28 Normal Within normal limits 8 8 0 29 Normal Within normal limits 8 0 0 2M P1 Normal Within normal limits 0 7 0

Skin abrasion Dry , Ears 0 1 0 P2 Normal Within normal limits 7 7 0 Skin abrasion Dry , Ears 1 1 0 P3 Normal Within normal limits 7 7 0 Skin abrasion Dry , Ears 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2M P4 Normal Within normal limits 7 7 0

Skin abrasion Dry , Ears 1 1 0 P5 Normal Within normal limits 7 7 0 Skin abrasion Dry , Ears 1 1 0 P6 Normal Within normal limits 7 8 0 Skin Scab, Ear

- Left 1 0 0 P7 Normal Within normal limits 8 8 0 P8 Normal Within normal l imits 8 8 0 P9 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2M P10 Normal Within normal limits 8 8 0 P11 Normal Within normal limits 8 8 0 P12 Normal Within normal limits 8 8 0 P13 Normal Within normal limits 8 8 0 P14 Normal Within normal limits 8 8 0 P15 Normal Within normal limits 8 8 0 1 Normal Within normal limits 8 8 0 2 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observat ions Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2M 3 Normal Within normal limits 8 8 0

4 Normal Within normal li mits 8 8 0 5 Normal Within normal limits 7 7 0 Skin abrasion Dry , Upper Dorsal Surface 1 1 0 6 Normal Within normal limits 8 8 0 7 Normal Within normal limits 7 7 0 Skin abrasion Dry , Head 1 1 0 8 Normal Within normal limits 7 7 0 Skin abrasion Dry , Head 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2M 9 Normal Within normal limits 7 7 0

Skin abrasion Dry , Head 1 1 0 10 Normal Within normal limits 7 7 0 Skin abrasion Dry , Head 1 1 0 11 Normal Within normal limits 8 8 0 12 Normal Within normal limits 8 8 0 13 Normal Within normal limits 8 8 0 14 Normal Within normal limits 7 7 0 Skin abrasion Dry , Head 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily ob servations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2M 15 Normal Within normal limi ts 7 7 0

Skin abrasion Dry , Head 1 1 0 16 Normal Within normal limits 7 7 0 Discharge Aqueous, Red, Anus 1 1 0 Reason for dispatch Prolapsed 0 1 0 17 Normal Within normal limits 6 6 0 Skin abr asion Dry , Hindlimb

- Right 1 1 0 18 Normal Within normal limits 5 5 0 Skin Scab, Dorsal surface 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2M 18 Skin abrasion Dry , Hindlimb

- Right 1 1 0 19 Normal Within normal limits 5 5 0 Skin Scab, Dorsal surfa ce 1 1 0 Skin abrasion Dry , Hindlimb

- Right 1 1 0 20 Normal Within normal limits 5 5 0 Skin Scab, Dorsal surface 1 1 0 Skin abrasion Dry , Hindlimb

- Right 1 1 0 21 Normal Within normal limits 7 7 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2 M 22 Normal Within normal limits 7 7 0 23 Normal Within normal limits 7 7 0 24 Normal Within normal limits 7 7 0 25 Normal Within normal limits 7 7 0 26 Normal Within normal limits 7 7 0 27 Normal Within no rmal limits 7 7 0 28 Normal Within normal limits 7 6 0 Skin abrasion Dry , Upper Dorsal Surface 0 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Do se (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2M 29 Normal Within normal limits 7 0 0 3M P1 Normal Within normal limits 0 7 0

Skin abrasion Dry , Ears 0 1 0 P2 Normal Within normal limits 6 6 0 Skin abrasion Dry , Ears 2 2 0 P3 Normal Within normal limits 6 7 0 Skin abrasion Dry , Ears 2 1 0 P4 Normal Within normal limits 6 6 0 Skin abrasion Dry , Ear s 2 2 0 P5 Normal Within normal limits 6 6 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affe cted /Sex Day Category Observation AM PM US PM 3M P5 Skin abrasion Dry , Ears 2 2 0 P6 Normal Within normal limits 6 6 0 Skin Scab, Ear

- Left 2 2 0 P7 Normal Within normal limits 6 6 0 Skin Scab, Ear

- L eft 2 2 0 P8 Normal Within normal limits 6 6 0 Skin Scab, Ear

- Left 2 2 0 P9 Normal Within normal limits 7 7 0 Skin Scab, Ear

- Left 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of obser vations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M P10 Normal Within normal limits 7 8 0

Skin Scab, Ear

- Le ft 1 0 0 P11 Normal Within normal limits 8 8 0 P12 Normal Within normal limits 8 7 0 Skin abrasion Wet, Ear
- Right 0 1 0 P13 Normal Within normal limits 7 8 0 Skin Scab, Ear

- Right 1 0 0 P14 N or mal Within normal limits 8 7 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Categor y Observation AM PM US PM 3M P14 Skin abrasion Dry , Head 0 1 0 P15 Normal Within normal limits 5 5 0 Skin abrasion Dry , Dorsal surface 1 1 0 Dry , Head 2 2 0 1 Normal Within normal limits 5 5 0 Skin abrasion Dry , Dorsal surface 1 1 0 Dry , Ear
- Left 0 1 0 Dry , Head 2 1 0 2 Normal Within normal limits 6 6 0 Skin abrasion Dry , Ear
- Left 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distrib ution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 2 Skin abrasion Dry , Head 1 1 0

3 Normal Wit hin normal limits 6 6 0 Skin abrasion Dry , Ear
- Left 1 1 0 Dry , Head 1 1 0 4 Normal Within normal limits 6 6 0 Skin abrasion Dry , Ear
- Left 1 1 1 Dry , Head 1 1 1 Dry , Lower Dorsal Surfac e 0 0 2 5 Normal Within normal limits 4 4 0 Skin abrasion Dry , Ear
- Left 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 5 Skin abrasion Dry , Head 3 3 0 Dry , Lower Dorsal Surface 2 2 0 Dry , Upper Dorsal Surface 2 2 0 6 Normal Within nor mal limits 3 3 0 Skin abrasion Dry , Ear
- Left 2 2 0 Dry , Head 3 3 0 Dry , Lower Dorsal Surface 2 2 0 Dry , Upper Dorsal Surface 2 2 0 7 Normal Within normal limits 4 4 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Dail y observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 7 Skin Scab, Dorsal surf ace 1 1 0 Scab, Ear

- Left 1 1 0 Scab, Lower Dorsal Surface 1 1 0 Skin abrasion Dry , Dorsal surface 1 1 0 Dry , Head 1 1 0 Dry , Lower Dorsal Surface 1 1 0 Dry , Upper Dorsal Surface 2 2 0 8 Normal Within normal limits 4 4 0 Skin Scab, Dorsal surface 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 8 Skin Scab, Ear

- Left 1 1 0 Scab, Lower Dorsal Surface 1 1 0 Skin abrasion Dry , Dorsal surface 1 1 0 Dry , Head 1 1 0 Dry , Lower Dorsal Surface 1 1 0 Dry , Upper Dorsal Surface 2 2 0 9 Normal Within normal limits 4 4 0 Skin Scab, Dorsal surface 1 1 0 Scab, Ear

- Left 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr o up distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 9 Skin Scab, Lower Dorsal Surface 1 1 0

Skin abrasion Dry , Dorsal surface 1 1 0 Dry , Head 1 1 0 Dry , Lower Dorsal Surface 1 1 0 Dry , Upper Dorsal Surface 2 2 0 10 Normal Within normal limits 4 5 0 Skin Scab, Dorsal surface 1 0 0 Scab, Ear

- Left 1 1 0 Scab, Lower Dorsal Surface 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 10 Skin abrasion Dry , Dorsal surface 1 0 0 Dry , Head 1 1 0 Dry , Lower Dorsal Surface 1 1 0 Dry , Upper Dorsal Surface 2 2 0 11 N or mal Within normal limits 6 6 0 Skin Scab, Ear

- Left 1 1 0 Scab, Lower Dorsal Surface 1 1 0 Skin abrasion Dry , Lower Dorsal Surface 1 1 0 Dry , Upper Dorsal Surface 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observ ations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 12 Normal Within normal limits 6 6 0

Skin Scab, Ear

- Left 1 1 0 Scab, Lower Dorsal Surface 1 1 0 Scab, Upper Dorsal Surface 2 2 0 13 Normal Within normal limits 6 6 0 Skin Scab, Ear

- Left 1 1 0 Scab, Lower Dorsal Surfa ce 1 1 0 Scab, Upper Dorsal Surface 2 2 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affec ted /Sex Day Category Observation AM PM US PM 3M 14 Normal Within normal limits 4 4 0

Skin Scab, Dorsal surface 1 1 0 Scab, Ear

- Left 1 1 0 Scab, Lower Dorsal Surface 1 1 0 Scab, Upper Dorsal Surfa ce 2 2 0 Skin abrasion Dry , Head 1 1 0 Dry , Upper Dorsal Surface 2 1 0 15 Normal Within normal limits 4 4 0 Skin Scab, Dorsal surface 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of obs ervations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 15 Skin Scab, Ear

- Left 1 1 0 Scab, Lower Dorsal Surf

ace 1 1 0 Scab, Upper Dorsal Surface 2 2 0 Skin abrasion Dry , Head 1 1 0 Dry , Upper Dorsal Surface 1 1 0 16 Normal Within normal limits 7 6 0 Skin Scab, Head 1 1 0 Skin abrasion Dry , Upper Dorsal Surface 0 1 0 17 Normal Within normal limits 6 6 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 17 Skin Scab, Head 1 1 0

Skin abrasion Dry , Upper Dorsal Surface 1 1 0 18 Normal Within normal limits 4 4 0 Skin Scab, Head 2 2 0 Ulcerati on, Ear
- Left 1 1 0 Skin abrasion Dry , Upper Dorsal Surface 1 1 0 19 Normal Within normal limits 3 3 0 Skin Scab, Head 2 2 0 Scab, Hindlimb

- Right 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup dist ribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 19 Skin Ulceration, Ear

- Left 1 1 0

Ski n abrasion Dry , Upper Dorsal Surface 1 1 0 20 Normal Within normal limits 2 2 0 Skin Scab, Head 3 3 0 Scab, Hindlimb

- Right 1 1 0 Ulceration, Ear

- Left 1 1 0 Skin abrasion Dry , Upper Dorsal Surface 1 1 0 21 Normal Within normal limits 3 3 0 Skin Scab, Ear

- Left 0 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 21 Skin Scab, Head 2 2 0 Scab, Hindlimb

- Right 1 1 0 Ulceration, Ear

- Left 1 0 0 Skin abrasion Dry , Upper Dorsal Surface 1 1 0 22 Normal Within normal limits 4 4 0 Skin Scab, Ear

- Left 1 1 0 Scab, Head 1 1 0 Scab, Hindlimb

- Right 1 1 0 Skin abrasion Dry , Upper Dorsal Surface 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily obser vations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 23 Normal Within normal limits 4 4 0

Skin Scab, Ear

- Left 1 1 0 Scab, Head 1 1 0 Scab, Hindlimb

- Right 1 1 0 Skin abrasion Dry , Upper Dorsal Surface 1 1 0 24 Normal Within normal limits 7 6 0 Skin Scab, Head 1 1 0 Skin abrasion Dry , Dorsal surface 0 1 0 25 Normal Within normal limits 6 6 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 25 Skin Scab, Head 1 1 0 Scab, Upper Dorsal Surface 0 1 0 Skin abrasion Dry , Dorsal surface 1 1 0 26 Normal Within normal l imits 6 6 0 Skin Scab, Head 1 1 0 Scab, Upper Dorsal Surface 1 1 0 Skin abrasion Dry , Dorsal surface 1 1 0 27 Normal Within normal limits 6 6 0 Skin Scab, Head 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily obs ervations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3M 27 Skin Scab, Upper Dorsal Su rface 1 1 0 Skin abrasion Dry , Dorsal surface 1 1 0 28 Normal Within normal limits 8 8 0 29 Normal Within normal limits 8 0 0 1F P1 Normal Within normal limits 0 7 0

Skin abrasion Dry , Ears 0 1 0 P2 Normal Within normal limits 7 6 0 Skin abrasion Dry , Ears 1 1 0 Dry , Head 0 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1F P3 Normal Within normal limits 6 6 0

Skin abrasion Dry , Ears 1 1 0 Dry , Head 1 1 0 P4 Normal Within normal li mits 6 6 0 Skin abrasion Dry , Ears 1 1 0 Dry , Head 1 1 0 P5 Normal Within normal limits 7 7 0 Skin Scab, Head 1 1 0 P6 Normal Within normal limits 8 8 0 P7 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1F P8 Normal Within normal limits 8 8 0 P9 Normal Within normal limits 8 8 0 P10 Normal Within normal limits 8 8 0 P11 Normal Within normal limits 8 8 0 P12 Normal Within normal limits 8 8 0 P13 Normal Wit hin normal limits 8 8 0 P14 Normal Within normal limits 8 8 0 P15 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1F Ra1 Normal Within normal limits 8 8 0 1 Normal Within normal limits 8 8 0 2 Normal Within normal limits 8 8 0 3 Normal Within normal limits 8 8 0 4 Normal Within normal limits 5 5 0 Skin abrasion Dry , Hindlimb

- Right 1 1 0 Dry , Upper Dorsal Surface 2 2 0 5 Normal Within normal limits 5 5 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (c ont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1F 5 Skin abrasion Dry , Hindlimb

- Right 1 1 0 Dry , Upper Dorsal Surface 2 2 0 6 Normal Within normal limits 7 7 0 Skin abrasion Dry , Upper Dorsal Surface 1 1 0 7 Normal Within normal limits 8 8 0 8 Normal Within normal l imits 8 8 0 9 Normal Within normal limits 8 8 0 10 Normal Within normal limits 8 6 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1F 10 Skin abrasion Dry , Head 0 1 0 Dry , Nose 0 1 0 11 Normal Within normal limits 7 7 0 Skin abrasion Dry , Head 1 1 0 12 Normal Within normal limits 8 8 0 13 Normal Within normal limits 8 8 0 14 Normal Within normal limits 8 8 0 15 Normal Within normal limits 8 8 0 16 Normal Within normal limits 7 7 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1F 16 Skin abr asion Dry , Head 1 1 0 17 Normal Within normal limits 6 7 0 Skin abrasion Dry , Head 1 0 0 Dry , Hindlimb

- Right 1 1 0 18 Normal Within normal limits 6 6 0 Skin Scab, Ear

- Left 1 1 0 Skin abra sion Dry , Hindlimb

- Right 1 1 0 19 Normal Within normal limits 6 6 0 Skin Scab, Ear

- Left 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1F 19 Skin abrasion Dry , Hindlimb

- Right 1 1 0 20 Normal Within normal limits 6 6 0 Skin Scab, Ear

- Left 1 1 0 Skin abrasion Dry , Hindlimb

- Right 1 1 0 21 Normal Within normal limits 7 7 0 Skin Scab, Ear

- Left 1 1 0 22 Normal Within normal limits 7 7 0 Skin Scab, Ear

- Left 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 1F 23 Normal Within normal l imits 8 8 0 24 Normal Within normal limits 8 8 0 25 Normal Within normal limits 8 8 0 26 Normal Within normal limits 8 8 0 27 Normal Within normal limits 8 8 0 28 Normal Within normal limits 8 8 0 29 Normal Within normal limits 8 0 0 2F P1 Normal Within normal limits 0 6 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2F P1 Skin abrasion Dry , Ears 0 1 0 Dry , Ventral Surface 0 1 0 P2 Normal Within normal limits 6 5 0 Skin abrasion Dry , Ears 1 1 0 Dry , Upper Dorsal Surface 0 1 0 Dry , Ventral Surface 1 1 0 P3 Normal Within normal limits 5 5 0 Skin abrasion Dry , Ears 1 1 0 Dry , Upper Dorsal Surface 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observation s - gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2F P3 Skin abrasion Dry , Ventral Surface 1 1 0 P4 Normal Within normal limits 5 5 0 Skin abrasion Dry , Ears 1 1 0 Dry , Upper Dorsal Surface 1 1 0 Dry , Ventral Surface 1 1 0 P5 Normal Within normal limits 7 7 0 Skin abrasion Dry , V entral Surface 1 1 0 P6 Normal Within normal limits 7 7 0 Skin abrasion Dry , Ventral Surface 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2F P7 Normal Within normal limits 8 8 0 P8 Normal Within normal limits 8 8 0 P9 Normal Within normal limits 8 8 0 P10 Normal Within normal limits 8 8 0 P11 Normal Within normal limits 8 8 0 P12 Normal Within normal limits 8 8 0 P13 Normal Within normal limits 8 8 0 P14 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABL E 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2F P15 Norma l Within normal limits 8 8 0 Ra1 Normal Within normal limits 8 8 0 1 Normal Within normal limits 8 8 0 2 Normal Within normal limits 8 8 0 3 Normal Within normal limits 8 8 0 4 Normal Within normal limits 8 8 0 5 Normal Within normal limits 7 7 0 Skin abrasion Dry , Hindlimb

- Right 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2F 6 Normal Within normal limits 6 6 0

Skin Scab, Hindlimb

- Right 1 1 0 Skin abrasion Dry , Lower Dorsal Surface 1 1 0 7 Normal Within normal limits 8 8 0 8 Normal Within normal limits 8 8 0 9 Normal Within normal limits 8 8 0 10 Normal Within normal limits 8 7 0 Skin abrasion Dry , Upper Ventral Surface 0 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (c ont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2F 10 Skin color A bnormal color, Red, Upper Dorsal Surface 0 1 0 11 Normal Within normal limits 7 7 0 Skin color Abnormal color, Red, Upper Dorsal Surface 1 1 0 12 Normal Within normal limits 8 8 0 13 Normal Within normal limits 8 8 0 14 Normal Within normal limits 8 8 0 15 Normal Within normal limits 8 8 0 16 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2F 17 Normal Within normal limits 7 7 0

Skin abrasion Dry , Ear
- Left 1 1 0 18 Normal Wit hin normal limits 7 7 0 Skin abrasion Dry , Ear
- Left 1 1 0 19 Normal Within normal limits 5 5 0 Skin abrasion Dry , Ear
- Left 1 1 0 Dry , Head 2 2 0 20 Normal Within normal limits 5 5 0 Skin abrasion Dry , Dorsal surface 0 1 0 Dry , Ear
- Left 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number o f animals affected /Sex Day Category Observation AM PM US PM 2F 20 Skin abrasion Dry , Head 2 2 0 21 Normal Within normal limits 5 5 0 Skin abrasion Dry , Dorsal surface 1 1 0 Dry , Ear
- Left 1 1 0 Dry , Head 2 2 0 22 Normal Within normal limits 5 5 0 Skin abrasion Dry , Dorsal surface 1 1 0 Dry , Ear
- Left 1 1 0 Dry , Head 2 2 0 23 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily obser vations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2F 24 Normal Within normal limits 8 8 0 25 Normal Within normal limits 7 7 0 Skin abrasion Dry , Dorsal surface 1 1 0 26 Normal Within normal limits 7 7 0 Skin abrasion Dry , Dorsal surface 1 1 0 27 Normal Within normal limits 7 7 0 Skin abrasion Dry , Dorsal surface 1 1 0 28 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 2F 29 Normal Within normal limits 8 0 0 3F P1 Normal Within normal limits 0 8 0 P2 Normal Within normal limits 8 8 0 P3 Normal Withi n normal limits 8 8 0 P4 Normal Within normal limits 8 8 0 P5 Normal Within normal limits 8 8 0 P6 Normal Within normal limits 8 8 0 P7 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3F P8 Normal Within normal limits 8 8 0 P9 Normal Within normal limits 8 8 0 P10 Normal Within normal limits 8 8 0 P11 Normal Within normal limits 8 8 0 P12 Normal Within normal limits 8 8 0 P13 Normal Within normal limits 8 8 0 P14 Normal Within normal limits 8 8 0 P15 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group N umber of animals affected /Sex Day Category Observation AM PM US PM 3F Ra1 Normal Within normal limits 8 8 0

1 Normal Within normal limits 8 8 0 2 Normal Within normal limits 8 8 0 3 Normal Within normal limits 8 8 0 4 Normal Within normal limits 5 5 0 Skin abrasion Dry , Head 3 3 0 5 Normal Within normal limits 5 5 0 Skin abrasion Dry , Head 3 3 0 Dry , Upper Dorsal Surface 1 1 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily obse rv ations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3F 6 Normal Within normal limits 7 7 0

Skin abrasion Dry , Ear
- Right 1 1 0 7 Normal Within normal limits 8 8 0 8 Normal Within normal limits 8 8 0 9 Normal Within normal limits 8 8 0 10 Normal Within normal limits 7 7 0 Skin S cab, Lower Dorsal Surface 1 1 0 11 Normal Within normal limits 7 7 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3F 11 Skin Scab, Lower Dorsal Surface 1 1 0 12 Normal Within normal limits 7 7 0 Skin Scab, Lower Dorsal Surface 1 1 0 13 Normal Within normal limits 7 7 0 Skin Scab, Lower Dorsal Surface 1 1 0 14 Normal Within normal limits 7 7 0 Skin Scab, Lower Dorsal Surface 1 1 0 15 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- grou

p distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3F 16 Normal Within normal limits 8 8 0 17 Normal Within normal limits 8 8 0 18 Normal Within normal limits 6 6 0 Skin Scab, Head 1 1 0 Scab, Hindlimb

- Right 1 1 0 19 Normal Within normal limits 6 6 0 Skin Scab, Head 1 1 0 Scab , Hindlimb

- Right 1 1 0 20 Normal Within normal limits 6 6 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution of observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Numbe r of animals affected /Sex Day Category Observation AM PM US PM 3F 20 Skin Scab, Head 1 1 0 Scab, Hindlimb

- Right 1 1 0 21 Normal Within normal limits 7 7 0 Skin Scab, Head 1 1 0 22 Normal Within norma l limits 7 7 0 Skin Scab, Head 1 1 0 23 Normal Within normal limits 8 8 0 24 Normal Within normal limits 8 8 0 25 Normal Within normal limits 8 8 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 (cont) Daily observations

- gr oup distribution o f observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation AM PM US PM 3F 26 Normal Within normal limits 8 8 0 27 Normal With in normal limits 8 8 0 28 Normal Within normal limits 8 8 0 29 Normal Within normal limits 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 1 M 1 Normal Within normal limits 8 8 0 0 2 Normal Within normal limits 8 8 0 0 3 Normal Within normal limits 8 8 0 0 4 Normal Within normal limits 8 8 0 0 5 Normal Within normal limits 8 8 0 0 6 Normal Within normal limits 8 8 0 0 7 Normal Within normal limits 8 8 0 0 8 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 1M 9 Normal Within normal limits 8 8 0 0 10 Normal Within normal limits 8 8 0 0 11 Normal Within normal limits 8 8 0 0 12 Normal Within normal limits 8 8 0 0 13 Normal Within normal limits 8 8 0 0 14 Normal Within normal limits 7 7 0 0 15 Normal Within normal limits 8 8 0 0 16 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observa tion 2 Hours 4 Hours US1 US2 1M 17 Normal Within normal limits 8 8 0 0 18 Normal Within normal limits 8 8 0 0 19 Normal Within normal limits 8 8 0 0 20 Normal Within normal limits 8 8 0 0 21 Normal Wit hin normal limits 8 8 0 0 22 Normal Within normal limits 8 8 0 0 23 Normal Within normal limits 8 8 0 0 24 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observatio ns

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 1M 25 Normal Within normal limits 8 8 0 0 26 Normal Within normal limits 8 8 0 0 27 Normal Within normal limits 8 8 0 0 28 Normal Within normal limits 8 8 0 0 2M 1 Normal Within normal limits 7 7 0 0

2 Normal Within normal limits 8 8 0 0 3 Normal Within normal limits 8 8 0 0 4 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Numb er of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 2M 5 Normal Within normal limits 8 8 0 0

6 Normal Within normal limits 8 8 0 0 7 Normal Within normal limits 8 8 0 0 8 Normal Within n ormal limits 8 8 0 0 9 Normal Within normal limits 8 8 0 0 10 Normal Within normal limits 8 8 0 0 11 Normal Within normal limits 8 8 0 0 12 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose obse rv ations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 2M 13 Normal Within normal limits 8 8 0 0 14 Normal Within normal limits 8 8 0 0 15 Normal Within normal limits 8 8 0 0 16 Normal Within normal limits 7 7 0 0 17 Normal Within normal limits 7 7 0 0 18 Normal Within norma l limits 7 7 0 0 19 Normal Within normal limits 7 7 0 0 20 Normal Within normal limits 7 7 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose ( ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 2M 21 Normal Within normal limits 7 7 0 0 22 Normal Within normal limits 7 7 0 0 23 Normal Within no rmal limits 7 7 0 0 24 Normal Within normal limits 7 7 0 0 25 Normal Within normal limits 7 7 0 0 26 Normal Within normal limits 7 7 0 0 27 Normal Within normal limits 7 7 0 0 28 Normal Within normal l imits 7 7 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Ho urs 4 Hours US1 US2 3M 1 Normal Within normal limits 8 8 0 0

2 Normal Within normal limits 8 8 0 0 3 Normal Within normal limits 8 8 0 0 4 Normal Within normal limits 8 8 0 0 5 Normal Within normal lim its 8 8 0 0 6 Normal Within normal limits 8 8 0 0 7 Normal Within normal limits 8 8 0 0 8 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Co

ntrol HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 3M 9 Normal Within normal limits 8 8 0 0 10 Normal Within normal limi ts 8 8 0 0 11 Normal Within normal limits 8 8 0 0 12 Normal Within normal limits 8 8 0 0 13 Normal Within normal limits 8 8 0 0 14 Normal Within normal limits 8 8 0 0 15 Normal Within normal limits 8 8 0 0 16 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals aff ected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 3M 17 Normal Within normal limits 8 8 0 0 18 Normal Within normal limits 8 8 0 0 19 Normal Within normal limits 8 8 0 0 20 Normal Within normal limits 8 8 0 0 21 Normal Within normal limits 8 8 0 0 22 Normal Within normal limits 8 8 0 0 23 Normal Within normal limits 8 8 0 0 24 Normal Within normal limits 8 7 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 3M 24 Muscle reaction Shivering 0 1 0 0 25 Normal Within normal limits 8 8 0 0 26 Normal Within normal limits 8 8 0 0 27 Normal Within normal limits 8 8 0 0 28 Normal Within normal limits 8 8 0 0 1F 1 Normal Within normal limits 8 8 0 0 2 Normal Within normal limits 8 8 0 0 3 Normal Within normal limits 8 8 0 0 4 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control H FO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 1F 5 Normal Within normal limits 8 8 0 0 6 Normal Within normal limits 8 8 0 0 7 Normal Within normal limits 8 8 0 0 8 Normal Within normal limits 8 8 0 0 9 Normal Within normal limits 8 8 0 0 10 Normal Within normal limits 8 8 0 0 11 Normal Within normal limits 8 8 0 0 12 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 1F 13 Normal Within normal limits 8 8 0 0 14 Normal Within normal limits 8 8 0 0 15 Normal Within normal limits 8 8 0 0 16 Normal Within normal limits 8 8 0 0 17 Normal Within normal limits 8 8 0 0 18 Normal Within normal limits 8 8 0 0 19 Normal Within normal limits 8 8 0 0 20 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distr ibution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 1F 21 Normal Within normal limits 8 8 0 0 22 Normal Within normal limits 8 8 0 0 23 Normal Within normal limits 8 8 0 0 24 Normal Within normal limits 8 8 0 0 25 Normal Within normal limits 8 8 0 0 26 Normal Within normal limits 8 8 0 0 27 Normal Within normal limits 8 8 0 0 28 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 2F 1 Normal Within normal limits 8 8 0 0 2 Normal Within normal limits 8 8 0 0 3 Normal Within normal limits 8 8 0 0 4 Normal Within normal limits 8 8 0 0 General condition Laceration, Tail 0 0 0 1 5 Normal Within normal limits 8 8 0 0 6 Normal Within normal limits 8 8 0 0 7 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 2F 8 Normal Within normal limits 8 8 0 0 9 Normal Within normal limits 8 8 0 0 10 Normal Within normal limits 8 8 0 0 11 Normal Within normal limits 8 8 0 0 12 Normal Within normal limits 8 8 0 0 13 Normal Within normal limits 8 8 0 0 14 Normal Within normal limits 8 8 0 0 15 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf D ose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 2F 16 Normal Within normal limits 8 8 0 0 17 Normal Within normal limits 8 8 0 0 18 Normal Within normal limits 8 8 0 0 19 Normal Within normal limits 8 8 0 0 20 Normal Within normal limits 8 8 0 0 21 Normal Within normal limits 8 8 0 0 22 Normal Within normal limits 8 8 0 0 23 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Ca tegory Observation 2 Hours 4 Hours US1 US2 2F 24 Normal Within normal limits 8 8 0 0 25 Normal Within normal limits 8 8 0 0 26 Normal Within normal limits 8 8 0 0 27 Normal Within normal limits 8 8 0 0 28 Normal Within normal limits 8 8 0 0 3F 1 Normal Within normal limits 8 8 0 0

General condition Laceration, Tail 0 0 1 0 2 Normal Within normal limits 7 7 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distri bution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 3F 2 General condition Laceration, Tail 1 1 0 0 3 Normal Within normal limits 8 8 0 0 4 Normal Within normal limits 8 8 0 0 5 Normal Within normal limits 8 8 0 0 6 Normal Within normal limits 8 8 0 0 7 Normal Within normal limits 8 8 0 0 8 Normal Within normal limits 8 8 0 0 9 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 3F 10 Normal Within normal limits 8 8 0 0 11 Normal Within normal limits 8 8 0 0 Br eathing Coughing 0 0 1 0 12 No rmal Within normal limits 8 8 0 0 13 Normal Within normal limits 8 8 0 0 14 Normal Within normal limits 8 8 0 0 15 Normal Within normal limits 8 8 0 0 16 Normal Within normal limits 8 8 0 0 17 Normal W ithin normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Ob servation 2 Hours 4 Hours US1 US2 3F 18 Normal Within normal limits 8 8 0 0 19 Normal Within normal limits 8 8 0 0 20 Normal Within normal limits 8 8 0 0 21 Normal Within normal limits 8 8 0 0 22 Norma l Within normal limits 8 8 0 0 23 Normal Within normal limits 8 8 0 0 24 Normal Within normal limits 8 8 0 0 25 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 2 (cont) Dose observations

- gr oup distribution of obser vations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Number of animals affected /Sex Day Category Observation 2 Hours 4 Hours US1 US2 3F 26 Normal Within normal limits 8 8 0 0 27 No rmal Within normal limits 8 8 0 0 28 Normal Within normal limits 8 8 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 3 Clinical signs

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Number of animals affected Category Observation Week Group/Sex: 1M 2M 3M 1F 2F 3F Initial no: 8 8 8 8 8 8 Normal Within normal limits P2 8 8 8 8 8 8 P3 8 8 5 8 8 8 1 7 7 4 8 8 8 2 6 7 4 8 8 7 3 7 6 3 8 6 7 4 8 7 8 8 8 8 Discharge Viscous, Red, Penis 2 1 0 0 0 0 0 Skin Scab, Dorsal surface 1 0 0 1 0 0 0 2 0 0 1 0 0 0 3 0 0 1 0 0 0 Scab, Ear

- Left 1 0 0 1 0 0 0 2 0 0 1 0 0 0 3 0 0 1 0 0 0 Scab, Ears 1 1 0 0 0 0 0 2 1 0 0 0 0 0 3 1 0 0 0 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 3 (cont) Clinical signs

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Number of animals affected Category Obser vation Week Group/Sex: 1M 2M 3M 1F 2F 3F Initial no: 8 8 8 8 8 8 Skin Scab, Hindlimb

- Right 1 1 0 0 0 0 0 2 1 0 0 0 0 0 3 1 0 0 0 0 0 Scab, Lower Dorsal Surface 1 0 0 1 0 0 0 2 0 0 1 0 0 1 3 0 0 1 0 0 0 Scab, Upper Dorsal Surface 1 0 0 1 0 0 0 2 0 0 1 0 0 0 3 0 0 1 0 0 0 Ulceration, Ear

- Left 3 0 0 1 0 0 0 Skin abrasion Dry , Dorsal surface P3 0 0 1 0 0 0 1 0 0 1 0 0 0 2 0 0 1 0 0 0 3 0 0 1 0 0 0 Dry , Ear
- Left 3 0 1 1 0 2 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 3 (cont) Clinical signs

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose G ro up 1 2 3 Dose (ppm) 5000 10000 Number of animals affected Category Observation Week Group/Sex: 1M 2M 3M 1F 2F 3F Initial no: 8 8 8 8 8 8 Skin abrasion Dry , Head P3 0 0 2 0 0 0 1 0 1 1 0 0 0 2 0 1 1 0 0 0 3 0 1 1 0 0 1 Dry , Lower Dorsal Surface 1 0 0 1 0 0 0 2 0 0 1 0 0 0 3 0 0 1 0 0 0 Dry , Upper Dorsal Surface 1 0 0 1 0 0 0 2 0 0 1 0 0 0 3 0 0 1 0 0 0Sponsor reference number:Huntingdon Life Sciences: 13-6434TABLE 4 Body weights - group mean values (kg)Vehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Week WeekChange Change Change Change/Sex P1 P2 P3 1 2 3 4 P3-1 P3-2 P3-3 P3-4Statistics test Av Av Av Wi Wi Wi Wi Wi Wi Wi Wi1M Mean 6.8 7.2 7.7 8.6 9.3 10.3 10.9 0.9 1.7 2.7 3.2SD 0.85 0.84 0.90 0.99 1.11 1.19 1.31 0.15 0.36 0.57 0.71N8 8 8 8 8 8 8 8 8 8 82M Mean 6.3 6.7 7.3 8.1 8.8 9.6 10.2 0.8 1.5 2.5 3.1SD 0.70 0.77 0.94 1.06 1.16 1.11 1.09 0.27 0.34 0.41 0.41N8 8 8 8 8 7 7 8 8 7 73M Mean 5.9 6.5 7.1 7.8 8.6 9.6 9.9 0.7 1.5 2.5 2.8SD 0.83 0.89 1.01 1.20 1.37 1.62 1.70 0.25 0.49 0.87 0.93N8 8 8 8 8 8 8 8 8 8 8Sponsor reference number:Huntingdon Life Sciences: 13-6434TABLE 4 (cont) Body weights - group mean values (kg)Vehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Week WeekChange Change Change Change/Sex P1 P2 P3 1 2 3 4 P3-1 P3-2 P3-3 P3-4Statistics test Av Av Av Wi Wi Wi Wi Wi Wi Wi Wi1F Mean 6.8 7.5 8.1 9.2 10.0 11.0 11.7 1.1 1.9 2.9 3.6SD 0.40 0.52 0.68 0.89 0.97 1.07 1.09 0.24 0.35 0.48 0.48N8 8 8 8 8 8 8 8 8 8 82F Mean 6.4 7.0 7.6 8.7 9.4 10.7 11.5 1.1 1.8 3.1 3.9SD 1.05 1.16 1.25 1.34 1.48 1.65 1.65 0.22 0.41 0.52 0.65N8 8 8 8 8 8 8 8 8 8 83F Mean 6.7 7.2 7.8 8.9 9.8 11.0 11.7 1.1 1.9 3.2 3.9SD 0.54 0.74 0.85 0.97 1.12 1.36 1.51 0.20 0.33 0.62 0.82N8 8 8 8 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 5 Body weight change

- gr oup mean values (kg)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Week Week /Sex P1
- P2 P2
- P3 P3
- 1 1
- 2 2
- 3 3
- 4 Statistics test Av Av Wi Wi Wi Wi 1M Mean 0.5 0.5 0.9 0. 8 1.0 0.5

SD 0.34 0.19 0.15 0.25 0.30 0.23 N 8 8 8 8 8 8 2M Mean 0.4 0.6 0.8 0.8 1.0 0.6

SD 0.25 0.25 0.27 0.17 0.17 0.08 N 8 8 8 8 7 7 3M Mean 0.5 0.6 0.7 0.8 0.9 0.3**

SD 0.20 0.24 0.25 0.28 0.47 0.12 N 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 5 (cont) Body weight change

- gr oup mean values (kg)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Week Week /Sex P1
- P2 P2
- P3 P3
- 1 1
- 2 2
- 3 3
- 4 Statistics test Av Av Wi Wi Wi Wi 1F Mean 0.6 0.7 1.1 0.7 1.0 0.7

SD 0.26 0.24 0.24 0.16 0.18 0.14 N 8 8 8 8 8 8 2F Mean 0.5 0.6 1.1 0.7 1.3 0.7

SD 0.27 0.14 0.22 0.28 0.22 0.27 N 8 8 8 8 8 8 3F Mean 0.5 0.6 1.1 0.9 1.2 0.7

SD 0.31 0.20 0.20 0.18 0.33 0.26 N 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 6 Visual food consumption

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Number of animals affected Category Observation Day Group/Sex: 1M 2M 3M 1F 2F 3F Init ial no: 8 8 8 8 8 8 Visual Food Consumption 4: All food consumed P8 8 8 8 8 8 8 P9 8 8 8 8 8 8 P10 8 8 8 8 8 8 P11 8 8 8 8 8 8 P12 8 8 8 8 8 8 P13 8 8 8 8 8 8 P14 8 8 8 8 8 8 P15 8 8 8 8 8 8 Ra1 0 0 0 8 8 8 1 8 8 8 8 8 8 2 8 8 8 8 8 8 3 8 8 8 8 8 8 4 8 8 8 8 8 8 5 8 8 8 8 8 8 6 8 8 8 8 8 8 7 8 8 8 8 8 8 8 8 8 8 8 8 8 9 8 8 8 8 8 8 10 8 8 8 8 8 8 11 8 8 8 8 8 8 12 8 8 8 8 8 8 13 8 8 8 8 8 8 14 8 8 8 8 8 8 15 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 6 (cont) Visual food consumption

- gr oup distribution of observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Number of animals affected Category Observation Day Group/Sex: 1M 2M 3M 1F 2F 3F Initial no: 8 8 8 8 8 8 Visual Food Consumption 4: All food consumed 16 8 7 8 8 8 8 17 8 7 8 8 8 8 18 8 7 8 8 8 8 19 8 7 8 8 8 8 20 8 7 8 8 8 8 21 8 7 8 8 8 8 22 8 7 8 8 8 8 23 8 7 8 8 8 8 24 8 7 8 8 8 8 25 8 7 8 8 8 8 26 8 7 8 8 8 8 27 8 7 8 8 8 8 28 8 7 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 Hematology

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Pretest 1 g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 1 Mean 12.4 38.5 7.69 269.9 627 50.5 16.2 32.2 17.4 13.57 SD 0.88 3.39 1.001 38.01 197.2 5.76 1.91 0.65 0.92 2.797 N 8 8 8 8 8 8 8 8 8 8 Group 2 Mean 11.6 36.2 7.40 249.5 63 6 49.1 15.7 31.9 18.5 11.97 SD 1.13 3.00 0.766 51.02 118.4 2.51 1.11 0.75 0.79 2.307 N 8 8 8 8 8 8 8 8 8 8 Group 3 Mean 12.0 37.3 7.62 261.6 666 49.3 15.8 32.0 18.8* 12.71 SD 0.89 2.80 0.662 70.46 180.5 5.93 1.94 0 .60 1.52 1.924 N 8 8 8 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Gr oup 1 2 3 Dose (ppm) 5000 10000

Occasion ANEU ALYM AMONO AEOS ABASO ALUC Pretest 1 x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 1 Mean 5.46 7.48 0.29 0.12 0.02 0.19 SD 2.5 68 2.044 0.112 0.043 0.006 0.102 N 8 8 8 8 8 8 Group 2 Mean 4.66 6.63 0.26 0.17 0.02 0.24 SD 0.919 1.933 0.090 0.065 0.009 0.105 N 8 8 8 8 8 8 Group 3 Mean 4. 65 7.44 0.24 0.14 0.02 0.22 SD 1.144 1.062 0.063 0.041 0.005 0.083 N 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup me an values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Pretest 2 g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 1 Mean 12.8 38.7 7.85 202.3 579 49.7 16.4 33.0 17.1 11.51 SD 0.81 2.33 0.659 44.62 171.2 5.72 2.04 0.71 0.92 1.976 N 8 8 8 8 8 8 8 8 8 8 Group 2 Mean 11.7 36.0 7.48 203.6 589 48.3 15.6 32.4 18.1 9.62 SD 1.17 3.21 0.738 78.34 165.5 3.15 1.17 0.71 0.90 1.683 N 8 8 8 8 8 8 8 8 8 8 Group 3 Mean 12.1 37.9 7.62 301.2 618 50.2 16.1 32.0* 19.0* 10.73 SD 1.27 3.53 0.787 173.25 126.3 6.15 1.99 0.68 2.57 2.135 N 8 8 8 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion ANEU ALYM AMONO AEOS ABASO ALUC Pretest 2 x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 1 Mean 5.02 5.96 0.23 0.11 0.01 0.19 SD 1.473 1.393 0.091 0.042 0.007 0. 042 N 8 8 8 8 8 8 Group 2 Mean 3.65 5.45 0.19 0.13 0.01 0.19 SD 0.462 1.540 0.064 0.088 0.006 0.041 N 8 8 8 8 8 8 Group 3 Mean 4.47 5.80 0.19 0.09 0.01 0.17 SD 2.005 0.729 0.028 0.019 0.007 0.043 N 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Males Vehicl e Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Term Day 21 g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 1 Mean 13.0 39 .1 7.92 203.5 506 49.7 16.5 33.2 17.2 10.87 SD 0.87 2.79 0.643 84.76 152.3 5.27 1.76 0.82 1.94 4.092 N 8 8 8 8 8 8 8 8 8 8 Group 2 Mean 12.2 36.9 7.99 144.3 515 46.2 15.2 32.8 17.3 8.52 SD 1.15 2.61 0.608 70.22 87. 5 2.56 1.19 1.03 1.03 1.927 N 7 7 7 7 7 7 7 7 7 7 Group 3 Mean 12.8 38.2 8.02 129.6 499 48.1 16.0 33.3 17.1 10.70 SD 1.26 3.54 0.900 52.60 147.9 5.50 1.90 0.39 1.34 2.027 N 8 8 8 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion A

NEU ALYM AMONO AEOS ABASO ALUC Term Day 21 x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 1 Mean 4.40 5.90 0.24 0.14 0.03 0.15 SD 2.867 1.745 0.075 0.077 0.056 0.069 N 8 8 8 8 8 8 Group 2 Mean 2.98 4.91 0.26 0.18 0.01 0.19 SD 0.932 1.290 0.078 0.055 0.005 0.066 N 7 7 7 7 7 7 Group 3 Mean 4.44 5.63 0.26 0.17 0.02 0.19 SD 1.382 0.974 0.053 0.0 43 0.025 0.074 N 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Gr oup 1 2 3 Dose (ppm) 5000 10000

Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Term Day 28 g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 1 Mean 13.8 41.7 8.37 164.5 496 50.1 16.6 3 3.1 17.4 9.76 SD 1.09 3.67 0.866 55.13 161.7 4.64 1.73 0.73 1.35 1.829 N 8 8 8 8 8 8 8 8 8 8 Group 2 Mean 12.9 39.0 8.35 162.8 519 46.8 15.5 33.1 17.9 8.41 SD 0.82 2.32 0.669 50.60 115.8 2.48 1.17 1.01 1.30 2.143 N 7 7 7 7 7 7 7 7 7 7 Group 3 Mean 13.4 40.7 8.37 138.4 520 49.1 16.1 32.7 17.4 10.90 SD 1.08 3.08 0.849 52.01 113.4 5.26 1.94 0.48 1.32 2.197 N 8 8 8 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion ANEU ALYM AMONO AEOS ABASO ALU C Term Day 28 x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 1 Mean 3.54 5.65 0.29 0.22 0.02 0.05 SD 1.038 1.277 0.057 0.086 0.005 0.020 N 8 8 8 8 8 8 Group 2 Mean 2.83 5.06 0.29 0.17 0.01** 0.04 SD 0.778 1.743 0.069 0.037 0.005 0.014 N 7 7 7 7 7 7 Group 3 Mean 4.33 5.93 0.34 0.23 0.02 0.06 SD 1.711 1.186 0.063 0.054 0.005 0.026 N 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Pretest 1 g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 1 Mean 13.1 40.5 7.98 241.4 643 51.2 16.5 32.3 17.1 13.69 SD 0.75 2. 23 0.688 75.55 100.8 5.82 2.05 0.55 1.24 1.840 N 8 8 8 8 8 8 8 8 8 8 Group 2 Mean 12.6 38.8 7.84 304.2 625 49.8 16.1 32.5 17.9 11.15 SD 0.68 2.40 0.624 60.02 137.4 5.71 1.82 0.62 1.22 2.223 N 8 8 8 8 8 8 8 8 8 8 Group 3 Mean 12.6 38.6 7.96 250.2 585 48.5 15.9 32.8 18.1 14.28 SD 1.01 2.77 0.581 53.68 124.0 3.41 1.44 0.86 1.00 3.102 N 8 8 8 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion ANEU ALYM AMONO AEOS ABASO ALUC Pretest 1 x10^3 /uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 1 Mean 3.12 9.79 0.23 0.20 0.04 0.31 SD 1.039 1.562 0.101 0.095 0.050 0.056 N 8 8 8 8 8 8 Group 2 Mean 2.68 7 .72 0.28 0.19 0.02 0.27 SD 0.870 1.772 0.092 0.061 0.005 0.106 N 8 8 8 8 8 8 Group 3 Mean 4.44 9.03 0.37* 0.21 0.03 0.21* SD 2.922 2.304 0.138 0.093 0.027 0.100 N 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Pretest 2 g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 1 Mean 12.7 39.4 7.76 204.6 660 51.1 16.5 32.2 17.0 11.23 SD 0.65 2.37 0.674 82.18 80.7 5.52 2.00 0.88 1.25 1.320 N 8 8 8 8 8 8 8 8 8 8 Group 2 Mean 12.3 37.6 7.62 256.1 641 49.4 16.1 32.6 18.0 8.99 SD 1.08 3.22 0.254 59.24 110.5 5.14 1.66 0.34 1.69 1.940 N 8 8 8 8 8 8 8 8 8 8 Group 3 Mean 12.7 39.4 8.01 286.3 575 49.4 15.9 32.1 18.5 10.51 SD 1.10 3.15 0.669 84.41 119.3 3.84 1.45 0.69 1.10 1.776 N 8 8 8 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion ANEU ALYM AMONO AEOS ABASO ALUC Pretest 2 x10^3/uL x10^3/uL x10^3/uL x10^3 /uL x10^3/uL x10^3/uL Group 1 Mean 2.55 8.07 0.22 0.12 0.02 0.25 SD 0.852 1.278 0.063 0.056 0.019 0.065 N 8 8 8 8 8 8 Group 2 Mean 1.90 6.58 0.23 0.10 0.02 0.17 SD 0.885 1.558 0.097 0.050 0.018 0.077 N 8 8 8 8 8 8 Group 3 Mean 2.18 7.79 0.22 0.10 0.04 0.18 SD 0.531 1.675 0.110 0.041 0.043 0.082 N 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion HGB HCT RBC RETIC PL T MCV MCH MCHC RDW WBC Term Day 21 g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 1 Mean 13.5 40.3 8.05 167.4 561 50.3 16.8 33.4 16.6 10.33 SD 0.73 2.17 0.679 82.96 89.1 5.38 2.00 0.73 1.70 1.146 N 8 8 8 8 8 8 8 8 8 8 Group 2 Mean 13.1 38.8 7.99 176.8 474 48.8 16.4 33.7 17.2 9.74 SD 1.00 3.23 0.432 69.86 159.4 5.08 1.73 0.59 1.22 1.648 N 8 8 8 8 8 8 8 8 8 8 Group 3 Mean 13.2 40 .6 8.12 209.3 515 50.2 16.4 32.5 18.5* 11.61 SD 1.30 3.47 0.559 39.06 87.4 4.96 1.89 1.24 1.03 1.601 N 8 8 8 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion ANEU ALYM AMONO AEOS ABASO ALUC Term Day 21 x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 1 Mean 2.01 7.61 0.23 0.23 0.03 0.23 SD 0.445 0.749 0.080 0.113 0.034 0.105 N 8 8 8 8 8 8 Group 2 Mean 2.46 6.69 0.23 0.20 0.01 0.15 SD 0.448 1.710 0.098 0 .067 0.004 0.082 N 8 8 8 8 8 8 Group 3 Mean 3.14** 7.79 0.23 0.25 0.03 0.16 SD 1.140 1.412 0.094 0.138 0.015 0.079 N 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Term Day 28 g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 1 Mean 13.4 40.4 7.93 178.4 561 51.3 17.0 33.2 17.6 10.76 SD 1.05 3.39 0.907 77.35 88.0 5.42 2.14 1.21 2.32 1.470 N 8 8 8 8 8 8 8 8 8 8 Group 2 Mean 12.9 38.8 7.92 136.2 576 49.1 16.3 33.2 17.2 9.64 SD 0.83 2.20 0.379 42.66 79.5 4.78 1.70 0.55 0.79 1.579 N 8 8 8 8 8 8 8 8 8 8 Group 3 Mean 13.3 40.5 8.05 182.1 503 50.4 1 6.6 32.8 18.7 11.04 SD 1.33 3.41 0.617 41.67 117.0 4.92 1.98 1.21 1.28 2.308 N 8 8 8 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 7 (cont) Hematology

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion ANEU ALYM AMONO AEOS ABASO ALUC Term Day 28 x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 1 Mean 2.30 7.73 0.34 0.29 0.03 0.07 SD 0.426 1.199 0.138 0.122 0.019 0.031 N 8 8 8 8 8 8 Group 2 Mean 2.36 6.71 0.26 0.25 0.02 0.05 SD 0.592 1.531 0.053 0.065 0.008 0.025 N 8 8 8 8 8 8 Group 3 Mean 3.08 7.30 0.25 0.32 0.04 0.05 SD 1.154 1.975 0.043 0.105 0.026 0.022 N 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 Clinical chemistry

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion AST ALT CK Pretest 1 U/L U/L U/L Group 1 Mean 26 47 378 SD 4.6 5.8 203.4 N 8 8 8 Group 2 Mean 32 40 681 SD 17.7 4.0 769.6 N 8 8 8 Group 3 Mean 33 45 741 SD 9.2 6.7 698.9 N 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Pretest 1 U/L % U/L % U/L NG/mL NG/mL Group 1 Mean 387 63.8 248 11.9 40.5 26.2 0.0 SD 215.1 13.62 152.8 4.86 21.92 13.89 0.00 N 8 8 8 8 8 8 8 Group 2 Mean 665 50.5 415 13.7 76.4 79.0 0.0 SD 740.1 17.54 569.0 4.52 65.73 140.13 0.00 N 8 8 8 8 8 8 8 Group 3 Mean 716 42.6 * 389 13.0 75.2 64.3 0.0 SD 651.7 16.72 484.1 6.36 49.21 77.79 0.00 N 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion AST ALT CK Pretest 2 U/L U/L U/L Group 1 Mean 38 45 630 SD 6.6 4.1 382.0 N 8 8 8 Group 2 Mean 30 38* 589 SD 12.4 4.8 524.4 N 8 8 8 Group 3 Mean 36 46 578 SD 7.9 5.7 528.4 N 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Pretest 2 U/L % U/L % U/L NG/mL NG/mL Group 1 Mean 617 53.7 375 16.0 96.6 34.0 0.0 SD 373.3 21.92 320.2 5.88 73.10 31.19 0.00 N 8 8 8 8 8 8 8 Group 2 Mean 549 55.7 338 11.4 57.3 47.0 0.0 SD 476.1 9.64 352.7 2.46 42.28 91.23 0.00 N 8 8 8 8 8 8 8 Group 3 Mean 539 51.0 283 12.4 63.2 29.1 0.0 SD 483.8 6.79 272.6 3. 24 48.65 24.26 0.00 N 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion AST ALT CK Term Day 21 U/L U/L U/L Group 1 Mean 29 43 424 SD 4.8 7.0 221.8 N 8 8 8 Group 2 Mean 26 36 302 SD 4.5 3.6 57.3 N 7 7 7 Group 3 Mean 32 44 684 SD 12.9 5.4 1026.7 N 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MY OGLOBI TPI Term Day 21 U/L % U/L % U/L NG/mL NG/mL Group 1 Mean 402 53.5 244 11.8 38.9 36.0 0.0 SD 212.6 20.51 214.1 5.49 12.88 29.20 0.00 N 8 8 8 8 8 8 8 Group 2 M ean 283 62.2 185 11.8 32.6 25.3 0.0 SD 51.8 27.45 95.8 3.49 8.86 13.72 0.00 N 7 7 7 7 7 7 7 Group 3 Mean 612 73.8 524 10.0 32.7 57.6 0.0 SD 875.9 17.24 846.3 4.50 9.94 88.76 0.01 N 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion AST ALT CK Term Day 28 U/L U/L U/L Group 1 Mean 28 43 301 SD 8.4 5.8 83.0 N 8 8 8 Group 2 Mean 26 38 532 SD 4.7 4.2 569.2 N 7 7 7 Group 3 Mean 29 44 660 SD 8.8 7.6 768.3 N 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup mean values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Term Day 28 U/L % U/L % U/L NG/mL NG/mL Group 1 Mean 286 27.7 80 16.7 48.1 25.0 0.0 SD 77.7 12.52 40.3 4.45 19.15 27.06 0.00 N 8 8 8 8 8 8 8 Group 2 Mean 490 36.8 231 13.0 57.1 43.4 0.0 SD 50 2.5 14.46 348.8 3.26 44.36 42.21 0.00 N 7 7 7 7 7 7 7 Group 3 Mean 598 38.8 322 11.8 * 58.5 50.2 0.0 SD 671.5 16.41 491.3 4.64 59.44 52.06 0.01 N 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion AST ALT CK Pretest 1 U/L U/L U/L Group 1 Mean 27 42 544 SD 4.8 5.6 201.8 N 8 8 8 Group 2 Mean 76 58 692 SD 127.6 52.2 447.4 N 8 8 7 Group 3 Mean 33 44 854 SD 14.1 11.4 432.6 N 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Cli nical chemistry

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Pretest 1 U/L % U/L % U/L NG/mL NG/mL Group 1 Mean 573 63.6 383 12.5 66.3 21.4 0.2 SD 187.1 18.82 231.2 4.70 23.86 12.52 0.59 N 8 8 8 8 8 8 8 Group 2 Mean 6559 78.5 6224 11.0 168.9 77.4 0.0 SD 16900.2 11.94 16349.0 6.15 305.5 8 96.22 0.11 N 8 8 8 8 8 8 8 Group 3 Mean 849 78.5 680 10.6 81.4 28.7 0.0 SD 414.3 10.31 376.7 5.89 37.20 17.92 0.00 N 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion AST ALT CK Pretest 2 U/L U/ L U/L Group 1 Mean 26 41 1432 SD 5.1 4.8 2433.5 N 8 8 8 Group 2 Mean 49 54 618 SD 64.7 45.3 591.2 N 8 8 7 Group 3 Mean 27 46 705 SD 5.2 12.6 288.3 N 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup me an values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Pretest 2 U/L % U/L % U/L NG/mL NG/mL Group 1 Mean 1163 71.9 972 8.9 68.6 44.0 0.3 SD 1751.8 18.97 1722.6 5.67 52.20 45.14 0.89 N 8 8 8 8 8 8 8 Group 2 Mean 2723 66.9 2412 10.2 152.2 146.3 0.0 SD 6091.9 20.29 5803.1 3.63 245.17 346.39 0.06 N 8 8 8 8 8 8 8 Group 3 Mean 652 68.8 455 13.5 78.4 45.7 0.0 SD 270.5 16.12 256.7 5.28 27.16 26.62 0.00 N 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion AST ALT CK Term Day 21 U/L U/L U/L Group 1 Mean 28 40 1055 SD 8.3 3.7 532.1 N 8 8 8 Group 2 Mean 29 60 1683 SD 18.6 63.4 1898.4 N 8 8 7 Group 3 Mean 23 42 1063 SD 3.7 7.3 690.5 N 8 8 5Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Term Day 21 U/L % U/L % U/L NG/mL NG/mL Group 1 Mean 1089 91.0 1002 5. 8 56.1 31.1 0.5 SD 446.0 6.82 433.3 3.44 27.31 37.00 1.39 N 8 8 8 8 8 8 8 Group 2 Mean 3774 86.1 3497 8.8 184.8 33.0 0.0 SD 6350.6 10.10 5958.4 5.46 255.78 39.36 0.03 N 8 8 8 8 8 8 8 Group 3 Mean 5854 61.9 * 5174 9.5 276.1 * 30.7 0.0 SD 7066.2 28.15 6800.8 5.99 266.83 17.40 0.00 N 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup mean values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion AST ALT CK Term Day 28 U/L U/L U/L Group 1 Mean 25 41 787 SD 4.9 4.0 373.2 N 8 8 8 Group 2 Mean 40 59 473 SD 49.1 64.7 238.8 N 8 8 7 Group 3 Mean 29 41 1214 SD 12.7 9.7 1054.9 N 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 8 (cont) Clinical chemistry

- gr oup mean values

Females Vehicle Contro l HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000

Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Term Day 28 U/L % U/L % U/L NG/mL NG/mL Group 1 Mean 726 47.8 370 15.0 110.6 41.5 0.5 SD 343.3 10.96 228.0 5.46 74.33 38.54 1.46 N 8 8 8 8 8 8 8 Group 2 Mean 5177 37.4 4725 9.7 * 154.2 45.8 0.0 SD 13397.5 25.75 12974.7 4.21 309.87 53.54 0.03 N 8 8 8 8 8 8 8 Group 3 Mean 1056 40.5 524 8.6 ** 87.7 167.3 0.0 SD 857.2 16.56 580.5 2.28 61.39 228.95 0.00 N 8 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 9 Organ weights

- gr oup mean absolute values (g)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group/ Sex Terminal

Body weight Br ain Heart Kidney s Liver Lungs and Br onchi Statistics test Wi Wi Wi Wi W i Wi 1M Mean 10750.0 57.217 60.056 71.203 234.307 89.734

SD 1331.0 3.040 11.035 11.046 41.527 14.197 N 8 8 8 8 8 8 2M Mean 10214.3 58.078 59.300 63.474 222.538 88.017

SD 1009.0 6.629 6.161 11.811 50.518 7.733 N 7 7 7 7 7 7 3M Mean 9850.0 56.548 61.060 72.587 232.517 83.012

SD 1725.4 3.309 9.540 13.441 57.898 13.276 N 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 9 (cont) Organ weights

- gr oup mean absolute values (g)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group/ Sex Terminal

Body weight Br ain Heart Kidney s Liver Lungs and Br onchi Statistics test Wi Wi Wi Wi Wi Wi 1F Mean 11571.3 60.711 50.808 53.208 223.714 83.071

SD 1212.6 4.339 7.837 7.299 31.323 8.011 N 8 8 8 8 8 8 2 F Mean 11083.8 57.416 49.035 52.355 252.527 83.066

SD 1581.9 3.493 4.627 8.533 48.929 10.424 N 8 8 8 8 8 7 3F Mean 11470.0 55.358* 51.797 52.664 272.062* 86.884

SD 1442.7 4.127 6.670 11.254 48.408 12.399 N 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 0 Organ weights

- gr oup mean values relative (%) to body weight (g)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group/ Sex Terminal

Body weight Br ain Heart Kidney s Liver Lungs and Br onchi Statistics tes t Wi Wi Wi Wi Wi Wi 1M Mean 10750.0 0.538 0.556 0.669 2.18 0.834

SD 1331.0 0.052 0.043 0.109 0.25 0.064 N 8 8 8 8 8 8 2M Mean 10214.3 0.569 0.583 0.620 2.17 0.866

SD 1009.0 0.037 0.054 0.084 0.37 0.075 N 7 7 7 7 7 7 3M Me an 9850.0 0.586 0.623* 0.739 2.34 0.851

SD 1725.4 0.082 0.047 0.072 0.21 0.108 N 8 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 0 (cont) Organ weights

- gr oup mean values relative (%) to body weight (g)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group/ Sex Terminal

Body weight Br ain Heart Kidney s Liver Lungs and Br onchi Statistics test Wi Wi Wi Wi Wi Wi 1F Mean 11571.3 0.529 0.440 0.459 1.93 0.721

SD 1212.6 0.056 0.054 0.037 0.20 0.061 N 8 8 8 8 8 8 2F Mean 11083.8 0.524 0.446 0.474 2.28** 0.742

SD 1581.9 0.053 0.042 0.055 0.29 0.067 N 8 8 8 8 8 7 3F Mean 11470.0 0.488 0.458 0.456 2.36** 0.762

SD 1442.7 0.058 0.084 0.062 0.17 0.093 N 8 8 8 8 8 8Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 1 Organ weights

- gr oup mean values relative (%) to brain weight (g)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group/ Sex Br ain Heart Kidney s Liver Lungs and Br onchi Statistics test Wi Wi Wi Wi W i 1M Mean 57.217 105 125 409 156

SD 3.040 17 20 65 20 N 8 8 8 8 8 2M Mean 58.078 103 109 383 153

SD 6.629 12 16 73 16 N 7 7 7 7 7 3M Mean 56.548 108 128 410 147

SD 3.309 14 23 95 25 N 8 8 8 8 8Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 1 (cont) Orga n w eights

- gr oup mean values relative (%) to brain weight (g) Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group/ Sex Br ain Heart Kidney s Liver Lungs and Br onchi Statistics test Wi Wi Wi Wi Wi 1F Mean 60. 711 83.5 87.7 371 137

SD 4.339 9.2 11.2 64 13 N 8 8 8 8 8 2F Mean 57.416 85.4 91.2 439 143

SD 3.493 6.3 14.0 74 14 N 8 8 8 8 7 3F Mean 55.358* 93.9 95.6 493** 158*

SD 4.127 13.0 23.5 89 24 N 8 8 8 8 8Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 2 Macropathology

- group distribution of findings

Terminal sacrifice Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Number of animals affected Group/Sex 1M 2M 3M 1F 2F 3F Tissue/Organ a

nd Findings No. of animals 8 7 8 8 8 8 Number of animals within normal limits 7 7 5 7 5 5 Heart Adhesion(s) 0 0 1 0 0 0 Pericaridial Fluid 0 0 1 0 0 0 Kidne ys Cyst(s) 0 0 0 1 0 0 Lungs and Bronchi Dark area(s) 1 0 1 0 1 2 Ly mph Node, Mandibular Dark 0 0 0 0 1 1 Rectum Dark area(s) 0 0 1 0 0 0 Stomach Dark area(s) 0 0 0 0 1 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 TABLE 1 2 (cont) Macropathology

- group distribution of findings

Un scheduled sacrifice Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Number of animals affected Group/Sex 1M 2M 3M 1F 2F 3F Tissue/Organ and Findings No. of animals 0 1 0 0 0 0 Colon Abnormal contents 0 1 0 0 0 0 Heart Thro mbus 0 1 0 0 0 0 Rectum Pr olapse 0 1 0 0 0 0Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 1 Daily observations

- individual observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation AM PM US PM 1M 1145 29 Normal Within normal limits P5
- P15, 1
- 3, 19
- 29 P5
- P15, 1
- 2, 16,

19 -28 Skin Scab, Ears 7
- 18 7
- 15, 17
- 18

Scab, Hindlimb

- Right 4
- 8 3
- 7 Scab, Tail 14
- 17 13
- 15, 17 Ulceration, Tail 13 Skin abrasion Dry , Head 6

Dry , Ventral Surface P2
- P4 P1
- P4 1146 29 Normal Within normal limits P5
- P15, 1
- 29 P5
- P15, 1
- 28

Skin abrasion Dry , Ears P2
- P4 P1
- P4 1147 29 Normal Within normal limits P5
- P15, 1
- 29 P5
- P15, 1
- 28

Skin abrasion Dry , Ventral Surface P2
- P4 P1
- P4Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 1 (cont) Daily observations

- individual observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation AM PM US PM 1M 1148 29 Normal Within normal limits P5
- P15, 1
- 13, 15, 17, 20, 24-29 P5
- P15, 1
- 12, 14
-

17, 20, 24-28 Discharge Aqueous, Red, Penis 16

Viscous, Red, Penis 14 13 13 Exudate Red Exudate In Cage 16 Skin Scab, Head 18
- 19 18
- 19 Skin abrasion Dry , Ear
- Left 21
- 23 21
- 23

Dry , Ears P2
- P4 P1
- P4 Dry , Ventral Surface P2
- P4 P1
- P4 1149 29 Normal Within normal limits P2
- P15, 1
- 29 P1
- P15, 1
- 28 1150 29 Normal Within normal limits P2
- P11, P13
- P15, 1 -19, 22- 29 P1
- P10, P13
- P15,

1 -19, 21- 28 Skin Br uise, HindLimb

- Right

- Slight P11

Br uise, Hindlimb

- Right P12 P12 Scab, Hindlimb

- Right 20
- 21 20 1151 29 Normal Within normal limits P2
- P15, 1
- 29 P1
- P15, 1
- 28 1152 29 Normal Within normal limits P2
- P15, 1
- 15, 21
- 29 P1
- P15, 1
- 15, 21
-

28 Skin abrasion Dry , Tail 16
- 20 16
- 20Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 1 (cont) Daily observations

- individual observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation AM PM US PM 2M 2145 29 Normal Within normal limits P2
- P15, 1
- 29 P1
- P15, 1
- 28

2146 29 Normal Within normal limits P2
- P15, 1
- 29 P1
- P15, 1
- 28 2147 16 Normal Within normal limits P2
- P15, 1
- 15 P1
- P15, 1
- 15

Discharge Aqueous, Red, Anus 16 16 Reason for dispatch Prolapsed 16 2149 29 Normal Within normal limits P2
- P15, 1
- 16, 21
- 29 P1
- P15, 1
- 16, 21
-

28 Skin abrasion Dry , Hindlimb

- Right 17
- 20 17
- 20 2150 29 Normal Within normal limits P2
- P15, 1
- 6, 11
- 29 P1
- P15, 1
- 6, 11
-

28 Skin abrasion Dry , Head 7
- 10 7
- 10 2151 29 Normal Within normal limits P2
- P15, 1
- 13, 16
- 17, 21 -29 P 1
- P15, 1
- 13, 16
-

17, 21 -27 Skin Scab, Dorsal surface 18
- 20 18
- 20 Skin abrasion Dry , Head 14
- 15 14
- 15

Dry , Upper Dorsal Surface 28 2152 29 Normal Within normal limits P2
- P15, 1
- 29 P1
- P15, 1
- 28Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 1 (cont) Daily observations

- individual observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation AM PM US PM 2M 2153 29 Normal Within normal limits P7
- P15, 1
- 4, 6
- 29 P6
- P15, 1
- 4, 6
- 28 Skin Scab, Ear

- Left P6 Skin abrasion Dry , Ears P2
- P5 P1
- P5

Dry , Upper Dorsal Surface 5 5 3M 3145 29 Normal Within normal limits P2
- P15, 1
- 4, 16, 24, 28 -29 P1
- P15, 1
- 4, 28 Skin Scab, Lower Dorsal Surface 7
- 15 7
- 15

Scab, Upper Dorsal Surface 12
- 15, 26
- 27 12
- 15, 25
- 27 Skin abrasion Dry , Dorsal surface 25
- 27 24
- 27

Dry , Head 5
- 6 5
- 6 4 Dry , Lower Dorsal Surface 5
- 11 5
- 11 4 Dry , Upper Dorsal Surface 14, 17
- 23 16
- 23 3146 29 Normal Within normal limits P2
- P14, 2
- 4, 11
- 13, 16
- 17, 21 -29 P1
- P13, 2
- 4, 10
-

13, 16
- 17, 21 -28 Skin Scab, Dorsal surface 7
- 10, 14
- 15 7
- 9, 14
- 15

Scab, Head 18
- 20 18
- 20 Skin abrasion Dry , Dorsal surface P15, 1, 7
- 10 P15, 1, 7
- 9

Dry , Head 5
- 6 P14, 5
- 6 Dry , Upper Dorsal Surface 5
- 6 5
- 6Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 1 (cont) Daily observations

- individual observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation AM PM US PM 3M 3147 29 Normal Within no rmal limits P2
- P12, P14, 11
- 13, 28 -29 P1
- P11, P13
- P14,

11 -13, 28 Skin Scab, Ear

- Right P13

Scab, Head 16
- 27 16
- 27 Skin abrasion Dry , Ear
- Left 2
- 6 1
- 6 4

Dry , Head P15, 1, 7
- 10, 14
- 15 P15, 7
- 10, 14
- 15 Dry , Lower Dorsal Surface 5
- 6 5
- 6 4 Dry , Upper Dorsal Surface 7
- 10, 14
- 15 7
- 10, 14
- 15 Wet, Ear
- Right P12 3148 29 Normal Within nor mal limits P2
- P14, 16
- 29 P1
- P14, 16
- 28

Skin Scab, Ear

- Left 7
- 15 7
- 15

Scab, Upper Dorsal Surface 12
- 15 12
- 15 Skin abrasion Dry , Head P15, 1
- 6 P15, 1
- 6

Dry , Upper Dorsal Surface 5
- 11 5
- 11 3149 29 Normal Within normal limits P9
- P15, 1
- 5, 7
- 19, 22 -29 P1, P3, P9
- P15,

1 -5, 7- 19, 22 -28 Skin Scab, Ear

- Left P6
- P8 P6
- P8

Scab, Head 20
- 21 20
- 21 Skin abrasion Dry , Ear
- Left 6 6

Dry , Ears P2
- P5 P2, P4
- P5Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 1 (cont) Daily observations

- individual observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 500 0 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation AM PM US PM 3M 3150 29 Normal Within normal limits P2
- P15, 1
- 29 P1
- P15, 1
- 28

3151 29 Normal Within no rmal limits P11
- P15, 1
- 18, 24 -29 P10
- P15, 1
- 18,

24 -28 Skin Scab, Ear

- Left P6
- P10 P6
- P9

Scab, Hindlimb

- Right 19
- 23 19
- 23 Skin abrasion Dry , Ears P2
- P5 P1
- P5 3152 29 Normal Within normal limits P2
- P15, 1
- 17, 24
- 29 P1
- P15, 1
- 17, 24
-

28 Skin Scab, Ear

- Left 22
- 23 21
- 23

Ulceration, Ear

- Left 18
- 21 18
- 20Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 1 (cont) Daily observations

- individual observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation AM PM US PM 1F 1645 29 Normal Within n ormal limits P2, P6
- P15, Ra1, 1 -3, 6-29 P1, P6
- P15, Ra1,

1 -3, 6-28 Skin Scab, Head P5 P5 Skin abrasion Dry , Head P3
- P4 P2
- P4

Dry , Upper Dorsal Surface 4
- 5 4
- 5 1646 29 Normal Within normal limits P2
- P15, Ra1, 1
- 29 P1
- P15, Ra1, 1
-

28 1647 29 Normal Within normal limits P2
- P15, Ra1, 1
- 16, 21 -29 P1
- P15, Ra1, 1
-

16, 21 -28 Skin abrasion Dry , Hindlimb

- Right 17
- 20 17
- 20 1648 29 Normal Within normal limits P2
- P15, Ra1, 1
- 15, 18 -29 P1
- P15, Ra1, 1
-

15, 17 -28 Skin abrasion Dry , Head 16
- 17 16 1649 29 Normal Within normal limits P5
- P15, Ra1, 1
- 3, 7 -29 P5
- P15, Ra1, 1
- 3,

7 -9, 11-28 Skin abrasion Dry , Ears P2
- P4 P1
- P4

Dry , Nose 10 Dry , Upper Dorsal Surface 4
- 6 4
- 6 1650 29 Normal Within normal limits P2
- P15, Ra1, 1
- 29 P1
- P15, Ra1, 1
-

28Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 1 (cont) Daily observations

- individual observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 G ro up Anim al Day of Day (s) observed /Sex Numb er Death Category Observation AM PM US PM 1F 1651 29 Normal Within normal limits P2
- P15, Ra1, 1
- 3, 6 -10, 12- 17, 23
- 29 P1
- P15, Ra1, 1
- 3,

6 -9, 12- 17, 23 -28 Skin Scab , Ear
- Left 18
- 22 18
- 22 Skin abrasion Dry , Head 11 10
- 11

Dry , Hindlimb

- Right 4
- 5 4
- 5 1652 29 Normal Within normal limits P2
- P15, Ra1, 1
- 29 P1
- P15, Ra1, 1
-

28 2F 2645 29 Normal Within normal limits P5
- P15, Ra1, 1
- 16, 23 -29 P5
- P15, Ra1, 1
-

16, 23 -28 Skin abrasion Dry , Ear
- Left 17
- 22 17
- 22

Dry , Ears P2
- P4 P1
- P4 2646 29 Normal Within normal limits P7
- P15, Ra1, 1
- 18, 23 -29 P7
- P15, Ra1, 1
-

18, 23 -28 Skin abrasion Dry , Head 19
- 22 19
- 22

Dry , Ventral Surface P2
- P6 P1
- P6 2647 29 Normal Within no rmal limits P2
- P15, Ra1, 1
- 24, 28 -29 P1
- P15, Ra1, 1
-

24, 28 Skin abrasion Dry , Dorsal surface 25
- 27 25
- 27Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 1 (cont) Daily observations

- individual observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation AM PM US PM 2F 2648 29 Normal Within normal limits P2
- P15, Ra1, 1
- 5, 7 -29 P1
- P15, Ra1, 1
- 5,

7 -28 Skin abrasion Dry , Lower Dorsal Surface 6 6 2649 29 Normal Within normal limits P2
- P15, Ra1, 1
- 4, 7 -10, 12- 18, 23
- 29 P1
- P15, Ra1, 1
- 4,

7 -9, 12- 18, 23 -28 Skin Scab, Hindlimb

- Right 6 6 Skin abrasion Dry , Dorsal surface 21
- 22 20
- 22

Dry , Head 19
- 22 19
- 22 Dry , Hindlimb

- Right 5 5 Dry , Upper Ventral Surface 10 Skin color Abnor mal color, Red, Upper Dorsal Surface 11 10
- 11 2650 29 Normal Within normal limits P2
- P15, Ra1, 1
- 29 P1
- P15, Ra1, 1
-

28 2651 29 Normal Within normal limits P2
- P15, Ra1, 1
- 29 P1
- P 15, Ra1, 1
-

28 2652 29 Normal Within normal limits P2, P5
- P15, Ra1, 1 -29 P1, P5
- P15, Ra1,

1 -28 Skin abrasion Dry , Upper Dorsal Surface P3
- P4 P2
- P4Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 1 (cont) D aily observations

- individual observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation AM PM US PM 3F 3645 29 Normal Within normal limits P2
- P15, Ra1, 1
- 5, 7 -17, 21- 29 P1
- P15, Ra1, 1
- 5,

7 -17, 21- 28 Skin Scab, Hindlimb

- Right 18
- 20 18
- 20 Skin abrasion Dry , Ear
- Right 6 6 3646 29 Nor mal Within normal limits P2
- P15, Ra1, 1
- 3, 6 -9, 15-29 P1
- P15, Ra1, 1
- 3,

6 -9, 15-28 Skin Scab, Lower Dorsal Surface 10
- 14 10
- 14 Skin abrasion Dry , Head 4
- 5 4
- 5 3647 29 Normal With in normal limits P2
- P15, Ra1, 1
- 3, 6 -17, 23- 29 P1
- P15, Ra1, 1
- 3,

6 -17, 23- 28 Skin Scab, Head 18
- 22 18
- 22 Skin abrasion Dry , Head 4
- 5 4
- 5 3648 29 Normal Within normal limits P2
- P1 5, Ra1, 1
- 29 P1
- P15, Ra1, 1
-

28 3649 29 Normal Within normal limits P2
- P15, Ra1, 1
- 29 P1
- P15, Ra1, 1
-

28 3650 29 Normal Within normal limits P2
- P15, Ra1, 1
- 3, 6 -29 P1
- P15, Ra1, 1
- 3,

6 -28 Skin abrasion Dry , Head 4
- 5 4
- 5

Dry , Upper Dorsal Surface 5 5Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 1 (cont) Daily observations

- individual observations Vehicle Control HFO -1234yf Dose Group 1 2 3 D ose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation AM PM US PM 3F 3651 29 Normal Within normal limits P2
- P15, Ra1, 1
- 29 P1
- P15, Ra1, 1
-

28 3 652 29 Normal Within normal limits P2
- P15, Ra1, 1
- 29 P1
- P15, Ra1, 1
-

28Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 2 Dose observations

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation 2 Hours 4 Hours US1 US2 1M 1145 29 Normal Within normal limits 1
- 28 1
- 28

1146 29 Normal Within normal limits 1
- 28 1
- 28 1147 29 Normal Within normal limi ts 1
- 28 1
- 28 1148 29 Normal Within normal limits 1
- 13, 15
- 28 1
- 13, 15
- 28 1149 29 Normal Within normal limits 1
- 28 1
- 28 1150 29 Normal Within normal limits 1
- 28 1
- 28 1151 29 Normal Within normal limits 1
- 28 1
- 28 1152 29 Normal Within norm al limits 1
- 28 1
- 28 2M 2145 29 Normal Within normal limits 1
- 28 1
- 28

2146 29 Normal Within normal limits 1
- 28 1
- 28 2147 16 Normal Within normal limits 1
- 15 1
- 15Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 2 (cont) Dose observations

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 500 0 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation 2 Hours 4 Hours US1 US2 2M 2149 29 Normal Within normal limits 1
- 28 1
- 28

2150 29 Norm al Within normal limits 1
- 28 1
- 28 2151 29 Normal Within normal limits 1
- 28 1
- 28 2152 29 Normal Within normal limits 1
- 28 1
- 28 2153 29 Normal Within normal limits 2
- 28 2
- 28 3M 3145 29 Normal Within normal limits 1
- 28 1
- 28

3146 29 Normal Wi thin normal limits 1
- 28 1
- 28 3147 29 Normal Within normal limits 1
- 28 1
- 23, 25
- 28

Muscle reaction Shivering 24 31 48 29 Normal Within normal limits 1
- 28 1
- 28 3149 29 Normal Within normal limits 1
- 28 1
- 28 3150 29 Normal Within normal limits 1
- 28 1
- 28Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 2 (cont) Dose observations

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er De ath Category Observation 2 Hours 4 Hours US1 US2 3M 3151 29 Normal Within normal limits 1
- 28 1
- 28

3152 29 Normal Within normal limits 1
- 28 1
- 28Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 2 (cont) Dose observations

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation 2 Hours 4 Hours US1 US2 1F 1645 29 Normal Within normal limits 1
- 28 1
- 28

1646 29 Normal Within normal limits 1
- 28 1
- 28 1647 29 Nor mal Within normal limits 1
- 28 1
- 28 1648 29 Normal Within normal limits 1
- 28 1
- 28 1649 29 Normal Within normal limits 1
- 28 1
- 28 1650 29 Normal Within normal limits 1
- 28 1
- 28 1651 29 Normal Within normal limits 1
- 28 1
- 28 1652 29 Normal Wit hin normal limits 1
- 28 1
- 28 2F 2645 29 Normal Within normal limits 1
- 28 1
- 28

2646 29 Normal Within normal limits 1
- 28 1
- 28 2647 29 Normal Within normal limits 1
- 28 1
- 28Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 2 (cont) Dose observations

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation 2 Hours 4 Hours US1 US2 2F 2648 29 Normal Within normal limits 1
- 28 1
- 28 General condition Lacerati on, Tail 4 2649 29 Normal Within normal limits 1
- 28 1
- 28 2650 29 Normal Within normal limits 1
- 28 1
- 28 2651 29 Normal Within normal limits 1
- 28 1
- 28 2652 29 Normal Within normal limits 1
- 28 1
- 28 3F 3645 29 Normal Within norm al limits 1
- 28 1
- 28

3646 29 Normal Within normal limits 1
- 28 1
- 28 3647 29 Normal Within normal limits 1
- 28 1
- 28 3648 29 Normal Within normal limits 1
- 28 1
- 28Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 2 (cont) Dose observations

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of Day (s) observed /Sex Numb er Death Category Observation 2 Hours 4 Hours US1 US2 3F 3649 29 Normal Within normal limits 1, 3
- 28 1, 3
- 28 General condition Laceration, Tail 2 2

Laceration, Tail, red exudate present 1
3650 29 Normal Within normal limits 1
- 28 1
- 28 3651 29 Normal Within normal limits 1
- 28 1
- 28

Br eathing Coughing 11 3652 29 Normal Within normal limits 1
- 28 1
- 28Spon sor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 3 Clinical signs

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Week of /Sex Numb er Death Phase Category Observation Week(s) observed 1M 1145 S1 5 Pr e - Treatment Normal Within normal limits P2
- P3 Treatment Normal Within normal limits 4

Skin Scab, Ears 1
- 3

Scab, Hindlimb

- Right 1
- 3 1146 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 1147 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 1148 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1, 3
- 4

Disc harge Viscous, Red, Penis 2 1149 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 1150 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 1151 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4
S1
- Scheduled Euthanasia 1Spon sor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 3 (cont) Clinical signs

- individual observations

Vehicle Control HFO -1234yf D ose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Week of /Sex Numb er Death Phase Category Observation Week(s) observed 1M 1152 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3 Treatment Normal Within normal limi ts 1
- 4 2M 2145 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3 Treatment Normal Within normal limits 1
- 4 2146 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 2147 WE 3 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 2 2149 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 2150 S1 5 Pre
- Treatment Norm al Within normal limits P2
- P3

Treatment Normal Within normal limits 2
- 4

Skin abrasion Dry , Head 1 2151 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1, 4

Skin abrasion Dry , Ear
- Left 3

Dry , Head 2
- 3
S1
- Scheduled Euthanasia 1, WE

- Euthanized for welfare reasonsSpon sor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 3 (cont) Clinical signs

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Week of /Sex Numb er Death Phase Category Observation Week(s) observed 2M 2152 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3 Treatment Normal Within normal limits 1
- 4 2153 S1 5 Pre
- Treatment Normal Withi n normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 3M 3145 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3 Treatment Normal Within normal limits 4

Skin Scab, Lower Dorsal Surface 1
- 3 Skin abrasion Dry , Lowe r Dorsal Surface 1
- 3 3146 S1 5 Pre
- Treatment Normal Within normal limits P2 Skin abrasion Dry , Dorsal surface P3 Treatment Normal Within normal limits 4

Skin Scab, Dorsal surface 1
- 3 Skin abrasion Dry , Dorsal surface 1
- 3 3147 S1 5 Pre
- Treatment Normal Within normal limits P2 Skin abrasion Dry , Head P3 Treatment Normal Within normal limits 4

Skin abrasion Dry , Ear
- Left 3

Dry , Head 1
- 3 Dry , Upper Dorsal Surface 1
- 3
S1
- S ch eduled Euthanasia 1Spon sor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 3 (cont) Clinical signs

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Week of /Sex Numb er Death Phase Category Observation Week(s) o bserved 3M 3148 S1 5 Pre
- Treatment Normal Within normal limits P2 Skin abrasion Dry , Head P3 Treatment Normal Within normal limits 4

Skin Scab, Ear

- Left 1
- 3

Scab, Upper Dorsal Surface 1
- 3 3149 S1 5 Pre
- Treatme nt Normal Within normal limits P2
- P3 Treatment Normal Within normal limits 1
- 4 3150 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 3151 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 3152 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 2, 4

Skin Ulceration, Ear

- Left 3
S1
- Scheduled Euthanasia 1Spon sor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 3 (cont) Clinical signs

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Week of /Sex Numb er Death Phase Category Observation Week(s) observed 1F 164 5 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3 Treatment Normal Within normal limits 1
- 4 1646 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 1647 S1 5 Pre
- Treatment Nor mal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 1648 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 1649 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 1650 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 1651 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment No rmal Within normal limits 1
- 4 1652 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4
S1
- Scheduled Euthanasia 1Spon sor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 3 (cont) Clinical signs

- individual observations

Veh icle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Week of /Sex Numb er Death Phase Category Observation Week(s) observed 2F 2645 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3 Treatment Normal Within normal limits 1
- 2, 4

Skin abrasion Dry , Ear
- Left 3 2646 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 2, 4

Skin abrasion Dry , Ear
- Left 3 2647 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 2648 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 2649 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 2650 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 2651 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4
S1
- Scheduled Euthanasia 1Spon sor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 3 (cont) Clinical signs

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Week of /Sex Numb er Death Phase Category Observation Week(s) observed 2F 2652 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3 Treatment Normal Within normal limits 1
- 4 3F 3645 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3 Treatment Normal Within normal limits 1
- 4 3646 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1, 3
- 4

Skin Scab, Lower Dorsal Surface 2 3647 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 2, 4

Skin abrasion Dry , Head 3 3648 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 3649 S1 5 Pre
- Treatment Nor mal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4 3650 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4
S1
- Scheduled Euthanasia 1Spon sor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 3 (cont) Clinical signs

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Week of /Sex Numb er Death Phase Category Observation Week(s) observed 3F 3651 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3 Treatment Normal Within normal limits 1
- 4 3652 S1 5 Pre
- Treatment Normal Within normal limits P2
- P3

Treatment Normal Within normal limits 1
- 4
S1
- Scheduled Euthanasia 1Sponsor reference number:Huntingdon Life Sciences: 13-6434APPENDIX 4 Body weights - individual values (kg)Vehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Animal Week WeekChange Change Change Change/Sex Number P1 P2 P3 1 23 4 P3-1 P3-2 P3-3 P3-41M 1145S1 7.8 8.4 8.7 9.5 10.3 10.8 11.4 0.8 1.6 2.1 2.71146S1 6.5 6.8 7.1 7.9 8.3 9.3 9.5 0.8 1.2 2.2 2.41147S1 6.3 7.2 7.5 8.4 9.3 10.8 11.8 0.9 1.8 3.3 4.31148S1 6.8 7.7 8.3 9.4 10.0 11.1 11.6 1.1 1.7 2.8 3.31149S1 6.5 6.8 7.5 8.6 9.8 11.0 11.5 1.1 2.3 3.5 4.01150S1 8.1 8.2 8.9 9.9 10.8 11.9 12.5 1.0 1.9 3.0 3.61151S1 5.4 5.9 6.3 7.0 7.6 8.3 8.8 0.7 1.3 2.0 2.51152S1 6.7 6.7 7.0 7.8 8.4 9.4 9.8 0.8 1.4 2.4 2.82M 2145S1 5.8 6.0 6.5 7.3 7.9 9.1 9.8 0.8 1.4 2.6 3.32146S1 5.4 6.1 6.1 6.8 7.4 8.2 8.9 0.7 1.3 2.1 2.82147WE 7.2 7.7 8.4 9.7 10.5 1.3 2.12149S1 5.6 5.6 6.1 6.7 7.3 8.2 8.7 0.6 1.2 2.1 2.62150S1 6.6 7.3 8.0 8.9 9.7 10.8 11.3 0.9 1.7 2.8 3.32151S1 6.9 7.3 7.9 8.5 9.3 10.3 10.9 0.6 1.4 2.4 3.02152S1 6.0 6.6 7.3 8.1 9.2 10.5 11.1 0.8 1.9 3.2 3.82153S1 7.0 7.3 8.1 8.5 9.3 10.3 10.9 0.4 1.2 2.2 2.8S1 - Scheduled Euthanasia 1, WE- Euthanized for welfare reasonsSponsor reference number:Huntingdon Life Sciences: 13-6434APPENDIX 4 (cont) Body weights - individual values (kg)Vehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Animal Week WeekChange Change Change Change/Sex Number P1 P2 P3 1 23 4 P3-1 P3-2 P3-3 P3-43M 3145S1 4.9 5.5 6.0 6.7 7.3 8.0 8.2 0.7 1.3 2.0 2.23146S1 5.1 5.7 6.4 6.9 7.3 7.8 8.1 0.5 0.9 1.4 1.73147S1 6.5 7.4 8.2 9.3 10.2 10.7 11.2 1.1 2.0 2.5 3.03148S1 6.1 6.7 7.2 8.2 9.5 11.4 11.8 1.0 2.3 4.2 4.63149S1 5.7 5.9 6.1 6.5 7.2 8.1 8.2 0.4 1.1 2.0 2.13150S1 6.2 6.7 7.7 8.3 8.9 9.8 10.0 0.6 1.2 2.1 2.33151S1 7.5 8.0 8.7 9.6 10.6 11.9 12.2 0.9 1.9 3.2 3.53152S1 5.5 5.9 6.5 7.1 8.0 8.8 9.1 0.6 1.5 2.3 2.6S1 - Scheduled Euthanasia 1Sponsor reference number:Huntingdon Life Sciences: 13-6434APPENDIX 4 (cont) Body weights - individual values (kg)Vehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Animal Week WeekChange Change Change Change/Sex Number P1 P2 P3 1 23 4 P3-1 P3-2 P3-3 P3-41F 1645S1 7.0 7.9 8.6 9.8 10.4 11.5 12.3 1.2 1.8 2.9 3.71646S1 7.1 7.4 8.3 9.5 10.3 11.2 11.8 1.2 2.0 2.9 3.51647S1 7.3 8.0 8.7 10.1 10.8 11.8 12.4 1.4 2.1 3.1 3.71648S1 6.5 6.8 7.2 8.0 8.4 9.4 10.0 0.8 1.2 2.2 2.81649S1 7.0 8.0 9.0 10.5 11.4 12.8 13.5 1.5 2.4 3.8 4.51650S1 6.1 6.8 7.5 8.5 9.3 10.3 11.1 1.0 1.8 2.8 3.61651S1 6.6 7.0 7.3 8.4 9.2 10.2 10.7 1.1 1.9 2.9 3.41652S1 7.1 7.7 8.2 9.1 9.8 10.6 11.5 0.9 1.6 2.4 3.32F 2645S1 5.7 6.2 6.9 7.9 8.2 9.4 9.9 1.0 1.3 2.5 3.02646S1 8.2 8.9 9.7 10.8 11.9 13.6 14.3 1.1 2.2 3.9 4.62647S1 5.7 5.9 6.5 7.4 8.1 9.2 9.7 0.9 1.6 2.7 3.22648S1 6.1 6.8 7.4 8.5 9.2 10.3 11.4 1.1 1.8 2.9 4.02649S1 7.8 8.4 9.2 10.3 10.9 12.4 12.8 1.1 1.7 3.2 3.62650S1 6.4 6.5 6.9 8.0 8.4 9.9 10.6 1.1 1.5 3.0 3.72651S1 6.4 7.3 7.8 9.4 10.4 11.7 12.7 1.6 2.6 3.9 4.92652S1 5.2 5.7 6.3 7.2 8.1 9.3 10.3 0.9 1.8 3.0 4.0S1 - Scheduled Euthanasia 1Sponsor reference number:Huntingdon Life Sciences: 13-6434APPENDIX 4 (cont) Body weights - individual values (kg)Vehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Animal Week WeekChange Change Change Change/Sex Number P1 P2 P3 1 23 4 P3-1 P3-2 P3-3 P3-43F 3645S1 7.1 7.2 8.0 9.4 10.2 12.0 12.9 1.4 2.2 4.0 4.93646S1 7.2 8.0 8.5 9.6 10.5 11.8 12.3 1.1 2.0 3.3 3.83647S1 5.7 6.1 6.5 7.3 8.0 9.0 9.4 0.8 1.5 2.5 2.93648S1 7.0 7.9 8.6 9.6 10.5 11.7 12.5 1.0 1.9 3.1 3.93649S1 6.2 6.4 7.1 8.2 9.0 10.2 11.3 1.1 1.9 3.1 4.23650S1 6.4 6.8 7.1 7.9 8.5 9.2 9.6 0.8 1.4 2.1 2.53651S1 7.1 8.0 8.9 10.0 11.2 12.7 13.6 1.1 2.3 3.8 4.73652S1 6.9 7.3 7.9 9.1 10.1 11.2 12.0 1.2 2.2 3.3 4.1S1 - Scheduled Euthanasia 1Sponsor reference nu mber: Huntingdon Life Sciences: 13
- 6434 APPENDIX 5 Body weight change

- individual values (kg)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Week Week /Sex Numb er P1
- P2 P2
- P3 P3
- 1 1
- 2 2
- 3 3
- 4 1M 1145 S1 0.6 0.3 0.8 0.8 0.5 0.6

1146 S1 0.3 0.3 0.8 0.4 1.0 0.2 1147 S1 0.9 0.3 0.9 0.9 1.5 1.0 1148 S1 0.9 0.6 1.1 0.6 1.1 0.5 1149 S1 0.3 0.7 1.1 1.2 1.2 0.5 1150 S1 0.1 0.7 1.0 0.9 1.1 0.6 1151 S1 0.5 0.4 0.7 0.6 0.7 0.5 1152 S1 0.0 0.3 0.8 0.6 1.0 0.4 2M 2145 S1 0.2 0.5 0.8 0.6 1.2 0.7

2146 S1 0.7 0.0 0.7 0.6 0.8 0.7 2147 WE 0.5 0.7 1.3 0.8 2149 S1 0.0 0.5 0.6 0.6 0.9 0.5 2150 S1 0.7 0.7 0.9 0.8 1.1 0.5 2151 S1 0.4 0.6 0.6 0.8 1.0 0.6 2152 S1 0.6 0.7 0.8 1.1 1.3 0.6 2153 S1 0.3 0.8 0.4 0.8 1.0 0.6
S1
- Scheduled Euthanasia 1, WE

- Euthanized for welfare reasonsSponsor reference nu mber: Huntingdon Life Sciences: 13
- 6434 APPENDIX 5 (cont) Body weight change

- individual values (kg)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Wee k Week /Sex Numb er P1
- P2 P2
- P3 P3
- 1 1
- 2 2
- 3 3
- 4 3M 3145 S1 0.6 0.5 0.7 0.6 0.7 0.2

3146 S1 0.6 0.7 0.5 0.4 0.5 0.3 3147 S1 0.9 0.8 1.1 0.9 0.5 0.5 3148 S1 0.6 0.5 1.0 1.3 1.9 0.4 3149 S1 0.2 0.2 0.4 0.7 0.9 0.1 3150 S1 0.5 1.0 0. 6 0.6 0.9 0.2 3151 S1 0.5 0.7 0.9 1.0 1.3 0.3 3152 S1 0.4 0.6 0.6 0.9 0.8 0.3
S1
- Scheduled Euthanasia 1Sponsor reference nu mber: Huntingdon Life Sciences: 13
- 6434 APPENDIX 5 (cont) Body weight change

- individual values (kg)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Week Week /Sex Numb er P1
- P2 P2
- P3 P3
- 1 1
- 2 2
- 3 3
- 4 1F 1645 S1 0.9 0.7 1.2 0.6 1.1 0.8

1646 S1 0.3 0.9 1.2 0.8 0.9 0.6 1647 S1 0.7 0.7 1.4 0.7 1.0 0.6 1648 S1 0.3 0.4 0.8 0.4 1.0 0.6 1649 S1 1.0 1.0 1.5 0.9 1.4 0.7 1650 S1 0.7 0.7 1.0 0.8 1.0 0.8 1651 S1 0.4 0.3 1.1 0.8 1.0 0.5 1652 S1 0.6 0.5 0.9 0.7 0.8 0.9 2F 2645 S1 0.5 0.7 1.0 0.3 1.2 0.5

2646 S1 0.7 0.8 1.1 1.1 1.7 0.7 2647 S1 0.2 0.6 0.9 0.7 1.1 0.5 2648 S1 0.7 0.6 1.1 0. 7 1.1 1.1 2649 S1 0.6 0.8 1.1 0.6 1.5 0.4 2650 S1 0.1 0.4 1.1 0.4 1.5 0.7 2651 S1 0.9 0.5 1.6 1.0 1.3 1.0 2652 S1 0.5 0.6 0.9 0.9 1.2 1.0
S1
- Scheduled Euthanasia 1Sponsor reference nu mber: Huntingdon Life Sciences: 13
- 6434 APPENDIX 5 (cont) Body weight change

- individual values (kg)

V ehicle Co

ntrol HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Week Week /Sex Numb er P1
- P2 P2
- P3 P3
- 1 1
- 2 2
- 3 3
- 4 3F 3645 S1 0.1 0.8 1.4 0.8 1.8 0.9

3646 S1 0.8 0.5 1.1 0.9 1.3 0.5 3647 S1 0.4 0.4 0.8 0.7 1.0 0.4 3648 S1 0.9 0.7 1.0 0.9 1.2 0.8 3649 S1 0.2 0.7 1.1 0.8 1.2 1.1 3650 S1 0.4 0.3 0.8 0.6 0.7 0.4 3651 S1 0.9 0.9 1.1 1.2 1.5 0.9 3652 S1 0.4 0.6 1.2 1.0 1.1 0.8
S1
- Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 Visual food consumption

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 1M 1145 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
1146 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Cons umption 4: All food consumed 1
- 28
1147 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
1148 S1 29 Pre
- Treatment Visual Food Consumption 4: All fo od consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
1149 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15

S1
- Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 (cont) Visual food consumptio n - individual observations Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 1M 1149 S1 29 Treatment Visual Food Consum ption 4: All food consumed 1
- 28
1150 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
1151 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
1152 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
2M 2145 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28

S1
- Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 (cont) Visual food consumption

- individual observations

Vehicl e Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 2M 2146 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
2147 WE 16 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 15
2149 S1 29 Pre
- Treatment Vi sual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
2150 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food co nsumed 1
- 28
2151 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15

S1
- Scheduled Euthanasia 1, WE

- Euthanized for welfare reasonsSponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 (cont) Visual food consumption

- individual observations

Veh icle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 2M 2151 S1 29 Treatment Visual Food Consumption 4: All food consumed 1
- 28
2152 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
2153 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Vis ual Food

Consumption 4: All food consumed 1
- 28
3M 3145 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
3146 S1 29 Pre
- Treatment Visual Food Consum ption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28

S1
- Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 (cont) Visual food consumption

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 3M 3147 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumpt ion 4: All food consumed 1
- 28
3148 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
3149 S1 29 Pre
- Treatment Visual Food Consumption 4: All food c onsumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
3150 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
3151 S1 29 P re - Treatment Visual Food Consumption 4: All food consumed P8
- P15

S1
- Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 (cont) Visual food consumption

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 3M 3151 S1 29 Treatment Visual Food Consumption 4: All food consumed 1
- 28
3152 S1 29 Pre
- Treatment Visual Food Consumption 4: All food con sumed P8
- P15 Treatment Visual Food

Consumption 4: All food consumed 1
- 28

S1
- Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 (cont) Visual food consumption

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 1F 1645 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food c onsumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
1646 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual F ood

Consumption 4: All food consumed 1
- 28
1647 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consume d 1
- 28
1648 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15

S1
- Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 (cont) Visual food consumption

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 1F 1648 S1 29 Randomization Visual Food Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
1649 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
1 650 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
1651 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1

S1
- Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 (cont) Visual food consumption

- individual observations

Vehicle Control HFO -1234yf Dos e Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 1F 1651 S1 29 Treatment Visual Food Consumption 4: All food consumed 1
- 28
1652 S1 29 Pre
- Treat ment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
2F 2645 S1 29 Pre
- Treatment Visual Food Consumption 4: A ll food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
2646 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Random ization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28

S1
- Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 (cont) Visual food consumption

- individual observations

Vehicle Control HF O-1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 2F 2647 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomi zation Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
2648 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: A ll food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
2649 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
2650 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15

S1
- Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 (cont) Visual food consumption

- individual observations

V ehicle Co

ntrol HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 2F 2650 S1 29 Randomization Visual Food Consumption 4: All food consumed Ra 1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
2651 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consum ption 4: All food consumed 1
- 28
2652 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
3F 3645 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1

S1
- Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 (cont) Visual food consumption

- individual ob servations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 3F 3645 S1 29 Treatment Visual Food Consumption 4: All food consumed 1
- 28
3646 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
3647 S1 2 9 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
3648 S1 29 Pre
- Treatment Visual Food Consump tion 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28

S1
- Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 (cont) Visual food consumption

- in dividual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 3F 3649 S1 29 Pre
- Treatment Visual Food Consumpt ion 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
3650 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
3651 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15 Randomization Visual Food

Consump tion 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28
3652 S1 29 Pre
- Treatment Visual Food Consumption 4: All food consumed P8
- P15

S1
- Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 6 (cont) Visual food consumption

- individual observations

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group Anim al Day of /Sex Numb er Death Phase Category Observation Day (s) observed 3F 3652 S1 29 Randomization Vis ual Food Consumption 4: All food consumed Ra1 Treatment Visual Food

Consumption 4: All food consumed 1
- 28

S1
- Scheduled Euthanasia 1Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 Hematology

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Number g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x1 0^3/uL Group 1 1145 Pretest 1 11.2 33.4 6.77 218.5 991 49.3 16.5 33.4 18.6 16.87

Pretest 2 12.6 37.7 7.52 247.7 939 50.1 16.7 33.3 18.3 10.95 Term Day 21 13.4 39.1 8.05 186.9 739 48.6 16.7 34.3 17.3 9.62 Term Day 28 14.4 42.3 8.60 162.7 677 49.2 16.7 34.0 16.8 8.85 1146 Pretest 1 14.0 44.3 8.26 263.3 727 53.7 17.0 31.7 16.9 15.97

Pretest 2 13.9 40.6 7.93 152.8 664 51.3 17.5 34.2 16.5 14.35 Term Day 21 13.4 38.8 7.78 176.0 584 49.9 17.2 34.5 16.6 20. 32 Term Day 28 13.4 40.8 7.83 149.1 756 52.1 17.2 32.9 19.2 10.11 1147 Pretest 1 13.0 41.3 9.05 345.1 328 45.6 14.3 31.4 17.1 13.92

Pretest 2 12.3 38.1 8.45 280.3 355 45.0 14.5 32.3 16.8 10.49 Term Day 21 12.9 39.1 8.68 283.2 371 45.0 1 4.8 32.9 17.4 9.78 Term Day 28 14.3 44.8 9.65 290.1 249 46.4 14.8 31.9 17.4 10.69 1148 Pretest 1 12.2 38.2 8.12 258.5 756 47.1 15.0 31.9 18.8 11.27

Pretest 2 12.9 39.8 8.41 209.8 496 47.4 15.3 32.3 18.3 8.59 Term Day 21 12.9 39.8 7.74 3 61.3 687 51.4 16.7 32.5 21.6 6.49 Term Day 28 15.5 47.9 9.48 136.4 370 50.5 16.3 32.3 18.7 7.66 1149 Pretest 1 12.0 36.7 6.58 240.5 530 55.8 18.3 32.8 16.0 13.50

Pretest 2 12.4 36.6 6.77 148.0 535 54.1 18.3 33.8 15.8 11.14 Term Day 21 1 2.0 35.8 6.69 79.8 438 53.5 17.9 33.6 15.5 9.52 Term Day 28 13.2 39.0 7.29 113.4 456 53.5 18.1 33.9 15.6 10.30Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion ANEU ALYM AMONO AEOS ABASO ALUC SC Number x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 1 1145 Pretest 1 11.27 5.05 0.19 0.10 0.02 0.23

Pretest 2 5.22 5.25 0.21 0.11 0 .02 0.14 Term Day 21 5.22 3.97 0.17 0.10 0.01 0.14 Term Day 28 4.31 4.12 0.22 0.14 0.02 0.04 1146 Pretest 1 5.46 9.88 0.24 0.14 0.03 0.22

Pretest 2 5.10 8.59 0.25 0.14 0.02 0.25 Term Day 21 10.86 8.80 0.23 0.06 0.1 7 0.20 Term Day 28 3.72 5.85 0.29 0.20 0.02 0.03 1147 Pretest 1 4.50 8.84 0.40 0.11 0.02 0.04 NCLP

Pretest 2 3.38 6.74 0.15 0.07 0.02 0.14 Term Day 21 3.48 5.90 0.17 0.10 0.02 0.12 Term Day 28 2.97 7.15 0.27 0.24 0. 02 0.03 CLSL 1148 Pretest 1 5.50 5.15 0.31 0.12 0.02 0.18

Pretest 2 3.30 4.67 0.25 0.18 0.01 0.17 Term Day 21 2.99 3.13 0.20 0.06 0.01 0.10 Term Day 28 3.00 4.17 0.25 0.19 0.01 0.04 1149 Pretest 1 3.80 8 .99 0.23 0.15 0.02 0.31

Pretest 2 3.81 6.78 0.18 0.12 0.01 0.24 Term Day 21 1.95 6.93 0.21 0.16 0.01 0.25 Term Day 28 2.70 6.97 0.35 0.20 0.02 0.06Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Males Vehicle Control HF O-1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Number g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 1 1150 Pretest 1 11.6 35.9 7.27 260.4 535 49.4 15.9 32.3 17.4 8.19

Pretest 2 12.7 38.7 7.98 191.4 539 48.5 15.9 32.9 17.3 9.91 Term Day 21 12.9 40.0 8.16 204.7 463 49.0 15.8 32.3 17.0 8.94 Term Day 28 13.0 39.1 8.11 124.4 473 48.2 16.0 33.3 16.9 7.41 1151 Pretes t 1 12.1 37.9 8.82 278.3 595 42.9 13.7 32.0 17.5 15.49

Pretest 2 11.5 35.3 8.58 187.6 608 41.2 13.4 32.5 17.3 13.16 Term Day 21 11.8 35.8 8.68 178.3 471 41.3 13.6 33.0 17.1 11.52 Term Day 28 12.0 36.4 8.52 179.7 537 42.7 14.0 32.9 18.7 13.13 1152 Pretest 1 12.8 40.1 6.63 294.8 557 60.4 19.2 31.8 16.9 13.33

Pretest 2 13.9 42.7 7.12 200.5 496 60.0 19.6 32.6 16.2 13.50 Term Day 21 14.6 44.7 7.60 158.0 298 58.8 19.2 32.7 15.3 10.76 Term Day 28 14.5 43.4 7.49 160.2 451 58.0 19.4 33.4 15 .9 9.90 Group 2 2145 Pretest 1 11.2 35.9 7.29 185.2 603 49.2 15.4 31.2 19.1 12.37

Pretest 2 11.5 36.5 7.61 161.5 556 48.0 15.1 31.4 18.5 8.96 Term Day 21 11.8 36.9 7.96 156.4 493 46.4 14.8 31.9 18.4 8.68 Term Day 28 13.2 40.8 8.66 178.1 494 47.1 15.3 32.5 19.6 9.47Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasio n ANEU ALYM AMONO AEOS ABASO ALUC SC Number x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 1 1150 Pretest 1 2.69 5.07 0.17 0.05 0.01 0.19

Pretest 2 5.32 4.21 0.15 0.05 0.01 0.17 Term Day 21 1.90 6.41 0.22 0.17 0.02 0.22 Term Day 28 2.15 4.77 0.26 0.18 0.01 0.04 1151 Pretest 1 5.94 8.87 0.27 0.11 0.02 0.28

Pretest 2 7.11 5.56 0.19 0.09 0.00 0.21 Term Day 21 4.57 6.29 0.36 0.25 0.00 0.04 Term Day 28 5.36 7.00 0.25 0.42 0.01 0.09 1152 Pretest 1 4.55 8.02 0.50 0.20 0.03 0.03

Pretest 2 6.91 5.90 0.43 0.08 0.01 0.17 Term Day 21 4.26 5.75 0.35 0.25 0.01 0.13 CLSE Term Day 28 4.13 5.14 0.39 0.18 0.01 0.04 Group 2 2145 Pretest 1 4.61 7.14 0.17 0.15 0.02 0.28

Pretest 2 3.44 5.11 0.12 0.09 0.01 0.19 Term Day 21 3.03 5.10 0.22 0.15 0.01 0.18 Term Day 28 3.71 5.22 0.28 0.20 0.00 0.05Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Number g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 2 2146 Pretest 1 11.3 36.8 8.23 236.2 472 44.7 13.7 30.8 18.8 12.44

Pretest 2 11.0 34.3 8.02 140.5 450 42.7 13.8 32.2 18.7 9.49 Term Day 21 11.3 35.4 8.56 127.4 363 41.4 13.1 31.8 17.6 8.9 6 Term Day 28 12.6 39.4 9.32 170.3 355 42.3 13.5 32.0 19.0 8.17 2147 Pretest 1 11.7 35.7 6.79 237.9 550 52.6 17.3 32.8 17.4 10.61

Pretest 2 11.4 34.1 6.66 128.3 638 51.2 17.2 33.6 16.5 9.07 Term Day 21 NS NS NS NS NS NS NS NS NS NS Te rm Day 28 NS NS NS NS NS NS NS NS NS NS 2149 Pretest 1 10.7 34.4 7.36 189.8 581 46.7 14.6 31.3 19.1 11.25

Pretest 2 10.2 32.4 7.18 173.8 456 45.1 14.3 31.6 18.5 8.97 Term Day 21 10.7 33.5 7.48 161.6 462 44.8 14.3 31.9 18.5 6.87 Term Day 28 11.9 37.3 8.31 187.9 384 44.9 14.4 32.0 19.1 6.44 2150 Pretest 1 11.1 35.0 6.85 321.6 691 51.0 16.2 31.8 18.8 9.29

Pretest 2 11.6 35.9 6.97 331.6 764 51.6 16.6 32.3 18.9 8.03 Term Day 21 12.1 35.8 7.31 86.4 589 48.9 16.5 33.7 15.9 5.6 3 Term Day 28 13.0 38.8 7.80 135.0 631 49.7 16.7 33.6 16.3 6.11 2151 Pretest 1 12.6 38.9 8.04 242.2 644 48.4 15.7 32.4 18.4 11.74

Pretest 2 12.9 39.5 8.27 190.6 380 47.7 15.6 32.7 18.2 9.11 Term Day 21 13.2 38.5 8.26 58.8 594 46.6 15.9 34.2 17.0 8.06 Term Day 28 12.9 37.1 7.89 61.1 604 47.0 16.4 34.8 17.2 7.72Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion ANEU ALYM AMONO AEOS ABASO ALUC SC Number x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 2 2146 Pretest 1 4.72 6.95 0.28 0.23 0.02 0.25

Pretest 2 4.02 5.14 0.10 0.08 0.00 0.14 Term Day 21 3.95 4.40 0.20 0.21 0.00 0.20 Term Day 28 3.39 4.38 0.21 0.15 0.01 0.04 2147 Pretest 1 3.04 6.71 0.24 0.27 0.02 0.33

Pretest 2 3.20 5.36 0.17 0.13 0.02 0.19 Term Day 21 NS NS NS NS NS NS Term Day 28 NS NS NS NS NS NS 2149 Pretest 1 5.29 5.29 0.23 0.12 0.01 0.31

Pretest 2 4.14 4.19 0.29 0.10 0.01 0.24 Term Day 21 1.99 3.96 0.40 0.20 0.01 0.32 Term Day 28 1.72 4.09 0.38 0.19 0.00 0.05 2150 Pretest 1 3.77 5.08 0.13 0.09 0.00 0.21

Pretest 2 2.82 4.80 0.14 0.09 0.01 0.16 Term Day 21 1.52 3.73 0.16 0.08 0.00 0.13 Term Day 28 1.78 3.97 0.19 0.12 0.00 0.04 2151 Pretest 1 5.97 5.19 0.39 0.13 0.01 0.04

Pretest 2 4.00 4.39 0.21 0.34 0.01 0.16 Term Day 21 3.17 4.25 0.24 0.23 0.01 0.14 Term Day 28 3.06 4.10 0.33 0.18 0.01 0.03Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Ani mal Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Number g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 2 2152 Pretest 1 10.1 31.6 6.25 318.2 871 50.6 16.1 31.9 19.4 10.99

Pretest 2 10.8 33.7 6.61 320.4 866 51.0 16.3 32.1 18.7 9.72 Term Day 21 11.9 36.4 7.47 279.1 602 48.7 15.9 32.6 17.6 10.02 Term Day 28 12.1 36.5 7.50 205.8 641 48.7 16.1 33.1 17.2 8.43 2153 Pretest 1 13.7 41.6 8.40 264.9 673 49.6 16.3 32.8 17.3 17.10

Pretest 2 13.8 41.9 8.53 182.2 600 49.2 16.2 32.9 16.9 13.60 Term Day 21 14.1 41.7 8.90 140.2 500 46.9 15.9 33.8 16.1 11.44 Term Day 28 14.4 43.0 8.99 201.2 522 47.8 16.1 33.6 16.9 12.50 Group 3 3145 Pretest 1 12.6 38.6 6.47 32 0.0 1077 59.6 19.4 32.6 18.5 9.58

Pretest 2 13.3 41.7 6.81 345.7 900 61.3 19.6 31.9 17.8 10.49 Term Day 21 13.7 40.5 6.99 136.4 755 58.0 19.6 33.9 15.8 9.21 Term Day 28 13.4 39.7 6.89 67.5 781 57.6 19.4 33.7 15.4 10.72 3146 Pretest 1 11 .5 36.4 7.91 271.3 494 46.0 14.5 31.5 17.9 13.16

Pretest 2 11.5 36.5 7.89 226.0 517 46.3 14.6 31.5 17.2 14.53 Term Day 21 13.0 38.7 9.03 118.4 250 42.9 14.4 33.6 15.7 11.44 Term Day 28 12.4 38.4 8.69 173.9 466 44.2 14.2 32.2 16.5 9.40Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion ANEU ALYM AMONO AEOS ABASO ALUC SC Number x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 2 2152 Pretest 1 4.64 5.71 0.37 0.12 0.01 0.13

Pretest 2 3.71 5.53 0.24 0.07 0.01 0.15 Term Day 21 4.01 5.41 0.29 0.15 0.01 0.14 Term Day 28 3.20 4.76 0.28 0.15 0.01 0.03 2153 Pretest 1 5.27 10.95 0.29 0.22 0.03 0.34

Pretest 2 3.88 9.09 0.21 0.15 0.02 0.25 Term Day 21 3.22 7.50 0.28 0.23 0.01 0.20 Term Day 28 2.96 8.88 0.34 0.23 0.01 0.07 Group 3 3145 Pretest 1 3.42 5.65 0.16 0.09 0.02 0.24

Pretest 2 3.66 6.35 0.20 0.09 0.02 0.18 Term Day 21 3.52 5.10 0.26 0.16 0.00 0.17 Term Day 28 5.19 4.76 0.43 0.26 0.01 0.07 3146 Pretest 1 5.72 6.79 0.24 0.20 0.02 0.20

Pretest 2 8.70 5.28 0.21 0.09 0.01 0.24 Term Day 21 5.31 5.40 0.29 0.23 0.01 0.19 CLSE Term Day 28 3.42 5.36 0.29 0.28 0.02 0.04Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Mal es Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Number g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 3 3147 Pretest 1 12.7 39.7 8.57 289.4 617 46.3 14.9 32.1 19.2 10.15

Pretest 2 12.6 38.8 8.50 200.6 578 45.7 14.9 32.6 18.6 8.33 Term Day 21 13.5 40.5 8.92 157.2 557 45.4 15.1 33.3 18.6 7.64 Term Day 28 14.6 44.6 9.52 121.4 508 46.9 15.4 32.8 18.9 8.77 3148 Pretest 1 10.7 33.0 7.13 222.5 688 46.3 15.0 32.5 18.5 13.92

Pretest 2 9.9 31.8 6.25 709.7 687 50.8 15.8 31.1 24.5 12.26 Term Day 21 10.3 31.5 6.63 105.6 580 47.5 15.6 32.7 18.3 13.48 Term Day 28 11.9 36.5 7.59 112.6 556 48.1 15.6 32.5 18.1 12.91 3149 Pretest 1 11.2 34.3 8.23 354.2 614 41.7 13.6 32.6 21.4 13.37

Pretest 2 11.5 35.2 8.49 292.0 571 41.5 13.6 32.7 19.9 10.55 Term Day 21 12.1 36.6 8.88 238.3 422 41.3 13.7 33.1 18.3 11.96 Term Day 28 12.6 38.8 9.26 23 9.3 448 41.9 13.6 32.4 18.6 14.48 3150 Pretest 1 13.4 41.5 7.47 136.4 710 55.5 17.9 32.2 16.1 12.65

Pretest 2 14.1 42.9 7.76 183.6 546 55.3 18.2 32.8 15.8 8.70 Term Day 21 14.3 43.1 8.10 102.9 541 53.3 17.6 33.1 15.3 8.98 Term Day 28 14 .9 45.1 8.27 142.8 484 54.6 18.0 33.0 15.8 8.79 3151 Pretest 1 11.8 38.3 7.33 296.5 593 52.3 16.1 30.9 19.8 15.32

Pretest 2 12.1 37.7 7.32 235.5 613 51.6 16.5 32.1 19.5 12.07 Term Day 21 13.1 39.0 7.83 121.1 477 49.8 16.8 33.7 17.2 10.18 Term Day 28 14.1 42.7 8.27 148.3 497 51.7 17.0 32.9 17.4 12.75Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion ANEU ALYM AMONO AEOS AB ASO ALUC SC Number x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 3 3147 Pretest 1 2.85 6.73 0.24 0.11 0.03 0.20

Pretest 2 3.24 4.64 0.22 0.07 0.01 0.15 Term Day 21 3.46 3.68 0.28 0.12 0. 01 0.10 Term Day 28 3.34 4.79 0.39 0.21 0.01 0.03 3148 Pretest 1 5.21 8.19 0.34 0.11 0.02 0.05

Pretest 2 5.43 6.41 0.15 0.07 0.01 0.19 Term Day 21 5.70 6.99 0.32 0.21 0.01 0.25 Term Day 28 4.45 7.80 0.36 0.21 0.02 0.07 3149 Pretest 1 4.83 8.02 0.16 0.13 0.01 0.22

Pretest 2 4.34 5.74 0.16 0.12 0.01 0.18 Term Day 21 5.04 6.21 0.18 0.20 0.01 0.32 Term Day 28 7.89 5.82 0.35 0.30 0.01 0.10 3150 Pretest 1 3.78 8.28 0.2 6 0.12 0.02 0.19

Pretest 2 2.13 6.17 0.19 0.09 0.03 0.09 Term Day 21 2.33 6.12 0.30 0.11 0.01 0.10 Term Day 28 2.20 6.18 0.23 0.15 0.02 0.02 3151 Pretest 1 5.71 8.85 0.24 0.17 0.02 0.33

Pretest 2 5.00 6.71 0.15 0.0 6 0.01 0.15 Term Day 21 3.75 5.90 0.18 0.15 0.01 0.20 Term Day 28 4.62 7.56 0.32 0.17 0.02 0.07Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Number g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 3 3152 Pretest 1 11.7 36.7 7.81 202.6 537 46.9 14.9 31.8 18.9 13.52

Pretest 2 12.1 38.6 7.92 216.1 528 48.8 15.2 31.2 19.0 8.90 Term Day 21 12.0 36.0 7.76 57.1 413 46.3 15.5 33.4 17.8 12.72 Term Day 28 13.0 40.1 8.45 101.0 417 47.4 15.4 32.4 18.2 9.40Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Males Vehicle Co

ntrol HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion ANEU ALYM AMONO AEOS ABASO ALUC SC Number x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 3 3152 Pretest 1 5.6 7 7.02 0.31 0.19 0.02 0.29

Pretest 2 3.29 5.12 0.20 0.10 0.01 0.18 Term Day 21 6.42 5.61 0.25 0.16 0.08 0.22 Term Day 28 3.54 5.14 0.38 0.27 0.02 0.06Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Females Vehicle C on trol HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Number g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 1 1645 Pretest 1 13.8 43.1 8.09 263.5 599 53.3 17.1 32.1 16.4 15.26

Pretest 2 13.1 40.2 7.71 173.0 552 52.1 17.0 32.6 16.0 12.50 Term Day 21 14.3 41.9 8.23 133.1 489 50.9 17.4 34.2 15.8 11.19 Term Day 28 14.1 39.5 7.34 179.0 483 53.8 19.2 35.6 18.6 12.52 1646 Pretest 1 13.1 40.4 8.52 376.5 693 47.4 15.3 32.3 18.3 13.93

Pretest 2 13.0 41.9 8.44 344.5 763 49.7 15.3 30.9 18.2 11.44 Term Day 21 13.2 40.0 8.53 214.6 622 46.9 15.4 32.8 17.0 10.79 Term Day 28 13.8 41.9 9.04 134.2 493 46.4 15.2 32.8 16.5 1 0.50 1647 Pretest 1 13.5 41.8 7.10 208.7 750 58.8 19.0 32.2 16.0 14.13

Pretest 2 13.2 40.8 6.96 166.7 724 58.5 18.9 32.3 15.5 12.18 Term Day 21 14.0 42.0 7.30 136.2 646 57.6 19.2 33.3 15.0 10.30 Term Day 28 13.9 42.6 7.19 188.5 630 59.3 19.4 32.7 16.3 11.90 1648 Pretest 1 14.0 43.6 8.20 181.0 484 53.2 17.0 32.0 16.2 14.99

Pretest 2 13.3 42.3 7.88 209.7 551 53.7 16.9 31.4 16.3 9.65 Term Day 21 14.3 43.5 8.09 157.3 428 53.8 17.7 32.9 15.4 10.09 Term Day 28 15.0 46.6 8.7 2 137.6 539 53.4 17.2 32.1 15.2 11.03 1649 Pretest 1 11.7 37.1 8.09 253.9 643 45.8 14.4 31.5 18.6 12.19

Pretest 2 11.5 35.4 7.74 198.3 705 45.7 14.8 32.5 18.6 10.07 Term Day 21 13.3 39.7 8.59 199.3 530 46.3 15.5 33.4 19.2 8.83 Term Day 28 13.1 39.7 8.44 186.1 561 47.1 15.5 33.0 19.5 8.21Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion ANEU ALYM AMONO AEOS ABASO ALUC S C Number x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 1 1645 Pretest 1 1.71 12.54 0.35 0.24 0.03 0.39

Pretest 2 1.55 10.10 0.33 0.22 0.01 0.30 Term Day 21 1.73 8.65 0.30 0.26 0.01 0.23 Term Day 28 2.00 9.73 0.41 0.28 0.02 0.07 1646 Pretest 1 4.20 9.16 0.16 0.13 0.02 0.27

Pretest 2 2.62 8.38 0.16 0.08 0.01 0.18 Term Day 21 2.58 7.56 0.18 0.17 0.02 0.29 Term Day 28 1.83 8.10 0.27 0.19 0.06 0.05 1647 Pretest 1 3.13 10.29 0.16 0.23 0.02 0.30

Pretest 2 2.64 8.96 0.24 0.14 0.03 0.17 Term Day 21 1.84 7.84 0.17 0.27 0.01 0.17 Term Day 28 2.77 8.49 0.27 0.30 0.02 0.05 1648 Pretest 1 3.31 10.56 0.37 0.23 0.16 0.36

Pretest 2 1.75 7.30 0.19 0.07 0.01 0.32 Term Day 21 1.82 7.42 0.33 0.22 0.02 0.29 Term Day 28 2.84 7.45 0.43 0.22 0.05 0.05 1649 Pretest 1 4.03 7.58 0.18 0.08 0.01 0.31

Pretest 2 3.78 5.82 0.16 0.06 0.00 0.25 Term Day 21 1.96 6.32 0.14 0.10 0.11 0.21 Term Day 28 1.90 5.73 0.26 0.22 0.01 0.09Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Number g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 1 1650 Pretest 1 13.3 40.1 6.78 179.7 521 59.1 19.7 33.3 15.4 16.18

Pretest 2 12.9 38. 5 6.61 141.0 633 58.2 19.6 33.7 15.8 12.45 Term Day 21 13.5 39.2 6.82 76.9 506 57.4 19.8 34.5 14.5 12.46 Term Day 28 13.1 38.3 6.67 55.3 476 57.4 19.6 34.1 14.8 12.28 1651 Pretest 1 12.4 38.7 8.80 312.7 708 44.0 14.1 32.0 18.0 12.01

Pre test 2 11.9 37.4 8.45 304.4 629 44.3 14.0 31.7 18.2 12.15 Term Day 21 12.7 39.2 8.82 334.9 569 44.4 14.3 32.3 18.4 9.51 Term Day 28 12.5 39.4 8.79 323.0 565 44.8 14.2 31.8 18.4 9.76 1652 Pretest 1 12.9 39.2 8.23 155.1 747 47.6 15.6 32.8 1 8.0 10.86

Pretest 2 12.6 38.3 8.27 98.8 720 46.3 15.2 32.8 17.5 9.37 Term Day 21 12.3 36.5 8.05 87.2 694 45.4 15.3 33.7 17.6 9.48 Term Day 28 11.6 35.1 7.28 223.6 737 48.1 15.9 33.1 21.6 9.88 Group 2 2645 Pretest 1 11.7 36.0 8.56 311.2 737 42.1 13.7 32.6 17.3 9.91

Pretest 2 10.3 31.7 7.56 270.1 779 41.9 13.7 32.6 18.9 7.87 Term Day 21 11.7 35.2 8.63 178.7 701 40.8 13.6 33.4 16.8 9.94 Term Day 28 11.7 35.2 8.40 151.5 730 41.9 13.9 33.1 18.4 10.01Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion ANEU ALYM AMONO AEOS ABASO ALUC SC Number x10^3/uL x10^3/ uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 1 1650 Pretest 1 4.24 10.78 0.34 0.39 0.07 0.35

Pretest 2 3.33 8.34 0.25 0.18 0.01 0.33 Term Day 21 2.74 8.49 0.34 0.47 0.02 0.39 Term Day 28 2.69 8.24 0. 62 0.57 0.02 0.14 1651 Pretest 1 2.69 8.72 0.17 0.14 0.02 0.27

Pretest 2 3.16 8.37 0.26 0.12 0.06 0.19 Term Day 21 2.04 7.06 0.24 0.14 0.01 0.03 Term Day 28 1.96 7.29 0.22 0.22 0.04 0.05 1652 Pretest 1 1.67 8.66 0.13 0.18 0.02 0.22

Pretest 2 1.58 7.29 0.15 0.11 0.02 0.22 Term Day 21 1.39 7.50 0.17 0.20 0.01 0.21 Term Day 28 2.44 6.83 0.23 0.30 0.01 0.07 Group 2 2645 Pretest 1 2.06 7.22 0.26 0.19 0. 01 0.16

Pretest 2 2.00 5.39 0.25 0.07 0.00 0.15 Term Day 21 2.62 6.64 0.26 0.27 0.01 0.14 Term Day 28 2.08 7.30 0.30 0.26 0.03 0.05Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Femal es Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Number g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 2 2646 Pretest 1 12.3 39.1 7.79 310.2 628 50.2 15.7 31.4 19.3 9.17

Pretest 2 11.9 36.9 7.51 211.3 625 49.2 15.8 32.1 18.4 6.89 Term Day 21 12.4 36.7 7.75 133.4 524 47.3 15.9 33.7 17.6 8.52 Term Day 28 13.1 40.2 8.17 143.8 534 49.2 16.1 32.6 17.8 9.50 2647 Pretest 1 12.6 38.6 8.62 278.8 304 44.8 14.6 32.6 18.5 12.54

Pretest 2 11.9 35.9 8.07 271.8 496 44.4 14.7 33.1 19.3 12.64 Term Day 21 12.3 35.5 7.98 225.4 357 44.5 15.4 34.6 19.8 10.73 Term Day 28 12.3 37.2 8.30 104.4 461 44.8 14.9 33.2 17.4 10.72 2648 Pretest 1 12.1 36.7 8.02 259.2 724 45.8 15.1 32.9 19.5 8.82

Pretest 2 12.2 37.3 7.80 356.7 694 47.8 15.6 32.7 20.7 6.92 Term Day 21 13.0 38.8 8.31 87.3 551 46.7 15.6 33.5 17.6 8.93 Term Day 28 12.6 37.6 8.08 95.3 5 26 46.5 15.6 33.6 17.7 6.73 2649 Pretest 1 13.4 41.1 6.83 247.4 616 60.2 19.6 32.5 16.3 9.13

Pretest 2 14.0 42.6 7.25 164.9 747 58.8 19.3 32.8 15.4 8.17 Term Day 21 14.4 42.2 7.42 146.4 275 56.9 19.4 34.2 16.1 7.10 Term Day 28 14.3 42.0 7.30 116.1 609 57.4 19.5 34.0 15.9 8.25 2650 Pretest 1 13.2 41.7 7.70 243.6 636 54.1 17.2 31.7 16.3 11.45

Pretest 2 13.1 40.4 7.66 208.5 562 52.8 17.0 32.3 16.5 10.08 Term Day 21 14.2 42.6 8.00 129.4 516 53.3 17.8 33.3 15.8 9.44 Term D ay 28 13.7 40.9 7.81 87.8 548 52.3 17.6 33.6 16.4 9.26Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion ANEU ALYM AMONO AEOS ABASO ALUC SC Number x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 2 2646 Pretest 1 2.26 6.19 0.15 0.20 0.01 0.37

Pretest 2 1.32 5.16 0.13 0.08 0.01 0.18 Term Day 21 2.02 6.00 0.12 0.17 0.01 0.19 Term Day 28 1.68 7.28 0.18 0.24 0.03 0.09 2647 Pretest 1 3.57 8.20 0.26 0.22 0.02 0.26 NCLP

Pretest 2 2.50 9.38 0.25 0.20 0.01 0.30 Term Day 21 2.55 7.56 0.15 0.23 0.01 0.21 Term Day 28 2.14 7.93 0.32 0.32 0.01 0.01 2648 Pretest 1 2.00 6.25 0.25 0.11 0.01 0.20

Pretest 2 1.21 5.37 0.11 0.06 0.01 0.15 Term Day 21 2.12 6.21 0.34 0.21 0.01 0.03 Term Day 28 2.05 4.25 0.20 0.19 0.01 0.03 2649 Pretest 1 2.15 6.44 0.20 0. 17 0.02 0.15

Pretest 2 1.65 6.11 0.15 0.08 0.06 0.14 Term Day 21 2.61 4.10 0.15 0.13 0.01 0.10 CLSE Term Day 28 2.36 5.42 0.22 0.20 0.02 0.03 2650 Pretest 1 3.83 6.78 0.40 0.19 0.01 0.24

Pretest 2 3.80 5.69 0.27 0.0 8 0.01 0.23 Term Day 21 3.24 5.58 0.39 0.16 0.01 0.05 Term Day 28 3.48 5.21 0.29 0.20 0.01 0.06Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 500 0 10000 Animal Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Number g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 2 2651 Pretest 1 13.4 41.1 8.06 402.6 660 51.0 16.6 32.6 18.1 13.78

Pretest 2 12 .8 38.6 7.74 282.1 506 49.9 16.5 33.0 17.3 10.06 Term Day 21 13.9 42.7 8.34 311.3 260 51.1 16.7 32.7 17.1 12.52 Term Day 28 13.0 39.0 7.76 200.8 607 50.3 16.7 33.3 17.2 11.15 2652 Pretest 1 11.9 35.8 7.15 380.9 698 50.0 16.6 33.3 18.2 14. 42

Pretest 2 12.1 37.1 7.40 283.2 722 50.2 16.3 32.5 17.3 9.26 Term Day 21 12.5 36.9 7.45 202.2 605 49.5 16.8 34.0 17.0 10.77 Term Day 28 12.4 38.4 7.57 189.5 590 50.7 16.4 32.3 17.1 11.46 Group 3 3645 Pretest 1 11. 6 36.0 7.57 253.2 665 47.5 15.3 32.3 18.5 12.78

Pretest 2 11.6 36.9 7.73 204.4 674 47.7 15.0 31.5 18.1 9.49 Term Day 21 11.6 35.9 7.41 204.5 480 48.4 15.6 32.3 19.1 11.61 Term Day 28 11.9 36.7 7.57 162.5 478 48.5 15.7 32.4 19.6 9.04 364 6 Pretest 1 14.1 43.2 8.44 317.0 569 51.2 16.7 32.6 17.1 12.58

Pretest 2 13.5 41.1 8.20 278.9 597 50.2 16.5 32.9 17.7 8.52 Term Day 21 13.9 41.3 8.17 167.4 512 50.5 17.0 33.6 17.7 10.52 Term Day 28 14.7 43.2 8.54 198.8 339 50.5 17.2 34.1 18.4 9.98Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion ANEU ALYM AMONO AEOS ABASO ALUC SC Number x1 0^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 2 2651 Pretest 1 1.81 11.00 0.29 0.32 0.02 0.33

Pretest 2 1.24 8.23 0.41 0.15 0.01 0.03 Term Day 21 1.84 9.91 0.25 0.32 0.02 0.18 CLSE Term Da y 28 2.06 8.41 0.27 0.36 0.02 0.03 2652 Pretest 1 3.74 9.65 0.42 0.15 0.02 0.45

Pretest 2 1.46 7.30 0.23 0.06 0.02 0.18 Term Day 21 2.67 7.52 0.17 0.14 0.01 0.27 Term Day 28 3.01 7.89 0.30 0.19 0.02 0.06 Group 3 3645 Pretest 1 2.63 9.47 0.26 0.13 0.01 0.29

Pretest 2 1.80 7.26 0.20 0.06 0.01 0.16 Term Day 21 4.30 6.78 0.13 0.20 0.01 0.19 Term Day 28 2.69 5.71 0.23 0.34 0.01 0.06 3646 Pretest 1 2.86 9.03 0.26 0.14 0.09 0.21

Pretest 2 2.02 6.22 0.10 0.04 0.02 0.12 Term Day 21 2.92 7.05 0.33 0.13 0.05 0.04 Term Day 28 3.14 6.25 0.23 0.31 0.02 0.03 CLSESponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- indiv idual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Number g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 3 3647 Pretest 1 12.5 37.1 7.55 282.6 315 49.2 16.5 33.6 18.7 10.00

Pretest 2 12.8 40.4 7.87 441.4 623 51.4 16.2 31.6 19.6 10.11 Term Day 21 13.0 41.5 8.08 215.4 352 51.4 16.1 31.3 18.6 10.94 Term Day 28 12.6 38.7 7.59 206.1 382 5 1.0 16.7 32.7 19.2 9.36 3648 Pretest 1 13.6 39.9 7.64 239.6 561 52.3 17.8 34.0 18.9 12.73

Pretest 2 13.6 40.8 7.62 213.3 514 53.6 17.8 33.3 18.4 9.18 Term Day 21 15.4 45.8 8.00 215.7 458 57.2 19.2 33.6 17.1 9.62 Term Day 28 15.7 46.9 8. 11 203.4 436 57.8 19.3 33.4 16.3 10.25 3649 Pretest 1 13.1 39.5 7.43 191.1 734 53.1 17.7 33.3 19.5 18.92

Pretest 2 13.7 42.5 7.70 283.0 708 55.2 17.8 32.2 20.4 11.32 Term Day 21 14.5 43.9 7.68 201.3 523 57.2 18.9 33.0 19.2 12.19 Term Da y 28 13.8 40.9 7.13 151.9 665 57.4 19.4 33.8 19.2 10.03 3650 Pretest 1 12.5 39.9 8.88 257.8 644 44.9 14.1 31.3 17.6 18.73

Pretest 2 12.7 40.6 8.99 336.9 626 45.1 14.1 31.3 17.6 13.53 Term Day 21 12.8 41.9 9.21 294.1 631 45.5 13.9 30.5 18. 4 15.02 Term Day 28 12.6 41.5 9.03 256.9 599 45.9 14.0 30.5 18.9 16.08 3651 Pretest 1 11.0 34.2 7.56 158.7 623 45.2 14.6 32.2 17.5 13.97

Pretest 2 10.5 32.7 7.04 194.3 329 46.4 14.9 32.1 18.7 12.53 Term Day 21 11.8 37.0 7.83 206.1 585 4 7.2 15.1 31.9 20.2 11.06 Term Day 28 12.2 38.2 7.96 148.4 508 48.0 15.3 31.9 20.4 11.03Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occas ion ANEU ALYM AMONO AEOS ABASO ALUC SC Number x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL Group 3 3647 Pretest 1 2.73 6.57 0.26 0.25 0.01 0.18 CLSE

Pretest 2 1.87 7.75 0.21 0.08 0.01 0.17 Ter m Day 21 1.59 8.90 0.12 0.13 0.02 0.18 Term Day 28 2.45 6.44 0.16 0.22 0.01 0.08 3648 Pretest 1 3.27 8.63 0.32 0.24 0.03 0.24

Pretest 2 2.18 6.49 0.14 0.09 0.03 0.24 Term Day 21 2.21 6.80 0.21 0.20 0.03 0.17 Term D ay 28 2.34 7.29 0.27 0.25 0.06 0.04 3649 Pretest 1 11.38 6.80 0.29 0.07 0.02 0.36

Pretest 2 3.45 7.18 0.24 0.11 0.02 0.32 Term Day 21 4.66 6.87 0.39 0.22 0.02 0.04 Term Day 28 3.43 6.04 0.26 0.27 0.01 0.02 3650 Pretest 1 3.67 14.07 0.56 0.31 0.04 0.08

Pretest 2 1.90 10.99 0.22 0.17 0.03 0.23 Term Day 21 3.22 10.70 0.28 0.56 0.03 0.23 Term Day 28 3.53 11.60 0.26 0.56 0.04 0.08 3651 Pretest 1 3.78 9.19 0.58 0.34 0.01 0.0 6

Pretest 2 2.07 9.67 0.47 0.13 0.14 0.05 CLSL Term Day 21 2.08 8.25 0.21 0.28 0.02 0.22 Term Day 28 1.60 8.72 0.31 0.28 0.06 0.06Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Females Vehicle Control HFO -1234yf Dose G ro up 1 2 3 Dose (ppm) 5000 10000 Animal Occasion HGB HCT RBC RETIC PLT MCV MCH MCHC RDW WBC Number g/dL % x10^6/uL x10^9/L x10^3/uL fL pg g/dL % x10^3/uL Group 3 3652 Pretest 1 12.7 38.6 8.61 301.3 565 44.9 14.7 32.8 16.6 14.50

Pretest 2 12.9 40.5 8.93 338.2 525 45.3 14.5 31.9 17.1 9.37 Term Day 21 12.8 37.7 8.57 169.8 578 44.0 15.0 34.0 17.5 11.90 Term Day 28 12.7 37.5 8.45 129.0 620 44.4 15.0 33.8 17.5 12.56Sponsor refer ence number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 7 (cont) Hematology

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion ANEU ALYM AMONO AEOS ABASO ALUC SC Number x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL x10^3/uL G ro up 3 3652 Pretest 1 5.16 8.44 0.46 0.20 0.02 0.22

Pretest 2 2.11 6.76 0.21 0.09 0.05 0.15 Term Day 21 4.14 6.98 0.20 0.30 0.05 0.23 Term Day 28 5.47 6.38 0.25 0.32 0.07 0.06Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 Clinical chemistry

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion AST ALT CK SC Number U/L U/L U/L Group 1 1 145 Pretest 1 27 49 541

Pretest 2 36 45 920 Term Day 21 28 45 278 Term Day 28 25 43 228 1146 Pretest 1 21 54 217

Pretest 2 30 49 489 Term Day 21 36 56 330 SHI Term Day 28 21 52 239 1147 Pretest 1 26 48 201

Pretest 2 38 41 271 Term Day 21 31 41 458 Term Day 28 25 39 321 1148 Pretest 1 28 49 574

Pretest 2 51 43 1366 Term Day 21 24 32 251 Term Day 28 47 34 478 SHI 1149 Pretest 1 18 39 128

Pretest 2 34 40 319 Term Day 21 23 38 349 Term Day 28 24 40 353Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Number U/L % U/L % U/L NG/mL NG/mL Group 1 1145 Pretest 1 578 36.4 210 15.2 88 27.48 0.00

Pretest 2 901 61.4 553 8.6 77 26.74 0.00 Term Day 21 259 33.5 87 18.7 48 40.08 0.00 Term Day 28 221 10.3 23 11.4 25 6.32 0.00 1146 Pretest 1 218 65.0 142 13.9 30 31.54 0.00

Pretest 2 503 53.6 270 23.2 117 13.40 0. 00 Term Day 21 304 44.6 136 9.6 29 52.52 0.00 Term Day 28 220 38.8 85 22.7 50 9.98 0.00 1147 Pretest 1 192 70.3 135 11.3 22 14.32 0.00

Pretest 2 260 18.3 48 11.1 29 14.24 0.00 Term Day 21 425 80.0 340 7.0 30 55.06 0.00 Term Day 28 309 51.4 159 10.5 32 11.94 0.00 1148 Pretest 1 585 72.5 424 9.4 55 24.86 0.00

Pretest 2 1333 73.4 978 19.9 265 102.60 0.00 Term Day 21 245 54.6 134 17.4 43 15.56 0.01 Term Day 28 447 24.0 107 18.2 81 89.60 0 .00 1149 Pretest 1 120 49.7 60 21.4 26 16.86 0.00

Pretest 2 299 74.4 222 15.0 45 15.78 0.00 Term Day 21 328 41.0 134 13.2 43 9.44 0.00 Term Day 28 342 19.9 68 19.6 67 18.16 0.00Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion AST ALT CK SC Number U/L U/L U/L Group 1 1150 Pretest 1 28 38 273

Pretest 2 45 43 853 Term Day 21 35 43 661 Term Day 28 26 40 250 1151 Pretest 1 26 52 405

Pretest 2 36 50 457 Term Day 21 29 47 846 Term Day 28 22 47 277 1152 Pretest 1 33 45 683

Pretest 2 36 50 364 Term Day 21 26 45 216 Term Day 28 32 48 263 Group 2 2145 Pretest 1 24 37 391

Pretest 2 24 36 403 Term Day 21 25 36 274 Term Day 2 8 25 37 490Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion CK CK(MM) CK(MM) CK(MB ) CK(MB) MYOGLOBI TPI Number U/L % U/L % U/L NG/mL NG/mL Group 1 1150 Pretest 1 283 69.4 196 9.8 28 22.62 0.00

Pretest 2 833 77.3 644 8.9 74 57.20 0.00 Term Day 21 638 56.1 358 9.8 63 91.04 0.00 Ter m Day 28 239 24.9 60 14.9 36 29.18 0.00 1151 Pretest 1 418 75.6 316 7.8 33 14.78 0.00

Pretest 2 447 37.3 167 19.3 86 16.84 0.00 Term Day 21 805 86.7 698 2.8 23 9.84 0.00 Term Day 28 265 29.6 78 21.1 56 13.84 0.00 1152 Pretest 1 701 71.5 501 6.2 43 56.96 0.00

Pretest 2 362 33.5 121 21.8 79 25.42 0.00 Term Day 21 208 31.2 65 15.9 33 14.08 0.00 Term Day 28 248 22.9 57 15.1 37 20.66 0.00 Group 2 2145 Pretest 1 385 50.0 193 12.3 47 27.08 0.00

Pretest 2 385 47.3 182 15.5 60 14.82 0.00 Term Day 21 253 31.7 80 14.0 35 14.80 0.00 Term Day 28 458 24.1 110 19.0 87 97.36 0.00Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemi stry - individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion AST ALT CK SC Number U/L U/L U/L Group 2 2146 Pretest 1 29 45 350

Pretest 2 33 46 310 Term Day 21 33 40 351 Term Day 28 26 41 239 2147 Pretest 1 73 44 2486

Pretest 2 29 41 1035 Term Day 21 NS NS NS Term Day 28 NS NS NS Un scheduled 32 38 118 5 2149 Pretest 1 31 45 324

Pretest 2 22 41 209 Term Day 21 24 41 365 Term Day 28 22 45 220 2150 Pretest 1 37 38 969

Pretest 2 30 33 476 Term Day 21 30 31 279 Te rm Day 28 30 34 469Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion C K CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Number U/L % U/L % U/L NG/mL NG/mL Group 2 2146 Pretest 1 343 25.9 89 8.0 27 57.28 0.00

Pretest 2 288 44.3 128 10.6 31 6.52 0.00 Term Day 21 334 60.7 203 10.9 3 6 31.50 0.00 Term Day 28 226 25.0 57 13.1 30 19.64 0.00 2147 Pretest 1 2387 72.7 1735 9.3 222 422.60 0.00

Pretest 2 974 71.2 693 9.5 93 12.22 0.01 Un scheduled 1100 54.4 598 20.5 22 6 136.48 0.00 2149 Pretest 1 310 56.3 175 14.1 44 22.00 0.00

Pretest 2 202 56.0 113 13.9 28 12.88 0.00 Term Day 21 340 91.7 312 5.9 20 53.16 0.00 Term Day 28 211 34.5 73 12.4 26 30.96 0.00 2150 Pretest 1 983 68.3 671 12.1 119 59.60 0.00

Pretest 2 444 52.9 235 8.2 36 43.44 0.00 Term Day 21 265 82.3 218 9.3 25 19.58 0.00 Term Day 28 446 44.7 199 9.8 44 21.06 0.00Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- in dividual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion AST ALT CK SC Number U/L U/L U/L Group 2 2151 Pretest 1 23 40 291

Pr etest 2 59 41 1713 Term Day 21 23 38 279 Term Day 28 18 38 239 2152 Pretest 1 22 36 505

Pretest 2 23 34 343 Term Day 21 28 35 355 Term Day 28 26 34 270 2153 Pretest 1 17 36 133

Pretest 2 21 33 225 Term Day 21 20 33 209 Term Day 28 32 34 1797 Group 3 3145 Pretest 1 29 46 337

Pretest 2 52 46 1830 Term Day 21 36 41 322 Term Day 28 27 43 216Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Number U/L % U/L % U/L NG/mL NG/mL Group 2 2151 Pretest 1 279 42.0 117 20.7 58 20.18 0.00

Pretest 2 1558 68.7 1070 9.4 146 270.80 0.00 Term Day 21 262 74.0 194 16.6 43 13.22 0.00 Term Day 28 229 24.1 55 13.4 31 9.62 0.00 2152 Pretest 1 500 61.1 306 13.6 68 18.80 0.00

Pretest 2 324 54.9 178 12.1 39 7.48 0.00 Term Day 21 326 77.1 251 12.7 41 24.74 0.00 Term Day 28 255 42.1 107 14.3 36 13.96 0.00 2153 Pretest 1 133 27.7 37 19.8 26 4.68 0.00

Pretest 2 216 50.0 108 12.0 26 7.56 0.00 Term Day 21 201 18.0 36 13.4 27 20.28 0.00 Term Day 28 1604 63.2 1014 9.1 146 110.88 0.00 Group 3 3145 P retest 1 320 32.9 105 27.1 87 10.76 0.00

Pretest 2 1679 55.2 927 9.6 161 73.40 0.00 Term Day 21 302 57.7 174 14.7 44 24.44 0.00 Term Day 28 202 25.7 52 21.6 44 11.08 0.00Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clin ical chemistry

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion AST ALT CK SC Number U/L U/L U/L Group 3 3146 Pretest 1 27 48 189

Pretest 2 37 49 279 Term Day 21 28 42 190 Term Day 28 27 43 238 3147 Pretest 1 48 36 1770

Pretest 2 37 38 681 Term Day 21 27 38 265 Term Day 28 35 36 1163 3148 Pretest 1 26 36 414

Pretest 2 27 38 265 Term Day 21 25 36 422 Term Day 28 19 34 146 3149 Pretest 1 32 55 471

Pretest 2 40 54 574 Term Day 21 62 48 3200 Term Day 28 34 49 634 3150 Pretest 1 29 51 546

Pretest 2 28 49 274 Term Day 21 21 49 213 Term Day 28 21 50 238Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Males Vehicle Control HFO -1234yf Dose Gr oup 1 2 3 Dose (ppm) 5000 10000 Animal Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Number U/L % U/L % U/L NG/mL NG/mL Group 3 3146 Pretest 1 192 31.2 60 14.4 28 13.68 0.00

Pretest 2 263 35.3 93 16.9 44 6.94 0.00 Term Day 21 173 41.4 72 11.2 19 10.72 0.00 Term Day 28 221 33.0 73 10.0 22 21.86 0.00 3147 Pretest 1 1702 70.0 1191 8.9 151 242.40 0.00

Pretest 2 662 51.1 338 17.5 116 47.60 0.00 Term Day 2 1 246 74.8 184 14.9 37 16.30 0.00 Term Day 28 1093 60.3 659 6.8 74 118.20 0.00 3148 Pretest 1 415 49.5 205 12.1 50 47.84 0.01

Pretest 2 252 52.0 131 10.0 25 5.54 0.01 Term Day 21 406 75.1 305 9.8 40 42.82 0.03 Term Day 28 133 28.0 37 11.0 15 9.30 0.03 3149 Pretest 1 477 23.0 110 6.8 32 55.12 0.00

Pretest 2 529 52.7 279 9.4 50 46.00 0.00 Term Day 21 2751 94.1 2589 1.4 39 272.80 0.00 Term Day 28 594 29.0 172 9.2 55 117.92 0.00 3150 Pretest 1 552 38.2 211 12.9 71 37.12 0.00

Pretest 2 254 49.8 126 12.6 32 24.68 0.00 Term Day 21 198 73.4 145 12.5 25 15.06 0.00 Term Day 28 219 33.8 74 15.3 34 11.40 0.00Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual val ues

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion AST ALT CK SC Number U/L U/L U/L Group 3 3151 Pretest 1 46 47 1941

Pretest 2 33 47 347 Term Day 21 33 51 631 Term Day 28 45 57 2367 3152 Pretest 1 24 44 257

Pretest 2 33 50 371 Term Day 21 26 43 231 Term Day 28 22 41 277Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Males Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Number U/L % U/L % U/L NG/mL NG/mL Group 3 3151 Pretest 1 1807 63.4 1146 8.0 145 97.80 0.00

Pretest 2 328 53.7 176 10.3 34 17.78 0.00 Term Day 21 609 88.6 540 6.4 39 63.20 0.00 Term Day 28 2060 69.2 1426 9.6 198 101.60 0.00 3152 Pretest 1 264 32.7 86 14.0 37 9.60 0.00

Pretest 2 341 57.8 197 12.8 44 10.82 0.00 Term Day 21 214 85.5 183 9.1 19 15.42 0.00 Term Day 28 259 31.3 81 10.5 27 10.10 0.00Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion AST ALT CK SC Number U/L U/L U/L Group 1 1645 Pretest 1 25 41 324 SHI

Pretest 2 20 39 420 Term Day 21 22 39 678 Term Day 28 24 42 526 1646 Pretest 1 25 51 569

Pretest 2 19 47 344 Term D ay 21 19 46 974 Term Day 28 18 46 477 1647 Pretest 1 31 44 473

Pretest 2 31 42 516 Term Day 21 33 37 1263 Term Day 28 27 40 1004 1648 Pretest 1 35 43 353 SHI

Pretest 2 22 41 453 Term Day 21 34 42 756 Term Day 28 33 37 856 SHI 1649 Pretest 1 23 31 925

Pretest 2 29 32 7431 Term Day 21 25 36 1862 Term Day 28 26 37 1290Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical che mistry

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Number U/L % U/L % U/L NG/mL NG/mL Group 1 1645 Pretest 1 420 39.2 165 12.4 52 10.46 0.00

Pretest 2 405 84.7 343 2.9 12 9.66 0.00 Term Day 21 648 90.4 586 6.1 40 22.06 0.00 Term Day 28 489 49.8 244 10.5 51 14.18 0.00 1646 Pretest 1 584 42.3 247 17.5 1 02 27.70 0.00

Pretest 2 332 85.1 283 5.4 18 6.50 0.00 Term Day 21 927 95.5 885 3.8 35 7.74 0.00 Term Day 28 448 31.5 141 11.3 51 15.46 0.00 1647 Pretest 1 490 46.5 228 17.7 87 9.08 1.68

Pretest 2 491 78.2 384 6.2 30 12. 88 2.52 Term Day 21 1181 91.2 1077 5.3 63 19.44 3.92 Term Day 28 935 53.2 497 15.2 142 14.34 4.13 1648 Pretest 1 420 68.3 287 11.8 50 14.62 0.00

Pretest 2 421 72.4 305 9.2 39 49.36 0.00 Term Day 21 702 94.0 660 4.4 31 1 9.86 0.00 Term Day 28 797 54.6 435 9.9 79 100.72 0.03 1649 Pretest 1 952 91.6 872 3.2 30 16.48 0.00

Pretest 2 5469 95.5 5223 2.1 115 18.80 0.00 Term Day 21 1687 88.3 1490 6.7 113 23.32 0.00 Term Day 28 1193 46.0 549 22. 0 262 87.04 0.00Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion AST ALT CK SC Number U/L U/L U/L Group 1 1650 Pretest 1 23 43 708

Pretest 2 33 45 955 Term Day 21 17 43 594 Term Day 28 20 42 520 1651 Pretest 1 30 39 596

Pretest 2 26 37 856 Term Day 21 39 36 516 Term Day 28 21 35 347 1652 Pretest 1 21 44 403

Pretest 2 26 44 483 Term Day 21 35 42 1794 Term Day 28 28 45 1278 Group 2 2645 Pretest 1 36 38 831

Pre test 2 27 34 227 Term Day 21 22 35 730 Term Day 28 19 37 366Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (p pm) 5000 10000 Animal Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Number U/L % U/L % U/L NG/mL NG/mL Group 1 1650 Pretest 1 712 77.0 548 9.4 67 20.82 0.00

Pretest 2 898 65.6 589 14.6 131 123.80 0.00 Term Day 21 551 75.8 418 13.6 75 18.20 0.00 Term Day 28 468 47.7 223 12.5 59 17.16 0.00 1651 Pretest 1 597 70.3 420 14.5 87 24.30 0.00

Pretest 2 819 59.2 485 16.9 138 102.56 0.00 Term Day 21 1412 95.5 13 48 3.6 51 16.32 0.00 Term Day 28 317 34.4 109 24.6 78 9.26 0.00 1652 Pretest 1 407 73.9 301 13.8 56 48.00 0.00

Pretest 2 467 34.7 162 14.1 66 28.22 0.00 Term Day 21 1601 97.1 1555 2.6 42 121.92 0.01 Term Day 28 1163 65. 5 762 14.0 163 73.48 0.01 Group 2 2645 Pretest 1 823 92.6 762 4.4 36 65.40 0.00

Pretest 2 209 44.2 92 10.2 21 8.60 0.00 Term Day 21 708 93.0 658 4.9 35 15.76 0.00 Term Day 28 344 45.1 155 16.3 56 12.22 0 .00Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion AST ALT CK SC Number U/L U/L U/L Group 2 2646 Pretest 1 33 37 803 SHI

Pretest 2 31 28 1939 Term Day 21 27 30 1961 Term Day 28 20 31 272 2647 Pretest 1 391 187 >7800

Pretest 2 209 165 >7800 Term Day 21 74 216 >7800 Term Day 28 160 219 >7800 2648 Pretest 1 25 47 298

Pretest 2 27 47 374 Term Day 21 19 44 455 Term Day 28 25 42 461 2649 Pretest 1 34 36 6 74

Pretest 2 28 35 480 Term Day 21 24 38 1540 Term Day 28 22 35 286 2650 Pretest 1 45 39 1554 SHI

Pretest 2 21 36 391 Term Day 21 23 42 5774 Term Day 28 18 38 722Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPEND IX 8 (cont) Clinical chemistry

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Number U/L % U/L % U/L NG/mL NG/mL Group 2 2646 Pretest 1 795 71.8 571 14.4 114 51.36 0.01

Pretest 2 1760 57.7 1016 14.7 259 25.48 0.02 Term Day 21 1824 92.8 1693 5.2 95 9.18 0.03 Term Day 28 255 20.5 52 11.0 28 22.94 0.03 2647 Pretest 1 48370 96.5 46677 1.9 919 115.80 0.00

Pretest 2 17750 94.4 16756 4.1 728 1003.20 0.00 Term Day 21 18520 93.4 17298 4.2 778 117.36 0.00 Term Day 28 38330 96.1 36835 2.4 920 168.40 0.00 2648 Pretest 1 301 70.3 212 16 .9 51 7.88 0.00

Pretest 2 352 33.6 118 10.4 37 30.00 0.00 Term Day 21 446 65.0 290 19.9 89 12.48 0.00 Term Day 28 434 20.7 90 8.2 36 59.98 0.00 2649 Pretest 1 31 86.1 27 8.4 3 44.96 0.00

Pretest 2 458 77.2 354 7.4 34 22 .10 0.00 Term Day 21 498 79.5 396 10.8 54 17.14 0.00 Term Day 28 268 22.3 60 8.0 21 18.16 0.00 2650 Pretest 1 1490 71.7 1068 7.6 113 299.40 0.00

Pretest 2 379 71.0 269 11.4 43 18.42 0.00 Term Day 21 6920 94.5 6539 4.5 3 11 68.70 0.00 Term Day 28 662 27.0 179 8.6 57 7.62 0.00Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion AST ALT CK SC Number U/L U/L U/L Group 2 2651 Pretest 1 25 40 451

Pretest 2 31 46 552 Term Day 21 21 35 1038 Term Day 28 36 35 885 2652 Pretest 1 18 41 231

Pretest 2 19 40 364 Term Day 21 18 36 284 Term Day 28 16 35 320 Group 3 3645 Pretest 1 21 40 365

Pretest 2 21 36 481 Term Day 21 22 37 1025 Term Day 28 30 34 982 3646 Pretest 1 37 72 887

Pretest 2 31 76 798 Term Day 21 27 59 >7800 Term Day 28 57 64 3271 SHISpo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Females Veh icle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Number U/L % U/L % U/L NG/mL NG/mL Group 2 2651 Pretest 1 441 76.8 339 1 7.7 78 11.58 0.00

Pretest 2 526 82.1 432 8.4 44 18.80 0.00 Term Day 21 1009 87.2 880 8.3 84 14.72 0.01 Term Day 28 824 43.9 362 9.0 74 59.02 0.00 2652 Pretest 1 224 62.5 140 16.4 37 22.50 0.30

Pretest 2 346 74.8 259 14. 9 52 43.78 0.17 Term Day 21 265 83.3 221 12.5 33 8.86 0.08 Term Day 28 297 23.5 70 14.0 42 17.68 0.09 Group 3 3645 Pretest 1 356 92.6 330 4.0 14 20.28 0.00

Pretest 2 444 77.4 344 14.5 64 49.82 0.00 Term Day 21 1010 53.9 544 14.0 141 53.58 0.00 Term Day 28 909 33.1 301 8.9 81 98.88 0.00 3646 Pretest 1 892 69.2 617 6.6 59 23.12 0.00

Pretest 2 758 80.9 613 8.3 63 20.90 0.00 Term Day 21 10790 95.1 10261 1.5 162 53.44 0.00 Term Day 28 2707 57.9 1567 7.3 198 562.20 0.00Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion AST ALT CK SC Number U/L U/L U/L Group 3 3647 Pretest 1 26 43 668

Pretest 2 25 45 527 Term Day 21 25 42 524 Term Day 28 22 41 564 3648 Pretest 1 29 38 1430

Pretest 2 26 41 815 Term Day 21 20 40 2246 Term Day 28 35 40 2432 3649 Pretest 1 31 39 358

Pretest 2 33 43 696 Term Day 21 24 38 >7800 Term Day 28 22 34 908 3650 Pretest 1 32 43 978 SHI

Pretest 2 22 46 310 Term Day 21 28 44 635 Term Day 28 23 40 337 3651 Pretest 1 24 37 654

Pretest 2 35 39 1272 Term Day 21 21 42 >7800 Term Day 28 24 38 586Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Number U /L % U/L % U/L NG/mL NG/mL Group 3 3647 Pretest 1 671 72.8 488 19.6 132 33.36 0.00

Pretest 2 480 74.9 360 11.1 53 43.32 0.00 Term Day 21 512 32.0 164 8.4 43 35.88 0.00 Term Day 28 524 40.0 210 10.9 57 49 .62 0.00 3648 Pretest 1 1396 87.9 1227 6.7 94 51.20 0.00

Pretest 2 760 58.2 442 14.4 109 36.78 0.00 Term Day 21 2056 62.2 1279 15.5 319 16.88 0.00 Term Day 28 2055 64.5 1325 7.8 160 508.80 0.00 3649 Pretest 1 368 62.5 230 16.4 60 7.64 0.00

Pretest 2 634 73.2 464 17.6 112 16.72 0.00 Term Day 21 18710 93.8 17550 4.4 823 28.32 0.00 Term Day 28 836 40.9 342 10.2 85 18.76 0.00 3650 Pretest 1 1007 84.7 853 7.4 75 28.86 0.00

Pret est 2 285 66.8 190 20.9 60 34.32 0.00 Term Day 21 631 26.1 165 10.0 63 14.24 0.00 Term Day 28 309 13.4 41 4.1 13 28.82 0.00 3651 Pretest 1 674 74.4 501 16.4 111 8.52 0.00

Pretest 2 1182 84.4 998 4.6 54 100.14 0.00 Term Day 21 12270 90.2 11068 4.1 503 35.94 0.00 Term Day 28 535 47.5 254 8.5 45 33.90 0.00Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (cont) Clinical chemistry

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion AST ALT CK SC Number U/L U/L U/L Group 3 3652 Pretest 1 66 42 1488

Pretest 2 24 41 743 Term Day 21 17 36 883 Term Day 28 17 37 630Spo nsor reference number: Huntingdon Life Sciences: 13
- 6434 APPENDIX 8 (con t) Clinical chemistry

- individual values

Females Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Animal Occasion CK CK(MM) CK(MM) CK(MB) CK(MB) MYOGLOBI TPI Number U/L % U/L % U/L NG/mL NG/mL Group 3 3652 Pretest 1 1431 83.6 1196 7.5 107 56.40 0.00

Pretest 2 672 34.4 231 16.6 112 63.36 0.00 Term Day 21 853 42.2 360 18.1 154 7.12 0.00 Term Day 28 569 26.3 150 11.0 63 37.72 0.00Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPEN DIX 9 Organ weights

- individual values (g)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group /Sex Animal

Number Terminal

Body weight Br ain Br ain Heart Heart Heart Kidney s Kidney s Kidney s Relative to Bo dy (%) Body (%) Br ain (%) Body (%) Br ain (%) 1M 1145 11300.0 56.145 0.497 68.308 0.604 122 96.366 0.853 172

1146 9300.0 53.764 0.578 48.181 0.518 90 69.044 0.742 128 1147 11500.0 59.261 0.515 58.563 0.509 99 70.882 0.616 120 1148 11800.0 62.54 4 0.530 65.105 0.552 104 73.724 0.625 118 1149 11300.0 56.310 0.498 65.089 0.576 116 60.046 0.531 107 1150 12400.0 58.425 0.471 77.921 0.628 133 67.398 0.544 115 1151 8700.0 53.209 0.612 46.361 0.533 87 63.053 0.725 119 1152 9700.0 58.075 0.599 50.918 0.525 88 69.113 0.713 119 2M 2145 10000.0 49.925 0.499 60.417 0.604 121 62.896 0.629 126

2146 9100.0 53.682 0.590 59.821 0.657 111 58.725 0.645 109 2149 8600.0 50.905 0.592 48.560 0.565 95 45.650 0.531 90 2150 11100.0 67.293 0.606 55.551 0.500 83 68.742 0.619 102 2151 10800.0 63.159 0.585 68.696 0.636 109 78.961 0.731 125 2152 10900.0 61.499 0.564 62.164 0.570 101 75.303 0.691 122 2153 11000.0 60.081 0.546 59.892 0.544 100 54.043 0.491 90Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPEN DIX 9 (cont) Organ weights

- individual values (g)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group /Sex Animal

Number Liver Liver Liver Lungs and Br onchi Lungs and

Br onchi Lungs and

Br onchi Relative to Body (%) Br ain (%) Body (%) Br ain (%) 1M 1145 300.731 2.66 536 79.082 0.700 141

1146 206.423 2.22 384 73.803 0.794 137 1147 268.473 2.33 453 100.887 0.877 170 1148 267.020 2.26 427 98.371 0.834 157 1149 218.405 1.93 388 95.507 0.845 170 1150 235.0 37 1.90 402 112.514 0.907 193 1151 176.556 2.03 332 73.581 0.846 138 1152 201.813 2.08 348 84.130 0.867 145 2M 2145 234.571 2.35 470 82.969 0.830 166

2146 191.784 2.11 357 83.324 0.916 155 2149 153.412 1.78 301 81.816 0.951 161 21 50 279.407 2.52 415 80.554 0.726 120 2151 203.820 1.89 323 91.179 0.844 144 2152 295.471 2.71 480 99.194 0.910 161 2153 199.304 1.81 332 97.086 0.883 162Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPEN DIX 9 (cont) Organ weights

- individual values (g)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group /Sex Animal

Number Terminal

Body weight Br ain Br ain Heart Heart Heart Kidney s Kidney s Kidney s Relative to Body (%) Body (%) Br ain (%) Body (%) Br ain (%) 3M 3145 8200.0 52.729 0.643 47.779 0.583 91 66.020 0.805 125

3146 8100.0 53.527 0.661 56.406 0.696 105 61.114 0.754 114 3147 10900.0 56.169 0.515 67.921 0.623 121 93.088 0.854 166 3148 11700.0 61.709 0.527 76.826 0.657 124 77.042 0.658 125 3149 8300.0 53.890 0.649 53.191 0.641 99 54.656 0.659 101 3150 9900.0 59.927 0.605 58.436 0.590 98 77.605 0.784 129 3151 12600.0 55.373 0.439 69.335 0.550 125 87.525 0.695 158 3152 9100.0 59.061 0.649 58.582 0.644 99 63.647 0.699 108Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPEN DIX 9 (cont) O rg an weights

- individual values (g)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group /Sex Animal

Number Liver Liver Liver Lungs and Br onchi Lungs and

Br onchi Lungs and

Br onchi Relative to Body (%) Br ain (%) Body (%) Br ain (%) 3M 3145 192.425 2.35 365 83.127 1.014 158

3146 185.388 2.29 346 80.181 0.990 150 3147 257.695 2.36 459 79.237 0.727 141 3148 316.082 2.70 512 91.052 0.778 148 3149 189.563 2.28 352 67.034 0.808 124 3150 199.843 2.02 333 73.318 0.741 122 3151 321.390 2.55 580 110.988 0.881 200 3152 197.748 2.17 335 79.156 0.870 134Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPEN DIX 9 (cont) Organ weights

- individual values (g)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group /Sex Animal

Number Terminal

Body weight Br ain Br ain Heart Heart Heart Kidney s Kidney s Kidney s Relative to Body (%) Body (%) Br ain (%) Body (%) Br ain (%) 1F 1645 12190.0 54.125 0.444 45.920 0.377 84.8 55.131 0.452 101.9

1646 12070.0 65.697 0.544 49.573 0.411 75.5 57.268 0.474 87.2 1647 12430.0 61.489 0.495 52.563 0.423 85.5 50.989 0.410 82.9 1648 9720.0 57.768 0.594 44.912 0.462 77.7 39.380 0.405 68.2 1649 13500.0 63.982 0.474 63.811 0.473 99.7 63.415 0.470 99.1 1650 11120 .0 57.095 0.513 45.403 0.408 79.5 54.964 0.494 96.3 1651 10390.0 59.444 0.572 43.061 0.414 72.4 47.383 0.456 79.7 1652 11150.0 66.085 0.593 61.217 0.549 92.6 57.133 0.512 86.5 2F 2645 9720.0 53.390 0.549 46.269 0.476 86.7 39.017 0.401 73.1

2646 13820.0 57.386 0.415 53.981 0.391 94.1 69.130 0.500 120.5 2647 9430.0 54.758 0.581 49.153 0.521 89.8 53.766 0.570 98.2 2648 10870.0 59.925 0.551 51.374 0.473 85.7 52.227 0.480 87.2 2649 12530.0 59.725 0.477 54.158 0.432 90.7 52.535 0. 419 88.0 2650 10210.0 55.881 0.547 45.187 0.443 80.9 45.933 0.450 82.2 2651 12170.0 63.728 0.524 51.262 0.421 80.4 54.831 0.451 86.0 2652 9920.0 54.535 0.550 40.896 0.412 75.0 51.401 0.518 94.3Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPEN DIX 9 (cont) Organ weights

- individual values (g)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group /Sex Animal

Number Liver Liver Liver Lungs and Br onchi Lungs and

Br onchi Lungs and

Br onchi Relative to Body (%) Br ain (%) Body (%) Br ain (%) 1F 1645 252.236 2.07 466 81.282 0.667 150

1646 220.168 1.82 335 77.795 0.645 118 1647 265.209 2.13 431 97.657 0.786 159 1648 211.665 2.18 366 71.000 0.730 123 1649 247.886 1.84 387 89.062 0.660 139 1650 229.358 2.06 402 78.878 0.709 1 38 1651 179.302 1.73 302 83.324 0.802 140 1652 183.885 1.65 278 85.568 0.767 129 2F 2645 195.165 2.01 366 74.840 0.770 140

2646 301.660 2.18 526 91.586 0.663 160 2647 239.892 2.54 438 68.762 0.729 126 2648 213.415 1.96 356 94.470 0.869 158 2649 318.409 2.54 533 93.523 0.746 157 2650 196.021 1.92 351 74.844 0.733 134 2651 294.424 2.42 462 83.438 0.686 131 2652 261.228 2.63 479 NW
- -
NW
- Not weighedSponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPEN DIX 9 (cont) Organ weights

- individual values (g)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group /Sex Animal

Number Terminal

Body weight Br ain Br ain Heart Heart Heart Kidney s Kidney s Kidney s Relative to Body (%) Body (%) Br ain (%) Body (%) Br ain (%) 3 F 3645 12510.0 57.308 0.458 51.633 0.413 90.1 60.227 0.481 105.1

3646 12010.0 48.665 0.405 45.524 0.379 93.5 69.302 0.577 142.4 3647 9270.0 50.597 0.546 54.672 0.590 108.1 33.672 0.363 66.5 3648 12220.0 60.602 0.496 59.313 0.485 97.9 55.958 0.458 92.3 3649 11030.0 58.433 0.530 45.391 0.412 77.7 48.202 0.437 82.5 3650 9550.0 53.533 0.561 54.307 0.569 101.4 45.051 0.472 84.2 3651 13430.0 55.615 0.414 60.710 0.452 109.2 61.406 0.457 110.4 3652 11740.0 58.114 0.495 42.824 0.365 73.7 47.493 0.405 81.7Sponsor reference number: Huntingdon Life Sciences: 13
- 6434 APPEN DIX 9 (cont) Organ weights

- individual values (g)

Vehicle Control HFO -1234yf Dose Group 1 2 3 Dose (ppm) 5000 10000 Group /Sex Animal

Number Liver Liver Liver Lungs and Br onchi Lungs and

Br onchi Lu ngs and

Br onchi Relative to Body (%) Br ain (%) Body (%) Br ain (%) 3F 3645 307.481 2.46 537 98.977 0.791 173

3646 285.991 2.38 588 87.674 0.730 180 3647 222.885 2.40 441 79.615 0.859 157 3648 267.733 2.19 442 88.356 0.723 146 3649 264.183 2.40 452 90.383 0.819 155 3650 201.229 2.11 376 78.417 0.821 146 3651 358.243 2.67 644 105.675 0.787 190 3652 268.751 2.29 462 65.975 0.562 114Sponsor reference number:Huntingdon Life Sciences: 13-6434APPENDIX 10 Macropathology - individual findingsVehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Animal Day (Week)/Sex Number of Death Phase TissueFindings1M 1145S1 29 (5) Treatment Lungs and BronchiDarkarea(s), right cranial lobe, red, diffuse, notedRemainder of animalNo macropathology findings1146S1 29 (5) Treatment All tissuesNo macropathology findings1147S1 29 (5) Treatment All tissuesNo macropathology findings1148S1 29 (5) Treatment All tissuesNo macropathology findings1149S1 29 (5) Treatment All tissuesNo macropathology findings1150S1 29 (5) Treatment All tissuesNo macropathology findings1151S1 29 (5) Treatment All tissuesNo macropathology findings1152S1 29 (5) Treatment All tissuesNo macropathology findings2M 2145S1 29 (5) Treatment All tissuesNo macropathology findingsS1 - Scheduled Euthanasia 1Sponsor reference number:Huntingdon Life Sciences: 13-6434APPENDIX 10 (cont) Macropathology - individual findingsVehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Animal Day (Week)/Sex Number of Death Phase TissueFindings2M 2146S1 29 (5) Treatment All tissuesNo macropathology findings2147WE 16 (3) Treatment ColonAbnormal contents, material, clear, gelatinousHeartThrombus, left ventricle, red, 10x30mm, 1 (one)Thrombus, right ventricle, red, 20x40mm, 1 (one)RectumProlapse,notedRemainder of animalNo macropathology findings2149S1 29 (5) Treatment All tissuesNo macropathology findings2150S1 29 (5) Treatment All tissuesNo macropathology findings2151S1 29 (5) Treatment All tissuesNo macropathology findings2152S1 29 (5) Treatment All tissuesNo macropathology findingsS1 - Scheduled Euthanasia 1, WE- Euthanized for welfare reasonsSponsor reference number:Huntingdon Life Sciences: 13-6434APPENDIX 10 (cont) Macropathology - individual findingsVehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Animal Day (Week)/Sex Number of Death Phase TissueFindings2M 2153S1 29 (5) Treatment All tissuesNo macropathology findings3M 3145S1 29 (5) Treatment All tissuesNo macropathology findings3146S1 29 (5) Treatment All tissuesNo macropathology findings3147S1 29 (5) Treatment All tissuesNo macropathology findings3148S1 29 (5) Treatment HeartPericaridial Fluid, clear (increased.)Remainder of animalNo macropathology findings3149S1 29 (5) Treatment All tissuesNo macropathology findings3150S1 29 (5) Treatment All tissuesNo macropathology findings3151S1 29 (5) Treatment Lungs and BronchiDark area(s), all lobes, red, </=1mm, 5+ (many)Remainder of animalNo macropathology findingsS1 - Scheduled Euthanasia 1Sponsor reference number:Huntingdon Life Sciences: 13-6434APPENDIX 10 (cont) Macropathology - individual findingsVehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Animal Day (Week)/Sex Number of Death Phase TissueFindings3M 3152S1 29 (5) Treatment HeartAdhesion(s),pericardium, focal, left, noted (adhered to leftventricle.)RectumDark area(s), mucosa, lower, red, </=1mm, 5+ (many)Remainder of animalNo macropathology findingsS1 - Scheduled Euthanasia 1Sponsor reference number:Huntingdon Life Sciences: 13-6434APPENDIX 10 (cont) Macropathology - individual findingsVehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Animal Day (Week)/Sex Number of Death Phase TissueFindings1F 1645S1 29 (5) Treatment All tissuesNo macropathology findings1646S1 29 (5) Treatment All tissuesNo macropathology findings1647S1 29 (5) Treatment All tissuesNo macropathology findings1648S1 29 (5) Treatment All tissuesNo macropathology findings1649S1 29 (5) Treatment All tissuesNo macropathology findings1650S1 29 (5) Treatment All tissuesNo macropathology findings1651S1 29 (5) Treatment All tissuesNo macropathology findings1652S1 29 (5) Treatment KidneysCyst(s), caudal pole, right, clear, 10-19mm, 2-5 (few)Remainder of animalNo macropathology findings2F 2645S1 29 (5) Treatment All tissuesNo macropathology findingsS1 - Scheduled Euthanasia 1Sponsor reference number:Huntingdon Life Sciences: 13-6434APPENDIX 10 (cont) Macropathology - individual findingsVehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Animal Day (Week)/Sex Number of Death Phase TissueFindings2F 2646S1 29 (5) Treatment All tissuesNo macropathology findings2647S1 29 (5) Treatment All tissuesNo macropathology findings2648S1 29 (5) Treatment StomachDark area(s), cardiac region, mucosa, red, 10-19mm, 2-5 (few)Remainder of animalNo macropathology findings2649S1 29 (5) Treatment Lungs and BronchiDark area(s), all lobes, 2-9mm, 5+ (many)Remainder of animalNo macropathology findings2650S1 29 (5) Treatment All tissuesNo macropathology findings2651S1 29 (5) Treatment Lymph Node, Mandibular Dark, bilateralRemainder of animalNo macropathology findings2652S1 29 (5) Treatment All tissuesNo macropathology findingsS1 - Scheduled Euthanasia 1Sponsor reference number:Huntingdon Life Sciences: 13-6434APPENDIX 10 (cont) Macropathology - individual findingsVehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Animal Day (Week)/Sex Number of Death Phase TissueFindings3F 3645S1 29 (5) Treatment All tissuesNo macropathology findings3646S1 29 (5) Treatment Lungs and BronchiDark area(s), all lobes, red, 2-9mm, 5+ (many)Remainder of animalNo macropathology findings3647S1 29 (5) Treatment All tissuesNo macropathology findings3648S1 29 (5) Treatment Lymph Node, Mandibular Dark, bilateralRemainder of animalNo macropathology findings3649S1 29 (5) Treatment All tissuesNo macropathology findings3650S1 29 (5) Treatment All tissuesNo macropathology findings3651S1 29 (5) Treatment Lungs and BronchiDark area(s), all lobes, red, </=1mm, notedS1 - Scheduled Euthanasia 1Sponsor reference number:Huntingdon Life Sciences: 13-6434APPENDIX 10 (cont) Macropathology - individual findingsVehicle Control HFO-1234yfDose Group 1 2 3Dose (ppm) 5000 10000Group Animal Day (Week)/Sex Number of Death Phase TissueFindings3F 3651S1 29 (5) Treatment StomachDark area(s),cardiac region, mucosa, red, 10-19mm, 2-5 (few)Dark area(s), pylorus, mucosa, red, 2-9mm, 1 (one) (raised)Remainder of animalNo macropathology findings3652S1 29 (5) Treatment All tissuesNo macropathology findingsS1 - Scheduled Euthanasia 1Sponsor reference number: Huntingdon Life Sciences: 13-6434 

### Annex 1 Certificates of analysisSponsor reference number: Huntingdon Life Sciences : 13
- 6434 

### Annex **2 Aerosol technology report** Sponsor reference number: Huntingdon Life Sciences: 13
- 6434

1 

### Working for a better future



## Aerosol Technology R eport

HLS study number: 13- 643 4 Sponsor study number: Version: Final Date: 17 January 2014

### SIGNATURE **PAGE Sponsor**  **reference number:**  **Huntingdon Life**  **Sciences: 13-6434** 
**The following**  **scientist was**  **responsible for**  **this portion**  **of the**  **study:**

**Date**

**2**Sponsor reference number: Huntingdon Life Sciences: 13
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3 

# 1. P re - study Atmosphere Characterization Inhalation exposure system characterized including determinations of:
• Achieved concentration
• Homogeneity of test substance distribution in the chamber 

# 2. Test Substance Handling and Processing for A tmosphere Generation As supplied , HFO
- 1234 yf metered directly from Sponsor cylinder as a gas. 

# 3. Exposure System A schematic of the exposure system is presented in Figure 1

. Components of the exposure system:
• W hole
- body exposure chambers : o Control Group – 1500 L internal volume o Treated Groups – 1000 L internal volume o Five separate chambers for Group 1

 

### Two chambers for males and two for females (Days 1 to 17 )

 

### Three chambers for males and two for females (Days 18 to 28 ) o Four separate chambers for each of Groups 2 and 3

 

### Two chambers for males and two for females
• Animal Restraint: o No direct restraint employed, animals free to move within the containment volume o Inhalation exposure chamber fitted with perforated rubber matting over a stainless steel floor grating o Group housed

 

### 4 animals/sex/chamber
• All Group 1 Female and two Group 1 Male chamber Days 1 to 17
• All Group 2 Female and one Group 2 Male chamber
• All Group 3 Male and Female chambers

 

### 3 animals/sex/chamber – single Group 2 Male chamber

 

### 1 animal/sex/chamber – single Group 1 Male chamber Days 18 to 28 o A nimal restrained separate from others for welfare reasons in each of Group 1 (male) and Group 2 (male)Sponsor reference number: Huntingdon Life Sciences: 13
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### o Chamber identification was as follows:

 

### Group 1: 101M (3 animals only starting Day 18), 102M, 101F, 102F

 

### Group 2: 201M (3 animals only starting Day 16), 202M, 201F, 202F

 

### Group 3: 301M, 302M, 301F, 302F

 

### An additional chamber introduced (103M) on Exposure Day 18 to permit separation of one animal for welfare reasons
• Atmosphere Ge neration System : o Single Sponsor cylinder for each of Groups 2 and 3 o Test substance metered as gas directly from a central Sponsor supplied cylinder to separate Mass Flowmeters for each male and female exposure chamber o Test substance flow monitored continuo usly using Mass Flowmeter displays and adjusted as required based on Infrared Gas Analyzer indicated concentration s o Group 1 exposed to r oom air only o Make
- up air for Groups 2 and 3 drawn passively from room environment by calibrated chamber exhaust
• Extract Airflow: o Drawn by in
- house extract system o Dra wn from base of exposure chamber o Filtered locally o Flow – individually calibrated to a target of 2 50 and 380 L/min ute for 1 000 and 1 5 00 L chambers, respectively
• Airflow Monitoring: o Magnehelic gauges; calibrated before study start and monitored continuously during exposures o D ifferential exposure chamber pressure recorded at 30 minute intervals 

# 4. Administration Exposure concentrations achieved by varying test substance flow rate

. Daily P rocedure:
• Miran Infra
- Red gas spectrophotometer calibration check performed
• Extract airflow runs continuously
• Pigs loaded i nto designated exposure chamber
• Sponsor cylinder flow (Groups 2 and 3) established
• Animals exposed for 6 hours o One animal in Group 1 (1148M) received shorter expo sures for welfare reasons on Days 16 and 17 ( 353 and 268 minutes, respectively )Sponsor reference number: Huntingdon Life Sciences: 13
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### • Exposure system operational pa rameters monitored continuously
• Chamber temperature, humidity , airflow rate and s tatic pressure documented every 30 minutes during exposure
• Genera tion terminated – test substance cylinder switched off
• Animals held in chambers for minimum 13 minute system clear out period after generation terminated
• Animals returned to home cage at end of exposure
• Animals exposed in the same chamber throughout the st udy 

# 5. Atmosphere Analysis

5.1 Concentration The atmosphere concentration was determined as follows:

• Atmosphere analysis - IR spectrophotometer
• Instrument and conditions - Wilks M iran 1A
- CVF ambient air analyzer o Wavelength – 3.2 6 μm (Groups 1 to 3) o Pathlength – 13.02 dial setting (Group 1 up to Exposure Day 22) 14.00 dial setting (Group 1 starting Exposure Day 23 , due to replacement of instrument , and Groups 2 to 3)
• Measurement frequency – a minimum of 4 samples/group / sex /exposure documented
• Sampl ing position rem ained constant ( animal breathing zone ) 

## 5.2 Chamber Temperature and Re lative Humidity Monitored using Extech Humidity and Thermometer gauges as follows:

• F requency – continuous monitoring; documented every 30 minutes
• Sample location – gauges located inside the e xposure chamber
• Gauge position remained constant 

## 5.3 Static Pressure Monitored using H 2 

### O Dwyer Magnehelic gauges as follows:

• F requency – continuous monitoring; documented every 30 minutes
• Gauge location – outside the exposure chamber 

## 5.4 Chamber Oxygen Levels Cham ber oxygen samples collected during habituation period as follows:

• Sample media – Servo Flex MiniMP (5200) Gas Analyzer
• Sample frequency – minimally one male and one female chamber
• Sample position remained constant (H1)Sponsor reference number: Huntingdon Life Sciences: 13
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## 5.5 Nominal Concentration Calculated daily as a summation of all test substance exposure chambers in each group . 

# 6. Data, Abbreviations and Calculations Data not presented here is retained in the study raw data and the HLS Archive. To minimize 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.



## 6.1 Abbreviations

Conc. = Mean atmosphere concentration ( ppm ) IR = In frared PPM = Parts per million SD = Standard Deviation A = Airflow D = Duration of exposure Wt = Weight °C = Degrees Celsius K = Kelvin L = L iter N/A = Not Applicable 

## 6.2 Calculations Each IR s pectrophotometer was calibrated using t est sub stance taken directly from the Sponsor cylinder. Absorbance measurements acquired by the IR spectrophotometer were used to calculate analyzed concentration (ppm) using a 3 rd 

### order fit subjected to least squares regression analysis. Nominal Conc

. (ppm) =



# 7. Results and Discussion Results are presented in Tables 1 to 3 of this report.Sponsor reference number: Huntingdon Life Sciences: 13
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## 7.1 Pre- study Oxygen Measurements Measured oxygen chamber levels were within protocol specifications above 19% (ranging between 21.1 to 21.2%). No additional oxygen measurements were required during the exposure period. 

## 7.2 Atmosphere Concentration Overall mean concentration s are presented in Table 1 and summarized below: Group Test Substance Atmosphere Concentration (ppm) Target Achieved Males Females 1 Air Control 0 0 0 2 HFO
- 1234 yf gas 50 00 5 190 5 100 3 HFO
- 1234 yf gas 10000 10200 10200 

### No HFO
- 1234 yf gas was detected in Group 1 samples. Mean atmosphere concentrations were 3.8% and 2.0% above target for Group 2 males and females, respectively; and 2. 0% above targe t for Group 3. The mean nominal concentration of 19100 ppm was 7 % less than the overall combined IR measured concentration of 20600 ppm for Group 2

. The mean nominal concentration of 39200 ppm was 4 % less than the overall combined IR measured concentratio n of 40800 ppm for Group 3. This was considered a reasonable experimental difference as seen previously at this laboratory. 

## 7.3 Chamber Temperature and Relative Humidity Overall mean chamber temperature and relative humidity data are presented in Table s 2 and 3 , and summari z ed below: Group Sex Chamber Number Temperature Relative Humidity ( °C ) (%) 1 Male 101M 21 59 102M 22 54 103M 21 52 Female 101F 23 54 102F 23 51 2 Male 201M 23 58 202M 24 59 Female 201F 24 55 202F 24 53Sponsor reference number: Huntingdon Life Sciences: 13
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### Group Sex Chamber Number Temperature Relative Humidity ( °C ) (%) 3 Male 301M 23 59 302M 23 60 Female 301F 23 56 302F 23 53 

### Chamber mean overall temperatures were within protocol specifications between 20 to 27 0 C. For the Group 1 chamber with only one animal (Chamber No. 103M) , the daily mean temperature was betw een 19.1 to 19.6 0 C on E xposure D ay s 1 8 to 20 - there was no evidence of impact on the study from this deviation

. Relative humidity was within protocol specifications between 30 to 70% on all occasions of measurements

. Relative humidity for the test subst ance groups was similar to the air control group.Sponsor reference number: Huntingdon Life Sciences: 13
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### F igure 1 Schematic of Inhalation Exposure SystemSponsor reference number: Huntingdon Life Sciences: 13
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### Table 1 Analytical Atmosphere Concentration – Individual, Mean Exposure and Nominal Values
Exposure Day Determined Concentration (ppm) a Nominal (ppm) a Group 1 Male Chambers Female Chambers 101M 102M 103M b Mean 101F 102F Mean 1 0 0
- 0
- - - N/A 2 0 0
- 0 0 0 0 N/A 3 0 0
- 0 0 0 0 N/A 4 0 0
- 0 0 0 0 N/A 5 0 0
- 0 0 0 0 N/A 6 0 0
- 0 0 0 0 N/A 7 0 0
- 0 0 0 0 N/A 8 0 0
- 0 0 0 0 N/A 9 0 0
- 0 0 0 0 N/A 10 0 0
- 0 0 0 0 N/A 11 0 0
- 0 0 0 0 N/A 12 0 0
- 0 0 0 0 N/A 13 0 0 - 0 0 0 0 N/A 14 0 0
- 0 0 0 0 N/A 15 0 0
- 0 0 0 0 N/A 16 0 0
- 0 0 0 0 N/A 17 0 0
- 0 0 0 0 N/A 18 0 0 0 0 0 0 0 N/A 19 0 0 0 0 0 0 0 N/A 20 0 0 0 0 0 0 0 N/A 21 0 0 0 0 0 0 0 N/A 22 0 0 0 0 0 0 0 N/A 23 0 0 0 0 0 0 0 N/A 24 0 0 0 0 0 0 0 N/A 25 0 0 0 0 0 0 0 N/A 26 0 0 0 0 0 0 0 N/A 27 0 0 0 0 0 0 0 N/A 28 0 0 0 0 0 0 0 N/A 29
- - - - 0 0 0 N/A Mean 0 0 0 0 0 0 0 N/A

SD
- - - - - - -
a Refer to Section 6 Data, Abbreviations and Calculations for details. b Animal 1148M was exposed in a separate chamber from Exposure Day 18 onward s.Sponsor reference number: Huntingdon Life Sciences: 13
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### Table 1 Analytical Atmosphere Concentration – Individual, Mean Exposure and Nominal Values (cont.)
Exposure Day Determined Concentration (ppm) a Nominal (ppm) a Group 2 Male Chambers Female Chambers 201M 202M Mean 201F 202F Mean 1 5400 5470 5440
- - - 9320 2 5460 5510 5490 5200 5040 5120 20000 3 5290 5360 5330 5200 5280 5240 19000 4 5140 5230 5190 5170 5230 5200 20000 5 5130 5290 5210 5110 5230 5170 19500 6 5180 5380 5280 5060 5070 5070 20900 7 5110 6170 5640 5110 4970 5040 24100 8 5290 5050 5170 5020 4970 5000 13900 9 5150 4930 5040 4910 4 990 4950 20000 10 5130 5010 5070 4780 5000 4890 21800 11 5120 5230 5180 4790 4870 4830 18100 12 5180 5190 5190 5430 5120 5280 21800 13 5170 5260 5220 5270 5150 5210 19500 14 5180 5190 5190 5110 5080 5100 17600 15 5020 4970 5000 5220 5220 5220 20900 16 5110 4930 5020 5410 5140 5280 19500 17 4940 5150 5050 5290 5070 5180 19500 18 4960 5030 5000 5200 5250 5230 21800 19 5030 5210 5120 5080 5080 5080 25100 20 5280 5220 5250 5470 4860 5170 18600 21 5200 5040 5120 5330 5080 5210 20000 22 5270 5010 514 0 4950 4860 4910 14900 23 5210 5260 5240 4780 4990 4890 20900 24 5100 5010 5060 4890 5240 5070 17200 25 5230 5020 5130 5190 5130 5160 26900 26 4910 4920 4920 5350 4920 5140 12100 27 5250 5380 5320 5410 4970 5190 27900 28 5390 5060 5230 5020 5170 5100 15800 29
- - - 4920 5040 4980 6010 Mean b 5170 5200 5190 5130 5070 5100 19100

SD 132.6 253.5 157.8 201.8 122.8 126.1 4680.4

a Refer to Section 6 Data, Abbreviations and Calculations for details. b Means are rounded to three significant figures.Sponsor reference number: Huntingdon Life Sciences: 13
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### Table 1 Analytical Atmosphere Concentration – Individual, Mean Exposure and Nominal Values (cont.)
Exposure Day Determined Concentration (ppm) a Nominal (ppm) a Group 3 Male Chambers Female Chambers 301M 302M Mean 301F 302F Mean 1 10300 10600 10500
- - - 19600 2 9670 10000 9840 10200 10700 10500 39600 3 9520 10300 9910 10100 9980 10000 38200 4 10000 10200 10100 10000 9430 9720 39200 5 10100 10300 10200 10200 9970 10100 39600 6 9910 10400 10200 10400 9850 10100 43800 7 10300 10100 10200 10200 9280 9740 39200 8 9850 10500 10200 10100 9750 9930 39600 9 9690 9910 9800 10100 9520 9810 40600 10 10300 9910 10100 10100 10100 10100 41500 11 10800 9950 10400 10200 10800 10500 42900 12 10600 10000 10300 10300 10200 10300 41000 13 10400 10100 10300 10100 10300 10200 40600 14 10400 9850 10100 10100 9820 10000 38700 15 10600 9580 10100 10500 10100 10300 40100 16 10800 10200 10500 10100 10000 10100 42000 17 10500 9890 10200 10400 9470 9900 41000 18 10700 10000 10400 10100 10200 1 0200 41500 19 10200 9920 10100 10900 10700 10800 42000 20 10400 9910 10200 10300 10400 10400 41000 21 10300 9830 10100 10900 9770 10300 41000 22 10500 9420 10000 10600 10200 10400 42000 23 10300 9720 10000 10400 10400 10400 40600 24 10200 10100 10200 10900 10800 10900 41500 25 10500 9940 10200 10700 10200 10500 40600 26 10300 9950 10100 9700 9930 9800 41000 27 10600 9730 10200 10300 10700 10500 38700 28 10600 9390 10000 10100 9820 10000 40100 29
- - - 10300 10300 10300 19700 Mean b 10300 9990 10200 10300 10100 10200 39200

SD 336.2 285.2 171.8 288.7 418.8 301.0 5562.3

a Refer to Section 6 Data, Abbreviations and Calculations for details. b Means are rounded to three significant figures.Sponsor reference number: Huntingdon Life Sciences: 13
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### Table 2 Chamber Temperature - Mean Values

Exposure Day Temperature (°C) a Group 1 Male Chambers Female Chambers 101M 102M 103M b 101F 102F 1 20.8 22.9
- - - 2 20.2 22.9
- 23.4 23.2 3 20.8 23.2
- 23.0 23.2 4 21.1 23.2
- 23.7 23.5 5 20.8 22.4
- 22.9 22.9 6 21.4 22.8
- 23. 4 23.2 7 20.4 22.3
- 22.6 22.8 8 20.7 21.9
- 22.6 22.4 9 20.6 22.1
- 22.9 22.6 10 20.5 21.8
- 22.5 22.3 11 19.9 21.5
- 22.7 22.0 12 20.8 22.2
- 22.8 22.4 13 20.2 22.1
- 22.4 22.4 14 19.9 22.4
- 22.9 22.6 15 20.9 22.6
- 23.0 22.5 16 21.0 22.7
- 22.4 22.7 17 20.6 22.4
- 23.2 22.7 18 20.2 22.5 19.6 23.2 22.4 19 20.0 22.2 19.1 22.5 22.3 20 20.2 22.9 19.5 23.1 22.3 21 21.3 23.1 20.8 24.0 23.5 22 22.0 22.8 21.8 23.7 22.8 23 21.6 22.3 20.5 22.8 22.1 24 21.5 22.2 21.2 22.0 22.0 25 21.3 21.9 21.1 22.7 22.1 26 21.2 21.8 21.0 22.6 22.1 27 22.0 22.8 21.0 23.4 22.4 28 21.3 22.6 20.6 22.3 22.5 29
- - - 22.7 22.0 Mean 20.8 22.4 20.6 22.9 22.6

SD 0.59 0.45 0.83 0.47 0.44

a Refer to Section 6 Data, Abbreviations and Calculat ions for details. b Animal 1148M was exposed in a separate chamber from Exposure Day 18 onwards.Sponsor reference number: Huntingdon Life Sciences: 13
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### Table 2 Chamber Temperature - Mean Values (cont.)

Exposure Day Temperature (°C) a Group 2 Male Chambers Female Chambers 201M 202M 201F 202F 1 23 .0 23.9
- - 2 23.6 24.1 24.3 24.0 3 23.9 24.4 24.2 24.2 4 24.3 24.8 25.4 24.8 5 23.9 24.5 24.7 24.6 6 24.0 24.7 24.7 24.4 7 22.6 23.6 23.2 23.4 8 22.6 23.6 23.9 23.5 9 23.1 23.5 24.2 23.9 10 23.2 23.8 23.7 23.2 11 23.0 23.5 23.7 23.7 12 22.8 23. 9 23.9 23.8 13 22.7 23.7 24.1 23.5 14 23.3 23.7 24.3 24.1 15 23.0 23.7 24.0 23.9 16 22.6 24.1 24.4 24.4 17 22.1 23.5 24.4 24.6 18 21.6 23.5 23.8 24.5 19 21.4 23.5 23.7 24.2 20 21.5 23.5 24.2 24.4 21 22.1 23.9 24.7 25.0 22 22.0 23.8 23.7 24.3 23 22.1 23.4 23.4 23.5 24 21.4 22.9 23.3 23.7 25 21.1 22.5 23.3 23.1 26 21.8 23.1 23.0 23.4 27 22.1 22.9 23.2 23.3 28 22.5 24.0 24.7 24.5 29
- - 23.1 23.9 Mean 22.6 23.7 24.0 24.0

SD 0.86 0.52 0.59 0.52

a Refer to Section 6 Data, Abbrevia tions and Calculations for details.Sponsor reference number: Huntingdon Life Sciences: 13
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### Table 2 Chamber Temperature - Mean Values (cont.)

Exposure Day Temperature (°C) a Group 3 Male Chambers Female Chambers 301M 302M 301F 302F 1 23.4 23.9
- - 2 22.5 23.1 22.9 23.3 3 23.8 24.0 23.3 23.9 4 2 4.1 24.5 23.9 24.9 5 23.8 23.9 23.4 24.3 6 23.9 24.1 23.8 24.6 7 22.0 22.3 22.0 22.8 8 22.5 22.5 21.7 22.9 9 22.4 23.0 22.3 22.9 10 22.9 22.7 22.2 23.3 11 22.2 22.2 22.0 23.3 12 22.4 22.9 22.8 22.8 13 22.8 23.1 22.5 23.3 14 23.2 22.2 22.5 23.7 1 5 23.6 22.9 22.8 24.1 16 24.2 23.3 23.7 24.5 17 23.4 23.2 23.0 24.0 18 23.2 22.8 22.5 23.4 19 21.9 21.6 22.5 23.2 20 23.6 23.0 23.0 23.5 21 23.5 22.7 23.1 23.2 22 23.1 22.7 22.6 23.3 23 22.2 22.0 21.4 22.4 24 22.5 22.2 22.1 22.8 25 22.5 22.6 22.1 22.5 26 22.6 22.3 22.1 22.8 27 22.6 22.1 21.6 22.8 28 22.9 22.3 22.7 23.1 29
- - 22.1 22.9 Mean 23.0 22.9 22.6 23.4

SD 0.66 0.71 0.65 0.65

a Refer to Section 6 Data, Abbreviations and Calculations for details.Sponsor reference number: Huntingdon Life Sciences: 13
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### Table 3 Chamber Relative Humidity - Mean Values

Exposure Day Relative Humidity (%) a Group 1 Male Chambers Female Chambers 101M 102M 103M b 101F 102F 1 64 56
- - - 2 63 56
- 55 51 3 67 60
- 57 54 4 66 59
- 59 53 5 65 60
- 60 55 6 68 62
- 61 61 7 58 53
- 53 49 8 57 53
- 52 49 9 62 55
- 56 52 10 65 58
- 58 54 11 57 54
- 52 50 12 60 56
- 55 52 13 63 57
- 57 52 14 59 54
- 53 51 15 63 57
- 56 54 16 66 60
- 60 55 17 57 51
- 50 48 18 55 51 55 50 48 19 53 48 52 48 45 20 53 48 51 47 46 21 56 52 54 52 50 22 51 52 49 52 48 23 51 51 51 49 46 24 52 54 50 54 50 25 52 53 49 55 50 26 52 54 52 54 52 27 52 50 52 50 48 28 53 51 52 49 47 29
- - - 53 50 Mean 59 5 4 52 54 51

SD 5.7 3.7 1.9 3.8 3.4

a Refer to Section 6 Data, Abbreviations and Calcul ations for details. b Animal 1148M was exposed in a separate chamber from Exposure Day 18 onwards.Sponsor reference number: Huntingdon Life Sciences: 13
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### Table 3 Chamber Relative Humidity - Mean Values (cont.)

Exposure Day Relative Humidity (%) a Group 2 Male Chambers Female Chambers 2 01M 2 02M 2 01F 2 02 F 1 60 64
- - 2 60 62 58 55 3 61 63 60 59 4 59 62 57 56 5 62 61 60 59 6 61 64 60 59 7 57 60 54 54 8 56 61 53 52 9 58 59 54 54 10 61 63 59 59 11 53 57 51 52 12 58 60 56 55 13 60 61 56 54 14 57 60 56 54 15 60 61 59 57 16 63 62 60 58 17 55 58 53 51 18 58 59 54 51 19 53 55 50 50 20 61 59 56 51 21 62 62 54 52 22 54 53 52 51 23 48 50 45 46 24 55 55 50 49 25 59 60 54 50 26 57 60 52 52 27 51 52 49 48 28 51 52 50 46 29
- - 58 53 Mean 58 59 55 53

SD 3.8 3.8 3.9 3.8

a Refer to Section 6 Data, Abbreviations and Calculations for details.Sponsor reference number: Huntingdon Life Sciences: 13
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18 

### Table 3 Chamber Relative Humidity - Mean Values (cont.)

Exposure Day Relative Humidity (%) a Group 3 Male Chambers Female Chambers 301M 302M 301F 302F 1 62 65
- - 2 65 65 60 58 3 63 66 62 58 4 62 63 59 54 5 61 63 60 57 6 63 64 61 58 7 59 61 57 55 8 60 60 57 55 9 61 63 58 56 10 64 65 62 57 11 60 59 56 52 12 63 65 57 57 13 61 62 58 55 14 59 61 58 55 15 61 63 61 57 16 62 64 60 58 17 58 59 55 53 18 56 58 55 52 19 56 58 52 52 20 56 60 55 54 21 62 62 57 56 22 52 56 52 49 23 50 51 46 45 24 52 54 49 46 25 55 55 51 49 26 56 60 53 49 27 50 52 48 46 28 52 52 48 47 29
- - 57 55 Mean 59 60 56 53

SD 4.4 4.3 4.5 4.1

a Refer to Section 6 Data, Abbrevi ations and Calculations for details.Sponsor reference number: Huntingdon Life Sciences : 13
- 6434 

### Annex **3 Clinical pathology report** Sponsor reference number: Huntingdon Life Sciences : 13
- 6434 

### Annex **4 Anatomic pathology report**  **– organ weights** Sponsor reference number: Huntingdon Life Sciences : 13
- 6434 

### Annex **5 Anatomic pathology report**  **– macroscopic and histopathology** Final Pathology Report HLS Study Number 13-6434

2 1/17/2014 TABLE OF CONTENTS 1.0 Executive Summary ......................................................................................................... 3 2.0 Introduction ....................................................................................................................... 4 2.1 Protocol .......................................................................................................................... 4 2.2 Objective ........................................................................................................................ 4 3.0 Methods ............................................................................................................................. 4 3.1 Compliance Statement ................................................................................................... 4 3.2 Study Design .................................................................................................................. 4 Table A. Study Design .......................................................................................................... 4 3.3 Necropsy ........................................................................................................................ 4 3.4 Histological Processing .................................................................................................. 5 4.0 Results ............................................................................................................................... 5 4.1 Animal Mortality .............................................................................................................. 5 4.2 Macroscopic Findings .................................................................................................... 5 4.3 Microscopic Evaluation .................................................................................................. 6 5.0 Conclusions ...................................................................................................................... 6 REFERENCES ............................................................................................................................ 7 Appendix A. Histopathology Incidence Tables .......................................................................... 8 Appendix B. Peer Review Statement ......................................................................................... 74 Appendix C. Quality Assurance Statement .............................................................................. 76Final Pathology Report HLS Study Number 13-6434

3 1/17/2014 1.0 Executive Summary The purpose of the study was to assess the toxicity (including cardiotoxicity and/or skeletal muscle toxicity) of the test substance when administered via whole-body inhalation to minipigs for 28 days. Methods: According to the protocol, 48 minipigs (24 males and 24 females) were assigned to three treatment groups in this study. Animals were exposed to clean air or the test substance by inhalation via whole body exposure for 6 hours per day for 7 days per week for up to 28 days. On Day 29, all surviving animals were euthanized and subjected to a complete gross necropsy at termination. Unscheduled deaths were also subjected to necropsy. Protocol specified tissues were collected and processed, embedded in paraffin, sectioned and stained with hematoxylin and eosin (H&E) at HLS. The resulting slides from all animals including unscheduled deaths were forwarded to HSRL and evaluated via light microscopy by at HSRL. A peer review was performed by of Experimental Pathology Laboratories, Sterling, VA. Conclusion: The purpose of the study was to assess the toxicity (including cardiotoxicity and/or skeletal muscle toxicity) of the test substance when administered via whole-body inhalation to minipigs for 28 days. At Day 29, there were no HFO-1234yf-related microscopic findings involving the heart (left ventricle, right ventricle, and septum) and skeletal muscle (rectus femoris, psoas, and soleus muscles as well as the diaphragm). Therefore, under the conditions of this study, there was no microscopic evidence of cardiotoxicity or skeletal muscle toxicity following whole body inhalation of the test substance at up to 10000 ppm for 28 days in male and female Gottingen minipigs.Final Pathology Report HLS Study Number 13-6434

4 1/17/2014 2.0 Introduction 2.1 Protocol This report presents the results of the microscopic evaluation of protocol-required tissues to assess the toxicity of HFO-1234yf when administered via inhalation to minipigs, HLS Study Number 13-6434, for All in-life procedures, tissue harvests, and histology were performed at HLS under the direction of , Study Director. Microscopic evaluation was completed by of HSRL. 2.2 Objective The purpose of the study was to assess the toxicity (including cardiotoxicity and/or skeletal muscle toxicity) of the test substance when administered via whole-body inhalation to minipigs for 28 days. 3.0 Methods 3.1 Compliance Statement The portions of this study conducted at HSRL were performed according to the Organization for Economic Cooperation and Development (OECD) Principles of Good Laboratory Practices ENV/MC/CHEM (98)17. An electronic copy of this report in portable document format (PDF) will be provided to HLS in addition to the hard copy. The PDF is a representation of the pathology report hard copy. However, only the signed hard copy of the pathology report is considered raw data. 3.2 Study Design According to the protocol, 48 animals (24 males and 24 females) were divided into three treatment groups. The study design is further described in Table A. Table A. Study Design
Group Exposure Level a Number of Animals Total on Study Terminal NecropsyDay 28 ppm mg/L Male Female Male Female 1 0 0 8 8 8 8 2 5000 26 8 8 8 8 3 10000 50 8 8 8 8 a Exposures were 6 hours per day for 7 days per week for up to 28 days. Exposure levels were expressed as ppm (part per million of test substance in air) and equivalent mg/L (mg of test substance per liter of air) of test substance but study results were reported as ppm. 3.3 Necropsy According to the protocol, all surviving animals were euthanized and subjected to a complete gross necropsy on Day 29. Unscheduled deaths were also subjected to necropsy. Necropsies consisted of an external examination as well as a detailed internal examination. At scheduled termination, the following organs (when present) were weighed before fixation (paired organsFinal Pathology Report HLS Study Number 13-6434

5 1/17/2014 were weighed together): brain, heart, kidneys, liver, and lungs (with mainstem bronchi). For all animals, the organs listed below were excised and preserved in 10% neutral buffered formalin. Brain Heart (left and right ventricles and septum)* Kidneys Liver Lungs (with mainstem bronchi) Muscle (diaphragm and bilateral psoas, bilateral rectus femoris and soleus)* Gross lesions * For histopathological evaluation 3.4 Histological Processing Protocol required tissues were processed, embedded in paraffin, sectioned and stained with hematoxylin and eosin (H&E) at HLS. A total of eight longitudinal sections were sampled from the heart. A cross section and a longitudinal section of three sample areas (midbody and towards each end) of the left and right rectus femoris were taken. In addition, a cross and longitudinal section of the psoas muscle, diaphragm, and soleus muscle were taken. All microscopic slides were forwarded to HSRL and evaluated by directly into PathData ® Systems (PDS) at HSRL. Microscopic findings and microscopic grading definitions are presented in the Histopathology Incidence Tables portion of this report, where the following abbreviations apply due to PDS character limitations: AOFT= Animal Organ Finding Table HEART (LEFT VENTR.)= Heart (Left Ventricle) HEART (L VENT. FREE)= Heart (Left Ventricular Free Wall) HEART (RIGHT VENTR.)= Heart (Right Ventricle) MUSCLE (L REC FEMOR)= Muscle (Left Rectus Femoris) MUSCLE (R REC FEMOR)= Muscle (Right Rectus Femoris) MUSCLE (RIGHT SOLEUS= Muscle (Right Soleus) A peer review was performed by Experimental Pathology Laboratories, Sterling, VA. 4.0 Results 4.1 Animal Mortality Group 2 male Animal 2147 was euthanized for welfare reasons on Day 16. At necropsy for this animal, the Testing Facility documented a prolapse of the rectum; the presence of clear, gelatinous material in the colon; and a single thrombus in the left ventricle as well as a single thrombus in the right ventricle. There was no evidence to suggest that these findings were associated with exposure to the test substance. 4.2 Macroscopic Findings At Day 29, there were a few sporadic macroscopic findings reported by the Testing Facility but there were no incidence patterns/trends for these findings to suggest a relationship to test substance exposure. Macroscopic findings reported included the following: Group 1 male Animal 1145 with diffuse red, dark areas of the right cranial lung lobe; Group 1 female Animal 1652 with a few, clear, 10-19 mm cysts involving the caudal pole of the right kidney; Group 2 female Animal 2648 with a few, 10-19 mm, red, dark areas involving the cardiac region of the gastric mucosa; Group 2 female Animal 2649 with many 2-9 mm dark areas involving all lung lobes; Group 2 female Animal 2651 with bilateral dark mandibular lymph nodes; Group 3 male Animal 3148 with increased pericardial fluid; Group 3 male Animal 3151 with many small ( ≤ 1 mm), red, dark areas involving all lungFinal Pathology Report HLS Study Number 13-6434

6 1/17/2014 lobes; Group 3 male Animal 3152 with focal adhesion of the pericardium to the left ventricle and many small ( ≤ 1 mm), red, dark areas involving the mucosa of the lower rectum; Group 3 female Animal 3646 with many 2-9 mm dark areas involving all lung lobes; Group 3 female Animal 3648 with bilateral dark mandibular lymph nodes; and Group 3 female Animal 3651 with many small ( ≤ 1 mm), red, dark areas involving all lung lobes as well as a few, 10-19 mm, red, dark areas involving the cardiac region of the gastric mucosa and one, raised, 2-9 mm dark area of the gastric mucosa of the pylorus. Histopathological evaluation of these macroscopic findings was not required per the protocol. 4.3 Microscopic Evaluation There were no HFO-1234yf-related microscopic findings involving the heart (left ventricle, right ventricle, and septum) and skeletal muscle (rectus femoris, psoas, and soleus muscles as well as the diaphragm). Microscopic observations involving the heart were of sporadic incidence and primarily limited to cellular infiltration (mononuclear or mixed cell) involving the epicardium, myocardium, and/or endocardium. These observations were of minimal, insignificant intensity and showed no predilection as to anatomic site. An additional irrelevant finding included the single occurrence of focal pigmented macrophages within the epicardium in a single cardiac specimen. For skeletal muscle, microscopic observations included sporadic mononuclear cell infiltration, neutrophil infiltration, histiocytic infiltration, cytoplasmic basophilia of myofibers, and myofiber degeneration involving the rectus femoris, soleus, psoas, and/or diaphragmatic muscle. These findings were of limited intensity as they predominantly occurred with minimal degree. A single animal, Group 2 female 2647, had minimal to moderate myofiber atrophy involving the rectus femoris (right and left), soleus (right and left), and psoas (right and left) muscles that was accompanied by slight myofiber mineralization of the left psoas muscle. As these atrophic changes were only observed in a single female at the low dose exposure level, they were deemed to be unrelated to HFO-1234yf. The aforementioned cardiac and skeletal muscle changes were incidental and many were those that can be observed in the age of Gottingen minipigs used in this study (McInnes, 2012; Svendson et al, 1998). Overall, these microscopic observations showed no consistent patterns/trends involving incidence or intensity to suggest a relationship to test substance exposure. 5.0 Conclusions The purpose of the study was to assess the toxicity (including cardiotoxicity and/or skeletal muscle toxicity) of the test substance when administered via whole-body inhalation to minipigs for 28 days. At Day 29, there were no HFO-1234yf-related microscopic findings involving the heart (left ventricle, right ventricle, and septum) and skeletal muscle (rectus femoris, psoas, and soleus muscles as well as the diaphragm). Therefore, under the conditions of this study, there was no microscopic evidence of cardiotoxicity or skeletal muscle toxicity following whole body inhalation of the test substance at up to 10000 ppm for 28 days in male and female Gottingen minipigs.Final Pathology Report HLS Study Number 13-6434

8 1/17/2014 Appendix A. Histopathology Incidence TablesPATHOLOGY REPORT PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ EXPLANATION OF CODES AND SYMBOLS
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
CODES AND SYMBOLS USED AT ANIMAL LEVEL:
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ M = Male animal F = Female animal K0 = Terminal sacrifice group + = Intercurrent death/sacrificed moribund +2 = Sacrificed moribund
CODES AND SYMBOLS USED AT ORGAN LEVEL:
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ ' = Histologic examination not required + = Organ examined, findings present - = Organ examined, no pathologic findings noted (AOFT only)
CODES AND SYMBOLS USED AT FINDING LEVEL:
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ GRADE 1 = Minimal / very few / very small GRADE 2 = Slight / few / small GRADE 3 = Moderate / moderate number / moderate size EXPLANATION OF TABLE TEXT(S) USED AT FINDING LEVEL:
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ HEART (LEFT VENTRICULAR FREE WALL) - Mix. cell inf.:endo. = Mixed cell infiltration:endocardium - Mono. cell inf.:epi. = Mononuclear cell infiltration:epicardium - Mono. cell inf.:myo. = Mononuclear cell infiltration:myocardium - Pigment = Pigment:macrophage cytoplasm HEART (LEFT VENTRICLE) - Mono. cell inf.:myo. = Mononuclear cell infiltration:myocardium HEART (RIGHT VENTRICLE) - Mono. cell inf.:myo. = Mononuclear cell infiltration:myocardium HEART (SEPTUM) - Mon. cell inf.:endo. = Mononuclear cell infiltration:endocardium - Mono. cell inf.:myo.PATHOLOGY REPORT PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ EXPLANATION OF CODES AND SYMBOLS
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ EXPLANATION OF TABLE TEXT(S) USED AT FINDING LEVEL:
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ = Mononuclear cell infiltration:myocardium MUSCLE (DIAPHRAGM) - Histiocyte infiltr. = Histiocyte infiltration - Mononuc. cell infil. = Mononuclear cell infiltration - Myofiber degen. = Myofiber degeneration MUSCLE (LEFT RECTUS FEMORIS) - Cytopl. basophilia = Cytoplasmic basophilia:myofiber - Histiocytic infiltr. = Histiocytic infiltration - Mononuc. cell infil. = Mononuclear cell infiltration:interstitium - Myofiber degen. = Myofiber degeneration MUSCLE (LEFT PSOAS) - Mineralization = Mineralization:myofiber - Mononuc. cell infil. = Mononuclear cell infiltration:interstitium MUSCLE (RIGHT RECTUS FEMORIS) - Histiocytic infiltr. = Histiocytic infiltration - Mononuc. cell infil. = Mononuclear cell infiltration:interstitium - Myofiber degen. = Myofiber degeneration - Neutrophil infiltr. = Neutrophil infiltration:interstitium MUSCLE (RIGHT PSOAS) - Mononuc. cell infil. = Mononuclear cell infiltration:interstitium - Myofiber degen. = Myofiber degeneration MUSCLE (RIGHT SOLEUS) - Myofiber degen. = Myofiber degenerationPATHOLOGY REPORT SUMMARY TABLES PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0, EXCEPT DEATHS
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ SEX : MALE DOSE GROUP: 1 2 3 NO.ANIMALS: 8 7 8
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ HEART (L VENT. FREE) : 8 7 8 - Mono. cell inf.:myo.: 1 - - Grade 1: 1 - - - Mono. cell inf.:epi.: - 1 1 Grade 1: - 1 1 - Pigment : - - 1 Grade 1: - - 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ HEART (LEFT VENTR.) : 8 7 8 - Mono. cell inf.:myo.: 1 - - Grade 1: 1 - -
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ MUSCLE (DIAPHRAGM) : 8 7 8 - Mononuc. cell infil.: 1 - - Grade 1: 1 - -
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ MUSCLE (R REC FEMOR) : 8 7 8 - Neutrophil infiltr. : 1 - - Grade 1: 1 - -
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ MUSCLE (RIGHT PSOAS) : 8 7 8 - Myofiber degen. : - 1 - Grade 1: - 1 - - Mononuc. cell infil.: 1 - - Grade 1: 1 - -
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT SUMMARY TABLES PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0, EXCEPT DEATHS
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ SEX : FEMALE DOSE GROUP: 1 2 3 NO.ANIMALS: 8 8 8
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ HEART (L VENT. FREE) : 8 8 8 - Mono. cell inf.:epi.: - - 1 Grade 1: - - 1 - Mix. cell inf.:endo.: 1 - - Grade 1: 1 - -
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ HEART (LEFT VENTR.) : 8 8 8 - Mono. cell inf.:myo.: - - 1 Grade 1: - - 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ HEART (RIGHT VENTR.) : 8 8 8 - Mono. cell inf.:myo.: - - 1 Grade 1: - - 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ HEART (SEPTUM) : 8 8 8 - Mono. cell inf.:myo.: - 1 - Grade 1: - 1 - - Mon. cell inf.:endo.: 1 - - Grade 1: 1 - -
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ MUSCLE (DIAPHRAGM) : 8 8 8 - Myofiber degen. : - 1 - Grade 1: - 1 - - Mononuc. cell infil.: 1 - 1 Grade 1: 1 - 1 - Histiocyte infiltr. : 1 - - Grade 1: 1 - -
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT SUMMARY TABLES PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0, EXCEPT DEATHS
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ SEX : FEMALE DOSE GROUP: 1 2 3 NO.ANIMALS: 8 8 8
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ MUSCLE (L REC FEMOR) : 8 8 8 - Myofiber atrophy : - 1 - Grade 3: - 1 - - Myofiber degen. : 1 1 - Grade 1: 1 1 - - Cytopl. basophilia : 1 - 2 Grade 1: 1 - 2 - Mononuc. cell infil.: - 1 - Grade 1: - 1 - - Histiocytic infiltr.: - 1 - Grade 2: - 1 -
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ MUSCLE (LEFT PSOAS) : 8 8 8 - Myofiber atrophy : - 1 - Grade 3: - 1 - - Mineralization : - 1 - Grade 2: - 1 - - Mononuc. cell infil.: - 1 - Grade 1: - 1 -
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ MUSCLE (LEFT SOLEUS) : 8 8 8 - Myofiber atrophy : - 1 - Grade 1: - 1 -
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ MUSCLE (R REC FEMOR) : 8 8 8 - Myofiber atrophy : - 1 - Grade 2: - 1 - - Myofiber degen. : - - 1 Grade 1: - - 1 - Mononuc. cell infil.: - - 1 Grade 1: - - 1 - Histiocytic infiltr.: - - 1 Grade 1: - - 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT SUMMARY TABLES PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX STATUS AT NECROPSY: K0, EXCEPT DEATHS
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ SEX : FEMALE DOSE GROUP: 1 2 3 NO.ANIMALS: 8 8 8
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ MUSCLE (RIGHT PSOAS) : 8 8 8 - Myofiber atrophy : - 1 - Grade 3: - 1 - - Mononuc. cell infil.: - 2 - Grade 1: - 2 -
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ MUSCLE (RIGHT SOLEUS : 8 8 8 - Myofiber atrophy : - 1 - Grade 1: - 1 - - Myofiber degen. : - 1 - Grade 1: - 1 -
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ ANIMAL NUMBER : 1145 1146 1147 1148 1149 1150 1151 1152 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ HEART (L VENT. FREE) - - + - - - - - - Mono. cell inf.:myo. . . 1. . . . . .

......................................................................... HEART (LEFT VENTR.) - - - - - - + - - Mono. cell inf.:myo. . . . . . . 1. .

......................................................................... HEART (RIGHT VENTR.) - - - - - - - -

......................................................................... HEART (SEPTUM) - - - - - - - -

......................................................................... MUSCLE (DIAPHRAGM) - - - - - - - + - Mononuc. cell infil. . . . . . . . 1.

......................................................................... MUSCLE (L REC FEMOR) - - - - - - - -

......................................................................... MUSCLE (LEFT PSOAS) - - - - - - - -

......................................................................... MUSCLE (LEFT SOLEUS) - - - - - - - -

......................................................................... MUSCLE (R REC FEMOR) - - + - - - - - - Neutrophil infiltr. . . 1. . . . . .

......................................................................... MUSCLE (RIGHT PSOAS) - - - - - + - - - Mononuc. cell infil. . . . . . 1. . .

......................................................................... MUSCLE (RIGHT SOLEUS - - - - - - - -

.........................................................................PATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ ANIMAL NUMBER : 1645 1646 1647 1648 1649 1650 1651 1652 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ HEART (L VENT. FREE) - + - - - - - - - Mix. cell inf.:endo. . 1. . . . . . .

......................................................................... HEART (LEFT VENTR.) - - - - - - - -

......................................................................... HEART (RIGHT VENTR.) - - - - - - - -

......................................................................... HEART (SEPTUM) - + - - - - - - - Mon. cell inf.:endo. . 1. . . . . . .

......................................................................... MUSCLE (DIAPHRAGM) - - + - - - + - - Mononuc. cell infil. . . . . . . 1. . - Histiocyte infiltr. . . 1. . . . . .

......................................................................... MUSCLE (L REC FEMOR) - + + - - - - - - Myofiber degen. . . 1. . . . . . - Cytopl. basophilia . 1. . . . . . .

......................................................................... MUSCLE (LEFT PSOAS) - - - - - - - -

......................................................................... MUSCLE (LEFT SOLEUS) - - - - - - - -

......................................................................... MUSCLE (R REC FEMOR) - - - - - - - -

......................................................................... MUSCLE (RIGHT PSOAS) - - - - - - - -

......................................................................... MUSCLE (RIGHT SOLEUS - - - - - - - -

.........................................................................PATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ ANIMAL NUMBER : 2145 2146 2147 2149 2150 2151 2152 2153 MK0 MK0 MK0+ MK0 MK0 MK0 MK0 MK0
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ HEART (L VENT. FREE) - - - - + - - - - Mono. cell inf.:epi. . . . . 1. . . .

......................................................................... HEART (LEFT VENTR.) - - - - - - - -

......................................................................... HEART (RIGHT VENTR.) - - - - - - - -

......................................................................... HEART (SEPTUM) - - - - - - - -

......................................................................... MUSCLE (DIAPHRAGM) - - - - - - - -

......................................................................... MUSCLE (L REC FEMOR) - - - - - - - -

......................................................................... MUSCLE (LEFT PSOAS) - - - - - - - -

......................................................................... MUSCLE (LEFT SOLEUS) - - - - - - - -

......................................................................... MUSCLE (R REC FEMOR) - - - - - - - -

......................................................................... MUSCLE (RIGHT PSOAS) - - - - - - + - - Myofiber degen. . . . . . . 1. .

......................................................................... MUSCLE (RIGHT SOLEUS - - - - - - - -

.........................................................................PATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ ANIMAL NUMBER : 2645 2646 2647 2648 2649 2650 2651 2652 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ HEART (L VENT. FREE) - - - - - - - -

......................................................................... HEART (LEFT VENTR.) - - - - - - - -

......................................................................... HEART (RIGHT VENTR.) - - - - - - - -

......................................................................... HEART (SEPTUM) - - - + - - - - - Mono. cell inf.:myo. . . . 1. . . . .

......................................................................... MUSCLE (DIAPHRAGM) - - + - - - - - - Myofiber degen. . . 1. . . . . .

......................................................................... MUSCLE (L REC FEMOR) - - + - - - - - - Myofiber atrophy . . 3. . . . . . - Myofiber degen. . . 1. . . . . . - Mononuc. cell infil. . . 1. . . . . . - Histiocytic infiltr. . . 2. . . . . .

......................................................................... MUSCLE (LEFT PSOAS) - - + - - - - - - Myofiber atrophy . . 3. . . . . . - Mineralization . . 2. . . . . . - Mononuc. cell infil. . . 1. . . . . .

......................................................................... MUSCLE (LEFT SOLEUS) - - + - - - - - - Myofiber atrophy . . 1. . . . . .

......................................................................... MUSCLE (R REC FEMOR) - - + - - - - - - Myofiber atrophy . . 2. . . . . .

......................................................................... MUSCLE (RIGHT PSOAS) + - + - - - - - - Myofiber atrophy . . 3. . . . . . - Mononuc. cell infil. 1. . 1. . . . . .

......................................................................... MUSCLE (RIGHT SOLEUS - - + - - - - - - Myofiber atrophy . . 1. . . . . . - Myofiber degen. . . 1. . . . . .

.........................................................................PATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ ANIMAL NUMBER : 3145 3146 3147 3148 3149 3150 3151 3152 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ HEART (L VENT. FREE) - - - - - - - + - Mono. cell inf.:epi. . . . . . . . 1. - Pigment . . . . . . . 1.

......................................................................... HEART (LEFT VENTR.) - - - - - - - -

......................................................................... HEART (RIGHT VENTR.) - - - - - - - -

......................................................................... HEART (SEPTUM) - - - - - - - -

......................................................................... MUSCLE (DIAPHRAGM) - - - - - - - -

......................................................................... MUSCLE (L REC FEMOR) - - - - - - - -

......................................................................... MUSCLE (LEFT PSOAS) - - - - - - - -

......................................................................... MUSCLE (LEFT SOLEUS) - - - - - - - -

......................................................................... MUSCLE (R REC FEMOR) - - - - - - - -

......................................................................... MUSCLE (RIGHT PSOAS) - - - - - - - -

......................................................................... MUSCLE (RIGHT SOLEUS - - - - - - - -

.........................................................................PATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ ANIMAL NUMBER : 3645 3646 3647 3648 3649 3650 3651 3652 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ HEART (L VENT. FREE) - - - - + - - - - Mono. cell inf.:epi. . . . . 1. . . .

......................................................................... HEART (LEFT VENTR.) - - - + - - - - - Mono. cell inf.:myo. . . . 1. . . . .

......................................................................... HEART (RIGHT VENTR.) - - - - - + - - - Mono. cell inf.:myo. . . . . . 1. . .

......................................................................... HEART (SEPTUM) - - - - - - - -

......................................................................... MUSCLE (DIAPHRAGM) + - - - - - - - - Mononuc. cell infil. 1. . . . . . . .

......................................................................... MUSCLE (L REC FEMOR) - - - - + - + - - Cytopl. basophilia . . . . 1. . 1. .

......................................................................... MUSCLE (LEFT PSOAS) - - - - - - - -

......................................................................... MUSCLE (LEFT SOLEUS) - - - - - - - -

......................................................................... MUSCLE (R REC FEMOR) - - - + - + - - - Myofiber degen. . . . 1. . . . . - Mononuc. cell infil. . . . . . 1. . . - Histiocytic infiltr. . . . . . 1. . .

......................................................................... MUSCLE (RIGHT PSOAS) - - - - - - - -

......................................................................... MUSCLE (RIGHT SOLEUS - - - - - - - -

.........................................................................PATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ ANIMAL HEADING DATA DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ ANIMAL SEX DEFINED AND FINAL TEST FIRST AND LAST DATE OF NUMBER M/F STATE OF NECROPSY DAYS DAY UNDER TEST NECROPSY

......................................................................... 1145 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 1146 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 1147 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 1148 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 1149 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 1150 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 1151 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 1152 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13

......................................................................... 1645 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 1646 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 1647 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 1648 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 1649 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 1650 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 1651 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 1652 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13

.........................................................................PATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1145 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1146 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1147 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS HEART (LEFT VENTRICULAR FREE WALL): -Mononuclear cell infiltration:myocardium, focal, grade 1 MUSCLE (RIGHT RECTUS FEMORIS): -Neutrophil infiltration:interstitium, focal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1148 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1149 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1150 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS MUSCLE (RIGHT PSOAS): -Mononuclear cell infiltration:interstitium, focal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1151 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS HEART (LEFT VENTRICLE): -Mononuclear cell infiltration:myocardium, focal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1152 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS MUSCLE (DIAPHRAGM): -Mononuclear cell infiltration, mesothelial surface, focal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1645 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1646 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS HEART (LEFT VENTRICULAR FREE WALL): -Mixed cell infiltration:endocardium, focal, grade 1 HEART (SEPTUM): -Mononuclear cell infiltration:endocardium, focal, grade 1 MUSCLE (LEFT RECTUS FEMORIS): -Cytoplasmic basophilia:myofiber, multifocal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1647 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS MUSCLE (DIAPHRAGM): -Histiocyte infiltration, multifocal, grade 1 MUSCLE (LEFT RECTUS FEMORIS): -Myofiber degeneration, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1648 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1649 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1650 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1651 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS MUSCLE (DIAPHRAGM): -Mononuclear cell infiltration, focal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 1, Group 1
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 1652 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ ANIMAL HEADING DATA DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ ANIMAL SEX DEFINED AND FINAL TEST FIRST AND LAST DATE OF NUMBER M/F STATE OF NECROPSY DAYS DAY UNDER TEST NECROPSY

......................................................................... 2145 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 2146 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 2147 M K0 +2 16 02-OCT-13 17-OCT-13 17-OCT-13 2149 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 2150 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 2151 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 2152 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 2153 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13

......................................................................... 2645 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 2646 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 2647 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 2648 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 2649 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 2650 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 2651 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 2652 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13

.........................................................................PATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2145 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2146 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2147 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 17-Oct-13 DAYS ON TEST : 16 DATE OF NECROPSY : 17-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : SACRIFICED MORIBUND

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2149 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2150 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS HEART (LEFT VENTRICULAR FREE WALL): -Mononuclear cell infiltration:epicardium, focal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2151 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2152 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS MUSCLE (RIGHT PSOAS): -Myofiber degeneration, focal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2153 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2645 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS MUSCLE (RIGHT PSOAS): -Mononuclear cell infiltration:interstitium, focal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2646 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2647 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS MUSCLE (DIAPHRAGM): -Myofiber degeneration, focal, grade 1 MUSCLE (LEFT RECTUS FEMORIS): -Myofiber atrophy, multifocal, grade 3 -Myofiber degeneration, focal, grade 1 -Mononuclear cell infiltration:interstitium, multifocal, grade 1 -Histiocytic infiltration, multifocal, grade 2 MUSCLE (LEFT PSOAS): -Myofiber atrophy, multifocal, grade 3 -Mineralization:myofiber, multifocal, grade 2 -Mononuclear cell infiltration:interstitium, multifocal, grade 1 MUSCLE (LEFT SOLEUS): -Myofiber atrophy, multifocal, grade 1 MUSCLE (RIGHT RECTUS FEMORIS): -Myofiber atrophy, multifocal, grade 2 MUSCLE (RIGHT PSOAS): -Myofiber atrophy, multifocal, grade 3 -Mononuclear cell infiltration:interstitium, multifocal, grade 1 MUSCLE (RIGHT SOLEUS): -Myofiber atrophy, multifocal, grade 1 -Myofiber degeneration, focal, grade 1PATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ CONT./FF. ANIMAL NO. : 2647

......................................................................... ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2648 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS HEART (SEPTUM): -Mononuclear cell infiltration:myocardium, focal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2649 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2650 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2651 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 2, Group 2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 2652 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ ANIMAL HEADING DATA DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ ANIMAL SEX DEFINED AND FINAL TEST FIRST AND LAST DATE OF NUMBER M/F STATE OF NECROPSY DAYS DAY UNDER TEST NECROPSY

......................................................................... 3145 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 3146 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 3147 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 3148 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 3149 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 3150 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 3151 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13 3152 M K0 K0 29 02-OCT-13 30-OCT-13 30-OCT-13

......................................................................... 3645 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 3646 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 3647 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 3648 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 3649 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 3650 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 3651 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13 3652 F K0 K0 29 03-OCT-13 31-OCT-13 31-OCT-13

.........................................................................PATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3145 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3146 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3147 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3148 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3149 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3150 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3151 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3152 SEX : MALE FIRST DAY ON TEST : 02-Oct-13 LAST DAY ON TEST : 30-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 30-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS HEART (LEFT VENTRICULAR FREE WALL): -Mononuclear cell infiltration:epicardium, multifocal, grade 1 -Pigment:macrophage cytoplasm, epicardium, focal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3645 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS MUSCLE (DIAPHRAGM): -Mononuclear cell infiltration, interstitium, focal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3646 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3647 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3648 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS HEART (LEFT VENTRICLE): -Mononuclear cell infiltration:myocardium, focal, grade 1 MUSCLE (RIGHT RECTUS FEMORIS): -Myofiber degeneration, multifocal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3649 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS HEART (LEFT VENTRICULAR FREE WALL): -Mononuclear cell infiltration:epicardium, focal, grade 1 MUSCLE (LEFT RECTUS FEMORIS): -Cytoplasmic basophilia:myofiber, multifocal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3650 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS HEART (RIGHT VENTRICLE): -Mononuclear cell infiltration:myocardium, focal, grade 1 MUSCLE (RIGHT RECTUS FEMORIS): -Mononuclear cell infiltration:interstitium, focal, grade 1 -Histiocytic infiltration, focal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3651 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS MUSCLE (LEFT RECTUS FEMORIS): -Cytoplasmic basophilia:myofiber, multifocal, grade 1 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄPATHOLOGY REPORT INDIVIDUAL ANIMAL DATA PROJECT :13-6434
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEST ITEM : HFO-1234yf PATHOL. NO.: 13077 DSG TEST SYSTEM : MINIPIG, 28 Day, Inhalation DATE : 17-JAN-14 SPONSOR : PATHDATA SYSTEM V6.2c2
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP : 3, Group 3
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ * ANIMAL NUMBER : 3652 SEX : FEMALE FIRST DAY ON TEST : 03-Oct-13 LAST DAY ON TEST : 31-Oct-13 DAYS ON TEST : 29 DATE OF NECROPSY : 31-Oct-13 DEFINED SACR.GROUP : TERMINAL SACRIFICE GROUP STATUS AT NECROPSY : TERMINAL SACRIFICE GROUP

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.
* MICROSCOPIC FINDINGS NO MICROSCOPIC FINDINGS NOTED.

ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄFinal Pathology Report HLS Study Number 13-6434

74 1/17/2014 Appendix B. Peer Review StatementFinal Pathology Report HLS Study Number 13-6434

76 1/17/2014 Appendix C. Quality Assurance Statement