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Working for a better future

REPORT

2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation 

Administration to CD Rats for 13 Weeks Followed by a 4 Week 

Recovery Period

HLS study number: WAG0014

Version ID: Final Report

Issue date: 24 October 2013
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Details of Sponsor and Test Facilities

Sponsor American Pacific Corporation

3883 Howard Hughes Parkway

Suite 700

Las Vegas

Nevada 89169

USA

Test facility Huntingdon Life Sciences

Primary location Huntingdon Research Centre

Woolley Road

Alconbury

Huntingdon

Cambridgeshire

PE28 4HS

UK

Test facility Huntingdon Life Sciences

Histology Eye Research Centre

Eye

Suffolk

IP23 7PX

UK
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Table of Contents

Details of Sponsor and Test Facilities ................................................................................... 2

Compliance with Good Laboratory Practice .......................................................................... 6

Quality Assurance Statement................................................................................................ 7

Contributing Scientists .......................................................................................................... 8

Summary .............................................................................................................................. 9

1. Introduction ................................................................................................................ 11

1.1 Objective......................................................................................................... 11

1.2 Regulatory compliance ................................................................................... 11

1.3 Test system .................................................................................................... 11

1.4 Route of administration................................................................................... 11

1.5 Treatment groups and doses .......................................................................... 12

2. Experimental Procedure............................................................................................. 13

2.1 Study schedule and structure.......................................................................... 13

2.1.1 Duration of treatment........................................................................... 13

2.1.2 Time schedule..................................................................................... 13

2.1.3 Identity of treatment groups................................................................. 13

2.2 Test substance ............................................................................................... 14

2.2.1 Test substance.................................................................................... 14

2.3 Animal management....................................................................................... 15

2.3.1 Animal supply, acclimatisation and allocation...................................... 15

2.3.2 Animal housing, diet and water supply ................................................ 15

2.3.3 Administration ..................................................................................... 16

2.4 Serial observations ......................................................................................... 17

2.4.1 Clinical observations ........................................................................... 17

2.4.2 Detailed physical examination and arena observations ....................... 17

2.4.3 Sensory reactivity and grip strength .................................................... 18

2.4.4 Motor activity....................................................................................... 19

2.4.5 Mortality .............................................................................................. 19

2.4.6 Bodyweight ......................................................................................... 19

2.4.7 Food consumption............................................................................... 19

2.4.8 Ophthalmic examination...................................................................... 19

2.4.9 Haematology, peripheral blood............................................................ 20

2.4.10 Blood chemistry................................................................................... 21

2.4.11 Urinalysis ............................................................................................ 21

2.5 Necropsy and Histology.................................................................................. 22

2.5.1 Method of kill....................................................................................... 22

2.5.2 Macroscopic pathology........................................................................ 23

2.5.3 Organ weights..................................................................................... 23

2.5.4 Fixation ............................................................................................... 24

2.5.5 Histology ............................................................................................. 25

2.6 Pathology........................................................................................................ 25

2.6.1 Light microscopy ................................................................................. 25

2.7 Computer systems.......................................................................................... 27

2.8 Data treatment................................................................................................ 27

2.8.1 Definition of “Week”............................................................................. 28

2.8.2 Signs................................................................................................... 28

2.8.3 Bodyweight ......................................................................................... 28
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2.8.4 Ophthalmic examination...................................................................... 28

2.8.5 Haematology....................................................................................... 29

2.8.6 Blood chemistry................................................................................... 29

2.8.7 Urinalysis ............................................................................................ 29

2.8.8 Organ weights..................................................................................... 29

2.8.9 Pathology............................................................................................ 29

2.8.10 Statistical analysis............................................................................... 30

2.9 Quality assurance and archiving procedures .................................................. 32

2.9.1 Quality assurance ............................................................................... 32

2.9.2 Archives .............................................................................................. 32

2.10 Deviations from protocol ................................................................................. 32

3. Results....................................................................................................................... 33

3.1 Chamber atmosphere conditions .................................................................... 33

3.2 Signs and mortality ......................................................................................... 33

3.3 Sensory reactivity and grip strength................................................................ 34

3.4 Motor activity .................................................................................................. 34

3.5 Bodyweight..................................................................................................... 35

3.6 Food consumption .......................................................................................... 35

3.7 Ophthalmic examination ................................................................................. 35

3.8 Haematology .................................................................................................. 35

3.9 Blood chemistry .............................................................................................. 36

3.10 Urinalysis........................................................................................................ 36

3.11 Organ weights................................................................................................. 37

3.12 Macropathology .............................................................................................. 38

3.13 Histopathology................................................................................................ 40

4. Discussion.................................................................................................................. 48

5. Conclusion ................................................................................................................. 50

6. References................................................................................................................. 51

List of Figures

Figure 1 Motor activity................................................................................................52

Figure 2 Bodyweight ..................................................................................................56

List of Tables

Table 1 Sensory reactivity and grip strength .............................................................58

Table 2 Motor activity................................................................................................60

Table 3 Bodyweight ..................................................................................................64

Table 4 Haematology................................................................................................70

Table 5 Blood chemistry ...........................................................................................78

Table 6 Urinalysis .....................................................................................................86

Table 7 Organ weights..............................................................................................88

Table 8 Macropathology ...........................................................................................96

Table 9 Histopathology ...........................................................................................101
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List of Appendices

Appendix 1 Clinical signs..............................................................................................119

Appendix 2 Signs associated with dosing .....................................................................139

Appendix 3 Sensory reactivity and grip strength ...........................................................324

Appendix 4 Motor activity..............................................................................................332

Appendix 5 Bodyweight ................................................................................................348

Appendix 6 Food consumption .....................................................................................360

Appendix 7 Ophthalmic examination.............................................................................364

Appendix 8 Haematology..............................................................................................366

Appendix 9 Blood chemistry .........................................................................................387

Appendix 10 Urinalysis ...................................................................................................401

Appendix 11 Organ weights............................................................................................413

Appendix 12 Macropathology and histopathology...........................................................425

List of Annexes

Annex 1 Certificate of analysis.................................................................................622

Annex 2 Aerosol technology and inhalation analysis report......................................624

Annex 3 Pathology report.........................................................................................643

Annex 4 External pathology peer review report........................................................661

Annex 5 GLP compliance statements ......................................................................687
No. 3 1 06, as amended by Statutory Instrument 2004 No. 994).

OECD Principles of Good Laboratory Practice (as revised in 1997),

ENV/MC/CHEM (98) 17.

EC Commission Directive 2004/10/EC of 11 February 2004 (Official Journal NoL 50/44).

These principles of Good Laboratory Practice are accepted by the regulatory authorities of

the United States of America and Japan on the basis of intergovernmental agreements.

Heart tissue slides from all males (main study and recovery) were independently peer

reviewed by an external consultant pathologist. The findings ofthis review, presented as an

expert pathology report, are included as Annex 4 ofthis report for information purposes only.

The expert pathology review was not conducted in accordance with Good Laboratory

Practice regulations and was not subj ect to Quality Assurance audit. No formal claim of GLP

compliance is made for this work.

3

Paul J H rfll BSc (Hons) IDT Date

Study Director

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6
Protocol Audit

Protocol Amendment No.1

Study Set Up

Protocol Amendment No.2

Study Management and

Conduct

Pre-Terminal 05 Oct 2012 05 Oct 2012

05 Oct 2012 02 Nov 2012

01 Nov2012 01 Nov2012

13Nov2012 13Nov2012

17Dec2012 17Dec2012

12Nov2012 12Nov2012

21 Jan2013-31 Jan2013 31 Jan2013

170ct2013 170ct2013

18 Oct 2013 18 Oct 2013

In addition, process based inspections were conducted of other routine and repetitive

procedures employed on this type ofstudy at or about the time this study was in progress.

Similarly an inspection ofthe facility where this study was conducted was carried out on an

annual basis. These inspections were reported to Company Management.

Th .SN\;\ l-v\ %Lf Cc/Vt) 2€V 20 I 3 Dilys Smith, MRQA Date

Lead Auditor

Department of Quality Assurance

Huntingdon Life Sciences

13 Mar2012

05 Jul 2012

09 Jul 2012

17 Jul 2012

01 Aug2012

15 Mar 2012

05 Jul 2012

10 Jul 2012

17 Jul 2012

01 Aug2012

Protocol Amendment No.3

Protocol Amendment No.4

Protocol Amendment No.5

Protocol Amendment No.6

Report Audit

7
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Contributing Scientists

2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation 

Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery 

Period

Study management

Paul J Horrell BSc (Hons) IDT

Study Director

William N Hooks MIBMS BSc (Hons)

Senior Toxicologist

Aerosol technology

Simon A Moore BSc (Hons) PhD MRSC

Head of Aerosol Technology

Inhalation analysis

Caroline Finucane PhD

Head of Formulation & Inhalation Analysis

Sensory reactivity, grip strength and motor activity

Martin J Collier BSc

Behavioural Scientist

Ophthalmic examination 

Helmut Ehall MagMedVet DrMedVet MRCVS

Named Veterinary Surgeon

Clinical pathology

John Smeraglia MSc

Associate Director of Bioanalysis and Clinical Pathology

Pathology

Kai Chiu Liu BSc MSc (Tox) PhD

Senior Pathologist

Statistics

Gareth D Thomas BSc (Hons)

Head of Statistics and Data Management
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Summary

The assessment of local and systemic toxic potential of 2-bromo-3,3,3-trifluoropropene (a 

fire extinguishing agent), to Crl:CD (SD) rats by inhalation administration was assessed over 

a period of 13 weeks, followed by a 4 week recovery (non-dosing) period. Three groups, 

each comprising ten male and ten female rats received 2-bromo-3,3,3-trifluoropropene at 

target exposure levels of 200, 500 or 3000 ppm, 5 days per week (6 hour exposure). A 

similarly constituted Control group received clean air only, under the same conditions as the 

test groups. A further ten male and ten female rats were assigned to each of the Control and 

high dose groups. These animals were treated for 13 weeks, followed by a 4 week period 

without treatment to assess recovery from any treatment related effect.

During the study, clinical observations, detailed physical examination and arena observations, 

sensory reactivity, grip strength, motor activity, bodyweight, food consumption, ophthalmic 

examination, haematology, blood chemistry, urinalysis, organ weight, macropathology and 

histopathology investigations were undertaken.

Results

The achieved aerosol concentrations were 199, 505 and 2876 ppm (100, 101 and 96% of 

target) for Groups 2-4 respectively.

There were no deaths that were considered to be a direct result of exposure to the test 

material, 2 bromo 3,3,3 trifluoropropene.

Treatment-related, but transient, clinical signs, related to inhalation of an irritant material 

(shallow breathing, piloerection, grinding teeth and hunched posture) or possible CNS effects

(unresponsiveness to external stimuli, underactivity, and partially closed eyelids), were 

evident during and after exposure at all exposure levels. Reductions in grip strength and 

motor activity were evident for animals exposed to 505 or 2876 ppm and were only partially 

reversible for animals previously exposed to 2876 ppm after a 4 week recovery period.

Lower bodyweight gain was evident, over the 13 week treatment period, for treated males

and females exposed to 505 ppm or higher, in a dosage related manner. Total food 

consumption was similarly lower for treated males and females exposed to 2876 ppm. 

Effects on bodyweight and food consumption showed evidence of recovery for animals 

previously exposed to 2876 ppm after a 4 week recovery period.

Histopathological changes related to treatment were seen in the liver (centrilobular 

hepatocyte hypertrophy), pancreas (acinar cell degranulation), heart (chronic inflammation), 

spleen (capsular inflammation and/or thickening and adhesion), thymus (involution/atrophy), 

nasal turbinates (findings related to minor local irritants), larynx (ventral squamous 

metaplasia) and teeth (pulp cavity necrosis). The majority of these findings were seen with

animals at 505 and 2876 ppm. Chronic inflammation in the heart and acinar cell 

degranulation in the pancreas were evident for animals exposed to 199 ppm, however, these 

changes are not considered to be adverse. The slight and moderate degrees of chronic 

inflammation in the heart observed at 505 and 2876 ppm are considered adverse.
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Following the 4 week recovery period, there was complete recovery of test material related 

histopathological changes seen in the liver, pancreas, heart, thymus, larynx and teeth and 

partial recovery for the findings see in the spleen (capsular inflammation and/or thickening) 

and nasal turbinates (atrophy/disorganisation/vacuolation of the olfactory epithelium and 

nasolacrimal duct inflammation).

Conclusion

Inhalation exposure of CD rats to atmospheres of 2 bromo 3,3,3-trifluoropropene for 

13 weeks, resulted in transient clinical signs, lower bodyweight gain, food consumption, grip 

strength and motor activity and histopathological changes in the liver, pancreas, heart, spleen, 

thymus, nasal turbinates, larynx and teeth. The majority of these findings were seen with 

animals exposed to 505 or 2876 ppm.

In the heart, chronic inflammation was seen in males exposed to 199 ppm and both sexes 

exposed to 505 or 2876 ppm and was considered adverse at 505 ppm or above.

The no observed adverse effect level (NOAEL) was considered to be 199 ppm.
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1. Introduction

1.1 Objective

The objective of this study was to assess the local and systemic toxic potential of

2-bromo-3,3,3-trifluoropropene, a fire extinguishing agent, when administered by inhalation

(whole body) to rats for 13 weeks. Recovery from any effects seen at the highest dose was 

assessed during a 4 week recovery period.

1.2 Regulatory compliance

The study was designed to meet the requirements of the following guidelines:

OECD Guideline for the Testing of Chemicals, No. 413: Subchronic Inhalation 

Toxicity: 90-Day Study (Adopted: 7 September 2009).

EC Directive 88/302/EEC B.29 Sub-Chronic Inhalation Toxicity Test: 90-Day 

Repeated Inhalation Dose Study using Rodent Species.

US EPA OPPTS Guideline 870.3465: 90-day Inhalation Toxicity Study, (August 

1998).

The study was conducted in accordance with the requirements of current, internationally

recognised Good Laboratory Practice Standards, and the applicable sections of the United 

Kingdom Animals (Scientific Procedures) Act 1986.

1.3 Test system

The rat was chosen as the test species because of its acceptance as a predictor of toxic change 

in man and the requirement for a rodent species by regulatory agencies. The Crl:CD (SD)

strain was used because of the historical control data available in this laboratory.

1.4 Route of administration

The inhalation route of administration was chosen to simulate the conditions of potential 

human exposure.
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1.5 Treatment groups and doses

In a previous 2-week dose range finding study (Huntingdon Life Sciences Study Number:

WAG0024), 3 groups of rats were exposed to 2-bromo-3,3,3-trifluoropropene for 6 hours per 

day, 5 days per week at achieved aerosol concentrations of 533, 1167 and 2980 ppm.

There were no unscheduled deaths at doses up to 2980 ppm. In-life findings, consisting of 

transient clinical signs, evident during and after exposure for all treated animals, and reduced 

bodyweight gain and food consumption, seen for all treated males, were not considered 

adverse.

Histopathological changes related to treatment were seen mainly in the nasal turbinates of 

rats exposed to 1167 or 2980 ppm and were consistent with a localised toxic effect of the test 

material. No histopathological changes were evident at 533 ppm and this was considered to 

be the no observed adverse effect level (NOAEL).

Although adverse histopathological findings were evident at 1167 ppm it was considered that 

these may not progress over 13 weeks and may be readily reversible during a 4 week 

off-exposure recovery period. A target high exposure level of 3000 ppm was thus selected 

for this study, as it was considered that exposure for 13 weeks at this level would have

adverse histopathological effects on rats which may or may not be reversible.

The target intermediate exposure level of 500 ppm was selected as it was shown to have no 

adverse effects after 2 weeks exposure.

Since the 500 and 3000 ppm target exposure levels were used on the 2-week study, their use 

on the 13-week study would also enable the relationship of changes over time to be explored.

The target low exposure level of 200 ppm was expected to have no adverse effects and would 

offer an acceptable worker safety margin.
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2. Experimental Procedure

2.1 Study schedule and structure

2.1.1 Duration of treatment

The test substance, 2-bromo-3,3,3-trifluoropropene, was administered over a period of 

13 consecutive weeks. The necropsy procedures were completed in 4 days for the main study

and 1 day for recovery phase, during which time treatment continued, and serial observations 

were recorded at appropriate intervals. The duration of treatment is reported as 13 weeks. 

Animals assigned to the recovery phase completed a further four weeks without treatment.

2.1.2 Time schedule

Study initiation:

(Protocol signed by Study Director)

09 March 2012

Experimental start date:

(Animal arrival)

05 July 2012

Treatment commenced: 10 July 2012

Necropsy completed:

Main Study 12 October 2012

Recovery Study 06 November 2012

Experimental completion date:

(pathology)

7 October 2013

Study completion: When the Study Director signs the final report.

2.1.3 Identity of treatment groups

The study consisted of one Control and three treated groups of rats, identified as follows:

Group Treatment

Target 

exposure level

(ppm)

Number of animals

Main study Recovery

Male Female Male Female

1 Control 0 10 10 10 10

2 2-bromo-3,3,3-

trifluoropropene

200 10 10 - -

3 2-bromo-3,3,3-

trifluoropropene

500 10 10 - -

4 2-bromo-3,3,3-

trifluoropropene

3000 10 10 10 10
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Group

Main study Recovery

Cage numbers Animal numbers Cage numbers Animal numbers

Male Female Male Female Male Female Male Female

1 13-14 5-6 61-70 21-30 17-18 9-10 81-90 41-50

2 21-22 11-12 101-110 51-60 - - - -

3 23-24 1-2 111-120 1-10 - - - -

4 3-4 7-8 11-20 31-40 15-16 19-20 71-80 91-100

Some serial observations needed to be performed without the knowledge of the treatment 

group; therefore the animal numbering system was such that it was not easy to identify a 

treatment group from the animal number.

2.2 Test substance

2.2.1 Test substance

Information supplied by the Sponsor regarding the test substance is contained in the test 

substance data sheet, which is retained in study records, and the Certificate of Analysis, 

which is presented in Annex 1.

The following information is given in summary:

Identification: 2-bromo-3,3,3-trifluoropropene (stabilized)

Action: Fire extinguishing agent

Description: Liquid at below 33C

Clear and may be colourless to light yellow tint

Storage conditions: At ambient temperature or in a refrigerator, stored under 

nitrogen (free from air and water).

Batch number: WNCC-BTP111128

Date of receipt: 02 March 2012

Quantity received: 4 × approximately 500 kg cylinders

2 × approximately 336 kg cylinders

Reassay date: 12 January 2013

Purity: >99.6% including stabilisers

Stabilisers:

The Sponsor was responsible for the characterisation of the test substance and the 

documentation of the methods of synthesis, fabrication or derivation and stability.
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2.3 Animal management

2.3.1 Animal supply, acclimatisation and allocation

Crl:CD (SD) rats (a total of 65 male and 65 female) were received from Charles River (UK) 

Ltd. The rats were ordered at 42 to 49 days of age and within a weight range of 180 to 210 g 

for males and 150 to 180 g for females.

On arrival, the animals were removed from the transit boxes and allocated to study cages. 

Using the sequence of cages in the battery, one animal at a time was placed in each cage with 

the procedure being repeated until each cage held the appropriate number of animals. Each 

sex was allocated separately.

Each animal was assigned a number and identified uniquely within the study by a tail tattoo. 

Each cage label was colour-coded according to group and was numbered uniquely with cage 

and study number, as well as the identity of the occupants.

On Day 3 of treatment, one male was found dead, before exposure, and was replaced with a 

spare animal of suitable weight from the same batch.

The animals were allowed to acclimatise to the conditions described below for at least 5 days 

before treatment commenced. For those animals selected for this study, their age at the start 

of treatment was 47 to 54 days and their bodyweights were in the range of 216 to 263 g for 

males and 160 to 224 g for females.

The spare animals were removed from the study room after treatment commenced.

2.3.2 Animal housing, diet and water supply

Animals were housed inside a restricted access rodent facility (Building Y14, Room 011). 

The facility was designed and operated to minimise the entry of external biological and 

chemical agents and to minimise the transference of such agents between rooms. Before the 

study the room was cleaned and disinfected.

Each animal room was supplied with filtered fresh air, which was passed to atmosphere and 

not re-circulated. The temperature and relative humidity controls were maintained within the 

range of 19 to 23°C and 40 to 70% respectively and monitored continuously. Although 

conditions were occasionally outside the indicated ranges, these deviations were minor and/or 

of short duration and were not considered to have influenced the health of the animals and/or 

the outcome of the study. Artificial lighting was controlled to give a cycle of 12 hours

continuous light and 12 hours continuous dark per 24 hours.

Alarms were activated if there was any failure of the ventilation system, or temperature limits 

were exceeded. A stand-by electricity supply was available to be automatically brought into 

operation should the public supply fail.

The animals were housed five of one sex per cage, unless this number was reduced by 

mortality or isolation. The cages were made of a polycarbonate body with a stainless steel

mesh lid. Softwood bark-free fibre was used as bedding and was sterilised by autoclaving 

and changed at appropriate intervals each week. Cages, food hoppers and water bottles were 

changed at appropriate intervals.
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The cages constituting each group were blocked together by sex and the groups were 

dispersed in batteries so that possible environmental influences arising from their spatial 

distribution were equilibrated, as far as was practicable. Additionally, batteries of cages were 

rotated around the room at weekly intervals to further minimise possible spatial variations.

The animals were allowed free access to a standard rodent diet (Rat and Mouse No. 1 

Maintenance Diet), except when urine was being collected and overnight before routine 

blood sampling. This diet contained no added antibiotic or other chemotherapeutic or 

prophylactic agent.

Potable water taken from the public supply was freely available via polycarbonate bottles 

fitted with sipper tubes, except when urine was being collected.

Each cage of animals was provided with an Aspen chew block and a plastic shelter for 

environmental enrichment. The soft white untreated wood blocks were provided throughout 

the study and were replaced when necessary; plastic shelters were replaced at the same time 

as the cages.

Each batch of diet was analysed routinely by the supplier for various nutritional components 

and chemical and microbiological contaminants. Supplier’s analytical certificates were 

scrutinised and approved before any batch of diet was released for use. The quality of the 

water supply is governed by regulations published by the Department for Environment, Food 

and Rural Affairs. Certificates of analysis were received routinely from the water supplier

and the suppliers of the bedding and Aspen chew blocks. Since the results of these various 

analyses did not provide evidence of contamination that might have prejudiced the study, 

they are not presented.

No other specific contaminants that were likely to have been present in the bedding, chew 

blocks, diet or water were analysed, as none that may have interfered with or prejudiced the 

outcome of the study was known.

2.3.3 Administration

Details of administration and analysis of the test atmospheres together with the results 

obtained are presented in Annex 2.

Each exposure system consisted of a Glass vaporiser and a whole body exposure chamber. 

Different doses of 2-bromo-3,3,3-trifluoropropene were achieved by varying the liquid feed 

rates of the test material in the system whilst keeping the duration of exposure constant. 

Group 1 was exposed to clean air only at a target concentration the same as the test groups.

Groups 2, 3 and 4 were exposed to 2-bromo-3,3,3-trifluoropropene, 6 hours/day for 5 days 

each week (Monday to Friday) for 13 weeks.
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2.4 Serial observations

Dated and signed records of all activities relating to the day by day running and maintenance 

of the study within the animal unit as well as to the group observations and examinations 

outlined in this experimental procedure were recorded in the Study Day Book. In addition, 

observations relating to individual animals made throughout the day were recorded.

All observations described below were performed in cage number sequence except where 

otherwise indicated.

2.4.1 Clinical observations

Animals were inspected visually at least twice daily for evidence of ill-health or reaction to 

treatment. Cages were inspected daily for evidence of ill-health amongst the occupant(s). 

Any deviation from normal was recorded at the time in respect of nature and severity, date 

and time of onset, duration and progress of the observed condition, as appropriate.

Daily, on exposure days during Week 1, detailed observations were performed immediately 

before dosing, during exposure and between one and two hours after completion of dosing 

and as late as possible in the working day for all groups. From Week 2 onwards, detailed 

observations were performed immediately before dosing and during exposure. 

During the acclimatisation period, observations of the animals and their cages were recorded 

twice per day.

In addition, a more detailed weekly physical examination was performed on each animal to 

monitor general health.

2.4.2 Detailed physical examination and arena observations

Before treatment commenced and during each week of treatment and recovery, detailed 

physical examination and arena observations were performed on each animal. Each week, 

the examinations were performed, before dosing during the treatment period, by an observer 

unaware of the experimental group to which the animal belonged.

After removal from the home cage, animals were assessed for physical condition and 

behaviour during handling and after being placed in a standard arena. Any deviation from

normal was recorded with respect to the nature and, where appropriate, degree of severity. 

Particular attention was paid to possible signs of neurotoxicity, such as convulsions, tremor 

and abnormalities of gait or behaviour.

Findings were either reported as "present" or assigned a severity grade - slight, moderate or 

marked.
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2.4.3 Sensory reactivity and grip strength

Sensory reactivity and grip strength assessments were performed (before dosing) on all main

study animals and all recovery phase animals during Week 12 of treatment. In addition, grip 

strength was assessed in all recovery phase animals during Week 4 of recovery. Animals 

were tested by an observer who was unaware of the treatment group to which each animal 

belonged. Before the start of observations, cage labels showing the treatment group were 

replaced by labels stating only the study, animal and cage numbers. Animals were not 

necessarily all tested on the same day, but the numbers of animals and the times of testing 

were balanced across the groups on each day of testing. 

The following measurements, reflexes and responses were recorded:

Approach response

A blunt probe was brought towards the animal’s head until it was close to the animal’s nose 

(but not touching the vibrissae). The animal’s reaction was recorded as:

1 No reaction or ignores probe

2 Normal awareness and reaction e.g. approaches and/or sniffs probe

3 Abnormally fearful or aggressive reaction

Touch response

The animal was stroked gently on the nape of the neck with a blunt probe and the reaction 

recorded as:

1 No reaction or ignores probe

2 Normal awareness and reaction e.g. turns towards or moves away

3 Abnormally fearful or aggressive reaction

Auditory startle reflex

The animal’s response to a sudden loud noise was assessed and scored as:

1 No response

2 Weak response e.g. ear twitch only

3 Normal response e.g. obvious flinch or startle

4 Exaggerated response e.g. all feet off floor

Tail pinch response

The animal’s tail was pinched sharply with forceps approximately one third from the tip and 

the response graded as:

1 No response

2 Weak response e.g. turns around slowly or weak vocalisation without 

moving away

3 Normal response e.g. jumps forward or turns around sharply, usually with

vocalisation

4 Exaggerated response e.g. excessive vocalisation, body movement or

aggression
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Grip strength

Forelimb and hindlimb grip strength was measured using Mecmesin Force Indicators. Three 

trials were performed.

At any point during the observations, additional comments were made as free text where 

considered appropriate.

2.4.4 Motor activity

During Week 12 of treatment (before dosing), the motor activity of all main study animals 

and all recovery phase animals was measured using a Rodent Activity Monitoring System

(Version 2.0.5), with hardware supplied by Pearson Technical Services and software 

developed and maintained by Huntingdon Life Sciences. In addition, all recovery phase 

animals were tested during Week 4 of recovery.

Animals were tested individually in clear polycarbonate cages and motor activity was 

measured by counting infra-red beam breaks over ten 6-minute intervals (one hour total). 

Ten beams were set at two height levels (five low and five high) to detect cage floor and 

rearing activity respectively. Animals were not necessarily all tested on the same day, but the 

numbers of animals and the times of testing were balanced across the groups on each day of 

testing. 

2.4.5 Mortality

Debilitated animals were observed carefully and, where necessary, isolated to prevent 

cannibalism. Animals were killed for reasons of animal welfare where necessary. Where 

possible, blood samples were taken ante mortem and analysed for the characteristics specified 

in the haematology and blood chemistry sections below. A complete necropsy was 

performed in all cases as described below.

2.4.6 Bodyweight

The weight of each rat was recorded one week before treatment commenced (Week -1), on 

the day that treatment commenced (Week 0), weekly throughout the treatment and recovery

periods, and before necropsy.

2.4.7 Food consumption

The weight of food supplied to each cage, that remaining and an estimate of any spilled was 

recorded for the week before treatment started (Week -1, 5 days of recording only), and each 

week throughout the treatment and recovery periods.

2.4.8 Ophthalmic examination

Before treatment commenced, the eyes of all animals allocated to the study (including spare 

animals) were examined by means of a binocular indirect ophthalmoscope. During Week 13 

of treatment the eyes of all animals of Groups 1 (Control) and 4 (2876 ppm) were similarly 

examined.

Prior to each examination, the pupils of each animal were dilated using tropicamide 

ophthalmic solution (Mydriacyl). The adnexae, conjunctiva, cornea, sclera, anterior chamber, 

iris (pupil dilated), lens, vitreous and fundus were examined.

As no treatment-related changes were observed, the examination was not extended to 

Groups 2 and 3 during Week 13 or the recovery phase.
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2.4.9 Haematology, peripheral blood

During Week 13 of treatment (before dosing on each occasion) and Week 4 of recovery,

blood samples were obtained from all animals after overnight withdrawal of food. Animals 

were held under light general anaesthesia induced by isoflurane and blood samples were 

withdrawn from the sublingual vein.

Blood samples (nominally 0.5 mL) were collected into tubes containing EDTA as 

anticoagulant and examined for the following characteristics using a Bayer Advia 120 

haematology analyser:

Haematocrit (Hct)

Haemoglobin concentration (Hb) 

Erythrocyte count (RBC)

Reticulocyte count (RETA)

Mean cell haemoglobin (MCH)

Mean cell haemoglobin concentration (MCHC)

Mean cell volume (MCV)

Total white cell count (WBC)

Differential WBC count

Neutrophils (N) 

Lymphocytes (L)

Eosinophils (E)

Basophils (B)

Monocytes (M)

Large unstained cells (LUC)

Platelet count (Plt)

Morphology flags were generated by the Advia 120 analyser. The most common 

morphological changes, anisocytosis, micro/macrocytosis and hypo/hyperchromasia were 

categorised as follows:

- = no abnormalities detected

+ = slight

++ = moderate

+++ = marked

Blood film (prepared for all samples) - Romanowsky stain, examined for abnormalities by 

light microscopy, in the case of flags from the Advia 120 analyser. Confirmation or a written 

description from the blood film was made where appropriate.

Additional blood samples (nominally 0.5 mL) were taken into tubes containing citrate 

anticoagulant and examined in respect of:

Prothrombin time (PTP) - using an ACL 9000 analyser and IL PT-Fibrinogen 

reagent. 

Activated partial thromboplastin time (APTT) - using an ACL 9000 Analyser and IL 

APTT reagent
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2.4.10 Blood chemistry

At the same time and using the same animals as for peripheral haematology, further blood 

samples (nominally 0.7 mL) were collected into tubes containing lithium heparin as 

anticoagulant. All tubes were mechanically agitated for at least two minutes and the sample 

subsequently centrifuged at 2000 g for 10 minutes in order to separate the plasma. After

separation, the plasma was examined in respect of:

Using a Roche P Modular Analyser:

Alkaline phosphatase (ALP)

Alanine aminotransferase (ALT)

Aspartate aminotransferase (AST)

Total bilirubin (Bili)

Urea

Creatinine (Creat)

Glucose (Gluc)

Total cholesterol (Chol)

Triglycerides (Trig)

Sodium (Na) 

Potassium (K) 

Chloride (Cl) 

Calcium (Ca)

Inorganic phosphorus (Phos)

Total protein (Total Prot)

Albumin (Alb)

Albumin/globulin ratio (A/G Ratio) was calculated from total protein concentration and 

analysed albumin concentration.

2.4.11 Urinalysis

During Week 13 of treatment, overnight urine samples were collected from all animals. 

Animals were placed in an individual metabolism cage without food or water at 

approximately 16.00 hours; urine was collected until approximately 07.00 hours the 

following day.

The individual samples were examined for the following characteristics:

Appearance (App) - by visual assessment using the following abbreviations:

PY Pale yellow PO Pale orange

MY Medium yellow DO Dark orange

DY Dark yellow

Volume (Vol)

pH - using a Radiometer PHM 92 pH meter

Specific gravity (SG) - using Atago UR-1 digital refractometer

Protein (Prot), sodium (TNAR), potassium (TUKR) and chloride (TCLR) - using Roche P

Modular
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Glucose (Gluc), ketones (Keto), bile pigments (Bili), blood pigments (UBld) by Multistix, 

diagnostic reagents used as qualitative indicators of analyte concentration. The reagent strips 

were interpreted using the Clinitek®500 instrument and results were categorised using the 

following convention:

NEG = negative

TRA = trace levels

1+ = ‘small amount’ of analyte

2+ = ‘moderate amount’ of analyte

3+ = ‘large amount’ of analyte

4+ = ‘very large amount’ of analyte

A microscopic examination of the urine sediment was performed. An aliquot of the urine 

sample was centrifuged, stained with Kova stain and the resulting deposit spread on a 

microscope slide. The number of elements seen in nine high or low power fields (HPF or 

LPF) was recorded in the raw data and entered onto the database and the number seen /HPF 

or /LPF was derived from these data as described below.

Casts/LPF (CAS)

Leucocytes (Leuc)

Erythrocytes (RBC)

Crystals (Cryst)

Spermatozoa (Sperm)

Epithelial cells/HPF (Epi)

Abnormalities (A)

2.5 Necropsy and Histology

2.5.1 Method of kill

Animals killed during the study and those surviving until the end of the scheduled treatment 

or recovery period were killed by overdose of sodium pentobarbitone solution by intravenous 

injection and subsequent exsanguination. The sequence in which the animals were killed 

after completion of treatment or recovery was selected to allow satisfactory inter-group 

comparison.
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2.5.2 Macroscopic pathology

All animals were subject to a detailed necropsy.

After a review of the history of each animal, a full macroscopic examination of the tissues 

was performed. All external features and orifices were examined visually. The cranial roof 

was removed to allow observation of the brain, pituitary gland and cranial nerves. After 

ventral mid-line incision, the neck and associated tissues and the thoracic, abdominal and 

pelvic cavities and their viscera were exposed and examined in situ. Any abnormal position, 

morphology or interaction was recorded.

The requisite organs were weighed and external and cut surfaces of the organs and tissues 

were examined as appropriate. Any abnormality in the appearance or size of any organ and 

tissue was recorded and the required tissue samples preserved in appropriate fixative.

The retained tissues were checked before disposal of the carcass.

2.5.3 Organ weights

The following organs, taken from each animal killed after 13 weeks of treatment or 4 weeks 

of recovery, were dissected free of adjacent fat and other contiguous tissue and the weights

recorded:

Adrenals Prostate

Brain Salivary glands (submandibular/sublingual)#

Epididymides Seminal vesicles 

Heart Spleen

Kidneys Testes

Liver Thymus

Lungs with mainstem bronchi Thyroid with parathyroids*

Ovaries Uterus with cervix 

Pituitary

* Weighed after partial fixation

# Weighed together and reported as salivary glands

Bilateral organs were weighed together. Organ weights were also adjusted for terminal 

bodyweight, using the weight recorded before necropsy.
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2.5.4 Fixation

Testes were fixed in modified Davidson's fluid and eyes were fixed in Davidson's fluid. 

Samples (or the whole) of the other tissues listed below from all animals were preserved in 

10% neutral buffered formalin:

Adrenals Ovaries

Aorta - thoracic Pancreas

Bone marrow smear Peyer’s patches

Brain Pituitary

Caecum Prostate

Colon Rectum

Duodenum Salivary glands - submandibular+

Epididymides - parotid+

Eyes - sublingual+

Femurs+ Sciatic nerves+

Harderian glands Seminal vesicles

Head# Skeletal muscle+

Heart Skin with mammary glands

Ileum Spinal cord

Jejunum Spleen

Kidneys Sternum

Lachrymal glands Stomach

Larynx Teeth - lower incisors (pair)

Liver Testes

Lungs Thymus

Lymph nodes - mandibular Thyroid with parathyroids

- mesenteric Tongue

- tracheobronchial Trachea

Nasal turbinates Urinary bladder

Oesophagus Uterus and cervix

Optic nerves Vagina

+ Only one processed for examination

# Not processed for examination

Samples of any abnormal tissues were also retained and processed for examination. In those

cases where a lesion was not clearly delineated, contiguous tissue was fixed with the grossly 

affected region and sectioned as appropriate.

Samples of the head (including nasal cavity, paranasal sinuses and nasopharynx) and the 

remaining femur, salivary gland, sciatic nerve and skeletal muscle were not examined 

histologically, but are retained against any future requirement for microscopic examination.
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2.5.5 Histology

For those animals specified in the Pathology section, the relevant tissues were subject to 

histological processing.

Those tissues subject to histological processing included the following regions:

Adrenals - cortex and medulla

Brain - cerebellum, cerebrum and midbrain

Femur with joint - longitudinal section including articular surface, epiphysial 

plate and bone marrow

Heart - included auricular and ventricular regions

Kidneys - included cortex, medulla and papilla regions

Liver - section from two main lobes

Lungs - section from all major lobes, to include bronchi

Spinal cord - transverse and longitudinal section at the cervical, lumbar and 

thoracic levels

Sternum - included bone marrow

Stomach - included keratinised, glandular and antrum in sections

Thyroid - included parathyroids in section where possible

Uterus - uterine body with cervix section

For bilateral organs, sections of both organs were prepared. A single section was prepared 

from each of the remaining tissues required for microscopic pathology.

2.6 Pathology

2.6.1 Light microscopy

Microscopic examination was performed as follows:

All tissues preserved for examination (as specified above) were examined for all 

animals of Groups 1 (Control) and 4 (2876 ppm) sacrificed on completion of the 

scheduled treatment period and for all animals killed or dying during the study.

Nasal turbinates, larynx, lungs, trachea (including bifurcation), heart, liver, pancreas, 

spleen, thymus, teeth and abnormalities preserved for examination were examined 

for all animals of Group 2 (199 ppm), Group 3 (505 ppm) and all recovery animals 

sacrificed on completion of the scheduled treatment period.

Tissues reported at macroscopic examination as being grossly abnormal were 

examined for Main and Recovery animals in line with current practice.

Findings were either reported as "present" or assigned a severity grade. In the latter case one 

of the following five grades was used - minimal, slight, moderate, marked or severe. A 

reviewing pathologist undertook a peer review of the microscopic findings.
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The descriptions listed below are an attempt to define the grades in general terms for all 

microscopic findings reported in a study and are not specific for a particular tissue. They are 

more strictly applicable to some types of lesion than to others, and there may therefore be a 

few lesions for which these definitions are not completely appropriate.

Thresholds for the grading of lesions for certain tissues may vary with type of study and also 

may vary, generally for all tissues or the majority of tissues, with the duration of the study.

In increasing order of degree/severity.

Minimal The lowest grade of a lesion which is discernible/distinguishable from 

normal and is often subtle and/or involving a very small area of the 

organ.

Slight Clearly discernible/distinguishable from normal with more extensive or 

more apparent changes than minimal.

Moderate Generally involves a significant proportion of the affected organ or 

tissue.

Marked Involves the majority of the affected organ or tissue.

Severe Involves all or almost all of an affected organ or tissue.

A reviewing pathologist undertook a peer review of the microscopic findings.

In addition, heart tissue slides from all males (main study and recovery) were independently 

peer reviewed by an external consultant pathologist. 
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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:

ClinAxys II (version 2.0.2) used for haematology, blood chemistry and urinalysis.

Liberate Release 2 in-house system used for reporting clinical signs, dosing signs, 

bodyweights, food consumption, organ weights, macropathology and 

histopathology, statistics.

Quasar (version 1.3) and SAS (version 9.1.3) in-house statistical analysis packages

used for bodyweights and organ weights statistics.

RAMS Rodent Activity Monitoring System (version 2.0) used for activity 

monitoring.

Responder - X (version 5.11) used for startle response.

Sample Registry System (version 1.0) used for Formulation and Inhalation Analysis 

data.

StarTox (version 3.2) in-house statistical analysis package used for grip strength and 

motor activity and clinical pathology statistics.

Waters Empower 2, Build 2154, Feature Release 4, Service Pack D and used for 

Formulation and Inhalation Analysis.

Xybion Path/Tox System (version 4.2.2) used for clinical signs, dosing signs, 

bodyweights, food consumption, ophthalmic examination, organ weights, 

macropathology and histopathology.

Xybion Pristima (version 6.3) used for Pharmacy test substance management.

2.8 Data treatment

This report contains serial observations pertaining to all weeks of treatment and recovery

completed, together with signs data collected during the necropsy period. The only serial 

observations relating to the acclimatisation period included in this report relate to the detailed 

physical examination and arena observations, Week -1 bodyweights, food consumption and 

ophthalmic examination.

Summary statistics (e.g. means and standard deviations) presented in this report were 

calculated from computer-stored individual raw data. The summary statistics and the 

individual data were stored in the computer to a certain number of decimal places, different 

for each parameter. For presentation purposes, however, they were usually rounded to fewer 

places. It is, therefore, not generally possible to reproduce the presented means and standard 

deviations exactly using the presented individual data.
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Throughout the report the following abbreviations are used:

M Male

F Female

R Recovery

N Number of animals/cages examined

SD Standard deviation

The death codes in the appendices have the following meaning:

T Scheduled kill

W Killed for reasons of animal welfare

2.8.1 Definition of “Week”

The first week of treatment started at midnight prior to treatment commencing and ended at 

midnight on the seventh day following. Subsequent experimental weeks of treatment and 

recovery were of the same duration.

2.8.2 Signs

Signs are considered in two parts: observations made in association with treatment, classified 

as “dosing signs” and extended changes in condition, classified as “clinical signs”. Both are 

presented for each animal that showed signs, providing detail of type of sign, day or week of 

occurrence and information on the duration of the sign applicable.

Observations during the recovery phase are recorded on a study week basis. Weeks of study

relate to weeks of recovery as follows:

Week of recovery Week of Study

R1 14

R2 15

R3 16

R4 17

2.8.3 Bodyweight

Group mean weight changes were calculated from the weight changes of individual animals

surviving the specified period.

2.8.4 Ophthalmic examination

For each animal that showed findings, observations are presented in the final report. 

Observations were bilateral unless otherwise indicated:

L Left eye

R Right eye
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2.8.5 Haematology

The abbreviations used in the Appendix have the following meanings:

NVR No valid result

CTD Clotted sample

2.8.6 Blood chemistry

Albumin to globulin ratio (A/G ratios) were calculated as:

A/G Ratio = Albumin concentration

Total protein – albumin concentration

2.8.7 Urinalysis

The abbreviations used in the Appendix have the following meanings:

TNQ Too numerous to quantify

INS Insufficient sample

Group means and standard deviations are presented for volume, pH, specific gravity, protein 

and electrolytes only.

2.8.8 Organ weights

The abbreviations used in the Appendix have the following meanings:

Thyroids + Paras Thyroids with parathyroids

2.8.9 Pathology

The abbreviations used in the Appendix have the following meanings: 

LN Lymph nodes

Bifurc. Bifurcation

C. Cord

Cerv. Cervical

Lumb. Lumbar

Thor. Thoracic

Fac. Con. Factors contributing

S.G. Salivary glands

inc. Including

Tissues which could not be examined are specified in the Appendix. The absence of a 

comment for a tissue scheduled for examination therefore indicates that the tissue was 

considered to be normal. In all tabular presentations of data the tissues specified in the 

protocol for histopathological examination precede other tissues.
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2.8.10 Statistical analysis

All statistical analyses were carried out separately for males and females.

All analyses were carried out using the individual animal as the basic experimental unit.

The following data types were analysed at each timepoint separately:

Grip strength and motor activity

Bodyweight, using gains over appropriate study periods

Blood chemistry, haematology and urinalysis

Organ weights, either absolute or adjusted for terminal bodyweight where 

appropriate

The following sequence of statistical tests was used for grip strength, motor activity, 

bodyweight, organ weight and clinical pathology data:

A parametric analysis was performed if Bartlett's test for variance homogeneity 

(Bartlett 1937) was not significant at the 1% level. The F1 approximate test was 

applied. This test is designed to detect significant departure from monotonicity of

means when the main test for the comparison of the means is a parametric 

monotonic trend test, such as Williams’ test (Williams 1971, 1972). The test 

statistic compares the mean square, NMS, for the deviations of the observed means 

from the maximum likelihood means, calculated under a constraint of monotonicity 

with the usual error mean square, EMS. 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 EMS degrees of 

freedom. If the F1 approximate test for monotonicity of dose-response was not 

significant at the 1% level, Williams' test for a monotonic trend was applied. If the 

F1 approximate test was significant, suggesting that the dose response was not 

monotone, Dunnett's test (Dunnett 1955, 1964) was performed instead. Where there 

were only two groups, comparisons were made using t-tests.

A non-parametric analysis was performed if Bartlett's test was still significant at the 

1% level following both logarithmic and square-root transformations. The H1

approximate test, the non-parametric equivalent of the F1 test described above, was 

applied. This test is designed to be used when the main test for comparison of the 

means is a non-parametric monotonic trend test, such as Shirley's test (Shirley 1977). 

The test statistic compares the non-monotonicity sums of squares, NRSS, for the 

deviations of the observed mean ranks from the maximum likelihood mean ranks 

with the non-parametric equivalent 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 χ2-distribution with 1 degree of freedom. If the H1

approximate test for monotonicity of dose-response was not significant at the 1% 

level, Shirley's test for a monotonic trend was applied. If the H1 approximate test 

was significant, suggesting that the dose-response was not monotone, Steel's test 

(Steel 1959) was performed instead. Where there were only two groups, 

comparisons were made using Wilcoxon rank sum tests (Wilcoxon 1945).
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For grip strength, motor activity and clinical pathology data, if 75% of the data (across all 

groups) were the same value, for example c, Fisher’s Exact tests (Fisher 1973) were 

performed. Treatment groups were compared using pairwise comparisons of each dose group 

against the control both for i) values <c versus values ≥c, and for ii) values ≤c versus values 

>c, as applicable.

For organ weight data, analysis of covariance was performed using terminal bodyweight as 

covariate (Angervall and Carlstrom, 1963), unless non-parametric methods were applied. 

The treatment comparisons were made on adjusted group means in order to allow for 

differences in bodyweight which might influence the organ weights.

Key to Tables

Significant differences between the groups compared were expressed at the 5% (p<0.05) or 

1% (p<0.01) level. The key to the annotation used on the tables that contain statistical results 

is given below.

l Data were log transformed for the statistical analysis.

Du Treated groups compared to Control using Dunnett’s test.

Sh Treated groups compared to Control using Shirley’s test.

Wi Treated groups compared to Control using Williams’ test.

Tt Group 4 compared with Control/Vehicle using t-test.

Wc Group 4 compared with Control/Vehicle using Wilcoxon rank sum test.

Codes placed above adjusted means indicate that the comparisons were based on adjusted 

means.

* p<0.05

** p<0.01
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2.9 Quality assurance and archiving procedures

2.9.1 Quality assurance

Details of the Quality Assurance inspections and audits (undertaken at Huntingdon Life 

Sciences) are presented on the Quality Assurance Statement.

2.9.2 Archives

Following completion of this study all raw data, specimens and samples, except those 

generated or used during any Sponsor’s or supplier’s analysis, were stored in the archives of 

Huntingdon Life Sciences. Types of sample and specimen which are unsuitable, by reason of 

instability, for long term retention and archiving may be disposed of after the periods stated 

in Huntingdon Life Sciences Standard Operating Procedures.

A copy of the final report and all Quality Assurance inspection records will be retained 

indefinitely. All other appropriate specimens and records will be retained for a minimum 

period of one year from the date of issue of the final report. At the end of this retention 

period the Sponsor will be contacted and advice sought on future archiving requirements. 

Under no circumstances will any item be discarded without the Sponsor’s knowledge.

2.10 Deviations from protocol

The following deviations from protocol occurred:

Section 5.1 of the protocol stated that pre-study characterization work would only be 

performed to “demonstrate reproducibility of test substance concentration”. 

However, additional work was also carried out to confirm that the spatial 

distribution of the test material around the chamber was consistent for the high 

number of animals dosed in each chamber. The deviation from protocol

strengthened the pre-study atmosphere characterization work and confirmed that it 

satisfied the needs of the study.

Treatment related effects on the teeth of Group 4 females (brittleness and breakage) 

resulted in a reduction in food consumption. Consequently, powdered diet (standard 

pelleted diet, as supplied to other study rats, ground down to powder) was supplied 

to all Group 4 females from Day 64 (Cage 7) or Day 72 (Cages 8, 19 and 20). Food 

consumption recording was unaffected by the supply of the powered diet.

These deviations were considered to have not affected the integrity or validity of the study.
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3. Results

3.1 Chamber atmosphere conditions

Annex 2

Summary data are presented below:

Group Aerosol concentration (ppm)

Target Study mean

1 0 -

2 200 199

3 500 505

4 3000 2876

The achieved aerosol concentrations were 100, 101 and 96% of the target concentration for 

Groups 2, 3 and 4, respectively.

3.2 Signs and mortality

Appendix 1 and Appendix 2

There were no deaths that were considered to be a direct result of exposure to the test 

material, 2 bromo 3,3,3 trifluoropropene.

Animal 79, a male exposed to 2876 ppm, died in its home cage prior to the start of exposures 

on Day 3. Animal 79 had no apparent abnormalities at the initial morning health check. 

However, its condition was then seen to decline over a period of less than an hour, and it died 

before a necropsy could be arranged. Macroscopic examination at necropsy revealed; dark 

lungs, incomplete collapse of the lungs and slightly dark tracheobronchial lymph nodes. This 

decedent was renumbered 79R and replaced with a spare rat given the original number (79). 

The replacement was made prior to the start of Day 3 exposures. No data from Animal 79R 

is presented in this report.

Animal 27, a Control female, was killed on welfare grounds on Day 52. At the initial 

morning health check Animal 27 was found to be underactive, with reduced body 

temperature, gasping breathing, piloerection, partially closed eyelids and pallor. The animal 

was subsequently sent to necropsy due to general poor clinical condition. Macroscopic 

examination at necropsy revealed; thickened pericardium of the heart with adhesions and 

copious amounts of dark pericardial fluid, irregular surface of the liver, dark tracheobronchial 

lymph nodes, copious amounts of clear, serous fluid in the thorax, and oedematous pancreas 

and thymus.
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Clinical signs seen during exposure over the 13 weeks of treatment, for all groups exposed to 

the test material, included: unresponsiveness to external stimuli, underactivity, slow and/or 

shallow breathing, hunched posture (Day 1 and 94 only), grinding teeth (at 505 ppm, Day 25 

only), piloerection and partially closed eyelids (closed eyelids on Day 1). These signs 

generally resolved quickly on cessation of exposure to the test article. The number and 

prevalence of signs increased with exposure level.

Abnormally pale, white teeth were evident for animals from all test material groups. 

Animal 92, a female exposed to 2876 ppm was observed as having broken teeth on Day 71. 

A proportion of females exposed to 2876 ppm, teeth were reported as having brittle teeth. 

Consequently, all females exposed to 2876 ppm received powdered diets from Day 64 

(Cage 7) or Day 72 (Cages 8, 19, and 20).

3.3 Sensory reactivity and grip strength

Table 1 and Appendix 3

Sensory reactivity observations for males and females were unaffected.

During Week 12 of treatment grip strength values were statistically significantly reduced for

animals exposed to 2876 ppm (forelimbs and hindlimbs) and in males exposed to 505 ppm 

(hindlimbs only). Grip strength for animals exposed to 199 ppm and for females exposed to 

505 ppm was unaffected. Forelimb grip strength values for animals previously exposed to 

2876 ppm were similar to those of controls during Week 4 of recovery but hindlimb values 

were still low, although to a lesser extent than during Week 12 of treatment.

3.4 Motor activity

Figure 1, Table 2 and Appendix 4

High beam and low beam motor activity scores (rearing and cage floor activity respectively) 

were consistently reduced in animals exposed to 2876 ppm throughout most of the 1-hour 

recording period during Week 12 of treatment. High beam scores for animals exposed to 

505 ppm were also reduced, as, to a lesser extent, were low beam scores for females exposed 

to 505 ppm, with a dose-relationship being evident. Motor activity for animals exposed to 

199 ppm was considered to be unaffected, despite statistically significant reductions for both 

high and low beam scores at a single timepoint (36 minutes). 

Low beam scores for females previously exposed to 2876 ppm were again low compared 

with control scores during Week 4 of recovery but the differences were less marked than 

during Week 12 of treatment. High and low beam scores for males previously exposed to 

2876 ppm were lower than control at a few of the 6-minute intervals (p<0.05 or 0.01) but the 

total activity scores over the 1-hour recording period did not attain statistical significance. 
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3.5 Bodyweight

Figure 2, Table 3 and Appendix 5

Bodyweight gain over the 13 weeks of treatment were statistically significantly lower for 

males receiving 199, 505 or 2876 ppm (0.78X, 0.73X and 0.52X control respectively) and for 

females receiving 505 or 2876 ppm (0.79X and 0.55X control respectively), with evidence of 

a dose relationship.

Differences from controls remained similar throughout the study period for animals receiving 

199 or 505 ppm. However, for animals receiving 2876 ppm, the reduction in bodyweight 

gain was more marked from Week 6 until the end of treatment.

Over the 4 week recovery period, bodyweight gains for males and females previously

receiving 2876 ppm showed evidence of recovery and were 1.82 and 1.77X control values 

respectively. However, gains were small for females, and overall bodyweights were still 

considerably reduced compared with control values.

3.6 Food consumption

Appendix 6

Mean food consumption over the 13 weeks of treatment was statistically significantly lower 

for treated males (0.90X, 0.85X and 0.74X control, with ascending dose) and females 

exposed to 2876 ppm compared with control (0.81X control), with evidence of a dose 

relationship in males.

Within groups, food consumption was consistent throughout the study period, with similar 

differences from control seen after 6 and 10 weeks to those seen after 13 weeks.

Over the 4 week recovery period, animals previously exposed to 2876 ppm showed some 

recovery of food consumption compared to treatment values, and were approximately 

0.9X control values over the recovery period.

3.7 Ophthalmic examination

Appendix 7

Ophthalmic examination revealed no treatment-related effects.

3.8 Haematology

Table 4 and Appendix 8

Week 13 group mean total white blood cell counts were lower than control for males and 

females exposed to 2876 ppm (0.78 and 0.68X control respectively), statistically significantly 

so for females. This was mainly as a result of statistically significantly lower lymphocytes 

counts (0.68 and 0.66X control for males and females exposed to 2876 ppm, respectively). 

During Week 4 of recovery, differences from control for total white blood cell and 

lymphocyte counts remained similar to Week 13 values for both sexes previously exposed to 

2876 ppm.
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Eosinophil counts were statistically significantly lower than control for all treated animals, 

with evidence of a dose-related response (0.26 to 0.47X and 0.27 to 0.64X control for males 

and females exposed to 199 and 2876 ppm respectively). However, during Week 4 of 

recovery eosinophil counts showed evidence of some recovery to control values. 

Monocyte counts were statistically significantly higher than control for males and females 

exposed to 505 and 2876 ppm (1.74 and 1.84X control for males, and 2.16 and 1.68X control 

for females respectively). However, during Week 4 of recovery monocyte counts were lower 

than control values for both sexes previously exposed to 2876 ppm.

Remaining differences from control that attained statistical significance were small, 

inconsistent between sexes and did not show clear dose relationships.

3.9 Blood chemistry

Table 5 and Appendix 9

Week 13 mean alkaline phosphatase (ALP) values for males and females exposed to 

2876 ppm were statistically significantly higher (1.32 and 1.43x control, respectively). 

During Week 4 of recovery, values for males previously exposed to 2876 ppm were 

unchanged. However, for females of the same group, values had lowered and were similar to 

Week 13 control values.

Group mean values for aspartate amino transferase (AST) were statistically significantly 

higher than control for treated males (2.31, 3.00 and 2.88X with ascending dose), and females 

exposed to 505 ppm (2.72X control). There was considerable intragroup variation for this 

parameter. However, the group mean changes seen were outside the range of available 

background data. During Week 4 of recovery, values for both sexes previously exposed to 

2876 ppm were similar to controls.

Group mean values for urea were statistically significantly higher than control for treated 

females (1.18, 1.24 and 1.54X control with ascending dose), and males exposed to 505 and 

2876 ppm (1.25 and 1.64X control, respectively).Group mean phosphate values were 

statistically significantly higher for treated females (1.42, 1.75 and 2.38X control, with

ascending dose) and males exposed to 2876 ppm (1.30X control). During Week 4 of

recovery, urea values for both sexes previously exposed to 2876 ppm had returned to control 

values.

Remaining differences from control that attained statistical significance were inconsistent 

between sexes and did not show clear dose relationships.

3.10 Urinalysis

Table 6 and Appendix 10

There were no treatment related effects on urinalysis parameters.

Differences between control and test values that attained statistical significance for urinalysis 

parameters were often inconsistent between sexes and were related to slight differences in 

urine volume.
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3.11 Organ weights

Table 7 and Appendix 11

After 13 weeks of treatment, thymus weights were statistically significantly lower for males 

and females exposed to 2876 ppm (0.63 and 0.54X control, respectively). However, after 

4 weeks recovery, thymus weights appeared to have fully recovered to control values.

Lung and bronchi weights were slightly elevated for males exposed to 505 or 2876 ppm (1.07 

and 1.12X control respectively), with similar values after 4 weeks of treatment for males

previously exposed to 2876 ppm.

Salivary gland weights were statistically significantly lower than control values for all treated 

females (0.81, 0.82 and 0.84X control, with ascending dose). For males, a reduction in 

salivary gland weights was also evident (between 0.88 and 0.89X control for all treated 

males), however, these did not achieve statistical significance. However, after 4 weeks 

recovery these have recovered to control values.

Remaining differences from control that attained statistical significance were inconsistent 

between sexes and considered to be due to individual variation and not of any toxicological 

importance.
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3.12 Macropathology

Table 8, Appendix 12 and Annex 3.

3.12.1 Animals killed after 13 weeks of treatment

The macroscopic examination performed after 13 weeks of treatment revealed the following 

intergroup differences of note:

Teeth

Pallor was noted in all animals exposed to 2876 ppm, the majority of animals exposed to 

505 ppm and a few animals exposed to 199 ppm. Thickening was seen in the majority of

females and one male exposed to 2876 ppm.

Summary of findings in the teeth for animals killed after 13 weeks of treatment

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Incisor(s) pale 0 3 7 10 0 3 9 10

Incisor(s) thickened 0 0 0 1 0 0 0 8

Number of animals examined 10 10 10 10 9 10 10 10

Spleen

Capsular thickening was observed in the majority of males and some females exposed to 

2876 ppm and a few animals exposed to 505 ppm. Adhesions were noted in some females 

exposed to 505 or 2876 ppm.

Summary of findings in the spleen for animals killed after 13 weeks of treatment

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Capsule thickened 1 1 4 8 0 1 2 5

Adhesions 0 0 0 0 0 0 2 5

Number of animals examined 10 10 10 10 9 10 10 10

The nature and incidence of all the other findings were consistent with the commonly seen 

background of macroscopic changes.
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3.12.2 Animals killed after 4 weeks of recovery

The macroscopic examination performed after 4 weeks of recovery revealed the following 

changes in teeth and spleen.

Teeth

Pallor was noted in all animals exposed to 2876 ppm. Thickening was seen in occasional 

females and one male previously exposed to 2876 ppm.

Summary of findings in the teeth for animals killed after 4 weeks of recovery

Group/sex 1M 4M 1F 4F

Dose (ppm) 0 2876 0 2876

Incisor(s) pale 0 10 0 10

Incisor(s) thickened 0 1 0 3

Number of tissues examined 10 10 10 10

Spleen

Capsular thickening was observed in one male previously exposed to 2876 ppm. Adhesions 

were noted in some males and one female previously exposed to 2876 ppm.

Summary of findings in the spleen for animals killed after 4 weeks of recovery

Group/sex 1M 4M 1F 4F

Dose (ppm) 0 2876 0 2876

Capsular thickened 0 1 0 0

Adhesions 0 2 0 1

Number of tissues examined 10 10 10 10

All other findings were considered to be unrelated to treatment.
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3.13 Histopathology

Table 9, Appendix 12, Annex 3 and Annex 4.

3.13.1 Animals killed after 13 weeks of treatment

Treatment related findings

Changes related to treatment with 2-bromo-3, 3, 3-trifluoropropene were seen in liver, 

pancreas, heart, spleen, thymus, larynx, nasal turbinates and teeth.

Liver

Centrilobular hepatocyte hypertrophy was seen in rats exposed to 2876 ppm and a female 

exposed to 505 ppm.

Summary of treatment related findings in the liver for animals killed after 13 weeks of treatment

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Hepatocyte Hypertrophy, 

Centrilobular

Minimal 0 0 0 2 0 0 1 4

Total 0 0 0 2 0 0 1 4

Number of tissues examined 10 10 10 10 9 10 10 10

Pancreas

Increased incidence of acinar cell degranulation was seen in rats at all exposure levels.

Summary of treatment related findings in the pancreas for animals killed after 13 weeks of treatment

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Acinar Cell Degranulation

Minimal 0 3 2 1 0 2 3 0

Slight 0 0 3 5 1 2 2 6

Moderate 0 0 0 1 0 0 0 0

Total 0 3 5 7 1 4 5 6

Number of tissues examined 10 10 10 10 9 10 10 10
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Heart

Increased incidence of chronic inflammation was seen in males exposed to 199 ppm and both 

sexes exposed to 505 or 2876 ppm.

Summary of treatment related findings in the heart for animals killed after 13 weeks of treatment

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Inflammation, Chronic

Minimal 0 4 2 1 0 0 4 7

Slight 0 0 7 3 0 0 0 2

Moderate 0 0 0 4 0 0 0 1

Total 0 4 9 8 0 0 4 10

Number of tissues examined 10 10 10 10 9 10 10 10

Spleen

Increased incidences of capsular inflammation and/ or thickening were seen in rats exposed 

to 505 or 2876 ppm.

Adhesion was seen in females exposed to 505 or 2876 ppm.

Summary of treatment related findings in the spleen for animals killed after 13 weeks of treatment

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Capsular Inflammation

Minimal 0 0 1 2 0 1 0 1

Slight 0 0 1 3 0 0 1 3

Moderate 0 0 1 0 0 0 0 2

Total 0 0 3 5 0 1 1 6

Capsular Thickening

Minimal 0 1 1 4 1 2 2 2

Slight 1 0 2 2 0 0 1 2

Moderate 0 0 0 0 0 0 0 4

Total 1 1 3 6 1 2 3 8

Adhesion

Total 0 0 0 0 0 0 1 3

Number of tissues examined 10 10 10 10 9 10 10 10
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Thymus

Involution/ atrophy was seen in one male and five female rats exposed to 2876 ppm.

Summary of treatment related findings in the thymus for animals killed after 13 weeks of treatment

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Involution/Atrophy

Minimal 0 0 0 0 0 0 0 2

Slight 0 0 0 0 0 0 0 1

Moderate 0 0 0 1 0 0 0 2

Total 0 0 0 1 0 0 0 5

Number of tissues examined 10 10 10 10 9 10 10 10

Larynx

Ventral squamous metaplasia was seen in five male and two female rats exposed to 

2876 ppm.

Summary of treatment related findings in the larynx for animals killed after 13 weeks of treatment

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Squamous Metaplasia - Ventral

Minimal 0 0 0 5 0 0 0 2

Total 0 0 0 5 0 0 0 2

Number of tissues examined 10 10 10 10 9 10 10 10

Nasal Turbinates

In the respiratory epithelium, atrophy/disorganization/vacuolation, inflammation and 

inflammatory cells in the lamina propria were seen in the rats exposed to 2876 ppm. A case 

of regenerative hyperplasia was also seen in a male at the same exposure level.

In the olfactory epithelium, atrophy/ disorganisation /vacuolation, was seen in rats exposed to 

505 or 2876 ppm. Inflammation and inflammatory cells in the lamina propria were seen in 

rats exposed to 2876 ppm. Respiratory metaplasia was seen in females exposed to 2876 ppm.

In the nasolacrimal duct, inflammation was seen in females exposed to 505 ppm and both 

sexes exposed to 2876 ppm. Epithelial squamous metaplasia and luminal inflammatory

exudates were seen in females exposed to 2876 ppm.

Inflammatory exudates in airways were seen in rats exposed to 2876 ppm.
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Summary of treatment related findings in the nasal turbinates for animals killed after 13 weeks of 

treatment

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Increased Vacuolation of 

Vomeronasal Organ Epithelium

Minimal 0 0 0 1 0 0 0 0

Slight 0 0 0 2 0 0 0 0

Total 0 0 0 3 0 0 0 0

Respiratory Epithelium

Atrophy/ Disorganisation/ 

Vacuolation

Minimal 0 1 0 1 1 1 1 1

Slight 0 0 0 4 0 0 0 6

Moderate 0 0 0 1 0 0 0 3

Total 0 1 0 6 1 1 1 10

Inflammation

Minimal 0 0 0 0 0 0 0 1

Slight 0 0 0 1 0 0 0 2

Total 0 0 0 1 0 0 0 3

Inflammatory Cells in the Lamina 

Propria

Minimal 0 0 0 0 0 0 0 2

Slight 0 0 0 0 0 0 0 8

Moderate 0 0 0 1 0 0 0 0

Total 0 0 0 1 0 0 0 10

Regenerative Hyperplasia

Slight 0 0 0 1 0 0 0 0

Total 0 0 0 1 0 0 0 0

Olfactory Epithelium

Atrophy/ Disorganisation/ 

Vacuolation

Minimal 1 2 5 0 0 0 2 0

Slight 0 0 3 8 1 0 3 4

Moderate 0 0 0 2 0 0 0 6

Total 1 2 8 10 1 0 5 10

Inflammation

Slight 0 0 0 3 1 0 0 2

Total 0 0 0 3 1 0 0 2

Inflammatory Cells in the Lamina 

Propria

Minimal 0 0 0 0 1 0 0 1

Slight 0 0 0 2 0 0 0 7

Total 0 0 0 2 1 0 0 8

Respiratory Metaplasia

Minimal 0 0 0 0 0 0 0 1

Slight 0 0 0 0 0 0 0 4

Total 0 0 0 0 0 0 0 5

Number of tissues examined 10 10 10 10 9 10 10 10
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Summary of treatment related findings in the nasal turbinates for animals killed after 13 weeks of 

treatment (Cont’d)

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Nasolacrimal Duct

Inflammation

Minimal 1 3 1 2 2 1 1 0

Slight 4 5 3 5 0 3 5 5

Moderate 0 0 0 1 0 0 1 4

Total 5 8 4 8 2 4 7 9

Epithelial Squamous Metaplasia

Minimal 0 1 0 0 1 0 0 1

Slight 1 0 0 0 1 3 2 2

Moderate 0 0 0 0 0 0 0 5

Total 1 1 0 0 2 3 2 8

Luminal Inflammatory Exudate

Minimal 0 0 0 0 0 0 0 1

Slight 0 0 0 0 0 0 0 1

Moderate 0 0 0 0 0 0 0 2

Total 0 0 0 0 0 0 0 4

Inflammatory Exudate in Airways

Minimal 0 0 0 1 0 0 0 3

Slight 0 0 0 0 0 0 0 2

Total 0 0 0 1 0 0 0 5

Number of tissues examined 10 10 10 10 9 10 10 10

Teeth

Pulp cavity necrosis was seen in females exposed to 2876 ppm.

Summary of treatment related findings in the teeth for animals killed after 13 weeks of treatment

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Pulp Cavity Necrosis

Slight 0 0 0 0 0 0 0 4

Moderate 0 0 0 0 0 0 0 1

Total 0 0 0 0 0 0 0 5

Number of tissues examined 10 10 10 10 9 10 10 10
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Findings of an uncertain relationship to treatment

Teeth

Ameloblast degeneration, odontoblast degeneration and pulp cavity increased inflammatory

cell infiltration at mostly minimal level were seen in a few rats exposed to 505 or 2876 ppm. 

As this finding was only evident for a small number of animals and there was no clear dose 

relationship, the toxicological significance is uncertain. 

Summary of findings of an uncertain relationship to treatment in the teeth after 13 weeks of treatment

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Ameloblast Degeneration

Minimal 0 0 0 1 0 0 0 2

Total 0 0 0 1 0 0 0 2

Odontoblast Degeneration

Minimal 0 0 0 1 0 0 2 1

Total 0 0 0 1 0 0 2 1

Pulp Cavity Increased 

Inflammatory Cell Infiltration

Minimal 0 0 0 0 0 0 0 1

Slight 0 0 0 0 0 0 0 1

Total 0 0 0 0 0 0 0 2

Number of tissues examined 10 10 10 10 9 10 10 10

Incidental findings

Pyelonephritis, with hyperplasia of both pelvic and papillary epithelium, in the kidneys and 

transitional cell hyperplasia and inflammation in the urinary bladder were seen in two 

females exposed to 2876 ppm. As these findings are occasionally in rats, including controls, 

they are considered to be incidental and unlikely to be related to exposure to the test material.

Malignant adenocarcinoma was seen in the Harderian gland of a female exposed to 2876 ppm 

and benign subcapsular cell adenoma was seen in the adrenal of a male exposed to 2876 ppm. 

Both findings are considered to be incidental.

All other histological changes were considered to be unrelated to treatment.
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3.13.2 Animals killed after 4 weeks of recovery

Treatment related findings

Spleen

Capsular inflammation and/ or thickening at slight level were seen in males previously 

exposed to 2876 ppm.

Summary of treatment-related changes in the spleen for animals killed after 4 weeks of recovery

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Capsular Inflammation

Minimal 0 - - 2 0 - - 0

Total 0 - - 2 0 - - 0

Capsular Thickening

Minimal 0 - - 0 0 - - 1

Slight 0 - - 2 0 - - 0

Total 0 - - 2 0 - - 1

Number of tissues examined 10 - - 10 10 - - 10
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Nasal Turbinates

In the olfactory epithelium, atrophy/ disorganisation/vacuolation, was seen in the rats 

previously exposed to 2876 ppm. 

In the nasolacrimal duct, inflammation was seen in females previously exposed to 2876 ppm. 

Summary of treatment-related changes in the nasal turbinates for animals killed after 4 weeks of 

recovery

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F

Dose (ppm) 0 199 505 2876 0 199 505 2876

Olfactory Epithelium

Atrophy/ Disorganisation/ 

Vacuolation

Minimal 0 - - 2 1 - - 2

Slight 0 - - 7 0 - - 5

Total 0 - - 9 1 - - 7

Nasolacrimal Duct

Inflammation

Minimal 4 - - 4 5 - - 3

Slight 1 - - 2 0 - - 6

Total 5 - - 6 5 - - 9

Number of tissues examined 10 - - 10 10 - - 10

Incidental findings

All other histological changes, including chronic inflammation seen in the heart of one 

control male and one male previously exposed to 2876 ppm, were considered to be unrelated 

to treatment.
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4. Discussion

The test article, 2-bromo-3,3,3-trifluoropropene, was administered to 3 groups of rats by

inhalation administration, using a whole-body exposure system, for 6 hours a day, 5 days a 

week, for 13 week at achieved aerosol concentrations of 199, 505 and 2876 ppm. A control 

group of rats received air only at the same airflow as the high dose group.

Treatment-related lower bodyweight gains were seen in males exposed to 199 ppm and both 

sexes exposed to 505 or 2876 ppm. These reductions were exposure level related and are 

considered to be result of treatment and correlate to some extent with reduced food 

consumption seen for treated males and females exposed to 2876 ppm.

There were no deaths that were considered to be a direct result of exposure to the test 

material, 2 bromo 3,3,3 trifluoropropene.

Clinical signs of shallow breathing, piloerection, grinding teeth and hunched posture, evident 

during and after exposure are indicative of exposure to an irritant material. Whereas, the 

clinical signs of unresponsiveness to external stimuli, underactivity, and partially closed 

eyelids, together with the reduced grip strength and motor activity responses seen at 505 or 

2876 ppm represent potential CNS effects.

The histopathological changes seen in the upper respiratory tract (larynx and nasal turbinates) 

of animals exposed to 2876 ppm and, to a lesser degree, animals exposed to 505 ppm, are 

consistent with a minor and localised irritant effect of the test material. They are similar, to

changes seen in the two previous 2-week dose range studies of the same test material 

(Huntingdon Life Sciences Study Numbers: WAG0013 and WAG0024).

In the heart, chronic inflammation was seen in males exposed to 199 ppm and both sexes 

exposed to 505 or 2876 ppm. The heart tissue samples from all males (main study and 

recovery) were independently peer reviewed by an external consultant pathologist and the 

findings agreed between the consultant and the study pathologist. The minimal degree 

observed at 199 ppm is considered unlikely to be associated with any alteration of heart 

function and is considered not adverse. The slight and moderate degrees observed at 505 and 

2876 ppm are considered adverse. This change may be related to the elevated alkaline 

phosphatase and aspartate amino transferase levels measured during Week 13 of exposures, 

however the toxicological importance of this is unclear. Complete recovery of the chronic 

inflammation was seen following the 4 week recovery period.

In the spleen, capsular inflammation and/or thickening and adhesion, with corresponding 

macroscopic observations, were seen in animals exposed to 2876 ppm and, to a lesser extent, 

animals exposed to 505 ppm. This is likely to be a toxic effect. Partial recovery was seen 

following the 4 week recovery period with the findings seen in 2 males previously exposed to 

2876 ppm.

In the thymus, involution/atrophy, with a corresponding reduction in organ weight, seen in 

animals exposed to 2876 ppm is likely to be related to the stress of daily exposures to the test 

material. This effect was also seen in the reductions in bodyweight gain and food 

consumption, experienced by the animals at this exposure level.
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In the liver, minimal centrilobular hepatocyte hypertrophy seen in some animals exposed to 

2876 ppm and a single female exposed to 505 ppm, is considered to be an adaptive change as 

a result of exposure to the test material and not an adverse effect. 

In the pancreas, increased incidence of acinar cell degranulation was seen in animals at all 

exposure levels. This is not considered to be a toxic response but rather a physiological

change and likely to be related to the lower food consumption recorded for these animals.

Clinical and macroscopic findings of pale, thickened and/or brittle incisors were not 

associated with histopathological changes. However, pulp cavity necrosis of the teeth, with 

corresponding macroscopic observations, was seen in females exposed to 2876 ppm, and it is 

considered to be a toxic effect. High levels of fluoride have been shown to disturb

development of dental enamel (Aoba 2002).

Increased mean lung weight and reduced mean salivary gland weight were not associated 

with any histopathological changes and are not considered to be of toxicological importance.

Lower values for total white cell, lymphocyte and eosinophil counts and higher values for 

monocyte counts, evident for all treated groups, were also not associated with any 

histopathological changes and are not considered to be of toxicological importance.

Following a 4 week off-exposure recovery period, animals previously exposed to 2876 ppm. 

showed evidence of recovery with regard to bodyweight gain and food consumption. 

However, only partial recovery was evident for grip strength and motor activity. For the

histopathological changes, full recovery was seen in the larynx, heart, thymus, liver, pancreas 

and teeth, but only partial recovery was evident for the changes in the nasal turbinates and 

spleen.
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5. Conclusion

Inhalation exposure of CD rats to atmospheres of 2 bromo 3,3,3-trifluoropropene for 

13 weeks, resulted in transient clinical signs, lower bodyweight gain, food consumption, grip 

strength and motor activity and histopathological changes in the liver, pancreas, heart, spleen, 

thymus, nasal turbinates, larynx and teeth. The majority of these findings were seen with 

animals exposed to 505 or 2876 ppm.

In the heart, chronic inflammation was seen in males exposed to 199 ppm and both sexes 

exposed to 505 or 2876 ppm and was considered adverse at 505 ppm or above.

The no observed adverse effect level (NOAEL) was considered to be 199 ppm.
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6. References 

Angervall L and Carlström E (1963). Theoretical criteria for the use of relative organ weights 

and similar ratios in biology. J Theoret Biol 4, 254-9 

Aoba T and Fejerskov O (2002). Dental fluorosis: chemistry and biology. Crit Rev Oral 

Biol Med 13(2), 155-170. 

Bartlett MS (1937). Properties of sufficiency and statistical tests. Proceedings of the Royal 

Society. Series A 160, 268-282. 

Dunnett CW (1955). A multiple comparison procedure for comparing several treatments with 

a control. Journal of the American Statistical Association 50, 1096-1121. 

Dunnett CW (1964). New tables for multiple comparisons with a control. Biometrics 20, 482-

491. 

Fisher RA (1973). Statistical Methods for Research Workers, 14th edn., p.96. Hafner 

Publishing Company, New York, USA. 

Huntingdon Life Sciences Study Number WAG0013 

2-Bromo-3,3,3-trifluoropropene: Dose Range Finding Study by Inhalation Administration to 

Rats for 2 Weeks 

Huntingdon Life Sciences Study Number: WAG0024 

2-bromo-3,3,3-trifluoropropene: Dose Range Finding Study by Inhalation Administration to 

Rats for 2 Weeks. 

Shirley EAC (1977). A non-parametric equivalent of Williams' test for contrasting increasing 

dose levels of a treatment. Biometrics 33, 386-389. 

Steel RGD (1959). A multiple comparison rank sum test: treatments versus control. 

Biometrics 15, 560-572. 

Wilcoxon F. (1945) Individual comparisons by ranking methods. Biometrics Bulletin, 1, 80-

83. 

Williams DA (1971). A test for differences between treatment means when several dose 

levels are compared with a zero dose control. Biometrics 27, 103-117. 

Williams DA (1972). The comparison of several dose levels with a zero dose control. 

Biometrics, 28, 519-531. 
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FIGURE 1

Motor activity - group mean scores (beam breaks) for males during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

 1M 2M 3M 4M

0

20

40

60

80

100

120

140

160

6 12 18 24 30 36 42 48 54 60

Number of beam breaks

Time (minutes)

High beams

0

50

100

150

200

250

300

6 12 18 24 30 36 42 48 54 60

Number of beam breaks

Time (minutes)

Low beams

0

250

500

750

1 2 3 4

Beam breaks

Group

Total scores

0

500

1000

1500

1 2 3 4

Beam breaks

Group

Total scores
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FIGURE 1 - continued

Motor activity - group mean scores (beam breaks) for females during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

 1F 2F 3F 4F

0

20

40

60

80

100

120

140

160

180

200

6 12 18 24 30 36 42 48 54 60

Number of beam breaks

Time (minutes)

High beams

0

50

100

150

200

250

300

6 12 18 24 30 36 42 48 54 60

Number of beam breaks

Time (minutes)

Low beams

0

250

500

750

1 2 3 4

Beam breaks

Group

Total scores

0

500

1000

1500

1 2 3 4

Beam breaks

Group

Total scores
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FIGURE 1 - continued

Motor activity - group mean scores (beam breaks) for males during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

 1M 4M

0

20

40

60

80

100

120

140

160

6 12 18 24 30 36 42 48 54 60

Number of beam breaks

Time (minutes)

High beams

0

50

100

150

200

250

300

350

6 12 18 24 30 36 42 48 54 60

Number of beam breaks

Time (minutes)

Low beams

0

250

500

750

1 4

Beam breaks

Group

Total scores

0

500

1000

1500

1 4

Beam breaks

Group

Total scores
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FIGURE 1 - continued

Motor activity - group mean scores (beam breaks) for females during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

 1F 4F

0

20

40

60

80

100

120

140

160

6 12 18 24 30 36 42 48 54 60

Number of beam breaks

Time (minutes)

High beams

0

50

100

150

200

250

300

350

6 12 18 24 30 36 42 48 54 60

Number of beam breaks

Time (minutes)

Low beams

0

250

500

750

1 4

Beam breaks

Group

Total scores

0

500

1000

1500

1 4

Beam breaks

Group

Total scores
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FIGURE 2

Bodyweight – group mean values (g) – main study animals

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876
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FIGURE 2 - continued

Bodyweight – group mean values (g) – recovery animals

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876
58

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TABLE 1

Sensory reactivity observations and grip strength - summary of findings during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/sex: Statistical 1M 2M 3M 4M Statistical 1F 2F 3F 4F

Number of animals: test (M) 20 10 10 20 test (F) 19 10 10 20

Parameter Grade

Approach response (1-3) 1 0 0 0 0 0 1 0 2

2 20 10 10 20 19 9 10 18

Touch response (1-3) 1 1 1 1 0 0 1 0 1

2 19 9 9 20 19 9 10 19

Auditory startle reflex (1-4) 2 4 3 2 4 3 2 1 3

3 16 7 8 16 16 8 9 17

Tail pinch response (1-4) 2 3 0 0 0 0 0 0 0

3 17 10 10 18 19 10 10 20

4 0 0 0 2 0 0 0 0

Forelimb grip strength (kg) Mean Wi 1.00 1.01 0.94 0.85** Wi 0.88 0.82 0.84 0.68**

SD 0.10 0.10 0.09 0.10 0.07 0.06 0.11 0.10

Hindlimb grip strength (kg) Mean Wi 0.61 0.59 0.54* 0.49** Wi 0.44 0.48 0.43 0.36**

SD 0.08 0.08 0.09 0.07 0.05 0.04 0.06 0.07

Additional observations^

Loose faeces 0 0 0 1 0 0 0 0

^ Each animal may have more than one observation
59

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TABLE 1

Sensory reactivity observations and grip strength - summary of findings during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/sex: Statistical 1M 4M Statistical 1F 4F

Number of animals: test (M) 10 10 test (F) 10 10

Parameter

Forelimb grip strength (kg) Mean Tt 1.12 1.07 Tt 0.87 0.86

SD 0.07 0.11 0.05 0.07

Hindlimb grip strength (kg) Mean Tt 0.67 0.57* Tt 0.52 0.48*

SD 0.10 0.07 0.04 0.05

^ Each animal may have more than one observation
60

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TABLE 2

Motor activity - group mean scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Number

of animals

Beam 

level

Time (minutes)

6 12 18 24 30 36 42 48 54 60 Total

Statistical test: Wi Wi Wi Wi Wi Wi Wi Sh Wi Wi Wi

1M 20 High 134.9 103.9 65.9 44.9 31.9 31.5 23.9 34.5 23.4 23.9 518.4

SD 17.9 23.0 16.2 21.3 15.8 19.2 20.7 25.7 21.8 18.9 107.5

2M 10 High 139.4 97.4 74.5 49.4 43.8 34.9 26.6 17.5 27.7 19.4 530.6

SD 25.0 24.6 30.1 19.9 28.0 14.4 19.8 11.1 13.0 19.5 151.4

3M 10 High 118.2 80.9* 57.4 38.2 31.2 16.2* 16.6 16.4 14.1 5.3* 394.5*

SD 18.4 19.1 23.3 15.8 17.4 17.1 19.1 9.4 15.4 16.4 121.8

4M 20 High 114.5* 63.0** 40.8** 28.6* 24.6 14.4** 10.9* 14.2** 8.3* 8.9** 327.9**

SD 29.9 21.1 21.5 25.3 24.3 16.9 13.6 19.3 16.2 11.7 130.9

Statistical test: Wi Wi Wi Wi Wi Wi Sh Wi Wi Wi Wi

1M 20 Low 251.2 188.8 150.5 104.3 89.8 78.8 57.4 66.7 54.3 54.2 1095.8

SD 49.2 45.9 45.2 38.5 31.3 30.3 29.9 38.0 36.4 36.5 223.4

2M 10 Low 256.7 182.7 159.6 126.4 90.3 96.5 80.0 60.8 88.7 70.1 1211.8

SD 49.9 49.3 51.2 40.6 56.8 34.3 37.6 33.3 37.4 37.4 316.6

3M 10 Low 229.1 176.7 133.3 116.9 89.2 60.9 73.0 56.0 41.3 17.8* 994.2

SD 61.2 36.0 34.7 47.4 38.7 39.8 74.9 38.6 36.9 26.3 270.7

4M 20 Low 209.7** 136.1** 99.3** 70.8* 57.5* 37.5** 28.0* 28.7** 22.1** 28.8* 718.3**

SD 30.5 32.1 42.0 38.7 48.7 37.8 37.1 25.0 25.8 33.7 227.2
61

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WAG0014

TABLE 2 - continued

Motor activity - group mean scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Number

of animals

Beam 

level

Time (minutes)

6 12 18 24 30 36 42 48 54 60 Total

Statistical test: Wi Wi Wi Wi Wi Wi Sh Wi Sh Wi Wi

1F 19 High 160.5 99.5 69.4 56.6 46.5 48.2 48.0 33.8 36.5 27.1 625.9

SD 25.5 29.7 21.3 17.3 22.3 31.7 47.7 25.4 33.7 27.3 172.8

2F 10 High 163.3 85.9 60.7 57.4 30.3 25.8* 28.3 31.4 28.3 9.9 521.3

SD 53.2 37.5 35.7 31.5 28.2 25.6 16.0 22.6 21.7 10.8 194.7

3F 10 High 151.7 93.5 61.7 41.8 36.9 25.5* 9.9* 14.9 11.4 15.9 463.2*

SD 27.9 19.5 25.4 16.6 26.2 26.2 16.1 15.1 12.8 18.0 139.5

4F 20 High 136.8* 86.1 58.4 36.4* 24.2* 14.9** 18.7** 20.2* 18.4* 12.0* 425.8**

SD 35.5 37.6 37.4 27.3 30.5 21.2 23.9 20.4 16.4 19.6 193.6

Statistical test: Wi Wi Wi Wi Wi Wi Wi Wi Wi Wi Wi

1F 19 Low 276.2 181.7 150.6 116.5 101.8 97.3 85.1 73.9 73.7 74.4 1231.1

SD 66.5 49.2 41.5 36.5 42.1 52.9 48.8 43.1 36.2 51.1 337.0

2F 10 Low 257.2 158.6 128.4 91.5 78.1 58.8* 82.8 91.1 64.5 50.7 1061.7

SD 52.9 45.1 44.0 46.0 51.0 47.2 39.8 34.7 37.7 46.2 329.9

3F 10 Low 249.5 174.6 145.7 96.7 92.0 58.6* 37.2* 35.9 47.5 59.4 997.1

SD 64.0 43.9 43.8 34.2 36.6 27.6 38.8 26.7 44.5 48.2 263.0

4F 20 Low 199.6* 129.8** 89.9** 67.3** 38.6** 35.6** 41.1** 49.3* 52.3 46.1 749.5**

SD 38.2 35.4 41.6 40.2 38.4 38.9 41.0 48.5 43.1 42.4 257.5
62

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WAG0014

TABLE 2 - continued

Motor activity - group mean scores (beam breaks) during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Number

of animals

Beam 

level

Time (minutes)

6 12 18 24 30 36 42 48 54 60 Total

Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt

1M 10 High 112.0 73.9 54.4 43.4 28.5 14.5 19.7 11.3 10.4 13.0 381.1

SD 11.1 15.6 21.0 25.3 22.0 14.0 23.8 13.5 16.4 14.8 151.5

4M 10 High 115.5 53.7* 39.0 25.0 24.9 15.3 8.0 9.1 7.6 11.6 309.7

SD 11.4 25.2 17.1 18.0 18.8 18.7 13.1 15.4 13.1 15.7 118.5

Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt

1M 10 Low 232.6 162.4 127.0 104.2 86.3 42.1 44.9 30.9 29.6 37.4 897.4

SD 34.0 35.3 27.4 36.5 41.1 33.0 48.0 33.2 34.3 38.4 241.6

4M 10 Low 200.3 119.1* 83.8** 67.7 60.5 50.8 33.7 36.1 32.5 35.6 720.1

SD 48.7 43.0 38.4 42.0 21.2 47.5 38.6 46.6 29.4 41.1 244.4
63

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WAG0014

TABLE 2 - continued

Motor activity - group mean scores (beam breaks) during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Number

of animals

Beam 

level

Time (minutes)

6 12 18 24 30 36 42 48 54 60 Total

Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt Wc Tt

1F 10 High 125.9 72.6 67.6 55.5 47.0 33.7 38.0 26.9 8.9 2.7 478.8

SD 28.8 18.5 34.2 28.0 18.0 15.4 20.1 16.4 11.3 5.0 123.8

4F 10 High 135.1 81.0 68.6 43.0 40.6 34.8 22.7 31.5 7.8 11.6 476.7

SD 22.3 20.1 46.4 30.3 21.2 20.7 23.4 27.4 10.7 16.7 175.0

Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt

1F 10 Low 260.1 168.8 160.4 139.1 130.0 104.4 112.6 89.5 41.2 17.3 1223.4

SD 45.7 46.3 65.1 45.5 48.5 59.6 56.8 48.9 41.1 23.5 334.0

4F 10 Low 201.6* 120.3* 105.5* 88.3* 80.6* 90.6 50.0* 54.1 24.7 24.7 840.4*

SD 48.5 28.8 36.6 49.2 40.1 46.6 40.5 33.3 27.9 34.5 274.7
64

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WAG0014

TABLE 3 Request ID: 289342

Bodyweight - group mean values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Week Week Week Week Week Week Week Week Week Week Week Week

/Sex -1 0 1 2 3 4 5 6 7 8 9 10

Statistical test:

1M Mean 187 236 294 347 397 435 470 493 512 538 559 575

SD 8.9 8.7 11.3 19.9 25.4 31.3 37.3 42.0 43.2 48.8 50.5 53.3

N 20 20 20 20 20 20 20 20 20 20 20 20

2M Mean 188 239 288 338 381 412 445 460 473 489 500 510

SD 8.5 11.7 14.3 19.1 23.9 26.4 30.6 32.4 32.7 37.4 36.9 38.9

N 10 10 10 10 10 10 10 10 10 10 10 10

3M Mean 186 237 273 313 355 393 421 438 452 465 479 488

SD 7.9 11.3 15.5 23.4 29.6 29.9 37.4 43.8 43.9 45.4 46.4 49.1

N 10 10 10 10 10 10 10 10 10 10 10 10

4M Mean 188 234 257 298 330 362 386 399 408 414 419 425

SD 7.0 10.8 12.8 16.7 22.6 27.1 32.4 35.5 37.0 39.1 39.3 40.5

N 20 20 20 20 20 20 20 20 20 20 20 20
65

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WAG0014

TABLE 3 - continued Request ID: 289342

Bodyweight - group mean values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Week Week Week Change As % of

/Sex 11 12 13 0-13 Control

Statistical test: Wi

1M Mean 579 590 594 359 -

SD 57.4 60.7 61.7 64.0

N 20 20 20 20

2M Mean 512 523 519 280** 78

SD 40.3 42.1 40.0 35.2

N 10 10 10 10

3M Mean 494 502 497 260** 73

SD 48.4 49.0 52.1 46.4

N 10 10 10 10

4M Mean 425 429 422 188** 52

SD 41.8 41.4 39.8 36.6

N 20 20 20 20
66

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WAG0014

TABLE 3 - continued Request ID: 289342

Bodyweight - group mean values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Week Week Week Week Week Week Week Week Week Week Week Week

/Sex -1 0 1 2 3 4 5 6 7 8 9 10

Statistical test:

1F Mean 167 189 214 229 250 261 273 280 285 292 297 303

SD 11.5 12.8 15.0 16.2 18.6 18.6 19.2 20.5 20.2 23.2 20.1 22.1

N 20 20 20 20 20 20 20 20 20 19 19 19

2F Mean 163 189 211 228 247 259 272 276 282 288 292 293

SD 9.2 12.2 10.4 10.9 10.9 11.0 11.8 15.7 11.5 12.3 10.6 11.1

N 10 10 10 10 10 10 10 10 10 10 10 10

3F Mean 168 191 208 223 241 247 264 267 271 278 281 284

SD 10.8 12.6 15.3 16.5 18.5 19.5 21.0 21.0 20.2 18.9 21.8 19.3

N 10 10 10 10 10 10 10 10 10 10 10 10

4F Mean 165 190 211 219 232 243 248 247 251 252 254 255

SD 11.5 14.2 15.5 17.3 15.4 20.4 20.9 19.6 22.2 21.7 24.9 26.7

N 20 20 20 20 20 20 20 20 20 20 20 20
67

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WAG0014

TABLE 3 - continued Request ID: 289342

Bodyweight - group mean values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Week Week Week Change As % of

/Sex 11 12 13 0-13 Control

Statistical test: Wi

1F Mean 303 302 303 114 -

SD 22.3 22.5 20.5 13.2

N 19 19 19 19

2F Mean 298 299 298 109 95

SD 12.3 8.4 15.6 16.2

N 10 10 10 10

3F Mean 284 283 281 90** 79

SD 23.1 19.3 21.2 13.3

N 10 10 10 10

4F Mean 260 262 253 63** 55

SD 24.2 28.2 25.7 21.1

N 20 20 20 20
68

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WAG0014

TABLE 3 Request ID: 290312

Bodyweight - group mean values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Week Week Week Week Week Change As % of

/Sex R0 R1 R2 R3 R4 R0-R4 Control

Statistical test: Tt

1M Mean 594 602 618 629 622 34 -

SD 61.7 77.8 77.1 76.8 77.4 11.6

N 20 10 10 10 10 10

4M Mean 422 445 464 481 483 62** 182

SD 39.8 48.7 50.1 52.5 53.0 10.5

N 20 10 10 10 10 10
69

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WAG0014

TABLE 3 - continued Request ID: 290312

Bodyweight - group mean values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Week Week Week Week Week Change As % of

/Sex R0 R1 R2 R3 R4 R0-R4 Control

Statistical test: Wc

1F Mean 303 310 314 314 312 9 -

SD 20.5 23.2 26.5 24.7 21.8 6.1

N 19 10 10 10 10 10

4F Mean 253 265 272 271 266 16 177

SD 25.7 17.3 18.1 17.8 18.3 18.8

N 20 10 10 10 10 10
70

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WAG0014

TABLE 4

Haematology - group mean values during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Hct Hb RBC RETA MCH MCHC MCV

/Sex L/L g/dL x1012/L x1012/L pg g/dL fL

Statistical test: Wi Wi Wi Wi Wi Wi Wi

1M Mean 0.429 15.7 8.19 0.193 19.2 36.5 52.4

SD 0.0205 0.69 0.308 0.0343 0.42 0.84 0.82

N 10 10 10 10 10 10 10

2M Mean 0.445 16.0 8.64* 0.193 18.5** 35.9 51.5

SD 0.0335 1.16 0.617 0.0199 0.47 0.38 1.53

N 10 10 10 10 10 10 10

3M Mean 0.445 16.1 8.79** 0.188 18.3** 36.1 50.7*

SD 0.0222 0.79 0.522 0.0377 0.64 0.44 2.03

N 10 10 10 10 10 10 10

4M Mean 0.454* 16.6* 9.06** 0.206 18.3** 36.5 50.1**

SD 0.0162 0.58 0.280 0.0594 0.39 0.36 1.08

N 10 10 10 10 10 10 10
71

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WAG0014

TABLE 4 - continued

Haematology - group mean values during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group WBC N L E B M LUC Plt PTP APTT

/Sex x109/L x109/L x109/L x109/L x109/L x109/L x109/L x109/L sec sec

Statistical test: lWi Wi lWi Wi Wi Wi lWi Wi lWi Wi

1M Mean 11.31 2.36 8.30 0.19 0.06 0.31 0.08 882 25.0 23.9

SD 2.623 1.196 1.882 0.066 0.033 0.138 0.025 159.7 4.21 2.98

N 10 10 10 10 10 10 10 9 10 10

2M Mean 10.63 2.92 7.05 0.09** 0.06 0.41 0.11 1017 22.3 21.6*

SD 3.556 2.546 2.748 0.043 0.049 0.199 0.060 154.3 1.72 2.47

N 10 10 10 10 10 10 10 10 10 10

3M Mean 10.61 2.65 7.19 0.05** 0.07 0.54** 0.11 976 23.8 20.8*

SD 2.781 0.810 2.054 0.018 0.065 0.150 0.047 119.2 1.80 1.42

N 10 10 10 10 10 10 10 10 10 10

4M Mean 8.87 2.35 5.66** 0.05** 0.04 0.57** 0.20** 898 24.7 22.1*

SD 1.791 1.125 1.122 0.020 0.026 0.178 0.087 70.8 1.46 2.03

N 10 10 10 10 10 10 10 10 9 9
72

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WAG0014

TABLE 4 - continued

Haematology - group mean values during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Hct Hb RBC RETA MCH MCHC MCV

/Sex L/L g/dL x1012/L x1012/L pg g/dL fL

Statistical test: Wi Wi Sh lWi Wi Wi Wi

1F Mean 0.422 15.5 7.92 0.158 19.6 36.8 53.3

SD 0.0116 0.39 0.312 0.0336 0.72 0.58 1.72

N 9 9 9 9 9 9 9

2F Mean 0.412 15.2 7.93 0.166 19.1 36.8 52.0

SD 0.0179 0.73 0.352 0.0485 0.80 0.85 1.61

N 10 10 10 10 10 10 10

3F Mean 0.427 15.6 8.20 0.176 19.0 36.5 52.0

SD 0.0200 0.73 0.325 0.0439 0.58 0.72 1.66

N 10 10 10 10 10 10 10

4F Mean 0.414 14.4** 8.05 0.329** 18.0** 34.8** 51.8

SD 0.0244 0.88 0.906 0.1400 1.57 1.34 3.88

N 10 10 10 10 10 10 10
73

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WAG0014

TABLE 4 - continued

Haematology - group mean values during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group WBC N L E B M LUC Plt PTP APTT

/Sex x109/L x109/L x109/L x109/L x109/L x109/L x109/L x109/L sec sec

Statistical test: lWi Wi lWi Wi lWi Wi Wi Wi Sh Wi

1F Mean 8.54 1.68 6.43 0.11 0.04 0.19 0.09 950 21.1 17.4

SD 3.455 1.122 2.302 0.043 0.049 0.099 0.049 139.3 0.86 1.14

N 9 9 9 9 9 9 9 9 9 9

2F Mean 7.59 0.86 6.26 0.07* 0.04 0.27 0.10 872 24.1* 19.0**

SD 1.527 0.292 1.368 0.033 0.019 0.092 0.048 94.7 0.82 1.18

N 10 10 10 10 10 10 10 10 10 10

3F Mean 7.02 1.18 5.19 0.07* 0.04 0.41** 0.13 839 23.4* 19.3**

SD 1.626 0.492 1.205 0.037 0.016 0.144 0.062 133.3 1.71 1.57

N 10 10 10 10 10 10 10 10 10 10

4F Mean 5.78* 1.07 4.24** 0.03** 0.03 0.32** 0.10 1070 26.4** 19.5**

SD 1.637 0.911 1.166 0.010 0.014 0.083 0.070 263.7 4.04 1.14

N 10 10 10 10 10 10 10 10 10 10
74

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WAG0014

TABLE 4 - continued

Haematology - group mean values during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Hct Hb RBC RETA MCH MCHC MCV

/Sex L/L g/dL x1012/L x1012/L pg g/dL fL

Statistical test: Tt Tt Tt Tt Tt Tt Tt

1M Mean 0.441 15.0 8.47 0.212 17.6 33.9 52.0

SD 0.0136 0.50 0.384 0.0446 0.51 0.33 1.75

N 10 10 10 10 10 10 10

4M Mean 0.449 15.3 8.42 0.163* 18.1 34.0 53.3

SD 0.0186 0.63 0.314 0.0462 0.59 0.28 1.59

N 10 10 10 10 10 10 10
75

Huntingdon Life Sciences

WAG0014

TABLE 4 - continued

Haematology - group mean values during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group WBC N L E B M LUC Plt PTP APTT

/Sex x109/L x109/L x109/L x109/L x109/L x109/L x109/L x109/L sec sec

Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt

1M Mean 10.77 1.75 8.39 0.14 0.10 0.28 0.12 1091 22.7 22.6

SD 2.526 0.802 2.050 0.047 0.063 0.094 0.053 191.5 1.71 4.17

N 10 10 10 10 10 10 10 10 10 10

4M Mean 7.78** 1.22 6.09** 0.12 0.07 0.19* 0.09 1099 21.9 21.2

SD 1.644 0.477 1.348 0.049 0.032 0.072 0.034 136.5 1.69 2.94

N 10 10 10 10 10 10 10 10 10 10
76

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WAG0014

TABLE 4 - continued

Haematology - group mean values during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Hct Hb RBC RETA MCH MCHC MCV

/Sex L/L g/dL x1012/L x1012/L pg g/dL fL

Statistical test: Tt Tt Tt Tth Tt Tt Tt

1F Mean 0.417 14.4 7.60 0.129 18.9 34.4 54.9

SD 0.0104 0.37 0.270 0.0336 0.73 0.37 1.69

N 10 10 10 10 10 10 10

4F Mean 0.428* 14.7 7.88** 0.132 18.6 34.4 54.3

SD 0.0095 0.37 0.136 0.0284 0.50 0.49 1.34

N 10 10 10 10 10 10 10
77

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WAG0014

TABLE 4 - continued

Haematology - group mean values during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group WBC N L E B M LUC Plt PTP APTT

/Sex x109/L x109/L x109/L x109/L x109/L x109/L x109/L x109/L sec sec

Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt

1F Mean 5.05 0.74 3.99 0.11 0.03 0.12 0.06 1006 21.7 20.9

SD 1.079 0.327 0.838 0.025 0.011 0.038 0.026 85.6 1.53 2.26

N 10 10 10 10 10 10 10 10 10 10

4F Mean 3.60* 0.73 2.64** 0.09 0.02 0.09 0.04 1010 22.2 19.6

SD 1.229 0.308 0.951 0.033 0.010 0.033 0.015 107.7 1.52 2.04

N 10 10 10 10 10 10 10 10 10 10
78

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WAG0014

TABLE 5

Blood chemistry - group mean values during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group ALP ALT AST Bili Urea Creat Gluc Chol Trig

/Sex U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L

Statistical test: Wi Wi Sh Wi lWi Wi lWi Wi Wi

1M Mean 72 31 75 2 5.11 35 8.18 1.74 0.69

SD 13.9 5.1 8.6 0.7 0.637 3.9 0.914 0.241 0.228

N 10 10 10 10 10 10 10 10 10

2M Mean 72 40* 173** 2 5.90 33 8.72 1.61 0.66

SD 10.2 9.7 117.5 0.3 0.861 3.2 1.130 0.425 0.269

N 10 10 10 10 10 10 10 10 10

3M Mean 78 39* 225** 1 6.40** 36 9.56 1.57 0.73

SD 17.7 5.5 58.6 0.5 1.061 7.3 2.539 0.519 0.174

N 10 10 10 10 10 10 10 10 10

4M Mean 95** 39* 216** 2 8.36** 34 8.01 1.03** 0.93

SD 27.3 10.7 76.3 0.3 2.022 5.1 1.207 0.342 0.419

N 10 10 10 10 10 10 10 10 10
79

Huntingdon Life Sciences

WAG0014

TABLE 5 - continued

Blood chemistry - group mean values during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Na K Cl Ca Phos Total Prot Alb A/G

/Sex mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio

Statistical test: Wi Wi Wi Wi lWi Wi Wi Wi

1M Mean 141 4.2 102 2.44 1.89 66 34 1.11

SD 0.8 0.32 0.9 0.038 0.147 3.1 1.1 0.106

N 10 10 10 10 10 10 10 10

2M Mean 142 4.5 104** 2.43 1.93 63 34 1.19

SD 1.0 0.29 1.1 0.059 0.289 2.7 1.3 0.090

N 10 10 10 10 10 10 10 10

3M Mean 143 4.8* 105** 2.48 2.10 61** 34 1.23**

SD 1.7 0.26 1.6 0.105 0.501 2.9 1.3 0.090

N 10 10 10 10 10 10 10 10

4M Mean 143 4.5* 108** 2.44 2.46** 60** 35 1.36**

SD 2.0 0.58 2.6 0.052 0.446 1.9 1.1 0.086

N 10 10 10 10 10 10 10 10
80

Huntingdon Life Sciences

WAG0014

TABLE 5 - continued

Blood chemistry - group mean values during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group ALP ALT AST Bili Urea Creat Gluc Chol Trig

/Sex U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L

Statistical test: lWi lWi lDu Du Wi Wi lWi Wi lWi

1F Mean 42 24 68 1 6.46 41 8.40 2.13 0.51

SD 11.6 5.4 9.6 0.5 0.870 3.9 1.414 0.401 0.159

N 9 9 9 9 9 9 9 9 9

2F Mean 37 29 77 3** 7.62* 41 6.63 1.67 0.58

SD 5.4 7.8 24.0 0.5 1.114 4.4 0.884 0.229 0.204

N 10 10 10 10 10 10 10 10 10

3F Mean 44 32 185** 2 8.00** 43 7.78 1.82 0.59

SD 9.1 13.0 78.2 0.7 1.118 6.6 2.493 0.643 0.194

N 10 10 10 10 10 10 10 10 10

4F Mean 60** 18* 83 2 9.95** 38 5.79** 1.14** 0.87*

SD 20.0 3.6 27.1 0.5 1.461 2.9 0.871 0.411 0.465

N 10 10 10 10 10 10 10 10 10
81

Huntingdon Life Sciences

WAG0014

TABLE 5 - continued

Blood chemistry - group mean values during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Na K Cl Ca Phos Total Prot Alb A/G

/Sex mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio

Statistical test: Wi Wi Sh Wi Sh Wi Wi Wi

1F Mean 140 4.1 102 2.48 1.18 70 39 1.29

SD 1.4 0.41 1.3 0.079 0.215 3.9 2.3 0.175

N 9 9 9 9 9 9 9 9

2F Mean 142 3.7 104* 2.43 1.68* 66** 39 1.43

SD 1.1 0.30 2.7 0.079 0.095 3.3 2.3 0.077

N 10 10 10 10 10 10 10 10

3F Mean 141 4.3 105** 2.44 2.07** 60** 35** 1.41

SD 0.8 0.60 1.0 0.054 0.523 2.7 1.4 0.100

N 10 10 10 10 10 10 10 10

4F Mean 140 4.2 105** 2.37** 2.81** 61** 35** 1.39

SD 2.1 0.36 3.2 0.065 0.494 2.6 2.9 0.219

N 10 10 10 10 10 10 10 10
82

Huntingdon Life Sciences

WAG0014

TABLE 5 - continued

Blood chemistry - group mean values during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group ALP ALT AST Bili Urea Creat Gluc Chol Trig

/Sex U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L

Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt

1M Mean 76 42 71 3 5.31 35 8.30 2.00 1.02

SD 14.3 11.8 18.7 1.0 0.580 6.6 0.910 0.761 0.323

N 10 10 10 10 10 10 10 10 10

4M Mean 93* 41 76 2 5.59 36 6.81** 1.62 0.63**

SD 20.5 12.3 32.5 0.7 0.573 5.8 0.863 0.266 0.242

N 10 10 10 10 10 10 10 10 10
83

Huntingdon Life Sciences

WAG0014

TABLE 5 - continued

Blood chemistry - group mean values during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Na K Cl Ca Phos Total Prot Alb A/G

/Sex mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio

Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt

1M Mean 140 4.2 100 2.50 1.75 66 34 1.07

SD 0.7 0.20 1.1 0.081 0.115 2.1 1.4 0.070

N 10 10 10 10 10 10 10 10

4M Mean 140 4.5* 101* 2.51 1.88 65 35 1.15*

SD 0.6 0.34 0.6 0.052 0.207 2.7 1.2 0.062

N 10 10 10 10 10 10 10 10
84

Huntingdon Life Sciences

WAG0014

TABLE 5 - continued

Blood chemistry - group mean values during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group ALP ALT AST Bili Urea Creat Gluc Chol Trig

/Sex U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L

Statistical test: Tt Tt Tt Fe Tt Tt Tt Tt Tt

1F Mean 33 49 103 2 6.28 43 6.96 2.23 0.79

SD 10.8 27.6 78.3 0.3 0.925 4.5 0.900 0.405 0.295

N 10 10 10 10 10 10 10 10 10

4F Mean 44* 50 105 2 6.17 41 6.82 1.84 0.65

SD 7.6 16.8 38.1 0.5 0.872 2.5 0.897 0.536 0.216

N 10 10 10 10 10 10 10 10 10
85

Huntingdon Life Sciences

WAG0014

TABLE 5 - continued

Blood chemistry - group mean values during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Na K Cl Ca Phos Total Prot Alb A/G

/Sex mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio

Statistical test: Tt lTt Tt Tt Tt Tt Tt Tt

1F Mean 139 3.7 100 2.53 1.17 71 40 1.27

SD 0.7 0.21 1.3 0.065 0.235 2.5 1.7 0.099

N 10 10 10 10 10 10 10 10

4F Mean 140* 3.9 102** 2.39** 1.15 67** 38 1.32

SD 1.1 0.62 1.5 0.060 0.165 2.9 2.0 0.125

N 10 10 10 10 10 10 10 10
86

Huntingdon Life Sciences

WAG0014

TABLE 6

Urinalysis - group mean values during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Vol pH SG Prot TCLR TNAR TUKR

/Sex mL g/L g/L mmol mmol mmol

Statistical test: Wi Wi Sh Wi Wi Wi Wi

1M Mean 5.3 7.6 1047 1.13 0.539 0.428 1.234

SD 1.61 0.76 16.6 0.200 0.2618 0.2208 0.3173

N 10 10 10 10 10 10 10

2M Mean 7.7* 7.0 1029** 1.03 0.592 0.596 0.991

SD 3.06 0.28 4.5 0.580 0.2196 0.2291 0.3049

N 10 10 10 10 10 10 10

3M Mean 8.9* 7.1 1026** 0.88 0.639 0.493 1.078

SD 3.00 0.61 4.7 0.277 0.2919 0.2249 0.3646

N 10 10 10 10 10 10 10

4M Mean 7.3* 6.8** 1034** 0.79 0.676 0.608 0.820**

SD 2.79 0.63 13.9 0.355 0.2768 0.3112 0.3166

N 10 10 10 10 10 10 10
87

Huntingdon Life Sciences

WAG0014

TABLE 6 - continued

Urinalysis - group mean values during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Vol pH SG Prot TCLR TNAR TUKR

/Sex mL g/L g/L mmol mmol mmol

Statistical test: Wi Wi Sh Wi Wi Wi Wi

1F Mean 2.8 6.4 1046 0.25 0.207 0.241 0.482

SD 1.66 0.55 16.8 0.080 0.1137 0.1096 0.2468

N 9 9 9 9 9 9 9

2F Mean 4.1 6.5 1044 0.18 0.274 0.295 0.608

SD 2.07 0.31 18.5 0.101 0.1341 0.1765 0.1396

N 10 10 10 10 10 10 10

3F Mean 5.0 6.3 1032 0.14 0.375 0.368 0.549

SD 2.13 0.42 4.7 0.044 0.2009 0.1850 0.2240

N 10 10 10 10 10 10 10

4F Mean 4.5 6.0 1036 0.20 0.500** 0.304 0.447

SD 2.14 0.45 13.6 0.142 0.2276 0.1870 0.2406

N 10 9 10 9 9 9 9
88

Huntingdon Life Sciences

WAG0014

TABLE 7 Request ID: 289354

Organ weights - group mean unadjusted and adjusted values (g) for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Terminal 

Bodyweight

Adrenals Brain Epididymides Heart Kidneys Liver Lungs + 

Bronchi

Pituitary Prostate

Unadjusted Means

Statistical test: Wi

1M Mean 601 0.056 2.114 1.522 1.805 3.375 20.357 1.761 0.014 1.246

SD 48 0.009 0.072 0.135 0.257 0.265 1.714 0.164 0.004 0.217

N 10 10 10 10 10 10 10 10 10 10

2M Mean 520** 0.046 2.084 1.355 1.675 2.923 17.348 1.655 0.011 1.052

SD 43 0.008 0.077 0.081 0.206 0.351 2.779 0.152 0.003 0.192

N 10 10 10 10 10 10 10 10 10 10

3M Mean 497** 0.047 2.035 1.292 1.518 2.781 16.310 1.644 0.012 0.886

SD 53 0.008 0.073 0.135 0.250 0.230 2.552 0.175 0.003 0.158

N 10 10 10 10 10 10 10 10 10 10

4M Mean 417** 0.043 1.940 1.178 1.416 2.376 14.211 1.506 0.011 0.832

SD 32 0.007 0.086 0.157 0.165 0.264 1.744 0.094 0.003 0.202

N 10 10 10 10 10 10 10 10 10 10

Adjusted Means

Statistical test: Wi Wi Wi Wi Wi Wi Wi Wi Wi

1M Mean 0.050 2.047 1.430 1.624 2.961 16.530 1.560 0.012 1.081

2M Mean 0.045 2.076 1.344 1.654 2.873 16.883 1.630 0.011 1.033

3M Mean 0.048 2.043 1.304 1.541 2.834 16.806 1.670 0.012 0.907

4M Mean 0.050 2.005 1.269 1.595 2.786 18.007 1.705 0.013 0.995
89

Huntingdon Life Sciences

WAG0014

TABLE 7 - continued Request ID: 289354

Organ weights - group mean unadjusted and adjusted values (g) for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Terminal 

Bodyweight

Salivary

Glands

Seminal 

Vesicles

Spleen Testes Thymus Thyroids + 

Paras

Unadjusted Means

Statistical test: Wi

1M Mean 601 0.724 2.067 0.947 3.898 0.280 0.025

SD 48 0.073 0.191 0.099 0.268 0.072 0.005

N 10 10 10 10 10 10 10

2M Mean 520** 0.588 1.711 0.867 3.613 0.255 0.025

SD 43 0.062 0.410 0.157 0.309 0.071 0.006

N 10 10 10 10 10 10 10

3M Mean 497** 0.580 1.452 0.890 3.644 0.220 0.025

SD 53 0.079 0.270 0.165 0.427 0.073 0.007

N 10 10 10 10 10 10 10

4M Mean 417** 0.516 1.279 0.695 3.238 0.111 0.023

SD 32 0.087 0.339 0.091 0.313 0.021 0.007

N 10 10 10 10 10 10 10

Adjusted Means

Statistical test: Wi Wi Wi Wi lWi Wi

1M Mean 0.659 1.929 0.809 3.728 0.219 0.022

2M Mean 0.580 1.694 0.850 3.593 0.237 0.025

3M Mean 0.589 1.470 0.908 3.666 0.213 0.025

4M Mean 0.581 1.416 0.832 3.407 0.138* 0.026
90

Huntingdon Life Sciences

WAG0014

TABLE 7 - continued Request ID: 289354

Organ weights - group mean unadjusted and adjusted values (g) for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Terminal 

Bodyweight

Adrenals Brain Heart Kidneys Liver Lungs + 

Bronchi

Ovaries Pituitary Salivary

Glands

Unadjusted Means

Statistical test: Wi

1F Mean 303 0.059 1.954 1.125 1.753 9.708 1.240 0.096 0.017 0.448

SD 25 0.010 0.061 0.141 0.157 1.148 0.076 0.012 0.003 0.039

N 9 9 9 9 9 9 9 9 9 9

2F Mean 297 0.066 1.873 1.068 1.841 10.603 1.227 0.083 0.016 0.363

SD 14 0.007 0.083 0.070 0.164 1.100 0.095 0.016 0.003 0.035

N 10 10 10 10 10 10 10 10 10 10

3F Mean 283 0.057 1.860 0.968 1.852 9.678 1.277 0.080 0.015 0.359

SD 22 0.004 0.073 0.088 0.162 1.076 0.121 0.022 0.003 0.045

N 10 10 10 10 10 10 10 10 10 10

4F Mean 254** 0.053 1.771 1.047 1.724 9.639 1.257 0.081 0.011 0.354

SD 28 0.013 0.119 0.091 0.156 1.032 0.107 0.018 0.003 0.057

N 10 10 10 10 10 10 10 10 10 10

Adjusted Means

Statistical test: Wi Wi Wi Wi Wi Wi Wi Wi Wi

1F Mean 0.056 1.914 1.115 1.712 9.109 1.192 0.094 0.017 0.438

2F Mean 0.064 1.845 1.061 1.813 10.193 1.195 0.082 0.016 0.356**

3F Mean 0.057 1.861 0.969 1.853 9.699 1.279* 0.080 0.015 0.360**

4F Mean 0.058 1.833 1.063 1.788 10.567** 1.330* 0.084 0.011** 0.370**
91

Huntingdon Life Sciences

WAG0014

TABLE 7 - continued Request ID: 289354

Organ weights - group mean unadjusted and adjusted values (g) for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Terminal 

Bodyweight

Spleen Thymus Thyroids + 

Paras

Uterus + 

Cervix

Unadjusted Means

Statistical test: Wi

1F Mean 303 0.617 0.229 0.017 0.752

SD 25 0.123 0.046 0.006 0.292

N 9 9 9 9 9

2F Mean 297 0.539 0.196 0.023 0.765

SD 14 0.070 0.057 0.005 0.174

N 10 10 10 10 10

3F Mean 283 0.538 0.167 0.018 0.741

SD 22 0.096 0.048 0.004 0.247

N 10 10 10 10 10

4F Mean 254** 0.698 0.077 0.021 0.596

SD 28 0.247 0.034 0.006 0.323

N 10 10 10 10 10

Adjusted Means

Statistical test: lWi Wi Wi Wi

1F Mean 0.579 0.207 0.015 0.679

2F Mean 0.517 0.181 0.022* 0.715

3F Mean 0.530 0.167 0.018* 0.743

4F Mean 0.715 0.111** 0.023** 0.709
92

Huntingdon Life Sciences

WAG0014

TABLE 7 - continued Request ID: 290346

Organ weights - group mean unadjusted and adjusted values (g) for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Terminal 

Bodyweight

Adrenals Brain Epididymides Heart Kidneys Liver Lungs + 

Bronchi

Pituitary Prostate

Unadjusted Means

Statistical test: Tt

1M Mean 623 0.060 2.137 1.598 1.791 3.281 20.400 1.780 0.015 1.256

SD 78 0.012 0.115 0.203 0.345 0.443 3.642 0.157 0.004 0.165

N 10 10 10 10 10 10 10 10 10 10

4M Mean 482** 0.053 1.993 1.320 1.671 2.622 16.199 1.592 0.011 1.227

SD 52 0.010 0.112 0.130 0.265 0.250 1.588 0.176 0.003 0.325

N 10 10 10 10 10 10 10 10 10 10

Adjusted Means

Statistical test: Tt Tt Tt Tt Tt Tt Tt Tt Tt

1M Mean 0.065 2.070 1.480 1.532 3.072 18.915 1.650 0.013 1.235

4M Mean 0.048* 2.061 1.438 1.930** 2.831 17.684 1.722 0.013 1.247
93

Huntingdon Life Sciences

WAG0014

TABLE 7 - continued Request ID: 290346

Organ weights - group mean unadjusted and adjusted values (g) for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Terminal 

Bodyweight

Salivary

Glands

Seminal 

Vesicles

Spleen Testes Thymus Thyroids + 

Paras

Unadjusted Means

Statistical test: Tt

1M Mean 623 0.778 2.023 0.904 3.842 0.230 0.028

SD 78 0.089 0.358 0.233 0.335 0.078 0.007

N 10 10 10 10 10 10 10

4M Mean 482** 0.621 1.839 0.891 3.781 0.163 0.025

SD 52 0.080 0.288 0.132 0.392 0.043 0.004

N 10 10 10 10 10 10 10

Adjusted Means

Statistical test: Tt Tt Tt Tt Tt Tt

1M Mean 0.714 1.952 0.830 3.616 0.201 0.024

4M Mean 0.684 1.910 0.964 4.008 0.193 0.028
94

Huntingdon Life Sciences

WAG0014

TABLE 7 - continued Request ID: 290346

Organ weights - group mean unadjusted and adjusted values (g) for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Terminal 

Bodyweight

Adrenals Brain Heart Kidneys Liver Lungs + 

Bronchi

Ovaries Pituitary Salivary

Glands

Unadjusted Means

Statistical test: Tt

1F Mean 312 0.065 1.911 1.066 1.858 9.347 1.242 0.092 0.017 0.440

SD 22 0.020 0.094 0.178 0.202 1.125 0.095 0.045 0.003 0.021

N 10 10 10 10 10 10 10 10 10 10

4F Mean 265** 0.059 1.812 1.133 1.751 8.429 1.222 0.170 0.014 0.439

SD 19 0.009 0.092 0.155 0.179 0.827 0.113 0.264 0.001 0.046

N 10 10 10 10 10 10 10 10 10 10

Adjusted Means

Statistical test: Tt Tt Tt Tt Tt Tt lTt Tt Tt

1F Mean 0.058 1.862 0.953 1.751 8.918 1.185 0.057 0.016 0.421

4F Mean 0.066 1.860 1.246** 1.859 8.857 1.278 0.158* 0.016 0.459
95

Huntingdon Life Sciences

WAG0014

TABLE 7 - continued Request ID: 290346

Organ weights - group mean unadjusted and adjusted values (g) for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Terminal 

Bodyweight

Spleen Thymus Thyroids + 

Paras

Uterus + 

Cervix

Unadjusted Means

Statistical test: Tt Wc

1F Mean 312 0.549 0.155 0.021 0.873

SD 22 0.066 0.030 0.005 0.310

N 10 10 10 10 10

4F Mean 265** 0.566 0.178 0.024 0.681

SD 19 0.182 0.033 0.005 0.036

N 10 10 10 10 10

Adjusted Means

Statistical test: lTt Tt Tt

1F Mean 0.473 0.159 0.023

4F Mean 0.631* 0.174 0.022
96

Huntingdon Life Sciences

WAG0014

TABLE 8 Request ID: 313011

Macropathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number Examined: 10 10 10 10 9 10 10 10

Eyes

Protruding 0 0 0 0 0 0 0 1

Harderian glands

Swelling(s) 0 0 0 0 0 0 0 1

Kidneys

Depression(s) 0 0 0 0 0 0 1 0

Pelvic dilatation 1 0 0 0 0 0 1 0

Liver

Adhesions 0 0 0 0 0 0 1 1

Cyst(s) 0 0 0 0 0 0 0 1

Dark area(s) 1 0 0 0 0 0 0 0

Ln bronchial

Small 0 0 0 1 0 0 0 0

Ln mandibular

Enlarged 0 0 0 0 1 0 0 0
97

Huntingdon Life Sciences

WAG0014

TABLE 8 - continued Request ID: 313011

Macropathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number Examined: 10 10 10 10 9 10 10 10

Lungs + bronchi

Adhesions 0 0 0 0 0 0 0 1

Dark area(s) 0 1 0 1 0 0 0 1

Pale area(s) 1 0 1 1 2 3 1 1

Petechiae 0 0 0 1 0 0 0 0

Ovaries

Cyst(s) - - - - 1 0 0 0

Skin

Hair loss 0 1 1 0 3 7 4 6

Scab(s) 0 0 1 1 2 0 1 0

Spleen

Adhesions 0 0 0 0 0 0 2 5

Capsule thickened 1 1 4 8 0 1 2 5

Cyst(s) 0 0 0 1 0 0 1 0

Stomach

Cyst(s) 0 1 0 0 0 0 0 0
98

Huntingdon Life Sciences

WAG0014

TABLE 8 - continued Request ID: 313011

Macropathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number Examined: 10 10 10 10 9 10 10 10

Teeth

Incisor(s) pale 0 3 7 10 0 3 9 10

Incisor(s) thickened 0 0 0 1 0 0 0 8

General comments

Situs inversus 0 0 0 1 0 0 0 0

Paws

Swelling(s) 0 0 0 0 0 1 0 0
99

Huntingdon Life Sciences

WAG0014

TABLE 8 - continued Request ID: 313012

Macropathology - group distribution of findings for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 4M 1F 4F

Tissue and Finding Number Examined: 10 10 10 10

Kidneys

Pelvic dilatation 0 1 0 1

Ln mandibular

Enlarged 0 1 0 0

Lungs + bronchi

Dark 1 0 0 0

Dark area(s) 1 1 0 0

Pale area(s) 1 0 1 0

Ovaries

Periovarian sac distension - - 1 1

Pituitary

Cyst(s) 0 1 0 0

Skin

Hair loss 4 0 0 2
100

Huntingdon Life Sciences

WAG0014

TABLE 8 - continued Request ID: 313012

Macropathology - group distribution of findings for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 4M 1F 4F

Tissue and Finding Number Examined: 10 10 10 10

Spleen

Adhesions 0 2 0 1

Capsule thickened 0 1 0 0

Teeth

Incisor(s) pale 0 10 0 10

Incisor(s) thickened 0 1 0 3

Thymus

Dark 1 0 0 0

Preputial glands

Distended 1 0 - -
101

Huntingdon Life Sciences

WAG0014

TABLE 9 Request ID: 313013

Histopathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number: 10 10 10 10 9 10 10 10

Aorta Thoracic Number Examined: 10 0 0 10 9 0 0 10

Trachea Number Examined: 10 10 10 10 9 10 10 10

Inflammation 0 0 1 0 0 2 0 1

Inflammatory Exudate in Lumen 0 0 0 0 0 0 0 1

Lungs + Bronchi Number Examined: 10 10 10 10 9 10 10 10

Aggregations of Alveolar Macrophages 1 1 3 3 3 3 0 3

Alveolar Congestion 0 0 0 0 0 0 1 0

Alveolar Septal Mineralisation 0 0 1 0 0 0 1 0

Alveolitis 2 0 3 4 2 1 2 5

Arterial Mural Mineralisation 5 3 3 3 3 2 0 1

Cholesterol Cleft Granuloma(ta) 0 0 0 0 0 2 0 0

Perivascular Inflammatory Cells 3 0 0 1 1 0 0 3

Perivascular Lymphoid Aggregates 0 0 0 0 0 0 0 1

Pleural Adhesion(s) 0 0 0 0 0 0 0 1

Pleural Fibrosis 0 1 0 0 0 0 0 0

Pleural Inflammation 0 2 0 1 0 1 0 0
102

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313013

Histopathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number: 10 10 10 10 9 10 10 10

Liver Number Examined: 10 10 10 10 9 10 10 10

Capsular Adhesions 0 0 0 0 0 0 1 1

Extramedullary Haemopoiesis 0 0 0 0 0 0 0 1

Hepatocyte Hypertrophy, Centrilobular 0 0 0 2 0 0 1 4

Hepatocyte Necrosis, Focal 0 0 1 0 0 0 0 0

Inflammation, Focal 6 3 5 3 2 1 6 1

Vascular Dilatation 0 0 0 0 0 0 0 1

Pancreas Number Examined: 10 10 10 10 9 10 10 10

Acinar Atrophy, Focal 0 0 1 0 0 1 0 1

Acinar Cell Degranulation 0 3 5 7 1 4 5 6

Arteritis/Periarteritis 0 1 0 0 0 0 0 0

Basophilic Acinar Cells, Focal 0 1 0 0 0 0 0 0

Inflammation 0 1 0 0 0 1 0 0

LN Mesenteric Number Examined: 10 0 0 10 9 0 0 10

Mastocytosis 0 0 0 0 1 0 0 0

Sinus Erythrocytosis/Erythrophagocytosis 0 0 0 1 1 0 0 0
103

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313013

Histopathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number: 10 10 10 10 9 10 10 10

Kidneys Number Examined: 10 0 0 10 9 0 2 10

Cortical Scarring 0 0 0 2 0 0 0 0

Cortical Tubular Basophilia 1 0 0 0 0 0 0 0

Hyperplasia, Papillary Epithelium 0 0 0 0 0 0 0 2

Hyperplasia, Pelvic Epithelium 0 0 0 0 0 0 0 2

Interstitial Inflammation 0 0 0 1 0 0 0 0

Mineralisation, Papilla 0 0 0 0 1 0 0 0

Pelvic Dilatation 0 0 0 0 0 0 1 0

Perivascular Lymphoid Aggregations 2 0 0 0 0 0 0 0

Pyelonephritis 0 0 0 0 0 0 0 2

Urinary Bladder Number Examined: 10 0 0 10 9 0 0 10

Erosion 0 0 0 0 0 0 0 1

Inflammation 0 0 0 0 0 0 0 3

Refluxed Seminal Colloid Plug 0 0 0 1 0 0 0 0

Transitional Cell Hyperplasia 0 0 0 0 1 0 0 5

Heart Number Examined: 10 10 10 10 9 10 10 10

Infiltrate, Cellular, Myocardium 3 3 3 5 2 1 2 2

Inflammation, Chronic 0 4 9 8 0 0 4 10
104

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313013

Histopathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number: 10 10 10 10 9 10 10 10

Spleen Number Examined: 10 10 10 10 9 10 10 10

Adhesion 0 0 0 0 0 0 1 3

Capsular Cyst(s) 0 0 0 1 0 0 1 0

Capsular Inflammation 0 0 3 5 0 1 1 6

Capsular Thickening 1 1 3 6 1 2 3 8

Haemosiderosis 0 0 0 0 0 0 1 0

Thymus Number Examined: 10 10 10 10 9 10 10 10

Involution/Atrophy 0 0 0 1 0 0 0 5

Thyroids Number Examined: 10 0 0 10 9 0 0 10

Follicular Cell Vacuolation 4 0 0 0 0 0 0 0

Follicular Dilatation 0 0 0 1 0 0 0 0

Parathyroids Number Examined: 10 0 0 8 8 0 0 8

Adrenals Number Examined: 10 0 0 10 9 0 0 10

B-Subcapsular Cell Adenoma 0 0 0 1 0 0 0 0

Cortical Hypertrophy 0 0 0 1 1 0 0 0

Cortical Vacuolation 6 0 0 6 0 0 0 0

Subcapsular Cell Hyperplasia, Focal 0 0 0 0 1 0 0 0
105

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313013

Histopathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number: 10 10 10 10 9 10 10 10

Pituitary Number Examined: 10 0 0 10 9 0 0 10

Cyst(s) 0 0 0 1 2 0 0 1

LN Mandibular Number Examined: 10 0 0 10 9 0 0 10

Paracortex - Increased Cellularity 0 0 0 0 2 0 0 0

Plasmacytosis 6 0 0 7 5 0 0 3

Sinus Erythrocytosis/Erythrophagocytosis 0 0 0 0 0 0 0 2

Sinus Histiocytosis 3 0 0 4 3 0 0 7

Salivary Glands Number Examined: 10 0 0 10 9 0 0 10

Inflammation 0 0 0 0 0 0 0 1

Tongue Number Examined: 10 0 0 10 9 0 0 10

Parotid S.G. Number Examined: 10 0 0 10 9 0 0 10

Acinar Atrophy 0 0 0 1 1 0 0 0

Mineralisation 0 0 0 0 1 0 0 0
106

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313013

Histopathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number: 10 10 10 10 9 10 10 10

Stomach Number Examined: 10 1 0 10 9 0 0 10

Dilated Glands 0 0 0 1 0 0 0 1

Mucosal Erosion - Glandular Region 0 0 0 1 0 0 0 0

Non-glandular Region - Squamous Cyst(s) 0 1 0 0 0 0 0 0

Submucosal Inflammation - Glandular Region 1 0 0 0 1 0 0 0

Oesophagus Number Examined: 10 0 0 10 9 0 0 10

Duodenum Number Examined: 10 0 0 10 9 0 0 10

Ileum Number Examined: 10 0 0 10 9 0 0 10

Peyer's Patch Number Examined: 10 0 0 10 9 0 0 9

Colon Number Examined: 10 0 0 10 9 0 0 10

Jejunum Number Examined: 10 0 0 10 9 0 0 10

Caecum Number Examined: 10 0 0 10 9 0 0 10

Rectum Number Examined: 10 0 0 10 9 0 0 10

Submucosal Oedema 1 0 0 0 0 0 0 0
107

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313013

Histopathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number: 10 10 10 10 9 10 10 10

Mammary Number Examined: 10 0 0 10 9 0 0 10

Acinar Atrophy 2 0 0 4 0 0 0 0

Site Only 0 0 0 0 1 0 0 2

Skin Number Examined: 10 0 1 10 9 0 1 10

Dermal Inflammation 0 0 1 1 2 0 0 1

Epidermal Hyperplasia 0 0 1 1 2 0 0 0

Epidermal Ulceration 0 0 0 0 1 0 0 0

Scab(s) 0 0 1 1 2 0 0 0

Skeletal Muscle Number Examined: 10 0 0 10 9 0 0 10

Inflammation 0 0 0 0 1 0 0 1

Lachrymal Glands Number Examined: 10 0 0 10 9 0 0 10

Lymphoid Aggregates 1 0 0 0 1 0 0 1

Eyes Number Examined: 10 0 0 10 9 0 0 10

Inflammation of the Sclera 0 0 0 0 0 0 0 1

Inflammatory Cells, Anterior Chamber 0 0 0 0 0 0 0 1

Iritis 0 0 0 0 0 0 0 1

Keratitis 0 0 0 0 0 0 0 1

Retinal Rosettes/Folds 1 0 0 0 0 0 0 0
108

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313013

Histopathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number: 10 10 10 10 9 10 10 10

Harderian Glands Number Examined: 10 0 0 10 9 0 0 10

Lymphoid Aggregates 0 0 0 0 2 0 0 0

M-Adenocarcinoma 0 0 0 0 0 0 0 1

Sternum + Marrow Number Examined: 10 0 0 10 9 0 0 10

Marrow - Fat Replacement 0 0 0 2 0 0 0 0

Femur inc. Joint Number Examined: 10 0 0 10 9 0 0 10

Synovitis 1 0 0 0 0 0 0 0

Sciatic Nerve Number Examined: 10 0 0 10 9 0 0 10

Brain Number Examined: 10 0 0 10 9 0 0 10

Spinal C. Cerv. Number Examined: 10 0 0 10 9 0 0 10

Spinal C. Thor. Number Examined: 10 0 0 10 9 0 0 10

Spinal C. Lumb. Number Examined: 10 0 0 10 9 0 0 10
109

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313013

Histopathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number: 10 10 10 10 9 10 10 10

Prostate Number Examined: 10 0 0 10 - - - -

Abscessation 0 0 0 1 - - - -

Lymphoid Aggregates 6 0 0 1 - - - -

Seminal Vesicles Number Examined: 10 0 0 10 - - - -

Epididymides Number Examined: 10 0 0 10 - - - -

Lymphoid Aggregates 0 0 0 3 - - - -

Testes Number Examined: 10 0 0 10 - - - -

Seminiferous Tubular Atrophy 0 0 0 1 - - - -

Optic nerves Number Examined: 10 0 0 10 9 0 0 10

Degenerate Fibres 0 0 0 1 0 0 0 0

Ovaries Number Examined: - - - - 9 0 0 10

Cyst(s) - - - - 1 0 0 0

Prominent Corpora Lutea - - - - 1 0 0 0
110

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313013

Histopathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number: 10 10 10 10 9 10 10 10

Vagina Number Examined: - - - - 9 0 0 10

Dioestrus - - - - 0 0 0 1

Metoestrus - - - - 7 0 0 6

Oestrus - - - - 1 0 0 3

Proestrus - - - - 1 0 0 0

Uterus Number Examined: - - - - 9 0 0 10

Polyploid Hyperplasia - - - - 1 0 0 1

Uterine cervix Number Examined: - - - - 9 0 0 10

Larynx Number Examined: 10 10 10 10 9 10 10 10

Foreign Body Reaction - Ventral Pouch 1 0 0 0 0 0 0 0

Inflammatory Cells in Lamina Propria 5 4 4 5 3 2 5 4

Squamous Metaplasia - Ventral 0 0 0 5 0 0 0 2

Tracheal Bifurc. Number Examined: 10 10 10 10 9 10 10 10

Inflammatory Cells in Lamina Propria 1 2 0 3 1 2 2 2

Loss of Cilia at Bifurcation 0 0 0 1 0 0 0 0
111

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313013

Histopathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number: 10 10 10 10 9 10 10 10

LN Bronchial Number Examined: 9 0 0 10 9 0 0 10

Decreased Cellularity - Generalised 0 0 0 1 0 0 0 0

Paracortex - Increased Cellularity 1 0 0 0 0 0 0 0

Sinus Histiocytosis 0 0 0 1 0 0 0 1
112

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313013

Histopathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number: 10 10 10 10 9 10 10 10

Nasal turbinates Number Examined: 10 10 10 10 9 10 10 10

Increased Vacuolation of Vomeronasal Organ Epithelium 0 0 0 3 0 0 0 0

Inflammatory Exudate in Airways 0 0 0 1 0 0 0 5

Nasolacrimal Duct - Epithelial Squamous Metaplasia 1 1 0 0 2 3 2 8

Nasolacrimal Duct - Inflammation 5 8 4 8 2 4 7 9

Nasolacrimal Duct - Luminal Inflammatory Exudate 0 0 0 0 0 0 0 4

Nasolacrimal Duct Epithelial Degeneration 2 1 0 5 0 0 0 0

Nasopharynx - Goblet Cell Hyperplasia 1 0 0 2 0 0 0 0

Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation 1 2 8 10 1 0 5 10

Olfactory Epithelium - Erosion 0 0 0 0 1 0 0 0

Olfactory Epithelium - Inflammation 0 0 0 3 1 0 0 2

Olfactory Epithelium - Inflammatory Cells in the Lamina 

Propria

0 0 0 2 1 0 0 8

Olfactory Epithelium - Respiratory Metaplasia 0 0 0 0 0 0 0 5

Olfactory Epithelium - Squamous Metaplasia 0 0 0 1 0 0 0 1

Periodontal Abscess 0 1 0 0 0 0 0 0

Periodontal Inflammatory Cell Infiltration 0 1 0 0 0 0 0 0

Red Blood Cells in Airways 0 2 0 0 2 0 0 0

Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation 0 1 0 6 1 1 1 10

Respiratory Epithelium - Erosion 0 0 0 0 1 0 0 2

Respiratory Epithelium - Goblet Cell Hyperplasia 0 0 0 4 0 1 0 0

Respiratory Epithelium - Inflammation 0 0 0 1 0 0 0 3

Respiratory Epithelium - Inflammatory Cells in the Lamina 

Propria

0 0 0 1 0 0 0 10

Respiratory Epithelium - Regenerative Hyperplasia 0 0 0 1 0 0 0 0

Respiratory Epithelium - Squamous Metaplasia 0 0 0 1 0 0 0 0
113

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313013

Histopathology - group distribution of findings for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 2M 3M 4M 1F 2F 3F 4F

Tissue and Finding Number: 10 10 10 10 9 10 10 10

Nasal turbinates (continued) Number Examined: 10 10 10 10 9 10 10 10

Squamous Epithelium - Inflammatory Cells in the Lamina 

Propria

0 0 0 0 0 0 0 1

Transitional Epithelium - Inflammatory Cells in the Lamina 

Propria

0 0 0 0 0 1 1 1

Teeth Number Examined: 10 10 10 10 9 10 10 10

Ameloblast Degeneration 0 0 0 1 0 0 0 2

Odontoblast Degeneration 0 0 0 1 0 0 2 1

Periodontal Ligament Inflammation 0 0 0 1 0 0 0 0

Pulp Cavity Increased Inflammatory Cell Infiltration 0 0 0 0 0 0 0 2

Pulp Cavity Necrosis 0 0 0 0 0 0 0 5

Paws Number Examined: 0 0 0 0 0 1 0 0

Oedema 0 0 0 0 0 1 0 0
114

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313015

Histopathology - group distribution of findings for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 4M 1F 4F

Tissue and Finding Number: 10 10 10 10

Trachea Number Examined: 10 10 10 10

Inflammation 3 0 0 0

Lungs + Bronchi Number Examined: 10 10 10 10

Aggregations of Alveolar Macrophages 4 3 2 0

Alveolar Congestion 1 0 0 0

Alveolar Eosinophilic Crystals 4 3 0 0

Alveolitis 4 4 0 0

Arterial Mural Mineralisation 6 3 4 4

Perivascular Inflammatory Cells 3 1 1 1

Pleural Inflammation 0 1 0 0

Liver Number Examined: 10 10 10 10

Hepatocyte Necrosis, Focal 0 0 1 1

Hepatocyte Vacuolation, Periportal 0 0 2 0

Inflammation, Focal 4 3 5 5

Perivascular Mineralisation 0 1 0 0

Pancreas Number Examined: 10 10 10 10

Acinar Atrophy, Focal 0 1 0 1

Acinar Cell Degranulation 0 0 1 0

Inflammation 0 0 1 1
115

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313015

Histopathology - group distribution of findings for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 4M 1F 4F

Tissue and Finding Number: 10 10 10 10

Kidneys Number Examined: 0 1 0 1

Pelvic Dilatation 0 0 0 1

Perivascular Lymphoid Aggregations 0 1 0 0

Heart Number Examined: 10 10 10 10

Infiltrate, Cellular, Myocardium 6 3 1 0

Inflammation, Chronic 1 1 0 0

Spleen Number Examined: 10 10 10 10

Adhesion 0 1 0 1

Capsular Inflammation 0 2 0 0

Capsular Thickening 0 2 0 1

Haemosiderosis 0 0 0 1

Thymus Number Examined: 10 10 9 10

Pituitary Number Examined: 0 1 0 0

Cyst(s) 0 1 0 0

LN Mandibular Number Examined: 0 1 0 0

Paracortex - Increased Cellularity 0 1 0 0

Plasmacytosis 0 1 0 0
116

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313015

Histopathology - group distribution of findings for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 4M 1F 4F

Tissue and Finding Number: 10 10 10 10

Ovaries Number Examined: - - 1 1

Cyst(s) - - 1 0

Haemorrhagic Cyst(s) - - 0 1

Larynx Number Examined: 10 10 10 10

Haemorrhage in Lamina Propria 1 0 0 0

Inflammatory Cells in Lamina Propria 3 3 6 5

Tracheal Bifurc. Number Examined: 10 10 10 10

Inflammatory Cells in Lamina Propria 2 3 0 1
117

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313015

Histopathology - group distribution of findings for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 4M 1F 4F

Tissue and Finding Number: 10 10 10 10

Nasal turbinates Number Examined: 10 10 10 10

Increased Vacuolation of Vomeronasal Organ Epithelium 0 0 1 0

Inflammatory Exudate in Airways 1 0 2 1

Nasolacrimal Duct - Epithelial Squamous Metaplasia 2 0 0 1

Nasolacrimal Duct - Inflammation 5 6 5 9

Nasolacrimal Duct - Luminal Inflammatory Exudate 0 0 0 1

Nasolacrimal Duct Epithelial Degeneration 0 1 0 0

Nasopharynx - Goblet Cell Hyperplasia 1 0 0 0

Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation 0 9 1 7

Olfactory Epithelium - Erosion 0 1 0 1

Olfactory Epithelium - Inflammatory Cells in the Lamina 

Propria

0 1 0 3

Olfactory Epithelium - Squamous Metaplasia 0 1 0 0

Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation 1 2 1 2

Respiratory Epithelium - Erosion 0 0 0 3

Respiratory Epithelium - Goblet Cell Hyperplasia 3 4 0 3

Respiratory Epithelium - Inflammatory Cells in the Lamina 

Propria

0 0 1 4

Respiratory Epithelium - Squamous Metaplasia 0 0 0 2

Transitional Epithelium - Inflammatory Cells in the Lamina 

Propria

2 0 1 2

Teeth Number Examined: 10 10 10 10

Ameloblast Degeneration 0 0 0 4
118

Huntingdon Life Sciences

WAG0014

TABLE 9 - continued Request ID: 313015

Histopathology - group distribution of findings for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/Sex: 1M 4M 1F 4F

Tissue and Finding Number: 10 10 10 10

Preputial glands Number Examined: 1 0 - -

Abscessation 1 0 - -
119

Huntingdon Life Sciences

WAG0014

APPENDIX 1 Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

1M 81 T 18 Coat Hair loss, Head 11-R5

82 T 18 Skin Abrasion Dry, Tail, Slight 10-11

85 T 18 Coat Hair loss, Forelimbs 11-R5

Skin Abrasion Dry, Tail, Slight 5-7

86 T 18 Coat Hair loss, Head R4-R5

87 T 18 Coat Hair loss, Head R4-R5

88 T 18 Behaviour Aggressive R5

89 T 18 Coat Hair loss, Dorsal Body Surface 3

Only animals with observations are presented
120

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

2M 101 T 14 Coat Hair loss, Head 9-14

Skin Abrasion Dry, Head, Slight 10

Dry, Tail, Slight 6-7

102 T 14 Coat Hair loss, Head 10-14

Staining Abnormal Colour, Brown, Head 4, 8-9

103 T 14 Skin Encrustation, Tail 4-5

Staining Abnormal Colour, Brown, Dorsal Body Surface 10-14

104 T 14 Coat Hair loss, Head 9-14

Skin Abrasion Dry, Head, Slight 10

Dry, Tail, Slight 9

106 T 14 Coat Hair loss, Dorsal Body Surface 6-11

109 T 14 Build Deformity Swollen Area, Nose 9-14

Only animals with observations are presented
121

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

3M 111 T 14 Behaviour Aggressive 10-11

Skin Abrasion Dry, Tail, Slight 5

112 T 14 Teeth Abnormal Colour, Pale 6-13

Abnormal Colour, Pale, Lower Jaw 5

113 T 14 Coat Hair loss, Head 11-14

Skin Abrasion Dry, Tail, Slight 13-14

Skin Encrustation, Tail 4-7

114 T 14 Behaviour Aggressive 8-11

115 T 14 Teeth Abnormal Colour, Pale 13-14

117 T 14 Teeth Abnormal Colour, Pale 8-14

118 T 14 Behaviour Aggressive 11

Teeth Absent, Pale 10

Abnormal Colour, Pale 11-14

119 T 14 Staining Abnormal Colour, Brown, Head 3

Teeth Abnormal Colour, Pale 9-14

Only animals with observations are presented
122

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

3M 120 T 14 Staining Abnormal Colour, Brown, Dorsal Body Surface 10-11

Only animals with observations are presented
123

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

4M 11 T 14 Behaviour Underactive 12-14

Coat Piloerection 12-14

Staining Abnormal Colour, Brown, Forepaws 12-14

Abnormal Colour, Brown, Head 12-14

Abnormal Colour, Brown, Dorsal Body Surface 8-9, 12-14

Teeth Abnormal Colour, Pale 4, 6-14

Abnormal Colour, Pale, Lower Jaw 5

12 T 14 Skin Colour Abnormal Colour, Brown, Dorsal Body Surface 13-14

Teeth Abnormal Colour, Pale 8-14

13 T 14 Behaviour Underactive 12-14

Teeth Abnormal Colour, Pale 6-14

14 T 14 Staining Abnormal Colour, Brown, Head 8-9

Abnormal Colour, Brown, Dorsal Body Surface 8-9, 11-12

Teeth Abnormal Colour, Pale 10-14

15 T 14 Teeth Abnormal Colour, Pale 9-14

Only animals with observations are presented
124

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

4M 16 T 14 Skin Abrasion Dry, Tail, Slight 10-14

Staining Abnormal Colour, Brown, Dorsal Body Surface 9-14

Teeth Abnormal Colour, Pale 6-14

Abnormal Colour, Pale, Lower Jaw 5

17 T 14 Skin Abrasion Dry, Tail, Slight 10-11

Staining Abnormal Colour, Brown, Head 3-9, 12-14

Abnormal Colour, Brown, Dorsal Body Surface 4-14

Teeth Abnormal Colour, Pale 6-14

Abnormal Colour, White 2

18 T 14 Build Deformity Kinked Tail 10-14

Skin Abrasion Dry, Tail, Slight 8-9

19 T 14 Coat Piloerection 11

Skin Abrasion Dry, Tail, Slight 13-14

Teeth Abnormal Colour, Pale 8-14

20 T 14 Staining Abnormal Colour, Brown, Dorsal Body Surface 6, 9-14

Teeth Abnormal Colour, Pale 8-14

Only animals with observations are presented
125

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

4M 71 T 18 Skin Abrasion Dry, Ventral Abdomen, Slight 10-11

Staining Abnormal Colour, Brown, Head 10-11

Abnormal Colour, Dorsal Body Surface 3

Abnormal Colour, Brown, Dorsal Body Surface 4-11

Teeth Abnormal Colour, Pale 10-R5

72 T 18 Staining Abnormal Colour, Brown, Dorsal Body Surface 9, 11-R1

Teeth Abnormal Colour, Pale 8-R5

73 T 18 Staining Abnormal Colour, Brown, Dorsal Body Surface 3, 6-9, 11-R2

Teeth Abnormal Colour, Pale 6-R5

Abnormal Colour, White 2-4

Abnormal Colour, Pale, Lower Jaw 5

74 T 18 Staining Abnormal Colour, Brown, Dorsal Body Surface 4-7, 9-R3

Teeth Abnormal Colour, Pale 4, 6-R5

Abnormal Colour, Pale, Lower Jaw 5

75 T 18 Staining Abnormal Colour, Brown, Dorsal Body Surface 5-R3

Teeth Abnormal Colour, Pale 8-R5

Abnormal Colour, White 2

Only animals with observations are presented
126

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

4M 76 T 18 Skin Abrasion Dry, Tail, Slight 11-12

Staining Abnormal Colour, Brown, Head 10

Abnormal Colour, Brown, Dorsal Body Surface 9-10

Teeth Abnormal Colour, Pale 8-11

77 T 18 Staining Abnormal Colour, Brown, Dorsal Body Surface 9-10, 13-R2

Teeth Abnormal Colour, Pale 10-11

78 T 18 Build Deformity Kinked Tail 3-R5

Staining Abnormal Colour, Brown, Head 13-R3

Teeth Abnormal Colour, Pale 4, 6-R5

Abnormal Colour, Pale, Lower Jaw 5

79 T 18 Build Deformity Kinked Tail R2-R5

Skin Abrasion Dry, Tail, Slight 11-R1

Staining Abnormal Colour, Brown, Head 6-7

Abnormal Colour, Brown, Dorsal Body Surface 6-7

Teeth Abnormal Colour, Pale 10-R5

80 T 18 Staining Abnormal Colour, Brown, Head 5-9

Abnormal Colour, Brown, Dorsal Body Surface 10-R2

Teeth Abnormal Colour, Pale 6-R5

Only animals with observations are presented
127

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

1F 23 T 14 Behaviour Vocalisation 6, 8-12

24 T 14 Behaviour Vocalisation 6-11, 13-14

26 T 14 Coat Hair loss, Forelimbs 11-14

Hair loss, Head 11-14

27 W 8 Behaviour Underactive 8

Body temperature Reduced 8

Breathing Gasping 8

Coat Piloerection 8

Hair loss, Dorsal Body Surface 4-5

Eyelids Partially Closed 8

Skin Colour Pallor 8

Reason for Dispatch General poor clinical condition 8

28 T 14 Behaviour Vocalisation 5-6, 8-12

Coat Hair loss, Head 9-14

Skin Abrasion Dry, Tail 9-10

Dry, Tail, Slight 11-12

Only animals with observations are presented
128

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

1F 29 T 14 Behaviour Vocalisation 10

Coat Hair loss, Head 10-12

Skin Abrasion Dry, Tail, Slight 13-14

30 T 14 Skin Abrasion Dry, Tail, Slight 6-9

43 T 18 Coat Hair loss, Head R1-R2

Teeth Abnormal Colour, White 2-3

44 T 18 Behaviour Vocalisation 8-13

48 T 18 Behaviour Aggressive R2

Vocalisation 10-12, R2

Teeth Abnormal Colour, Pale 4-8

49 T 18 Behaviour Vocalisation 6-8, 12, R2-R3

50 T 18 Behaviour Vocalisation 5-R2

Build Deformity Partially absent appendage, Tail R2-R5

Only animals with observations are presented
129

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

2F 51 T 14 Behaviour Vocalisation 8-14

Coat Hair loss, Dorsal Body Surface 6-11

52 T 14 Build Deformity Swollen Area, Forepaw (Left) 11-14

Skin Encrustation, Tail 4

53 T 14 Coat Hair loss, Forelimb (Left) 10

Hair loss, Forelimbs 11-14

Hair loss, Dorsal Body Surface 9-11, 13-14

54 T 14 Coat Hair loss, Dorsal Body Surface 13-14

55 T 14 Coat Hair loss, Forelimbs 13-14

Hair loss, Dorsal Body Surface 8-9

Teeth Abnormal Colour, Pale 6-11

Abnormal Colour, Pale, Lower Jaw 5

56 T 14 Behaviour Vocalisation 6-14

Coat Hair loss, Head 5-9

Teeth Abnormal Colour, White 2

57 T 14 Behaviour Vocalisation 11-14

Teeth Abnormal Colour, White 2

Only animals with observations are presented
130

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

2F 58 T 14 Behaviour Vocalisation 8-14

Build Deformity Kinked Tail 12-14

Coat Hair loss, Head 6-8, 10-14

Staining Abnormal Colour, Brown, Head 3

Teeth Abnormal Colour, White 2

59 T 14 Behaviour Aggressive 8-11

Vocalisation 5-14

Coat Hair loss, Head 5-9

Hair loss, Head 10-14

Skin Abrasion Dry, Tail, Slight 13-14

60 T 14 Coat Hair loss, Forelimb (Left) 4

Hair loss, Forelimbs 5-14

Hair loss, Hindlimbs 5-14

Hair loss, Head 4-14

Hair loss, Dorsal Body Surface 5-14

Only animals with observations are presented
131

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

3F 1 T 14 Behaviour Vocalisation 5-14

Staining Abnormal Colour, Head 12

Abnormal Colour, Brown, Muzzle 6

2 T 14 Behaviour Vocalisation 6-14

Staining Abnormal Colour, Brown, Head 11-14

3 T 14 Behaviour Vocalisation 4, 6-7, 9-11

Skin Abrasion Dry, Tail, Slight 13-14

Staining Abnormal Colour, Brown, Head 6-7, 13-14

4 T 14 Teeth Abnormal Colour, Pale 10-11

5 T 14 Behaviour Vocalisation 4-6, 8-14

Coat Hair loss, Dorsal Body Surface 5-7

6 T 14 Behaviour Aggressive 10

Vocalisation 6, 10-14

Coat Hair loss, Head 10-14

Hair loss, Dorsal Body Surface 6-11

Staining Abnormal Colour, Brown, Head 3

Only animals with observations are presented
132

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

3F 7 T 14 Coat Hair loss, Head 12-14

Hair loss, Dorsal Body Surface 8-14

Staining Abnormal Colour, Brown, Cervical 3-9

Abnormal Colour, Brown, Dorsal Body Surface 10-14

8 T 14 Behaviour Aggressive 11-14

Vocalisation 6, 8-14

Coat Hair loss, Dorsal Body Surface 10-14

Staining Abnormal Colour, Brown, Cervical 5-9

9 T 14 Behaviour Vocalisation 4-6, 8-12

Coat Hair loss, Head 11-14

Hair loss, Dorsal Body Surface 6-14

Staining Abnormal Colour, Brown, Cervical 8-9

10 T 14 Coat Hair loss, Head 10-14

Hair loss, Dorsal Body Surface 4-14

Skin Abrasion Dry, Tail, Slight 13-14

Skin Encrustation, Dorsal Body Surface 5-8

Only animals with observations are presented
133

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

4F 31 T 14 Coat Hair loss, Dorsal Body Surface 8-11

Skin Abrasion Dry, Tail 12-14

Staining Abnormal Colour, Brown, Head 3-9

Abnormal Colour, Brown, Dorsal Body Surface 12-14

Teeth Abnormal Colour, Pale 4, 6-14

Abnormal Colour, Pale, Lower Jaw 5

32 T 14 Behaviour Underactive 13-14

Coat Hair loss, Dorsal Body Surface 8-14

Eyelids Partially Closed 13-14

Muscle Reaction Reduced Body Tone, Whole Body 5-14

Abnormal Gait, Elevated 3-12

Skin Abrasion Dry, Tail, Slight 13-14

Skin Encrustation, Tail 5-7

Staining Abnormal Colour, Brown, Head 3-14

Teeth Abnormal Colour, Pale 9-14

Brittle 10

33 T 14 Coat Hair loss, Forelimb (Left) 6-14

Only animals with observations are presented
134

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

4F 34 T 14 Coat Hair loss, Dorsal Body Surface 9-14

Muscle Reaction Abnormal Gait, Elevated 10-12

Staining Abnormal Colour, Brown, Head 4

Teeth Abnormal Colour, Pale 13-14

35 T 14 Coat Hair loss, Head 6-14

Staining Abnormal Colour, Brown, Head 8-9

Teeth Abnormal Colour, Pale 8-14

Brittle 11

36 T 14 Build Deformity Swollen Area, Eye (Left) 12-14

Skin Abrasion Dry, Tail, Slight 13-14

Staining Abnormal Colour, Brown, Head 8-9

Abnormal Colour, Brown, Dorsal Body Surface 8-14

Teeth Abnormal Colour, Pale 4, 6-14

Abnormal Colour, Pale, Lower Jaw 5

37 T 14 Behaviour Underactive 13-14

Body temperature Reduced 13-14

Muscle Reaction Reduced Body Tone 13-14

Staining Abnormal Colour, Brown, Head 9

Abnormal Colour, Brown, Muzzle 13-14

Teeth Abnormal Colour, Pale 10-14

Only animals with observations are presented
135

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

4F 38 T 14 Coat Hair loss, Head 10-11

Eyelids Red-Rimmed 13-14

Teeth Abnormal Colour, Pale 9-14

39 T 14 Behaviour Vocalisation 7

Coat Hair loss, Head 10-11

Teeth Abnormal Colour, Pale 9-14

40 T 14 Skin Abrasion Dry, Tail, Slight 4-9

Staining Abnormal Colour, Brown, Head 8-14

Teeth Abnormal Colour, Pale 9-14

91 T 18 Behaviour Excessive chewing 13-14

Underactive 13-14

Coat Piloerection 13-14

Eyelids Partially Closed 13-14

Muscle Reaction Reduced Body Tone, Whole Body 13-14

Skin Abrasion Dry, Tail, Slight 3

Staining Abnormal Colour, Brown, Head 7

Abnormal Colour, Brown, Muzzle 13-14

Teeth Abnormal Colour, Pale 8-R5

Only animals with observations are presented
136

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

4F 92 T 18 Behaviour Vocalisation 10-11, R2-R5

Teeth Broken 11-13

Abnormal Colour, Pale 6-R5

Brittle 11

93 T 18 Behaviour Aggressive 10

Vocalisation 10

Build Deformity Kinked Tail 12-R5

Coat Hair loss, Head 6-7

Staining Abnormal Colour, Brown, Head 5-9

Teeth Abnormal Colour, Pale 6-R5

94 T 18 Behaviour Excessive chewing 11

Coat Hair loss, Head 13-R3

Eye Dull 11

Muscle Reaction Reduced Body Tone 11-13

Abnormal Gait 11

Staining Abnormal Colour, Brown, Head 7, 11

Teeth Abnormal Colour, Pale 9-R5

95 T 18 Skin Abrasion Dry, Tail, Slight 11

Staining Abnormal Colour, Brown, Head 7, 13

Teeth Abnormal Colour, Pale 9-R5

Only animals with observations are presented
137

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

4F 96 T 18 Coat Hair loss, Forelimb (Right) 5-9

Hair loss, Head 5-R5

Hair loss, Dorsal Body Surface 5-R5

Staining Abnormal Colour, Brown, Dorsal Body Surface 13

Teeth Abnormal Colour, Pale 8-R5

97 T 18 Coat Hair loss, Head 8-R5

Hair loss, Dorsal Body Surface 5-R5

Staining Abnormal Colour, Brown, Head 8-9

Teeth Abnormal Colour, Pale 6-11

Abnormal Colour, Pale, Lower Jaw 5

98 T 18 Skin Encrustation, Tail 5

Staining Abnormal Colour, Brown, Head 7-R2

Abnormal Colour, Brown, Dorsal Body Surface 10-13

Teeth Abnormal Colour, Pale 9-R5

99 T 18 Coat Hair loss, Head 8-R5

Hair loss, Dorsal Body Surface 6-R3

Staining Abnormal Colour, Brown, Head 8-10

Teeth Abnormal Colour, Pale 6-R5

Only animals with observations are presented
138

Huntingdon Life Sciences

WAG0014

APPENDIX 1 - continued Request ID: 296730

Clinical signs - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Death Week of

/Sex Number Code Death Category Observation Week(s)

4F 100 T 18 Coat Hair loss, Head 2-R5

Hair loss, Dorsal Body Surface 8-R3

Staining Abnormal Colour, Brown, Head 5-10

Teeth Abnormal Colour, Pale 9-R5

Only animals with observations are presented
139

Huntingdon Life Sciences

WAG0014

APPENDIX 2 Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2M 101 Behaviour

 Underactive 3, 15, 24-25, 15-18, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

 Unresponsive 18

Breathing

 Slow 18

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88, 92

Eyelids (Left)

 Partially Closed 24 18, 23-24

Eyelids (Right)

 Partially Closed 24 18, 23-24
140

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2M 102 Behaviour

 Underactive 3, 15, 24-25, 15-18, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

 Unresponsive 18

Breathing

 Slow 18

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88, 92

Eyelids (Left)

 Partially Closed 24 18, 23-24

Eyelids (Right)

 Partially Closed 24 18, 23-24
141

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2M 103 Behaviour

 Underactive 3, 15, 24-25, 15-18, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

 Unresponsive 18

Breathing

 Slow 18

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88, 92

Eyelids (Left)

 Partially Closed 24 18, 23-24

Eyelids (Right)

 Partially Closed 24 18, 23-24
142

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2M 104 Behaviour

 Underactive 3, 15, 24-25, 15-18, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

 Unresponsive 18

Breathing

 Slow 18

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88, 92

Eyelids (Left)

 Partially Closed 24 18, 23-24

Eyelids (Right)

 Partially Closed 24 18, 23-24
143

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2M 105 Behaviour

 Underactive 3, 15, 24-25, 15-18, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

 Unresponsive 18

Breathing

 Slow 18

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88, 92

Eyelids (Left)

 Partially Closed 24 18, 23-24

Eyelids (Right)

 Partially Closed 24 18, 23-24
144

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2M 106 Behaviour

 Underactive 3, 15, 24-25, 15-18, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52, 94

 Unresponsive 18

Breathing

 Slow 18

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88, 94 43-44, 46, 52,

70, 88, 92-94

Eyelids (Left)

 Partially Closed 24 18, 23-24

Eyelids (Right)

 Partially Closed 24 18, 23-24
145

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2M 107 Behaviour

 Underactive 3, 15, 24-25, 15-18, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52, 94

 Unresponsive 18

Breathing

 Slow 18

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88, 94 43-44, 46, 52,

70, 88, 92-94

Eyelids (Left)

 Partially Closed 24 18, 23-24

Eyelids (Right)

 Partially Closed 24 18, 23-24
146

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2M 108 Behaviour

 Underactive 3, 15, 24-25, 15-18, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52, 94

 Unresponsive 18

Breathing

 Slow 18

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88, 94 43-44, 46, 52,

70, 88, 92-94

Eyelids (Left)

 Partially Closed 24 18, 23-24

Eyelids (Right)

 Partially Closed 24 18, 23-24
147

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2M 109 Behaviour

 Underactive 3, 15, 24-25, 15-18, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52, 94

 Unresponsive 18

Breathing

 Slow 18

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88, 94 43-44, 46, 52,

70, 88, 92-94

Eyelids (Left)

 Partially Closed 24 18, 23-24

Eyelids (Right)

 Partially Closed 24 18, 23-24
148

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2M 110 Behaviour

 Underactive 3, 15, 24-25, 15-18, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52, 94

 Unresponsive 18

Breathing

 Slow 18

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88, 94 43-44, 46, 52,

70, 88, 92-94

Eyelids (Left)

 Partially Closed 24 18, 23-24

Eyelids (Right)

 Partially Closed 24 18, 23-24
149

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 111 Behaviour

 Underactive 1-4, 7-8, 14-15, 1-4, 7, 9, 14-18,

17-18, 21-25, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

63-67, 70, 88 88

 Unresponsive 1, 17-18, 29-30, 1, 15, 17-18,

38, 51 21, 30, 35,

38, 63

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88
150

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 111 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 63, 49-50, 56, 63,

65, 71-74, 65, 71-74,

77-81, 84-88, 77-81, 84-88,

91 91

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88
151

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 112 Behaviour

 Underactive 1-4, 7-8, 14-15, 1-4, 7, 9, 14-18,

17-18, 21-25, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

63-67, 70, 88 88

 Unresponsive 1, 17-18, 29-30, 1, 15, 17-18,

38, 51 21, 30, 35,

38, 63

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88
152

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 112 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 63, 49-50, 56, 63,

65, 71-74, 65, 71-74,

77-81, 84-88, 77-81, 84-88,

91 91

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88
153

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 113 Behaviour

 Underactive 1-4, 7-8, 14-15, 1-4, 7, 9, 14-18,

17-18, 21-25, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

63-67, 70, 88 88

 Unresponsive 1, 17-18, 29-30, 1, 15, 17-18,

38, 51 21, 30, 35,

38, 63

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88
154

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 113 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 63, 49-50, 56, 63,

65, 71-74, 65, 71-74,

77-81, 84-88, 77-81, 84-88,

91 91

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88
155

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 114 Behaviour

 Underactive 1-4, 7-8, 14-15, 1-4, 7, 9, 14-18,

17-18, 21-25, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

63-67, 70, 88 88

 Unresponsive 1, 17-18, 29-30, 1, 15, 17-18,

38, 51 21, 30, 35,

38, 63

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88
156

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 114 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 63, 49-50, 56, 63,

65, 71-74, 65, 71-74,

77-81, 84-88, 77-81, 84-88,

91 91

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88
157

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 115 Behaviour

 Underactive 1-4, 7-8, 14-15, 1-4, 7, 9, 14-18,

17-18, 21-25, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

63-67, 70, 88 88

 Unresponsive 1, 17-18, 29-30, 1, 15, 17-18,

38, 51 21, 30, 35,

38, 63

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88
158

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 115 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 63, 49-50, 56, 63,

65, 71-74, 65, 71-74,

77-81, 84-88, 77-81, 84-88,

91 91

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88
159

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 116 Behaviour

 Underactive 1-4, 7-8, 14-15, 1-4, 7, 9, 14-18,

17-18, 21-25, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

63-67, 70, 88 88, 92-93

 Unresponsive 1, 17-18, 29-30, 1, 15, 17-18,

38, 51 21, 30, 35,

38, 63

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88,

92-93
160

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 116 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 63, 49-50, 56, 63,

65, 71-74, 65, 71-74,

77-81, 84-88, 77-81, 84-88,

91-93 91-93

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-93

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-93
161

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 117 Behaviour

 Underactive 1-4, 7-8, 14-15, 1-4, 7, 9, 14-18,

17-18, 21-25, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

63-67, 70, 88 88, 92-93

 Unresponsive 1, 17-18, 29-30, 1, 15, 17-18,

38, 51 21, 30, 35,

38, 63

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88,

92-93
162

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 117 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 63, 49-50, 56, 63,

65, 71-74, 65, 71-74,

77-81, 84-88, 77-81, 84-88,

91-93 91-93

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-93

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-93
163

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 118 Behaviour

 Underactive 1-4, 7-8, 14-15, 1-4, 7, 9, 14-18,

17-18, 21-25, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

63-67, 70, 88 88, 92-93

 Unresponsive 1, 17-18, 29-30, 1, 15, 17-18,

38, 51 21, 30, 35,

38, 63

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88,

92-93
164

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 118 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 63, 49-50, 56, 63,

65, 71-74, 65, 71-74,

77-81, 84-88, 77-81, 84-88,

91-93 91-93

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-93

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-93
165

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 119 Behaviour

 Underactive 1-4, 7-8, 14-15, 1-4, 7, 9, 14-18,

17-18, 21-25, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

63-67, 70, 88 88, 92-93

 Unresponsive 1, 17-18, 29-30, 1, 15, 17-18,

38, 51 21, 30, 35,

38, 63

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88,

92-93
166

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 119 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 63, 49-50, 56, 63,

65, 71-74, 65, 71-74,

77-81, 84-88, 77-81, 84-88,

91-93 91-93

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-93

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-93
167

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 120 Behaviour

 Underactive 1-4, 7-8, 14-15, 1-4, 7, 9, 14-18,

17-18, 21-25, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

63-67, 70, 88 88, 92-93

 Unresponsive 1, 17-18, 29-30, 1, 15, 17-18,

38, 51 21, 30, 35,

38, 63

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88,

92-93
168

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3M 120 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 63, 49-50, 56, 63,

65, 71-74, 65, 71-74,

77-81, 84-88, 77-81, 84-88,

91-93 91-93

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-93

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 22-24, 28-29,

35, 44, 50, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-93
169

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 11 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-92 84-88, 91-92

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88,

92
170

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 11 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-92 84-87, 91-92

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-92 84-88, 91-92

Eyelids (Right)

 Closed 1 1
171

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 11 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91-92 91-92

Posture

 Hunched 1 1
172

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 12 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-92 84-88, 91-92

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88,

92
173

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 12 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-92 84-87, 91-92

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-92 84-88, 91-92

Eyelids (Right)

 Closed 1 1
174

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 12 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91-92 91-92

Posture

 Hunched 1 1
175

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 13 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-92 84-88, 91-92

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88,

92
176

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 13 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-92 84-87, 91-92

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-92 84-88, 91-92

Eyelids (Right)

 Closed 1 1
177

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 13 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91-92 91-92

Posture

 Hunched 1 1
178

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 14 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-92 84-88, 91-92

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88,

92
179

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 14 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-92 84-87, 91-92

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-92 84-88, 91-92

Eyelids (Right)

 Closed 1 1
180

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 14 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91-92 91-92

Posture

 Hunched 1 1
181

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 15 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-92 84-88, 91-92

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88,

92
182

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 15 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-92 84-87, 91-92

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-92 84-88, 91-92

Eyelids (Right)

 Closed 1 1
183

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 15 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91-92 91-92

Posture

 Hunched 1 1
184

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 16 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-94 84-88, 91-94

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88, 94 72, 77, 88,

93-94

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24
185

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 16 Breathing

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88, 58, 70, 88,

94 92-94

Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-94 84-87, 91-94

Eyelids (Left)

 Closed 1 1
186

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 16 Eyelids (Left)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-94 84-88, 91-94

Eyelids (Right)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91-94 91-94

Posture

 Hunched 1 1
187

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the

working day

4M 17 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-94 84-88, 91-94

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88, 94 72, 77, 88,

93-94

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24
188

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 17 Breathing

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88, 58, 70, 88,

94 92-94

Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-94 84-87, 91-94

Eyelids (Left)

 Closed 1 1
189

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 17 Eyelids (Left)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-94 84-88, 91-94

Eyelids (Right)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91-94 91-94

Posture

 Hunched 1 1
190

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 18 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-94 84-88, 91-94

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88, 94 72, 77, 88,

93-94

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24
191

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 18 Breathing

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88, 58, 70, 88,

94 92-94

Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-94 84-87, 91-94

Eyelids (Left)

 Closed 1 1
192

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 18 Eyelids (Left)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-94 84-88, 91-94

Eyelids (Right)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91-94 91-94

Posture

 Hunched 1 1
193

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 19 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-94 84-88, 91-94

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88, 94 72, 77, 88,

93-94

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24
194

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 19 Breathing

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88, 58, 70, 88,

94 92-94

Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-94 84-87, 91-94

Eyelids (Left)

 Closed 1 1
195

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 19 Eyelids (Left)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-94 84-88, 91-94

Eyelids (Right)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91-94 91-94

Posture

 Hunched 1 1
196

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 20 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-94 84-88, 91-94

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88, 94 72, 77, 88,

93-94

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24
197

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 20 Breathing

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88, 58, 70, 88,

94 92-94

Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-94 84-87, 91-94

Eyelids (Left)

 Closed 1 1
198

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 20 Eyelids (Left)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-94 84-88, 91-94

Eyelids (Right)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91-94 91-94

Posture

 Hunched 1 1
199

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 71 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
200

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 71 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
201

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 71 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91 91

Posture

 Hunched 1 1
202

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 72 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
203

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 72 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
204

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 72 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91 91

Posture

 Hunched 1 1
205

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 73 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
206

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 73 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
207

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 73 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91 91

Posture

 Hunched 1 1
208

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 74 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
209

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 74 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
210

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 74 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91 91

Posture

 Hunched 1 1
211

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 75 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
212

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 75 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
213

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 75 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91 91

Posture

 Hunched 1 1
214

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 76 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
215

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 76 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
216

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 76 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91 91

Posture

 Hunched 1 1
217

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 77 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
218

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 77 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
219

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 77 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91 91

Posture

 Hunched 1 1
220

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 78 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
221

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 78 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
222

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 78 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91 91

Posture

 Hunched 1 1
223

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 79 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
224

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 79 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
225

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 79 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91 91

Posture

 Hunched 1 1
226

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 80 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-60, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23, 21, 23-25,

25, 29-31, 29-31, 35-36,

35-36, 39, 49, 39, 43, 49,

51-52, 56-57, 51-52, 56-57,

59-60, 64-67, 59-60, 64-67,

88 72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 18, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
227

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the

working day

4M 80 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59-60, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
228

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4M 80 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58, 56, 58, 63,

63, 65-67, 65-67, 70-74,

70-74, 77-81, 77-81, 84-88,

84-88, 91 91

Posture

 Hunched 1 1
229

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2F 51 Behaviour

 Underactive 3, 15, 24-25, 15-17, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88

Eyelids (Left)

 Partially Closed 24 23-24

Eyelids (Right)

 Partially Closed 24 23-24
230

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2F 52 Behaviour

 Underactive 3, 15, 24-25, 15-17, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88

Eyelids (Left)

 Partially Closed 24 23-24

Eyelids (Right)

 Partially Closed 24 23-24
231

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2F 53 Behaviour

 Underactive 3, 15, 24-25, 15-17, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88

Eyelids (Left)

 Partially Closed 24 23-24

Eyelids (Right)

 Partially Closed 24 23-24
232

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2F 54 Behaviour

 Underactive 3, 15, 24-25, 15-17, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88

Eyelids (Left)

 Partially Closed 24 23-24

Eyelids (Right)

 Partially Closed 24 23-24
233

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2F 55 Behaviour

 Underactive 3, 15, 24-25, 15-17, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88

Eyelids (Left)

 Partially Closed 24 23-24

Eyelids (Right)

 Partially Closed 24 23-24
234

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2F 56 Behaviour

 Underactive 3, 15, 24-25, 15-17, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88, 92-93

Eyelids (Left)

 Partially Closed 24 23-24

Eyelids (Right)

 Partially Closed 24 23-24
235

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2F 57 Behaviour

 Underactive 3, 15, 24-25, 15-17, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88, 92-93

Eyelids (Left)

 Partially Closed 24 23-24

Eyelids (Right)

 Partially Closed 24 23-24
236

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2F 58 Behaviour

 Underactive 3, 15, 24-25, 15-18, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88, 92-93

Eyelids (Left)

 Partially Closed 24 18, 23-24

Eyelids (Right)

 Partially Closed 24 18, 23-24
237

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2F 59 Behaviour

 Underactive 3, 15, 24-25, 15-17, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88, 92-93

Eyelids (Left)

 Partially Closed 24 23-24

Eyelids (Right)

 Partially Closed 24 23-24
238

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

2F 60 Behaviour

 Underactive 3, 15, 24-25, 15-17, 23-25,

28-29, 32, 35, 28-29, 32, 35-37,

39, 50, 52 39, 42-43,

50-52

Coat

 Piloerection 3, 8-9, 15, 1-4, 8-9, 15-17,

25, 32, 35, 22-23, 25, 29,

44, 52, 70, 32, 35, 37,

88 43-44, 46, 52,

70, 88, 92-93

Eyelids (Left)

 Partially Closed 24 23-24

Eyelids (Right)

 Partially Closed 24 23-24
239

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 1 Behaviour

 Grinding Teeth 25

 Underactive 1-4, 7-8, 14, 1-4, 7, 9, 14-18,

17-18, 21-24, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

64-67, 70, 88 88, 92

 Unresponsive 1, 15, 17-18, 1, 17-18, 21,

29-30, 38, 51, 30, 35, 38,

64 63-64

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88,

92
240

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 1 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 64-65, 49-50, 56, 63-65,

71-74, 77-81, 71-74, 77-81,

84-88, 91-92 84-88, 91-92

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92
241

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 2 Behaviour

 Grinding Teeth 25

 Underactive 1-4, 7-8, 14, 1-4, 7, 9, 14-18,

17-18, 21-24, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

64-67, 70, 88 88, 92

 Unresponsive 1, 15, 17-18, 1, 17-18, 21,

29-30, 38, 51, 30, 35, 38,

64 63-64

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88,

92
242

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 2 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 64-65, 49-50, 56, 63-65,

71-74, 77-81, 71-74, 77-81,

84-88, 91-92 84-88, 91-92

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92
243

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 3 Behaviour

 Grinding Teeth 25

 Underactive 1-4, 7-8, 14, 1-4, 7, 9, 14-18,

17-18, 21-24, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

64-67, 70, 88 88, 92

 Unresponsive 1, 15, 17-18, 1, 17-18, 21,

29-30, 38, 51, 30, 35, 38,

64 63-64

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88,

92
244

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 3 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 64-65, 49-50, 56, 63-65,

71-74, 77-81, 71-74, 77-81,

84-88, 91-92 84-88, 91-92

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92
245

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 4 Behaviour

 Grinding Teeth 25

 Underactive 1-4, 7-8, 14, 1-4, 7, 9, 14-18,

17-18, 21-24, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

64-67, 70, 88 88, 92

 Unresponsive 1, 15, 17-18, 1, 17-18, 21,

29-30, 38, 51, 30, 35, 38,

64 63-64

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88,

92
246

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 4 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 64-65, 49-50, 56, 63-65,

71-74, 77-81, 71-74, 77-81,

84-88, 91-92 84-88, 91-92

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92
247

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 5 Behaviour

 Grinding Teeth 25

 Underactive 1-4, 7-8, 14, 1-4, 7, 9, 14-18,

17-18, 21-24, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

64-67, 70, 88 88, 92

 Unresponsive 1, 15, 17-18, 1, 17-18, 21,

29-30, 38, 51, 30, 35, 38,

64 63-64

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88 46, 51-53,

58, 70, 88,

92
248

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 5 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 64-65, 49-50, 56, 63-65,

71-74, 77-81, 71-74, 77-81,

84-88, 91-92 84-88, 91-92

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92
249

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 6 Behaviour

 Grinding Teeth 25

 Underactive 1-4, 7-8, 14, 1-4, 7, 9, 14-18,

17-18, 21-24, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

64-67, 70, 88, 88, 92-94

94

 Unresponsive 1, 15, 17-18, 1, 17-18, 21,

29-30, 38, 51, 30, 35, 38,

64 63-64

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88, 46, 51-53,

94 58, 70, 88,

92-94
250

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 6 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 64-65, 49-50, 56, 63-65,

71-74, 77-81, 71-74, 77-81,

84-88, 91-94 84-88, 91-94

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-94

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-94
251

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 6 Posture

 Hunched 94 94
252

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 7 Behaviour

 Grinding Teeth 25

 Underactive 1-4, 7-8, 14, 1-4, 7, 9, 14-18,

17-18, 21-24, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

64-67, 70, 88, 88, 92-94

94

 Unresponsive 1, 15, 17-18, 1, 17-18, 21,

29-30, 38, 51, 30, 35, 38,

64 63-64

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88, 46, 51-53,

94 58, 70, 88,

92-94
253

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 7 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 64-65, 49-50, 56, 63-65,

71-74, 77-81, 71-74, 77-81,

84-88, 91-94 84-88, 91-94

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-94

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-94
254

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 7 Posture

 Hunched 94 94
255

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 8 Behaviour

 Grinding Teeth 25

 Underactive 1-4, 7-8, 14, 1-4, 7, 9, 14-18,

17-18, 21-24, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

64-67, 70, 88, 88, 92-94

94

 Unresponsive 1, 15, 17-18, 1, 17-18, 21,

29-30, 38, 51, 30, 35, 38,

64 63-64

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88, 46, 51-53,

94 58, 70, 88,

92-94
256

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 8 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 64-65, 49-50, 56, 63-65,

71-74, 77-81, 71-74, 77-81,

84-88, 91-94 84-88, 91-94

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-94

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-94
257

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 8 Posture

 Hunched 94 94
258

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 9 Behaviour

 Grinding Teeth 25

 Underactive 1-4, 7-8, 14, 1-4, 7, 9, 14-18,

17-18, 21-24, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

64-67, 70, 88, 88, 92-94

94

 Unresponsive 1, 15, 17-18, 1, 17-18, 21,

29-30, 38, 51, 30, 35, 38,

64 63-64

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88, 46, 51-53,

94 58, 70, 88,

92-94
259

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 9 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 64-65, 49-50, 56, 63-65,

71-74, 77-81, 71-74, 77-81,

84-88, 91-94 84-88, 91-94

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-94

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-94
260

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 9 Posture

 Hunched 94 94
261

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 10 Behaviour

 Grinding Teeth 25

 Underactive 1-4, 7-8, 14, 1-4, 7, 9, 14-18,

17-18, 21-24, 21-25, 28-32,

28-32, 35-39, 35-39, 42-46,

42, 44-46, 49-53, 56-60,

49-53, 56, 58-60, 63-67, 70, 72,

64-67, 70, 88, 88, 92-94

94

 Unresponsive 1, 15, 17-18, 1, 17-18, 21,

29-30, 38, 51, 30, 35, 38,

64 63-64

Breathing

 Shallow 23

 Slow 28, 32, 42, 25, 28-29,

44, 52-53, 32, 36, 42-44,

58, 70, 88, 46, 51-53,

94 58, 70, 88,

92-94
262

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 10 Coat

 Piloerection 1-4, 7-9, 15-16, 1-4, 7-9, 11,

18, 21, 23, 15-18, 21-23,

25, 30-31, 25, 30-31,

35, 37, 39, 35, 37, 39,

42, 44-45, 42, 44-45,

49-50, 56, 64-65, 49-50, 56, 63-65,

71-74, 77-81, 71-74, 77-81,

84-88, 91-94 84-88, 91-94

Eyelids (Left)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-94

Eyelids (Right)

 Partially Closed 1-4, 7, 22, 1, 3-4, 7, 9,

24, 28, 32, 18, 22-24,

35, 44, 50, 28-29, 32, 35-36,

52-53, 58, 70, 42-44, 46, 50-53,

88 58, 70, 88,

92-94
263

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

3F 10 Posture

 Hunched 94 94
264

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 31 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-59, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59, 64-67, 51-52, 56-57,

88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
265

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 31 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
266

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 31 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
267

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 32 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
268

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 32 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
269

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 32 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
270

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 33 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
271

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 33 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
272

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 33 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
273

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 34 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
274

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 34 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
275

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 34 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
276

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 35 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
277

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 35 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
278

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 35 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
279

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 36 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88,

93

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24
280

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 36 Breathing

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88,

92-93

Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-93 84-87, 91-93

Eyelids (Left)

 Closed 1 1
281

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 36 Eyelids (Left)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

Eyelids (Right)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

Posture

 Hunched 1
282

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 37 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88,

93

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24
283

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 37 Breathing

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88,

92-93

Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-93 84-87, 91-93

Eyelids (Left)

 Closed 1 1
284

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 37 Eyelids (Left)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

Eyelids (Right)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

Posture

 Hunched 1
285

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 38 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88,

93

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24
286

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 38 Breathing

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88,

92-93

Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-93 84-87, 91-93

Eyelids (Left)

 Closed 1 1
287

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 38 Eyelids (Left)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

Eyelids (Right)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

Posture

 Hunched 1
288

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 39 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88,

93

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24
289

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 39 Breathing

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88,

92-93

Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11, 1 1

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-93 84-87, 91-93

Eyelids (Left)

 Closed 1 1
290

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 39 Eyelids (Left)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

Eyelids (Right)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

Posture

 Hunched 1
291

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 40 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88,

93

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24
292

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 40 Breathing

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88,

92-93

Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91-93 84-87, 91-93

Eyelids (Left)

 Closed 1 1
293

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 40 Eyelids (Left)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

Eyelids (Right)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91-93 84-88, 91-93

Posture

 Hunched 1
294

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 91 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
295

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 91 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
296

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 91 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
297

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 92 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
298

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 92 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
299

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 92 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
300

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 93 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
301

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 93 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
302

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 93 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
303

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 94 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
304

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 94 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
305

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 94 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
306

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 95 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
307

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 95 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
308

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 95 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
309

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 96 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
310

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 96 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
311

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 96 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
312

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 97 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
313

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 97 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
314

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 97 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
315

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 98 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
316

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 98 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
317

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 98 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
318

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 99 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
319

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 99 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
320

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 99 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
321

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 100 Behaviour

 Underactive 1-4, 7-8, 10-11, 1-4, 7-11,

14-18, 21-25, 14-18, 21-25,

28-32, 35-39, 28-32, 35-39,

42-46, 49-53, 42-46, 49-53,

56-60, 63-67, 56-59, 63-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

 Unresponsive 1, 10-11, 14-15, 1, 10-11, 14-18,

17-18, 21, 23-25, 21, 23-25,

29-31, 35-36, 29-31, 35-36,

39, 49, 51-52, 39, 43, 49,

56-57, 59-60, 51-52, 56-57,

64-67, 88 59, 64-67,

72, 77, 88

Breathing

 Shallow 1-4, 7-8, 24 1-4, 7-9, 15,

17, 22-24

 Slow 22, 28, 32, 25, 28-29,

35, 38, 42, 32, 35-38,

44, 46, 49-53, 42-44, 46, 49-53,

58, 70, 88 58, 70, 88
322

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 100 Coat

 Piloerection 1-4, 7-9, 14-18, 1-4, 7-9, 11,

21, 23-25, 14-18, 21-25,

29-32, 37, 39, 29-32, 37, 39,

45, 49, 56-57, 45, 49, 56-57,

59-60, 63-67, 59, 63-67,

71-74, 77-81, 71-74, 77-81,

84-87, 91 84-87, 91

Eyelids (Left)

 Closed 1 1

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Eyelids (Right)

 Closed 1 1
323

Huntingdon Life Sciences

WAG0014

APPENDIX 2 - continued Request ID: 289355

Signs associated with dosing - individual observations

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Days

Group 

/Sex

Animal 

Number Sign

Approximately 

2 hours during 

exposure

Approximately 

4 hours during 

exposure

1 to 2 hours after 

completion of 

dosing all groups

As late as 

possible in the 

working day

4F 100 Eyelids (Right)

 Partially Closed 2-4, 7-8, 14, 2-4, 7, 9, 14-18,

22, 24-25, 21-25, 28-32,

28-32, 35, 38-39, 35-39, 42-44,

42, 44, 46, 46, 49-53,

49-53, 56, 58-59, 56, 58-59,

63, 65-67, 63, 65-67,

70-74, 77-81, 70-74, 77-81,

84-88, 91 84-88, 91

Posture

 Hunched 1
324

Huntingdon Life Sciences

WAG0014

APPENDIX 3

Sensory reactivity observations and grip strength - individual findings during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/sex: 1M

Animal number: 61 62 63 64 65 66 67 68 69 70 81 82 83 84 85 86 87 88 89 90

Parameter (Grade range)

Approach response (1-3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2

Touch response (1-3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 1 2

Auditory startle reflex (1-4) 3 3 3 3 2 2 3 3 3 3 3 3 3 3 3 3 3 2 3 2

Tail pinch response (1-4) 2 3 3 3 2 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3

Forelimb grip strength (kg) Trial 1 1.06 0.96 1.33 0.92 1.01 1.09 1.02 0.98 1.20 0.99 1.01 0.87 0.91 0.82 0.89 1.15 1.14 1.27 1.09 0.91

Trial 2 1.12 0.88 1.04 0.92 0.92 1.08 0.88 0.96 1.01 1.05 0.82 0.99 0.94 0.84 0.80 1.32 1.04 0.96 1.09 0.99

Trial 3 1.11 1.01 1.02 0.95 0.90 1.09 0.72 1.00 1.06 0.97 1.03 0.94 1.02 0.83 0.96 1.34 0.94 0.90 0.99 1.00

Mean 1.10 0.95 1.13 0.93 0.94 1.09 0.87 0.98 1.09 1.00 0.95 0.93 0.96 0.83 0.88 1.27 1.04 1.04 1.06 0.97

Hindlimb grip strength (kg) Trial 1 0.54 0.70 0.65 0.70 0.78 0.61 0.55 0.56 0.59 0.57 0.65 0.53 0.67 0.68 0.36 0.78 0.52 0.54 0.53 0.56

Trial 2 0.65 0.63 0.74 0.54 0.74 0.46 0.71 0.71 0.65 0.57 0.59 0.62 0.62 0.55 0.54 0.76 0.54 0.54 0.65 0.63

Trial 3 0.63 0.62 0.64 0.74 0.67 0.56 0.56 0.56 0.60 0.52 0.58 0.56 0.64 0.55 0.57 0.82 0.42 0.43 0.66 0.54

Mean 0.61 0.65 0.68 0.66 0.73 0.54 0.61 0.61 0.61 0.55 0.61 0.57 0.64 0.59 0.49 0.79 0.49 0.50 0.61 0.58

Additional observations - - - - - - - - - - - - - - - - - - - -
325

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APPENDIX 3 - continued

Sensory reactivity observations and grip strength - individual findings during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/sex: 2M 3M

Animal number: 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120

Parameter (Grade range)

Approach response (1-3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2

Touch response (1-3) 2 2 2 2 2 2 2 2 1 2 2 2 2 2 2 2 2 2 1 2

Auditory startle reflex (1-4) 2 3 3 3 3 2 3 3 2 3 3 3 3 3 3 2 3 3 2 3

Tail pinch response (1-4) 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3

Forelimb grip strength (kg) Trial 1 1.10 0.86 1.21 1.13 1.13 1.01 1.09 0.87 1.00 0.94 0.72 1.03 0.87 0.94 0.92 0.94 0.84 1.08 1.03 0.99

Trial 2 0.86 0.93 1.03 1.25 0.96 1.18 0.98 0.97 0.85 0.82 0.80 0.88 0.91 0.94 1.00 0.86 0.98 0.73 1.07 1.12

Trial 3 0.98 0.90 0.85 1.18 1.06 1.15 1.22 1.03 0.98 0.86 0.82 0.91 0.93 0.84 1.08 0.96 0.95 0.82 1.08 1.13

Mean 0.98 0.90 1.03 1.19 1.05 1.11 1.10 0.96 0.94 0.87 0.78 0.94 0.90 0.91 1.00 0.92 0.92 0.88 1.06 1.08

Hindlimb grip strength (kg) Trial 1 0.76 0.49 0.65 0.56 0.63 0.54 0.64 0.69 0.54 0.63 0.51 0.28 0.53 0.62 0.43 0.59 0.56 0.63 0.55 0.36

Trial 2 0.68 0.38 0.58 0.67 0.62 0.68 0.54 0.72 0.47 0.53 0.46 0.33 0.57 0.65 0.68 0.58 0.70 0.57 0.58 0.57

Trial 3 0.60 0.36 0.43 0.59 0.60 0.62 0.58 0.70 0.59 0.63 0.40 0.40 0.57 0.69 0.68 0.56 0.53 0.59 0.31 0.59

Mean 0.68 0.41 0.55 0.61 0.62 0.61 0.59 0.70 0.53 0.60 0.46 0.34 0.56 0.65 0.60 0.58 0.60 0.60 0.48 0.51

Additional observations - - - - - - - - - - - - - - - - - - - -
326

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APPENDIX 3 - continued

Sensory reactivity observations and grip strength - individual findings during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/sex: 4M

Animal number: 11 12 13 14 15 16 17 18 19 20 71 72 73 74 75 76 77 78 79 80

Parameter (Grade range)

Approach response (1-3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2

Touch response (1-3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2

Auditory startle reflex (1-4) 3 3 3 3 3 3 2 3 3 2 3 2 3 3 3 3 3 3 3 2

Tail pinch response (1-4) 3 3 4 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 4

Forelimb grip strength (kg) Trial 1 0.73 0.85 0.70 0.82 1.07 0.71 0.87 0.79 0.70 0.89 0.84 1.04 0.70 0.72 0.84 0.95 0.88 1.00 0.88 1.01

Trial 2 0.68 0.80 0.70 0.68 0.96 0.63 0.96 0.82 0.75 1.12 0.73 0.99 0.76 0.89 0.89 0.94 1.00 0.96 1.00 0.85

Trial 3 0.65 0.91 0.80 0.88 0.90 0.67 0.88 0.81 0.73 0.89 0.76 0.84 0.79 0.80 0.79 1.00 0.77 1.00 0.90 0.88

Mean 0.69 0.85 0.73 0.79 0.98 0.67 0.90 0.81 0.73 0.97 0.78 0.96 0.75 0.80 0.84 0.96 0.88 0.99 0.93 0.91

Hindlimb grip strength (kg) Trial 1 0.41 0.60 0.48 0.54 0.67 0.43 0.54 0.53 0.35 0.57 0.44 0.63 0.47 0.50 0.46 0.38 0.48 0.48 0.48 0.49

Trial 2 0.42 0.56 0.47 0.55 0.65 0.35 0.58 0.50 0.37 0.44 0.51 0.56 0.38 0.48 0.37 0.46 0.45 0.49 0.44 0.44

Trial 3 0.44 0.52 0.49 0.44 0.63 0.32 0.54 0.55 0.39 0.51 0.40 0.56 0.44 0.48 0.52 0.51 0.41 0.56 0.45 0.54

Mean 0.42 0.56 0.48 0.51 0.65 0.37 0.55 0.53 0.37 0.51 0.45 0.58 0.43 0.49 0.45 0.45 0.45 0.51 0.46 0.49

Additional observations - - - a - - - - - - - - - - - - - - - -

a Loose faeces
327

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WAG0014

APPENDIX 3 - continued

Sensory reactivity observations and grip strength - individual findings during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/sex: 1F

Animal number: 21 22 23 24 25 26 28 29 30 41 42 43 44 45 46 47 48 49 50

Parameter (Grade range)

Approach response (1-3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2

Touch response (1-3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2

Auditory startle reflex (1-4) 3 2 3 3 3 3 3 3 3 2 3 3 3 3 3 3 2 3 3

Tail pinch response (1-4) 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3

Forelimb grip strength (kg) Trial 1 0.93 1.02 0.92 1.08 0.92 1.04 0.79 0.96 0.83 0.69 1.05 0.81 0.84 0.84 0.92 0.86 0.70 0.75 0.82

Trial 2 0.88 0.96 0.82 0.96 0.92 0.92 1.02 0.87 0.79 0.76 0.95 0.90 0.97 0.96 1.01 0.90 0.78 0.82 0.92

Trial 3 0.89 0.78 0.87 1.02 0.82 0.87 0.88 0.84 0.71 0.72 0.82 0.88 0.71 0.86 0.94 0.86 0.85 0.92 0.82

Mean 0.90 0.92 0.87 1.02 0.89 0.94 0.90 0.89 0.78 0.72 0.94 0.86 0.84 0.89 0.96 0.87 0.78 0.83 0.85

Hindlimb grip strength (kg) Trial 1 0.50 0.49 0.46 0.47 0.30 0.46 0.47 0.47 0.47 0.44 0.46 0.39 0.53 0.50 0.43 0.41 0.49 0.38 0.38

Trial 2 0.54 0.43 0.57 0.45 0.36 0.50 0.52 0.39 0.42 0.44 0.46 0.49 0.50 0.40 0.57 0.42 0.45 0.42 0.36

Trial 3 0.59 0.35 0.38 0.43 0.33 0.36 0.46 0.40 0.43 0.33 0.44 0.42 0.38 0.47 0.60 0.38 0.49 0.46 0.40

Mean 0.54 0.42 0.47 0.45 0.33 0.44 0.48 0.42 0.44 0.40 0.45 0.43 0.47 0.46 0.53 0.40 0.48 0.42 0.38

Additional observations - - - - - - - - - - - - - - - - - - -
328

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APPENDIX 3 - continued

Sensory reactivity observations and grip strength - individual findings during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/sex: 2F 3F

Animal number: 51 52 53 54 55 56 57 58 59 60 1 2 3 4 5 6 7 8 9 10

Parameter (Grade range)

Approach response (1-3) 2 2 2 2 2 2 2 1 2 2 2 2 2 2 2 2 2 2 2 2

Touch response (1-3) 2 2 2 2 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2

Auditory startle reflex (1-4) 3 3 2 3 3 2 3 3 3 3 3 3 2 3 3 3 3 3 3 3

Tail pinch response (1-4) 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3

Forelimb grip strength (kg) Trial 1 0.81 0.81 0.79 0.72 0.74 0.74 0.88 0.96 0.94 0.83 0.98 1.08 0.76 1.19 0.82 0.87 0.69 0.81 0.86 0.79

Trial 2 0.79 0.89 0.73 0.76 0.82 0.90 0.82 0.91 0.94 0.77 0.92 0.72 0.74 1.11 0.82 0.70 0.70 0.79 0.84 0.92

Trial 3 0.80 0.84 0.82 0.77 0.77 0.74 0.82 0.97 0.81 0.74 1.01 0.70 0.73 0.92 0.94 0.78 0.75 0.66 0.84 0.83

Mean 0.80 0.85 0.78 0.75 0.78 0.79 0.84 0.95 0.90 0.78 0.97 0.83 0.74 1.07 0.86 0.78 0.71 0.75 0.85 0.85

Hindlimb grip strength (kg) Trial 1 0.48 0.41 0.53 0.44 0.50 0.45 0.42 0.54 0.57 0.55 0.50 0.47 0.33 0.50 0.59 0.50 0.33 0.43 0.50 0.40

Trial 2 0.47 0.42 0.51 0.53 0.49 0.46 0.48 0.49 0.56 0.52 0.52 0.46 0.33 0.48 0.44 0.39 0.38 0.46 0.52 0.34

Trial 3 0.47 0.34 0.50 0.44 0.47 0.49 0.45 0.51 0.51 0.41 0.48 0.46 0.33 0.35 0.49 0.47 0.36 0.40 0.44 0.36

Mean 0.47 0.39 0.51 0.47 0.49 0.47 0.45 0.51 0.55 0.49 0.50 0.46 0.33 0.44 0.51 0.45 0.36 0.43 0.49 0.37

Additional observations - - - - - - - - - - - - - - - - - - - -
329

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APPENDIX 3 - continued

Sensory reactivity observations and grip strength - individual findings during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/sex: 4F

Animal number: 31 32 33 34 35 36 37 38 39 40 91 92 93 94 95 96 97 98 99 100

Parameter (Grade range)

Approach response (1-3) 1 2 2 2 2 2 2 2 1 2 2 2 2 2 2 2 2 2 2 2

Touch response (1-3) 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 1 2

Auditory startle reflex (1-4) 2 3 3 3 2 3 3 3 3 3 3 3 3 3 3 3 3 3 2 3

Tail pinch response (1-4) 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3

Forelimb grip strength (kg) Trial 1 0.76 0.48 0.82 0.84 0.85 0.74 0.68 0.62 0.67 0.66 0.77 0.50 0.58 0.51 0.69 0.75 0.62 0.68 0.76 0.78

Trial 2 0.75 0.53 0.75 0.77 0.72 0.78 0.64 0.84 0.66 0.66 0.70 0.55 0.60 0.50 0.72 0.70 0.50 0.79 0.80 0.70

Trial 3 0.60 0.42 0.88 0.65 0.75 0.74 0.68 0.76 0.82 0.68 0.91 0.60 0.54 0.51 0.73 0.64 0.52 0.64 0.78 0.81

Mean 0.70 0.48 0.82 0.75 0.77 0.75 0.67 0.74 0.72 0.67 0.79 0.55 0.57 0.51 0.71 0.70 0.55 0.70 0.78 0.76

Hindlimb grip strength (kg) Trial 1 0.41 0.24 0.41 0.41 0.44 0.36 0.37 0.35 0.36 0.25 0.37 0.27 0.38 0.30 0.33 0.32 0.42 0.33 0.50 0.37

Trial 2 0.33 0.29 0.43 0.48 0.40 0.42 0.31 0.46 0.43 0.21 0.42 0.26 0.30 0.24 0.32 0.34 0.39 0.34 0.46 0.41

Trial 3 0.35 0.24 0.45 0.48 0.41 0.36 0.32 0.42 0.33 0.22 0.34 0.32 0.33 0.28 0.39 0.39 0.28 0.34 0.50 0.46

Mean 0.36 0.26 0.43 0.46 0.42 0.38 0.33 0.41 0.37 0.23 0.38 0.28 0.34 0.27 0.35 0.35 0.36 0.34 0.49 0.41

Additional observations - - - - - - - - - - - - - - - - - - - -
330

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APPENDIX 3 - continued

Sensory reactivity observations and grip strength - individual findings during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/sex: 1M 4M

Animal number: 81 82 83 84 85 86 87 88 89 90 71 72 73 74 75 76 77 78 79 80

Parameter

Forelimb grip strength (kg) Trial 1 1.10 1.08 1.20 1.26 1.08 1.26 0.99 1.20 1.28 1.19 1.02 1.00 1.06 0.89 1.22 0.90 1.10 1.37 1.04 1.06

Trial 2 1.16 1.10 1.10 1.09 1.28 1.40 1.17 0.97 1.14 1.10 0.84 0.94 1.17 1.28 1.01 1.20 1.02 1.20 0.92 1.14

Trial 3 1.13 0.99 0.86 1.09 1.08 1.19 1.10 1.00 1.09 0.96 1.06 1.14 1.21 0.93 1.10 0.85 1.21 1.34 0.81 0.97

Mean 1.13 1.06 1.05 1.15 1.15 1.28 1.09 1.06 1.17 1.08 0.97 1.03 1.15 1.03 1.11 0.98 1.11 1.30 0.92 1.06

Hindlimb grip strength (kg) Trial 1 0.68 0.66 0.60 0.79 0.69 0.70 0.50 0.68 0.80 0.68 0.64 0.73 0.57 0.51 0.62 0.64 0.53 0.60 0.42 0.50

Trial 2 0.79 0.48 0.78 0.69 0.60 0.73 0.50 0.66 0.85 0.70 0.58 0.60 0.63 0.49 0.51 0.65 0.60 0.60 0.42 0.59

Trial 3 0.63 0.43 0.66 0.70 0.69 0.76 0.46 0.67 0.77 0.71 0.54 0.61 0.68 0.51 0.54 0.58 0.58 0.58 0.46 0.56

Mean 0.70 0.52 0.68 0.73 0.66 0.73 0.49 0.67 0.81 0.70 0.59 0.65 0.63 0.50 0.56 0.62 0.57 0.59 0.43 0.55

Additional observations - - - - - - - - - - - - - - - - - - - -
331

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APPENDIX 3 - continued

Sensory reactivity observations and grip strength - individual findings during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group/sex: 1F 4F

Animal number: 41 42 43 44 45 46 47 48 49 50 91 92 93 94 95 96 97 98 99 100

Parameter

Forelimb grip strength (kg) Trial 1 0.88 0.88 0.76 0.82 0.89 0.99 1.03 0.84 0.94 1.09 0.98 0.83 0.89 0.86 1.02 0.99 0.74 0.80 1.02 0.87

Trial 2 0.78 0.82 0.89 0.78 0.90 0.88 0.84 0.81 0.87 0.84 0.85 0.85 0.70 0.79 0.84 0.76 0.73 0.75 1.01 1.00

Trial 3 0.90 0.66 0.84 0.99 0.83 0.90 0.84 0.76 0.97 0.84 1.01 0.88 0.73 0.84 0.97 0.79 0.80 0.81 0.78 0.83

Mean 0.85 0.79 0.83 0.86 0.87 0.92 0.90 0.80 0.93 0.92 0.95 0.85 0.77 0.83 0.94 0.85 0.76 0.79 0.94 0.90

Hindlimb grip strength (kg) Trial 1 0.60 0.44 0.56 0.54 0.52 0.64 0.54 0.54 0.54 0.43 0.52 0.43 0.38 0.42 0.54 0.50 0.49 0.46 0.65 0.54

Trial 2 0.53 0.59 0.55 0.50 0.52 0.62 0.55 0.56 0.46 0.40 0.47 0.40 0.48 0.48 0.42 0.44 0.45 0.48 0.47 0.52

Trial 3 0.49 0.48 0.59 0.47 0.46 0.50 0.56 0.50 0.47 0.49 0.46 0.31 0.51 0.53 0.44 0.39 0.50 0.56 0.49 0.53

Mean 0.54 0.50 0.57 0.50 0.50 0.59 0.55 0.53 0.49 0.44 0.48 0.38 0.46 0.48 0.47 0.44 0.48 0.50 0.54 0.53

Additional observations - - - - - - - - - - - - - - - - - - - -
332

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APPENDIX 4

Motor activity - individual scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

1M 61 High 111 120 61 36 50 19 23 42 8 31 501

62 163 108 65 48 32 6 2 0 14 4 442

63 136 108 72 47 55 60 20 36 36 26 596

64 148 113 83 41 25 49 24 14 2 0 499

65 110 132 54 62 19 37 22 0 0 43 479

66 140 76 28 8 9 3 0 0 0 0 264

67 123 105 88 83 66 41 65 84 44 20 719

68 148 107 44 74 22 12 23 5 22 0 457

69 106 96 76 54 1 0 14 40 26 0 413

70 144 144 65 28 45 35 0 0 0 0 461

81 142 91 48 34 32 18 0 18 50 36 469

82 117 88 84 41 23 23 22 53 4 42 497

83 125 102 69 74 20 42 77 66 66 47 688

84 113 63 63 19 27 15 45 48 27 42 462

85 125 80 68 13 45 42 32 62 18 18 503

86 140 56 63 49 30 27 34 36 26 22 483

87 156 130 52 80 46 30 39 34 41 22 630

88 167 115 62 38 32 53 7 49 0 48 571

89 147 118 97 37 21 64 13 69 69 57 692

90 136 125 76 32 37 53 16 34 14 19 542
333

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WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

1M 61 Low 221 170 138 83 87 78 84 106 37 97 1101

62 319 286 228 193 104 98 29 0 87 41 1385

63 314 182 201 86 32 115 67 93 42 85 1217

64 210 178 141 161 112 100 72 64 47 5 1090

65 207 112 107 59 85 70 101 23 2 79 845

66 237 158 161 33 96 19 17 0 16 9 746

67 247 275 218 152 98 91 62 84 60 81 1368

68 241 153 112 105 98 67 44 108 38 11 977

69 204 151 95 98 23 19 77 102 85 3 857

70 290 219 166 88 110 54 9 0 2 0 938

81 252 178 142 85 66 66 4 45 118 137 1093

82 143 127 85 77 54 45 78 54 31 40 734

83 237 206 101 86 120 106 94 59 125 76 1210

84 218 172 125 84 71 55 41 66 68 84 984

85 262 256 193 125 130 94 70 105 52 70 1357

86 325 195 143 106 132 88 77 111 87 60 1324

87 271 197 157 106 102 84 105 83 86 48 1239

88 210 145 100 100 53 80 38 42 0 38 806

89 277 194 231 91 95 135 39 86 35 66 1249

90 338 222 165 168 128 111 39 103 68 54 1396
334

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WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

2M 101 High 150 94 87 57 35 36 31 6 28 17 541

102 134 73 55 37 50 19 19 13 35 17 452

103 128 85 48 41 24 46 17 6 16 13 424

104 145 120 120 63 39 50 26 24 43 26 656

105 110 90 70 52 55 39 5 29 34 0 484

106 129 70 29 6 1 23 16 17 19 0 310

107 139 100 78 80 84 35 66 26 38 26 672

108 174 102 57 50 76 51 18 36 0 4 568

109 103 86 77 43 7 7 11 2 26 24 386

110 182 154 124 65 67 43 57 16 38 67 813

101 Low 198 149 138 135 147 113 118 56 138 94 1286

102 287 177 199 170 133 124 79 69 91 62 1391

103 235 173 126 134 41 105 99 23 72 51 1059

104 263 133 122 104 112 75 81 19 114 71 1094

105 232 152 116 127 90 83 63 91 69 142 1165

106 216 171 118 44 13 91 16 47 52 15 783

107 341 305 282 187 177 155 151 125 152 80 1955

108 326 207 167 122 111 118 43 71 30 17 1212

109 200 153 152 91 8 32 82 28 83 88 917

110 269 207 176 150 71 69 68 79 86 81 1256
335

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WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

3M 111 High 121 83 51 25 26 16 1 19 0 0 342

112 144 82 77 51 51 61 62 28 45 52 653

113 102 101 51 42 20 16 29 21 26 0 408

114 108 49 17 18 0 0 0 21 6 0 219

115 130 70 29 28 55 9 2 4 0 0 327

116 140 102 68 63 16 12 16 19 26 0 462

117 86 50 47 15 24 0 0 8 25 0 255

118 113 86 69 48 43 18 25 2 8 0 412

119 132 94 69 46 31 11 15 13 0 0 411

120 106 92 96 46 46 19 16 29 5 1 456

111 Low 224 125 92 69 84 98 32 34 0 0 758

112 377 230 136 96 126 102 74 135 62 74 1412

113 186 192 122 143 128 70 111 79 106 5 1142

114 172 151 96 79 0 0 17 71 27 0 613

115 273 215 118 204 116 31 27 2 5 7 998

116 196 154 172 105 64 49 70 47 28 0 885

117 206 137 106 48 65 0 6 29 90 0 687

118 207 160 147 146 98 71 73 26 54 12 994

119 261 191 141 162 113 80 54 46 0 24 1072

120 189 212 203 117 98 108 266 91 41 56 1381
336

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WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

4M 11 High 75 14 0 0 20 6 0 0 0 29 144

12 152 74 44 30 65 9 32 14 0 0 420

13 58 60 25 25 0 0 0 6 36 30 240

14 92 34 12 7 19 0 12 0 0 0 176

15 86 59 28 45 4 0 0 0 0 15 237

16 79 52 53 37 33 26 18 0 0 2 300

17 123 61 17 17 11 24 34 6 0 0 293

18 115 66 36 60 43 51 25 41 57 22 516

19 150 60 33 0 0 25 2 0 0 5 275

20 85 58 21 3 34 4 0 5 0 0 210

71 125 75 42 47 38 19 0 3 0 0 349

72 143 55 26 5 0 0 0 0 0 0 229

73 114 65 63 60 29 0 0 13 1 0 345

74 139 54 45 16 1 8 7 25 4 6 305

75 98 76 67 41 24 25 0 23 6 0 360

76 97 71 67 40 64 43 32 76 22 28 540

77 145 70 58 21 4 0 0 29 35 2 364

78 112 57 32 0 7 0 0 0 0 0 208

79 165 128 80 97 83 45 27 10 4 28 667

80 136 71 67 21 12 2 28 32 0 10 379
337

Huntingdon Life Sciences

WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

4M 11 Low 159 86 0 1 73 40 6 0 26 110 501

12 225 111 120 111 83 77 78 16 17 8 846

13 156 128 84 58 1 8 6 41 76 75 633

14 224 106 70 24 78 10 74 2 1 14 603

15 238 109 66 52 24 3 0 1 1 61 555

16 235 147 113 101 88 32 7 0 0 9 732

17 193 102 75 37 46 30 52 18 0 2 555

18 162 114 68 61 53 59 48 33 49 51 698

19 197 122 84 63 2 90 7 0 0 16 581

20 176 131 81 51 73 19 0 25 2 0 558

71 251 119 123 91 75 64 0 12 0 4 739

72 200 133 79 68 0 0 0 23 0 0 503

73 179 170 127 117 84 10 0 53 20 20 780

74 223 170 94 77 2 16 21 39 12 5 659

75 206 185 114 106 65 41 1 48 43 0 809

76 234 186 160 104 78 85 43 54 66 60 1070

77 216 148 120 51 41 3 3 58 61 15 716

78 228 98 92 18 12 0 0 14 0 0 462

79 252 186 211 163 215 141 102 44 19 89 1422

80 239 171 105 62 56 22 111 93 49 36 944
338

Huntingdon Life Sciences

WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

1F 21 High 177 139 101 80 28 34 0 0 64 0 623

22 180 127 75 73 56 51 34 29 45 67 737

23 156 85 47 28 20 7 18 31 24 1 417

24 123 109 62 65 38 66 5 63 34 50 615

25 155 129 93 71 89 102 200 20 144 0 1003

26 146 51 31 38 27 28 30 47 18 7 423

28 131 79 54 47 37 33 38 41 9 24 493

29 155 122 54 70 59 16 79 38 3 0 596

30 151 130 94 72 42 90 21 10 31 103 744

41 193 82 62 66 45 31 68 0 1 0 548

42 144 69 59 35 32 42 23 9 31 0 444

43 177 117 75 57 33 35 12 9 23 22 560

44 174 84 76 72 102 57 59 71 68 40 803

45 160 110 93 43 48 10 13 2 7 29 515

46 124 55 40 32 32 26 35 29 19 34 426

47 174 136 100 67 34 60 28 40 60 34 733

48 223 101 60 72 72 126 71 58 34 37 854

49 176 117 91 57 64 71 123 80 66 20 865

50 130 48 51 30 25 30 55 66 12 46 493
339

Huntingdon Life Sciences

WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

1F 21 Low 332 220 228 132 57 139 40 19 50 131 1348

22 243 181 187 121 103 99 58 55 88 115 1250

23 271 164 167 127 45 35 53 90 113 26 1091

24 208 135 117 68 41 100 21 43 67 77 877

25 194 128 123 75 100 104 44 15 52 7 842

26 309 163 117 137 90 104 152 97 79 31 1279

28 279 279 203 181 149 174 106 108 81 163 1723

29 236 128 142 89 103 31 92 90 26 12 949

30 154 106 90 79 33 64 93 20 36 71 746

41 313 174 152 100 89 35 82 8 1 18 972

42 192 114 112 124 76 89 33 47 51 6 844

43 352 231 121 156 159 130 37 73 87 101 1447

44 319 194 146 121 91 127 70 119 91 101 1379

45 285 234 190 121 90 43 43 47 64 40 1157

46 238 143 132 75 111 52 113 76 61 142 1143

47 392 201 182 191 172 172 118 124 113 125 1790

48 376 209 127 111 151 216 202 164 133 130 1819

49 329 257 225 142 165 88 158 114 146 44 1668

50 225 191 100 63 110 46 102 95 61 73 1066
340

Huntingdon Life Sciences

WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

2F 51 High 155 54 26 24 4 0 23 35 20 0 341

52 178 133 83 78 45 65 41 44 2 22 691

53 128 46 26 0 0 0 48 23 13 2 286

54 156 118 63 57 38 44 48 29 27 27 607

55 155 122 99 106 85 12 39 84 54 6 762

56 157 84 29 75 28 34 31 3 23 0 464

57 138 96 66 87 13 5 5 43 9 7 469

58 304 122 131 64 63 61 20 25 50 10 850

59 156 31 28 38 0 0 4 14 68 25 364

60 106 53 56 45 27 37 24 14 17 0 379

51 Low 277 159 117 63 47 1 53 98 49 9 873

52 284 200 205 125 119 105 134 112 5 17 1306

53 155 103 58 0 0 3 73 28 46 9 475

54 309 252 160 152 114 90 129 126 88 105 1525

55 223 130 143 89 77 22 40 80 35 38 877

56 293 156 95 117 113 99 94 136 45 18 1166

57 201 143 98 93 61 16 22 76 61 35 806

58 326 188 179 142 151 104 118 105 139 44 1496

59 269 149 103 49 0 34 54 107 80 88 933

60 235 106 126 85 99 114 111 43 97 144 1160
341

Huntingdon Life Sciences

WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

3F 1 High 153 88 33 41 14 18 1 13 6 0 367

2 167 75 60 81 84 12 1 23 18 27 548

3 112 86 36 46 39 45 0 11 0 10 385

4 192 106 99 36 59 27 28 45 17 8 617

5 128 82 76 42 10 12 0 0 14 29 393

6 121 84 75 41 52 30 20 0 0 0 423

7 127 85 29 36 0 4 3 21 0 0 305

8 183 108 73 23 22 0 0 0 0 0 409

9 163 81 43 21 32 17 0 5 20 36 418

10 171 140 93 51 57 90 46 31 39 49 767

1 Low 294 179 203 157 71 74 16 69 53 0 1116

2 223 151 146 136 140 88 79 57 106 66 1192

3 170 127 47 48 54 21 1 0 0 13 481

4 227 154 144 102 116 51 97 56 90 50 1087

5 197 150 167 77 78 37 1 34 67 102 910

6 323 212 127 113 117 79 82 4 4 70 1131

7 173 145 120 68 30 26 20 60 0 60 702

8 279 200 187 61 68 50 11 0 0 0 856

9 361 275 178 110 116 54 0 28 107 156 1385

10 248 153 138 95 130 106 65 51 48 77 1111
342

Huntingdon Life Sciences

WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

4F 31 High 122 80 70 61 0 0 0 0 0 0 333

32 209 82 64 82 42 0 41 39 14 0 573

33 139 79 51 0 0 0 40 19 14 0 342

34 183 99 89 48 101 23 39 0 0 14 596

35 151 91 51 20 10 0 3 41 0 9 376

36 98 58 20 0 0 0 0 0 0 0 176

37 93 53 14 26 4 8 1 11 44 13 267

38 141 117 72 49 11 0 0 0 0 0 390

39 109 34 0 0 0 0 0 0 6 36 185

40 205 204 153 80 34 27 12 24 28 37 804

91 101 55 44 25 2 12 0 0 11 18 268

92 148 81 0 0 0 56 0 0 0 0 285

93 127 78 39 13 32 4 15 37 43 8 396

94 87 38 70 16 0 0 0 21 15 0 247

95 108 78 53 60 22 1 2 0 25 0 349

96 123 80 100 56 44 17 41 45 23 0 529

97 155 100 93 63 92 44 53 65 36 20 721

98 176 140 96 65 50 70 81 44 29 79 830

99 144 71 30 31 0 0 6 37 34 6 359

100 116 103 58 32 40 35 40 20 45 0 489
343

Huntingdon Life Sciences

WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 12 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

4F 31 Low 257 152 85 79 0 0 0 0 0 0 573

32 199 126 74 97 38 0 55 56 66 64 775

33 208 160 122 7 0 1 136 64 98 108 904

34 181 100 89 60 70 72 25 1 5 22 625

35 272 144 96 57 115 0 59 74 0 55 872

36 187 112 70 41 0 0 0 0 0 0 410

37 248 154 110 126 49 29 77 129 98 71 1091

38 174 106 79 99 19 0 0 0 10 0 487

39 216 111 7 0 1 4 2 1 39 113 494

40 255 232 187 105 57 87 129 69 106 99 1326

91 192 131 95 139 10 53 6 4 47 101 778

92 199 65 0 0 0 74 0 0 0 0 338

93 160 124 93 53 56 26 40 105 71 60 788

94 154 96 48 28 0 0 2 27 31 0 386

95 144 124 121 98 57 14 37 148 80 26 849

96 225 161 110 108 68 107 61 79 98 0 1017

97 193 101 137 82 127 93 82 106 39 29 989

98 132 101 69 47 40 68 34 33 25 75 624

99 209 161 110 54 7 2 40 83 112 94 872

100 187 135 96 66 57 81 36 7 121 5 791
344

Huntingdon Life Sciences

WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

1M 81 High 101 65 40 25 19 6 0 0 0 15 271

82 106 73 30 28 14 0 0 0 0 0 251

83 104 84 38 63 21 28 31 29 13 8 419

84 136 91 87 83 84 45 74 40 52 46 738

85 111 80 30 43 23 6 13 9 0 0 315

86 105 61 46 33 29 6 0 16 5 4 305

87 119 62 73 39 39 20 23 9 21 19 424

88 124 65 52 13 13 15 0 6 0 10 298

89 110 104 78 85 36 18 40 4 13 28 516

90 104 54 70 22 7 1 16 0 0 0 274

81 Low 242 130 134 87 36 17 2 4 6 86 744

82 184 124 66 74 65 8 25 10 0 0 556

83 249 153 163 147 99 95 131 58 100 81 1276

84 178 181 126 112 63 65 66 106 59 43 999

85 263 210 132 91 85 10 11 33 1 0 836

86 229 166 140 109 117 18 0 38 32 12 861

87 197 128 114 122 161 21 24 2 48 33 850

88 259 125 103 31 37 69 0 2 0 12 638

89 266 207 149 159 133 85 98 46 50 100 1293

90 259 200 143 110 67 33 92 10 0 7 921
345

Huntingdon Life Sciences

WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

4M 71 High 116 33 24 22 14 4 0 0 0 0 213

72 102 54 34 0 0 1 0 0 0 0 191

73 136 64 49 36 9 38 8 0 0 0 340

74 111 39 38 23 27 43 17 10 40 28 376

75 117 70 19 43 44 15 2 41 2 0 353

76 122 86 65 27 40 5 12 1 0 46 404

77 123 43 38 11 25 2 0 0 6 17 265

78 96 20 25 26 6 1 0 0 0 0 174

79 122 97 69 59 60 44 41 34 21 7 554

80 110 31 29 3 24 0 0 5 7 18 227

71 Low 152 78 68 101 74 15 1 5 12 26 532

72 183 127 148 12 26 16 5 10 5 6 538

73 177 134 87 65 56 131 45 4 41 4 744

74 188 86 70 138 61 91 120 37 75 58 924

75 147 121 25 99 56 36 22 54 24 0 584

76 225 123 45 46 80 21 42 16 10 55 663

77 213 184 120 42 69 20 0 4 29 122 803

78 175 77 69 39 23 11 0 0 0 0 394

79 314 191 130 111 77 128 72 140 87 9 1259

80 229 70 76 24 83 39 30 91 42 76 760
346

Huntingdon Life Sciences

WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

1F 41 High 79 59 53 47 23 29 62 7 0 0 359

42 118 49 20 39 56 17 23 11 0 0 333

43 148 91 96 119 58 17 23 53 0 5 610

44 151 96 88 63 73 42 59 34 2 0 608

45 131 51 60 54 39 34 22 30 22 16 459

46 121 70 28 34 19 37 58 13 4 3 387

47 148 85 129 56 51 49 40 53 27 2 640

48 141 97 98 84 54 61 17 26 0 0 578

49 149 70 54 27 65 39 61 15 9 0 489

50 73 58 50 32 32 12 15 27 25 1 325

41 Low 206 159 163 117 121 125 158 50 9 2 1110

42 246 125 95 145 119 36 48 42 1 0 857

43 226 126 116 102 151 31 61 95 53 2 963

44 240 137 130 146 81 97 100 77 8 9 1025

45 268 143 178 129 141 125 96 68 73 61 1282

46 255 155 57 84 48 75 134 46 8 35 897

47 347 212 223 236 146 139 229 143 94 10 1779

48 303 236 202 153 214 126 91 58 0 0 1383

49 303 250 280 184 183 232 155 127 58 1 1773

50 207 145 160 95 96 58 54 189 108 53 1165
347

Huntingdon Life Sciences

WAG0014

APPENDIX 4 - continued

Motor activity - individual scores (beam breaks) during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal Beam 

level

Time (minutes)

number 6 12 18 24 30 36 42 48 54 60 Total

4F 91 High 111 72 36 7 29 7 0 9 1 0 272

92 137 63 12 26 0 0 0 0 0 0 238

93 155 94 55 24 34 27 44 32 0 0 465

94 146 82 66 18 76 32 67 36 0 0 523

95 112 80 40 33 28 34 18 0 0 0 345

96 163 119 115 108 63 54 44 29 24 36 755

97 126 58 59 55 54 48 36 56 18 32 542

98 139 73 69 45 38 28 4 88 26 10 520

99 100 62 57 37 34 55 7 18 8 0 378

100 162 107 177 77 50 63 7 47 1 38 729

91 Low 154 110 117 24 62 102 0 26 3 0 598

92 174 96 27 57 0 0 5 0 0 0 359

93 245 163 141 61 110 76 85 65 4 4 954

94 187 89 89 58 68 97 58 70 0 2 718

95 176 108 109 97 66 65 60 1 0 0 682

96 168 135 137 166 145 99 111 65 45 70 1141

97 205 127 97 64 101 133 96 76 51 74 1024

98 162 79 71 69 72 49 5 74 68 8 657

99 236 135 119 174 63 168 60 66 60 10 1091

100 309 161 148 113 119 117 20 98 16 79 1180
348

Huntingdon Life Sciences

WAG0014

APPENDIX 5 Request ID: 289239

Bodyweights - individual values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Week Week Week Week Week Week Week Week Week Week Week Week

/Sex Number -1 0 1 2 3 4 5 6 7 8 9 10

1M 61 185 227 296 339 389 432 473 508 530 563 591 606

62 194 248 308 354 404 450 489 513 513 543 564 578

63 197 240 300 367 432 477 504 530 533 554 588 603

64 189 238 296 354 416 455 501 529 553 587 606 629

65 180 223 272 326 370 403 446 468 490 511 538 550

66 181 236 301 366 426 469 531 568 585 625 642 663

67 191 237 284 323 375 415 455 469 494 516 524 548

68 189 246 302 348 394 425 450 466 481 492 516 536

69 187 237 296 345 392 426 466 489 505 534 560 582

70 191 242 297 345 390 430 469 485 500 522 545 564

81 187 232 289 340 387 425 447 477 501 525 549 559

82 188 239 296 352 393 425 463 479 499 538 561 586

83 178 228 294 344 400 446 472 495 514 538 551 574

84 211 258 318 377 421 451 472 483 493 520 536 546

85 175 227 295 350 406 462 501 525 549 587 616 633

86 182 224 282 325 372 407 444 472 500 534 553 566

87 193 231 279 326 365 386 408 434 451 466 485 493

88 177 229 292 360 402 445 476 493 520 537 562 565

89 173 234 312 394 456 502 549 585 612 642 659 675

90 197 239 281 313 348 368 388 400 414 429 439 445
349

Huntingdon Life Sciences

WAG0014

APPENDIX 5 - continued Request ID: 289239

Bodyweights - individual values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Week Week Week Week Week Week Week

/Sex Number 11 12 13/R0 R1 R2 R3 R4

1M 61 617 631 627

62 562 577 578

63 611 623 628

64 645 656 653

65 557 569 576

66 674 688 690

67 552 564 576

68 537 533 535

69 578 587 592

70 561 559 552

81 564 579 584 605 622 629 629

82 574 585 579 586 609 620 607

83 567 589 603 609 632 646 649

84 543 567 586 596 620 624 624

85 643 656 660 684 703 721 702

86 570 575 590 610 614 633 629

87 509 507 509 525 543 557 555

88 571 578 588 596 607 613 607

89 697 719 730 746 759 763 754

90 443 453 450 459 475 484 466
350

Huntingdon Life Sciences

WAG0014

APPENDIX 5 - continued Request ID: 289239

Bodyweights - individual values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Week Week Week Week Week Week Week Week Week Week Week Week

/Sex Number -1 0 1 2 3 4 5 6 7 8 9 10

2M 101 190 243 290 341 383 426 474 496 511 528 546 561

102 180 223 271 321 355 390 419 433 440 450 465 462

103 197 247 299 356 405 443 481 501 516 538 547 558

104 186 231 283 322 369 395 425 438 457 479 494 510

105 186 233 283 352 400 427 461 482 492 511 518 522

106 178 235 291 336 387 412 444 461 479 497 503 520

107 193 249 292 341 381 416 438 445 457 466 483 490

108 204 263 319 374 423 456 488 498 499 519 525 535

109 183 232 273 313 346 372 394 409 414 419 427 438

110 180 230 275 321 362 388 424 437 461 477 495 506

3M 111 187 241 296 338 382 425 461 495 500 525 541 565

112 196 240 258 292 328 364 386 402 412 427 444 448

113 185 230 271 303 350 397 429 444 475 487 509 525

114 191 233 259 293 337 367 403 416 442 442 448 467

115 184 242 279 317 354 392 419 423 435 444 468 469

116 179 232 264 291 333 368 396 410 430 440 450 452

117 175 222 258 296 331 385 385 399 403 416 422 430

118 187 240 280 328 359 379 403 418 423 438 453 461

119 175 225 266 315 352 392 422 442 458 475 488 501

120 199 262 301 361 426 461 505 534 546 556 566 569
351

Huntingdon Life Sciences

WAG0014

APPENDIX 5 - continued Request ID: 289239

Bodyweights - individual values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Week Week Week

/Sex Number 11 12 13

2M 101 567 576 572

102 461 468 472

103 565 580 574

104 520 530 516

105 516 522 520

106 524 539 540

107 492 499 501

108 537 544 540

109 442 449 449

110 499 521 508

3M 111 568 576 578

112 458 465 455

113 528 542 533

114 479 490 492

115 472 474 472

116 454 467 464

117 432 442 433

118 464 465 460

119 510 517 497

120 570 578 584
352

Huntingdon Life Sciences

WAG0014

APPENDIX 5 - continued Request ID: 289239

Bodyweights - individual values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Week Week Week Week Week Week Week Week Week Week Week Week

/Sex Number -1 0 1 2 3 4 5 6 7 8 9 10

4M 11 194 243 259 293 325 353 380 400 408 423 425 433

12 190 235 244 307 360 395 415 426 437 440 441 450

13 192 244 280 326 368 406 436 448 446 448 456 457

14 199 251 264 308 345 375 397 416 433 446 450 465

15 185 229 254 303 342 372 398 411 420 433 447 452

16 186 236 247 292 324 359 378 387 393 397 393 386

17 189 231 256 289 318 349 377 376 388 395 411 417

18 201 245 267 306 342 365 388 402 417 421 431 433

19 188 224 253 287 305 331 341 354 374 365 372 371

20 179 216 245 293 325 358 390 399 411 421 432 439

71 181 226 254 292 321 358 381 398 406 417 427 433

72 182 232 263 310 346 394 432 450 465 472 474 486

73 188 232 260 288 309 343 362 367 371 382 382 385

74 181 224 253 295 329 359 387 407 411 421 428 433

75 195 258 290 337 368 406 443 454 465 466 465 470

76 176 233 251 306 341 368 404 438 454 462 467 476

77 195 243 273 307 342 377 393 393 400 404 402 406

78 186 237 242 281 313 347 374 385 396 394 398 402

79 178 217 239 261 284 305 319 326 323 323 330 338

80 187 227 254 280 297 313 328 338 348 347 349 362
353

Huntingdon Life Sciences

WAG0014

APPENDIX 5 - continued Request ID: 289239

Bodyweights - individual values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Week Week Week Week Week Week Week

/Sex Number 11 12 13/R0 R1 R2 R3 R4

4M 11 431 400 397

12 457 462 434

13 460 464 450

14 465 469 464

15 461 463 454

16 394 385 366

17 420 433 425

18 437 444 434

19 369 380 377

20 446 458 427

71 393 416 410 446 470 489 487

72 486 483 488 512 538 559 560

73 380 391 386 401 420 436 434

74 442 445 447 468 491 504 495

75 470 480 476 505 517 534 549

76 468 472 470 487 504 527 533

77 406 412 406 441 459 467 469

78 412 414 414 439 457 475 479

79 337 343 348 375 389 398 409

80 361 364 368 381 399 416 419
354

Huntingdon Life Sciences

WAG0014

APPENDIX 5 - continued Request ID: 289239

Bodyweights - individual values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Week Week Week Week Week Week Week Week Week Week Week Week

/Sex Number -1 0 1 2 3 4 5 6 7 8 9 10

1F 21 168 186 216 230 258 268 282 289 289 304 310 318

22 150 169 187 216 229 240 251 253 258 264 270 276

23 162 179 213 225 234 241 253 263 270 267 273 281

24 164 194 213 235 245 265 286 285 280 298 308 311

25 162 179 207 213 240 244 258 261 262 266 280 281

26 182 206 234 255 272 283 301 309 305 320 328 329

27 176 197 226 228 251 271 280 289 305

28 178 202 223 250 276 295 294 301 309 324 325 332

29 163 188 210 224 242 252 256 270 274 277 288 293

30 157 169 207 225 233 252 262 263 284 288 298 299

41 151 177 205 223 249 245 264 268 276 279 286 290

42 187 209 233 256 278 279 307 309 302 323 319 325

43 167 193 217 225 256 257 263 282 295 294 293 306

44 179 217 249 258 286 302 303 313 329 337 329 348

45 158 183 199 218 228 243 254 251 273 281 282 283

46 175 198 221 229 266 273 292 295 296 305 309 315

47 180 191 222 241 258 264 282 296 300 311 311 321

48 161 179 198 213 233 249 262 269 261 265 278 289

49 172 187 204 216 234 247 263 280 277 276 288 292

50 146 184 192 198 225 242 246 247 252 267 268 266
355

Huntingdon Life Sciences

WAG0014

APPENDIX 5 - continued Request ID: 289239

Bodyweights - individual values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Week Week Week Week Week Week Week

/Sex Number 11 12 13/R0 R1 R2 R3 R4

1F 21 312 325 316

22 275 273 275

23 279 272 281

24 308 319 320

25 278 273 280

26 319 323 326

27

28 332 331 333

29 299 290 293

30 309 313 308

41 290 289 292 303 304 304 306

42 315 323 327 325 323 322 330

43 309 304 298 306 313 310 298

44 353 342 332 349 369 363 349

45 285 287 281 285 296 294 293

46 318 314 319 324 332 333 324

47 329 319 321 334 334 337 336

48 290 286 290 300 295 295 306

49 291 287 296 304 301 297 300

50 266 273 273 272 275 283 279
356

Huntingdon Life Sciences

WAG0014

APPENDIX 5 - continued Request ID: 289239

Bodyweights - individual values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Week Week Week Week Week Week Week Week Week Week Week Week

/Sex Number -1 0 1 2 3 4 5 6 7 8 9 10

2F 51 172 199 219 227 263 266 272 268 281 292 294 293

52 162 194 211 224 251 267 286 290 288 296 290 295

53 157 184 205 228 251 254 269 268 281 281 291 293

54 171 192 202 224 229 247 265 246 262 265 282 288

55 157 189 212 226 241 253 271 287 281 294 287 293

56 169 188 215 230 248 252 279 276 292 292 306 299

57 164 192 212 234 252 264 264 278 278 288 288 289

58 152 166 197 212 237 252 257 272 288 288 294 289

59 180 211 233 254 259 282 294 304 304 308 312 318

60 151 177 203 219 235 249 259 268 271 272 276 274

3F 1 169 189 215 224 253 263 282 278 289 287 291 300

2 171 201 215 246 261 263 291 290 287 293 296 298

3 158 176 184 197 211 212 226 227 230 240 233 238

4 180 197 222 233 258 261 275 286 283 286 299 298

5 176 200 223 240 250 266 280 280 290 291 292 289

6 178 205 225 232 257 263 272 288 287 300 307 299

7 157 177 189 208 222 227 241 247 250 257 265 283

8 170 191 202 223 227 243 262 261 267 281 281 287

9 147 170 191 200 221 226 243 249 258 262 266 266

10 174 204 216 230 248 247 271 269 274 283 276 281
357

Huntingdon Life Sciences

WAG0014

APPENDIX 5 - continued Request ID: 289239

Bodyweights - individual values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Week Week Week

/Sex Number 11 12 13

2F 51 302 305 294

52 299 297 286

53 299 302 301

54 282 288 282

55 295 300 286

56 315 309 323

57 295 298 299

58 294 293 299

59 320 311 326

60 281 286 283

3F 1 308 297 292

2 301 295 294

3 234 243 236

4 293 302 294

5 299 297 299

6 308 301 298

7 266 263 254

8 281 278 283

9 270 272 271

10 282 283 289
358

Huntingdon Life Sciences

WAG0014

APPENDIX 5 - continued Request ID: 289239

Bodyweights - individual values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Week Week Week Week Week Week Week Week Week Week Week Week

/Sex Number -1 0 1 2 3 4 5 6 7 8 9 10

4F 31 147 172 192 200 209 216 217 216 224 221 216 216

32 159 182 185 196 212 218 219 215 210 210 189 211

33 162 186 228 234 245 261 273 273 275 275 284 294

34 163 190 209 208 232 247 244 262 261 257 258 264

35 163 192 213 221 230 249 255 259 256 253 257 233

36 178 200 241 241 261 255 284 265 273 286 283 294

37 171 197 214 225 235 260 255 258 261 265 273 271

38 171 194 211 217 236 243 245 251 247 249 256 250

39 166 190 219 228 245 271 265 272 287 279 284 289

40 157 189 215 220 229 247 240 234 241 250 251 260

91 177 201 216 225 246 279 263 267 265 269 270 275

92 144 160 184 190 199 201 205 209 209 210 216 201

93 176 195 219 228 229 244 255 244 250 261 253 259

94 175 191 212 224 228 233 237 236 233 233 242 238

95 176 211 222 248 247 259 270 259 280 270 273 278

96 168 194 213 220 232 236 243 244 248 252 251 248

97 155 179 198 194 215 221 222 228 231 235 240 238

98 148 167 193 194 217 222 235 239 233 238 241 246

99 188 224 239 248 249 265 273 270 267 269 274 277

100 166 195 206 220 235 234 256 248 262 256 260 254
359

Huntingdon Life Sciences

WAG0014

APPENDIX 5 - continued Request ID: 289239

Bodyweights - individual values (g)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Week Week Week Week Week Week Week

/Sex Number 11 12 13/R0 R1 R2 R3 R4

4F 31 217 217 211

32 218 207 207

33 291 312 294

34 259 269 271

35 254 255 257

36 284 291 272

37 273 277 256

38 261 260 253

39 287 286 279

40 264 263 265

91 279 287 220 266 279 284 283

92 214 216 209 232 236 239 240

93 269 260 251 267 279 275 263

94 231 240 237 248 260 262 256

95 285 303 284 285 292 288 297

96 256 257 253 269 273 271 261

97 247 247 251 260 265 263 253

98 249 246 249 256 263 257 254

99 284 282 286 292 302 303 291

100 270 267 265 273 275 274 264
360

Huntingdon Life Sciences

WAG0014

APPENDIX 6 Request ID: 289244

Food consumption - individual values (g/animal/week)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Cage Week Week Week Week Week Week Week Week Week Week Week Week

/Sex Number -1 1 2 3 4 5 6 7 8 9 10 11

1M 13 132 206 204 211 207 220 214 208 214 224 222 207

14 137 204 201 211 207 222 213 209 215 225 218 202

17 136 218 218 224 223 218 217 208 227 229 225 206

18 133 208 215 213 203 211 207 208 211 211 204 196

2M 21 134 190 197 191 191 204 199 193 191 192 189 187

22 140 196 196 196 194 200 195 187 190 188 182 179

3M 23 136 166 168 177 186 193 192 192 189 192 188 184

24 143 175 184 184 188 193 191 186 183 175 174 173

4M 3 135 137 180 174 177 189 177 170 169 158 156 159

4 130 134 171 161 163 168 165 161 154 144 143 144

15 132 148 178 164 178 185 180 174 167 154 154 140

16 135 130 161 149 159 169 164 156 151 141 146 141
361

Huntingdon Life Sciences

WAG0014

APPENDIX 6 - continued Request ID: 289244

Food consumption - individual values (g/animal/week)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Cage Week Week Week Week Week Week

/Sex Number 12 13 R1 R2 R3 R4

1M 13 212 195

14 191 186

17 218 218 237 236 228 199

18 199 206 207 212 202 181

2M 21 184 169

22 179 163

3M 23 184 160

24 171 145

4M 3 138 128

4 144 120

15 154 157 195 186 193 177

16 141 150 193 179 182 170
362

Huntingdon Life Sciences

WAG0014

APPENDIX 6 - continued Request ID: 289244

Food consumption - individual values (g/animal/week)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Cage Week Week Week Week Week Week Week Week Week Week Week Week

/Sex Number -1 1 2 3 4 5 6 7 8 9 10 11

1F 5 89 130 123 127 127 139 124 127 133 134 127 127

6 92 139 127 135 137 143 130 135 134 138 138 137

9 103 144 135 152 143 154 150 151 152 143 146 139

10 97 136 130 142 140 153 147 146 147 146 141 138

2F 11 99 132 128 126 132 133 133 132 135 125 127 122

12 97 127 129 134 138 142 147 145 141 137 134 131

3F 1 102 127 125 131 132 137 136 134 128 126 123 124

2 95 120 116 121 127 138 135 138 134 133 136 130

4F 7 92 111 109 110 118 114 106 105 111 94 94 92

8 100 118 117 116 124 117 116 118 119 111 116 117

19 98 119 117 112 113 117 109 112 111 108 108 105

20 103 120 119 120 113 124 115 117 115 115 113 115
363

Huntingdon Life Sciences

WAG0014

APPENDIX 6 - continued Request ID: 289244

Food consumption - individual values (g/animal/week)

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Cage Week Week Week Week Week Week

/Sex Number 12 13 R1 R2 R3 R4

1F 5 127 122

6 130 126

9 134 142 155 150 147 130

10 140 148 152 143 148 137

2F 11 123 115

12 128 125

3F 1 117 111

2 126 125

4F 7 97 88

8 108 85

19 108 85 147 126 122 112

20 114 108 153 139 131 113
364

Huntingdon Life Sciences

WAG0014

APPENDIX 7

Ophthalmic examination - individual observations before commencement of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group and sex

Structure Observation 1M 2M 3M 4M 1F 2F 3F 4F

Animal number/site

Cornea Scratch, faint 86L

Superficial opacity, faint 63, 84 101, 

104, 

109

113, 

119, 

120

15, 19, 

72

26, 30, 

42, 45

57 1, 2, 3, 

4, 6

93

Iris Iritis, slight 101R

Lens Anterior subcapsular opacity, faint, lateral 62L

Anterior suture line opacity, faint 37R

Nuclear opacity, faint 118L 13 8R

Nuclear opacity, slight 34

Persistent hyaloid artery 101, 

102, 

104, 

114, 

116R

18, 76, 

78

28L, 

44L, 49

6 36L, 

38L, 95

Posterior subcapsular opacity, slight 44L

Posterior subcapsular opacity, moderate 57R

Vitreous Haemorrhage, slight 116R 44L 38L

Fundus Optic disc coloboma, slight 10R 38L

Number of animals examined : 20 10 10 20 20 10 10 20
365

Huntingdon Life Sciences

WAG0014

APPENDIX 7 - continued

Ophthalmic examination - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group and sex

Structure Observation 1M 4M 1F 4F

Animal number/site

Conjunctiva Conjunctivitis, faint 94R

Cornea Superficial opacity, faint 63, 84L 15L, 

17L, 19

26, 30, 

42

93

Superficial opacity, slight 76L

Lens Anterior subcapsular opacity, faint, lateral 62L

Anterior suture line opacity, faint 37R

Nuclear opacity, faint 13

Nuclear opacity, slight 34

Persistent hyaloid artery 18, 76, 

78

28L, 

44L, 49

38L, 95

Posterior subcapsular opacity, slight 44L

Vitreous Haemorrhage, slight 44L 38L

Fundus Optic disc coloboma, slight 38L

Number of animals examined : 20 20 19 20
366

Huntingdon Life Sciences

WAG0014

APPENDIX 8

Haematology - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Hct Hb RBC RETA MCH MCHC MCV

/Sex Number L/L g/dL x1012/L x1012/L pg g/dL fL

1M 61 0.433 15.7 8.23 0.192 19.0 36.2 52.6

62 0.418 15.0 7.98 0.211 18.7 35.8 52.3

63 0.468 16.9 8.72 0.184 19.4 36.2 53.7

64 0.438 16.0 8.37 0.228 19.1 36.5 52.3

65 0.444 16.1 8.58 0.158 18.8 36.2 51.8

66 0.398 14.5 7.76 0.255 18.7 36.5 51.4

67 0.421 15.0 8.00 0.213 18.8 35.7 52.6

68 0.418 15.8 8.06 0.175 19.7 37.9 51.8

69 0.409 15.6 7.88 0.178 19.8 38.2 51.8

70 0.445 16.1 8.27 0.139 19.5 36.2 53.9

2M 101 0.430 15.3 8.27 0.206 18.5 35.6 52.0

102 0.406 14.7 8.06 0.184 18.2 36.2 50.4

103 0.424 15.5 8.15 0.219 19.0 36.6 52.0

104 0.475 17.0 8.97 0.177 18.9 35.7 53.0

105 0.432 15.6 8.69 0.175 18.0 36.1 49.7

106 0.480 17.1 9.50 0.234 18.0 35.7 50.5

107 0.418 15.1 8.42 0.187 17.9 36.1 49.7

108 0.459 16.2 8.40 0.186 19.3 35.3 54.6

109 0.418 14.9 8.12 0.186 18.4 35.6 51.5

110 0.508 18.3 9.86 0.177 18.6 36.1 51.5
367

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal WBC N L E B M LUC

/Sex Number x109/L x109/L x109/L x109/L x109/L x109/L x109/L

1M 61 9.63 1.42 7.69 0.15 0.03 0.25 0.08

62 12.71 3.64 8.26 0.22 0.07 0.40 0.12

63 13.04 1.24 11.37 0.13 0.08 0.17 0.06

64 7.25 1.35 5.52 0.12 0.02 0.19 0.05

65 8.48 1.56 6.44 0.17 0.02 0.23 0.06

66 14.98 4.41 9.48 0.35 0.09 0.55 0.11

67 14.83 3.11 10.93 0.18 0.12 0.38 0.10

68 11.96 3.53 7.58 0.21 0.04 0.51 0.08

69 9.62 2.14 6.96 0.16 0.05 0.20 0.11

70 10.58 1.24 8.81 0.16 0.07 0.24 0.07

2M 101 10.12 0.91 8.67 0.07 0.05 0.31 0.11

102 7.63 1.99 5.10 0.07 0.02 0.37 0.07

103 17.69 3.44 13.20 0.15 0.17 0.58 0.15

104 8.93 2.73 5.51 0.10 0.03 0.47 0.09

105 11.72 1.63 9.59 0.06 0.07 0.30 0.08

106 12.26 3.87 7.31 0.17 0.10 0.66 0.14

107 7.59 1.44 5.72 0.09 0.02 0.27 0.05

108 7.20 1.99 4.83 0.08 0.01 0.21 0.07

109 8.04 1.52 6.22 0.02 0.03 0.19 0.06

110 15.13 9.67 4.32 0.08 0.05 0.77 0.25
368

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Plt PTP APTT Aniso- Micro- Macro- Hypo- Hyper-

/Sex Number x109/L sec sec cytosis cytosis cytosis chromasia chromasia

1M 61 949 30.2 27.7 - - - - -

62 972 25.7 22.2 - - - - -

63 974 22.7 20.9 - - - - -

64 493 25.7 26.5 - - - - -

65 782 21.3 25.0 - - - - -

66 914 22.0 21.1 - - - - -

67 NVR 22.0 23.4 - - - - -

68 933 34.2 29.1 - - - - -

69 912 22.1 22.3 - - - - -

70 1013 23.9 21.1 - - - - -

2M 101 1123 19.5 19.3 - - - - -

102 962 23.4 24.2 - - - - -

103 983 23.8 20.8 - - - - -

104 1212 21.0 21.0 - - - - -

105 878 21.6 20.2 - - - - -

106 1224 22.5 20.2 - - - - -

107 822 25.3 27.4 - - - - -

108 907 21.5 20.7 - - - - -

109 1184 20.9 19.8 - - - - -

110 873 23.5 22.2 - - - - -
369

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Hct Hb RBC RETA MCH MCHC MCV

/Sex Number L/L g/dL x1012/L x1012/L pg g/dL fL

3M 111 0.438 15.9 9.11 0.225 17.4 36.2 48.1

112 0.429 15.9 8.78 0.151 18.1 37.0 48.9

113 0.481 17.1 9.23 0.139 18.5 35.5 52.1

114 0.467 16.8 9.58 0.179 17.5 36.0 48.7

115 0.444 16.1 8.47 0.171 19.0 36.2 52.4

116 0.470 17.3 9.36 0.174 18.5 36.7 50.3

117 0.428 15.5 8.76 0.260 17.7 36.2 48.8

118 0.443 16.0 8.31 0.159 19.2 36.0 53.4

119 0.407 14.6 7.95 0.201 18.4 35.9 51.2

120 0.447 15.9 8.38 0.218 19.0 35.7 53.3

4M 11 0.437 16.1 8.68 0.093 18.5 36.8 50.3

12 0.432 15.9 8.72 0.255 18.3 36.9 49.6

13 0.455 16.6 9.34 0.207 17.8 36.5 48.8

14 0.469 16.9 8.95 0.227 18.9 36.0 52.4

15 0.484 17.6 9.60 0.234 18.3 36.3 50.4

16 0.462 16.9 9.17 0.236 18.5 36.7 50.3

17 0.438 15.9 9.05 0.191 17.6 36.3 48.4

18 0.447 16.1 8.92 0.261 18.1 36.1 50.1

19 0.463 17.2 9.21 0.107 18.6 37.1 50.3

20 0.453 16.6 8.97 0.244 18.5 36.7 50.5
370

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal WBC N L E B M LUC

/Sex Number x109/L x109/L x109/L x109/L x109/L x109/L x109/L

3M 111 12.74 3.18 8.64 0.04 0.04 0.70 0.14

112 7.21 1.48 5.13 0.04 0.02 0.45 0.08

113 12.36 3.69 7.66 0.06 0.10 0.70 0.14

114 10.20 2.01 7.44 0.05 0.07 0.52 0.11

115 12.63 3.82 7.67 0.09 0.09 0.78 0.18

116 10.68 2.59 7.42 0.04 0.06 0.50 0.08

117 9.37 2.32 6.34 0.05 0.05 0.53 0.08

118 7.00 1.58 5.02 0.04 0.03 0.27 0.05

119 8.24 2.82 4.85 0.03 0.02 0.44 0.08

120 15.71 2.98 11.68 0.07 0.24 0.55 0.19

4M 11 7.35 0.51 6.48 0.03 0.02 0.24 0.07

12 6.56 2.02 3.59 0.05 0.07 0.55 0.28

13 8.97 2.98 4.89 0.04 0.06 0.77 0.23

14 11.66 3.29 7.45 0.05 0.09 0.67 0.10

15 9.77 2.63 6.33 0.03 0.04 0.58 0.15

16 8.40 2.15 5.52 0.05 0.02 0.50 0.17

17 8.61 1.36 6.35 0.08 0.02 0.42 0.37

18 6.79 1.64 4.45 0.04 0.02 0.41 0.23

19 11.70 4.59 6.05 0.08 0.07 0.73 0.18

20 8.87 2.34 5.51 0.02 0.03 0.79 0.18
371

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Plt PTP APTT Aniso- Micro- Macro- Hypo- Hyper-

/Sex Number x109/L sec sec cytosis cytosis cytosis chromasia chromasia

3M 111 1134 21.7 19.2 - - - - -

112 1014 24.5 20.3 - - - - -

113 919 22.4 21.5 - - - - -

114 1059 25.6 18.5 - - - - -

115 1059 21.8 19.3 - - - - -

116 910 22.6 21.2 - - - - -

117 1041 26.6 22.3 - - - - -

118 755 25.0 22.0 - - - - -

119 1044 22.6 22.6 - - - - -

120 826 25.5 21.2 - - - - -

4M 11 821 23.8 22.1 - - - - -

12 945 25.6 19.6 - - - - -

13 1004 26.1 25.6 - - - - -

14 792 22.4 23.2 - - - - -

15 970 24.3 20.9 - - - - -

16 886 CTD CTD - - - - -

17 936 24.0 19.2 - - - - -

18 890 24.5 23.9 - - - - -

19 922 27.4 22.2 - - - - -

20 814 24.2 21.9 - - - - -
372

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Hct Hb RBC RETA MCH MCHC MCV

/Sex Number L/L g/dL x1012/L x1012/L pg g/dL fL

1F 21 0.407 14.8 7.78 0.200 19.1 36.4 52.3

22 0.406 15.4 7.75 0.099 19.9 37.9 52.3

23 0.431 15.5 8.06 0.156 19.3 36.0 53.5

24 0.417 15.5 7.75 0.203 20.0 37.1 53.8

25 0.436 15.9 7.88 0.144 20.1 36.4 55.3

26 0.422 15.3 8.38 0.187 18.3 36.4 50.3

28 0.416 15.5 7.45 0.146 20.8 37.3 55.8

29 0.423 15.5 7.82 0.134 19.8 36.7 54.1

30 0.438 16.2 8.41 0.156 19.3 37.0 52.1

2F 51 0.436 15.8 8.15 0.210 19.3 36.2 53.4

52 0.393 14.1 7.82 0.169 18.1 36.0 50.2

53 0.422 15.5 7.85 0.135 19.7 36.7 53.8

54 0.409 15.7 7.82 0.129 20.0 38.3 52.3

55 0.388 13.9 7.60 0.207 18.2 35.7 51.1

56 0.406 14.8 8.04 0.131 18.5 36.5 50.6

57 0.441 16.1 8.40 0.185 19.2 36.5 52.5

58 0.422 15.6 8.53 0.090 18.3 37.1 49.5

59 0.395 15.1 7.52 0.150 20.0 38.1 52.6

60 0.409 15.1 7.52 0.253 20.1 36.9 54.3
373

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal WBC N L E B M LUC

/Sex Number x109/L x109/L x109/L x109/L x109/L x109/L x109/L

1F 21 8.05 2.42 5.25 0.10 0.02 0.19 0.06

22 4.98 0.34 4.41 0.08 0.01 0.07 0.06

23 8.75 2.01 6.23 0.13 0.03 0.29 0.05

24 4.38 0.69 3.48 0.06 0.02 0.10 0.03

25 6.43 0.55 5.59 0.07 0.02 0.14 0.06

26 10.07 2.22 7.42 0.08 0.03 0.19 0.15

28 12.72 2.78 9.12 0.12 0.17 0.39 0.15

29 14.69 3.39 10.74 0.12 0.06 0.22 0.15

30 6.77 0.71 5.61 0.20 0.04 0.14 0.06

2F 51 7.42 0.84 5.86 0.14 0.08 0.41 0.10

52 6.85 0.96 5.57 0.03 0.02 0.25 0.03

53 6.80 0.76 5.73 0.04 0.02 0.17 0.08

54 7.41 0.39 6.60 0.06 0.03 0.16 0.17

55 11.14 1.09 9.57 0.04 0.05 0.28 0.10

56 9.03 1.50 6.88 0.07 0.03 0.44 0.09

57 8.15 0.71 6.90 0.05 0.04 0.25 0.19

58 5.94 0.93 4.61 0.08 0.04 0.22 0.07

59 6.63 0.70 5.48 0.10 0.02 0.25 0.07

60 6.53 0.75 5.41 0.05 0.02 0.23 0.08
374

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Plt PTP APTT Aniso- Micro- Macro- Hypo- Hyper-

/Sex Number x109/L sec sec cytosis cytosis cytosis chromasia chromasia

1F 21 1236 21.5 18.8 - - - - -

22 843 21.2 16.4 - - - - -

23 1023 20.8 17.6 - - - - -

24 853 20.6 19.0 - - - - -

25 797 20.8 18.3 - - - - -

26 871 22.2 15.9 - - - - -

28 960 22.0 16.9 - - - - -

29 896 21.2 17.2 - - - - -

30 1071 19.3 16.2 - - - - -

2F 51 747 25.6 19.9 - - - - -

52 853 24.0 17.8 - - - - -

53 932 23.9 21.5 - - - - -

54 985 23.8 18.1 - - - - -

55 997 23.9 19.4 - - - - -

56 798 24.6 18.1 - - - - -

57 758 24.4 18.8 - - - - -

58 822 24.0 19.6 - - - - -

59 849 24.7 19.4 - - - - -

60 978 22.4 17.7 - - - - -
375

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Hct Hb RBC RETA MCH MCHC MCV

/Sex Number L/L g/dL x1012/L x1012/L pg g/dL fL

3F 1 0.426 15.5 7.97 0.212 19.4 36.3 53.4

2 0.418 14.7 7.96 0.136 18.5 35.3 52.5

3 0.465 16.5 8.89 0.255 18.6 35.6 52.3

4 0.397 14.4 8.03 0.201 18.0 36.4 49.5

5 0.416 15.7 8.43 0.137 18.7 37.8 49.4

6 0.435 16.2 8.31 0.137 19.5 37.2 52.3

7 0.412 15.1 8.17 0.226 18.5 36.8 50.4

8 0.411 15.0 7.72 0.147 19.4 36.5 53.2

9 0.439 16.0 8.13 0.156 19.6 36.4 54.0

10 0.446 16.4 8.38 0.148 19.6 36.8 53.2

4F 31 0.425 15.2 8.04 0.376 18.9 35.7 52.9

32 0.370 13.1 6.03 0.627 21.7 35.4 61.3

33 0.407 15.2 8.44 0.230 18.0 37.4 48.2

34 0.433 15.7 8.50 0.210 18.4 36.2 50.9

35 0.387 13.5 7.30 0.462 18.5 34.9 53.0

36 0.415 14.0 7.85 0.323 17.9 33.9 52.8

37 0.397 13.5 8.07 0.336 16.8 34.1 49.2

38 0.436 14.6 8.45 0.362 17.3 33.5 51.6

39 0.424 14.2 8.35 0.192 17.0 33.4 50.8

40 0.450 15.1 9.50 0.175 15.9 33.7 47.3
376

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal WBC N L E B M LUC

/Sex Number x109/L x109/L x109/L x109/L x109/L x109/L x109/L

3F 1 6.82 1.24 4.93 0.02 0.06 0.43 0.14

2 10.50 1.54 7.88 0.13 0.03 0.70 0.20

3 5.24 1.17 3.52 0.07 0.05 0.36 0.07

4 7.11 1.19 5.10 0.08 0.02 0.47 0.25

5 6.49 0.67 5.34 0.08 0.04 0.29 0.07

6 8.03 1.79 5.44 0.05 0.04 0.56 0.15

7 4.38 0.31 3.80 0.03 0.02 0.18 0.05

8 7.07 1.35 5.15 0.06 0.03 0.37 0.11

9 7.08 1.84 4.69 0.08 0.01 0.34 0.10

10 7.47 0.74 6.03 0.13 0.05 0.41 0.12

4F 31 5.86 1.37 4.00 0.02 0.01 0.38 0.07

32 6.09 1.00 4.71 0.02 0.02 0.21 0.13

33 4.49 0.61 3.40 0.03 0.02 0.38 0.05

34 5.41 0.67 4.22 0.03 0.04 0.37 0.08

35 4.03 1.19 2.56 0.02 0.01 0.19 0.06

36 8.76 3.39 4.77 0.02 0.02 0.33 0.24

37 3.30 0.31 2.66 0.01 0.01 0.25 0.06

38 7.56 0.33 6.48 0.04 0.05 0.44 0.22

39 6.73 1.40 4.86 0.02 0.03 0.35 0.08

40 5.59 0.46 4.73 0.04 0.04 0.27 0.05
377

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Plt PTP APTT Aniso- Micro- Macro- Hypo- Hyper-

/Sex Number x109/L sec sec cytosis cytosis cytosis chromasia chromasia

3F 1 784 25.4 18.0 - - - - -

2 1064 20.5 16.9 - - - - -

3 601 24.0 21.3 - - - - -

4 709 22.8 21.2 - - - - -

5 853 23.9 19.5 - - - - -

6 940 22.2 20.0 - - - - -

7 788 26.3 17.4 - - - - -

8 944 24.2 20.1 - - - - -

9 919 22.7 18.3 - - - - -

10 790 22.0 20.5 - - - - -

4F 31 1369 25.7 20.6 - - - - -

32 1052 31.1 19.4 + - - - -

33 1033 28.9 20.1 - - - - -

34 683 25.7 20.0 - - - - -

35 803 27.1 18.6 - - - - -

36 1496 28.1 18.4 - - - - -

37 1203 27.4 17.9 - - - - -

38 785 24.0 21.4 - - - - -

39 1248 29.8 20.3 - - - - -

40 1032 16.6 18.5 - - - - -
378

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Hct Hb RBC RETA MCH MCHC MCV

/Sex Number L/L g/dL x1012/L x1012/L pg g/dL fL

1M 81 0.424 14.7 8.72 0.291 16.8 34.6 48.6

82 0.450 15.3 9.05 0.183 16.9 33.9 49.7

83 0.453 15.3 8.65 0.233 17.7 33.8 52.3

84 0.439 15.0 8.21 0.167 18.2 34.1 53.5

85 0.460 15.7 8.77 0.180 17.9 34.1 52.5

86 0.428 14.3 8.26 0.257 17.3 33.4 51.9

87 0.424 14.3 7.99 0.182 17.9 33.7 53.1

88 0.448 15.1 8.63 0.197 17.5 33.8 51.9

89 0.428 14.4 7.83 0.260 18.3 33.6 54.6

90 0.451 15.4 8.63 0.169 17.8 34.1 52.2

4M 71 0.446 15.4 8.34 0.181 18.5 34.5 53.5

72 0.451 15.2 8.24 0.156 18.4 33.7 54.8

73 0.434 14.8 8.11 0.177 18.3 34.1 53.5

74 0.471 15.9 8.69 0.144 18.3 33.8 54.2

75 0.432 14.7 7.89 0.263 18.7 34.1 54.7

76 0.444 15.0 8.21 0.156 18.3 33.9 54.1

77 0.490 16.7 8.92 0.116 18.7 34.1 54.9

78 0.451 15.3 8.65 0.123 17.7 33.9 52.1

79 0.438 14.7 8.61 0.111 17.0 33.5 50.8

80 0.433 14.8 8.54 0.204 17.3 34.1 50.7
379

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal WBC N L E B M LUC

/Sex Number x109/L x109/L x109/L x109/L x109/L x109/L x109/L

1M 81 11.41 3.12 7.50 0.18 0.03 0.46 0.13

82 12.28 2.98 8.66 0.16 0.12 0.23 0.15

83 9.17 0.97 7.65 0.16 0.06 0.29 0.05

84 8.99 1.40 7.12 0.12 0.06 0.24 0.06

85 9.31 1.49 7.20 0.16 0.10 0.25 0.10

86 16.80 2.11 13.52 0.24 0.26 0.43 0.24

87 9.63 0.73 8.40 0.08 0.11 0.21 0.11

88 10.74 1.23 8.99 0.12 0.11 0.17 0.13

89 11.55 2.02 8.95 0.10 0.10 0.24 0.14

90 7.84 1.45 5.86 0.11 0.06 0.25 0.11

4M 71 9.21 1.18 7.55 0.09 0.05 0.19 0.15

72 6.73 0.87 5.44 0.10 0.05 0.20 0.07

73 6.36 1.14 4.80 0.14 0.04 0.16 0.09

74 9.49 1.63 7.34 0.13 0.10 0.20 0.08

75 9.98 1.65 7.87 0.18 0.07 0.14 0.07

76 6.24 0.96 4.95 0.08 0.07 0.10 0.07

77 5.10 0.99 3.74 0.14 0.03 0.16 0.05

78 7.69 0.83 6.19 0.13 0.06 0.34 0.14

79 7.86 0.72 6.85 0.04 0.07 0.12 0.06

80 9.13 2.24 6.16 0.21 0.14 0.27 0.11
380

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Plt PTP APTT Aniso- Micro- Macro- Hypo- Hyper-

/Sex Number x109/L sec sec cytosis cytosis cytosis chromasia chromasia

1M 81 1080 21.2 17.6 + - - - -

82 1067 23.3 24.8 + - - - -

83 1117 20.4 18.6 - - - - -

84 621 23.1 23.6 - - - - -

85 1011 20.5 27.3 - - - - -

86 1301 23.6 20.3 - - - - -

87 1305 24.2 22.8 - - - - -

88 1180 22.9 19.6 - - - - -

89 1149 21.6 20.6 - - - - -

90 1077 25.7 30.9 - - - - -

4M 71 1227 17.7 13.9 - - - - -

72 1109 20.9 22.3 - - - - -

73 1079 22.1 24.0 - - - - -

74 1173 21.7 23.5 - - - - -

75 1221 22.5 22.3 - - - - -

76 914 23.1 18.7 - - - - -

77 866 22.0 21.5 - - - - -

78 1250 23.5 22.7 - - - - -

79 1168 23.5 21.4 - - - - -

80 979 21.5 21.6 - - - - -
381

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Hct Hb RBC RETA MCH MCHC MCV

/Sex Number L/L g/dL x1012/L x1012/L pg g/dL fL

1F 41 0.409 14.4 7.21 0.108 19.9 35.1 56.8

42 0.418 14.5 7.68 0.082 18.9 34.6 54.4

43 0.420 14.2 7.97 0.189 17.9 33.9 52.8

44 0.401 13.7 7.61 0.152 17.9 34.1 52.7

45 0.426 14.5 7.50 0.172 19.4 34.1 56.8

46 0.438 15.1 8.00 0.100 18.9 34.5 54.7

47 0.410 14.2 7.29 0.123 19.4 34.6 56.2

48 0.412 14.1 7.80 0.136 18.1 34.2 52.8

49 0.423 14.6 7.57 0.105 19.3 34.5 55.9

50 0.415 14.4 7.37 0.127 19.6 34.8 56.3

4F 91 0.435 15.1 7.82 0.129 19.3 34.6 55.7

92 0.406 14.0 7.74 0.112 18.1 34.4 52.4

93 0.427 14.5 8.00 0.149 18.1 34.0 53.4

94 0.432 14.6 8.05 0.139 18.2 33.9 53.6

95 0.421 14.8 7.81 0.073 19.0 35.3 53.9

96 0.422 14.3 7.94 0.104 18.0 33.8 53.1

97 0.430 14.7 7.85 0.142 18.7 34.1 54.8

98 0.440 15.0 7.84 0.168 19.1 34.1 56.1

99 0.433 15.2 8.09 0.155 18.7 35.0 53.5

100 0.431 14.8 7.67 0.150 19.2 34.3 56.2
382

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal WBC N L E B M LUC

/Sex Number x109/L x109/L x109/L x109/L x109/L x109/L x109/L

1F 41 4.93 0.46 4.20 0.08 0.04 0.10 0.05

42 5.77 0.85 4.47 0.13 0.05 0.15 0.12

43 5.58 0.54 4.75 0.11 0.03 0.08 0.06

44 3.78 0.46 3.12 0.08 0.01 0.08 0.03

45 4.19 0.54 3.35 0.10 0.03 0.13 0.03

46 5.87 0.96 4.66 0.07 0.03 0.09 0.06

47 5.72 0.65 4.70 0.14 0.03 0.14 0.06

48 6.90 1.55 4.91 0.14 0.02 0.19 0.08

49 4.00 0.71 2.96 0.11 0.03 0.13 0.05

50 3.76 0.72 2.79 0.10 0.03 0.07 0.05

4F 91 3.43 0.48 2.69 0.05 0.01 0.15 0.04

92 6.58 1.41 4.87 0.09 0.02 0.13 0.07

93 2.32 0.70 1.37 0.16 0.01 0.06 0.02

94 2.98 0.58 2.17 0.11 0.02 0.06 0.04

95 3.78 0.78 2.78 0.06 0.04 0.08 0.05

96 2.36 0.44 1.78 0.06 0.01 0.04 0.03

97 3.66 0.54 2.89 0.08 0.02 0.08 0.04

98 4.33 0.92 3.17 0.10 0.03 0.07 0.05

99 3.66 0.98 2.44 0.08 0.03 0.08 0.04

100 2.85 0.44 2.21 0.06 0.02 0.10 0.02
383

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Plt PTP APTT Aniso- Micro- Macro- Hypo- Hyper-

/Sex Number x109/L sec sec cytosis cytosis cytosis chromasia chromasia

1F 41 913 22.9 25.2 - - - - -

42 952 22.9 21.3 - - - - -

43 1155 22.8 22.3 - - - - -

44 1021 22.8 19.3 - - - - -

45 997 22.3 20.6 - - - - -

46 1072 18.2 23.0 - - - - -

47 1003 22.1 20.7 - - - - -

48 956 20.0 17.1 - - - - -

49 1104 22.0 19.9 - - - - -

50 882 21.4 19.2 - - - - -

4F 91 1054 20.5 16.6 - - - - -

92 961 21.7 23.2 - - - - -

93 1036 22.9 21.2 - - - - -

94 1222 23.0 20.4 - - - - -

95 897 24.3 19.1 - - - - -

96 904 22.8 20.2 - - - - -

97 916 23.9 20.2 - - - - -

98 1014 21.3 16.7 - - - - -

99 1144 21.7 20.3 - - - - -

100 949 19.4 18.1 - - - - -
384

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations sporadic sample

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Hct Hb RBC RETA MCH MCHC MCV

/Sex Number L/L g/dL x1012/L x1012/L pg g/dL fL

1F 27 0.527 17.4 8.78 0.377 19.8 32.9 60.0
385

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations sporadic sample

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal WBC N L E B M LUC

/Sex Number x109/L x109/L x109/L x109/L x109/L x109/L x109/L

1F 27 4.80 2.97 1.43 0.01 0.02 0.33 0.03
386

Huntingdon Life Sciences

WAG0014

APPENDIX 8 - continued

Haematology - individual observations sporadic sample

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Plt PTP APTT Aniso- Micro- Macro- Hypo- Hyper-

/Sex Number x109/L sec sec cytosis cytosis cytosis chromasia chromasia

1F 27 1339 25.5 18.3 + - - - -
387

Huntingdon Life Sciences

WAG0014

APPENDIX 9

Blood chemistry - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal ALP ALT AST Bili Urea Creat Gluc Chol Trig

/Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L

1M 61 74 33 82 2 4.93 40 6.69 1.77 0.85

62 99 38 94 1 5.92 29 7.45 1.62 0.44

63 89 23 71 2 5.16 29 8.68 1.81 1.07

64 59 26 74 2 4.49 34 8.74 1.70 0.84

65 76 37 71 1 5.61 37 10.03 1.81 0.66

66 61 24 73 3 4.97 40 8.66 1.65 0.88

67 70 31 63 2 4.79 32 7.57 1.65 0.44

68 55 32 81 1 6.24 36 7.79 1.60 0.59

69 75 34 72 1 4.21 35 8.11 2.35 0.73

70 62 31 70 2 4.76 36 8.04 1.44 0.37

2M 101 88 29 94 2 5.49 37 7.15 2.32 0.82

102 63 44 74 2 6.34 29 8.37 1.55 0.47

103 66 38 136 2 5.84 35 8.77 1.11 0.42

104 84 41 250 2 4.71 28 8.53 1.89 1.24

105 78 27 85 2 5.55 31 7.54 1.60 0.63

106 78 39 216 2 5.06 36 7.80 2.07 0.75

107 77 48 105 1 6.55 33 10.11 1.07 0.53

108 61 41 118 2 6.25 33 9.21 1.29 0.31

109 58 32 188 2 7.73 37 10.82 1.29 0.86

110 69 60 462 2 5.49 34 8.92 1.90 0.58
388

Huntingdon Life Sciences

WAG0014

APPENDIX 9 - continued

Blood chemistry - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Na K Cl Ca Phos Total Prot Alb A/G

/Sex Number mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio

1M 61 142 3.8 100 2.47 1.78 67 36 1.16

62 142 4.1 102 2.44 1.92 70 34 0.94

63 142 4.6 102 2.44 2.09 62 33 1.14

64 143 4.2 103 2.44 2.12 61 34 1.26

65 141 4.5 102 2.40 1.83 63 34 1.17

66 140 4.6 101 2.42 2.05 64 34 1.13

67 141 4.5 103 2.43 1.76 66 33 1.00

68 141 3.7 102 2.36 1.81 69 35 1.03

69 141 4.1 102 2.46 1.74 69 35 1.03

70 141 4.2 101 2.50 1.77 65 36 1.24

2M 101 142 4.4 104 2.43 2.02 62 35 1.30

102 141 4.3 104 2.44 1.78 65 34 1.10

103 141 4.4 103 2.39 1.98 62 33 1.14

104 144 4.0 105 2.46 1.95 60 34 1.31

105 141 4.2 104 2.38 2.15 63 34 1.17

106 142 5.0 105 2.54 1.67 67 37 1.23

107 142 4.8 105 2.33 1.50 63 35 1.25

108 143 4.5 106 2.41 1.61 61 34 1.26

109 143 4.6 104 2.44 2.41 61 32 1.10

110 142 4.6 102 2.49 2.22 68 35 1.06
389

Huntingdon Life Sciences

WAG0014

APPENDIX 9 - continued

Blood chemistry - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal ALP ALT AST Bili Urea Creat Gluc Chol Trig

/Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L

3M 111 57 39 191 1 5.84 34 7.45 2.55 0.53

112 98 44 191 1 7.09 33 8.87 1.08 1.06

113 100 48 310 2 6.85 50 10.83 1.76 0.63

114 83 38 175 2 7.82 36 10.31 1.16 0.65

115 79 42 257 2 7.39 34 12.56 2.38 0.82

116 65 31 190 1 5.93 31 7.03 1.47 0.76

117 80 40 129 1 7.07 28 7.79 1.17 0.45

118 101 31 245 1 4.18 34 6.83 1.16 0.77

119 63 41 266 1 5.76 34 9.38 1.49 0.77

120 55 34 298 2 6.02 49 14.55 1.45 0.86

4M 11 64 30 68 2 8.55 29 6.71 1.19 0.45

12 119 45 323 2 7.14 34 8.18 1.31 0.96

13 111 38 209 2 11.93 36 9.30 0.43 1.39

14 62 25 188 2 5.76 31 9.75 1.53 0.85

15 92 39 248 2 7.42 34 9.85 1.08 0.58

16 135 40 267 2 11.12 31 7.43 0.62 1.70

17 83 37 137 2 6.22 35 7.28 1.15 0.54

18 74 33 189 1 9.55 47 7.65 1.27 0.95

19 81 65 301 2 8.62 31 7.33 1.00 0.57

20 133 37 234 2 7.26 31 6.65 0.72 1.29
390

Huntingdon Life Sciences

WAG0014

APPENDIX 9 - continued

Blood chemistry - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Na K Cl Ca Phos Total Prot Alb A/G

/Sex Number mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio

3M 111 141 4.6 103 2.49 1.43 68 36 1.13

112 141 4.9 107 2.30 1.46 61 33 1.18

113 144 5.0 105 2.42 1.87 61 32 1.10

114 141 4.8 104 2.53 2.12 61 35 1.35

115 141 5.1 104 2.44 1.90 59 33 1.27

116 144 4.4 106 2.49 2.49 61 34 1.26

117 141 4.5 105 2.35 1.99 59 33 1.27

118 144 4.6 108 2.51 2.39 57 33 1.38

119 144 4.8 105 2.55 2.25 59 32 1.19

120 145 5.2 107 2.67 3.12 62 34 1.21

4M 11 145 3.7 111 2.34 1.61 57 33 1.38

12 139 4.7 107 2.47 1.99 59 34 1.36

13 143 4.0 105 2.38 2.90 60 35 1.40

14 143 4.9 109 2.46 2.10 61 34 1.26

15 140 5.5 106 2.53 2.30 64 36 1.29

16 145 5.0 112 2.44 2.85 59 36 1.57

17 144 4.4 107 2.47 2.87 60 34 1.31

18 142 5.0 109 2.46 2.66 58 33 1.32

19 143 4.3 106 2.43 2.83 60 35 1.40

20 142 3.9 104 2.42 2.53 61 35 1.35
391

Huntingdon Life Sciences

WAG0014

APPENDIX 9 - continued

Blood chemistry - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal ALP ALT AST Bili Urea Creat Gluc Chol Trig

/Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L

1F 21 30 21 65 2 6.07 47 6.59 2.47 0.46

22 35 20 63 1 5.75 38 8.14 2.16 0.71

23 37 29 77 2 6.88 45 5.76 2.20 0.49

24 38 20 54 2 5.59 42 8.34 1.94 0.42

25 30 28 57 1 5.36 36 8.93 2.46 0.51

26 67 19 77 2 7.87 44 8.96 1.94 0.29

28 42 35 83 1 6.45 38 9.04 2.77 0.43

29 45 22 69 1 7.58 40 9.97 1.71 0.82

30 50 24 66 1 6.59 37 9.89 1.50 0.50

2F 51 40 23 141 3 6.41 42 7.65 1.64 0.37

52 40 30 72 2 6.28 43 6.60 1.63 1.04

53 35 34 51 3 8.38 32 6.71 1.68 0.45

54 33 24 77 3 7.79 45 5.87 1.65 0.52

55 33 23 77 2 7.17 41 6.19 1.47 0.60

56 42 25 63 3 7.66 42 7.31 1.70 0.35

57 39 31 67 2 9.64 45 5.50 1.40 0.62

58 26 48 78 3 8.89 46 6.97 1.60 0.69

59 33 23 76 2 7.56 39 5.48 1.64 0.69

60 44 28 67 2 6.44 36 8.06 2.26 0.44
392

Huntingdon Life Sciences

WAG0014

APPENDIX 9 - continued

Blood chemistry - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Na K Cl Ca Phos Total Prot Alb A/G

/Sex Number mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio

1F 21 141 3.7 103 2.61 1.33 76 42 1.24

22 142 4.1 104 2.50 1.00 69 40 1.38

23 141 3.4 101 2.53 1.56 66 37 1.28

24 142 3.7 102 2.44 1.46 66 38 1.36

25 140 4.1 102 2.58 1.17 70 41 1.41

26 141 4.4 103 2.42 1.02 75 41 1.21

28 139 4.4 101 2.43 1.01 68 37 1.19

29 138 4.7 100 2.37 1.10 71 35 0.97

30 139 4.1 101 2.47 1.00 65 40 1.60

2F 51 142 3.9 105 2.43 1.69 69 40 1.38

52 141 4.0 104 2.41 1.67 65 40 1.60

53 141 4.2 104 2.55 1.58 71 42 1.45

54 140 3.5 101 2.34 1.67 66 39 1.44

55 143 3.9 110 2.37 1.73 62 36 1.38

56 142 3.6 105 2.42 1.82 63 37 1.42

57 141 3.5 103 2.48 1.79 63 37 1.42

58 143 3.3 100 2.57 1.69 70 42 1.50

59 143 3.5 106 2.37 1.70 64 37 1.37

60 141 3.4 104 2.37 1.49 63 36 1.33
393

Huntingdon Life Sciences

WAG0014

APPENDIX 9 - continued

Blood chemistry - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal ALP ALT AST Bili Urea Creat Gluc Chol Trig

/Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L

3F 1 58 25 217 2 8.32 40 9.77 1.18 0.53

2 49 21 191 2 6.01 49 12.85 2.09 0.54

3 32 64 274 3 9.14 52 4.25 1.36 0.32

4 32 20 104 2 8.84 43 9.70 1.51 0.55

5 41 32 93 1 7.95 32 6.48 2.95 0.44

6 43 38 328 1 8.10 39 8.18 1.92 0.71

7 44 22 85 3 6.46 37 5.52 0.78 0.84

8 42 36 174 2 7.47 50 6.30 1.73 0.61

9 58 34 204 2 8.15 48 7.97 2.34 0.94

10 39 28 177 2 9.58 39 6.82 2.35 0.40

4F 31 76 17 80 1 10.10 41 4.97 1.52 1.29

32 78 16 57 1 9.28 37 5.56 1.04 0.76

33 40 25 129 2 12.52 38 6.76 0.79 0.89

34 49 18 98 2 8.07 34 6.54 0.75 1.65

35 89 19 58 2 9.09 40 4.79 1.10 0.44

36 81 16 80 2 8.87 35 6.23 1.93 0.45

37 64 15 58 2 12.00 42 4.90 0.72 0.97

38 45 13 69 1 9.32 37 6.13 1.62 1.43

39 40 22 127 2 9.09 36 7.09 0.92 0.33

40 36 15 69 2 11.11 42 4.89 1.03 0.45
394

Huntingdon Life Sciences

WAG0014

APPENDIX 9 - continued

Blood chemistry - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Na K Cl Ca Phos Total Prot Alb A/G

/Sex Number mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio

3F 1 142 4.0 107 2.44 2.07 58 34 1.42

2 142 5.2 104 2.54 2.37 59 33 1.27

3 141 5.5 106 2.47 3.06 58 34 1.42

4 141 4.0 104 2.44 2.16 59 35 1.46

5 140 3.8 105 2.49 1.44 63 36 1.33

6 142 4.2 106 2.40 1.46 64 36 1.29

7 141 4.0 106 2.37 1.74 60 37 1.61

8 143 4.2 105 2.38 2.71 57 34 1.48

9 141 4.0 105 2.48 1.80 64 37 1.37

10 141 3.7 106 2.41 1.93 58 34 1.42

4F 31 141 4.8 109 2.36 3.11 61 33 1.18

32 145 4.3 110 2.26 3.60 58 31 1.15

33 138 4.0 99 2.31 2.18 60 37 1.61

34 141 3.8 103 2.42 2.89 65 39 1.50

35 140 4.2 106 2.40 3.07 57 33 1.38

36 137 4.3 104 2.37 2.27 64 33 1.06

37 141 3.8 106 2.30 3.37 59 34 1.36

38 140 4.3 105 2.47 2.83 63 38 1.52

39 139 4.8 108 2.43 2.26 62 36 1.38

40 140 3.9 104 2.34 2.49 61 39 1.77
395

Huntingdon Life Sciences

WAG0014

APPENDIX 9 - continued

Blood chemistry - individual observations during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal ALP ALT AST Bili Urea Creat Gluc Chol Trig

/Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L

1M 81 89 45 66 2 5.33 28 9.17 1.85 1.36

82 64 38 61 2 4.60 31 7.77 1.21 1.14

83 59 36 55 2 5.30 31 8.57 3.15 0.99

84 62 36 65 2 4.46 29 8.62 1.46 0.96

85 57 23 55 2 5.32 44 9.53 1.50 1.73

86 94 56 81 4 5.10 29 9.01 2.39 0.81

87 80 49 71 2 6.17 43 8.23 1.54 0.85

88 78 61 119 4 6.19 43 6.54 2.92 0.71

89 81 28 64 4 4.99 40 8.29 2.87 0.93

90 94 44 76 2 5.68 33 7.24 1.14 0.67

4M 71 87 33 53 2 5.75 31 6.51 2.11 0.98

72 84 31 52 1 4.79 32 7.97 1.71 0.91

73 60 39 78 2 5.78 35 5.73 1.37 0.42

74 102 25 64 2 5.41 47 6.21 1.67 0.56

75 84 56 162 3 6.71 45 8.13 1.91 0.60

76 118 63 74 2 5.78 36 5.82 1.53 0.23

77 75 41 65 2 4.91 32 6.12 1.36 0.37

78 80 29 57 1 5.36 32 6.96 1.37 0.73

79 113 38 65 2 6.13 31 7.40 1.35 0.76

80 123 50 92 3 5.24 37 7.22 1.79 0.78
396

Huntingdon Life Sciences

WAG0014

APPENDIX 9 - continued

Blood chemistry - individual observations during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Na K Cl Ca Phos Total Prot Alb A/G

/Sex Number mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio

1M 81 140 4.1 100 2.50 1.72 68 35 1.06

82 140 3.9 99 2.51 1.94 66 35 1.13

83 139 4.1 98 2.56 1.69 67 34 1.03

84 140 4.2 102 2.43 1.74 64 33 1.06

85 140 4.0 100 2.37 1.56 63 34 1.17

86 139 4.4 99 2.62 1.79 67 35 1.09

87 139 4.5 99 2.46 1.64 67 32 0.91

88 141 4.5 100 2.61 1.92 67 35 1.09

89 140 4.2 100 2.49 1.76 63 32 1.03

90 139 4.3 101 2.43 1.73 69 36 1.09

4M 71 141 4.3 100 2.55 2.02 69 37 1.16

72 139 4.4 101 2.54 2.26 64 34 1.13

73 140 4.0 101 2.48 1.64 65 35 1.17

74 140 4.4 101 2.47 1.98 65 35 1.17

75 140 4.3 101 2.52 1.81 65 35 1.17

76 140 4.3 101 2.41 1.64 63 33 1.10

77 140 5.0 100 2.49 1.72 63 35 1.25

78 140 4.5 100 2.58 2.12 63 33 1.10

79 140 4.9 102 2.51 1.79 64 35 1.21

80 139 5.0 101 2.57 1.86 71 36 1.03
397

Huntingdon Life Sciences

WAG0014

APPENDIX 9 - continued

Blood chemistry - individual observations during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal ALP ALT AST Bili Urea Creat Gluc Chol Trig

/Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L

1F 41 22 41 64 2 7.62 51 7.48 2.66 0.63

42 26 120 312 2 6.34 35 8.31 2.17 0.69

43 46 63 152 2 5.29 41 6.82 1.90 0.42

44 28 33 75 2 5.57 46 6.31 1.61 0.76

45 24 26 58 2 4.97 40 7.30 2.21 0.49

46 25 53 77 2 6.31 46 8.13 2.14 0.92

47 41 33 58 2 7.29 46 7.10 2.47 1.39

48 38 34 71 3 7.19 43 5.60 2.26 0.70

49 23 33 83 2 6.72 45 6.77 1.86 1.16

50 52 49 79 2 5.47 40 5.79 3.00 0.78

4F 91 56 29 60 2 5.86 40 7.40 1.76 0.77

92 46 69 151 2 6.72 38 8.49 2.31 1.15

93 31 69 162 2 6.26 41 7.26 2.74 0.54

94 49 64 141 1 5.91 44 6.64 2.51 0.61

95 38 45 97 2 8.10 39 5.41 1.26 0.39

96 39 32 59 2 5.23 40 7.45 1.58 0.68

97 50 65 104 1 6.50 44 6.39 1.09 0.46

98 51 35 82 2 5.78 40 6.98 1.49 0.72

99 44 57 126 2 4.96 46 5.77 1.76 0.47

100 38 32 70 1 6.36 41 6.39 1.92 0.66
398

Huntingdon Life Sciences

WAG0014

APPENDIX 9 - continued

Blood chemistry - individual observations during Week 4 of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Na K Cl Ca Phos Total Prot Alb A/G

/Sex Number mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio

1F 41 139 3.9 99 2.62 1.18 75 41 1.21

42 138 3.8 99 2.54 1.32 68 38 1.27

43 139 3.8 99 2.40 1.04 67 38 1.31

44 140 3.6 102 2.56 1.10 73 39 1.15

45 139 3.8 101 2.57 0.94 73 42 1.35

46 139 3.9 100 2.54 1.31 71 39 1.22

47 139 3.3 100 2.59 1.08 72 43 1.48

48 139 3.9 100 2.45 1.47 70 39 1.26

49 138 3.5 98 2.52 1.51 73 39 1.15

50 140 3.5 102 2.53 0.76 71 40 1.29

4F 91 140 3.4 101 2.44 1.16 68 36 1.13

92 139 3.4 101 2.49 1.30 72 41 1.32

93 140 4.0 102 2.42 1.07 70 40 1.33

94 140 3.7 102 2.44 1.15 69 38 1.23

95 138 3.8 99 2.32 1.47 62 35 1.30

96 142 3.5 103 2.33 0.97 68 40 1.43

97 141 3.6 103 2.31 1.13 64 38 1.46

98 139 5.4 104 2.35 1.27 68 36 1.13

99 140 4.5 104 2.40 0.93 67 40 1.48

100 140 3.6 102 2.41 1.02 66 38 1.36
399

Huntingdon Life Sciences

WAG0014

APPENDIX 9 - continued

Blood chemistry - individual observations sporadic sample

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal ALP ALT AST Bili Urea Creat Gluc Chol Trig

/Sex Number U/L U/L U/L μmol/L mmol/L μmol/L mmol/L mmol/L mmol/L

1F 27 86 27 196 1 11.51 24 16.14 2.01 1.75
400

Huntingdon Life Sciences

WAG0014

APPENDIX 9 - continued

Blood chemistry - individual observations sporadic sample

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Na K Cl Ca Phos Total Prot Alb A/G

/Sex Number mmol/L mmol/L mmol/L mmol/L mmol/L g/L g/L Ratio

1F 27 132 5.5 92 2.60 2.16 53 31 1.41
401

Huntingdon Life Sciences

WAG0014

APPENDIX 10

Urinalysis - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal App Vol pH SG Gluc Keto Bili UBld

/Sex Number mL g/L

1M 61 MY 6.4 7.3 1044 NEG 1+ NEG NEG

62 MY 6.2 7.1 1042 NEG 2+ NEG NEG

63 MY 4.0 8.2 1047 NEG 2+ NEG NEG

64 PY 7.2 7.0 1036 NEG TRA NEG NEG

65 MY 7.2 8.0 1035 NEG 1+ NEG NEG

66 MY 6.2 7.2 1038 NEG 1+ NEG TRA

67 MY 4.4 7.7 1078 NEG 1+ 1+ NEG

68 PY 3.8 8.6 1027 NEG 1+ NEG NEG

69 MY 5.0 8.5 1046 NEG 2+ NEG NEG

70 MY 2.4 6.2 1074 NEG 1+ 1+ NEG

2M 101 MY 6.2 7.3 1032 NEG 1+ NEG NEG

102 MY 4.4 6.7 1033 NEG 1+ NEG NEG

103 MY 7.0 7.3 1033 NEG 1+ NEG NEG

104 MY 5.0 6.5 1034 NEG 1+ NEG 2+

105 PY 8.4 7.1 1025 NEG 1+ NEG TRA

106 MY 9.5 7.2 1028 NEG 1+ NEG TRA

107 MY 9.2 7.3 1031 NEG 1+ NEG NEG

108 PY 6.4 6.9 1025 NEG TRA NEG NEG

109 MY 6.2 7.1 1029 NEG 2+ NEG TRA

110 PY 15.0 6.8 1020 NEG 2+ NEG TRA
402

Huntingdon Life Sciences

WAG0014

APPENDIX 10 - continued

Urinalysis - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal CAS A Leuc RBC Cryst Sperm Epi

/Sex Number /LPF

1M 61 0 0 0 0 TNQ 7 0

62 0 0 0 0 1 7 0

63 0 0 0 0 TNQ TNQ 0

64 0 0 0 0 12 0 0

65 0 0 0 0 1 0 0

66 0 0 0 0 9 0 0

67 0 0 0 0 23 0 0

68 0 0 0 0 5 0 0

69 0 0 0 0 4 2 0

70 0 0 0 0 3 0 0

2M 101 0 0 0 0 13 22 0

102 0 0 0 0 1 0 0

103 0 0 0 0 5 0 0

104 0 0 0 0 2 TNQ 0

105 0 0 0 0 16 0 0

106 0 0 0 0 6 0 0

107 0 0 0 0 13 TNQ 0

108 0 0 0 0 9 11 0

109 0 0 0 0 TNQ 0 0

110 0 0 0 0 2 TNQ 0
403

Huntingdon Life Sciences

WAG0014

APPENDIX 10 - continued

Urinalysis - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Prot TCLR TNAR TUKR

/Sex Number g/L mmol mmol mmol

1M 61 1.18 0.736 0.608 1.501

62 1.36 0.360 0.279 1.324

63 1.46 0.388 0.452 0.944

64 0.93 0.864 0.727 1.429

65 0.94 0.850 0.576 1.447

66 1.03 0.397 0.298 1.392

67 1.22 0.810 0.642 1.404

68 0.82 0.217 0.125 0.665

69 1.18 0.580 0.480 1.475

70 1.19 0.190 0.089 0.761

2M 101 0.80 0.564 0.434 0.998

102 1.28 0.317 0.374 0.629

103 0.82 0.546 0.490 1.215

104 0.87 0.520 0.395 0.915

105 0.63 0.613 0.706 0.903

106 0.75 0.589 0.589 1.216

107 1.19 1.040 0.975 1.481

108 0.76 0.371 0.461 0.483

109 2.57 0.471 0.533 0.822

110 0.67 0.885 1.005 1.245
404

Huntingdon Life Sciences

WAG0014

APPENDIX 10 - continued

Urinalysis - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal App Vol pH SG Gluc Keto Bili UBld

/Sex Number mL g/L

3M 111 PY 8.8 7.0 1029 NEG 1+ NEG NEG

112 MY 6.0 6.5 1033 NEG 2+ NEG TRA

113 PY 10.0 7.2 1026 NEG 1+ NEG 3+

114 PY 11.0 7.7 1021 NEG 1+ NEG NEG

115 PO 7.4 6.3 1032 NEG 1+ NEG TRA

116 PY 8.2 8.3 1023 NEG 1+ NEG TRA

117 PY 9.8 7.0 1025 NEG 1+ NEG TRA

118 PY 4.8 6.6 1029 NEG TRA NEG 1+

119 PY 15.5 6.8 1022 NEG 1+ NEG 2+

120 MY 7.2 7.5 1019 NEG 1+ NEG 2+

4M 11 PY 6.0 6.6 1022 NEG TRA NEG NEG

12 PY 10.5 6.3 1030 NEG 1+ NEG 2+

13 MY 10.5 6.3 1032 NEG 3+ NEG TRA

14 PO 7.0 6.5 1031 NEG 1+ 1+ NEG

15 MY 8.4 6.5 1030 NEG 3+ NEG 1+

16 DO 2.6 7.2 1050 NEG 3+ NEG 1+

17 MY 4.8 8.2 1062 NEG 1+ NEG TRA

18 PY 8.2 6.9 1023 NEG 1+ NEG NEG

19 MY 4.6 7.1 1044 NEG 3+ 1+ NEG

20 PY 10.5 6.0 1017 NEG 3+ NEG 1+
405

Huntingdon Life Sciences

WAG0014

APPENDIX 10 - continued

Urinalysis - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal CAS A Leuc RBC Cryst Sperm Epi

/Sex Number /LPF

3M 111 0 0 0 0 1 0 0

112 0 0 0 0 2 0 0

113 0 0 0 0 4 TNQ 0

114 0 0 0 0 0 3 0

115 0 0 0 0 5 9 0

116 0 0 0 0 1 0 0

117 0 0 0 0 0 2 0

118 0 0 0 0 0 0 0

119 0 0 0 0 0 1 0

120 0 0 0 0 TNQ TNQ 0

4M 11 0 0 0 0 2 0 0

12 0 0 0 0 2 0 0

13 0 0 0 0 1 0 0

14 0 0 0 0 1 0 0

15 0 0 0 0 1 11 0

16 0 0 0 0 3 2 0

17 0 0 0 0 0 0 0

18 0 0 0 0 1 0 0

19 0 0 0 0 TNQ 0 0

20 0 0 0 0 0 0 0
406

Huntingdon Life Sciences

WAG0014

APPENDIX 10 - continued

Urinalysis - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Prot TCLR TNAR TUKR

/Sex Number g/L mmol mmol mmol

3M 111 0.99 0.554 0.607 1.008

112 0.88 0.228 0.138 0.873

113 1.14 0.630 0.450 1.360

114 0.65 1.078 0.737 1.293

115 1.32 0.400 0.215 1.006

116 0.60 0.771 0.648 0.816

117 0.70 0.706 0.578 0.779

118 0.51 0.475 0.427 0.593

119 0.83 1.132 0.822 1.860

120 1.22 0.418 0.310 1.195

4M 11 0.14 0.660 0.444 0.585

12 0.48 0.725 0.977 0.662

13 0.63 1.166 1.061 1.229

14 1.15 0.658 0.427 0.903

15 1.24 0.748 0.798 0.895

16 1.15 0.255 0.226 0.475

17 0.65 0.389 0.202 0.542

18 0.56 0.804 0.746 0.754

19 1.01 0.391 0.373 0.683

20 0.88 0.966 0.830 1.470
407

Huntingdon Life Sciences

WAG0014

APPENDIX 10 - continued

Urinalysis - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal App Vol pH SG Gluc Keto Bili UBld

/Sex Number mL g/L

1F 21 PY 1.8 7.6 1040 NEG NEG NEG NEG

22 PY 1.4 6.0 1049 NEG TRA NEG NEG

23 MY 1.8 5.7 1064 NEG TRA NEG NEG

24 PY 1.4 6.5 1030 NEG NEG NEG NEG

25 MY 1.4 5.9 1076 NEG 1+ 1+ NEG

26 MY 3.0 6.3 1058 NEG TRA NEG NEG

28 PY 5.6 6.5 1029 NEG NEG NEG NEG

29 PY 3.6 6.4 1034 NEG NEG NEG NEG

30 PY 5.2 6.6 1033 NEG NEG NEG NEG

2F 51 PY 5.6 7.0 1026 NEG TRA NEG NEG

52 MY 2.8 6.3 1046 NEG TRA NEG NEG

53 PY 7.6 6.6 1026 NEG NEG NEG NEG

54 MY 2.2 6.7 1068 NEG 1+ 1+ NEG

55 PY 7.0 6.5 1030 NEG TRA NEG NEG

56 MY 1.6 6.3 1072 NEG 1+ 1+ NEG

57 PY 4.8 6.8 1028 NEG TRA NEG NEG

58 MY 3.2 6.0 1043 NEG NEG NEG NEG

59 MY 2.4 6.2 1066 NEG TRA 1+ NEG

60 MY 4.2 6.3 1033 NEG TRA NEG NEG
408

Huntingdon Life Sciences

WAG0014

APPENDIX 10 - continued

Urinalysis - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal CAS A Leuc RBC Cryst Sperm Epi

/Sex Number /LPF

1F 21 0 0 0 0 1 0 0

22 INS INS INS INS INS INS INS

23 0 0 0 0 0 0 0

24 INS INS INS INS INS INS INS

25 INS INS INS INS INS INS INS

26 0 0 0 0 0 0 0

28 0 0 0 0 0 0 0

29 0 0 0 0 0 0 0

30 0 0 0 0 0 0 0

2F 51 0 0 0 0 1 0 0

52 0 0 0 0 0 0 0

53 0 0 0 0 1 0 0

54 0 0 0 0 TNQ 0 0

55 0 0 0 0 0 0 0

56 INS INS INS INS INS INS INS

57 0 0 0 0 7 0 0

58 0 0 0 0 1 0 0

59 0 0 0 0 2 0 0

60 0 0 0 0 1 0 0
409

Huntingdon Life Sciences

WAG0014

APPENDIX 10 - continued

Urinalysis - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Prot TCLR TNAR TUKR

/Sex Number g/L mmol mmol mmol

1F 21 0.18 0.085 0.205 0.391

22 0.28 0.176 0.165 0.240

23 0.32 0.191 0.148 0.327

24 0.18 0.034 0.070 0.190

25 0.40 0.217 0.217 0.391

26 0.27 0.177 0.333 0.726

28 0.21 0.414 0.414 0.728

29 0.22 0.313 0.349 0.436

30 0.15 0.255 0.265 0.907

2F 51 0.09 0.213 0.347 0.596

52 0.24 0.188 0.151 0.500

53 0.10 0.471 0.372 0.840

54 0.17 0.163 0.156 0.712

55 0.09 0.315 0.686 0.725

56 0.40 0.230 0.184 0.325

57 0.09 0.456 0.451 0.586

58 0.26 0.429 0.291 0.630

59 0.22 0.108 0.185 0.544

60 0.15 0.168 0.122 0.617
410

Huntingdon Life Sciences

WAG0014

APPENDIX 10 - continued

Urinalysis - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal App Vol pH SG Gluc Keto Bili UBld

/Sex Number mL g/L

3F 1 PY 6.6 6.0 1030 NEG 1+ NEG TRA

2 PY 1.2 5.9 1032 NEG TRA NEG NEG

3 PY 4.8 6.9 1032 NEG 2+ NEG NEG

4 PY 7.8 5.8 1024 NEG 1+ NEG NEG

5 PY 7.6 6.8 1025 NEG TRA NEG NEG

6 MY 3.6 6.0 1039 NEG 1+ NEG TRA

7 MY 4.8 6.5 1035 NEG 1+ NEG NEG

8 MY 2.6 6.7 1036 NEG 1+ NEG NEG

9 MY 6.2 5.9 1033 NEG 1+ NEG TRA

10 MY 4.6 6.5 1034 NEG 1+ NEG NEG

4F 31 PY 5.8 5.8 1021 NEG 2+ NEG NEG

32 PY 0.6 INS 1050 NEG 2+ NEG NEG

33 PY 6.8 5.5 1032 NEG 2+ NEG NEG

34 MY 5.4 6.9 1029 NEG 2+ NEG NEG

35 DY 2.4 6.4 1044 NEG 3+ NEG NEG

36 MY 7.0 6.0 1030 NEG 2+ NEG NEG

37 PY 4.8 6.1 1026 NEG 2+ NEG TRA

38 PY 6.0 5.7 1027 NEG 2+ NEG NEG

39 MY 2.2 5.8 1066 NEG 3+ NEG NEG

40 MY 4.2 5.5 1034 NEG 3+ NEG NEG
411

Huntingdon Life Sciences

WAG0014

APPENDIX 10 - continued

Urinalysis - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal CAS A Leuc RBC Cryst Sperm Epi

/Sex Number /LPF

3F 1 0 0 0 0 0 0 0

2 INS INS INS INS INS INS INS

3 0 0 0 0 0 0 0

4 0 0 0 0 0 0 0

5 0 0 0 0 1 0 0

6 0 0 0 0 0 0 0

7 0 0 0 0 2 0 0

8 0 0 0 0 0 0 0

9 0 0 0 0 0 0 0

10 0 0 0 0 1 0 0

4F 31 0 0 0 0 0 0 0

32 INS INS INS INS INS INS INS

33 0 0 0 0 0 0 0

34 0 0 0 0 0 0 0

35 0 0 0 0 0 0 0

36 0 0 0 0 0 0 0

37 0 0 0 0 0 0 0

38 0 0 0 0 0 0 0

39 0 0 0 0 TNQ 0 0

40 0 0 0 0 0 0 0
412

Huntingdon Life Sciences

WAG0014

APPENDIX 10 - continued

Urinalysis - individual observations during Week 13 of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group Animal Prot TCLR TNAR TUKR

/Sex Number g/L mmol mmol mmol

3F 1 0.11 0.680 0.601 0.832

2 0.20 0.065 0.096 0.110

3 0.11 0.278 0.413 0.545

4 0.10 0.577 0.484 0.527

5 0.10 0.426 0.494 0.688

6 0.23 0.076 0.083 0.641

7 0.15 0.437 0.307 0.521

8 0.15 0.286 0.208 0.309

9 0.13 0.415 0.453 0.843

10 0.16 0.511 0.543 0.474

4F 31 0.55 0.319 0.168 0.328

32 INS INS INS INS

33 0.10 0.707 0.435 0.887

34 0.11 0.594 0.416 0.413

35 0.17 0.382 0.146 0.383

36 0.16 0.903 0.686 0.784

37 0.09 0.384 0.216 0.192

38 0.17 0.552 0.336 0.495

39 0.27 0.130 0.081 0.216

40 0.18 0.525 0.256 0.321
413

Huntingdon Life Sciences

WAG0014

APPENDIX 11 Request ID: 289241

Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal

Number

Terminal 

Bodyweight

Adrenals Brain Epididymides Heart Kidneys Liver Lungs + 

Bronchi

Pituitary Prostate

1M 61 631 0.052 2.159 1.812 2.085 3.556 21.287 1.764 0.011 1.212

62 580 0.055 2.101 1.533 1.984 3.469 20.036 1.921 0.019 1.225

63 627 0.061 2.256 1.637 1.883 3.462 21.249 1.851 0.013 1.143

64 649 0.072 2.197 1.394 2.037 3.766 21.404 1.778 0.022 1.470

65 574 0.062 2.110 1.483 2.168 3.483 20.323 1.530 0.013 1.048

66 691 0.059 2.102 1.395 1.680 3.509 23.517 1.988 0.013 1.358

67 575 0.045 2.086 1.584 1.587 3.336 17.945 1.909 0.012 1.203

68 533 0.049 2.045 1.423 1.457 2.859 18.173 1.527 0.012 1.145

69 596 0.041 2.019 1.392 1.649 3.019 20.920 1.746 0.011 0.947

70 555 0.065 2.059 1.565 1.518 3.288 18.717 1.596 0.014 1.704

2M 101 574 0.044 2.085 1.312 1.574 3.499 21.994 1.877 0.015 1.306

102 463 0.043 2.166 1.440 1.611 2.760 18.184 1.669 0.012 0.819

103 585 0.066 2.052 1.358 1.609 3.515 21.784 1.801 0.012 1.241

104 519 0.049 2.099 1.361 1.543 2.967 17.557 1.537 0.017 1.099

105 521 0.052 2.112 1.394 1.555 2.759 15.705 1.652 0.014 1.012

106 537 0.045 1.985 1.283 1.741 2.754 16.189 1.470 0.008 1.361

107 500 0.037 2.071 1.297 1.510 2.552 13.760 1.474 0.008 0.920

108 543 0.040 2.210 1.463 2.164 3.087 18.005 1.835 0.011 0.923

109 449 0.048 2.108 1.208 1.893 2.512 14.650 1.513 0.008 1.000

110 508 0.039 1.947 1.438 1.557 2.830 15.648 1.720 0.010 0.845
414

Huntingdon Life Sciences

WAG0014

APPENDIX 11 - continued Request ID: 289241

Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal

Number

Salivary

Glands

Seminal 

Vesicles

Spleen Testes Thymus Thyroids + 

Paras

1M 61 0.784 2.002 1.036 3.824 0.276 0.032

62 0.753 2.098 0.981 4.197 0.272 0.021

63 0.791 1.715 0.908 4.290 0.258 0.018

64 0.759 2.177 0.833 3.691 0.284 0.031

65 0.769 1.804 0.956 3.572 0.323 0.031

66 0.793 2.003 1.099 3.849 0.438 0.023

67 0.579 2.332 0.978 4.124 0.326 0.026

68 0.653 2.143 0.760 4.017 0.228 0.021

69 0.701 2.241 0.914 3.476 0.175 0.029

70 0.657 2.157 1.008 3.943 0.221 0.021

2M 101 0.600 1.879 0.876 3.375 0.304 0.019

102 0.499 2.245 0.828 3.407 0.248 0.029

103 0.605 1.079 1.086 3.771 0.412 0.031

104 0.623 2.124 0.726 3.204 0.258 0.026

105 0.564 1.666 0.916 3.748 0.171 0.029

106 0.503 1.943 0.726 3.497 0.282 0.023

107 0.657 1.413 0.689 3.324 0.184 0.016

108 0.692 1.914 1.072 4.210 0.185 0.026

109 0.541 1.050 0.706 3.911 0.266 0.018

110 0.594 1.794 1.045 3.685 0.240 0.033
415

Huntingdon Life Sciences

WAG0014

APPENDIX 11 - continued Request ID: 289241

Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal

Number

Terminal 

Bodyweight

Adrenals Brain Epididymides Heart Kidneys Liver Lungs + 

Bronchi

Pituitary Prostate

3M 111 578 0.051 2.098 1.528 1.664 2.939 19.625 1.665 0.014 0.833

112 460 0.036 1.920 1.160 1.322 2.756 14.903 1.394 0.011 0.999

113 537 0.056 2.021 1.403 1.991 2.897 18.137 1.965 0.015 1.037

114 493 0.055 1.981 1.370 1.492 2.536 15.675 1.620 0.015 1.068

115 472 0.051 2.063 1.422 1.597 3.012 17.853 1.454 0.013 0.984

116 457 0.038 2.004 1.168 1.152 2.767 13.777 1.561 0.009 0.739

117 429 0.041 2.012 1.121 1.278 2.311 13.829 1.558 0.007 0.789

118 457 0.041 2.096 1.243 1.383 2.677 13.232 1.641 0.009 0.694

119 499 0.059 1.981 1.303 1.527 2.837 15.636 1.696 0.014 0.665

120 585 0.039 2.170 1.202 1.770 3.077 20.438 1.881 0.011 1.054

4M 11 380 0.038 1.887 1.006 1.279 2.169 12.431 1.485 0.013 0.552

12 428 0.049 2.008 1.370 1.299 2.357 14.366 1.548 0.013 0.861

13 446 0.056 2.036 1.277 1.589 2.930 17.110 1.705 0.010 0.919

14 450 0.039 2.049 1.221 1.324 2.582 15.179 1.500 0.012 1.106

15 451 0.042 1.952 1.210 1.293 2.348 15.185 1.500 0.016 0.842

16 362 0.042 1.754 0.945 1.440 2.132 11.720 1.431 0.008 0.610

17 419 0.039 1.926 1.363 1.600 2.349 12.868 1.446 0.007 1.172

18 421 0.042 1.967 1.015 1.355 2.594 15.614 1.476 0.008 0.643

19 380 0.034 1.915 1.069 1.257 2.040 12.474 1.368 0.008 0.758

20 433 0.055 1.904 1.308 1.727 2.255 15.165 1.598 0.012 0.862
416

Huntingdon Life Sciences

WAG0014

APPENDIX 11 - continued Request ID: 289241

Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal

Number

Salivary

Glands

Seminal 

Vesicles

Spleen Testes Thymus Thyroids + 

Paras

3M 111 0.586 1.291 1.052 4.302 0.320 0.032

112 0.547 1.199 0.684 2.980 0.302 0.016

113 0.557 1.856 0.715 4.015 0.185 0.017

114 0.636 1.471 1.080 4.082 0.210 0.035

115 0.575 1.672 0.977 3.884 0.126 0.023

116 0.666 1.557 0.840 3.211 0.167 0.030

117 0.453 1.048 0.654 3.423 0.130 0.018

118 0.500 1.134 0.840 3.464 0.246 0.019

119 0.557 1.611 0.988 3.753 0.201 0.026

120 0.724 1.686 1.068 3.330 0.315 0.031

4M 11 0.399 1.293 0.761 2.808 0.139 0.024

12 0.539 1.347 0.811 3.645 0.100 0.016

13 0.483 1.267 0.764 3.363 0.110 0.038

14 0.516 1.829 0.623 2.919 0.128 0.019

15 0.445 1.247 0.688 3.455 0.121 0.023

16 0.612 0.582 0.532 2.892 0.097 0.028

17 0.607 1.486 0.621 3.656 0.091 0.012

18 0.409 1.122 0.788 3.118 0.114 0.029

19 0.503 1.016 0.623 3.096 0.135 0.019

20 0.651 1.602 0.736 3.428 0.074 0.022
417

Huntingdon Life Sciences

WAG0014

APPENDIX 11 - continued Request ID: 289241

Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal

Number

Terminal 

Bodyweight

Adrenals Brain Heart Kidneys Liver Lungs + 

Bronchi

Ovaries Pituitary Salivary

Glands

1F 21 316 0.070 2.098 1.067 1.805 10.947 1.293 0.091 0.017 0.474

22 271 0.046 1.984 0.913 1.798 8.691 1.129 0.103 0.020 0.384

23 271 0.073 1.896 1.171 1.730 10.024 1.257 0.093 0.020 0.432

24 318 0.062 1.946 1.204 1.657 9.619 1.339 0.100 0.019 0.473

25 277 0.061 1.921 1.062 2.123 9.143 1.172 0.111 0.020 0.475

26 326 0.041 1.960 1.342 1.647 11.007 1.292 0.079 0.013 0.454

28 337 0.062 1.934 1.027 1.750 11.205 1.314 0.108 0.017 0.503

29 300 0.059 1.900 1.034 1.581 8.513 1.207 0.099 0.014 0.395

30 307 0.058 1.947 1.309 1.688 8.228 1.157 0.078 0.015 0.444

2F 51 293 0.063 1.845 1.081 1.989 8.800 1.219 0.089 0.020 0.366

52 287 0.053 2.049 1.194 1.698 9.442 1.124 0.060 0.021 0.346

53 297 0.064 1.887 1.045 1.700 10.402 1.171 0.104 0.016 0.321

54 278 0.065 1.810 0.992 2.016 9.912 1.322 0.075 0.017 0.430

55 285 0.065 1.896 1.087 1.796 11.760 1.082 0.072 0.018 0.412

56 315 0.065 1.956 0.956 1.924 10.121 1.272 0.104 0.016 0.364

57 296 0.076 1.865 1.137 1.783 11.572 1.341 0.096 0.015 0.364

58 306 0.064 1.855 1.023 1.926 10.830 1.243 0.062 0.013 0.316

59 320 0.080 1.810 1.110 2.039 12.382 1.354 0.096 0.012 0.364

60 288 0.064 1.754 1.055 1.541 10.809 1.145 0.073 0.015 0.352
418

Huntingdon Life Sciences

WAG0014

APPENDIX 11 - continued Request ID: 289241

Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal

Number

Spleen Thymus Thyroids + 

Paras

Uterus + 

Cervix

1F 21 0.638 0.168 0.023 1.319

22 0.502 0.172 0.021 0.585

23 0.623 0.251 0.015 0.636

24 0.600 0.273 0.025 1.189

25 0.558 0.208 0.008 0.703

26 0.718 0.271 0.020 0.515

28 0.852 0.293 0.018 0.659

29 0.637 0.199 0.009 0.555

30 0.422 0.230 0.014 0.606

2F 51 0.628 0.190 0.025 0.693

52 0.490 0.129 0.016 0.730

53 0.432 0.168 0.017 1.125

54 0.423 0.136 0.020 0.779

55 0.608 0.227 0.027 0.665

56 0.591 0.287 0.027 0.835

57 0.563 0.265 0.024 0.690

58 0.539 0.250 0.025 0.484

59 0.554 0.148 0.019 0.949

60 0.564 0.165 0.030 0.702
419

Huntingdon Life Sciences

WAG0014

APPENDIX 11 - continued Request ID: 289241

Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal

Number

Terminal 

Bodyweight

Adrenals Brain Heart Kidneys Liver Lungs + 

Bronchi

Ovaries Pituitary Salivary

Glands

3F 1 294 0.059 1.857 1.049 1.979 10.039 1.493 0.096 0.017 0.327

2 297 0.057 1.836 1.013 2.032 10.858 1.263 0.049 0.018 0.348

3 233 0.056 1.761 0.825 1.600 7.227 1.129 0.071 0.015 0.399

4 298 0.051 1.936 1.026 2.046 9.512 1.331 0.078 0.015 0.338

5 294 0.059 1.897 1.025 1.987 10.084 1.324 0.071 0.017 0.294

6 304 0.064 1.921 1.016 1.878 10.960 1.230 0.061 0.019 0.443

7 257 0.058 1.931 0.871 1.761 8.849 1.104 0.130 0.013 0.339

8 291 0.060 1.813 1.067 1.695 9.265 1.183 0.075 0.012 0.406

9 271 0.054 1.733 0.925 1.870 9.936 1.313 0.083 0.011 0.328

10 291 0.050 1.916 0.864 1.667 10.050 1.405 0.088 0.010 0.373

4F 31 211 0.034 1.575 1.062 1.595 7.823 1.060 0.042 0.009 0.360

32 205 0.032 1.585 1.191 1.585 9.220 1.155 0.071 0.009 0.301

33 293 0.071 1.884 1.009 2.053 11.395 1.316 0.085 0.019 0.416

34 269 0.050 1.797 0.997 1.612 9.251 1.143 0.084 0.014 0.334

35 259 0.055 1.808 0.983 1.779 9.967 1.307 0.103 0.011 0.380

36 265 0.047 1.757 1.124 1.744 8.992 1.301 0.108 0.010 0.362

37 249 0.062 1.759 1.191 1.788 9.805 1.284 0.074 0.011 0.237

38 247 0.056 1.729 0.997 1.561 8.927 1.429 0.075 0.010 0.344

39 282 0.064 1.921 0.965 1.653 10.898 1.305 0.090 0.010 0.440

40 262 0.060 1.897 0.949 1.874 10.108 1.266 0.076 0.011 0.362
420

Huntingdon Life Sciences

WAG0014

APPENDIX 11 - continued Request ID: 289241

Organ weights - individual absolute values (g) for animals killed after 13 weeks of treatment

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal

Number

Spleen Thymus Thyroids + 

Paras

Uterus + 

Cervix

3F 1 0.548 0.208 0.022 0.595

2 0.596 0.225 0.024 0.654

3 0.368 0.131 0.019 0.534

4 0.542 0.185 0.012 0.519

5 0.684 0.162 0.021 0.897

6 0.625 0.243 0.022 1.020

7 0.452 0.138 0.011 0.641

8 0.619 0.153 0.016 0.875

9 0.471 0.085 0.019 1.211

10 0.478 0.138 0.018 0.460

4F 31 0.509 0.047 0.009 0.705

32 0.814 0.015 0.016 0.232

33 0.558 0.115 0.027 1.449

34 0.378 0.116 0.025 0.463

35 1.268 0.109 0.022 0.549

36 0.881 0.087 0.021 0.481

37 0.707 0.049 0.022 0.434

38 0.610 0.079 0.026 0.584

39 0.586 0.100 0.017 0.506

40 0.673 0.056 0.020 0.558
421

Huntingdon Life Sciences

WAG0014

APPENDIX 11 - continued Request ID: 289499

Organ weights - individual absolute values (g) for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal

Number

Terminal 

Bodyweight

Adrenals Brain Epididymides Heart Kidneys Liver Lungs + 

Bronchi

Pituitary Prostate

1M 81 632 0.061 2.082 1.437 1.678 3.883 25.493 1.985 0.011 1.071

82 609 0.078 2.214 1.501 2.164 3.192 17.177 1.893 0.013 1.577

83 647 0.073 2.215 1.818 1.717 3.641 24.667 1.722 0.018 1.375

84 625 0.054 2.062 1.664 1.728 3.448 19.070 1.890 0.012 1.160

85 706 0.035 2.167 1.775 2.176 2.759 16.907 1.752 0.014 1.398

86 629 0.058 2.335 1.663 1.687 3.757 22.550 1.811 0.016 1.316

87 555 0.071 2.140 1.394 1.607 3.044 21.133 1.674 0.017 1.296

88 608 0.055 1.993 1.403 1.488 2.870 21.126 1.708 0.015 1.074

89 755 0.055 2.209 1.945 2.387 3.589 22.009 1.921 0.025 1.127

90 465 0.062 1.954 1.377 1.274 2.633 13.874 1.444 0.012 1.164

4M 71 490 0.054 2.006 1.326 1.804 2.906 16.147 1.690 0.011 1.401

72 559 0.048 2.056 1.331 2.254 2.953 17.961 1.867 0.012 1.217

73 433 0.063 1.964 1.230 1.573 2.305 14.771 1.487 0.007 0.959

74 491 0.053 2.082 1.394 1.472 2.655 14.370 1.586 0.013 1.474

75 544 0.052 1.986 1.168 1.852 2.606 18.998 1.571 0.017 0.832

76 532 0.039 2.032 1.634 1.699 2.925 18.133 1.887 0.011 1.357

77 466 0.042 1.998 1.284 1.331 2.645 15.519 1.523 0.009 1.910

78 476 0.065 2.168 1.220 1.752 2.502 15.193 1.522 0.005 1.064

79 408 0.045 1.756 1.359 1.529 2.241 15.582 1.340 0.010 0.884

80 422 0.069 1.887 1.253 1.443 2.481 15.314 1.444 0.010 1.170
422

Huntingdon Life Sciences

WAG0014

APPENDIX 11 - continued Request ID: 289499

Organ weights - individual absolute values (g) for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal

Number

Salivary

Glands

Seminal 

Vesicles

Spleen Testes Thymus Thyroids + 

Paras

1M 81 0.765 2.454 0.749 3.681 0.180 0.030

82 0.819 1.649 0.872 3.928 0.253 0.022

83 0.822 2.249 1.040 4.244 0.386 0.024

84 0.759 1.966 0.980 3.928 0.164 0.033

85 0.862 1.398 0.723 4.106 0.247 0.033

86 0.839 2.531 1.280 4.090 0.139 0.020

87 0.754 1.966 0.796 3.635 0.237 0.032

88 0.716 1.952 0.867 3.342 0.182 0.023

89 0.870 2.275 1.220 4.160 0.332 0.040

90 0.570 1.791 0.511 3.309 0.184 0.019

4M 71 0.542 2.084 0.921 3.718 0.214 0.024

72 0.650 1.837 0.939 3.924 0.161 0.030

73 0.640 1.815 0.756 3.570 0.071 0.021

74 0.588 1.878 0.777 3.981 0.155 0.026

75 0.728 2.058 0.680 3.400 0.235 0.027

76 0.655 2.053 0.980 4.771 0.147 0.020

77 0.631 2.028 0.871 3.713 0.168 0.024

78 0.673 1.167 0.941 3.584 0.169 0.030

79 0.664 1.938 1.152 3.686 0.160 0.021

80 0.441 1.529 0.889 3.466 0.155 0.028
423

Huntingdon Life Sciences

WAG0014

APPENDIX 11 - continued Request ID: 289499

Organ weights - individual absolute values (g) for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal

Number

Terminal 

Bodyweight

Adrenals Brain Heart Kidneys Liver Lungs + 

Bronchi

Ovaries Pituitary Salivary

Glands

1F 41 306 0.057 1.854 1.054 1.655 8.641 1.145 0.073 0.013 0.467

42 329 0.061 1.953 1.305 1.872 8.009 1.323 0.072 0.016 0.460

43 301 0.063 1.900 1.035 1.981 8.588 1.171 0.088 0.014 0.448

44 350 0.114 2.090 1.420 2.319 11.281 1.424 0.219 0.020 0.449

45 293 0.055 1.833 0.981 1.730 8.651 1.240 0.078 0.017 0.411

46 325 0.051 1.856 0.916 1.983 9.267 1.189 0.073 0.022 0.451

47 335 0.047 1.803 1.148 1.718 10.058 1.147 0.064 0.017 0.420

48 303 0.054 2.026 0.933 1.656 8.240 1.237 0.080 0.016 0.458

49 301 0.087 1.957 1.011 1.884 10.860 1.352 0.091 0.021 0.416

50 280 0.060 1.835 0.852 1.782 9.870 1.192 0.084 0.014 0.422

4F 91 281 0.075 1.772 1.320 1.726 9.451 1.231 0.104 0.013 0.418

92 237 0.054 1.758 1.115 1.571 7.935 1.102 0.040 0.012 0.408

93 261 0.050 1.834 1.007 1.925 7.942 1.242 0.062 0.015 0.414

94 253 0.049 1.936 1.426 1.608 7.161 1.300 0.084 0.013 0.499

95 298 0.069 1.918 1.258 1.729 8.820 1.407 0.125 0.015 0.493

96 261 0.052 1.720 1.105 1.820 8.246 1.114 0.070 0.016 0.397

97 251 0.056 1.682 1.030 1.462 7.461 1.057 0.118 0.014 0.390

98 253 0.063 1.725 1.039 1.741 9.227 1.357 0.080 0.016 0.420

99 289 0.052 1.895 1.102 1.863 8.494 1.240 0.917 0.015 0.515

100 263 0.064 1.878 0.927 2.070 9.552 1.167 0.099 0.015 0.442
424

Huntingdon Life Sciences

WAG0014

APPENDIX 11 - continued Request ID: 289499

Organ weights - individual absolute values (g) for animals killed after 4 weeks of recovery

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Group

/Sex

Animal

Number

Spleen Thymus Thyroids + 

Paras

Uterus + 

Cervix

1F 41 0.449 0.121 0.017 1.220

42 0.593 0.205 0.018 0.582

43 0.548 0.103 0.020 0.780

44 0.691 0.170 0.019 0.824

45 0.487 0.159 0.021 0.522

46 0.570 0.161 0.024 1.051

47 0.500 0.141 0.033 0.670

48 0.553 0.143 0.024 1.387

49 0.564 0.160 0.021 1.151

50 0.535 0.186 0.017 0.541

4F 91 0.487 0.198 0.016 0.679

92 0.443 0.231 0.032 0.754

93 0.531 0.156 0.025 0.667

94 0.497 0.136 0.023 0.636

95 0.651 0.146 0.016 0.662

96 0.513 0.199 0.026 0.689

97 0.463 0.149 0.027 0.647

98 0.529 0.218 0.024 0.661

99 1.058 0.165 0.022 0.683

100 0.489 0.185 0.025 0.729
425

Huntingdon Life Sciences

WAG0014

APPENDIX 12 Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 61 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 630.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Kidneys Kidneys

 Pelvic dilatation, Left, Slight No significant lesions

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Thyroids

 Follicular Cell Vacuolation, Bilateral, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, LN Bronchial, LN 

Mandibular, LN Mesenteric, Lachrymal Glands, Larynx, Liver, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., 

Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. 

Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Testes, Thymus, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder
426

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 62 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 580.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Kidneys

 Cortical Tubular Basophilia, Focal, Slight

LN Mandibular

 Plasmacytosis, Moderate

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi Lungs + Bronchi

 Pale area(s), Left, Punctate, One, subpleural. Arterial Mural Mineralisation, Minimal

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, LN Bronchial, LN 

Mesenteric, Lachrymal Glands, Larynx, Mammary, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, 

Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, 

Stomach, Teeth, Testes, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder
427

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 63 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 626.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Adrenals

 Cortical Vacuolation, Bilateral, Minimal

LN Mandibular

 Plasmacytosis, Slight

 Sinus Histiocytosis, Slight

Lachrymal Glands

 Lymphoid Aggregates, Focal, Minimal

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

 Aggregations of Alveolar Macrophages, Minimal
428

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 63 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 626.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight

 Nasolacrimal Duct Epithelial Degeneration, Slight

Prostate

 Lymphoid Aggregates, Focal, Minimal

Spleen Spleen

 Capsule thickened Capsular Thickening, Slight

Thyroids

 Follicular Cell Vacuolation, Bilateral, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, Kidneys, LN Bronchial, LN 

Mesenteric, Larynx, Mammary, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, 

Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Teeth, Testes, Thymus, Tongue, 

Trachea, Tracheal Bifurc., Urinary Bladder
429

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 64 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 648.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

LN Mandibular

 Sinus Histiocytosis, Minimal

Lungs + Bronchi

 Alveolitis, Minimal

Mammary

 Acinar Atrophy, Slight

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight

 Nasopharynx - Goblet Cell Hyperplasia, Slight

Prostate

 Lymphoid Aggregates, Focal, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, Kidneys, LN 

Bronchial, LN Mesenteric, Lachrymal Glands, Larynx, Liver, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, 

Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, 

Stomach, Teeth, Testes, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder
430

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 65 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 574.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Adrenals

 Cortical Vacuolation, Bilateral, Minimal

Eyes

 Retinal Rosettes/Folds, Unilateral, Minimal

Femur inc. Joint

 Synovitis, Minimal

LN Mandibular

 Plasmacytosis, Slight

Lungs + Bronchi

 Alveolitis, Minimal

 Perivascular Inflammatory Cells, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight
431

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 65 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 574.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Prostate

 Lymphoid Aggregates, Focal, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Harderian Glands, Heart, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Lachrymal 

Glands, Liver, Mammary, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, 

Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Testes, Thymus, 

Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder
432

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 66 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 690.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Adrenals

 Cortical Vacuolation, Bilateral, Minimal

Heart

 Infiltrate, Cellular, Myocardium, Minimal

LN Mandibular

 Plasmacytosis, Moderate

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

 Perivascular Inflammatory Cells, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Prostate

 Lymphoid Aggregates, Focal, Minimal

Stomach

 Submucosal Inflammation - Glandular Region, Minimal
433

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 66 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 690.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Thyroids

 Follicular Cell Vacuolation, Bilateral, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN 

Mesenteric, Lachrymal Glands, Liver, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, 

Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, 

Teeth, Testes, Thymus, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder
434

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 67 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 575.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Kidneys

 Perivascular Lymphoid Aggregations, Focal, Minimal

LN Bronchial

 Paracortex - Increased Cellularity, Slight

LN Mandibular

 Plasmacytosis, Marked

Liver

 Inflammation, Focal, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

 Foreign Body Reaction - Ventral Pouch, Focal, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, LN Mesenteric, 

Lachrymal Glands, Lungs + Bronchi, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, 

Prostate, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + 

Marrow, Stomach, Teeth, Testes, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder
435

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 68 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 532.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Adrenals

 Cortical Vacuolation, Bilateral, Minimal

LN Mandibular

 Sinus Histiocytosis, Minimal

Liver Liver

 Dark area(s), Median lobe, One, subcapsular, 2mm. Inflammation, Focal, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Prostate

 Lymphoid Aggregates, Focal, Moderate

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, Kidneys, LN Bronchial, LN 

Mesenteric, Lachrymal Glands, Larynx, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, 

Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, 

Stomach, Teeth, Testes, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder
436

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 69 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 595.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Adrenals

 Cortical Vacuolation, Bilateral, Slight

Heart

 Infiltrate, Cellular, Myocardium, Minimal

LN Bronchial

 Tissue missing

LN Mandibular

 Plasmacytosis, Slight

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Perivascular Inflammatory Cells, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight
437

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 69 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 595.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

Thyroids

 Follicular Cell Vacuolation, Bilateral, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Mesenteric, Lachrymal 

Glands, Mammary, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, 

Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Testes, Thymus, 

Tongue, Trachea, Urinary Bladder
438

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 70 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 555.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Adrenals

 Cortical Vacuolation, Slight

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Kidneys

 Perivascular Lymphoid Aggregations, Focal, Minimal

Liver

 Inflammation, Focal, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Mammary

 Acinar Atrophy, Slight

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Minimal

 Nasolacrimal Duct Epithelial Degeneration, Slight
439

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 70 Sex: Male Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 555.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Prostate

 Lymphoid Aggregates, Focal, Slight

Rectum

 Submucosal Oedema, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Bronchial, LN Mandibular, LN 

Mesenteric, Lachrymal Glands, Lungs + Bronchi, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Salivary Glands, 

Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Testes, 

Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder
440

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 81 Sex: Male Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 632.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi Lungs + Bronchi

 Dark area(s), A few, subpleural, up to 3mm. Arterial Mural Mineralisation, Slight

 Aggregations of Alveolar Macrophages, Slight

 Alveolitis, Slight

Skin

 Hair loss, Cranial region

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

Trachea

 Inflammation, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Nasal turbinates, Pancreas, Spleen, Teeth, Thymus
441

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 82 Sex: Male Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 609.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Lungs + Bronchi

 Alveolar Eosinophilic Crystals, Slight

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight

 Inflammatory Exudate in Airways, Minimal

Preputial glands Preputial glands

 Distended Abscessation, Moderate

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
442

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 83 Sex: Male Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 646.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Lungs + Bronchi

 Perivascular Inflammatory Cells, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
443

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 84 Sex: Male Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 624.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Heart

 Inflammation, Chronic, Moderate

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

 Alveolitis, Minimal

 Alveolar Eosinophilic Crystals, Minimal

Nasal turbinates

 Respiratory Epithelium - Goblet Cell Hyperplasia, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
444

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 85 Sex: Male Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 705.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Nasal turbinates

 Respiratory Epithelium - Goblet Cell Hyperplasia, Slight

 Nasolacrimal Duct - Inflammation, Minimal

 Nasopharynx - Goblet Cell Hyperplasia, Slight

 Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Slight

Skin

 Hair loss, Forelimb(s), diffuse.

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal
445

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 85 Sex: Male Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 705.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Trachea

 Inflammation, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Pancreas, Spleen, Teeth, Thymus
446

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 86 Sex: Male Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 628.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Lungs + Bronchi

 Perivascular Inflammatory Cells, Minimal

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Minimal

Skin

 Hair loss, Side(s) of face

Trachea

 Inflammation, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Pancreas, Spleen, Teeth, Thymus, Tracheal Bifurc.
447

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 87 Sex: Male Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 554.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi Lungs + Bronchi

 Pale area(s), A few, subpleural, up to 1mm Arterial Mural Mineralisation, Minimal

 Aggregations of Alveolar Macrophages, Minimal

 Alveolar Congestion, Moderate

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Skin

 Hair loss, Side(s) of face

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Nasal turbinates, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
448

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 88 Sex: Male Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 607.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver

 Inflammation, Focal, Slight

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

 Aggregations of Alveolar Macrophages, Minimal

Nasal turbinates

 Respiratory Epithelium - Goblet Cell Hyperplasia, Slight

Thymus Thymus

 Dark, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Pancreas, Spleen, Teeth, Trachea, Tracheal Bifurc.
449

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 89 Sex: Male Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 754.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Lungs + Bronchi Lungs + Bronchi

 Dark, Patchy Aggregations of Alveolar Macrophages, Minimal

 Alveolitis, Slight

 Perivascular Inflammatory Cells, Slight

 Alveolar Eosinophilic Crystals, Moderate

Larynx

 Inflammatory Cells in Lamina Propria, Slight

 Haemorrhage in Lamina Propria, Slight

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Minimal

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
450

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 90 Sex: Male Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 465.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

 Alveolitis, Minimal

 Alveolar Eosinophilic Crystals, Minimal

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
451

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 101 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 573.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Minimal

Skin

 Hair loss, Side(s) of face, Left, diffuse.

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Liver, Lungs + Bronchi, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
452

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 102 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 462.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver

 Inflammation, Focal, Minimal

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight

 Red Blood Cells in Airways, Slight

Pancreas

 Acinar Cell Degranulation, Minimal

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

Teeth Teeth

 Incisor(s) pale, Lower No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Lungs + Bronchi, Spleen, Thymus, Trachea
453

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 103 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 585.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Lungs + Bronchi

 Pleural Inflammation, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight

Stomach Stomach

 Cyst(s), Pale, One, forestomach, 2mm. Non-glandular Region - Squamous Cyst(s), Focal, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
454

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 104 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 518.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

 Infiltrate, Cellular, Myocardium, Minimal

Lungs + Bronchi

 Aggregations of Alveolar Macrophages, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

Pancreas

 Basophilic Acinar Cells, Focal, Minimal

Teeth Teeth

 Incisor(s) pale, Lower, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Liver, Spleen, Thymus, Trachea, Tracheal Bifurc.
455

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 105 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 521.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Pleural Fibrosis, Slight

 Pleural Inflammation, Slight

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Minimal

Spleen Spleen

 Capsule thickened, a few areas. Capsular Thickening, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Pancreas, Teeth, Thymus, Trachea, Tracheal Bifurc.
456

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 106 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 536.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Minimal

 Nasolacrimal Duct Epithelial Degeneration, Slight

Pancreas

 Arteritis/Periarteritis, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
457

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 107 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 499.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Minimal

Teeth Teeth

 Incisor(s) pale, Lower, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
458

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 108 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 542.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Heart

 Inflammation, Chronic, Minimal

 Infiltrate, Cellular, Myocardium, Minimal

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight

 Periodontal Abscess, Slight

 Periodontal Inflammatory Cell Infiltration, Slight

Pancreas

 Acinar Cell Degranulation, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Liver, Lungs + Bronchi, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
459

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 109 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 449.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Heart

 Inflammation, Chronic, Minimal

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight

Pancreas

 Inflammation, Minimal

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Spleen, Teeth, Thymus, Trachea
460

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 110 Sex: Male Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 508.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

 Infiltrate, Cellular, Myocardium, Minimal

Lungs + Bronchi Lungs + Bronchi

 Dark area(s), Right, caudal lobe, One, subpleural, 2mm. No significant lesions

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Red Blood Cells in Airways, Slight

Pancreas

 Acinar Cell Degranulation, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Liver, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
461

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 111 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 577.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Heart

 Inflammation, Chronic, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

 Alveolitis, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
462

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 112 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 459.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Slight

Lungs + Bronchi Lungs + Bronchi

 Pale area(s), Right, caudal lobe, Punctate, One, subpleural. Arterial Mural Mineralisation, Slight

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

Trachea

 Inflammation, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Liver, Pancreas, Spleen, Teeth, Thymus, Tracheal Bifurc.
463

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 113 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 537.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Slight

Liver

 Inflammation, Focal, Minimal

Skin Skin

 Hair loss, Side(s) of face, diffuse. Scab(s), Slight

 Scab(s), Tail, One, 5mm. Epidermal Hyperplasia, Slight

 Dermal Inflammation, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Lungs + Bronchi, Nasal turbinates, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
464

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 114 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 493.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Slight

 Infiltrate, Cellular, Myocardium, Minimal

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Alveolar Septal Mineralisation, Focal, Minimal

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

Teeth Teeth

 Incisor(s) pale, Lower, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
465

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 115 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 471.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Slight

Liver

 Hepatocyte Necrosis, Focal, Moderate

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

Pancreas

 Acinar Atrophy, Focal, Slight

Spleen Spleen

 Capsule thickened, Anterior pole Capsular Thickening, Minimal

Teeth Teeth

 Incisor(s) pale, Lower No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Lungs + Bronchi, Thymus, Trachea, Tracheal Bifurc.
466

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 116 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 457.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

 Infiltrate, Cellular, Myocardium, Minimal

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

 Aggregations of Alveolar Macrophages, Minimal

 Alveolitis, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Pancreas

 Acinar Cell Degranulation, Slight

Teeth Teeth

 Incisor(s) pale, Lower No significant lesions
467

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 116 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 457.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Nasal turbinates, Spleen, Thymus, Trachea, Tracheal Bifurc.
468

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 117 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 428.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Nasolacrimal Duct - Inflammation, Slight

Pancreas

 Acinar Cell Degranulation, Minimal

Spleen Spleen

 Capsule thickened, Diffuse. Capsular Inflammation, Focal, Minimal

 Capsular Thickening, Slight

Teeth Teeth

 Incisor(s) pale, Lower, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Lungs + Bronchi, Thymus, Trachea, Tracheal Bifurc.
469

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 118 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 457.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Slight

 Infiltrate, Cellular, Myocardium, Minimal

Liver

 Inflammation, Focal, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Slight

Pancreas

 Acinar Cell Degranulation, Slight

Spleen Spleen

 Capsule thickened, Anterior pole, a few areas, up to 3mm. Capsular Inflammation, Focal, Slight
470

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 118 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 457.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Teeth Teeth

 Incisor(s) pale, Lower No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Lungs + Bronchi, Thymus, Trachea, Tracheal Bifurc.
471

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 119 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 498.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Slight

Lungs + Bronchi

 Aggregations of Alveolar Macrophages, Minimal

 Alveolitis, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Nasolacrimal Duct - Inflammation, Minimal

Pancreas

 Acinar Cell Degranulation, Slight

Spleen Spleen

 Capsule thickened, patchy, diffuse. Capsular Inflammation, Focal, Moderate

 Capsular Thickening, Slight
472

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 119 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 498.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Teeth Teeth

 Incisor(s) pale, Lower No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Liver, Thymus, Trachea, Tracheal Bifurc.
473

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 120 Sex: Male Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 585.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Slight

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Aggregations of Alveolar Macrophages, Minimal

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Nasolacrimal Duct - Inflammation, Slight

Pancreas

 Acinar Cell Degranulation, Minimal

Teeth Teeth

 Incisor(s) pale, Lower No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Spleen, Thymus, Trachea, Tracheal Bifurc.
474

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 11 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 379.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Adrenals

 B-Subcapsular Cell Adenoma

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

LN Mesenteric

 Sinus Erythrocytosis/Erythrophagocytosis, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

 Squamous Metaplasia - Ventral, Minimal
475

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 11 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 379.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Increased Vacuolation of Vomeronasal Organ Epithelium, Slight

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Respiratory Epithelium - Goblet Cell Hyperplasia, Minimal

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct Epithelial Degeneration, Slight

Pancreas

 Acinar Cell Degranulation, Slight

Prostate

 Abscessation, Focal, Minimal

Sternum + Marrow

 Marrow - Fat Replacement, Slight
476

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 11 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 379.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Spleen Spleen

 Capsule thickened Capsular Inflammation, Focal, Slight

 Capsular Thickening, Minimal

Thyroids

 Follicular Dilatation, Bilateral, Minimal

Teeth Teeth

 Incisor(s) pale No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN 

Mandibular, Lachrymal Glands, Liver, Mammary, Oesophagus, Optic nerves, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, 

Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Stomach, Testes, Thymus, Tongue, Trachea, Tracheal 

Bifurc., Urinary Bladder
477

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 12 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 428.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Adrenals

 Cortical Vacuolation, Bilateral, Slight

Heart

 Inflammation, Chronic, Moderate

Lungs + Bronchi

 Aggregations of Alveolar Macrophages, Minimal

 Alveolitis, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Mammary

 Acinar Atrophy, Moderate
478

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 12 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 428.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Increased Vacuolation of Vomeronasal Organ Epithelium, Slight

 Respiratory Epithelium - Goblet Cell Hyperplasia, Minimal

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate

Pancreas

 Acinar Cell Degranulation, Moderate

Pituitary

 Cyst(s), Focal, Minimal

Prostate

 Lymphoid Aggregates, Focal, Minimal

Teeth Teeth

 Incisor(s) pale Ameloblast Degeneration, Minimal

 Odontoblast Degeneration, Minimal
479

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 12 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 428.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN 

Mandibular, LN Mesenteric, Lachrymal Glands, Liver, Oesophagus, Optic nerves, Parathyroids, Parotid S.G., Peyer's Patch, Rectum, Salivary Glands, Sciatic 

Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Testes, Thymus, 

Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder
480

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 13 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 445.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Adrenals

 Cortical Vacuolation, Bilateral, Minimal

Heart

 Inflammation, Chronic, Moderate

 Infiltrate, Cellular, Myocardium, Minimal

LN Mandibular

 Plasmacytosis, Slight

 Sinus Histiocytosis, Slight

Lungs + Bronchi Lungs + Bronchi

 Dark area(s), A few, subpleural, up to 1mm. Aggregations of Alveolar Macrophages, Minimal

 Alveolitis, Slight

 Perivascular Inflammatory Cells, Slight

Larynx

 Squamous Metaplasia - Ventral, Minimal
481

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 13 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 445.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Increased Vacuolation of Vomeronasal Organ Epithelium, Minimal

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct Epithelial Degeneration, Slight

Spleen Spleen

 Capsule thickened Capsular Inflammation, Focal, Minimal

 Capsular Thickening, Minimal

Stomach

 Dilated Glands, Minimal

Teeth Teeth

 Incisor(s) pale No significant lesions
482

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 13 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 445.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN 

Mesenteric, Lachrymal Glands, Liver, Mammary, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, 

Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Testes, Thymus, 

Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder
483

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 14 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 449.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Adrenals

 Cortical Vacuolation, Bilateral, Slight

Epididymides

 Lymphoid Aggregates, Focal, Minimal

Heart

 Inflammation, Chronic, Minimal

LN Mandibular

 Sinus Histiocytosis, Slight

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

 Aggregations of Alveolar Macrophages, Minimal

 Alveolitis, Minimal

Larynx

 Squamous Metaplasia - Ventral, Minimal
484

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 14 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 449.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct Epithelial Degeneration, Slight

Optic nerves

 Degenerate Fibres, Unilateral, Minimal

Pancreas

 Acinar Cell Degranulation, Minimal

Spleen Spleen

 Capsule thickened, a few areas. Capsular Inflammation, Focal, Minimal

 Capsular Thickening, Minimal

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal
485

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 14 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 449.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Teeth Teeth

 Incisor(s) pale No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Lachrymal 

Glands, Liver, Mammary, Oesophagus, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, 

Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Testes, Thymus, Thyroids, Tongue, Trachea, Urinary 

Bladder
486

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 15 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 451.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Adrenals

 Cortical Vacuolation, Bilateral, Minimal

 Cortical Hypertrophy, Focal, Minimal

Heart

 Inflammation, Chronic, Slight

 Infiltrate, Cellular, Myocardium, Minimal

LN Mandibular

 Plasmacytosis, Slight

 Sinus Histiocytosis, Minimal

Liver

 Hepatocyte Hypertrophy, Centrilobular, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight
487

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 15 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 451.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Slight

 Nasopharynx - Goblet Cell Hyperplasia, Minimal

Sternum + Marrow

 Marrow - Fat Replacement, Slight

Spleen Spleen

 Capsule thickened Capsular Thickening, Minimal

Teeth Teeth

 Incisor(s) pale No significant lesions
488

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 15 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 451.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN 

Mesenteric, Lachrymal Glands, Lungs + Bronchi, Mammary, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, 

Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Stomach, Testes, Thymus, 

Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder
489

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 16 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 362.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Adrenals

 Cortical Vacuolation, Bilateral, Minimal

Epididymides

 Lymphoid Aggregates, Focal, Minimal

Heart

 Inflammation, Chronic, Moderate

Kidneys

 Cortical Scarring, Focal, Minimal

LN Bronchial

 Sinus Histiocytosis, Slight

LN Mandibular

 Plasmacytosis, Slight

 Sinus Histiocytosis, Slight

Liver

 Inflammation, Focal, Minimal

 Hepatocyte Hypertrophy, Centrilobular, Minimal
490

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 16 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 362.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Mammary

 Acinar Atrophy, Moderate
491

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 16 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 362.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate

 Respiratory Epithelium - Goblet Cell Hyperplasia, Minimal

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Moderate

 Respiratory Epithelium - Squamous Metaplasia, Slight

 Respiratory Epithelium - Inflammation, Slight

 Respiratory Epithelium - Regenerative Hyperplasia, Slight

 Olfactory Epithelium - Inflammation, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Nasolacrimal Duct - Inflammation, Moderate

 Nasolacrimal Duct Epithelial Degeneration, Slight
492

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 16 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 362.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Pancreas

 Acinar Cell Degranulation, Slight

Skin Skin

 Scab(s), Tail, Two, distal, up to 4mm. Scab(s), Marked

 Epidermal Hyperplasia, Moderate

 Dermal Inflammation, Slight

Stomach

 Mucosal Erosion - Glandular Region, Focal, Slight

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

Teeth Teeth

 Incisor(s) pale Periodontal Ligament Inflammation, Minimal

 Incisor(s) thickened

Thymus

 Involution/Atrophy, Moderate
493

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 16 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 362.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

General Comments

 Situs inversus

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Mesenteric, Lachrymal Glands, Larynx, 

Oesophagus, Optic nerves, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, Seminal Vesicles, Skeletal 

Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Testes, Thyroids, Tongue, Trachea, Urinary Bladder
494

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 17 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 418.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Adrenals

 Cortical Vacuolation, Bilateral, Minimal

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Kidneys

 Interstitial Inflammation, Unilateral, Minimal

LN Mandibular

 Plasmacytosis, Slight

Lungs + Bronchi Lungs + Bronchi

 Pale area(s), Left, Punctate, One, subpleural. Alveolitis, Minimal

 Pleural Inflammation, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight
495

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 17 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 418.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Goblet Cell Hyperplasia, Minimal

 Olfactory Epithelium - Squamous Metaplasia, Focal, Slight

 Olfactory Epithelium - Inflammation, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Minimal

 Inflammatory Exudate in Airways, Minimal

Spleen Spleen

 Capsule thickened, Anterior pole, an area, 3mm. No significant lesions

Tracheal Bifurc.

 Loss of Cilia at Bifurcation, Minimal

Teeth Teeth

 Incisor(s) pale, Lower No significant lesions
496

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 17 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 418.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Bronchial, LN Mesenteric, 

Lachrymal Glands, Liver, Mammary, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary 

Glands, Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Testes, 

Thymus, Thyroids, Tongue, Trachea, Urinary Bladder
497

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 18 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 421.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Slight

 Infiltrate, Cellular, Myocardium, Minimal

LN Bronchial LN Bronchial

 Small Decreased Cellularity - Generalised, Slight

LN Mandibular

 Plasmacytosis, Slight

Larynx

 Squamous Metaplasia - Ventral, Minimal

Mammary

 Acinar Atrophy, Marked
498

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 18 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 421.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Minimal

Pancreas

 Acinar Cell Degranulation, Slight

Spleen Spleen

 Capsule thickened Capsular Inflammation, Focal, Slight

 Capsular Thickening, Slight

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions
499

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 18 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 421.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Mesenteric, 

Lachrymal Glands, Liver, Lungs + Bronchi, Oesophagus, Optic nerves, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, 

Sciatic Nerve, Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Testes, Thymus, 

Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder
500

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 19 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 379.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Epididymides

 Lymphoid Aggregates, Focal, Minimal

Heart

 Inflammation, Chronic, Slight

LN Mandibular

 Plasmacytosis, Slight

Liver

 Inflammation, Focal, Minimal

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Slight

Pancreas

 Acinar Cell Degranulation, Slight

Parathyroids

 Both missing
501

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 19 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 379.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Parotid S.G.

 Acinar Atrophy, Focal, Slight

Spleen Spleen

 Capsule thickened No significant lesions

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

Teeth Teeth

 Incisor(s) pale No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, 

Lachrymal Glands, Larynx, Lungs + Bronchi, Mammary, Oesophagus, Optic nerves, Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, 

Seminal Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Testes, Thymus, Thyroids, Tongue, 

Trachea, Urinary Bladder
502

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 20 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 432.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Moderate

Kidneys

 Cortical Scarring, Focal, Minimal

LN Mandibular

 Plasmacytosis, Slight

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi Lungs + Bronchi

 Petechiae, Left, A few No significant lesions

Larynx

 Inflammatory Cells in Lamina Propria, Slight

 Squamous Metaplasia - Ventral, Minimal

Mammary

 Acinar Atrophy, Slight
503

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 20 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 432.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Olfactory Epithelium - Inflammation, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Nasolacrimal Duct Epithelial Degeneration, Minimal

 Nasopharynx - Goblet Cell Hyperplasia, Slight

Pancreas

 Acinar Cell Degranulation, Slight

Parathyroids

 Both missing
504

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 20 Sex: Male Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 432.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Spleen Spleen

 Capsule thickened, Patchy Capsular Inflammation, Focal, Slight

 Cyst(s), Anterior pole, Clear fluid, One, 3mm. Capsular Thickening, Slight

 Capsular Cyst(s), Focal, Slight

Testes

 Seminiferous Tubular Atrophy, Unilateral, Minimal

Teeth Teeth

 Incisor(s) pale, Lower No significant lesions

Urinary Bladder

 Refluxed Seminal Colloid Plug, Present

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Epididymides, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Bronchial, LN 

Mesenteric, Lachrymal Glands, Oesophagus, Optic nerves, Parotid S.G., Peyer's Patch, Pituitary, Prostate, Rectum, Salivary Glands, Sciatic Nerve, Seminal 

Vesicles, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thymus, Thyroids, Tongue, Trachea, Tracheal 

Bifurc.
505

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 71 Sex: Male Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 489.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Kidneys Kidneys

 Pelvic dilatation Perivascular Lymphoid Aggregations, Focal, Minimal

Lungs + Bronchi

 Alveolitis, Minimal

 Alveolar Eosinophilic Crystals, Slight

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Respiratory Epithelium - Goblet Cell Hyperplasia, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Slight

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Liver, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
506

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 72 Sex: Male Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 558.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Aggregations of Alveolar Macrophages, Minimal

 Alveolitis, Minimal

 Pleural Inflammation, Focal, Minimal

Nasal turbinates

 Respiratory Epithelium - Goblet Cell Hyperplasia, Slight

 Nasolacrimal Duct - Inflammation, Minimal

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions
507

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 72 Sex: Male Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 558.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Pancreas, Spleen, Thymus, Trachea
508

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 73 Sex: Male Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 432.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Slight

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
509

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 74 Sex: Male Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 491.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Nasal turbinates

 Respiratory Epithelium - Goblet Cell Hyperplasia, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Minimal

 Nasolacrimal Duct Epithelial Degeneration, Slight

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

 Incisor(s) thickened

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
510

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 75 Sex: Male Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 544.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Lungs + Bronchi Lungs + Bronchi

 Dark area(s), A few, subpleural, 2mm. Perivascular Inflammatory Cells, Minimal

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

Pituitary Pituitary

 Cyst(s), Clear, One, 2mm. Cyst(s), Moderate

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Liver, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
511

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 76 Sex: Male Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 532.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Liver

 Perivascular Mineralisation, Slight

Lungs + Bronchi

 Aggregations of Alveolar Macrophages, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Minimal

Spleen Spleen

 Adhesions, Slight, to omental fat. Capsular Inflammation, Focal, Minimal

 Capsule thickened, Anterior pole Capsular Thickening, Slight
512

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 76 Sex: Male Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 532.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Pancreas, Thymus, Trachea
513

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 77 Sex: Male Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 466.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

 Alveolitis, Slight

 Alveolar Eosinophilic Crystals, Slight

Larynx

 Inflammatory Cells in Lamina Propria, Slight
514

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 77 Sex: Male Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 466.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Goblet Cell Hyperplasia, Slight

 Olfactory Epithelium - Squamous Metaplasia, Minimal

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal

 Nasolacrimal Duct - Inflammation, Minimal

Pancreas

 Acinar Atrophy, Focal, Slight

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Liver, Spleen, Thymus, Trachea
515

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 78 Sex: Male Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 476.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

 Aggregations of Alveolar Macrophages, Slight

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
516

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 79 Sex: Male Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 407.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

Spleen Spleen

 Adhesions, Anterior pole, to left abdominal wall. Capsular Inflammation, Focal, Minimal

 Capsular Thickening, Slight

 Adhesion, Present

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Pancreas, Thymus, Trachea, Tracheal Bifurc.
517

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 80 Sex: Male Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 422.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

LN Mandibular LN Mandibular

 Enlarged, Left, One, 12mm. Plasmacytosis, Moderate

 Paracortex - Increased Cellularity, Moderate

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Alveolitis, Minimal

 Alveolar Eosinophilic Crystals, Minimal

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Erosion, Focal, Moderate

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
518

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 21 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 316.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Kidneys

 Mineralisation, Papilla, Unilateral, Minimal

LN Mandibular

 Plasmacytosis, Moderate

 Sinus Histiocytosis, Slight

Larynx

 Inflammatory Cells in Lamina Propria, Moderate
519

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 21 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 316.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Erosion, Focal, Slight

 Olfactory Epithelium - Inflammation, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal

 Olfactory Epithelium - Erosion, Focal, Slight

 Nasolacrimal Duct - Inflammation, Minimal

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Minimal

Parotid S.G.

 Acinar Atrophy, Focal, Slight

 Mineralisation, Focal, Minimal

Uterus

 Polyploid Hyperplasia, Focal, Slight
520

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 21 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 316.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Vagina

 Oestrus, Present

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, LN Bronchial, LN Mesenteric, 

Lachrymal Glands, Liver, Lungs + Bronchi, Mammary, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Peyer's Patch, Pituitary, Rectum, Salivary 

Glands, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Thymus, Thyroids, 

Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix
521

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 22 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 271.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Adrenals

 Subcapsular Cell Hyperplasia, Focal, Unilateral, Slight

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

 Aggregations of Alveolar Macrophages, Minimal

LN Mesenteric

 Mastocytosis, Slight

Ovaries

 Prominent Corpora Lutea, Present

Pituitary

 Cyst(s), Focal, Minimal

Vagina

 Metoestrus, Present
522

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 22 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 271.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mandibular, 

Lachrymal Glands, Larynx, Liver, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Rectum, Salivary 

Glands, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Thymus, Thyroids, 

Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus
523

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 23 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 271.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Heart

 Infiltrate, Cellular, Myocardium, Minimal

LN Mandibular

 Plasmacytosis, Slight

 Sinus Histiocytosis, Slight

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

 Aggregations of Alveolar Macrophages, Minimal

 Alveolitis, Minimal

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Red Blood Cells in Airways, Slight

Skeletal Muscle

 Inflammation, Minimal
524

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 23 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 271.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Vagina

 Metoestrus, Present

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, 

Lachrymal Glands, Larynx, Liver, Mammary, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary 

Glands, Sciatic Nerve, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Thymus, Thyroids, Tongue, 

Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus
525

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 24 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 317.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Mammary

 Site Only, Present

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Minimal

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight

 Red Blood Cells in Airways, Slight

Pituitary

 Cyst(s), Focal, Minimal

Vagina

 Proestrus, Present
526

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 24 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 317.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, Kidneys, LN Bronchial, LN 

Mandibular, LN Mesenteric, Lachrymal Glands, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Rectum, Salivary 

Glands, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Thymus, Thyroids, 

Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus
527

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 25 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 276.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

LN Mandibular

 Sinus Histiocytosis, Moderate

Lungs + Bronchi Lungs + Bronchi

 Pale area(s), Left, Punctate, One, subpleural. No significant lesions

LN Mesenteric

 Sinus Erythrocytosis/Erythrophagocytosis, Minimal

Urinary Bladder

 Transitional Cell Hyperplasia, Slight

Vagina

 Metoestrus, Present

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, Kidneys, LN Bronchial, Lachrymal 

Glands, Larynx, Liver, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, 

Salivary Glands, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, Thymus, 

Thyroids, Tongue, Trachea, Tracheal Bifurc., Uterine cervix, Uterus
528

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 26 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 326.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

LN Mandibular

 Plasmacytosis, Moderate

Lungs + Bronchi Lungs + Bronchi

 Pale area(s), A few, subpleural, up to 1mm. No significant lesions

Skin Skin

 Scab(s), Side(s) of face, Punctate, A few Scab(s), Slight

 Hair loss, Side(s) of face Epidermal Hyperplasia, Slight

 Dermal Inflammation, Minimal

 Epidermal Ulceration, Focal, Moderate

Vagina

 Metoestrus, Present

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, Kidneys, LN Bronchial, LN 

Mesenteric, Lachrymal Glands, Larynx, Liver, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Parotid S.G., Peyer's 

Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, 

Stomach, Teeth, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus
529

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 27 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Killed for welfare reasons

Date of Death: 30-Aug-12 Day of Death: 52 Week of Death: 8 Subgroup: 1 Terminal Bodyweight: 291.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Adrenals

 Sinusoidal Dilatation/Congestion, Unilateral, Moderate

Caecum

 Submucosal Oedema, Moderate

Fac con to death

 Pericarditis, Present

Heart Heart

 Adhesion(s), to pericardium. Infiltrate, Cellular, Myocardium, Minimal

 Pericardial fluid, Dark, copious. Pericarditis, Marked

 Pericardium thickened Adhesion, Present

 Pericardial Haemorrhage, Marked

 Pericardial Fibrosis, Marked

Kidneys

 Pelvic Dilatation, Unilateral, Slight
530

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 27 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Killed for welfare reasons

Date of Death: 30-Aug-12 Day of Death: 52 Week of Death: 8 Subgroup: 1 Terminal Bodyweight: 291.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

LN Bronchial LN Bronchial

 Dark Sinus Erythrocytosis/Erythrophagocytosis, Slight

Liver Liver

 Irregular surface Inflammation, Focal, Slight

 Hepatocyte Necrosis, Focal, Minimal

Lungs + Bronchi

 Perivascular Haemorrhage, Focal, Slight

 Pleural Fibrosis, Slight

LN Mesenteric

 Sinus Erythrocytosis/Erythrophagocytosis, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal
531

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 27 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Killed for welfare reasons

Date of Death: 30-Aug-12 Day of Death: 52 Week of Death: 8 Subgroup: 1 Terminal Bodyweight: 291.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Pancreas Pancreas

 Oedematous Oedema, Slight

Spleen

 Capsular Thickening, Minimal

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Slight

Thorax

 Contained fluid, Clear, serous, copious.

Thymus Thymus

 Oedematous Involution/Atrophy, Moderate

 Oedema, Moderate

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Mandibular, Lachrymal Glands, Mammary, Oesophagus, 

Optic nerves, Ovaries, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal 

C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Teeth, Thyroids, Tongue, Trachea, Urinary Bladder, Uterine cervix, Uterus, Vagina
532

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 28 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 336.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

LN Mandibular

 Plasmacytosis, Slight

 Paracortex - Increased Cellularity, Slight

Lungs + Bronchi

 Aggregations of Alveolar Macrophages, Slight

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Ovaries Ovaries

 Cyst(s), Left, Clear fluid, One, 2mm. Cyst(s), Focal, Slight

Skin Skin

 Hair loss, Side(s) of face, diffuse. No significant lesions

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Slight

Vagina

 Metoestrus, Present
533

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 28 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 336.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Heart, Ileum, Jejunum, Kidneys, LN Bronchial, LN 

Mesenteric, Lachrymal Glands, Liver, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, 

Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Teeth, 

Thymus, Thyroids, Tongue, Trachea, Urinary Bladder, Uterine cervix, Uterus
534

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 29 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 299.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Adrenals

 Cortical Hypertrophy, Bilateral, Slight

Harderian Glands

 Lymphoid Aggregates, Focal, Minimal

Heart

 Infiltrate, Cellular, Myocardium, Minimal

LN Mandibular LN Mandibular

 Enlarged, Right, One, 15mm. Plasmacytosis, Moderate

 Paracortex - Increased Cellularity, Slight

Lachrymal Glands

 Lymphoid Aggregates, Focal, Minimal

Liver

 Inflammation, Focal, Minimal

Pancreas

 Acinar Cell Degranulation, Slight
535

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 29 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 299.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Parathyroids

 Both missing

Skin Skin

 Scab(s), Side(s) of face, Left, A few, up to 2mm. Scab(s), Moderate

 Hair loss, Side(s) of face, Left Epidermal Hyperplasia, Slight

 Dermal Inflammation, Minimal

Stomach

 Submucosal Inflammation - Glandular Region, Slight

Vagina

 Metoestrus, Present

The following examined tissues had no gross observations and no findings microscopically:

 Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, Larynx, Lungs + Bronchi, 

Mammary, Nasal turbinates, Oesophagus, Optic nerves, Ovaries, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, 

Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Teeth, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, 

Uterine cervix, Uterus
536

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 30 Sex: Female Dose Group: 1 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 306.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Harderian Glands

 Lymphoid Aggregates, Focal, Minimal

Lungs + Bronchi

 Alveolitis, Minimal

 Perivascular Inflammatory Cells, Minimal

Spleen

 Capsular Thickening, Minimal

Vagina

 Metoestrus, Present

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Heart, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mandibular, LN 

Mesenteric, Lachrymal Glands, Larynx, Liver, Mammary, Nasal turbinates, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Parotid S.G., Peyer's 

Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, 

Teeth, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus
537

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 41 Sex: Female Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 306.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Larynx

 Inflammatory Cells in Lamina Propria, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Liver, Lungs + Bronchi, Nasal turbinates, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
538

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 42 Sex: Female Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 328.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Liver

 Inflammation, Focal, Minimal

 Hepatocyte Vacuolation, Periportal, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
539

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 43 Sex: Female Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 301.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Nasolacrimal Duct - Inflammation, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Lungs + Bronchi, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
540

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 44 Sex: Female Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 350.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Liver

 Inflammation, Focal, Minimal

 Hepatocyte Vacuolation, Periportal, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Inflammatory Exudate in Airways, Minimal

Ovaries Ovaries

 Periovarian sac distension, Left, Clear, Minimal, 7mm. Cyst(s), Unilateral, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
541

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 45 Sex: Female Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 293.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

 Perivascular Inflammatory Cells, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Slight

Pancreas

 Inflammation, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Liver, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
542

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 46 Sex: Female Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 325.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Liver

 Inflammation, Focal, Slight

 Hepatocyte Necrosis, Focal, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Minimal

 Inflammatory Exudate in Airways, Minimal

Thymus

 Tissue missing

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Pancreas, Spleen, Teeth, Trachea, Tracheal Bifurc.
543

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 47 Sex: Female Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 335.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Liver

 Inflammation, Focal, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Lungs + Bronchi, Nasal turbinates, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
544

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 48 Sex: Female Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 302.5 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver

 Inflammation, Focal, Slight

Lungs + Bronchi Lungs + Bronchi

 Pale area(s), A few, subpleural, up to 2mm. Aggregations of Alveolar Macrophages, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Increased Vacuolation of Vomeronasal Organ Epithelium, Slight

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
545

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 49 Sex: Female Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 301.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Lungs + Bronchi

 Aggregations of Alveolar Macrophages, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Minimal

Pancreas

 Acinar Cell Degranulation, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Liver, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
546

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 50 Sex: Female Dose Group: 1 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 279.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

***ANIMAL HAS NO MACROSCOPIC FINDINGS RECORDED***

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Liver, Lungs + Bronchi, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
547

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 51 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 293.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Lungs + Bronchi Lungs + Bronchi

 Pale area(s), Right, caudal lobe, Punctate, A few, subpleural. Arterial Mural Mineralisation, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Liver, Nasal turbinates, Pancreas, Spleen, Teeth, Thymus, Trachea
548

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 52 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 286.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Lungs + Bronchi

 Cholesterol Cleft Granuloma(ta), Minimal

Nasal turbinates

 Respiratory Epithelium - Goblet Cell Hyperplasia, Slight

Paws Paws

 Swelling(s), Left fore, One, 3x2mm. Oedema, Slight

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Liver, Pancreas, Spleen, Teeth, Thymus, Trachea
549

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 53 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 296.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Lungs + Bronchi

 Alveolitis, Minimal

 Pleural Inflammation, Minimal

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Minimal

Skin

 Hair loss, Forelimb(s), Slight

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Pancreas, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
550

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 54 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 278.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Lungs + Bronchi

 Aggregations of Alveolar Macrophages, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

Skin

 Hair loss, Scapular region(s), diffuse.

Spleen

 Capsular Thickening, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Liver, Pancreas, Teeth, Thymus, Trachea, Tracheal Bifurc.
551

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 55 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 284.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Skin

 Hair loss, Forelimb(s), Right, diffuse.

Spleen Spleen

 Capsule thickened, Anterior pole, a few areas, diffuse. Capsular Inflammation, Focal, Minimal

 Capsular Thickening, Minimal

Teeth Teeth

 Incisor(s) pale, Lower No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Lungs + Bronchi, Nasal turbinates, Pancreas, Thymus, Trachea, Tracheal Bifurc.
552

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 56 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 315.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Lungs + Bronchi Lungs + Bronchi

 Pale area(s), Right, caudal lobe, Punctate, A few, subpleural. Aggregations of Alveolar Macrophages, Minimal

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight

Pancreas

 Inflammation, Minimal

Teeth Teeth

 Incisor(s) pale, Lower, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Spleen, Thymus, Trachea, Tracheal Bifurc.
553

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 57 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 296.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver

 Inflammation, Focal, Minimal

Nasal turbinates

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight

Pancreas

 Acinar Cell Degranulation, Minimal

 Acinar Atrophy, Focal, Minimal

Skin

 Hair loss, Dorsal surface, diffuse.

Trachea

 Inflammation, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Lungs + Bronchi, Spleen, Teeth, Thymus, Tracheal Bifurc.
554

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 58 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 306.3 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Lungs + Bronchi

 Aggregations of Alveolar Macrophages, Minimal

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight

Pancreas

 Acinar Cell Degranulation, Minimal

Skin

 Hair loss, Side(s) of face, diffuse.

Teeth Teeth

 Incisor(s) pale, Lower No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Spleen, Thymus, Trachea, Tracheal Bifurc.
555

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 59 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 320.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Nasal turbinates

 Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Minimal

Pancreas

 Acinar Cell Degranulation, Slight

Skin

 Hair loss, Side(s) of face, diffuse.

Trachea

 Inflammation, Slight

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Spleen, Teeth, Thymus, Tracheal Bifurc.
556

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 60 Sex: Female Dose Group: 2 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 287.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Lungs + Bronchi Lungs + Bronchi

 Pale area(s), A few, subpleaural, up to 1mm. Cholesterol Cleft Granuloma(ta), Focal, Minimal

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight

Pancreas

 Acinar Cell Degranulation, Slight

Skin

 Hair loss, dorsal region and limbs, diffuse.

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Spleen, Teeth, Thymus, Trachea, Tracheal Bifurc.
557

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 1 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 293.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Nasolacrimal Duct - Inflammation, Minimal

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Liver, Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
558

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 2 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 296.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi Lungs + Bronchi

 Pale area(s), Punctate, Multiple, subpleural. Alveolitis, Minimal

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight

Pancreas

 Acinar Cell Degranulation, Slight
559

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 2 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 296.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Spleen Spleen

 Cyst(s), Clear fluid, A few, capsular, up to 2mm. Capsular Inflammation, Focal, Slight

 Capsule thickened, a few areas. Capsular Thickening, Slight

 Adhesions, Anterior pole, to left retroperitoneal adipose tissue. Capsular Cyst(s), Focal, Slight

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Thymus, Trachea, Tracheal Bifurc.
560

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 3 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 232.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Alveolitis, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight

Pancreas

 Acinar Cell Degranulation, Slight

Skin Skin

 Scab(s), Tail, Two, up to 4mm. No significant lesions

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions
561

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 3 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 232.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Spleen, Thymus, Trachea, Tracheal Bifurc.
562

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 4 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 297.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

Liver

 Inflammation, Focal, Minimal

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Slight

Pancreas

 Acinar Cell Degranulation, Minimal

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Larynx, Lungs + Bronchi, Spleen, Thymus, Trachea
563

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 5 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 294.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver Liver

 Adhesions, Posterior caudate lobe, to stomach. Capsular Adhesions, Present

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Nasolacrimal Duct - Inflammation, Moderate

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight

Spleen Spleen

 Adhesions, to stomach, posterior caudate liver lobe and omental adipose 

tissue.

 Capsular Thickening, Minimal

 Adhesion, Present

Teeth Teeth

 Incisor(s) pale, Lower No significant lesions
564

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 5 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 10-Oct-12 Day of Death: 93 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 294.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Lungs + Bronchi, Pancreas, Thymus, Trachea, Tracheal Bifurc.
565

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 6 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 303.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver

 Inflammation, Focal, Minimal

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

Pancreas

 Acinar Cell Degranulation, Minimal

Teeth Teeth

 Incisor(s) pale, Patchy Odontoblast Degeneration, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Lungs + Bronchi, Spleen, Thymus, Trachea, Tracheal Bifurc.
566

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 7 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 257.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight

Skin

 Hair loss, Thoracic region, Dorsal

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

Teeth Teeth

 Incisor(s) pale, Lower No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Liver, Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea
567

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 8 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 290.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Infiltrate, Cellular, Myocardium, Minimal

Kidneys Kidneys

 Pelvic dilatation, Right Pelvic Dilatation, Unilateral, Moderate

Liver

 Inflammation, Focal, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Minimal

Skin

 Hair loss, Side(s) of face, extending to lateral cervical regions, diffuse.

Teeth Teeth

 Incisor(s) pale, Lower, Patchy No significant lesions
568

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 8 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 290.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
569

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 9 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 270.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

Lungs + Bronchi

 Alveolar Septal Mineralisation, Minimal

 Alveolar Congestion, Slight

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Skin

 Hair loss, Side(s) of face, diffuse.

Spleen Spleen

 Capsule thickened Capsular Thickening, Minimal

Teeth Teeth

 Incisor(s) pale, Lower, Patchy Odontoblast Degeneration, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Liver, Nasal turbinates, Pancreas, Thymus, Trachea, Tracheal Bifurc.
570

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 10 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 291.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Kidneys Kidneys

 Depression(s), Right, One, 2mm. No significant lesions

Liver

 Inflammation, Focal, Minimal

 Hepatocyte Hypertrophy, Centrilobular, Minimal

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Nasolacrimal Duct - Inflammation, Slight

Pancreas

 Acinar Cell Degranulation, Minimal

Skin

 Hair loss, Thoracic region, Dorsal, extending to cranial region.

Spleen

 Haemosiderosis, Slight
571

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 10 Sex: Female Dose Group: 3 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 12-Oct-12 Day of Death: 95 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 291.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Lungs + Bronchi, Teeth, Thymus, Trachea, Tracheal Bifurc.
572

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 31 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 211.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Slight

Kidneys

 Pyelonephritis, Bilateral, Moderate

 Hyperplasia, Papillary Epithelium, Bilateral, Moderate

 Hyperplasia, Pelvic Epithelium, Bilateral, Slight

LN Mandibular

 Plasmacytosis, Slight

 Sinus Histiocytosis, Slight
573

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 31 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 211.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Nasolacrimal Duct - Inflammation, Moderate

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Moderate

 Inflammatory Exudate in Airways, Minimal

 Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Slight
574

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 31 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 211.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Pancreas

 Acinar Cell Degranulation, Slight

Skin Skin

 Hair loss, Thoracic region, Patchy, diffuse. No significant lesions

Skeletal Muscle

 Inflammation, Slight

Spleen Spleen

 Capsule thickened, multiple areas, diffuse. Capsular Thickening, Minimal

Stomach

 Dilated Glands, Minimal

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Minimal

Teeth Teeth

 Incisor(s) pale Pulp Cavity Necrosis, Unilateral, Moderate

 Incisor(s) thickened
575

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 31 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 211.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Thymus

 Involution/Atrophy, Minimal

Urinary Bladder

 Transitional Cell Hyperplasia, Moderate

 Inflammation, Moderate

 Erosion, Moderate

Uterus

 Polyploid Hyperplasia, Focal, Slight

Vagina

 Oestrus, Present

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Bronchial, LN Mesenteric, Lachrymal 

Glands, Larynx, Liver, Lungs + Bronchi, Mammary, Oesophagus, Optic nerves, Ovaries, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary 

Glands, Sciatic Nerve, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Thyroids, Tongue, Trachea, Uterine cervix
576

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 32 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 205.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Slight

Liver Liver

 Adhesions, between all lobes. Extramedullary Haemopoiesis, Slight

 Capsular Adhesions, Present

Lungs + Bronchi Lungs + Bronchi

 Adhesions, between right cranial and middle lobes. Arterial Mural Mineralisation, Minimal

 Aggregations of Alveolar Macrophages, Slight

 Alveolitis, Slight

 Perivascular Inflammatory Cells, Slight

 Pleural Adhesion(s), Slight

Mammary

 Site Only, Present
577

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 32 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 205.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Respiratory Epithelium - Erosion, Focal, Minimal

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate

 Olfactory Epithelium - Respiratory Metaplasia, Slight

 Nasolacrimal Duct - Inflammation, Moderate

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Moderate

 Nasolacrimal Duct - Luminal Inflammatory Exudate, Moderate

 Inflammatory Exudate in Airways, Minimal
578

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 32 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 205.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Skin Skin

 Hair loss, Thoracic region, Patchy, diffuse. No significant lesions

Spleen Spleen

 Capsule thickened Capsular Inflammation, Focal, Slight

 Adhesions, to omental and left mesovarian adipose tissue. Capsular Thickening, Moderate

Teeth Teeth

 Incisor(s) pale Pulp Cavity Necrosis, Unilateral, Slight

 Incisor(s) thickened

Thymus

 Involution/Atrophy, Moderate

Vagina

 Metoestrus, Present

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mandibular, 

LN Mesenteric, Lachrymal Glands, Larynx, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary 

Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thyroids, Tongue, Trachea, Tracheal 

Bifurc., Urinary Bladder, Uterine cervix, Uterus
579

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 33 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 293.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Moderate

Lungs + Bronchi Lungs + Bronchi

 Dark area(s), A few, subpleural, up to 2mm. Alveolitis, Minimal

 Pale area(s), Right, middle lobe, Punctate, A few, subpleural. Perivascular Inflammatory Cells, Minimal

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Nasolacrimal Duct - Inflammation, Slight
580

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 33 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 293.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Skin Skin

 Hair loss, Forelimb(s), Left, diffuse. No significant lesions

Teeth Teeth

 Incisor(s) pale Pulp Cavity Increased Inflammatory Cell Infiltration, Minimal

Vagina

 Oestrus, Present

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mandibular, 

LN Mesenteric, Lachrymal Glands, Larynx, Liver, Mammary, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, 

Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Thymus, 

Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, Uterus
581

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 34 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 268.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

LN Mandibular

 Sinus Histiocytosis, Slight

 Sinus Erythrocytosis/Erythrophagocytosis, Minimal

Lachrymal Glands

 Lymphoid Aggregates, Focal, Minimal

Liver Liver

 Cyst(s), Median lobe, Clear fluid, Two, subcapsular,, up to 3mm. Vascular Dilatation, Slight

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Mammary

 Site Only, Present
582

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 34 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 268.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Minimal

Parathyroids

 Both missing

Pituitary

 Cyst(s), Focal, Minimal
583

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 34 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 268.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Skin Skin

 Hair loss, Cervical region, diffuse. No significant lesions

Teeth Teeth

 Incisor(s) pale No significant lesions

 Incisor(s) thickened

Urinary Bladder

 Transitional Cell Hyperplasia, Slight

 Inflammation, Slight

Vagina

 Metoestrus, Present

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, 

Lungs + Bronchi, Oesophagus, Optic nerves, Ovaries, Pancreas, Parotid S.G., Peyer's Patch, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. 

Cerv., Spinal C. Lumb., Spinal C. Thor., Spleen, Sternum + Marrow, Stomach, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Uterine cervix, Uterus
584

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 35 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 258.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

LN Mandibular

 Sinus Histiocytosis, Slight

Lungs + Bronchi

 Alveolitis, Minimal

 Perivascular Inflammatory Cells, Minimal
585

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 35 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 258.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Moderate

 Nasolacrimal Duct - Luminal Inflammatory Exudate, Minimal

Skin Skin

 Hair loss, Scapular region(s), Left, diffuse. No significant lesions
586

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 35 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 258.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Spleen Spleen

 Adhesions, to omental, left mesovarian and left retroperitoneal adipose tissue. Capsular Inflammation, Focal, Moderate

 Capsular Thickening, Moderate

 Adhesion, Present

Teeth Teeth

 Incisor(s) pale Ameloblast Degeneration, Minimal

 Incisor(s) thickened Odontoblast Degeneration, Minimal

 Pulp Cavity Necrosis, Unilateral, Slight

Urinary Bladder

 Transitional Cell Hyperplasia, Slight

Vagina

 Oestrus, Present
587

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 35 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 09-Oct-12 Day of Death: 92 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 258.7 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, 

Lachrymal Glands, Larynx, Liver, Mammary, Oesophagus, Optic nerves, Ovaries, Pancreas, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary 

Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thymus, Thyroids, Tongue, Trachea, 

Tracheal Bifurc., Uterine cervix, Uterus
588

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 36 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 265.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Eyes Eyes

 Protruding, Left Keratitis, Unilateral, Moderate

 Inflammatory Cells, Anterior Chamber, Unilateral, Slight

 Iritis, Unilateral, Moderate

 Inflammation of the Sclera, Unilateral, Moderate

Harderian Glands Harderian Glands

 Swelling(s), Left, One, 6mm. Cut surface: purulent exudate. M-Adenocarcinoma

Heart

 Inflammation, Chronic, Minimal

LN Bronchial

 Sinus Histiocytosis, Slight

LN Mandibular

 Plasmacytosis, Slight

 Sinus Histiocytosis, Slight
589

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 36 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 265.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Liver

 Hepatocyte Hypertrophy, Centrilobular, Minimal

Lungs + Bronchi

 Alveolitis, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

 Squamous Metaplasia - Ventral, Minimal
590

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 36 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 265.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Respiratory Epithelium - Erosion, Slight

 Olfactory Epithelium - Squamous Metaplasia, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Moderate

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight

 Nasolacrimal Duct - Luminal Inflammatory Exudate, Moderate

 Inflammatory Exudate in Airways, Minimal

 Squamous Epithelium - Inflammatory Cells in the Lamina Propria, Slight
591

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 36 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 265.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Pancreas

 Acinar Cell Degranulation, Slight

Spleen Spleen

 Capsule thickened Capsular Inflammation, Focal, Moderate

 Adhesions, to omental and left mesovarian adipose tissue. Capsular Thickening, Moderate

 Adhesion, Present

Teeth Teeth

 Incisor(s) pale Ameloblast Degeneration, Minimal

 Incisor(s) thickened Pulp Cavity Necrosis, Unilateral, Slight

Vagina

 Metoestrus, Present

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Femur inc. Joint, Ileum, Jejunum, Kidneys, LN Mesenteric, Lachrymal Glands, Mammary, 

Oesophagus, Optic nerves, Ovaries, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Skin, Spinal C. 

Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thymus, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary Bladder, Uterine cervix, 

Uterus
592

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 37 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 249.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

 Infiltrate, Cellular, Myocardium, Minimal

LN Mandibular

 Sinus Histiocytosis, Slight

Larynx

 Inflammatory Cells in Lamina Propria, Slight

 Squamous Metaplasia - Ventral, Minimal
593

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 37 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 249.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Respiratory Epithelium - Inflammation, Slight

 Olfactory Epithelium - Inflammation, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Olfactory Epithelium - Respiratory Metaplasia, Slight

 Nasolacrimal Duct - Inflammation, Moderate

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Moderate

 Nasolacrimal Duct - Luminal Inflammatory Exudate, Slight
594

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 37 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 249.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Pancreas

 Acinar Cell Degranulation, Slight

Parathyroids

 Both missing

Salivary Glands

 Inflammation, Slight

Spleen Spleen

 Capsule thickened, Patchy Capsular Inflammation, Focal, Slight

 Adhesions, to left mesovarian adipose tissue. Capsular Thickening, Moderate

 Adhesion, Present

Teeth Teeth

 Incisor(s) pale No significant lesions

Thymus

 Involution/Atrophy, Moderate

Vagina

 Metoestrus, Present
595

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 37 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 249.4 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, 

Lachrymal Glands, Liver, Lungs + Bronchi, Mammary, Oesophagus, Optic nerves, Ovaries, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Sciatic Nerve, 

Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thyroids, Tongue, Trachea, Tracheal Bifurc., Urinary 

Bladder, Uterine cervix, Uterus
596

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 38 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 246.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

 Infiltrate, Cellular, Myocardium, Minimal

Kidneys

 Pyelonephritis, Bilateral, Slight

 Hyperplasia, Papillary Epithelium, Bilateral, Moderate

 Hyperplasia, Pelvic Epithelium, Bilateral, Moderate

LN Mandibular

 Sinus Histiocytosis, Slight

Liver

 Inflammation, Focal, Slight

 Hepatocyte Hypertrophy, Centrilobular, Minimal

Lungs + Bronchi

 Aggregations of Alveolar Macrophages, Minimal
597

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 38 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 246.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Respiratory Epithelium - Inflammation, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Olfactory Epithelium - Respiratory Metaplasia, Slight

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Moderate

 Inflammatory Exudate in Airways, Slight
598

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 38 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 246.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Pancreas

 Acinar Cell Degranulation, Slight

Peyer's Patch

 Tissue missing

Skin Skin

 Hair loss, Side(s) of face No significant lesions

Spleen

 Capsular Inflammation, Focal, Minimal

 Capsular Thickening, Slight

Teeth Teeth

 Incisor(s) pale, Patchy Pulp Cavity Increased Inflammatory Cell Infiltration, Slight

 Incisor(s) thickened

Thymus

 Involution/Atrophy, Minimal
599

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 38 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 246.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Urinary Bladder

 Transitional Cell Hyperplasia, Moderate

 Inflammation, Slight

Vagina

 Metoestrus, Present

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, LN Bronchial, LN Mesenteric, Lachrymal 

Glands, Larynx, Mammary, Oesophagus, Optic nerves, Ovaries, Parathyroids, Parotid S.G., Pituitary, Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, 

Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thyroids, Tongue, Trachea, Tracheal Bifurc., Uterine cervix, Uterus
600

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 39 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 281.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

LN Mandibular

 Plasmacytosis, Slight

 Sinus Histiocytosis, Slight

 Sinus Erythrocytosis/Erythrophagocytosis, Minimal

Liver

 Hepatocyte Hypertrophy, Centrilobular, Minimal

Lungs + Bronchi

 Aggregations of Alveolar Macrophages, Slight

 Alveolitis, Moderate

 Perivascular Lymphoid Aggregates, Moderate
601

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 39 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 281.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Olfactory Epithelium - Inflammation, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Moderate

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Olfactory Epithelium - Respiratory Metaplasia, Slight

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight

 Inflammatory Exudate in Airways, Slight
602

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 39 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 281.8 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Pancreas

 Acinar Cell Degranulation, Slight

 Acinar Atrophy, Focal, Slight

Spleen

 Capsular Thickening, Minimal

Teeth Teeth

 Incisor(s) pale Pulp Cavity Necrosis, Unilateral, Slight

 Incisor(s) thickened

Urinary Bladder

 Transitional Cell Hyperplasia, Slight

Vagina

 Metoestrus, Present

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mesenteric, 

Lachrymal Glands, Larynx, Mammary, Oesophagus, Optic nerves, Ovaries, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, Rectum, Salivary Glands, Sciatic 

Nerve, Skeletal Muscle, Skin, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thymus, Thyroids, Tongue, Trachea, Tracheal 

Bifurc., Uterine cervix, Uterus
603

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 40 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 262.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Heart

 Inflammation, Chronic, Minimal

Liver

 Hepatocyte Hypertrophy, Centrilobular, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight
604

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 40 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 262.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal

 Respiratory Epithelium - Inflammation, Minimal

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal

 Olfactory Epithelium - Respiratory Metaplasia, Minimal

Pancreas

 Acinar Cell Degranulation, Slight

Skin

 Dermal Inflammation, Minimal
605

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 40 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 262.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Spleen Spleen

 Capsule thickened Capsular Inflammation, Focal, Slight

 Adhesions, to left mesovarian and retroperitoneal adipose tissue. Capsular Thickening, Slight

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Moderate

Trachea

 Inflammatory Exudate in Lumen, Slight

 Inflammation, Moderate

Teeth Teeth

 Incisor(s) pale No significant lesions

 Incisor(s) thickened

Thymus

 Involution/Atrophy, Slight

Vagina

 Dioestrus, Present
606

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 40 Sex: Female Dose Group: 4 Phase: Treatment Sacrifice Status: Final phase sacrifice

Date of Death: 11-Oct-12 Day of Death: 94 Week of Death: 14 Subgroup: 1 Terminal Bodyweight: 262.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Adrenals, Aorta Thoracic, Brain, Caecum, Colon, Duodenum, Eyes, Femur inc. Joint, Harderian Glands, Ileum, Jejunum, Kidneys, LN Bronchial, LN Mandibular, 

LN Mesenteric, Lachrymal Glands, Lungs + Bronchi, Mammary, Oesophagus, Optic nerves, Ovaries, Parathyroids, Parotid S.G., Peyer's Patch, Pituitary, 

Rectum, Salivary Glands, Sciatic Nerve, Skeletal Muscle, Spinal C. Cerv., Spinal C. Lumb., Spinal C. Thor., Sternum + Marrow, Stomach, Thyroids, Tongue, 

Urinary Bladder, Uterine cervix, Uterus
607

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 91 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 280.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Nasal turbinates

 Respiratory Epithelium - Goblet Cell Hyperplasia, Slight

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Respiratory Epithelium - Erosion, Slight

 Nasolacrimal Duct - Inflammation, Slight

 Nasolacrimal Duct - Luminal Inflammatory Exudate, Slight

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
608

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 92 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 237.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver

 Hepatocyte Necrosis, Focal, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight
609

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 92 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 237.1 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Respiratory Epithelium - Erosion, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Olfactory Epithelium - Erosion, Minimal

 Nasolacrimal Duct - Inflammation, Minimal

 Nasolacrimal Duct - Epithelial Squamous Metaplasia, Slight

Teeth Teeth

 Incisor(s) pale, Patchy Ameloblast Degeneration, Minimal

 Incisor(s) thickened

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
610

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 93 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 260.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver

 Inflammation, Focal, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Nasolacrimal Duct - Inflammation, Slight

 Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Slight

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
611

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 94 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 253.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Kidneys Kidneys

 Pelvic dilatation, Right Pelvic Dilatation, Unilateral, Slight

Liver

 Inflammation, Focal, Slight

Lungs + Bronchi

 Perivascular Inflammatory Cells, Minimal

Nasal turbinates

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Nasolacrimal Duct - Inflammation, Slight

Pancreas

 Acinar Atrophy, Focal, Slight
612

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 94 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 253.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

 Incisor(s) thickened

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Spleen, Thymus, Trachea, Tracheal Bifurc.
613

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 95 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 298.2 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Nasal turbinates

 Respiratory Epithelium - Goblet Cell Hyperplasia, Slight

 Respiratory Epithelium - Squamous Metaplasia, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Slight

 Inflammatory Exudate in Airways, Slight

 Transitional Epithelium - Inflammatory Cells in the Lamina Propria, Slight

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

 Incisor(s) thickened

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
614

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 96 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 260.6 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Nasal turbinates

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Minimal

 Nasolacrimal Duct - Inflammation, Slight

Pancreas

 Inflammation, Minimal

Skin

 Hair loss, Side(s) of face

Teeth Teeth

 Incisor(s) pale, Patchy Ameloblast Degeneration, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Liver, Spleen, Thymus, Trachea, Tracheal Bifurc.
615

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 97 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 251.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver

 Inflammation, Focal, Minimal

Lungs + Bronchi

 Arterial Mural Mineralisation, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal

 Respiratory Epithelium - Erosion, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Minimal

Skin

 Hair loss, Side(s) of face, Left
616

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 97 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 251.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Teeth Teeth

 Incisor(s) pale, Patchy Ameloblast Degeneration, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
617

Huntingdon Life Sciences

WAG0014

APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 98 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 253.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver

 Inflammation, Focal, Minimal

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Respiratory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Minimal

 Nasolacrimal Duct - Inflammation, Minimal

Spleen

 Haemosiderosis, Slight

Tracheal Bifurc.

 Inflammatory Cells in Lamina Propria, Slight
618

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APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 98 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 253.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

Teeth Teeth

 Incisor(s) pale, Patchy Ameloblast Degeneration, Minimal

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Lungs + Bronchi, Pancreas, Thymus, Trachea
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APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 99 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 289.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Liver

 Inflammation, Focal, Minimal

Nasal turbinates

 Respiratory Epithelium - Goblet Cell Hyperplasia, Slight

 Respiratory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

 Olfactory Epithelium - Atrophy/Disorganisation/Vacuolation, Slight

 Nasolacrimal Duct - Inflammation, Slight

Ovaries Ovaries

 Periovarian sac distension, Right, Dark fluid, 15mm. Haemorrhagic Cyst(s), Unilateral, Moderate

Spleen Spleen

 Adhesions, to adipose tissue. Capsular Thickening, Minimal

 Adhesion, Present

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions
620

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APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 99 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 289.0 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

continued from previous page...

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Larynx, Lungs + Bronchi, Pancreas, Thymus, Trachea, Tracheal Bifurc.
621

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APPENDIX 12 - continued Request ID: 313014

Macropathology and histopathology - individual findings

Group : 1 2 3 4

Compound : Control 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene 2-bromo-3,3,3-trifluoropropene

Exposure level (ppm) : 0 199 505 2876

Animal Number: 100 Sex: Female Dose Group: 4 Phase: Recovery Sacrifice Status: Final phase sacrifice

Date of Death: 06-Nov-12 Day of Death: 29 Week of Death: 5 Subgroup: 1 Terminal Bodyweight: 262.9 g

PATHOLOGY OBSERVATIONS

MACROPATHOLOGY HISTOPATHOLOGY

Larynx

 Inflammatory Cells in Lamina Propria, Slight

Nasal turbinates

 Respiratory Epithelium - Squamous Metaplasia, Slight

 Olfactory Epithelium - Inflammatory Cells in the Lamina Propria, Slight

Teeth Teeth

 Incisor(s) pale, Patchy No significant lesions

The following examined tissues had no gross observations and no findings microscopically:

 Heart, Liver, Lungs + Bronchi, Pancreas, Spleen, Thymus, Trachea, Tracheal Bifurc.
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Annex 1 Certificate of Analysis
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Annex 2 Aerosol Technology and Inhalation Analysis report
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Page 1 of 18

Working for a better future

Aerosol Technology Report 

HLS study number: WAG0014 

Author A Grasiewicz

Version ID: )LQDO

Issue date: 2FWREHU

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Table of Contents 

Signature Page ....................................................................................................................... 3

1. Pre-study Atmosphere Characterization ......................................................................... 4

2. Test Article Handling and Processing for Inhalation Generation ..................................... 4

3. Exposure System ............................................................................................................ 4

4. Administration ................................................................................................................. 5

5. Atmosphere Analysis ...................................................................................................... 5

5.1 Vapour Concentration ................................................................................... 5

5.2 Flow diagram of the analytical method for the analysis of 2-bromo-3,3,3-

trifluoropropene in test atmosphere samples .......................................................... 5

5.3 Nominal Concentration .................................................................................. 6

5.4 Chamber Temperature .................................................................................. 6

5.5 Chamber Humidity ........................................................................................ 6

6. Data and Calculations ..................................................................................................... 6

7. Results and Discussion ................................................................................................... 6

7.1 Aerosol Concentrations ................................................................................. 6

7.2 Chamber Temperature .................................................................................. 7

7.3 Chamber Humidity ........................................................................................ 7

List of Tables 

Table 1 Chamber atmosphere concentration of 2-bromo-3,3,3-trifluoropropene – daily

means and individual exposure values – Group 2........................................... 8

Table 2 Chamber atmosphere concentration of 2-bromo-3,3,3-trifluoropropene – daily 

means and individual exposure values – Group 3......................................... 10

Table 3 Chamber atmosphere concentration of 2-bromo-3,3,3-trifluoropropene – daily 

means and individual exposure values – Group 4......................................... 12

Table 4 Chamber Temperature - daily mean values .................................................. 14

Table 5 Chamber Humidity - daily mean values ......................................................... 16

List of Figures 

Figure 1 Schematic of Inhalation Exposure System .................................................... 18

626
%‘e Or7E 2i2

Antony Grasiewicz MIAT

Senior Aerosol Technologist Date

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1. Pre-study Atmosphere Characterization 

Inhalation exposure system characterized including determinations of: 

Achieved vapour concentration 

Spatial distribution around the chamber 

2. Test Article Handling and Processing for Inhalation 

Generation 

As supplied, 2-Bromo-3,3,3-trifluoro-1-propene was easily vapourised using warmed air 

through a sintered glass vapouriser. 

3. Exposure System 

A schematic of the exposure system is presented in Figure 1. Components of the exposure 

system: 

Directed flow Whole body exposure chamber: 

0.75 m3 chamber of stainless steel and glass construction 

Animal Restraint: 

Wire mesh modular caging 

Aerosol Generator: 

Sintered glass vaporiser for Groups 2 to 4 all in a water bath set at 40°C 

Syringe driver, polypropylene syringe for Group 2 

Liquid reservoir and feed rate used to alter concentration Groups 3 and 4 

Test groups - 30 L/min 

Diluent Airflow: 

From in-house compressed air system – breathing quality 

Group 1 - 149 L/min 

Group 2 to 4 - 119 L/min 

Extract Airflow: 

Drawn by a fan extract system 

Drawn from base of exposure system 

Controlled by a gate clamp situated at the rear of the chamber 

Airflow Monitoring: 

In-line flowmeters monitored continuously for generation and diluent 

airflows 

Chamber pressure differential monitored by Magnahelic set at -1 to 

-5 mm H2O to ensure a slight negative pressure within the chamber ~ 

150 L/min. 

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4. Administration 

Animals exposed for 6 hours per day, 5 days a week for 13 consecutive weeks. 

Exposure system operational parameters monitored continuously 

Airflows documented initially and monitored during exposure 

5. Atmosphere Analysis 

5.1 Vapour Concentration 

Vapour samples collected as follows: 

Sample frequency – minimum of 3 samples/group/exposure 

Sample location – representative animal level 

Sample position remained constant 

Sample analysis 

Infra-red spectrophotometer 

5.2 Flow diagram of the analytical method for the analysis of 

2-bromo-3,3,3-trifluoropropene in test atmosphere samples 

Sample Assay 

Test atmosphere sample (Gas bag or chamber) 

↓

Sample directly using the IR spectrophotometer 

↓

Perform a single measurement on the IR 

spectrophotometer 

Calibration 

Prepare a set of calibration standards by direct addition of 

a suitable volume of test item directly into gas bags 

containing a suitable volume of air 

↓

Prepare a set of calibration standards for analysis at 

nominal concentrations of 146, 388, 1167, 2042, 2918 

and 3880 ppm 

↓

Measure the response of each calibration standard using 

the IR spectrophotometer for calibration 

IR conditions 

Instrument: MIRAN SapphIRe model 205B 

 

Path length: Short (0.5m) 

 

Wavelength: 10.699 μm 

 

The IR spectrophotometer was calibrated using external standards. Absorbance measurements acquired by the 

IR spectrophotometer were used to calculate analysed concentration (ppm) using a 2nd order fit subjected to least 

squares regression analysis. 

Standards were shared with another concurrent and related study. 

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5.3 Nominal Concentration 

A mean daily nominal concentration was calculated for all test groups from the mass of test 

article used over the exposure period and the airflow through the exposure chamber. The 

ideal gas equation was used with the molecular weight of the test article and the measured 

chamber conditions to compute the volume of vapour produced from the mass of test article 

used. This data is not reported but retained in the raw data. 

5.4 Chamber Temperature 

Monitored using a liquid in glass thermometer. 

5.5 Chamber Humidity 

Monitored using wet and dry liquid in glass thermometers, with humidity calculated using 

proprietary tables. 

6. Data and Calculations 

To minimize the cumulative errors from repeated rounding of numbers, data in this report has 

been calculated continuously using unrounded numbers and only rounded for printing. 

Consequently, presented data may include rounding errors in the last significant figure. 

All data not presented in this report is retained in the study data files and archives. 

7. Results and Discussion 

7.1 Aerosol Concentrations 

Individual exposure concentrations and daily means are presented in Table 1 to 3 and 

summarized below: 

Group Concentration (ppm) 

 Target Mean 

 

2 200 199 

3 500 505 

4 3000 2876 

 

All groups were close to target. 

Additional samples were taken for confirmation of atypical results and after minor generation 

rate adjustments. 

All samples collected for Group 1 were negative for the presence of test article. This 

information is not tabulated but is retained in the study data files. 

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7.2 Chamber Temperature 

The chamber temperature was monitored continuously for all groups and recorded at 

30 minute intervals. Daily means are presented in Table 4 and were within expected 

parameters for this type of exposure system. 

7.3 Chamber Humidity 

The chamber humidity was derived from wet and dry bulb thermometers for all groups. 

These temperatures were recorded at 30 minute intervals and the subsequent humidity 

determined from propriatory tables. Daily means are presented in Table 5 and were within 

expected parameters for this type of exposure system. 

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Table 1 Chamber atmosphere concentration of 

2-bromo-3,3,3-trifluoropropene – daily means and individual 

exposure values – Group 2 

Chamber concentration (ppm) 

Week/ 

Exposure Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Daily mean 

1.1 190 188 190 189 

1.2 190 188 188 189 

1.3 231 192 198 207 

1.4 223 188 194 202 

1.5 188 196 200 195 

2.1 189 195 189 191 

2.2 191 214 191 199 

2.3 63 92 115 147 147 178 124 

2.4 166 92 187 174 155 

2.5 201 206 212 206 

3.1 115 203 212 177 

3.2 1891

 2061 2081 

3.3 86 176 195 187 161 

3.4 199 180 203 194 

3.5 201 206 206 204 

4.1 183 192 194 190 

4.2 188 190 190 189 

4.3 181 194 196 190 

4.4 186 192 196 191 

4.5 181 192 194 189 

5.1 190 192 192 191 

5.2 192 192 192 192 

5.3 190 195 197 194 

5.4 188 195 195 193 

5.5 190 190 197 192 

6.1 192 194 180 189 

6.2 202 209 207 206 

6.3 213 215 213 214 

6.4 205 211 217 211 

6.5 202 215 219 212 

7.1 211 217 219 216 

7.2 215 215 221 217

7.3 191 197 209 199 

7.4 189 201 203 198 

7.5 188 192 194 191 

8.1 197 199 203 200 

8.2 202 204 212 206 

8.3 202 206 204 204 

8.4 204 210 212 209 

8.5 206 208 204 206 

9.1 205 220 216 214 

9.2 207 212 216 212 

9.3 203 210 218 210 

9.4 216 216 220 217 

9.5 205 220 225 217 

 

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Table 1 Chamber atmosphere concentration of 

2-bromo-3,3,3-trifluoropropene – daily means and individual 

exposure values – Group 2 (continued) 

Chamber concentration (ppm) 

Week/ 

Exposure Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Daily mean 

 

10.1 203 207 210 207 

10.2 175 193 201 190 

10.3 212 214 222 216 

10.4 185 193 210 196 

10.5 212 218 220 217 

11.1 193 200 195 196 

11.2 204 202 208 205 

11.3 232 185 230 216 

11.4 202 210 204 205 

11.5 195 202 202 200 

12.1 205 195 201 200 

12.2 264 187 203 218 

12.3 201 205 207 204 

12.4 199 205 203 202 

12.5 199 205 209 204 

13.1 258 202 193 218 

13.2 189 184 197 190 

13.3 184 189 193 189 

13.4 189 189 193 190 

13.5 193 193 193 193 

14.1 192 196 196 195 

14.2 188 194 196 193 

14.3 192 196 196 195 

 

Mean 1992

sd 15.7 

CV (%) 7.9 

 

1 For exposures 3.2 the samples have been excluded due to standard check bag failures. 

The samples and test article usage are within expected tolerances. 2 Overall mean from occasions 1.1 to 13.5 

sd Standard deviation 

CV (%) Coefficient of variation (sd × 100/mean) 

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Table 2 Chamber atmosphere concentration of 

2-bromo-3,3,3-trifluoropropene – daily means and individual 

exposure values – Group 3 

Chamber concentration (ppm) 

Week/ 

Exposure Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Sample 7 Daily mean 

1.1 553 749 519 677 625 

1.2 132 697 287 708 456 

1.3 485 465 439 463 

1.4 459 503 441 468 

1.5 509 513 467 496 

2.1 464 443 469 459 

2.2 389 486 1 438 

2.3 308 299 786 571 499 471 839 539 

2.4 417 551 456 475 

2.5 346 299 735 630 503 

3.1 394 456 469 440 

3.2 4902

 5662 5162 

3.3 458 486 490 478 

3.4 503 392 564 486 

3.5 407 687 531 467 523 

4.1 462 522 518 501 

4.2 495 409 608 362 469 

4.3 329 453 453 412 

4.4 475 469 608 517 

4.5 460 489 531 493 

5.1 549 505 539 531 

5.2 489 354 503 539 471 

5.3 483 451 489 474 

5.4 517 567 580 555 

5.5 430 517 535 537 505 

6.1 453 453 578 495 

6.2 476 566 615 552 

6.3 498 459 541 499 

6.4 512 516 549 526 

6.5 613 615 642 599 586 541 506 586 

7.1 111 548 409 475 437 810 756 507 

7.2 347 488 453 429

7.3 465 455 518 479 

7.4 536 494 500 510 

7.5 537 513 499 516 

8.1 537 510 522 523 

8.2 511 466 501 493 

8.3 451 507 619 557 534 

8.4 491 852 575 509 607 

8.5 501 466 523 497 

9.1 540 500 487 509 

9.2 743 511 481 571 577 

9.3 716 593 558 520 597 

9.4 476 476 450 467 

9.5 453 452 505 470 

 

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Table 2 Chamber atmosphere concentration of 

2-bromo-3,3,3-trifluoropropene – daily means and individual 

exposure values – Group 3 (continued) 

Chamber concentration (ppm) 

Week/ 

Exposure 

Sample 

1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Sample 7 Daily mean 

 

10.1 511 484 463 486 

10.2 488 469 465 474 

10.3 482 559 534 525 

10.4 488 488 534 503 

10.5 633 528 648 824 593 645 

11.1 520 551 461 511 

11.2 540 538 527 535 

11.3 452 505 514 490 

11.4 468 472 479 473 

11.5 470 509 479 486 

12.1 542 497 501 513 

12.2 515 474 524 504 

12.3 478 466 495 480 

12.4 542 478 505 508 

12.5 476 495 433 468 

13.1 552 469 485 502 

13.2 449 396 507 451 

13.3 516 668 443 542 

13.4 569 523 460 517 

13.5 518 608 561 562 

14.1 395 655 574 541 

14.2 534 534 510 526 

14.3 427 554 514 498 

 

Mean 5053

sd 45.0 

CV (%) 8.9 

 

1 Electrical fault with analyser no sample taken. 2 For exposures 3.2 the samples have been excluded due to standard check bag failures. 

The samples and test article usage are within expected tolerances. 

3 Overall mean from occasions 1.1 to 13.5 

sd Standard deviation 

CV (%) Coefficient of variation (sd × 100/mean) 

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Table 3 Chamber atmosphere concentration of 

2-bromo-3,3,3-trifluoropropene – daily means and individual 

exposure values – Group 4 

Chamber concentration (ppm) 

Week/ 

Exposure Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Daily mean 

1.1 2854 2716 2902 2824 

1.2 2726 2838 2392 2652 

1.3 2490 2621 2713 2608 

1.4 2379 2147 2414 2313 

1.5 2364 2110 1788 2087 

2.1 2265 2240 2253 2253 

2.2 702 2104 1992 1 1599 

2.3 3175 3332 3191 3092 2817 3121 

2.4 2860 2584 2362 2602 

2.5 1990 2293 3007 2430 

3.1 3095 2975 3356 3142 

3.2 26972 29442 27072 

3.3 2046 2224 2771 2278 2330 

3.4 2586 3863

 3148 3228 2987 

3.5 2871 3856 3268 1575 2864 2887 

4.1 3274 3030 3111 3138 

4.2 3030 3415 3518 3184 3287 

4.3 2426 3316 3297 3013 

4.4 3297 3027 3349 3224 

4.5 2845 3200 3168 3071 

5.1 3043 2858 3095 2999 

5.2 3422 3016 1707 2994 2888 2805 

5.3 2301 3087 2745 2711 

5.4 2977 3696 2734 3136 

5.5 2615 2745 3040 2874 2819 

6.1 2711 2795 3377 2961 

6.2 2766 3262 2401 3341 2943 

6.3 2908 2751 3256 2972 

6.4 3224 3243 3181 3216 

6.5 2483 3181 2714 2546 3458 2876 

7.1 719 2939 2550 3526 3387 2958 2680 

7.2 2345 2435 3136 2917 2708

7.3 2476 2936 2721 2606 2684 2685 

7.4 2338 2710 2826 2625 

7.5 2734 2990 2721 2815 

8.1 2731 2809 3023 2854 

8.2 2717 3088 2880 2895 

8.3 2638 2707 3287 2877 

8.4 3214 3106 2955 3092 

8.5 4103 3168 2717 2702 3173 

9.1 3217 2953 2783 2984 

9.2 3209 2796 2791 2932 

9.3 2877 3179 2806 2954 

9.4 3017 2882 2838 2912 

9.5 2895 2778 3030 2901 

 

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Table 3 Chamber atmosphere concentration of 

2-bromo-3,3,3-trifluoropropene – daily means and individual 

exposure values – Group 4 (continued) 

Chamber concentration (ppm) 

Week/ 

Exposure Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Daily mean 

 

10.1 2138 2974 3216 2816 2786 

10.2 2983 3108 3111 3067 

10.3 3276 2706 3162 3048 

10.4 2716 3097 3602 2430 2961 

10.5 4242 2824 2631 2805 3126 

11.1 3236 3016 2790 3014 

11.2 2809 2793 2683 2762 

11.3 3211 2899 2753 2954 

11.4 2822 2936 2925 2894 

11.5 3043 3076 2848 2989 

12.1 2761 2700 2929 2797 

12.2 3472 3163 2758 3131 

12.3 2996 2964 2755 2905 

12.4 3447 3608 3006 3354 

12.5 3048 3334 3160 3181 

13.1 3412 3096 2750 3086 

13.2 2750 2807 3111 2889 

13.3 2818 1932 2986 2579 

13.4 2912 2929 3134 2992 

13.5 3427 3415 3448 3430 

14.1 3328 3229 3247 3268 

14.2 3707 3107 3219 2911 3236 

14.3 2864 3014 2814 2897 

 

Mean 28764

sd 304 

CV (%) 10.6 

 

1 Electrical fault with analyser no sample taken. 2 For exposures 3.2 the samples have been excluded due to standard check bag failures. The samples and 

test article usage are within expected tolerances.

3 Value omitted from daily mean due to sample taken when pressure vessel was empty, vessel refilled 

and sample repeated. 4 Overall mean from occasions 1.1 to 13.5 

sd Standard deviation 

CV (%) Coefficient of variation (sd × 100/mean) 

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Table 4 Chamber Temperature - daily mean values 

Exposure 

Week/Day 

Chamber Temperature (°C) 

Group 1 Group 2 Group 3 Group 4 

 

1.1 23.8 22.1 22.1 22.9 

1.2 23.8 22.8 22.7 23.0 

1.3 24.7 22.5 22.3 23.0 

1.4 24.5 22.2 22.0 22.4 

1.5 24.7 22.9 22.5 23.2 

2.1 24.6 22.6 22.5 22.9 

2.2 24.4 22.5 22.2 22.7 

2.3 25.9 23.9 23.0 23.8 

2.4 24.8 23.9 23.0 23.6 

2.5 26.0 23.7 23.2 24.3 

3.1 24.7 23.4 22.7 24.2 

3.2 24.1 22.5 21.9 24.3 

3.3 24.9 22.8 21.8 23.7 

3.4 25.3 22.9 22.8 23.4 

3.5 25.0 23.8 23.6 24.2 

4.1 25.4 24.0 23.2 24.4 

4.2 24.8 24.3 23.3 24.3 

4.3 25.1 24.5 23.3 24.2 

4.4 24.8 24.2 23.4 25.0 

4.5 25.6 24.8 23.8 24.2 

5.1 25.2 24.3 23.7 24.4 

5.2 25.3 24.6 23.9 24.8 

5.3 25.5 24.8 23.6 25.0 

5.4 25.9 24.5 23.9 24.4 

5.5 25.5 24.9 23.8 24.7 

6.1 25.5 24.3 23.4 25.4 

6.2 25.7 23.8 23.0 24.8 

6.3 25.4 23.8 22.9 25.3 

6.4 25.3 24.3 22.9 24.6 

6.5 26.2 23.8 22.4 24.6 

7.1 25.7 22.7 22.8 24.9 

7.2 25.8 22.6 23.4 25.0 

7.3 26.2 23.8 23.2 24.0 

7.4 25.8 23.6 23.4 23.8 

7.5 25.6 24.1 24.3 25.3 

8.1 26.1 24.3 23.8 25.8 

8.2 25.8 23.8 23.7 24.9 

8.3 25.8 23.8 23.3 24.5 

8.4 26.5 24.7 23.8 25.0 

8.5 26.6 24.7 23.0 24.3 

9.1 25.9 24.0 23.3 24.9 

9.2 25.5 23.7 23.9 24.4 

9.3 25.6 24.0 22.3 25.1 

9.4 24.7 22.3 22.6 24.2 

9.5 25.6 22.9 21.6 23.6 

10.1 24.2 21.7 22.8 23.9 

10.2 25.0 23.8 22.5 23.8 

10.3 24.9 23.1 22.8 23.6 

10.4 23.9 22.9 22.6 23.0 

10.5 25.3 23.0 22.1 23.8 

 

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Table 4 Chamber Temperature - daily mean values- (Continued) 

Exposure 

Week/Day 

Chamber Temperature (°C) 

Group 1 Group 2 Group 3 Group 4 

 

11.1 24.3 23.0 22.3 23.6 

11.2 24.8 23.5 23.0 24.2 

11.3 24.9 23.1 22.9 23.5 

11.4 24.9 23.0 22.7 23.8 

11.5 24.8 22.8 22.3 23.0 

12.1 24.9 23.4 22.7 24.4 

12.2 24.9 23.1 22.8 24.0 

12.3 24.9 22.9 22.8 24.1 

12.4 24.9 23.1 22.8 24.0 

12.5 25.1 23.1 22.7 24.1 

13.1 24.3 22.4 21.6 23.2 

13.2 22.8 20.9 20.8 21.6 

13.3 22.7 19.5 20.8 22.3 

13.4 22.9 21.0 20.9 22.1 

13.5 23.7 21.8 21.2 22.2 

14.1 21.0 20.9 20.5 20.9 

14.2 20.9 20.2 20.0 20.7 

14.3 20.6 20.0 20.0 20.5 

 

Mean 24.9 23.2 22.7 23.9 

sd 1.19 1.17 0.94 1.10 

CV (%) 4.8 5.1 4.2 4.6 

 

sd Standard deviation 

CV (%) Coefficient of variation (sd × 100/mean) 

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Table 5 Chamber Humidity - daily mean values 

Exposure 

Week/Day 

Chamber Humidity (%) 

Group 1 Group 2 Group 3 Group 4 

 

1.1 31.1 27.2 32.8 36.8 

1.2 29.1 22.9 22.8 38.6 

1.3 25.0 26.2 25.7 37.2 

1.4 26.8 26.5 34.8 42.7 

1.5 25.2 21.7 24.2 37.0 

2.1 28.0 35.9 28.5 38.5 

2.2 29.6 34.3 30.6 39.0 

2.3 30.9 49.6 32.9 47.2 

2.4 52.0 51.2 29.9 51.2 

2.5 30.2 37.5 40.2 39.2 

3.1 72.5 46.2 48.6 60.2 

3.2 50.9 48.0 40.2 53.1 

3.3 34.5 50.1 48.9 78.0 

3.4 35.8 36.5 51.2 68.1 

3.5 49.9 31.6 41.6 51.6 

4.1 28.3 37.1 47.8 53.1 

4.2 44.2 29.1 38.1 64.4 

4.3 35.8 30.8 47.9 50.9 

4.4 41.5 36.5 44.0 54.9 

4.5 34.5 30.7 44.6 57.0 

5.1 39.7 35.2 47.7 49.9 

5.2 36.7 38.5 44.8 49.8 

5.3 34.8 38.0 49.4 48.2 

5.4 39.0 35.0 44.4 57.7 

5.5 33.5 32.0 41.6 50.2 

6.1 33.0 39.0 42.9 50.7 

6.2 31.5 36.8 49.2 53.8 

6.3 34.0 39.6 38.3 41.8 

6.4 40.8 38.3 42.4 47.8 

6.5 35.2 43.5 41.2 56.5 

7.1 29.8 51.4 60.1 44.7 

7.2 29.5 51.6 53.8 45.5 

7.3 28.7 41.3 46.3 63.8 

7.4 32.1 43.8 50.0 61.0 

7.5 29.2 32.2 43.6 47.8 

8.1 25.9 29.0 38.5 48.4 

8.2 29.8 37.0 38.1 49.3 

8.3 27.3 32.6 41.1 55.5 

8.4 31.3 30.2 40.6 48.4 

8.5 33.0 33.0 44.1 54.7 

9.1 29.0 38.4 44.4 47.2 

9.2 32.1 32.5 50.1 58.9 

9.3 32.6 29.2 40.3 44.5 

9.4 30.2 27.8 39.6 42.6 

9.5 29.4 26.8 34.9 49.2 

10.1 24.8 49.5 37.5 41.2 

10.2 20.4 32.7 36.8 38.9 

10.3 21.9 18.3 33.1 45.4 

10.4 21.9 21.1 27.8 54.0 

10.5 18.5 21.2 33.8 47.6 

 

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Table 5 Chamber Humidity - daily mean values- (Continued) 

Exposure 

Week/Day 

Chamber Humidity (%) 

Group 1 Group 2 Group 3 Group 4 

 

11.1 20.8 21.2 35.1 40.8 

11.2 20.3 22.0 31.8 34.5 

11.3 18.7 22.2 33.8 39.8 

11.4 23.1 19.6 31.0 38.1 

11.5 14.5 21.2 32.3 49.9 

12.1 20.9 24.2 32.4 39.3 

12.2 22.2 19.9 31.2 42.1 

12.3 23.5 23.0 33.5 43.7 

12.4 22.8 21.4 32.8 42.7 

12.5 20.0 25.3 30.7 49.4 

13.1 20.9 24.0 28.6 49.7 

13.2 21.5 25.0 30.7 49.5 

13.3 26.0 20.7 30.5 47.5 

13.4 23.2 21.1 31.8 47.8 

13.5 16.5 21.3 30.1 49.5 

14.1 22.2 23.7 28.1 46.5 

14.2 20.6 25.8 30.2 43.8 

14.3 22.5 21.2 35.1 50.5 

 

Mean 29.9 31.9 38.3 48.5 

sd 9.49 9.28 7.99 8.08 

CV (%) 31.8 29.1 20.8 16.7 

 

sd Standard deviation 

CV (%) Coefficient of variation (sd × 100/mean) 

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Figure 1 Schematic of Inhalation Exposure System 

D

A B

F

C

E

F

H

I

J

K

Front view Side view

L

Generation Trolley

G

N M

P

Q

O

Key 

A Whole body chamber J Water bath 

B Test material delivery tubing K Generation flowmeters 

C Elutriator L Control valves 

D Secondary generation trolley M Balance for more accurate weighing 

E Magnahelics N Harvard Syringe driver 

F Pressure Vessels O Sampling port 

G Load cells P Extract plenum inside chamber 

H Air-line coil Q Drain for washing down 

I Sintered glass vaporiser Closed during exposure 

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Annex 3 Pathology report
Huntingdon Life Sciences

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Working for a better future

PATHOLOGY REPORT 

2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation 

Administration to CD Rats for 13 Weeks Followed by a 4 Week 

Recovery Period 

HLS study number: WAG0014 

Version ID: Final 2 Report 

Issue date: 07 October 2013 

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Table of Contents 

Signature Page ....................................................................................................................... 2

1. Introduction .................................................................................................................... 4

1.1 Objective ............................................................................................................ 4

2. Results ........................................................................................................................... 4

2.1 Decedents .......................................................................................................... 4

2.2 Macroscopic Pathology ...................................................................................... 4

2.2.1 Animals killed after 13 weeks of treatment ............................................. 4

2.2.2 Animals killed after 4 weeks of recovery ................................................ 5

2.3 Microscopic Pathology ....................................................................................... 6

2.3.1 Animals killed after 13 weeks of treatment ............................................. 6

2.3.2 Animals killed after 4 weeks of recovery .............................................. 13

3. Discussion .................................................................................................................... 14

4. Conclusion ................................................................................................................... 16

5. References ................................................................................................................... 17

. 

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1. Introduction 

1.1 Objective 

Assessment of local and systemic toxic potential in a 13 week inhalation study in CD Rats 

with assessment of reversibility, progression, or delayed appearance of any observed effects 

over both a 4 week recovery (non-dosing) period. 

Group Treatment 

Achieved 

Exposure level 

(ppm) 

Number of animals 

Main study Recovery Phase 

Male Female Male Female 

 

1 Control 0 10 10 10 10 

2 2-bromo-3,3,3-trifluoropropene 199 10 10 - - 

3 2-bromo-3,3,3-trifluoropropene 505 10 10 - - 

4 2-bromo-3,3,3-trifluoropropene 2876 10 10 10 10 

 

2. Results 

2.1 Decedents 

One female control animal (No. 27) was killed on Day 52, due to poor clinical condition. 

Irregular surface of the liver; oedematous pancreas and thymus; thickened pericardium, 

adhesion to pericardium and pericardial fluid with the heart; dark bronchial lymph node and 

fluid filled thorax were seen at necropsy. Following microscopic examination, significant 

findings were seen in the lung (perivascular haemorrhage and pleural fibrosis); heart (marked 

pericarditis, adhesion, marked pericardial haemorrhage and marked pericardial fibrosis) and 

the thymus (moderate atrophy). The factor contributory to death is pericarditis. 

2.2 Macroscopic Pathology 

2.2.1 Animals killed after 13 weeks of treatment 

The macroscopic examination performed after 13 weeks of treatment revealed the following 

intergroup differences of note: 

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Teeth 

Pallor was noted in all animals exposed to 2876 ppm, the majority of animals exposed to 

505 ppm and a few animals exposed to 199 ppm. Thickening was seen in the majority of 

females and one male exposed to 2876 ppm. 

Summary of findings in the teeth for animals killed after 13 weeks of treatment 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Incisor(s) pale 0 3 7 10 0 3 9 10 

Incisor(s) thickened 0 0 0 1 0 0 0 8 

 

Number of animals examined 10 10 10 10 9 10 10 10 

Spleen 

Capsular thickening was observed in the majority of males and some females exposed to 

2876 ppm and a few animals exposed to 505 ppm. Adhesions were noted in some females 

exposed to 505 or 2876 ppm. 

Summary of findings in the spleen for animals killed after 13 weeks of treatment 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Capsule thickened 1 1 4 8 0 1 2 5 

Adhesions 0 0 0 0 0 0 2 5 

 

Number of animals examined 10 10 10 10 9 10 10 10 

The nature and incidence of all the other findings were consistent with the commonly seen 

background of macroscopic changes. 

2.2.2 Animals killed after 4 weeks of recovery 

The macroscopic examination performed after 4 weeks of recovery revealed the following 

changes in teeth and spleen. 

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Teeth 

Pallor was noted in all animals exposed to 2876 ppm. Thickening was seen in occasional 

females and one male previously exposed to 2876 ppm. 

Summary of findings in the teeth for animals killed after 4 weeks of recovery 

Group/sex 1M 4M 1F 4F 

Dose (ppm) 0 2876 0 2876 

 

Incisor(s) pale 0 10 0 10 

Incisor(s) thickened 0 1 0 3 

Number of tissues examined 10 10 10 10 

 

Spleen 

Capsular thickening was observed in one male previously exposed to 2876 ppm. Adhesions 

were noted in some males and one female previously exposed to 2876 ppm. 

Summary of findings in the spleen for animals killed after 4 weeks of recovery 

Group/sex 1M 4M 1F 4F 

Dose (ppm) 0 2876 0 2876 

 

Capsular thickened 0 1 0 0 

Adhesions 0 2 0 1 

Number of tissues examined 10 10 10 10 

 

All other findings were considered to be unrelated to treatment. 

2.3 Microscopic Pathology 

2.3.1 Animals killed after 13 weeks of treatment 

Treatment related findings 

Changes related to treatment with 2-bromo-3, 3, 3-trifluoropropene were seen in liver, 

pancreas, heart, spleen, thymus, larynx, nasal turbinates and teeth. 

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Liver 

Centrilobular hepatocyte hypertrophy was seen in rats exposed to 2876 ppm and a female 

exposed to 505 ppm. 

Summary of treatment related findings in the liver for animals killed after 13 weeks of treatment 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Hepatocyte Hypertrophy, 

Centrilobular 

Minimal 0 0 0 2 0 0 1 4 

Total 0 0 0 2 0 0 1 4 

 

Number of tissues examined 10 10 10 10 9 10 10 10 

 

Pancreas 

Increased incidence of acinar cell degranulation was seen in rats at all exposure levels. 

Summary of treatment related findings in the pancreas for animals killed after 13 weeks of treatment 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Acinar Cell Degranulation 

Minimal 0 3 2 1 0 2 3 0 

Slight 0 0 3 5 1 2 2 6 

Moderate 0 0 0 1 0 0 0 0 

Total 0 3 5 7 1 4 5 6 

 

Number of tissues examined 10 10 10 10 9 10 10 10 

 

Heart 

Increased incidence of chronic inflammation was seen in males exposed to 199 ppm and both 

sexes exposed to 505 or 2876 ppm. 

Summary of treatment related findings in the heart for animals killed after 13 weeks of treatment 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Inflammation, Chronic 

Minimal 0 4 2 1 0 0 4 7 

Slight 0 0 7 3 0 0 0 2 

Moderate 0 0 0 4 0 0 0 1 

Total 0 4 9 8 0 0 4 10 

 

Number of tissues examined 10 10 10 10 9 10 10 10 

 

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Spleen 

Increased incidences of capsular inflammation and/ or thickening were seen in rats exposed 

to 505 or 2876 ppm. 

Adhesion was seen in females exposed to 505 or 2876 ppm. 

Summary of treatment related findings in the spleen for animals killed after 13 weeks of treatment 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Capsular Inflammation 

Minimal 0 0 1 2 0 1 0 1 

Slight 0 0 1 3 0 0 1 3 

Moderate 0 0 1 0 0 0 0 2 

Total 0 0 3 5 0 1 1 6 

Capsular Thickening 

Minimal 0 1 1 4 1 2 2 2 

Slight 1 0 2 2 0 0 1 2 

Moderate 0 0 0 0 0 0 0 4 

Total 1 1 3 6 1 2 3 8 

Adhesion 

Total 0 0 0 0 0 0 1 3 

 

Number of tissues examined 10 10 10 10 9 10 10 10 

 

Thymus 

Involution/ atrophy was seen in one male and five female rats exposed to 2876 ppm. 

Summary of treatment related findings in the thymus for animals killed after 13 weeks of treatment 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Involution/Atrophy 

Minimal 0 0 0 0 0 0 0 2 

Slight 0 0 0 0 0 0 0 1 

Moderate 0 0 0 1 0 0 0 2 

Total 0 0 0 1 0 0 0 5 

 

Number of tissues examined 10 10 10 10 9 10 10 10 

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Larynx 

Ventral squamous metaplasia was seen in five male and two female rats exposed to 

2876 ppm. 

Summary of treatment related findings in the larynx for animals killed after 13 weeks of treatment 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Squamous Metaplasia - Ventral 

Minimal 0 0 0 5 0 0 0 2 

Total 0 0 0 5 0 0 0 2 

 

Number of tissues examined 10 10 10 10 9 10 10 10 

 

Nasal Turbinates 

In the respiratory epithelium, atrophy/disorganization/vacuolation, inflammation and 

inflammatory cells in the lamina propria were seen in the rats exposed to 2876 ppm. A case 

of regenerative hyperplasia was also seen in a male at the same exposure level. 

In the olfactory epithelium, atrophy/ disorganisation /vacuolation, was seen in rats exposed to 

505 or 2876 ppm. Inflammation and inflammatory cells in the lamina propria were seen in 

rats exposed to 2876 ppm. Respiratory metaplasia was seen in females exposed to 2876 ppm. 

In the nasolacrimal duct, inflammation was seen in females exposed to 505 ppm and both 

sexes exposed to 2876 ppm. Epithelial squamous metaplasia and luminal inflammatory 

exudates were seen in females exposed to 2876 ppm. 

Inflammatory exudates in airways were seen in rats exposed to 2876 ppm. 

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Summary of treatment related findings in the nasal turbinates for animals killed after 13 weeks of 

treatment 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Increased Vacuolation of 

Vomeronasal Organ Epithelium 

Minimal 0 0 0 1 0 0 0 0 

Slight 0 0 0 2 0 0 0 0 

Total 0 0 0 3 0 0 0 0 

Respiratory Epithelium 

Atrophy/ Disorganisation/ 

Vacuolation 

 

Minimal 0 1 0 1 1 1 1 1 

Slight 0 0 0 4 0 0 0 6 

Moderate 0 0 0 1 0 0 0 3 

Total 0 1 0 6 1 1 1 10 

Inflammation 

Minimal 0 0 0 0 0 0 0 1 

Slight 0 0 0 1 0 0 0 2 

Total 0 0 0 1 0 0 0 3 

Inflammatory Cells in the Lamina 

Propria 

 

Minimal 0 0 0 0 0 0 0 2 

Slight 0 0 0 0 0 0 0 8 

Moderate 0 0 0 1 0 0 0 0 

Total 0 0 0 1 0 0 0 10 

Regenerative Hyperplasia 

Slight 0 0 0 1 0 0 0 0 

Total 0 0 0 1 0 0 0 0 

Olfactory Epithelium 

Atrophy/ Disorganisation/ 

Vacuolation 

 

Minimal 1 2 5 0 0 0 2 0 

Slight 0 0 3 8 1 0 3 4 

Moderate 0 0 0 2 0 0 0 6 

Total 1 2 8 10 1 0 5 10 

Inflammation 

Slight 0 0 0 3 1 0 0 2 

Total 0 0 0 3 1 0 0 2 

Inflammatory Cells in the Lamina 

Propria 

 

Minimal 0 0 0 0 1 0 0 1 

Slight 0 0 0 2 0 0 0 7 

Total 0 0 0 2 1 0 0 8 

Respiratory Metaplasia 

Minimal 0 0 0 0 0 0 0 1 

Slight 0 0 0 0 0 0 0 4 

Total 0 0 0 0 0 0 0 5 

 

Number of tissues examined 10 10 10 10 9 10 10 10 

 

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Summary of treatment related findings in the nasal turbinates for animals killed after 13 weeks of 

treatment (Cont’d) 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Nasolacrimal Duct 

Inflammation 

Minimal 1 3 1 2 2 1 1 0 

Slight 4 5 3 5 0 3 5 5 

Moderate 0 0 0 1 0 0 1 4 

Total 5 8 4 8 2 4 7 9 

Epithelial Squamous Metaplasia 

Minimal 0 1 0 0 1 0 0 1 

Slight 1 0 0 0 1 3 2 2 

Moderate 0 0 0 0 0 0 0 5 

Total 1 1 0 0 2 3 2 8 

Luminal Inflammatory Exudate 

Minimal 0 0 0 0 0 0 0 1 

Slight 0 0 0 0 0 0 0 1 

Moderate 0 0 0 0 0 0 0 2 

Total 0 0 0 0 0 0 0 4 

 

Inflammatory Exudate in Airways 

Minimal 0 0 0 1 0 0 0 3 

Slight 0 0 0 0 0 0 0 2 

Total 0 0 0 1 0 0 0 5 

 

Number of tissues examined 10 10 10 10 9 10 10 10 

Teeth 

Pulp cavity necrosis was seen in females exposed to 2876 ppm. 

Summary of treatment related findings in the teeth for animals killed after 13 weeks of treatment 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Pulp Cavity Necrosis 

Slight 0 0 0 0 0 0 0 4 

Moderate 0 0 0 0 0 0 0 1 

Total 0 0 0 0 0 0 0 5 

 

Number of tissues examined 10 10 10 10 9 10 10 10 

 

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Findings of an uncertain relationship to treatment 

Teeth 

Ameloblast degeneration, odontoblast degeneration and pulp cavity increased inflammatory 

cell infiltration at mostly minimal level were seen in a few rats exposed to 505 or 2876 ppm. 

As this finding was only evident for a small number of animals and there was no clear dose 

relationship, the toxicological significance is uncertain. 

Summary of findings of an uncertain relationship to treatment in the teeth after 13 weeks of treatment 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Ameloblast Degeneration 

Minimal 0 0 0 1 0 0 0 2 

Total 0 0 0 1 0 0 0 2 

Odontoblast Degeneration 

Minimal 0 0 0 1 0 0 2 1 

Total 0 0 0 1 0 0 2 1 

Pulp Cavity Increased 

Inflammatory Cell Infiltration 

 

Minimal 0 0 0 0 0 0 0 1 

Slight 0 0 0 0 0 0 0 1 

Total 0 0 0 0 0 0 0 2 

 

Number of tissues examined 10 10 10 10 9 10 10 10 

 

Incidental findings 

Pyelonephritis, with hyperplasia of both pelvic and papillary epithelium, in the kidneys and 

transitional cell hyperplasia and inflammation in the urinary bladder were seen in two 

females exposed to 2876 ppm. As these findings are occasionally in rats, including controls, 

they are considered to be incidental and unlikely to be related to exposure to the test material. 

Malignant adenocarcinoma was seen in the Harderian gland of a female exposed to 2876 ppm 

and benign subcapsular cell adenoma was seen in the adrenal of a male exposed to 2876 ppm. 

Both findings are considered to be incidental. 

All other histological changes were considered to be unrelated to treatment. 

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2.3.2 Animals killed after 4 weeks of recovery 

Treatment related findings 

Spleen 

Capsular inflammation and/ or thickening at slight level were seen in males previously 

exposed to 2876 ppm. 

Summary of treatment-related changes in the spleen for animals killed after 4 weeks of recovery 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Capsular Inflammation 

Minimal 0 - - 2 0 - - 0 

Total 0 - - 2 0 - - 0 

 

Capsular Thickening 

Minimal 0 - - 0 0 - - 1 

Slight 0 - - 2 0 - - 0 

Total 0 - - 2 0 - - 1 

 

Number of tissues examined 10 - - 10 10 - - 10 

 

Nasal Turbinates 

In the olfactory epithelium, atrophy/ disorganisation/vacuolation, was seen in the rats 

previously exposed to 2876 ppm. 

In the nasolacrimal duct, inflammation was seen in females previously exposed to 2876 ppm. 

Summary of treatment-related changes in the nasal turbinates for animals killed after 4 weeks of 

recovery 

Group/sex 1M 2M 3M 4M 1F 2F 3F 4F 

Dose (ppm) 0 199 505 2876 0 199 505 2876 

 

Olfactory Epithelium 

Atrophy/ Disorganisation/ 

Vacuolation 

Minimal 0 - - 2 1 - - 2 

Slight 0 - - 7 0 - - 5 

Total 0 - - 9 1 - - 7 

 

Nasolacrimal Duct 

Inflammation 

Minimal 4 - - 4 5 - - 3 

Slight 1 - - 2 0 - - 6 

Total 5 - - 6 5 - - 9 

 

Number of tissues examined 10 - - 10 10 - - 10 

 

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Incidental findings 

All other histological changes, including chronic inflammation seen in the heart of one 

control male and one male previously exposed to 2876 ppm, were considered to be unrelated 

to treatment. 

3. Discussion 

Minor localised toxic effects were seen in the upper respiratory tract (larynx and nasal 

turbinates) of animals exposed to 2876 ppm and, to a lesser degree, animals exposed to 505 

ppm. Similar changes were seen in the two previous 2-week dose range studies of the same 

test material (Huntingdon Life Sciences Study Numbers: WAG0013 and WAG0024). 

Following a 4 week recovery period, full recovery was seen for the larynx finding and partial 

recovery for the nasal turbinate findings. 

In the heart, chronic inflammation was seen in males exposed to 199 ppm and both sexes 

exposed to 505 or 2876 ppm. The minimal degree observed at 199 ppm is considered 

unlikely to be associated with any alteration of heart function and is considered not adverse. 

The slight and moderate degrees observed at 505 and 2876 ppm are considered adverse. This 

change may be related to the elevated alkaline phosphatase and aspartate amino transferase 

levels measured during Week 13 of exposures. Complete recovery was seen following the 4 

week recovery period. 

In the spleen, capsular inflammation and/or thickening and adhesion, with corresponding 

macroscopic observations, were seen in animals exposed to 2876 ppm and, to a lesser extent, 

animals exposed to 505 ppm. This is likely to be a toxic effect. Partial recovery was seen 

following the 4 week recovery period with the findings seen in 2 males previously exposed to 

2876 ppm. 

In the thymus, involution/atrophy, with corresponding reduction in organ weight, was seen in 

animals exposed to 2876 ppm. This is likely to be related to stress, as indicated by the effect 

on the body weight and food consumption, experienced by the animals, in the presence of the 

test material, at this exposure level. Complete recovery was seen following the 4 week 

recovery period. 

In the liver, centrilobular hepatocyte hypertrophy at minimal level was seen in animals 

exposed to 2876 ppm and also a female exposed to 505 ppm. This is considered to be an 

adaptive change as a result of exposure to the test material. Complete recovery was seen 

following the 4 week recovery period. 

In the pancreas, increased incidence of acinar cell degranulation was seen in animals at all 

exposure levels. This is not considered to be a toxic response but rather a physiological 

change and likely to be related to the reduced food consumption recorded for these animals. 

Complete recovery was seen following the 4 week recovery period. 

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In the teeth, pulp cavity necrosis, with corresponding macroscopic observations, was seen in 

females exposed to 2876 ppm, and it is considered to be a toxic effect. Full recovery was 

seen following the 4 week recovery period. There were no histopathological changes to 

account for the pale and/or thickened incisors seen macroscopically. 

There were no histopathological changes seen in the study to account for the increased lung 

weight or the reduced salivary gland weight recorded for the treated animals. 

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4. Conclusion 

Following exposure of CD rats to atmospheres of 2-bromo-3,3,3-trifluoropropene for 

13 weeks, test substance related findings were seen in the liver (centrilobular hepatocyte 

hypertrophy), pancreas (acinar cell degranulation), heart (chronic inflammation), spleen 

(capsular inflammation and/or thickening and adhesion), thymus (involution/atrophy), nasal 

turbinates (findings related to minor local irritants), larynx (ventral squamous metaplasia) and 

teeth (pulp cavity necrosis). The majority of these findings were seen with animals at 505 

and 2876 ppm. Chronic inflammation in the heart and acinar cell degranulation in the 

pancreas were evident for animals exposed to 199 ppm, however, these changes are not 

considered to be adverse. 

Following the 4 week recovery period, there was complete recovery of test material related 

histopathological changes seen in the liver, pancreas, heart, thymus, larynx and teeth and 

partial recovery for the findings see in the spleen (capsular inflammation and/or thickening) 

and nasal turbinates (atrophy/disorganisation/vacuolation of the olfactory epithelium and 

nasolacrimal duct inflammation). 

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5. References 

Huntingdon Life Sciences Study Number: WAG0013 

2-bromo-3,3,3-trifluoropropene: Dose Range Finding Study by Inhalation Administration to 

Rats for 2 Weeks 

Huntingdon Life Sciences Study Number: WAG0024 

2-bromo-3,3,3-trifluoropropene: Dose Range Finding Study by Inhalation Administration to 

Rats for 2 Weeks 

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Annex 4 External pathology peer review report
Nova Pathology, PC

Histopathology Review of the Heart in Male Rats: 

 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation 

Administration to CD Rats for 13 Weeks Followed by a 4 Week 

Recovery Period 

Nova Pathology Study Number: 13-025 

Test Facility Study Number: WAG0014 

Submitted By: 

Michael J Tomlinson, D.V.M, Ph.D. 

Diplomate, ACVP 

Nova Pathology, PC 

1015 Railroad Ave., Suite 103 

Bellingham, WA 98225, USA 

Sponsor: 

American Pacific Corporation 

3883 Howard Hughes Parkway, Suite 700 

Las Vegas, NV 89169, USA 

Test Facility: 

Huntingdon Life Sciences 

Eye, Suffolk 

1P23 7PX 

England 

Huntingdon Life Sciences

WAG0014

662
Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study 

by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period 

Test Facility Study Number: WAG0014 

 

Table of Contents 

1 Quality Assurance 3 

2 Signature Page 3

3 Summary of Histologic Findings 4 

4 Introduction 5 

 4.1 Experimental Design 5 

 4.2 Evaluation Procedure 5 

 4.3 Diagnostic Terms 6 

5 Results / Discussion 6 

6 Conclusions 9 

In-Text Tables 

1 Summary of Experimental Design 5 

2 Summary of Selected Histologic Findings in the Heart: Main Study 7 

3 Summary of Selected Histologic Findings in the Heart: Recovery 8 

Data Tables 

1 Summary of Histologic Findings: Main Study 10 

2 Summary of Histologic Findings: Recovery 12 

3 Individual Animal Data 14 

4 Tabulated Summary of Study Pathologist and Reviewing Pathologist Findings 23 

 

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664
Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study 

by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period 

Test Facility Study Number: WAG0014 

 

3 Summary of Test Article-Related Histologic Findings 

The objective of this independent histopathology review was to more completely characterize the 

test article-related histologic findings in the heart of male rats in all groups in study WAG0014, 

Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study 

by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period, 

conducted by Huntingdon Life Sciences, Eye, Suffolk, 1P23 7PX, England. The findings 

attributed to the test article by the reviewing pathologist are: 

2-bromo-3,3,3-trifluoropropene 199 ppm 

1. Minimal chronic inflammation in the heart in 4 of 10 males in the main study. 

2-bromo-3,3,3-trifluoropropene 505 ppm 

1. Minimal to slight chronic inflammation in the heart in 9 of 10 males in the main study. 

2-bromo-3,3,3-trifluoropropene 2,876 ppm 

1. Minimal to moderate chronic inflammation in the heart in 8 of 10 males in the main study. 

Huntingdon Life Sciences

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665
Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study 

by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period 

Test Facility Study Number: WAG0014 

 

4 Introduction

The objective of this independent histopathology review was to more completely characterize the 

test article-related histologic findings in the heart of male rats in all groups in study WAG0014, 

Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study 

by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period, 

conducted by Huntingdon Life Sciences, Eye, Suffolk, 1P23 7PX, England. 

4.1 Experimental Design 

This was a 13 week repeat exposure inhalation toxicity study in Crl:CD (SD) rats followed by a 4 

week recovery period. The animals received clean air (control) or 2-bromo-3,3,3-trifluoropropene

6 hours/day, for 5 days each week for 13 weeks. The study included 10 rats per sex per group per 

scheduled sacrifice as outlined in the Summary of Experimental Design. 

In-Text Table 1: 

Summary of Experimental Design

Group Dose (ppm) 

2-bromo-3,3,3-trifluoropropene

Number of Animals 

Main Study Recovery 

Male Female Male Female 

1 0 10 10 10 10 

2 199 10 10 - - 

3 505 10 10 - - 

4 2,876 10 10 10 10 

4.2 Evaluation Procedure 

This review was conducted at Nova Pathology, 1015 Railroad Ave., Suite 103, Bellingham, WA 

98225, USA on April 14 and 15, 2013. While this review was not a peer-review (no interaction 

between study pathologist and reviewing pathologist), the reviewing pathologist followed as 

appropriate the guidelines set forth in the recommendations for peer review published by the 

Society of Toxicologic Pathology (Morton, D, et al, Toxicologic Pathology, 38: 1118-1127, 

2010). Slides containing hematoxylin and eosin (H&E) stained sections of heart from all male 

rats in this study were evaluated by light microscopy. Initially the slides from control and highdose males were reviewed in order to identify baseline findings in controls and possible test 

article-related findings in high-dose animals in the main study. The slides from mid and low dose 

main study groups and control and high-dose recovery groups were then evaluated. The 

reviewing pathologist entered the histologic findings into a validated data management program 

(Graham StarToxTM version 3.0.0). The findings of the reviewing pathologist are presented in the 

data tables (1, 2 and 3). The relationship of observed histologic findings to the test article, 2-

bromo-3,3,3-trifluoropropene, was determined from the incidence and severity of those findings. 

An increase in either incidence or severity with increasing exposure to the test article relative to 

the control group indicated that finding to be related to the test article. No statistical evaluation of 

the data from this review was performed due to the nature of histopathology data and the low 

number of animals in each group. 

Major differences between the study pathologist and the reviewing pathologist included absence 

of a diagnosis for a non-proliferative or proliferative lesion which was present or the presence of 

a diagnosis for a non-proliferative or proliferative lesion which was not present. Minor 

differences between the study pathologist and the reviewing pathologist included a difference of 

one severity grade or a difference of a severity grade of minimal and not present. 

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4.3 Diagnostic Terms 

The following diagnostic terms are defined to aid in the interpretation and discussion of the data. 

Other diagnostic terms used were considered to be self-explanatory. 

Inflammation, Chronic: Myocardial infiltrates of macrophages with fewer lymphocytes, 

interstitial fibroplasia/fibrosis and capillary dilatation, most often observed in the apex, 

interventricular septum and free wall of the left ventricle. 

Infiltrate, Cellular, Myocardium: Focal aggregates of infiltrating lymphocytes with fewer 

macrophages in the myocardium; most often but not exclusively found in the free wall of the left 

and right ventricles (equivalent to cardiomyopathy). 

Hemorrhage: Extravascular blood within the myocardium; associated with foci of inflammation 

or cellular infiltrates. 

The scheme for severity scoring of histologic findings used in the WAG0014 pathology report 

was maintained for consistency. 

Minimal: The lowest grade of a lesion which is discernible/distinguishable from normal and is 

often subtle and/or involves a very small area of the organ. 

Slight: Clearly discernible/distinguishable from normal with more extensive or more apparent 

changes than minimal. 

Moderate: Generally involves a significant portion of the affected organ or tissue. 

Marked: Involves the majority of the affected organ or tissue. 

Severe: Involves all or almost all of an affected organ or tissue. 

5 Results / Discussion 

The histologic findings in the heart recorded by the reviewing pathologist are presented in the 

following data tables. 

 Table 1: Summary of Histologic Findings, Main study 

 Table 2: Summary of Histologic Findings, Recovery 

 Table 3: Individual Animal Data 

 Table 4: Tabulated Summary of Study Pathologist and Reviewing Pathologist Findings 

The histologic findings recorded were assigned semi-quantitative severity scores based on the 

following scheme; minimal = 1, slight = 2, moderate = 3, marked = 4 and severe = 5 . 

The study pathologist identified myocardial inflammatory cell infiltration/fibrosis as a test articlerelated histologic finding in males at 199, 505 and at 2,876 ppm. The reviewing pathologist 

identified this finding as described by the study pathoogist but recognized a second finding 

identified as cellular infiltrate, myocardium, which was distinct both morphologically and in 

distribution from chronic inflammation. After review of all male hearts from main study and 

recovery males, it was unclear to the reviewing pathologist whether or not the diagnostic term 

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used by the study pathologist, myocardial inflammatory cell infiltration/fibrosis study pathologist 

included the finding of myocardial cellular infiltrates identified by the reviewing pathologist. 

Main Study 

The only histologic finding in the heart that was attributed to the test article in main study animals 

by the reviewing pathologist was chronic inflammation in Groups 2, 3 and 4. The incidence and 

incidence by severity of this finding are presented in the following table. 

In-Text Table 2: 

Summary of Selected Histologic Findings in the Heart: Main Study 

Finding Incidence / Incidence by 

Severity 

Group 

1 2 3 4 

Within Normal Limits Incidence 6/10 6/10 1/10 1/10 

Inflammation, Chronic 

Incidence 0/10 4/10 9/10 8/10 

minimal 0/10 4/10 3/10 1/10 

slight 0/10 0/10 6/10 4/10 

moderate 0/10 0/10 0/10 3/10 

Infiltrate, Myocardium 

Cellular 

Incidence 4/10 2/10 2/10 4/10 

minimal 4/10 2/10 2/10 4/10 

Incidence = Number Affected / Number Evaluated 

In the main study, based on the data summarized above, chronic inflammation in the myocardium 

was considered to be related to the test article in males at 199, 505 and at 2,876 ppm. This 

finding was regionally diffuse and most common in the apex and interventricular septum when of 

minimal severity and but was also present in the ventricular free walls at slight or moderate 

severity. 

Chronic inflammation was present in 4 of 10, 9 of 10 and 8 of 10 rats exposed to the test article at 

199, 505 or 2,876 ppm, respectively. The severity of this finding was generally similar, minimal 

to moderate, in animals exposed at 505 or 2,876 ppm but was of minimal severity in the 4 

affected animals exposed at 199 ppm. Chronic inflammation of minimal severity consisted 

predominantly of cellular infiltrates and capillary dilatation with fibroplasia/fibrosis being a 

minor part of the finding, even at slight or moderate severity. 

Cellular infiltrates in the myocardium were focal and most often in the free wall of the left and 

right ventricles. This finding occurred in all dose groups, was of minimal severity in all affected 

animals and did not have a dose-related incidence. Sometimes referred to as cardiomyopathy, 

this is a common finding in naïve male rats (Chanut, F. et al, Toxicologic Pathology, 00: 1-11, 

2013, online). Based on its incidence and severity in this study, this finding was considered to be 

incidental and unrelated to the test article. Hemorrhage in one control rat was considered 

incidental. 

Recovery 

After the 4 week recovery period, both the incidence and severity of chronic inflammation in the 

myocardium were reduced relative to the main study high-dose group. The incidence and 

incidence by severity of this finding are presented in the following table. 

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by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period 

Test Facility Study Number: WAG0014 

 

In-Text Table 3: 

Summary of Summary of Selected Histologic Findings in the Heart: Recovery 

Finding Incidence / Incidence by 

Severity 

Group 

1 4 

Within Normal Limits Incidence 3/10 6/10 

Inflammation, Chronic 

Incidence 1/10 1/10 

minimal 0/10 1/10 

slight 1/10 0/10 

Infiltrate, Myocardium Cellular Incidence 6/10 3/10 

minimal 6/10 3/10 

Incidence = Number Affected / Number Evaluated 

After a 4 week recovery period, chronic inflammation was minimal in 1 of 10 high-dose animals. 

Chronic inflammation was also present in 1 of 10 control animals after the recovery period. The 

chronic inflammation in the affected control animal occurred in the apex and interventricular 

septum. Similar to the distribution within the heart, the morphologic features of this finding 

were also similar to those in the groups exposed to the test article though the interventricular 

septum contained a large focal infiltrate of mainly lymphocytes and was associated with 

hemorrhage. Based on the similarity of the incidence and morphology of chronic inflammation in 

the affected control and high-dose recovery animals, this finding was considered to have resolved 

after the 4 week recovery period. 

Minimal cellular infiltrates in the myocardium were present in 6 of 10 control rats and in 3 of 10 

high-dose rats and were considered to be incidental and unrelated to the test article. Hemorrhage 

in one control rat was considered incidental. 

Comparison of Study Pathologist and Reviewing Pathologist Findings 

This histopathology review was limited to sections of the heart of male rats from Study 

WAG0014. The findings of the study pathologist and the reviewing pathologist are compared in 

data Table 4: Tabulated Summary of Study Pathologist and Reviewing Pathologist Findings. 

Myocardial inflammatory cell infiltration/fibrosis was the only histologic finding in the heart that 

was attributed to the test article by the study pathologist. The reviewing pathologist identified 

chronic inflammation in the myocardium as a test article-related finding. The reviewing 

pathologist also identified a second finding, myocardial cellular infiltrates (sometimes referred to 

as cardiomyopathy), which was not a test article-related finding. The study pathologist did not 

record the presence of cellular infiltrates, of cardiomyopathy or of another equivalent term. It 

was unclear to the reviewing pathologist whether the study pathologist considered cellular 

infiltrates to be part of the finding of myocardial inflammatory cell infiltration/fibrosis or were 

considered incidental and were not recorded. 

The study pathologist (myocardial inflammatory cell infiltration/fibrosis) and the reviewing 

pathologist (chronic inflammation) both identified equivalent test article-related histologic 

findings in the heart of male rats at exposures of 199, 505 and 2,876 ppm of 2-bromo-3,3,3-

trifluoropropene at the end of the exposure period and both pathologists considered these findings 

to have resolved after a 4 week recovery period. For these reasons, the study pathologist and the 

reviewing pathologist were in general agreement. 

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6 Conclusions 

In this independent expert review, sections of heart from all main study and recovery male rats in 

this study were examined by light microscopy. The only histologic finding in the heart that was 

attributed to 2-bromo-3,3,3-trifluoropropene was chronic inflammation in the myocardium. This 

finding was related to 2-bromo-3,3,3-trifluoropropene in males at 199, 505 and 2,876 ppm in 

main study animals. This finding was considered to have resolved after a 4 week recovery 

period. 

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Test Facility Study Number: WAG0014 

 

Data Table 1 

Summary of Histologic Findings: 

Main Study 

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Summary of Histologic Findings: Main Study

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Organs Group: Group 1 Group 2 Group 3 Group 4

Diagnoses Sacrifice: MS MS MS MS

Modifiers Sex: M M M M

Total Animals Selected: [10] [10] [10] [10]

Heart (10) (10) (10) (10)

Within Normal Limits 6 6 1 1

Hemorrhage 1 0 0 0

minimal 1 0 0 0

Infiltrate, Cellular, Myocardium 4 2 2 4

minimal 4 2 2 4

Inflammation, Chronic 0 4 9 8

minimal 0 4 3 1

slight 0 0 6 4

moderate 0 0 0 3

Group 1=Control

Group 2=2-bromo-3,3,3-trifluoropropene, 199 ppm

Group 3=2-bromo-3,3,3-trifluoropropene, 505 ppm

Group 4=2-bromo-3,3,3-trifluoropropene, 2,876 ppm

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by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period 

Test Facility Study Number: WAG0014 

 

Data Table 2 

Summary of Histologic Findings: 

Recovery 

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Summary of Histologic Findings: Recovery

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Organs Group: Group 1 Group 4

Diagnoses Sacrifice: RE RE

Modifiers Sex: M M

Total Animals Selected: [10] [10]

Heart (10) (10)

Within Normal Limits 3 6

Hemorrhage 1 0

minimal 1 0

Infiltrate, Cellular, Myocardium 6 3

minimal 6 3

Inflammation, Chronic 1 1

minimal 0 1

slight 1 0

Group 1=Control

Group 4=2-bromo-3,3,3-trifluoropropene, 2,876 ppm

Page: 2

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Data Table 3 

Individual Animal Data 

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Gp: ( 1) Control Animal Number: 61 Species: Rat Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 1) Control Animal Number: 62 Species: Rat Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 1) Control Animal Number: 63 Species: Rat Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 1) Control Animal Number: 64 Species: Rat Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 1) Control Animal Number: 65 Species: Rat Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 1) Control Animal Number: 66 Species: Rat Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, apex, focal, minimal

Gp: ( 1) Control Animal Number: 67 Species: Rat Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 1) Control Animal Number: 68 Species: Rat Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, atrium, focal, minimal

Gp: ( 1) Control Animal Number: 69 Species: Rat Sex: Male 

Microscopic Results

Heart Hemorrhage, focal, apex, minimal

Infiltrate, Cellular, Myocardium, apex, left ventricle, right ventricle, minimal

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Individual Animal Data

Study Number: WAG0014

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Eye, Suffolk, 1P23 7PX, England

Gp: ( 1) Control Animal Number: 70 Species: Rat Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, left ventricle, focal, minimal

Gp: ( 1) Control Animal Number: 81 Species: Rat Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, focal, minimal

Gp: ( 1) Control Animal Number: 82 Species: Rat Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, apex, minimal

Gp: ( 1) Control Animal Number: 83 Species: Rat Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, left ventricle, focal, minimal

Gp: ( 1) Control Animal Number: 84 Species: Rat Sex: Male 

Microscopic Results

Heart Hemorrhage, myocardium, interventricular septum, minimal

Inflammation, Chronic, apex, interventricular septum, slight

 One large focus in the IVS is associated with the hemorrhage.

Gp: ( 1) Control Animal Number: 85 Species: Rat Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, left ventricle, right ventricle, minimal

Gp: ( 1) Control Animal Number: 86 Species: Rat Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 1) Control Animal Number: 87 Species: Rat Sex: Male 

Microscopic Results

Heart Within Normal Limits

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Individual Animal Data

Study Number: WAG0014

Hintingdon Life Sciences

Eye, Suffolk, 1P23 7PX, England

Gp: ( 1) Control Animal Number: 88 Species: Rat Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 1) Control Animal Number: 89 Species: Rat Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, apex, left ventricle, minimal

Gp: ( 1) Control Animal Number: 90 Species: Rat Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, right ventricle, minimal

Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 101 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 102 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 103 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 104 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, minimal

Infiltrate, Cellular, Myocardium, interventricular septum, focal, minimal

Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 105 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

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Table Number: 3

Individual Animal Data

Study Number: WAG0014

Hintingdon Life Sciences

Eye, Suffolk, 1P23 7PX, England

Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 106 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 107 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 108 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, minimal

Infiltrate, Cellular, Myocardium, focal, minimal

Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 109 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, minimal

Gp: ( 2) 2-bromo-3,3,3-trifluoropropene, 199 ppm Animal Number: 110 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, minimal

Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 111 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, interventricular septum, focal, minimal

Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 112 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, right ventricle, slight

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Table Number: 3

Individual Animal Data

Study Number: WAG0014

Hintingdon Life Sciences

Eye, Suffolk, 1P23 7PX, England

Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 113 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, minimal

Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 114 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, left ventricle, slight

Infiltrate, Cellular, Myocardium, right ventricle, focal, minimal

Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 115 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, left ventricle, interventricular septum, slight

Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 116 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, left ventricle, minimal

Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 117 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 118 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, interventricular septum, left ventricle, slight

Infiltrate, Cellular, Myocardium, right ventricle, focal, minimal

Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 119 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, left ventricle, interventricular septum, atrium, slight

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Table Number: 3

Individual Animal Data

Study Number: WAG0014

Hintingdon Life Sciences

Eye, Suffolk, 1P23 7PX, England

Gp: ( 3) 2-bromo-3,3,3-trifluoropropene, 505 ppm Animal Number: 120 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, left ventricle, interventricular septum, slight

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 11 Species: Rat 

Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, left ventricle, focal, minimal

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 12 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, right ventricle, left ventricle, interventricular septum, moderate

 Infiltrates of macrophages and fewer lymphocytes, interstitial fibroplasia/fibrosis and capillary 

 dilatation.

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 13 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, right ventricle, left ventricle, interventricular septum, moderate

Infiltrate, Cellular, Myocardium, focal, left ventricle, minimal

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 14 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, left ventricle, interventricular septum, minimal

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 15 Species: Rat 

Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, right ventricle, focal, minimal

Inflammation, Chronic, apex, interventricular septum, left ventricle, slight

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 16 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, left ventricle, interventricular septum, slight

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Table Number: 3

Individual Animal Data

Study Number: WAG0014

Hintingdon Life Sciences

Eye, Suffolk, 1P23 7PX, England

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 17 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 18 Species: Rat 

Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, left ventricle, focal, minimal

Inflammation, Chronic, apex, left ventricle, interventricular septum, moderate

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 19 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, left ventricle, interventricular septum, slight

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 20 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, left ventricle, right ventricle, interventricular septum, slight

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 71 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 72 Species: Rat 

Sex: Male 

Microscopic Results

Heart Inflammation, Chronic, apex, minimal

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 73 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

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Table Number: 3

Individual Animal Data

Study Number: WAG0014

Hintingdon Life Sciences

Eye, Suffolk, 1P23 7PX, England

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 74 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 75 Species: Rat 

Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, right ventricle, focal, minimal

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 76 Species: Rat 

Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, apex, focal, minimal

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 77 Species: Rat 

Sex: Male 

Microscopic Results

Heart Infiltrate, Cellular, Myocardium, right ventricle, left ventricle, minimal

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 78 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 79 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

Gp: ( 4) 2-bromo-3,3,3-trifluoropropene, 2,876 ppm Animal Number: 80 Species: Rat 

Sex: Male 

Microscopic Results

Heart Within Normal Limits

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by Inhalation Administration to CD Rats for 13 Weeks Followed by a 4 Week Recovery Period 

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Data Table 4 

Tabulated Summary of Study Pathologist and Reviewing Pathologist 

Findings 

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Test Facility Study Number: WAG0014 

Main Study, Group 1 

Pathologist Observation Animal Number 

61 62 63 64 65 66 67 68 

Study Myocardial Inflammatory Cell Infiltration / Fibrosis - - - - - 1 - - 

Reviewing Inflammation, Chronic - - - - - - - - 

Infiltrate, Cellular, Myocardium - - - - - 1 - 1 

Main Study, Group 2 

Pathologist Observation Animal Number 

101 102 103 104 105 106 107 108 

Study Myocardial Inflammatory Cell Infiltration / Fibrosis - - - 2 - - - 1 

Reviewing Inflammation, Chronic - - - 1 - - - 1 

Infiltrate, Cellular, Myocardium - - - 1 - - - 1 

Main Study, Group 3 

Pathologist Observation Animal Number 

111 112 113 114 115 116 117 118 

Study Myocardial Inflammatory Cell Infiltration / Fibrosis 1 2 2 3 2 2 - 2 

Reviewing Inflammation, Chronic 1 2 1 2 2 1 - 2 

Infiltrate, Cellular, Myocardium - - - 1 - - - 1 

Main Study, Group 4 

Pathologist Observation Animal Number 

11 12 13 14 15 16 17 18 

Study Myocardial Inflammatory Cell Infiltration / Fibrosis - 3 3 1 2 3 1 2 

Reviewing Inflammation, Chronic - 3 3 1 2 2 - 3 

Infiltrate, Cellular, Myocardium 1 - 1 - 1 - - 1 

- = Not Present, 1 = minimal, 2 = slight, 3 = moderate; Incidence = number affected / number evaluated 

685

685
Histopathology Review of Heart from Male Rats: 2-bromo-3,3,3-trifluoropropene: Toxicity Study by Inhalation Admini

Weeks Followed by a 4 Week Recovery Period 

Test Facility Study Number: WAG0014 

Recovery, Group 1 

Pathologist Observation Animal Number 

81 82 83 84 85 86 87 88 

Study Myocardial Inflammatory Cell Infiltration / Fibrosis 1 1 - 3 2 - - - 

Reviewing Inflammation, Chronic - - - 2 - - - - 

Infiltrate, Cellular, Myocardium 1 1 1 - 1 - - - 

Recovery, Group 4 

Pathologist Observation Animal Number 

71 72 73 74 75 76 77 78 

Study Myocardial Inflammatory Cell Infiltration / Fibrosis - 1 - - - - 1 - 

Reviewing Inflammation, Chronic - 1 - - - - - - 

Infiltrate, Cellular, Myocardium - - - - 1 1 1 - 

- = Not Present, 1 = minimal, 2 = slight, 3 = moderate; Incidence = number affected / number evaluated 

686

686
Huntingdon Life Sciences

WAG0014

687 

Annex 5 GLP compliance statements 
Huntingdon Life Sciences

WAG0014

688 

EYE RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2011 
Huntingdon Life Sciences

WAG0014

689 

EYE RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2012 
Huntingdon Life Sciences

WAG0014

690 

HUNTINGDON RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2011 
Huntingdon Life Sciences

WAG0014

691 

HUNTINGDON RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2012