### STUDYTITLE 

### 2-BROM0-3,3,3-TRIFLUOROPROPENE,E-1-BROM0-3,3,3-TRIFLUOROPROPENE AND 1-BROM0-2-TRIFLUOROMETHYL-3,3,3-TRIFLUOROPROPENE: ANACUTE (4-HOUR)INHALATIONTOXICITY STUDYINTHERAT VIANOSE-ONLYEXPOSURE

DATAREQUIREMENTS 

### OECDPart403 OPPTS 870.1300 AUTHOR 

### GaryM. Hoffman, B.A., D.A.B.T. STUDY COMPLETIONDATE 

### 14 January 2004 PERFORMINGLABORATORY 

### HuntingdonLife Sciences Mettlers Road, P.O. Box 2360 EastMillstone, New Jersey08875-2360 LABORATORYPROJECTNUMBER 

### 02-5449 SPONSOR 

### AmericanPacific Corporation 3770HowardHughes Parkway Suite 300 Las Vegas, Nevada 89109 TOTALPAGES 

### 172

### HuntingdonLife Sciences 02-5449
GLP COMPLIANCE STATEMENT 

### Page 2 FinalReport

This study was conducted in compliance with the OECD Principles of Good Laboratory Practices ENV /MC/CHEM (98)17 and the United States Environmental Protection Agency's GoodLaboratoryPractice Standards 40 CFRPart792 (TSCA).
StudyDirector:

# £~ 14-JM,o4--

## ~·**~** GaryM. offman, B.A., D.A.B.T.

### Huntingdon Life Sciences

SCIENTISTS 

### 02-5449
SIGNATUREPAGE 

### Page 3 Final Report

The following Scientists were responsible for the overall conduct of this study. Departmental supervisory personnel are listed on the personnel page of this report (AppendixD).

# ~~ 

# - He:i.V.M.,Ph.D. Pathologist
SCIENTIFIC REVIEW 

### Thefollowing Scientistshavereviewed and approved this report.

CarolS. Auletta, MBA, D.A.B.T., R.A.C. SeniorDirector, SafetyAssessment

# Sylv~h.D., Diplomate A.C.V.P. SeniorVicePresident, SafetyAssessment Date

/23

### ~- 

### dL(

Date

### HuntingdonLife Sciences 02-5449 Page4 FinalReport QUALITYASSURANCE STATEMENT 

### Listedb,elow are the dates thatthis studywas inspectedbythe QualityAssuranceUnitof HuntingdonLife Sciences, EastMillstone, NewJersey, andthe dates that findings were reportedto the StudyDirector andManagement. Thisreportreflects theraw data as far as canbereasonably established. Type of Inspection 

### GLP Protocol Review Exposure, Monitoring, Equipment& TrainingRecords TerminalNecropsy & Training

Records FinalReport & StudyData Date(s) of Inspection 

### 07 Jun 02 17 Sep 02

01 Oct 02

06 10 Jan03

Nancy L. 

### Beck Senior QualityAssurance Auditor Reported to StudyDirector andManagement 

### 07 Jun02 17 Sep 02

04 Oct 02

10 Jan03

# 141ct"'"i?C~ J_col{ Date/ 

## \

.. 

### HuntingdonLife Sciences 02-5449 

### 2-BROM0-3,3,3-TRIFLUOROPROPENE, E-1-BROM0-3,3,3-TRIFLUOROPROPENE Page 5 FinalReport



### ANI) 1-BROM0-2-TRIFLUOROMETHYL-3,3,3-TRIFLUOROPROPENE:

AN ACUTE (4-HOUR) INHALATIONTOXICITYSTUDYINTHERAT VIA NOSE-ONLYEXPOSURE SUMMARY This study was designed to assess the potential and comparative acute inhalation toxicity of 2-Bromo-3,3,3-Trifluoropropene, E-1-Bromo-3,3,3-Trifluoropropene and 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene when administered via nose-only exposure. The test substances were initially administered as a vapor to groups of Sprague-Dawley CD® rats (5/sex/group) for four hours at a target concentration of 25,000 ppm. These exposures were performed on 17 September 2002. Based on the resulting mortality, additional exposures were required. 2-Bromo-3,3,3-Trifluoropropene was exposed at a targeted concentration of 5,000 ppm for four hours. E-1-Bromo-3,3,3-Trifluoropropene was exposed at a targeted concentration of 50,000 ppm for four hours. These exposures were performed on 21 October 2002. The exposure levels were determinedusing aMIRAN®AmbientAirAnalyzer. Observations for signs of toxicity were conducted on all animals at 15-minute intervals during the first hour ofexposure and hourly for the remainder ofthe exposure. Detailed physical observations were performed on all animalsjustprior to exposure, immediately upon removal from the chamber, hourly for two hours post-exposure and once daily thereafter. Body weight measurements were obtainedjust prior to exposure and weekly thereafter. After a 14-day post-exposure observation period, survivors were sacrificed. Complete macroscopic postmortem examinations were performed on all animals at the time of death or sacrifice. Selected organs were weighed for all terminally sacrificed animals andthe lungs were examinedmicroscopicallyfor all test animals. Theresults ofthe exposures and subsequentmortality are summarizedas follows: TestSubstance Analytical Mortality Mortality Mortality Concentration Males Females Total (ppm) 2-Bromo-3,3,3- 26,580 

### 515 515 10/10 Trifluoropropene 2-Bromo-3,3,3- 5,173 0/5 0/5 0/10 Trifluoropropene E-1-Bromo-3,3,3- 45,850 2/5 0/5 2/10 Tri:fluoropropene E-1-Bromo-3,3,3- 25,650 

### 015 0/5 0/10 Trifluoropropene 1-Bromo-2- 24,800 5/5 

### 515 10/10 Tri:fluoromethyl-3,3,3- Trifluoropropene

### HuntingdonLife Sciences 02-5449


### SUMMARY Page 6 DraftFinalReport

All of**t~e** 

### animals exposed to 2-Bromo-3,3,3-Trifluoropropene at 26,580 ppmwere found dead or were euthanized in poor condition on the day after the exposure. All of the animals exposed to 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene at 24,800 ppm were found dead within 30 minutes ofthe start ofthe exposure. Both ofthe male animals exposed to E-1-Bromo-3,3,3-Trifluoropropene at 45,850 ppm that were found dead died on the day ofthe exposure. All other animals survivedto termination. Basedon the above results, the LC50 

### values were calculatedto be: TestSubstance Animals 

## LCso 95% ConfidenceLimits (ppm) (ppm) 2-Bromo-3,3,3- Combined 11726 9054to 15186 Trifluoropropene Males 11726 7584to 18129 Females 11726 7584to 18129 E-1-Bromo-3,3,3- Combined 70955 51449 to 97857 Trifluoropropene Males 50950 35358 to73418 Females >45850 NotCalculable 1-Bromo-2- Combined <24,800 NotCalculable Trifluoromethyl-3,3,3- Males <24,800 NotCalculable Trifluoropropene Females <24,800 NotCalculable 

### All surviving animals in all test groups gained weight (or didnotlose weight) duringboth weeks ofobservations. 2-Bromo-3,3,3-Trifluoropropene: The only sign oftoxicity noted during the exposure period was labored breathing or gasping during the last hour ofeach exposure. Clinical signs of toxicity noted immediately following the exposures of 2-Bromo-3,3,3-Trifluoropropene included clear or red nasal discharge, excessive salivation, laboredbreathing and moistrales. The severity andfrequency ofthe signs was increased after the higher level exposure of 26,580 ppm compared to the lower level exposure of5,173 ppm. Gasping and decreased activity were also noted but only after the higher exposure level. There were no apparent effects ofexposure on the organs that were weighed. Macroscopically, one or more rats from both exposure levels had red discolorations ofthe lungs. Fluid was present in the lungs ofone male from the higher level exposure of 26,580 ppm. Test substance-related findings were microscopically present in lungs ofrats in the higherlevel exposure of26,580 ppm. All oftherats, in this group only, had bronchiolar lesions consisting of desquamated epithelium, bronchiolar/peribronchiolar acute/subacute inflammation and/or intraluminal debris; the severity of the findings ranged from slight to moderate. Alveolar/intraalveolar macrophages (minimal to moderate) normally present in the lungs, were most numerous in several oftheserats.

### (·· HuntingdonLife Sciences 02-5449
SUMMARY 

### Page 7 DraftFinalReport

E-1-Bromo-3,3,3-Trifluoropropene: 

### The only sign of toxicity noted during the exposure period was tail quivering and/ortremors during each exposure. Clinical signs of toxicitynotedimmediatelyfollowing the exposures ofE-1-Bromo-3,3,3-Trifluoropropene includedred nasal discharge. The severity and frequency ofthe signs was increased after the higher level exposure of 45,850 ppm compared to the lower level exposure of 25,650 ppm. Excessive salivation, labored breathing and moist rales were also noted but only after the higher exposure level. A few signs of toxicity similar to those seen immediately after the exposures were noted during the first week of the post-exposure observation period. A complete recovery in surviving animals was seen during the remainder of the post-exposure observation period. There were no apparent effects of exposure on the organs that were weighed. Macroscopically, one or more rats from the lowerlevel exposure of25,650 ppmhadred discolorations ofthe lungs. Fluid was present in the lungs oftwo males from the higherlevel exposure of45,850ppm. 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene: 

### All animals were found dead within 30 minutes ofthe exposure initiation. Macroscopically, one or more rats had red discoloration ofthe lungs. In conclusion, the 4-hour acute inhalation toxicity in rats of 2-Bromo-3,3,3-Trifluoropropene, E-1-Bromo-3,3,3-Trifluoropropene and 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene was compared. On the basis oftoxic responses and subsequent mortality, E-1-Bromo-3,3,3-Trifluoropropene was considered the least toxic with an LC50 

### of**~70,955** 

### ppm, 2-Bromo-3,3,3-Trifluoropropene was considered moderately toxic with an LC50 

### of**~**

### 11,726 ppm and 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene was considered the most toxic with an LCso substantiallyless than the onlytested level of24,800 ppm.

### HuntingdonLife Sciences 02-5449
TABLE OF CONTENTS 

### Page 8 Final Report

COVERPAGE
.....................................................................................................................1 GLP COMPLIANCE STATEMENT
..................................................................................2 SIGNATUREPAGE
............................................................................................................3 QUALITY ASSURANCE STATEMENT
..........................................................................4 SUMMARY
.........................................................................................................................5 TABLE OF CONTENTS
.....................................................................................................8 1. 

### INTRODUCTION................................................................................................

### 10 2. 

### MATERIALS AND METHODS 

### 2.1. StudyManagement
....................................................................................10 2.2. StudyDates
................................................................................................10 2.3. Experimental Outline
.................................................................................11 2.4. Justifications
..............................................................................................12 2.5. Test Substances
..........................................................................................12 2.6. TestAnimals
..............................................................................................14 2.7. Animal Assignment
...................................................................................15 2.8. Animal Identification
.................................................................................15 2.9. Veterinary Care
..........................................................................................15 2.10. HusbandryDuringNon-ExposurePeriods
.................................................16 2.11. HusbandryDuringExposure
......................................................................17 2.12. Test Substance Administration and ChamberOperation
...........................18 2.13. Exposure Chamber Sampling
....................................................................22 2.14. ExperimentalEvaluations
..........................................................................23 2.15. Postmortem
................................................................................................24 2.16. Statistical Analysis
.....................................................................................26 2.17. DataStorage
...............................................................................................26 2.18. RegulatoryReferences
...............................................................................26 2.19. ProtocolDeviations
....................................................................................27 3. 

### RESULTS ANDDISCUSSION 

### 3.1. ChamberMonitoring
..................................................................................28 3.2. Mortality
.....................................................................................................28 3.3. BodyWeights
.............................................................................................29 3.4. Physical Observations
................................................................................29 3.5. Pathology
...................................................................................................31 4. 

### CONCLUSION
....................................................................................................

### 32

### HuntingdonLife Sciences**FIGU~S** 

### 02-5449
TABLE OF CONTENTS Page 9 FinalReport

1. 

### DiagramofGeneration and Sampling System (Groups 1- 

### 3)
.....................................33 2. Diagram ofGeneration and Sampling System (Group 4)
............................................34 3. Diagram ofGeneration and Sampling System (Group 5)
............................................35 TABLES 1. ChamberConcentrations, Particle SizeDeterminations and ChamberEnvironment..36 2. BodyWeights andBodyWeight Changes from Day 0
................................................41 3. SummaryofDay0 Observations
.................................................................................43 4. Su:mn1ary of 14-DayPost-Exposure Observations
......................................................47 5. Individual Observations
...............................................................................................51 6. Animal TerminationHistory
........................................................................................61 7. Mean OrganWeights
...................................................................................................62 8. Individual Organ Weights
............................................................................................69 9. Incidence SummaryReportfor Gross Necropsy Observations
....................................76 10. LesionIncidence SummarywithExpandedSeverityLevels
.......................................80 11. Individual Animal Gross andMicroscopic Observations
............................................89 APPENDICES A. EquipmentList
...........................................................................................................140 B. MIRAN®Calibration
.................................................................................................141 C. Protocol andProtocol Amendments
..........................................................................152 D. TestingFacilityPersonnel.
.........................................................................................171 E. ReportAmendments
..................................................................................................172r I 

### ' 

### HuntingdonLife Sciences 02-5449 Page 10 Final Report 1. INTRODUCTION



## 2. The purpose of this study was to assess the potential and comparative acute inhalation toxicity of 2-Bromo-3,3,3-Trifluoropropene, E-1-Bromo-3,3,3- Trifluoropropene and 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene when administeredfor 4 hours via nose-only exposure. MATERIALSAND METHODS 

## 2.1. STUDYMANAGEMENT 

## 2.1.1. SPONSOR 

### American Pacific Corporation 3770HowardHughes Parkway Suite 300 Las Vegas, Nevada 89109 

## 2.1.2. SPONSORREPRESENTATIVE 

### Bradford Colton 

## 2.1.3. TESTINGFACILITY 

### HuntingdonLife Sciences P.O. Box 2360 Mettlers Road EastMillstone,NewJersey08875-2360 

## 2.1.4. STUDYDIRECTOR 

### GaryM. Hoffman, B.A., D.A.B.T. 

## 2.2. STUDYDATES 

## 2.2.1. STUDYINITIATION 

### 15 August 2002 (Date StudyDirector signedthe Protocol)(: 

### HuntingdonLife Sciences 02-5449



## 2.2.2. DATES OFANIMAL RECEIPT Page 11 FinalReport

10 September2002: Groups 1- 3 (Experimental StartDate) 15 October2002: Groups 4- 5 

## 2.2.3. DATES OFEXPOSURE 17 September2002: Groups 1

- 3 21 October2002: Groups 4- 5 

## 2.2.4. TERMINAL SACRIFICES 01 October2002: Groups 1- 3 04November2002: Groups 4-5 

## 2.2.5. EXPERIMENTALTERMINATION 14 January 2004 (Date Final Reportis signedbythe Pathologist) 

## 2.2.6. STUDY COMPLETION \. •·· 14 January 2004 (Date Final Report is signed by the Study Director) 

## 2.3. EXPERIMENTAL OUTLINE Group Test Substance Target Durationof Concentration Exposure (ppm) (Hours) 1 2-Bromo-3,3,3-Trifluoropropene 25,000 4 2 E-1-Bromo-3,3,3-Trifluoropropene 25,000 4 3 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene 25,000 4 4 2-Bromo-3,3,3-Trifluoropropene 5,000 4 5 E-1-Bromo-3,3,3-Trifluoropropene 50,000 4 

### Each group consistedof5male and 5female Sprague-Dawleyrats. All survivors were held for a 14-daypost-exposure observation period. At the end ofthe observation period, a macroscopic and microscopic necropsy examination was performed on all animals.

### HuntingdonLife Sciences 02-5449


### 2.4. JUSTIFICATIONS 2.4.1. ROUTE, DURATIONANDFREQUENCY Page 12 FinalReport

The inhalation route is one of the potential routes of human exposure to these test substances and is the route·specified in the referenced guidelines. The duration ofthe study and frequency of exposures are as recommendedinthereferenced guidelines. 

### 2.4.2. TEST ANIMAL SELECTION The rat is a rodent animal model commonly utilized in toxicity testing as per the regulatoryrequirements. In 

### addition, a historical databaseis availablefor comparativeevaluation. 

### 2.4.3. NUMBER OFANIMALS The number of animals in the study was considered to be the minimumnecessary for scientific and statistical reasons in orderto evaluatethe datawith sufficientconfidencelevels. 

### 2.4.4. EXPOSURE LEVELSELECTION The exposure levels were specified by the Sponsor based on prior testing ofthese or similarchemicals. 

### 2.5. TEST SUBSTANCES 2-Bromo-3,3,3-Trifluoropropene E-1-Bromo-3,3,3-Trifluoropropene 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene 

### 2.5.1. TEST SUBSTANCE CATEGORY Industrial Gases 

### 2.5.2. CAS NUMBER 2-Bromo-3,3,3-Trifluoropropene: 1514-82-5 E-1-Bromo-3,3,3-Trifluoropropene: 149597-47-7 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene: N/ A

## ( HuntingdonLife Sciences 02-5449



### 2.5.3. SUPPLIER AmericanPacific Corp.

- HalotronDivision 10622West, 6400 North Cedar City, Utah 84720 

### 2.5.4. LOT NUMBERS Page 13 FinalReport

2-Bromo-3,3,3-Trifluoropropene: KGA154-2B E-1-Bromo-3,3,3-Trifluoropropene: KGA154-1A (Container#!) 59-57 (Container#2) 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene: 98-27 

### 2.5.5. PURITY 2-Bromo-3,3,3-Trifluoropropene:**~99.5%** 

### E-1-Bromo-3,3,3-Trifluoropropene: 98.3% (Container#l)a 98% (Container#2)b 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene:**~** 

### 99% 

### 2.5.6. DESCRIPTION Colorless volatileliquid 

### 2.5.7. DATES RECEIVED 22 August 2002 (Container#1 ofthe 3 test substances) 14 October 2002 (Container #2 of E-1-Bromo-3,3,3- Trifluoropropene) 

### 2.5.8. EXPIRATIONDATE Not available (stable, perMSDS) 

### 2.5.9. ANALYSIS Documentation of the identity, strength, purity, compos1t10n, stability, and method ofsynthesis, fabrication, and/or derivation of the test substances and the maintenance of these records were the responsibility ofthe Sponsor. "Other impurities in this lot are: 0.5% Z-1-bromo-3,3,3-trifluoropropene and 1.0% 2-bromo3,3,3-trifluoropropene. bOther impurities in this lot are: 0.4% Z-1-bromo-3,3,3-trifluoropropene and 0.8% 2-bromo3,3,3-trifluoropropene.

### ( HuntingdonLife Sciences 02-5449 Page 14 FinalReport

2.6. 2.5.10. STORAGE Roomtemperature 2.5.11. ARCHIVAL SAMPLE An archival sample ofeachtest substance was nottaken. 2.5.12. DISPOSITION The unused portion of the test substances and any empty test substance containers were returned to the Sponsor on 13 November2002. TESTANIMALS 2.6.1. SPECIES Albino Rats (Outbred) VAF/Plus® Sprague-Dawley Crl:CD® (SD) IGS BR 2.6.2. SUPPLIER CharlesRiverLaboratories Kingston, New York 12484 2.6.3. NUMBEROFANIMALS Received: 60 total (30 males, 30females) Placed on test: 50 total (25 males, 25 females) Females were nulliparous andnon-pregnant. 2.6.4. AGEATRECEIPT Approximately7 weeks 2.6.5. AGEATEXPOSURE Approximately 8weeks

### HuntingdonLife Sciences 02-5449
2.6.6. WEIGHTAT EXPOSURE (GRAMS) Male: Female: Mean 256 205 Range 227-280 181-225 Page 15 FinalReport

Individual weights of animals placed on test were within ±20% of the mean weightfor each sex. 2.6.7. ACCLIMATIONPERIOD Animals were acclimated for one week. All animals were checked for viability twice daily. Prior to assignment to study, all animals were examinedto ascertain suitabilityfor study. 2.7. ANIMAL ASSIGNMENT More animals than required for the study were purchased and acclimated. Animals were arbitrarily placed in cages upon receipt and were placed on study and assigned to groups as available at time of study initiation. Animals considered unsuitable for the study on the basis of pretest physical examinations and outlying body weight data were excluded. Disposition ofall animals not utilized in the study were maintained onfile at the TestingFacility. 2.8. ANIMAL IDENTIFICATION Each rat was assigned a temporary identification number upon receipt. After selection for study, each rat was ear-tagged with a number assigned by the Testing Facility. The assigned animal number plus the study number comprised the unique animal numberfor each animal. In addition, each cage was provided with a cage card, which was color-coded for exposure level identification and contained study number and animal numberinformation. 2.9. VETERINARY CARE Animals were monitoredby the technical stafffor any conditions requiring possible veterinary care andtreated as necessary.

### HuntingdonLife Sciences 02-5449
2.10. HUSBANDRYDURINGNON-EXPOSUREPERIODS 

### Page 16 FinalReport

2.10.1. FACILITIES MANAGEMENT/ANIMALHUSBANDRY 

### Currently acceptable practices of good animal husbandry were followed, e.g., Guidefor the Care and Use of LaboratoryAnimals; 

### National Academy Press, 1996. Huntingdon Life Sciences, East Millstone, New Jersey is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC). 2.10.2. HOUSING 

### Rats were group-housed (2-6/cage) during acclimation, then individually in suspended stainless steel wire mesh cages during the study. 2.10.3. FEED 

### Certified Rodent Diet, No. 5002; (Meal) (PMI Nutrition International, St. Louis, Missouri) was available without restriction. Freshfeed was presented as required. 2.10.4. ANALYSIS OFFEED 

### Analysis ofeach feed lot used during this study was performed by the manufacturer. Results are maintained on file by the manufacturer. There were no known contaminants in the feed which were expectedto interfere with the results ofthis study. 2.10.5. WATER 

### Water was available without restriction via an automated watering system (ElizabethtownWaterCompany). 2.10.6. WATERANALYSIS 

### Water analyses are conducted by Elizabethtown Water Company, Westfield, New Jersey (Raritan-East Millstone Plant) to ensure that water meets standards specified under the EPA Federal Safe Drinking Water Act Regulations (40 CFR Part 141). 

### In addition, water samples are collected biannually from representative rooms in the Testing Facility; chemical and microbiological water. _j 

### Huntingdon Life Sciences 02-5449 Page 17 FinalReport analyses are conducted on these samples by a subcontract laboratory. Results of all water analyses are maintained on file at the Testing Facility. There were no known contaminants in the water which were expected to interfere with the results of this study. 

### 2.10.7. ENVIRONMENTAL CONDITIONS Light/DarkCycle A twelve-hour light/dark cycle controlled via an automatic timer was provided. Temperature Temperature was monitored in accordance with the Testing Facility SOPs and maintained within the specified range to the maximumextentpossible. DesiredRange: Actual Range: DailyAverageRange: RelativeHumidity 18 to 26°C 21.0 to 23.5°C 21.0 to 22.6°C

Relative humidity was monitored in accordance with the Testing Facility SOPs and maintained within the specified range to the maximum extent possible. Excursions outside the specified range were notconsideredto have affectedtheintegrity ofthe study. DesiredRange: ActualRange: DailyAverageRange 30to 70% 19.06 to 72.49% 25.62 to 57.27% 

### 2.11. HUSBANDRYDURINGEXPOSURE 2.11.1. HOUSING Animals were individually housed in polycarbonate tubes attached to aflow-past nose-only exposure chamber.

### HuntingdonLife Sciences 02-5449

2.11. HUSBANDRYDURINGEXPOSURE 2.11.1. HOUSING 

### Page 18 FinalReport

Animals were individually housed inpolycarbonate tubes attached to aflow-past nose-onlyexposure chamber. 2.11.2. FEED 

### Nonewas provided during exposure. 2.11.3. WATER 

### None was providedduring exposure. 2.11.4. ENVIRONMENTAL CONDITIONS 

### Chamber temperature and relative humidity were recorded at the initiation of exposure equilibrium period, at initiation of 4-hour exposure and every half-hour during exposure and maintained, to the maximum extent possible, within the ranges presented below. Excursions outside the specified ranges were not considered to have affectedthe integrityofthe study. Temperature 

### DesiredRange: ActualRange: Relative Humidity 

### DesiredRange: Actual Range: 20 to 24°C 15 to 20°C

30to 70% 34to 58% 2.12. TEST SUBSTANCE ADMINISTRATION AND CHAMBER OPERATION 2.12.1. ROUTE OFADMINISTRATION 

### Inhalation, vianose-onlyexposure. 2.12.2. FREQUENCYAND DURATIONOFADMINISTRATION 

### The test substances were each administered for 4 hours for 1exposure.

### HuntingdonLife Sciences 02-5449

2.12.3. PRE-STUDY TRIALS Page 19 FinalReport

Trials wereperformedto evaluate the optimal set ofconditions and equipment to generate stable atmospheres at the targeted exposure levels. 2.12.4. CHAMBEROPERATION The exposure chambers were operated dynamically under equilibrium pressure. The total chamber airflow rate and 99% equilibriumtime (T99) foreach group are summarizedbelow: Group AirflowRate T99 

### (Lpm) (min) 

### 1 10.0 3 

### 2 10.0 3 3 

### 10.0 3 4 

### 11.1 2 5 6.5 4 

### This chamber size and airflow rate was considered adequate to maintain the oxygen above 19%. The chamber was exhausted through a system consisting ofa coarse filter, a HEPAfilter and an activatedcharcoalbed. All animals remainedin the chamberfor a minimum of30minutes (Group 3 remainedinthe chamberfor only 3 minutes) at the endof the exposure. During this time the chamber was operated at the same flow rate as usedduringthe exposureusingclean air only. Recordings of airflow rate and static pressure were made T99 prior toinitiation, atinitiation and everyhalf-hourduring exposure. Referto Figures 1, 

### 2 and 3 andAppendix A forequipment details. 2.12.5. EXPOSUREPROCEDURE Groups 1-3 Foreach exposure, the test substance was placedin a glass bubbler with a frittedbottom.

### HuntingdonLife Sciences 02-5449 Page 20 FinalReport House-line air was delivered from a regulator and a backpressure gauge, via 1 

### 4" 

### tubing, to a stainless steel "T" tube, which split the airflow into the generation and dilution systems. The generation air was directed via W' 

### tubing from the stainless steel 

### "T' tube, through a flowmeter, regulated by ametering valve. The outlet of the flowmeter was attached to the inlet of the glass bubbler via %" 

### tubing. The test substance laden air stream was directed from the glass bubbler to one side of a second stainless steel "T" tube via W'

### Teflon tubing
. The dilution air was directed, via W'

### tubing, from the first stainless steel "T" tube, to a flowmeter regulated by a metering valve. The air was then directed to the opposite side of the second stainless steel "T" and then into the inlet ofthe MIR.AN®. From the outlet ofthe MIRAN®, the test substance laden airflow was directed into theinlet ofthe flow-past nose-onlyexposure chamber. Referto Figure 1andAppendix A for equipment details. The generation and dilution flowrates are summarized in the following table. Group 4 

### The test substance was placed in a glass bubbler with a fritted bottom and coveredin foil. House-line nitrogen was delivered at a rate of 0.1 Lpm from a regulator and a backpressure gauge, via %" 

### tubing, and connected to the inlet ofthe generation flowmeter, which was regulated by a metering valve. The outlet of the generation flowmeter was attached to the inlet of the glass bubbler via %" tubing. The test substance laden air stream was then directed, via %" 

### Teflon tubing, from the outlet ofthe glass bubbler to one side of a stainless steel "T." 

### House-line air was delivered at arate of 11.0Lpmfrom aregulator and abackpressure gauge, via %" tubing, to the inlet ofthe dilution flowmeter, which was regulated by a metering valve. The air was directed from the flowmeter to the opposite side of the stainless

# ( HuntingdonLife Sciences 02-5449 Page 21 Final Report steel "T" outlined above. From the "T," the test substance laden air stream was directed into the inlet of the MIRAN®. From the outlet of the MIRAN®, the test substance laden airflow was directed into the inlet of the flow-past nose-only exposure chamber. Referto Figure 2 and Appendix A for equipment details. The generation and dilution flowrates are summarized in the following table. 

### Group 5 The test substance was placed in a glass bubbler with a fritted bottom and coveredinfoil. House-line air was delivered from a regulator and a backpressure gauge, via %" 

### tubing, to a stainless steel "T" tube, which split the airflow into the generation and dilution systems. For the generation system, a flowmeter was connected to a stainless steel "T" via %" 

### tubing. A meteringvalve was attachedto the flowmeter's inletto maintain the flowrate at 0.5 Lpm. A second generation flow used house-line nitrogen delivered from aregulator and abackpressure gauge, via %" tubing, andconnected to the opposite side of the stainless steel "T" described above. A metering valve was attached to the inlet of the flowmeter to maintain the flowrate at 0.5 Lpm. The outlet of the house-line air/nitrogen 

### ''T" was attached to the inlet ofthe glass bubbler via %" 

### tubing. The test substance laden air stream was then directed from the bubbler outlet to one side of a second stainless steel "T" via %" Teflon tubing. House-line air was delivered from a regulator and a backpressure gauge, via W' 

### tubing, and connected to the inlet of the dilution flowmeter, which was regulated by a metering valve. The airflow of5.5 Lpmwas directedfrom the flowmeter to the opposite side of the second stainless steel "T." From the "T," the test substance laden air stream was directed into the inlet ofthe MIRAN®. From the outlet of the MIRAN®, the test substance laden airflow was

### HuntingdonLife Sciences 02-5449 Page 22 FinalReport directed into the inlet of the flow-past nose-only exposure chamber. Referto Figure 3 and Appendix A for equipment details. The generation and dilution flowrates are summarized in the table below: Group GenerationFlow DilutionFlow (Lpm) (Lpm) Total Air 

### Nz 

### 1 0.6 0.6 0.0 9.4 2 0.75 0.75 0.0 9.25 3 

### 1.4 1.4 0.0 8.6 4 0.10 0.0 0.10 11.0 5 1.0 0.5 0.5 5.5 The exposure chambers were enclosed m a 10 m3 

### glass and stainless steel chamber. 2.13. EXPOSURE CHAMBERSAMPLING 2.13.1. CHAMBERSAMPLING Determination ofthe exposure levels were made using a MIRAN® Ambient Air analyzer equipped with a strip chart recorder and digital multimeter. The test atmospheres were continuously generated through the MIRAN® and measurements were recorded 4 times during the exposures. The exposure levels were determined by comparison of the measured absorbance to a calibrated response curve constructed using the same instrument settings. Referto Appendix A for equipment details. 2.13.2. PARTICLE SIZE DISTRIBUTIONANALYSIS Particle size samples were drawn at 4 intervals during each exposure for the chambers and room air using a TSI Aerodynamic Particle Sizer. The samples were drawn for 20 seconds at arate of 5.0 Lpm. The mass median aerodynamic diameter, geometric

### HuntingdonLife Sciences 02-5449 Page 23 Final Report standard deviation and total mass concentration were calculated. A computer was used to program the system to the appropriate settings prior to sampling. The particle size distributions were calculatedby the computer andprinted out. Referto Appendix A for equipment details. 2.13.3. NOMINAL CONCENTRATION The nominal concentrations (ppm) were determined by weighing the generation apparatus containing the test substance before and afterthe exposure and calculating as follows:
Cone (ppm)= amount consumed (g) x 1000 (mg/g) x 1000 (Ug/mg) x 22.4 (uUumole)x 295°K exposure duration (min) x airflow (Lpm) x MW (J.lg/J.lmole) x 273°K 

### The molecular weight (MW) ofeach test substanceis as follows: 2-Bromo-3,3,3-Trifluoropropene

# =174.95 E-1-Bromo-3,3,3-Trifluoropropene = 

### 174.95 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene = 

### 242.95 2.14. EXPERIMENTALEVALUATIONS 2.14.1. VIABILITY CHECKS Animals were observed in their cages for mortality and general condition twice daily (once in the morning and once in the afternoon). 2.14.2. PHYSICALEXAMINATIONS Examinations included but were not limited to, evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects, including tremors and convulsions, changes in the level of motor activity, gait and posture, reactivity to handling or sensory stimuli, grip strength, and stereotypies orbizarre behavior (e.g., self-mutilation, walkingbackwards).

### HuntingdonLife Sciences 02-5449 Day0 (Day ofExposure) 

### Page 24 FinalReport

Animals were observed individually prior to exposure, as a group at fifteen-minute intervals during the first hour of exposure, and hourly for the remainder of the exposure. They were observed individually upon removal from the chamber and hourly for two hours post-exposure. Days 1-14 

### Detailed general observations were recorded once daily. 2.14.3. BODYWEIGHT 

### Animals were removed from their cages and weighed on Day 0 (justpriorto exposure), Day 7 andDay 14 (justpriorto sacrifice). 2.15. POSTMORTEM 2.15.1.NECROPSYINFORMATION 

### All survivors (up to 5/sex/group) were euthanized by exsanguination following carbon dioxide inhalation at termination on TestDay 14. 2.15.2. MACROSCOPICEXAMINATIONS 

### Complete macroscopic postmortem examinations were performed on all animals. The macroscopic postmortem examination included examination of the external surface and all orifices; the organs and tissues of the cranial, thoracic, abdominal and pelvic cavities andneck; andtheremainder ofthe carcass for the presence ofmacroscopic morphologic abnormalities. 2.15.3. ORGANWEIGHTS 

### Organs indicatedin TableI (page 25) were weighedfor all animals at the scheduled sacrifice interval. Prior to weighing, the organs were carefully dissected and properly trimmed to remove adipose and other contiguous tissues in a uniform manner. Organs were weighed as soon as possible after dissection in order to avoid drying. Paired organs were weighedtogether.

### HuntingdonLife Sciences 02-5449 Page 25 Final Report 2.15.4. TISSUES PRESERVED AND EXAMINED HISTOPATHOLOGICALLY

TABLEI

ORGANNAME 

### adrenal glands brain kidneys lungs liver ovaries testes gross lesions The tissues listed in Table I (page 25) were obtained at sacrifice and preserved for all animals. In 

### addition, slides ofthe lungs were prepared and examined microscopically for all animals. Any abnormalities not noted during macroscopic examinations which were seen during histologyprocessingwererecorded.

EXAMINED WEIGHED PRESERVED MICROSCOPICALLY 

### X X X X X X X X X X 

### X X X X X X Preservatives 

### All tissues

- 10% neutral bufferedformalin. Testes were placed in Modified Davidson's solution initially and then retained in 10% formalin. Lungs were infused with formalin priorto theirimmersioninto alarger volume ofthe samefixative. Processing 

### Afterfixation, the lungs from all animals were routinely processed, embedded in paraffin, cut at a microtome setting of 4-7 microns, mounted on glass slides, stained with hematoxylin and eosin and examinedbylight microscopy.

### Huntingdon Life Sciences 02-5449



### 2.16. STATISTICALANALYSIS Page 26 FinalReport

A calculation of an estimate ofthe median lethal concentration, with 95% confidence limits was performed for the combined sexes, the males and the females for 2-Bromo-3,3,3-Trifluoropropene and E-1-Bromo-3,3,3- Trifluoropropene, using the method ofLitchfield and Wilcoxon. Reference for this method is as follows: Litchfield, J.T., Jr. and F. 

### Wilcoxon, 1949, J. Pharma. Exp. Therp., 96:99-113. 

### 2.17. DATA STORAGE All raw data, preserved specimens, and retained samples, as well as the original study protocol and the original final report are to bemaintainedin the Archives of the Testing Facility upon completion of the study. The Sponsorwill determine thefinal disposition ofthese materials. 

### 2.18. REGULATORY REFERENCES 2.18.1. TEST GUIDELINES The Organization for Economic Cooperation and Development (OECD) Guidelines: Acute Inhalation (12 May 1981), Part403. Health Effects Test Guidelines, Office of Prevention, Pesticides and Toxic Substances, United States Environmental Protection Agency (OPPTS), August, 1998; OPPTS 870.1300, Acute InhalationToxicity. 

### 2.18.2. GOOD LABORATORYPRACTICES This study was conductedin compliance with OECD Principles of Good Laboratory Practices ENV/MC/CHEM (98) 17 and Environmental Protection Agency GoodLaboratoryPractices as set forth in 40 CFRPart792 (TSCA). 

### 2.18.3. ANIMAL WELFARE ACT COMPLIANCE This study complied with all appropriate parts of the Animal Welfare Actregulations: 9 CFRParts 1 and 2Final Rules, Federal Register, Volume 54, No. 168, August 31, 1989, pp. 36112-36163, effective October 30, 1989 and 9 CFR Part 3 Animal Welfare

### HuntingdonLife Sciences 02-5449 Page 27 FinalReport Standards; Final Rule, Federal Register, Volume 56, No. 32, February 15, 1991, pp. 6426-6505, effectiveMarch 18, 1991. 

### 2.19. PROTOCOL DEVIATIONS The following protocol deviation occurred during the study but was not consideredto have compromisedthe validity orintegrity ofthe study: Since all animals in Group 3 died during the exposure on StudyDay 0, the chamber was cleared for only 3 minutes rather than the protocol-specified 30-minuteperiod.

# ( HuntingdonLife Sciences 02-5449 Page 28 FinalReport 

### 3. RESULTS AND DISCUSSION 3.1. CHAMBERMONITORING (Table 1) The target, analytical (IR) and nominal concentrations for each test group are summarized as follows: Group TestSubstance Target Analytical Nominal Concentration Concentration Concentration (ppm) (ppm) (ppm) 1 2-Bromo-3,3,3- 25,000 26,580 29,400 Trifluoropropene 2 E-1-Bromo-3,3,3- 25,000 25,650 30,600 Trifluoropropene 3 1-Bromo-2- 25,000 24,800 28,700 Trifluoromethyl-3,3,3- Trifluoropropene 4 2-Bromo-3,3,3- 5,000 5,173 6,220 TrifluorQQropene 5 E-1-Bromo-3,3,3- 50,000 45,850 52,200 TrifluorQQTopene 

### Particle sizing results demonstrated that all of the exposures were vaporonly since the chamber samples were comparable to room air samples. Chamber environmental conditions averaged l7°C temperature and 47% relative humidity. 

### 3.2. MORTALITY (Table6) Themortalityfor each test group is summarized as follows: Group TestSubstance Analytical Mortality Mortality Mortality Concentration Males Females Total (ppm) 1 2-Bromo-3,3,3- 26,580 

### 515 515 10/10 Trifluoropropene 4 2-Bromo-3,3,3- 5,173 0/5 0/5 0/10 Trifluoropropene 5 E-1-Bromo-3,3,3- 45,850 2/5 0/5 2/10 Trifluoropropene 2 E-1-Bromo-3,3,3- 25,650 0/5 0/5 0/10 Trifluoropro_]J_ene 3 1-Bromo-2- 24,800 

### 515 515 10/10 Trifluoromethyl-3,3,3- Trifluoropropene

### Huntingdon Life Sciences 02-5449 Page 29 FinalReport All of the animals exposed to 2-Bromo-3,3,3-Trifluoropropene at 26,580 ppm were found dead or were euthanizedin poor condition on the day after the exposure. All of the animals exposed to 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene at 24,800 ppm were found dead within 30 minutes of the start of the exposure. Both of the male animals exposed to E-1-Bromo-3,3,3-Trifluoropropene at 45,850 ppm that were found dead died on the day of the exposure. All other animals survivedto termination. Basedon the above results, the LC50 values were calculatedto be: TestSubstance 2-Bromo-3,3,3- Trifluoropropene E-1-Bromo-3,3,3- Trifluoropropene 1-Bromo-2-Trifluoromethyl3,3,3-Trifluoropropene 

## 3.3. BODYWEIGHTS (Table2) Animals Combined

Males Females Combined

Males Females Combined

Males Females LCSO 95% ConfidenceLimits (ppm) (ppm) 11726 9054to 15186 11726 7584to 18129 11726 7584to 18129 70955 51449 to 97857 50950 35358 to 73418 >45850 NotCalculable <24,800 NotCalculable <24,800 NotCalculable <24,800 NotCalculable



### All surviving animals gained weight (or did not lose weight) during both weeks ofobservations. 

## 3.4. PHYSICAL OBSERVATIONS 3.4.1. EXPOSUREPERIOD (Table3) The only sign of toxicity noted during the exposure period of 2-Bromo-3,3,3-Trifluoropropene was labored breathing or gasping during the lasthour ofeach exposure. The only sign of toxicity noted during the exposure period of E-1-Bromo-3,3,3-Trifluoropropene was tail quivering and/or tremors during each exposure. The mechanism for this central nervous system (CNS) effect was not clear.

### HuntingdonLife Sciences 02-5449 Page 30 FinalReport There were no signs oftoxicity noted during the exposureperiodof 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene prior to all animals were found dead within 30 minutes of the exposure initiation. 

### 3.4.2. UPON REMOVAL FROM EXPOSURE CHAMBER AND OVER THE TWO-HOUR POST-EXPOSURE OBSERVATIONPERIOD (Tables 

### 3 

## & 5) Clinical signs of toxicity noted immediately following the exposures of2-Bromo-3,3,3-Trifluoropropene included clearorred nasal discharge, excessive salivation, labored breathing and moist rales. The severity and frequency ofthe signs was increased after the higher level exposure of 26,580 ppm compared to the lower level exposure of 5,173 ppm. Gasping and decreased activity were also notedbut only afterthe higherexposurelevel. Clinical signs of toxicity noted immediately following the exposures ofE-1-Bromo-3,3,3-Trifluoropropene includedrednasal discharge. The severity and frequency ofthe signs was increased after the higher level exposure of 45,850 ppm compared to the lower level exposure of25,650 ppm. Excessive salivation, labored breathing and moist rales were also noted but only after the higher exposure level. 

### 3.4.3. DAILY OBSERVATIONS DURING THE 14-DAY POSTEXPOSURE OBSERVATIONPERIOD (Tables 4 & 

### 5) 

### A few signs oftoxicity similar to those seen immediately after the exposures were noted during the first week of the post-exposure observation period. A complete recovery in surviving animals was seen during the remainder ofthe post-exposure observationperiod.

### HuntingdonLife Sciences 02-5449


### 3.5. PATHOLOGY 3.5.1. ORGANWEIGHTS (Tables 7 & 8) 

### Page 31 Final Report

There were no apparent effects ofexposure on the organs that were weighed. This was based on a comparison of the lower level exposure ofthe 2-Bromo-3,3,3-Trifluoropropene to the lowerlevel exposure of the E-1-Bromo-3,3,3-Trifluoropropene and to the higherlevel exposure ofthe 1-Bromo-3,3,3-Trifluoropropene. 3.5.2. MACROSCOPIC (Table 9) 

### One or more rats from both exposure levels of 2-Bromo-3,3,3- Trifluoropropene had red discoloration of the lungs. Fluid was present in the lungs ofone male from the higher level exposure of 26,580ppm. One or more rats from the lower level exposure of 25,650 ppm of E-1-Bromo-3,3,3-Trifluoropropene had red discoloration of the lungs. Fluid was presentin the lungs oftwo males from thehigher level exposure of45,850ppm. One or more rats had red discoloration of the lungs from the exposure of 24,800 ppm of 1-Bromo-2-Trifluoromethyl-3,3,3- Trifluoropropene. Microscopically, in the unscheduled deaths, the discoloration was due to vascular congestion which is commonly seen in rats not exsanguinated (found dead) or inadequately exsanguinated (moribund) prior to postmortem examination. The scattered red foci were agonal hemorrhages. 3.5.3. MICROSCOPIC (Tables 10 & 

### 11) 

### The lungs of all animals on test were routinely processed, cut at 5 microns, mounted on glass slides, stained with hematoxylin and eosin and examinedbylightmicroscopy.

# ( HuntingdonLife Sciences 02-5449 Page 32 FinalReport

4. 

### Test substance-related findings were microscopically present in lungs of rats in the higher level exposure of 26,580 ppm of 2-Bromo-3,3,3-Trifluoropropene. All of the rats, in this group only, had bronchiolar lesions consisting of desquamated epithelium, bronchiolar/peribronchiolar acute/subacute inflammation and/or intraluminal debris; the severity of the findings ranged from slight to moderate. Alveolar/intraalveolar macrophages (minimal to moderate) normally present in the lungs, were mostnumerous in several ofthese rats. In the rats which were found dead or humanely sacrificed, the lungs had vascular congestion. This is a common finding in rats which are not exsanguinated (found dead) or incompletely exsanguinated (moribund) prior to postmortem examination. Therefore, the significance of this finding with respect to the test substanceis notknown. Other findings in the lungs occurred sporadically and were not considered to be test substance-related; these findings have been seen in rats ofthis strain and age usedin similar studies conducted in this facility. CONCLUSION 

### The 4-hour acute inhalation toxicity in rats was compared of 2-Bromo-3,3,3- Trifluoropropene, E-1-Bromo-3,3,3-Trifluoropropene and 1-Bromo-2- Trifluoromethyl-3,3,3-Trifluoropropene. On the basis of toxic responses and subsequent mortality, E-1-Bromo-3,3,3-Trifluoropropene was considered the least toxic with an LC50 

### of -70,955 ppm, 2-Bromo-3,3,3-Trifluoropropene was considered moderately toxic with an LC5

### o 

### of -11,726 ppm and 1-Bromo-2- Trifluoromethyl-3,3,3-Trifluoropropene was considered the most toxic with an LCso 

### substantiallyless than the onlytestedlevel of24,800 ppm.

### Huntingdon Life Sciences
Groups 1 - 3

House-Line**Air~=** Regulator and Backpressure Gauge 

### 02-5449
Diagram of Generation and Sampling Systema

Glass Bubbler with Fritted Bottom and Test Substance Nupro Valve 

## I 

# ,, ""Hl II ,.=== Gen Flowmeter
"'ram1ess Steel "T" 

## / Nupro Valve Flowmeter Stainless Steel Strip Chart Recorder

aSystem enclosed in 10 m3glass and stainless steel chan]ber. 

### Page 33 Final Report Figure 1

Differential Gauge

### Huntingdon Life Sciences 02-5449 Page 34 Final Report Group 4 Diagram of Generation and Sampling Systema Figure 2

Regulator and Backpressure Gauge Nupro Valve Glass Bubbler r------, with Fritted Bottom and Test Substance

oil Covered)**House-Lin~ ~fi=====;,**  Nitrogen -'<.>'

- 9 II 

### r'? 11 Multimeter
Generation Flowmeter Stainless Steel "T" Nupro Valve House-Line-+**~!1========'-'** Air I Regulator and Backpressure Gauge Dilution Flowmeter

aSystem enclosed in 10 m3glass and stainless steel chamber. ll-+1--------- Filter

Pressure Differential Gauge

### Huntingdon Life Sciences
Group 5

House-Line Air-1- Regulator and 

## 02-5449
Diagram of Generation and Sampling Systema

----·-··-······-···················- House-Line -1- Nitrogen
Glass Bubblerwith Fritted Bottom and Test Substance (Foil Covered)

Stainless Steel "T" Nupro Valve

Dilution Flowmeter Strip Chart Recorder

asystem enclosed in a 10 m3glass and stainless steel chamber. 

# I

Pressure Differential Gauge 

### Page 35 Final Report Figure 3

### Huntingdon Life Sciences 02-5449
Chamber Concentrations, Particle Size Page 36 Final Report Grqup 1 Determinations and Chamber Environment Table 1

Exposure Hour



### 1 2 

### 3 

### 4 Mean S.D. Exposure Hour


### Tee 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Mean S.D. Chamber Concentrations Exposure Analytical Hour (ppm)

1 30,400 2 26,500 3 24,400 4 25,000 Mean 

### 26,580 S.D. 

### 2,699 Particle Size Determinations MMAD GSD

{pm) 0.984 2.516 1.264 2.517 

### 1.820 0.812 1.595 1.981 1.789 2.322 

### 1.922 0.310 Chamber Environment Temperature Relative Humidity 

### (%) (OC)

17 17 17 17 17 17 17 17 17 17 17.0 

### 0.0 58 58 57 56 56 56 56 56 54 54 

### 56.1 1.4 1.28E-03 1.81 E-03 1.09E-03 1.39E-03 1.39E-03 3.05E-04

Total Chamber Airflow (Lpm)

10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 

### 10.0 0.0

Key: MMAD = mass median aerodynamic diameter; GSD = geometric standard deviation; TMC =total mass concentration; Lpm =Liters per minute. aAverage room airsamples were 1.81 E-03 mg/m3

.

### Huntingdon Life Sciences 02-5449
Chamber Concentrations, Particle Size Group 2 Determinations and Chamber Environment Chamber Concentrations Exposure Analytical Hour (ppm)

1 27,100 2 26,200 3 24,100 4 25,200 Mean 25,650 S.D. 1,292 Particle Size Determinations Exposure MMAD GSD Hour (pm)

1 1.417 2.471 2 0.932 1.597 3 0.990 1.712 4 1.057 1.565 Mean 1.099 1.836 S.D. 0.218 0.428 Chamber Environment Exposure 

### Page 37 Final Report
Table 1

TMCa (mg/m3) 1.53E-03 9.10E-04 7.03E-04 6.57E-04 9.50E-04 4.02E-04

Total Hour Temperature Relative Humidity Chamber Airflow CC) 

### (%) (Lpm) Tgg 19 58 10.0 0.0 19 58 10.0 0.5 19 58 10.0 1.0 19 57 10.0 1.5 20 56 10.0 2.0 20 56 10.0 2.5 20 56 10.0 3.0 20 54 10.0 3.5 20 53 10.0 4.0 20 53 10.0 Mean 19.6 55.9 10.0 S.D. 0.5 2.0 0.0

Key: MMAD = mass median aerodynamic diameter; GSD = geometric standard deviation; TMC =total mass concentration; Lpm =Liters per minute. aAverage room air samples were 1.44E-03 mg/m3

.

### Huntingdon Life Sciences 02-5449 Page 38 Final Report Chamber Concentrations, Particle Size Group 3 Determinations and Chamber Environment Table 

### 1

Exposure Hour

1 2 

### 3 

### 4 Mean S.D. Exposure Hour

Tss 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Mean S.D. Chamber Concentrations Exposure Analytical Hour (ppm)



### 1 2 3 

### 4 Mean S.D. 24,800 a


### 24,800
Particle Size Determinations MMAD GSD

(pm) 3.409 1.799



### 3.409 1.799
Chamber Environment Temperature Relative Humidity (%) 

### (oC)

19 19 19



### 19.0 0.0 

### 44 44 44

44.0 0.0 TMCb (mg/m3) 9.85E-05



### 9.85E-05

Total ChamberAirflow (Lpm)

10.0 10.0 10.0



### 10.0 0.0
Key: MMAD =mass median aerodynamic diameter; GSD =geometric standard deviation; TMC =total mass concentration; Lpm = Liters per minute. aExposure ended at33 minutes after all animals were found dead. bAverage room air samples were 6.91 E-04 mg/m3

.

### Huntingdon Life Sciences 02-5449 Page 39 Final Report Chamber Concentrations, Particle Size Group 4 Determinations and Chamber Environment Table 

### 1

Exposure Hour



### 1 2 

### 3 

### 4 Mean S.D. Exposure Hour

Tgg 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Mean S.D. Chamber Concentrations Exposure Analytical Hour (ppm)

1 6,250 2 5,310 3 4,800 4 4,330 Mean 5,173 S.D. 822 Particle Size Determinations MMAD GSD

(Jim) 1.202 1.925 1.228 1.714 2.330 2.037 1.590 1.938 1.588 1.904 0.526 0.136 Chamber Environment Temperature Relative Humidity 

### (OC) (%)

16 45 16 45 17 44 17 41 15 40 15 40 15 40 15 40 15 40 15 39 15.6 41.4 0.8 2.3 TMC3 (mg/m3) 8.70E-04 7.31 E-04 1.15E-03 8.85E-04 9.09E-04 1.75E-04
Total Chamber Airflow (Lpm)

11.1 11.1 11.1 11.1 11.1 11.1 11.1 11.1 11.1 11.1 11.1 0.0
Key: MMAD = mass median aerodynamic diameter; GSD = geometric standard deviation; TMC =total mass concentration; Lpm =Liters per minute. 3Average room air samples were 1.18E-03 mg/m3

.I I,. 

### Huntingdon Life Sciences 02-5449
Chamber Concentrations, Particle Size Page 40 Final Report Group 5 Determinations and Chamber Environment Table 1 Chamber Concentrations Exposure Analytical Hour (ppm)

1 36,500 2 39,600 3 50,400 4 56,900 Mean 45,850 S.D. 9,474 Particle Size Determinations Exposure MMAD GSD TMCa Hour (Jim) (mg/m3)

1 0.975 1.533 8.08E-04 2 0.943 1.480 6.03E-04 3 1.252 1.769 8.48E-04 4 1.116 1.519 7.89E-04 Mean 1.072 1.575 7.62E-04 S.D. 0.142 0.131 1.09E-04 Chamber Environment Exposure Total Hour Temperature Relative Humidity ChamberAirflow CC) 

### (%) (Lpm) Tss 16 46 6.5 0.0 16 45 6.5 0.5 16 44 6.5 1.0 16 41 6.5 1.5 16 36 6.5 2.0 16 36 6.5 2.5 16 34 6.5 3.0 16 36 6.5 3.5 16 38 6.5 4.0 16 38 6.5 Mean 16.0 39.4 6.5 S.D. 0.0 4.3 0.0

Key: MMAD = mass median aerodynamic diameter; GSD = geometric standard deviation; TMC =total mass concentration; Lpm = Liters per minute. aAverage room air samples were 2.24E-03 mg/m3

.

### Huntingdon Life Sciences 02-5449 BodyWeights and Body Weight Changes M9-les from Day 0 Page 41 Final Report
Table 2 Animal Number BodyWeight (grams) BodyWeight Change from Day 0 (grams) DAY 0 DAY 7 DAY 14 DAY 7 DAY 14 Group 1 - 2-Bromo-3,3,3-Trifluoropropene (26,580 ppm) 1046 275 AD AD 1047 262 AD AD 1048 263 AD AD 1049 256 AD AD 1050 273 AD AD Mean 266 S.D. 8.0 Group 2- E-1-Bromo-3,3,3-Trifluoropropene (25,650 ppm) 2046 276 319 377 43 101 2047 280 340 407 60 127 2048 268 326 388 58 120 2049 260 315 366 55 106 2050 254 291 329 37 75 Mean 268 318 373 51 106 S.D. 10.8 17.9 29.1 10.1 20.1 Group 3- 1-Bromo-2-Trifluoromethyi-3,3,3-Trifluoropropene (24,800 ppm) 3046 264 AD AD 3047 263 AD AD 3048 252 AD AD 3049 269 AD AD 3050 260 AD AD Mean 262 S.D. 6.3 Group 4 - 2-Bromo-3,3,3-Trifluoropropene (5,173 ppm) 4046 240 269 335 29 95 4047 239 275 337 36 98 4048 241 273 341 32 100 4049 236 248 318 12 82 4050 266 306 373 40 107 Mean 244 274 341 30 96 S.D. 12.2 20.8 20.0 10.8 9.2 Group 5- E-1-Bromo-3,3,3-Trifluoropropene (45,850 ppm) 5046 240 306 367 66 127 5047 242 AD AD 5048 239 300 358 61 119 5049 240 AD AD 5050 227 278 314 51 87 Mean 238 295 346 59 111 S.D. 6.0 14.7 28.4 7.6 21.2 AD =Animal Dead.1·. 

### Huntingdon Life Sciences 02-5449 BodyWeights and BodyWeight Changes Females from Day 0 Page 42 Final Report
Table 2 Animal Number BodyWeight (grams) BODY WEIGHT CHANGE from Day 0 (grams) DAY 0 DAY 7 DAY 14 DAY7 DAY14 Group 1- 2-Bromo-3,3,3-Trifluoropropene (26,580 ppm) 1546 196 AD AD 1547 215 AD AD 1548 202 AD AD 1549 203 AD AD 1550 204 AD AD Mean 204 S.D. 6.9 Group 2- E-1-Bromo-3,3,3-Trifluoropropene (25,650 ppm) 2546 187 199 205 12 2547 212 222 246 10 2548 199 218 235 19 2549 205 223 231 18 2550 207 228 256 21 Mean 202 218 235 16 S.D. 9.6 11.2 19.2 4.7 18 34 36 26 49 33 11.6 Group 3 -1-Bromo-2-Trifluoromethyi-3,3,3-Trifluoropropene (24,800 ppm) 3546 181 AD AD 3547 203 AD AD 3548 199 AD AD 3549 187 AD AD 3550 204 AD AD Mean 195 S.D. 10.3 Group 4- 2-Bromo-3,3,3-Trifluoropropene (5,173 ppm) 4546 218 242 280 24 62 4547 212 221 232 9 20 4548 209 223 247 14 38 4549 225 231 247 6 22 4550 221 221 248 0 27 Mean 217 228 251 11 34 S.D. 6.5 9.0 17.6 9.0 17.2 Group 5- E-1-Bromo-3,3,3-Trifluoropropene (45,850 ppm) 5546 205 216 234 11 29 5547 203 221 236 18 33 5548 209 220 238 11 29 5549 217 226 237 9 20 5550 211 218 247 7 36 Mean 209 220 238 11 29 S.D. 5.5 3.8 5.0 4.1 6.0 AD =Animal Dead.(•

.. \ 

### Huntingdon Life Sciences 02-5449
Summary of Day 0 Observations

HOURS INTO EXPOSUREa PRETESTb 

### 1/4 1/2 3/4 1 2 

### 3 

### 4 M/F Group 1 - 2-Bromo-3,3,3-Trifluoropropene (26,580 ppm) No. of Animals Observed 5/5 10 10 10 10 10 10 10 NORMAL Within Normal Limits 5/5 10 10 10 10 10 10 5 SECRETORY Clear Nasal Discharge 0/0 0 0 0 0 0 0 0 Excessive Salivation 0/0 0 0 0 0 0 0 0 RESPIRATORY Labored Breathing 0/0 0 0 0 0 0 0 5 Gasping 0/0 0 0 0 0 0 0 0 Moist Rales 0/0 0 0 0 0 0 0 0 GENERAL Decreased Activity 0/0 0 0 0 0 0 0 0

T* =Animals were observed upon removal from the chamber. aAnimals were observed as a group. bAnimals were observed individually. Number represents animals exhibiting signs. M = Male, F = Female 

### Page 43 Final Report
Table 3 HOURSPOSTEXPOSUREb
T* 

### 1 2 M/F M/F M/F 5/5 5/5 5/5

0/0 0/0 0/0

4/4 5/4 5/5 3/2 3/2 3/2

3/0 3/1 4/1 1/0 1/0 1/0 1/4 1/4 0/4

3/0 4/0 4/0I' I

. \ 

### Huntingdon Life Sciences 02-5449
Summary of Day 0 Observations

HOURS INTO EXPOSURE3 PRETESTb 

### 1/4 1/2 

### 3/4 1 2 

### 3 M/F Group 2- E-1-Bromo-3,3,3-Trifluoropropene (25,650 ppm) No. of Animals Observed 5/5 10 10 10 10 10 10 NORMAL Within Normal Limits 5/5 3 3 3 3 3 3 SECRETORY Red Nasal Discharge 0/0 0 0 0 0 0 0 GENERAL Quivering Tail 0/0 

### 7 7 7 7 7 7 Group 3 -1-Bromo-2-Trifluoromethyi-3,3,3-Trifluoropropene (24,800 ppm) No. of Animals Observed 5/5 10 10 

### 0°
NORMAL Within Normal Limits
DEAD Found Dead 5/5 

### 0 0

0/0 10 10 

### 4

10

8

0

2

T* = Animals were observed upon removal from the chamber. aAnimals were observed as a group. bAnimals were observed individually. Number represents animals exhibiting signs. M 

### = Male, F 

### = Female cExposure ended at 33 minutes after all animals were found dead. 

### Page 44 Final Report
Table 3 HOURSPOSTEXPOSUREb T* 1 2 M/F M/F M/F
5/5 5/5 5/5

1/4 2/5 2/5

4/1 3/0 3/0

0/0 0/0 0/0I 

### Huntingdon Life Sciences 02-5449
Summary of Day 0 Observations

HOURS INTO EXPOSUREa PRETESTb 1/4 1/2 3/4 1 

### 2 

### 3 

### 4 M/F Group 

### 4- 2-Bromo-3,3,3-Trifluoropropene 

### (5, 173 ppm) No. of Animals Observed 

### 5/5 10 10 10 10 10 10 10
NORMAL Within Normal Limits 

### 5/5 10 10 10 10 10 10 

### 9 SECRETORY Red Nasal Discharge 0/0 0 0 0 0 0 0 0 Red Dried Material on Face 0/0 0 0 0 0 0 0 0 RESPIRATORY Labored Breathing 0/0 0 0 0 0 0 0 0 Moist Rales 0/0 0 0 0 0 0 0 0 Gasping 0/0 0 0 0 0 0 0 1

T* =Animals were observed upon removal from the chamber. aAnimals were observed as a group. bAnimals were observed individually. Number represents animals exhibiting signs. M = Male, F = Female 

### Page 45 Final Report
Table 3 HOURSPOSTEXPOSUREb
T* 1 2 M/F M/F M/F


### 5/5 5/5 5/5

2/3 2/3 2/3

1/1 0/1 0/1 2/0 0/0 0/0

0/1 0/1 0/1 2/0 3/0 3/0 0/0 0/0 0/0

### Huntingdon Life Sciences 02-5449
Summary of Day 0 Observations

HOURS INTO EXPOSUREa PRETESTb 

### 1/4 1/2 3/4 M/F Group 5- E-1-Bromo-3,3,3-Trifluoropropene (45,850 ppm) No. of Animals Observed 5/5 10 10 10 NORMAL Within Normal Limits 5/5 5 5 5 SECRETORY Lacrimation 0/0 0 0 0 Clear Nasal Discharge 0/0 0 0 0 Red Nasal Discharge 0/0 0 0 0 Excessive Salivation 0/0 0 0 0 Chromodacryorrhea 0/0 0 0 0 RESPIRATORY Labored Breathing 0/0 0 0 0 Moist Rales 0/0 0 0 0 GENERAL Tremors!rail Quivering 0/0 5 5 5 DEAD Found Dead 0/0 0 0 0



### .T* = Animals were observed upon removal from the chamber.

a Animals were observed as a group. 

### 1 2 3 4

10 10 10 10

5 5 4 4

0 0 1 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0 0 0

5 5 5 4

0 0 0 1

bAnimals were observed individually. Number represents animals exhibiting signs. M

## =Male, F

## =Female 

### Page 46 Final Report
Table 3 HOURSPOSTEXPOSUREb T* 

### 1 2 M/F M/F M/F

3/5 3/5 3/5

0/2 0/2 0/2

0/1 0/1 0/1 0/0 0/0 1/0 2/2 3/2 2/2 2/1 1/1 0/1 0/1 0/1 0/1

1/0 1/0 1/1 1/1 1/1 1/1

0/0 0/0 0/0

1/0 0/0 0/0

### Huntingdon Life Sciences 02-5449 Summary of 14-Day Post-Exposure Observations Da 

### 1 2 3 4 5 

### 6 7 

### 8 Group 1 - 2-Bromo-3,3,3-Trifluoropropene (26,580 ppm) Males No. of Animals Examined 5 0 0 0 0 0 0 0 Within Normal Limits 0 0 0 0 0 0 0 0 SECRETORY Clear Nasal Discharge 

### 4 0 0 0 0 0 0 0 Excessive Salivation 1 0 0 0 0 0 0 0 Chromodacryorrhea 2 0 0 0 0 

### 0 0 0 RESPIRATORY Labored Breathing 3 0 0 0 

### 0 0 0 0 Gasping 1 0 0 0 0 

### 0 0 

### 0 GENERAL Decreased Activity 3 0 0 0 

### 0 0 0 0 Yellow Ano-Genital Staining 1 0 0 0 0 

### 0 0 0 DEAD Found Dead 1 0 0 0 

### 0 0 0 

### 0 Humane Sacrifice 

### 4 0 0 0 0 0 0 

### 0 Females No. of Animals Examined 5 0 0 0 0 

### 0 0 0 Within Normal Limits 0 0 0 0 0 0 0 0 SECRETORY Clear Nasal Discharge 5 

### 0 0 0 0 0 0 0 Excessive Salivation 3 0 0 0 0 0 0 0 Dried Red Material Facial Area 1 0 0 0 0 0 0 0 RESPIRATORY Gasping 3 0 0 0 0 0 0 0 Moist Rales 2 0 0 0 0 0 0 0 GENERAL Yellow Ano-Genital Staining 2 0 0 0 0 0 0 0 DEAD Found Dead 1 0 0 0 0 

### 0 0 

### 0 Humane Sacrifice 

### 4 0 0 0 0 0 0 0 

### 9 10 11

0 0 0 0 0 0
0 0 0 0 0 0 0 0 0
0 0 0 0 0 0


### 0 0 0 0 0 0
0 0 0 0 0 0

0 0 0 0 0 0
0 0 0 0 0 0 0 0 0
0 0 0 0 0 0
0 0 0
0 0 0 0 0 0 

### Page 47 Final Report
Table 4

12 13 14

0 0 0 0 0 0
0 0 0 0 0 0 0 0 0
0 0 0 0 0 0
0 0 0 0 0 0
0 0 0 0 0 

### 0

0 0 0 0 0 0
0 0 0 0 0 0 0 0 0
0 0 

### 0 0 0 

### 0
0 0 

### 0
0 0 0 0 0 0

### Huntingdon Life Sciences 02-5449 Summary of 14-Day Post-Exposure ObseNations Da 

### 1 2 3 4 5 

### 6 7 

### 8 9 Group 2- E-1-Bromo-3,3,3-Trifluoropropene (25,650 ppm) Males No. of Animals Examined 5 5 

### 5 5 5 5 5 5 

### 5 Within Normal Limits 5 

### 5 5 

### 5 5 5 5 5 5 Females No. of Animals Examined 5 

### 5 5 5 5 5 5 5 5 Within Normal Limits 5 5 5 

### 5 5 5 

### 5 5 5 Group 3- 1-Bromo-2-Trifluoromethyi-3,3,3-Trifluoropropene (24,800 ppm) Males No. of Animals Examineda 

### 0 0 0 0 0 

### 0 0 0 

### 0 Females No. of Animals Examineda 

### 0 0 

### 0 0 0 

### 0 0 0 0

aAnimals died during exposure. 

### 10 11

5 

### 5 5 5



### 5 5 5 5



### 0 0

0 

### 0 

### Page 48 Final Report
Table 4

12 13 14

5 5 5 

### 5 5 5



### 5 5 5 5 5 

### 5

0 

### 0 0

0 

### 0 0

### Huntingdon Life Sciences 02-5449 Summary of 14-Day Post-Exposure Observations Da 

### 1 2 3 4 5 6 7 

### 8 Group 4- 2-Bromo-3,3,3-Trifluoropropene (5,173 ppm) Males No. of Animals Examined 5 5 

### 5 5 5 5 5 5 Within Normal Limits 

### 0 0 1 4 3 3 4 4 RESPIRATORY Gasping 1 

### 0 0 0 0 0 0 0 Moist Rales 3 4 4 1 2 2 1 1 GENERAL Decreased Fecal Volume 5 5 

### 0 0 0 0 0 0 Females No. of Animals Examined 

### 5 5 5 5 

### 5 5 5 5 Within Normal Limits 

### 0 2 2 4 2 5 5 4 SECRETORY Red Nasal Discharge 

### 0 1 1 

### 0 0 0 RESPIRATORY Labored Breathing 1 

### 0 0 0 0 0 0 0 Moist Rales 2 

### 3 3 

### 0 1 

### 0 0 0 GENERAL Alopecia- Extremities/Snout 

### 0 0 0 0 1 

### 0 0 0 No Stool 1 

### 0 0 0 0 0 0 0 Decreased Fecal Volume 4 1 

### 0 0 0 0 0 0 Incisors Maloccluded 

### 0 0 0 0 0 0 0 1 

### 9 

### 10 11

5 5 5 5 

### 5 5


### 0 0 0 0 0 0
0 0 0

5 5 5 4 4 4


### 0 0 0
0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 1 1 1 

### Page 49 Final Report
Table 4

12 13 14

5 

### 5 5 5 5 5


### 0 0 0 0 0 0
0 0 0



### 5 5 5 4 4 4


### 0 0 0
0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 1 1 1

### Huntingdon Life Sciences 02-5449 Summary of 14-Day Post-Exposure ObseNations Da 

### 1 2 3 4 

### 5 6 7 

### 8 Group 

### 5- E-1-Bromo-3,3,3-Trifluoropropene 

### (45,850 ppm) Males No. of Animals Examined 3 3 3 3 3 3 3 3 Within Normal Limits 

### 2 2 3 3 3 3 3 3 RESPIRATORY Labored Breathing 1 

### 0 0 0 0 0 0 Females No. of Animals Examined 

### 5 5 5 5 5 5 

### 5 5 Within Normal Limits 3 

### 5 5 5 5 5 5 5 SECRETORY Red Nasal Discharge 

### 2 0 0 0 0 0 0 0 RESPIRATORY Labored Breathing 1 

### 0 0 0 0 0 0 0 

### 9 10 11

3 3 3 3 3 3


### 0 0 0



### 5 5 5 5 5 5
0 0 0
0 0 0 

### Page 50 Final Report
Table 4

12 13 14

3 3 3 3 3 3


### 0 0 0



### 5 5 5 5 5 5
0 0 0
0 0 0

### Huntingdon Life Sciences 

## 02-5449

Males 

# I Individual Observations Animal Number Observations 

### 1 2 

### 3 Pre T* 

### 1 2 Group 1 - 2-Bromo-3,3,3-Trifluoropropene (26,580 ppm) 1046 Within Normal Limits p Clear Nasal Discharge p p p p Excessive Salivation p p p Chromodacryorrhea p Labored Breathing p p Decreased Activity p p p p Humane Sacrifice p 1047 Within Normal Limits p Clear Nasal Discharge p p p p Excessive Salivation p p p p Chromodacryorrhea p Labored Breathing p p p p Moist Rales 

# s s Decreased Activity p p p p Humane Sacrifice p 1048 Within Normal Limits p Clear Nasal Discharge p p p p Gasping p p p p Yellow Ana-Genital Staining 

# s Humane Sacrifice p

Key: P = Present; S = Slight; M = Moderate; E = Extreme. 

# I Da 4 

### 5 6 7 

### 8 9 10 11 

### Table 5 Page 51 Final Reoort

12 13 14

### Huntingdon Life Sciences 02-5449 Page 52 Final Reoort 

# I Males 

# I Individual Observations · 

# I Table 5 

# I
Animal Day Number Observations 0 1 2 

### 3 4 

### 5 6 7 

### 8 9 10 11 12 13 14 Pre T* 1 2 1049 Within Normal Limits 

### p Clear Nasal Discharge 

### p p p p Labored Breathing 

### p p p p Decreased Activity 

### p p p p Humane Sacrifice 

### p 1050 Within Normal Limits 

### p Clear Nasal Discharge 

### p p Excessive Salivation 

### p p p Labored Breathing 

### p p p Decreased Activity 

### p p Found Dead 

### p

Key: P = Present; S = Slight; M = Moderate; E = Extreme.

### Huntingdon Life Sciences 02-5449 Page 53 Final Reoort 

# I

# ~::es I Individual Observations 

# I Table 5 

# I

Animal Day: Number Observations 0 

### 1 2 

### 3 4 

### 5 6 7 8 

### 9 10 11 12 13 14 Pre T* 1 

### 2 Group 2- E-1-Bromo-3,3,3-Trifluoropropene (25,650 ppm) 2046 Within Normal Limits 

### p p p p p p p p p p p p p p p Red Nasal Discharge 

### p p p 2047 Within Normal Limits 

### p p p p p p p p p p p p p p p Red Nasal Discharge 

### p p p 2048 Within Normal Limits 

### p p p p p p p p p p p p p p p Red Nasal Discharge 

### p p p 2049 Within Normal Limits 

### p p p p p p p p p p p p p p p p p Red Nasal Discharge 

### p 2050 Within Normal Limits 

### p p p p p p p p p p p p p p p p p p Group 3- 1-Bromo-2-Trifluoromethyi-3,3,3-Trifluoropropene (24,800 ppm) 3046 Within Normal Limits 

### p Died During Exposure 

### p 3047 Within Normal Limits 

### p Died During Exposure 

### p 3048 Within Normal Limits 

### p Died During Exposure 

### p 3049 Within Normal Limits 

### p Died During Exposure 

### p 3050 Within Normal Limits 

### p Died During Exposure 

### p Key: P

## =Present; S

## =Slight; M

## =Moderate; E

## =Extreme.

### Huntingdon Life Sciences 02-5449 Page 54 

# I Males 

# I Individual ObseNations 

# I Table 5 

# I Animal Day: Number Observations 0 1 2 

### 3 4 

### 5 6 7 

### 8 

### 9 10 11 12 13 14 Pre T* 1 2 Group 4- 2-Bromo-3,3,3-Trifluoropropene (5, 173 ppm) 4046 Within Normal Limits 

### p p p p p p p p p p p p Red Nasal Discharge 

### p Red Dried Material on Face 

# s Moist Rales 

# s s s s s Decreased Fecal Volume 

### p p 4047 Within Normal Limits 

### p p p p p p p p p p p p p p p p Decreased Fecal Volume 

### p p 4048 Within Normal Limits 

### p p p p p p p p p p Moist Rales 

# s s s s s s s s Decreased Fecal Volume 

### p p 4049 Within Normal Limits 

### p p p p p p p p p p Gasping 

### p Moist Rales 

# s s s s s s s Decreased Fecal Volume 

### p p 4050 Within Normal Limits 

### p p p p p p p p p p p p Red Dried Material on Face 

# s Moist Rales 

# s s s M 

# s s Decreased Fecal Volume 

### p p
Key: P

## =Present; S

## =Slight; M

## =Moderate; E

## =Extreme.

### Huntingdon Life Sciences 02-5449 Page 55 

# I Males 

# I Individual Observations 

# I Table 5 

# I Animal Day: Number Observations 0 1 2 

### 3 4 

### 5 6 7 

### 8 9 10 11 12 13 14 Pre T* 1 2 Group 

### 5- E-1-Bromo-3,3,3-Trifluoropropene 

### (45,850 ppm) 

### 5046 Within Normal Limits 

### p p p p p p p p p p p p p Red Nasal Discharge 

### p p p Excessive Salivation 

### p p Labored Breathing 

### p p p p p 

### 5047 Within Normal Limits 

### p Found Dead During Exposure 

### p 

### 5048 Within Normal Limits 

### p p p p p p p p p p p p p p p Red Nasal Discharge 

### p p p Excessive Salivation 

### p 

### 5049 Within Normal Limits 

### p Dead 

### p 

### 5050 Within Normal Limits 

### p p p p p p p p p p p p p p p Clear Nasal Discharge 

### p Red Nasal Discharge 

### p Moist Rales 

# s s s

Key: P

## =Present; S

## =Slight; M

## =Moderate; E

## =Extreme.

### Huntingdon Life Sciences 02-5449

Females 

# I Individual Observations Animal Number Observations 0 1 

### 2 3 Pre T* 1 2 Group 1 - 2-Bromo-3,3,3-Trifluoropropene {26,580 ppm) 1546 Within Normal Limits 

### p Clear Nasal Discharge 

### p p p p Red Dried Material on Face 

# s Gasping 

### p Moist Rales M M 

# s Humane Sacrifice 

### p 1547 Within Normal Limits 

### p Clear Nasal Discharge 

### p p p p Excessive Salivation 

### p Labored Breathing 

### p p Gasping 

### p Humane Sacrifice 

### p 1548 Within Normal Limits 

### p Clear Nasal Discharge 

### p p Excessive Salivation 

### p Moist Rales 

# s s s s Yellow Ana-Genital Staining 

# s Found Dead 

### p

Key: P 

### = Present; S 

### = Slight; M 

### = Moderate; E 

### = Extreme. 

## I Da

-------------- --· ··-- ··-··-·-· --- 

### 4 5 6 7 

### 8 9 10 11 

### Table 5 Page 56 Final Renort

12 13 14

### Huntingdon Life Sciences 02-5449 Page 57 

## Eioal BepQ!:t
Females 

# I Individual Observations 

## I Table 5 Animal Da Number Observations 0 1 2 

### 3 4 

### 5 6 7 

### 8 9 10 11 12 13 14 Pre T* 1 2 1549 Within Normal Limits p Clear Nasal Discharge p p p p Excessive Salivation p p p p Gasping p Moist Rales 

# s s s Yellow Ana-Genital Staining 

# s Humane Sacrifice p 1550 Within Normal Limits p Clear Nasal Discharge p p p p Excessive Salivation p p p Moist Rales 

# s s s Humane Sacrifice p Group 2- E-1-Bromo-3,3,3-Trifluoropropene (25,650 ppm) 2546 Within Normal Limits p p p p p p p p p p p p p p p p p p 2547 Within Normal Limits p p p p p p p p p p p p p p p p p p 2548 Within Normal Limits p p p p p p p p p p p p p p p p p p 2549 Within Normal Limits p p p p p p p p p p p p p p p p p p 2550 Within Normal Limits p p p p p p p p p p p p p p p p p Red Nasal Discharge p Key: P

## =Present; S

## =Slight; M

## =Moderate; E

## =Extreme.

### Huntingdon Life Sciences 02-5449

Females Individual Observations Table 5 Dav 

### Page 58 Final Reoort

Animal Number Observations 

### 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Pre T* 1 2 Group 3 - 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene (24,800 ppm) 3546 Within Normal Limits 

### p Died During Exposure 

### p 3547 Within Normal Limits 

### p Died During Exposure 

### p 3548 Within Normal Limits 

### p Died During Exposure 

### p 3549 Within Normal Limits 

### p Died During Exposure 

### p 3550 Within Normal Limits 

### p Died During Exposure p

Key: P

## =Present; S

## =Slight; M

## =Moderate; E

## =Extreme.

### Huntingdon Life Sciences 02-5449 Page 59 

## Eioal Bepm:t
Females 

# I Individual Observations 

# I Table 5 

# I
Animal Day

___ Number Observations 

### 0 1 2 

### 3 4 

### 5 6 7 

### 8 9 10 11 12 13 14 Pre T* 

### 1 2 Group 4- 2-Bromo-3,3,3-Trifluoropropene (5, 173 ppm) 4546 Within Normal Limits 

### p p p p p p p p p p p p p p p p p Decreased Fecal Volume 

### p 4547 Within Normal Limits 

### p p p p p p p p p p p p p p p p Alopecia- Extremities/Snout M Decreased Fecal Volume 

### p 4548 Within Normal Limits 

### p p p p p p p p p p Red Nasal Discharge 

### p p p p Labored Breathing 

### p p p p Moist Rales 

# s s No Stool 

### p Decreased Fecal Volume 

### p 4549 Within Normal Limits 

### p p p p Red Nasal Discharge 

### p p p Moist Rales M M 

# s s Decreased Fecal Volume 

### p p Incisors Maloccluded 

### p p p p p p p 4550 Within Normal Limits 

### p p p p p p p p p p p 

### p p p p Moist Rales 

# s s s Decreased Fecal Volume 

### p
Key: P

## =Present; S

## =Slight; M

## =Moderate; E

## =Extreme.

### Huntingdon Life Sciences 

## 02-5449

Females 

# I Individual Observations Animal Number Observations 0 1 2 

### 3 Pre T* 1 

### 2 Group 

### 5- E-1-Bromo-3,3,3-Trifluoropropene 

### (45,850 ppm) 

### 5546 Within Normal Limits 

### p p p p Moist Rales 

# s s s 5547 Within Normal Limits 

### p p p Red Nasal Discharge 

### p p p p Chromodacryorrhea p p p 

### 5548 Within Normal Limits p p p p p p p 

### 5549 Within Normal Limits p p 

### p Lacrimation M M M Red Nasal Discharge p p p p Excessive Salivation p p p Labored Breathing p p 

### 5550 Within Normal Limits p p p p p p p

Key: P

## =Present; S

## =Slight; M

## =Moderate; E

## = Extreme. 

## I Da 4 

### 5 6 

### 7 8



### p p p p p
p p p p p

p p p p p 

### p p p p p

p p p p p 

### 9 10 11



### p p p
p p p

p p p p p p

p p p 

### Table 5 Page 60 Final Reoort

12 13 14



### p p p
p p p

p p p p p p

p p p

### Huntingdon Life Sciences 02-5449



### Animal Termination History Animal Date of Type of Study Animal Date of Type of Number Death Death3 

## Dal Number Death Deatha Males Females Group 1 - 2-Bromo-3,3,3-Trifluoropropene (26,580 ppm) 1046 18 Sep 02 H 1 1546 18 Sep 02 H 1047 18 Sep 02 H 1 1547 18 Sep 02 H 1048 18 Sep 02 H 1 1548 18 Sep 02 F 1049 18 Sep 02 H 1 1549 18 Sep 02 H 1050 18 Sep 02 F 1 1550 18 Sep 02 H Group 2- E-1-Bromo-3,3,3-Trifluoropropene (25,650 ppm) 2046 01 Oct 02 T 14 2546 01 Oct 02 T 2047 01 Oct 02 T 14 2547 01 Oct 02 T 2048 01 Oct 02 T 14 2548 01 Oct 02 T 2049 01 Oct 02 T 14 2549 01 Oct 02 T 2050 01 Oct 02 T 14 2550 01 Oct 02 T Group 3- 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene (24,800 ppm) 3046 17 Sep 02 F 0 3546 17 Sep 02 F 3047 17 Sep 02 F 0 3547 17 Sep 02 F 3048 17 Sep 02 

### F 0 3548 17 Sep 02 F 3049 17 Sep 02 F 0 3549 17 Sep 02 F 3050 17 Sep 02 F 0 3550 17 Sep 02 F Group 4- 2-Bromo-3,3,3-Trifluoropropene (5,173 ppm) 4046 04 Nov 02 T 14 4546 04 Nov02 

### T 4047 04 Nov 02 T 14 4547 04 Nov 02 

### T 4048 04 Nov 02 T 14 4548 04 Nov 02 T 4049 04 Nov02 T 14 4549 04 Nov02 T 4050 04 Nov 02 T 14 4550 04 Nov02 T Group 5- E-1-Bromo-3,3,3-Trifluoropropene (45,850 ppm) 5046 04 Nov 02 T 14 5546 04 Nov 02 T 5047 21 Oct 02 F 0 5547 04 Nov 02 T 5048 04 Nov 02 T 14 5548 04 Nov02 T 5049 21 Oct 02 F 0 5549 04 Nov 02 T 5050 04 Nov02 T 14 5550 04 Nov 02 T
aH =Humane Sacrifice; F =Found Dead; T =Terminal Sacrifice. bDay of exposure is defined as Day 0. 

### Page 61 Final Report
Table 6 Study 

## Dal

1 1 1 1 1

14 14 14 14 14

0 0 0 0 0

14 14 14 14 14

14 14 14 14 14

### Huntingdon Life Sciences 02-5449 Page 62 Final Report Mean Organ Weights Preface Table 7 Table of Contents Absolute Organ Weights

.....................................................................................63 %Organ to BodyWeight Ratios

.........................................................................65 %Organ to Brain Weight Ratios

.........................................................................67 Key to Abbreviations: g 

## wt. observ. = Grams = Weight = Observed Corresponding exposure levels for each group were as follows: Group 1 Group 2 Group 3 Group 4 Group 5. Note: 2-Bromo-3,3,3-Trifluoropropene (26,580 ppm) E-1-Bromo-3,3,3-Trifluoropropene (25,650 ppm) 1-Bromo-2-Trifluoromethyi-3,3,3-Trifluoropropene (24,800 ppm) 2-Bromo-3,3,3-Trifluoropropene (5,173 ppm) E-1-Bromo-3,3,3-Trifluoropropene (45,850 ppm)
Organs were not weighed for Groups 1 and 3 because all animals were found dead or humanely sacrificed.Huntingdon Life Sciences Princeton Research Center East Millstone, New Jersey Terminal Sacrifice Group

2 M e a n: Standard deviation: Number of observ. : 4 Me an: Standard deviation: Number of observ. : 5 M e a n: Standard deviation: Number of observ. : Terminal Body wt. (g)

373.4

29.1

(5)
340.8

20.0

(5)
346.3

28.4

(3) Summary statistics for absolute organ weights (g) Study number: 025449
Brain Liver Adrenal Glands Kidneys M a 1 e A n i m a 1 s 0.0637 2.2003 3.5118 17.2573 0.0051 0.1439 0.0758 1.3656 (5) (5) (5) (5)
0.0571 1.9022 2.9483 14.5060 0.0089 0.0702 0.2360 0.6510 (5) (5) (5) (5)
0.0499 2.0213 3.1764 15.2994 0.0067 0.0657 0.3363 2.3093 (3) (3) (3) (3) Printed: 08-Jan-03 Version 4.2.2 Testes Lungs

1.7918 3.3099 0.1113 0.2281 (5) (5)
1.4642 3.0933 0.0919 0.1254 (5) (5)
1.5696 3.0283 0.3246 0.1112 (3) (3)

"U Pl (Q <D (j) 

### c.vHuntingdon Life Sciences Princeton Research Center East Millstone, New Jersey Terminal Sacrifice Group

2 M e a n: Standard deviation: Number of observ. : 4 M e a n: Standard deviation: Number of observ. : 5 M e a n: Standard deviation: Number of observ. : Terminal Body wt. (g)

234.6

19.2

(5)
250.8

17.6

(5)
238.4

5.0 (5) Summary statistics for absolute organ weights (g) Study number: 025449
Brain Liver Adrenal Glands Kidneys F e m a l e A n i m a l s 0.0716 1.9653 2.3739 10.1943 0.0049 0.0622 0.1854 1.2445 (5) (5) (5) (5)
0.0760 1.8957 2.1833 11.1084 0.0058 0.0833 0.1977 2.4203 (5) (5) (5) (5)
0.0675 1.9013 2.0216 10.6981 0.0067 0.0658 0.1218 0.2301 (5) (5) (5) (5) Printed: 08-Jan.-03 Version 4.2.2 ovaries Lungs

1.4059 0.0935 0.0794 0.0056 (5) (5)
1.4306 0.1020 0.2357 0.0152 (5) (5)
1.3208 0
..0945 0.0602 0.0139 (5) (5)



### -o SJ) (Q <D (J) ..f::>.Huntingdon Life Sciences Summary Statistics for % Organ to Body Weight Printed: 08-Jan-03 Princeton Research Center Study number: 025449 East Millstone, New Jersey Version 4.2.2 Terminal Sacrifice Group Terminal Brain Liver Testes Body wt. (g) Adrenal Glands Kidneys Lungs**---------------------------------------------------------------------------------------------------------------------~~------------** M a l e A n i m a l s 2 M e a n: 373.4 0.0171 0.5940 0.9461 4.6265 0.4811 0.8937 Standard deviation: 29.1 0. 0014 0.0792 0. 0918 0.2528 0. 0296 0.1226 Number of observ. : (5) (5) (5) (5) (5) (5) (5) 4 Me an: 340.8 0.0168 0.5601 0.8648 4.2623 0.4319 0.9089 Standard deviation: 20.0 0.0026 0.0447 0.0403 0.1936 0.0502 0.0380 Number of observ. : (5) (5) (5) (5) (5) (5) (5) 5 M e a n: 346.3 0.0144 0.5862 0.9178 4.4028 0.4504 0.8789 Standard deviation: 28.4 0.0014 0.0496 0. 0726 0.3715 0.0639 0.0866 Number of observ. : (3) (3) (3) (3) (3) (3) (3)



### -u !l) 

### co CD Q) ()1Huntingdon Life Sciences Summary Statistics for % Organ to Body Weight Printed: 08-Jan-03 Princeton Research Center Study number: 025449 East Millstone, New Jersey Version 4.2.2 Terminal Sacrifice Group Terminal Brain Liver ovaries Body wt. (g) Adrenal Glands Kidneys Lungs**-----------------------------------------------------------------------------------------------------------------------~-----------** F e m a l e A n i m a l s 2 M e a n: 234.6 0.0308 0.8421 1.0154 4.3368 0.6005 0.0400 Standard deviation: 19.2 0.0038 0.0727 0.0880 0.2318 0.0222 0.0036 Number of observ. : (5) (5) (5) (5) (5) (5) (5) 4 M e a n: 250.8 0.0304 0.7582 0.8698 4.3952 0.5706 0.0408 Standard deviation: 17.6 0.0030 0.0529 0.0274 0.6150 0.0884 0.0063 Number of observ. : (5) (5) (5) (5) (5) (5) (5) 5 M e a n: 238.4 0.0283 0.7977 0.8481 4.4903 0.5541 0.0397 Standard deviation: 5.0 0.0026 0.0300 0.0508 0.1791 0.0256 0.0062 Number of observ. : (5) (5) (5) (5) (5) (5) (5)



### -u 0> (Q CD (J) (J)Huntingdon Life Sciences Princeton Research Center East Millstone, New Jersey Terminal Sacrifice Group Terminal Body wt. (g)
2 M e a n: 373.4 Standard deviation: 29.1 Number of observ. : (5) 4 M e a n: 340.8 Standard deviation: 20.0 Number of observ. : (5) 5 M e a n: 346.3 Standard deviation: 28.4 Number of observ. : (3) Summary Statistics for % Organ to Brain Weight Study number: 025449
Brain Liver Adrenal Glands Kidneys M a 1 e A n i m a 1 s 2.9061 100.0000 160.0990 787.7351 0.3013 0.0000 10.0132 88.5729 (5) (5) (5) (5)
3.0182 100.0000 155.1873 763.1697 0.5697 0.0000 14.2520 38.8130 (5) (5) (5) (5)
2.4749 100.0000 156.9516 756.1699 0.3896 0.0000 12.3757 103.9140 (3) (3) (3) (3) Printed: 08-Jan-03 Version 4.2.2 Testes Lungs

81.9524 150.5403 10.3061 7.5646 (5) (5)
77.0101 162.9808

4.7813 12.5995 (5) (5)
77.5256 149.8154 14.8739 2.0838 (3) (3)



### -u m (Q CD (J) -....,JHuntingdon Life Sciences Princeton Research Center East Millstone, New Jersey Terminal Sacrifice Group Terminal Body wt. (g)
2 M e a n: 234.6 Standard deviation: 19.2 Number of observ. : (5) 4 M e a n: 250.8 Standard deviation: 17.6 Number of observ. : (5) 5 M e a n: 238.4 Standard deviation: 5.0 Number of observ. : (5) Summary Statistics for % Organ to Brain Weight Study number: 025449
Brain Liver Adrenal Glands Kidneys F e m a 1 e A n i m a 1 s 3.6530 100.0000 121.0075 518.2682 0.3581 0.0000 11.8241 55.0725 (5) (5) (5) (5)
4.0194 100.0000 115.1597 585.5146 0.3796 0.0000 8.6870 118.8030 (5) (5) (5) (5)
3.5583 100.0000 106.5000 563.2047 0.4511 0.0000 8.6047 23.0241 (5) (5) (5) (5) Printed: 08-Jan-03 Version 4.2.2 Ovaries Lungs

71.5945 4.7534

4.5674 0.1722 (5) (5)
75.6661 5.4022 13.4477 0.9180 (5) (5)
69.5197 4.9744

3.5674 0.7266 (5) (5)

'"U P> (Q (!) 0) ())

### Huntingdon Life Sciences

Table of Contents 02-5449
Individual Organ Weights Preface Page 69 Final Report
Table 8

Absolute Organ Weights

.....................................................................................70 %Organ to Body Weight Ratios

.........................................................................72 %Organ to Brain Weight Ratios

.........................................................................74 Key to Abbreviations: 

## g wt. observ. 

# = Grams 

# = Weight = 

### Observed Corresponding exposure levels for each group were as follows: Group 1 Group 2 Group 3 Group 4 Group 5 Note: 2-Bromo-3,3,3-Trifluoropropene (26,580 ppm) E-1-Bromo-3,3,3-Trifluoropropene (25,650 ppm) 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene (24,800 ppm) 2-Bromo-3,3,3-Trifluoropropene (5, 173 ppm) E-1-Bromo-3,3,3-Trifluoropropene (45,850 ppm)
Organs were not weighed for Groups 1 and 3 because all animals were found dead or humanely sacrificed.Huntingdon Life Sciences summary statistics for absolute organ weights (g) Printed: 06-Jan-03 Princeton Research Center Study number: 025449 East Millstone, New Jersey Version '4-·. 2." Terminal Sacrifice Animal Group/ Terminal Brain Liver Testes No/sex Subgroup Body wt. (g) Adrenal Glands Kidneys Lungs



## ----------------------------------------------------------------------------------------------------------------------------------- M a 1 e A n i m a 1 s 2046/M 2/1 377 .o 0.0684 2.2544 3.4068 17.6379 1.6755 3.2399 2047/M 2/1 407.0 0,0600 2.0259 3.5122 17.3541 1.9566 2.9476 2048/M 2/1 388.0 0.0685 2.0765 3.4737 18.2689 1.8488 3.3805 2049/M 2/1 366.0 0.0646 2.3692 3.5702 18.1211 1.7438 3.5192 2050/M 2/1 329.0 0.0571 2.2754 3.5959 14.9046 1.7344 3.4621 M e a n: 373.4 0.0637 2.2003 3.5118 17.2573 1.7918 3.3099 Standard deviation: 29.1 0.0051 0.1439 0.0758 1.3656 0.1113 0.2281 Number of observ. : (5) (5) (5) (5) (5) (5) (5) 4046/M 4/1 335.0 0.0576 1.8952 2.7983 14.3762 1.4783 3.1343 4047/M 4/1 337.0 0.0563 1.9204 3.0356 14.1729 1,4080 3.0534 4048/M 4/1 341.0 0.0429 1.9985 3 .1143 15.4086 1.4637 2.9500 4049/M 4/1 318.0 0.0620 1.8947 2.6141 13.7135 1.6069 3.0439 4050/M 4/1 373.0 0.0667 1.8022 3.1793 14.8588 1.3639 3.2847 M e a n: 340.8 0.0571 1.9022 2.9483 14.5060 1.4642 3.0933 St.a.ndard deviation: 20.0 0.0089 0.0702 0.2360 0.6510 0.0919 0.1254 Number of observ. ; (5) (5) (5) (5) (5) (5) (5) 5046/M 5/1 367,0 0.0576 1.9707 3.1005 16.0453 1.6682 2.9134 5048/M 5/1 358.0 0.0464 2.0955 3.5442 17.1436 1.8335 3.1353 5050/M 5/1 314.0 0.0457 1.9977 2.8845 12.7094 1.2072 3.0363 M e a n: 346.3 0.0499 2.0213 3.1764 15.2994 1,5696 3.0283 Standard deviation: 28.4 0.0067 

### o·. 0657 0.3363 2.3093 0. 3246 0. 1112 Number of observ. ; (3) (3) (3) (3) (3) (3) (3)



### -o s:u (0 CD ""-! 0Huntingdon Life Sciences Summary statistics for absolute organ weights (g) Printed: 06-Jan-03 Princeton Research Center Study number: 025449 East Millstone, New Jersey Vers"lon 4 . 2 . 2 Terminal Sacrifice Animal Group/ Terminal Brain Liver Ovaries No/sex subgroup Body wt. (g) Adrenal Glands Kidneys Lungs



## ----------------------------------------------------------------------------------------------------------------------------------- F e m a l e A n i m a l s 2546/F 2/1 205.0 0.0710 1.9891 2 .1349 8. 8112 1.2743 0.0947 2547/F 2/1 246.0 0.0680 2.0002 2.4986 10.9119 1.4844 0.0915 2548/F 2/1 235.0 0.0748 1.8890 2.3878 10.0819 1.4285 0.0882 2549/F 2/1 231.0 0.0781 1.9120 2.5966 9.2695 1.4018 0.0904 2550/F 2/1 256.0 0.0662 2.0361 2.2515 11.8970 1.4407. 0.1025 M e a n: 234.6 0.0716 1.9653 2.3739 10.1943 1.4059 0.0935 Standard deviation: 19.2 0.0049 0.0622 0.1854 1.2445 0.0794 0.0056 Number of observ. : (5) (5) (5) (5) (5) (5) (5) 4546/F 4/1 280.0 0. 0722 1.9596 2.5268 15.2965 1.5157 0. 1125 4547/F 4/1 232.0 0.0680 1.9099 2.0489 9.0264 1.2297 0.1093 4548/F 4/1 247.0 0.0787 1.7682 2.0898 10.5843 1.3648 0.1095 4549/F 4/1 247.0 0.0824 1.9750 2.1749 10.1937 1.2442 0.0754 4550/F 4/1 248.0 0.0789 1.8657 2.0759 10.4412 1.7988 0.1033 M e a n: 250.8 0.0760 1.8957 2.1833 11.1084 1.4306 0.1020 Standard deviation: 17.6 0.0058 0.0833 0.1977 2.4203 0.2357 0.0152 Number of observ. :. (5) (5) (5) (5) (5) (5) (5) 5546/F 5/1 234.0 0.0744 1.8000 2.1160 10.8435 1.3010 0.1023 5547/F 5/1 236.0 0.0611 1.9149 1.8109 10.6102 1.2447 0.0787 5548/F 5/1 238.0 0.0665 1.9758 2.0299 10.7891 1.3141 0 .ll05 5549/F 5/1 237.0 0.0610 1.9325 2.0676 10.9097 1.4109 0.1000 5550/F 5/1 247.0 0.0743 1.8833 2.0838 10.3378 l.3334 0.0812 M e a n: 238.4 0.0675 1.9013 2.0216 10.6981 1.3208 0.0945 Standard deviation: 5.0 0.0067 0.0658 0.1218 0.2301 0.0602 0.0139 Number of observ. : (5) (5) (5) (5) (5) (5) (5)

"'0 Po> (Q CD --.J 

### _._Huntingdon Life Sciences summary Statistics for % Organ to Body Weight Printed: 06-Jan-03 Princeton Research Center Study number: 025449 East Millstone, New Jersey Version 4.2.2 Terminal Sacrifice Animal Group/ Terminal Brain Liver Testes No/sex Subgroup Body wt. (g) Adrenal Glands Kidneys Lungs**----------------------------------------------------------------------------------------------------------------------~~-----------** M a l e A n i m a l s 2046/M 2/1 377.0 0.0181 0.5980 0.9037 4.6785 0.4444 0.8594 2047/M 2/1 407.0 0.0147 0.4978 0.8629 4.2639 0.4807 0.7242 2048/M 2/1 388.0 0.0177 0.5352 0.8953 4.7085 0.4765 0.8713 2049/M 2/1 366.0 0.0177 0.6473 0.9755 4.9511 0.4764 0.9615 2050/M 2/1 329.0 0.0174 0.6916 1.0930 4.5303 0.5272 1.0523 M e a n: 373.4 0. 0171 0.5940 0.9461 4.6265 0.4811 0.8937 Standard deviation: 29.1 0.0014 0.0792 0.0918 0.2528 0.0296 0.1226 Number of observ. : (5) (5) (5) (5) (5) (5) (5) 4046/M 4/1 335.0 0.0172 0.5657 0.8353 4.2914 0.4413 0.9356 4047/M 4/1 337.0 0.0167 0.5699 0.9008 4.2056 0.4178 0.9061 4048/M 4/1 341.0 0.0126 0.5861 0.9133 4.5187 0.4292 0.8651 4049/M 4/1 318.0 0.0195 0.5958 0.8220 4.3124 0.5053 0.9572 4050/M 4/1 373.0 0.0179 0.4832 0.8524 3.9836 0.3657 0.8806 M e a n: 340.8 0.0168 0,5601 0.8648 4.2623 0.4319 0.9089 Standard deviation: 20.0 0.0026 0.0447 0.0403 0.1936 0.0502 0.0380 Number of observ. : (5) (5) (5) (5) (5) (5) (5) 5046/M 5/1 367.0 0.0157 0.5370 0.8448 4.3720 0.4546 0.7938 5048/M 5/1 358.0 0.0130 0.5853 0.9900 4.7887 0.5122 0.8758 5050/M 5/1 314.0 0.0146 0.6362 0.9186 4.0476 0.3845 0.9670 M e a n: 346.3 0.0144 0.5862 0.9178 4.4028 0.4504 0.8789 Standard deviation: 28.4 0.0014 0.0496 0.0726 0.3715 0.0639 0.0866 Number of observ. : (3) (3) (3) (3) (3) (3) (3)

"lJ Pl c.o CD -....j 1\:)Huntingdon Life Sciences summary Statistics for % Organ to Body Weight Printed: 06-Jan-03 Princeton Research Center Study number: 025449 East Millstone, New Jersey Version 4.2
.. 2 Terminal Sacrifice Animal Group/ Terminal Brain Liver Ovaries No/sex subgroup Body wt. (g) Adrenal Glands Kidneys Lungs**------------------------------------------------------------------------------------------------------------------------~----------** Female A n i m a l s 2546/F 2/1 205.0 0.0346 0.9703 1.0414 4.2981 0.6216 0.0462 2547/F 2/1 246.0 0.0276 0.8131 1·. 0157 4.4357 0.6034 0.0372 2548/F 2/1 235.0 0.0318 0.8038 1.0161 4.2902 0.6079 0.0375 2549/F 2/1 231.0 0.0338 0.8277 1.1241 4.0128 0.6068 0.0391 2550/F 2/1 256.0 0.0259 0.7954 0.8795 4.6473 0.5628 0.0400 M e a n: 234.6 0.0308 0.8421 1.0154 4.3368 0.6005 0.0400 Standard deviation: 19.2 0.0038 0.0727 0.0880 0.2318 0.0222 0.0036 Number of observ. : (5) (5) (5) (5) (5) (5) (5) 4546/F 4/1 280.0 0.0258 0.6999 0.9024 5.4630 0.5413 0.0402 4547/F 4/1 232.0 0.0293 0.8232 0.8831 3.8907 0.5300 0.0471 4548/F 4/1 247.0 0.0319 0.7159 0.8461 4.2851 0.5526 0.0443 4549/F 4/1 247.0 0.0334 0.7996 0.8805 4.1270 0.5037 0.0305 4550/F 4/1 248.0 0.0318 0.7523 0.9371 4.2102 

### o. 7253 0.0417 M e a n: 250.8 0.0304 0.7582 0.8698 4.3952 0.5706 0.0409 Standard deviation: 17.6 0.0030 0.0529 0.0274 0.6150 0.0884 0.0063 Number of observ. : (5) (5) (5) (5) (5) (5) (5) 5546/F 5/1 234.0 0.0318 0.7692 0.9043 4.6340 0.5560 0.0437 5547/F 5/1 236.0 0.0259 0. 8114 0.7673 4.4958 0.5274 0.0333 5548/F 5/1 239.0 0.0279 0.9302 0.8529 4.5332 0.5521 0.0464 5549/F 5/1 237.0 0.0257 0.9154 0.8724 4.6032 0.5953 0.0422 5550/F 5/1 247.0 0.0301 0.7625 0.9436 4.1953 0.5399 0.0329 M e a n: 238.4 0.0283 0.7977 0.8481 4.4903 0.5541 0.0397 Standard deviation: 5.0 0.0026 0.0300 0.0508 0.1791 0.0256 0.0062 Number of observ. : (5) (5) (5) (5) (5) (5) (5)

"1J Ill 

### co CD -....! VJHuntingdon Life Sciences Summary Statistics for % Organ. to Brain Weight ?rinted: 06-Jan-03 ?rinceton Research Center Study number: 025449 East Millstone, New Jersey Version 4.2.2 Terminal sacrifice Animal Group/ Terminal Brain Liver Testes No/sex Subgroup Body wt. (g) Adrenal Glands Kidneys Lungs



## ----------------------------------------------------------------------------------------------------------------------------------- M a 1 e A n i m a 1 s 2046/M 2/1 377.0 3.0341 100.0000 151.1178 782.3767 74.3213 143.7145 2047/M 2/1 407.0 2.9616 100.0000 173,3649 856.6119 96.5793 145.4958 2048/M 2/1 388.0 3.2988 100.0000 167.2863 879.7930 89.0344 162.7980 2049/M 2/1 366.0 2.7267 100.0000 150.6922 764.8616 73.6029 148.5396 2050/M 2/1 329.0 2.5094 100.0000 158.0338 655.0322 76.2240 152.1535 M e a n: 373.4 2.9061 100.0000 160.0990 787.7351 81.9524 150.5403 Standard deviation: 29.1 0.3013 0.0000 10.0132 88.5729 10.3061 7.5646 Number of observ. : (5) (5) (5) (5) (5) (5) (5) 4046/M 4/1 335.0 3.0393 100.0000 147.6520 758.5585 78.0023 165.3810 4047/M 4/1 337,0 2.9317 100.0000 158.0712 738.0182 73.3181 158.9981 4048/M 4/1 341.0 2.1466 100.0000 155.8319 771.0083 73.2399 147.6107 4049/M 4/1 318.0 3.2723 100.0000 137.9691 723.7822 84 '8103 160.6534 4050/M 4/1 373.0 3.7010 100.0000 176.4122 824.4813 75.6797 182.2606 M e a n: 340.8 3.0182 100.0000 155
.. 1873 763.1697 77.0101 162.9808 Standard deviation: 20.0 0.5697 0.0000 14.2520 38.8130 4.7813 12.5995 Number of observ. : (5) (5) (5) (5) (5) (5) (5) 5046/M 5/1 367.0 2.9228 100.0000 157.3299 814.1930 84.6501 147.8358 5048/M 5/1 358.0 2.2143 100.0000 169.1339 818.1151 87.4970 149.6206 5050/M 5/1 314.0 2.2876 100.0000 144.3911 636.2017 60.4295 151.9898 M e a n: 346.3 2.4749 100.0000 156.9516 756.1699 77.5256 149.8154 Standard deviation: 28.4 0.3896 0.0000 12.3757 103.9140 14.8739 2.0838 Number of observ. : (3) (3) (3) (3) (3) (3) (3)



### -u Ol (Q <D

## ~Huntingdon Life Sciences Summary Statistics for % Organ to Brain Weight Printed: 06-Jan-03 Princeton Research Center study number: 025449 East Millstone, New Jersey Version 4.2.2 Terminal Sacrifice Animal Group/ Terminal Brain Liver Ovaries No/sex Subgroup Body wt. (g) Adrenal Glands Kidneys Lungs 

## ----------------------------------------------------------------------------------------------------------------------.------------- ·Female A n i m a 1 s 2546/F 2/1 205.0 3.5695 100.0000 107.3300 442.9743 64.0642 4.7609 2547/F 2/1 246.0 3.3997 100.0000 124.9175 545.5405 74.2126 4.5745 2548/F 2/1 235.0 3.9598 100.0000 126.4055 533.7163 75.6220 4.6691 2549/F 2/1 231.0 4.0847 100.0000 135.8055 484.8065 73.3159 4.7280 2550/F 2/1 256.0 3.2513 100.0000 110.5791 584.3034. 70.7578 5.0341 M e a n: 234.6 3.6530 100.0000 121.0075 518.2682 71.5945 4.7534 Standard deviation: 19.2 0.3581 0.0000 11.8241 55.0725 4.5674 0.1722 Number of observ. : (5) (5) (5) (5) (5) (5) (5) 4546/F 4/1 280.0 3.6844 100.0000 128.9447 780.5931 77.3474 5.7410 4547/F 4/1 232.0 3.5604 100.0000 107.2779 472.6112 64.3856 5.7228 4548/F 4/1 247.0 4.4509 100.0000 118.1880 598.5919 77.1858 6.1927 4549/F 4/1 247.0 4.1722 100.0000 110.1215 516.1368 62.9975 3.8177 4550/F 4/1 248.0 4.2290 100.0000 111.2666 559.6399 96.4142 5.5368 M e 

### a: n: 250.8 4.0194 100.0000 115.1597 585.5146 75.6661 5.4022 Standard deviation: 17.6 0.3796 0.0000 8.6870 118.8030 13.4477 0.9180 Number of observ. : (5) (5) (5) (5) (5) (5) (5)

·5546/F 5/1 234.0 4.1333 100.0000 117.5556 602.4167 72.2778 5,6833 5547/F 5/1 236.0 3.1908 100.0000 94.5669 554.0665 65.0008 4.1099 5548/F 5/1 238.0 3.3657 100.0000 102.7381 546.0624 66.5098 5.5927 5549/F 5/1 237.0 3.1565 100.0000 106.9910 564.5383 73.0091 5.1746 5550/F 5/1 247.0 3.9452 100.0000 110.6462 548.9196 70.8013 4.3116 M e a n: 238.4 3.5583 100.0000 106.5000 563.2047 69.5197 4.9744 Standard deviation: 5.0 0.4511 0.0000 8·.6047 23.0241 3.5674 0.7266 Number of observ. : (5) (5) (5) (5) (5) (5) (5)

"'U s::u (Q CD -....j CJ1

### Huntingdon Life Sciences 02-5449 Page 76 Final Report Incidence Summary Report ', 

### for Gross Necropsy ObseNations Preface Table 9 Table of Contents Terminal Sacrifice

...............................................................................................77 Unscheduled Deaths

............................................................................................78 All Sacrifices

.......................................................................................................79 Corresponding exposure levels for each group were as follows: Group 1 Group 2 Group 3 Group 4 Group 5 2-Bromo-3,3,3-Trifluoropropene (26,580 ppm) E-1-Bromo-3,3,3-Trifluoropropene (25,650 ppm) 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene (24,800 ppm) 2-Bromo-3,3,3-Trifluoropropene (5, 173 ppm) E-1-Bromo-3,3,3-Trifluoropropene (45,850 ppm)Huntingdon Life Sciences Princeton Research Center East Millstone, New Jersey Incidence Summary Report for Gross Necropsy Observations Study number: 025449 Printed: 02-Jan-03 Page: 1

Version 4.2.2 Terminal**Sacrif=i~c~e----------------------------------~------------------~----------------------------------------------------------------**

- Males ·- 

### I -- Females Group: Number in group: Within normal limits 

### ............... Lungs Discolored 

### ..................... Adhesion 

### ....................... 1 0 0

0 0 2 3 4 5 1 1 2 3 5 

### o s 3 I 

### o s o 4 0 5 3 0 4 0

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1 0 5 5 5

0 0



## -u P.l 

### co CD 

# "" ""Huntingdon Life Sciences Princeton Research Center East Millstone, New Jersey Unscheduled Deaths Group: Number in group: Within normal limits
•• 0 •• 0 .... 0. 0. 0 Lungs Discolored
..................... Abnormal Contents

...... 0 •••• 0 ••• Trachea Abnormal Contents 0. 0 .... 0 0 ••• 0 .. 0 1 5 2

3 1

1 Incidence summary Report for Gross Necropsy Observations study number: 025449
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0 Printed: 02-Jan-03 Page: 1

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## -u p) 

### co <D -.....! (X)Huntingdon Life Sciences Princeton Research Center East Millstone, New Jersey All Sacrifices Group: Number in group: Within normal limits 

## .........**~** 

## .... Lungs Discolored
..................... Adhesion
....................... Abnormal Contents 

## .............. Trachea Abnormal Contents
.............. 1 5 2

3 0 1
1 Incidence Summary Report for Gross Necropsy Observations Study number: 025449
Males 2 3 5 5 4 0

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### I I 1 5 3
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### -a P.> (Q <D -.....) <.o' I· I 

### Huntingdon Life Sciences

', 

### Table of Contents 02-5449
Lesion Incidence Summary with Expanded Severity Levels Preface Page 80 Final Report

Table 10
Terminal Sacrifice

...............................................................................................81 Unscheduled Deaths

............................................................................................83 All Sacrifices

.......................................................................................................86 Key to Abbreviations NAD = 

### No abnormal diagnoses Corresponding exposure levels for each group were as follows: Group 

### 1 Group 2 Group 3 Group 4 Group 5 Note: 2-Bromo-3,3,3-Trifluoropropene (26,580 ppm) E-1-Bromo-3,3,3-Trifluoropropene (25,650 ppm) 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene (24,800 ppm) 2-Bromo-3,3,3-Trifluoropropene (5,173 ppm) E-1-Bromo-3,3,3-Trifluoropropene (45,850 ppm)
Due to computer limitations, Group 1 appears as CTLS (Controls) on the following table. There was no Control Group for this study.02-Jan-03; 18:28 Huntingdon Life Sciences 025449 -

An Acute (4-Hour) Inhalation Toxicity study in the Rat via Nose-Only Exposure Lesion Incidence Summary With Expanded Severity Levels

__________________________________ ; __ !
__________________________________________________________**·--~~-------------------------------**

-- A n i m a l s A f f e c t e d Controls from group(s): 1 Animal sex: -- M a l e s

-- 

### I

-- F e m a l e s Dosage group: Ctls 2 3 4 5 

### I Ctls 2 3 4 5 T i s s u e s 

### wi t h D i a 9 n o s e s No. in grouE: 0 5 0 5 3 

### I 0 5 0 5 5 Lungs ..................•.......................Number examined: 0 5 0 5 3 

### I 0 5 0 5 5 CONGESTION Nad> 0 5 0 5 3 

### I 0 5 0 4 5 Slight> 0 0 0 0 0 

### I 0 0 0 1 0

............................Total Incidence of Finding Observed: 0 0 0 0 0 

### I 0 0 0 1 0 EDEMA Nad> 0 5 0 5 3 

### I 0 5 0 5 5

............................Total Incidence of Finding Observed: 0 0 0 0 0 I 0 0 0 0 0 HEMORRHAGE(£) Nad> 0 4 0 5 3 I 0 4 0 4 5 Slight> 0 1 0 0 0 

### I 0 1 0 1 0 ..................•.........Total Incidence of Finding Observed: 0 l 0 0 0 I 0 1 0 1 0 ARTERIES: MEDIAL HYPERTROPHY Nad> 0 3 0 1 0 I 0 2 0 2 3 Minimal> 0 2 0 4 3 

### I 0 3 0 3 2

............................Total Incidence of Finding Observed: 0 2 0 4 3 I 0 3 0 3 2 ALVEOLAR/INTRAALVEOLAR MACROPHAGE£ Minimal> 0 2 0 3 3 I 0 l 0 3 4 Slight> 0 3 0 2 0 

### I 0 4 0 2 1

............................Total Incidence of Finding Observed: 0 5 0 5 3 I 0 5 0 5 5 BRONCHIOLAR EPITHELIUM: DEQUAMATED Nad> 0 5 0 5 3 I 0 5 0 5 5

............................Total Incidence of Finding Observed: 0 0 0 0 0 I 0 0 0 0 0 BRONCHIOLAR/PERIBRONCHIOLAR ACUTE/SUBACUTE INFLAMMATION Nad> 0 5 0 5 3 I 0 5 0 5 5

..... , ......................Total Incidence of Finding Obs.erved: 0 0 0 0 0 I 0 0 0 0 0 All Diagnoses; Death types: All scheduled; Date of death range: 01-0ct-02 To 04-Nov-02 

### -a p) c.o (!) (X) 

### _...02-Jan-03; 18:28 Huntingdon Life Sciences 025449
An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Lesion Incidence summary With Expanded Severity Levels

-- A n i m a 1 s Controls from group(s): 1 Animal sex: -- M a 1 e s

-- Dosage group: Ctls 2 3 4 5 T i s s u e s 

### wi t h D i a 

### s n o s e s No. in grouE: 0 5 0 5 3 Lungs
..........................................Number examined: 0 5 0 5 3 BRONCHIOLAR LUMENS: DESQUAMATED EPITHELIAL -CELLS/INFLAMMATORY CELLS/CELL DEBRIS Nad> 0 5 0 5 3

............................Total Incidence of Finding Observed: 0 0 0 0 0 LYMPHOID CELL AGGREGATE(S) Nad> 0 3 0 3 1 Minimal> 0 2 0 2 2 ......................•.....Total Incidence of Finding Observed: 0 2 0 2 2 SUBACUTE (CHRONIC ACTIVE)/CHRONIC INFLAMMATION Nad> 0 2 0 5 3 Minimal> 0 3 0 0 0

Slight> 0 0 0 0 0

............................Total Incidence of Finding Observed: 0 3 0 0 0 INTERSTITIUM: OSSEOUS METAPLASIA Nad> 0 5 0 4 2 Minimal> 0 0 0 1 1

............................Total Incidence of Finding Observed: 0 0 0 1 1 VESSEL(S): MINERAL DEPOSIT(S) Nad> 0 4 0 5 3 Minimal> 0 1 0 0 0

............................Total Incidence of Finding Observed: 0 1 0 0 0 VISCERAL PLEURA/CAPSULE: FIBROSIS Nad> 0 5 0 5 3 Minimal> 0 0 0 0 0 .................•..........Total Incidence of Finding Observed: 0 0 0 0 0 All Diagnoses; Death types: All scheduled; Date of death range: 01-0ct-02 To 04-Nov-02 A f f e c t e d 

### I

-- F e m a 1 e s 

### I Ctls 2 3 4 

### I 0 5 0 5 

### I 0 5 0 5 

### I 0 5 0 5 I 0 0 0 0 

### I 0 1 0 1 

### I 0 4 0 4 I 0 4 0 4
0 4 0 5 0 0 0 0 0 1 0 0 0 1 0 0 

### I 0 5 0 5 

### I 0 0 0 0 I 0 0 0 0 

### I 0 5 0 5 

### I 0 0 0 0 I 0 0 0 0 

### I 0 4 0 5 

### I 0 1 0 0 I 0 1 0 0 5 5 5
5 0
4 1 1
5 0 0 0

4 1 1
5 0 0

5 0 0



### -u ll> <0 <D ()) 1\)02-Jan-03; 18:28 Huntingdon Life Sciences 025449
An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Lesion Incidence Summary With Expanded Severity Levels

-- An i m a 1 s Controls from group(s): 1 Animal sex: -- M a 1 e s

-- Dosage group: Ctls 2 3 4 5 T i s s u e s 

### wi t h D i a g n o s e s No. in grou12: 5 0 5 0 2 Lungs .......•..................................Number examined: 5 0 5 0 2 CONGESTION Nad> 3 0 0 0 l Minimal> 0 0 0 0 0

Slight> l 0 3 0 0 Moderate> 1 0 2 0 1

............................Total Incidence of Finding Observed: 2 0 5 0 l EDEMA Nad> 4 0 5 0 2 Slight> 1 0 0 0 0 .......................••...Total Incidence of Finding Observed: l 0 0 0 0 HEMORRHAGE(S) Nad> 3 0 4 0 2 Minimal> 0 0 0 0 0

Slight> 2 0 1 0 0

............................Total Incidence of Finding Observed: 2 0 1 0 0 ARTERIES: MEDIAL HYPERTROPHY Nad> 0 0 1 0 2 Minimal> 4 0 3 0 0

Slight> 1 0 1 0 0

............................Total Incidence of Finding Observed: 5 0 4 0 0 ALVEOLAR/INTRAALVEOLAR MACROPHAGES Minimal> 0 0 2 0 2 Slight> 2 0 3 0 0 Moderate> 3 0 0 0 0

............................Total Incidence of Finding Observed: 5 0 5 0 2 All Diagnoses; Death types: All unscheduled; Date of death range: 17-Sep-02 To 21-0ct-02 A f f e c t e d 

### I

-- F e m a 1 e s 

### I Ctls 2 3 4 

### I 5 0 5 0 

### I 5 0 5 0 l 0 0 0 l 0 ·0 0 3 0 4 0 0 0 1 0 4 0 5 0 I 5 0 5 0 

### I 0 0 0 0 I 0 0 0 0
4 0 4 0 0 0 1 0 1 0 0 0 1 0 1 0
1 0 2 0 4 0 3 0 0 0 0 0 4 0 3 0

0 0 3 0 4 0 2 0 1 0 0 0 5 0 5 0

,j. 5 0 0 0 0 0 0 0

0 0 0
0 0 0 0

0 0 0 0

0 0 0 0



## -a ll> (Q ([) 

### co w02-Jan-03; 18:28 Huntingoon Life Sciences 025449 --,

An Acute (4-Hour) Inhalation Toxicity Stuoy in the Rat via Nose-Only Exposure Lesion Incioence Summary With Expanded Severity Levels

-- A n i m a 1 s Controls from group(s): l Animal sex: -- M a 1 e s

-- Dosage group: Ctls 2 3 4 5 

### I T i s s u e s W i t h D i a g n o s e s No. in group: 5 o 5 o 2 

### I Lungs ........................•.....•...........Number examined: 5 o 5 0 2 

### I BRONCHIOLAR EPITHELIUM: DEQUAMATED Nad> Slight> Moderate>

............................Total Incidence of Finding Observed: BRONCHIOLAR/PERIBRONCHIOLAR ACUTE/SUBACUTE INFLAMMATION Nad> Slight> .........................•..Total Incidence of Finding Observed: BRONCHIOLAR LUMENS: DESQUAMATED EPITHELIAL -CELLS/INFLAMMATORY CELLS/CELL DEBRIS Nad> Slight> Moderate>

............................Total Incidence ctf Finding Observed: LYMPHOID CELL AGGREGATE(S) Nad> Minimal>

................... , ........Total Incidence of Finding Observed: SUBACUTE (CHRONIC ACTIVE)/CHRONIC INFLAMMATION Nad> Minimal>

............................Total Incidence of Finding Observed: INTERSTITIUM: OSSEOUS METAPLASIA Nad> Minimal> .....................••.....Total Incidence of Finding Observed: 0 l 4 5
0 5 5

2 0 3 3

4 l l

2 3 3

5 0 0 0 0 0 0

0 0 0

0 0 0 0
0 0 0

0 0 0

0 0 0 5 0 0 0
5 0 0

5 0 0 0
2 3 3

5 0 0

4 l l 0 0 0 0
0 0 0

0 0 0 0
0 0 0

0 0 0

0 0 0 All Diagnoses; Death types: All unscheduled; Date of death range: 17-Sep-02 To 21-0ct-02 2 0 0 0
2 0 0

2 0 0 0
l l l

2 0 0

2 0 0 A f f e c t e d F e m a 1 e s ctls 2 3 4 5 5 0 4 l 5
0 5 5

0 5 0 5
5 0 0

3 2 2

4 l l 0 0 0 0 0 0
0 0 0

0 0 0 0
0 0 0

0 0 0

0 0 0 5 5 5 0 0 0
5 0 0

5 0 0 0
2 3 3
5 0 0
5 0 0 0 0 0 0 0 0
0 0 0

0 0 0 0

0 0 0
0 0 0

0 0 0 5 0 0 0 0 0 0
0 0 0

0 0 0 0
0 0 0
0 0 0

0 0 0 ""0 0> (Q CD CX> ..j::..02-Jan-03; 18:28 Huntingdon Life Sciences 025449
An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Lesion Incidence summary With Expanded Severity Levels

-- A n i m a 1 s Controls from group(s): 1 Animal sex: -- M a 1 e s

-- Dosage group: Ctls 2 3 4 5 

### I T i s s u e s W i t h D i a g n o s e s No. in group: 5 0 5 o 2 _ _j Lungs ...............•..........................Number examined: 5 o . 5 o 2 

### I VESSEL(S): MINERAL DEPOSIT(S) Nad> 5 0 5 0 2 

### I

............................Total Incidence of Finding Observed: 0 o o o o 

### I VISCERAL PLEURA/CAPSULE: FIBROSIS Nad>

............................Total Incidence of Finding Observed: 5 0 0 0 5 0 0 0 All Diagnoses; Death types: All unscheduled; Date of death range: 17-Sep-02 To 21-0ct-02 2 0 A f f e c t e d F e m a 1 e s Ctls 2 3 4 5 0 5 0 5 0 5 0 5 0 5 0 0 0 0 0
5 0 5 0 0 0 0 0 5 0 0 0 0
0 0

"U 

### m (Q CD 

### co 0102-Jan-03; 18:29 Huntingdon Life Sciences 025449
An Acute (4-Hour) Inhalation.Toxicity Study in the Rat via Nose-Only Exposure Lesion Incidence Summary With Expanded Severity Levels

-- A n i m a l s Controls from group(s): 1 Animal sex: -- M a 1 e s

-- Dosage group: Ctls 2 3 4 5 T i s s u e s 

### wi t h D i a g n o s e s No. in grou12: 5 5 5 5 5 Lungs
..........................................Number examined: 5 5 5 5 5 CONGESTION Nad> 3 5 0 5 4 Minimal> 0 0 0 0 0

Slight> 1 0 3 0 0 Moderate> 1 0 2 0 1 ..•.........................Total Incidence of Finding observed: 2 0 5 0 1 EDEMA Nad> 4 5 5 5 5 Slight> 1 0 0 0 0 ......................•.....Total Incidence of Finding Observed: 1 0 0 0 0 HEMORRHAGE(S) Nad> 3 4 4 5 5 Minimal> 0 0 0 0 0

Slight> 2 1 1 0 0 .................•..........Total Incidence of Finding Observed; 2 1 1 0 0 ARTERIES: MEDIAL HYPERTROPHY Nad> 0 3 1 1 2 Minimal> 4 2 3 4 3

Slight> 1 0 1 0 0 ...................•........Total Incidence of Finding Observed: 5 2 4 4 3 ALVEOLAR/INTRAALVEOLAR MACROPHAGES Minimal> 0 2 2 3 5 Slight> 2 3 3 2 0 Moderate> 3 0 0 0 0 .........................••.Total Incidence of Finding Observed: 5 5 5 5 5 All Diagnoses; Death types: All; Date of death range: 17-Sep-02 To 04-Nov-02 A f f e c t e d 

### I

-- F e m a l e s 

### I Ctls 2 3 4 

### I 5 5 5 5 

### I 5 5 5 5 1 5. 0 4 1 0 0 0 3 0 4 1 0 0 1 0 4 0 5 1 

### I 5 5 5 5 

### I 0 0 0 0 I 0 0 0 0

4 4 4 4 0 0 1 0 1 1 0 1 1 1 1 1 

### I 1 2 2 2 

### I 4 3 3 3 

### I 0 0 0 0 I 4 3 3 3 

### I 0 1 3 3 

### I 4 4 2 2 

### I 1 0 0 0 I 5 5 5 5 5 5 5 5 0 0 0 0
5 0 0

5 0 0 0

3 2 0 2
4 1 0 5

"U P> (Q CD (X) 0)02-Jan-03; 18:29 Huntingdon Life Sciences 025449
An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Lesion Incidence Summary With Expanded Severity Levels

-- An i m a 1 s Controls from group(s): 1 Animal sex: -- M a l e s

-- 

### I Dosage group: Ctls 2 3 4 5 

### I T i s s u e s W i t h D i a g n o s e s No. in group: 5 5 5 5 5 

### I Lungs
..........................................Number examined: 5 5 5 5 5 

### I BRONCHIOLAR EPITHELIUM: DEQUAMATED Nad> Slight> Moderate>

............................Total Incidence of Finding Observed: BRONCHIOLAR/PERIBRONCHIOLAR ACUTE/SUBACUTE INFLAMMATION Nad> Slight>

............................Total Incidence of Finding Observed: BRONCHIOLAR LUMENS: DESQUAMATED EPITHELIAL -CELLS/INFLAMMATORY CELLS/CELL DEBRIS Nad> Slight> Moderate>

............................Total Incidence of Finding Observed: LYMPHOID CELL AGGREGATE(S) Nad> Minimal>

............................Total Incidence of Finding Observed: SUBACUTE (CHRONIC ACTIVE)/CHRONIC INFLAMMATION Nad> Minimal>

Slight>

... , . · .................••....Total Incidence of Finding Observed: INTERSTITIUM: OSSEOUS METAPLASIA Nad> Minimal> ...............•............Total Incidence of Finding Observed: 0 1 4 5

0 5 5

2 0 3 3

4 1 1

2 3 0 3

5 0 0 All Diagnoses; Death types: All; Date of death range: 17-Sep-02 To 04-Nov-025 0 0 0
5 0 0

5 0 0 0
3. 2 2
2 3 0 3

5 0 0 5 0 0 0
5 0 0

5 0 0 0

2 3 3
5 0 0 0

4 1 1 5 0 0 0
5 0 0

5 0 0 0
3 2 2
5 0 0 0

4 1 1 5 0 0 0
5 0 0

5 0 0 0

2 3 3
5 0 0 0

4 1 1 A f f e c t e d F e m a l Ctls 5 5 0 4 1 5
0 5 5

0 5 0 5

5 0 0

3 2 0 2

4 1 1 2 3 5 5 5 5 5 0 0 0

5 0 0

5 0 0 0
1 4 4
4 0 1 1

5 0 0 5 0 0 0
5 0 0

5 0 0 0

2 3 3
.5 0 0 0

5 0 0 e s 4 5 5 5 0 0 0
5 0 0

5 0 0 0
1 4 4
5 0 0 0

5 0 0 5 5 5 5 0 0 0

5 0 0

5 0 0 0

4 1 1
5 0 0 0

4 1 1 '"'0 0) 

### co CD (X) -....!02-Jan-03; 18:29 Huntingdon Life Sciences 025449
An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Lesion Incidence summary With Expanded Severity Levels

-- A n i m a 1 s Controls from group(s): 1 Animal sex: -- M a 1 e s

-- Dosage group: Ctls 2 3 4 5 T i s s u e s 

### w i t h D i a q n o s e s No. in s:rou12: 5 5 5 5 5 Lungs
..........................................Number examined: 5 5 5 5 5 VESSEL(S): MINERAL DEPOSIT(S) Nad> 5 4 5 5 5 Minimal> 0 1 0 0 0 ..................•.........Total Incidence of Finding Observed: 0 1· 0 0 0 VISCERAL PLEURA/CAPSULE: FIBROSIS Nad> 5 5 5 5 5 Minimal> 0 0 0 0 0

............................Total Incidence of Finding Observed: 0 0 0 0 0 All Diagnoses; Death types: All; Date of death range: 17-Sep-02 To 04-Nov-02 A f f e c t e d 

### I

-- F e m a 1 e s 

### I Ctls 2 3 4 

### I 5 5 5 5 

### I 5 5 5 5 

### I 5 5 5 5 

### I 0 0 0 0 I 0 0 0 0 I 5 4 5 5 

### I 0 1 0 0 I 0 1 0 0 5 5 5 5 0 0

5 0 0



### -u P.l (Q CD co co

### Huntingdon Life Sciences 02-5449 Page 89 Final Report Individual Animal Gross and Microscopic Observations ', 

### Preface Table 11 Corresponding exposure levels for each group were as follows: Group 

### 1 Group 2 Group 3 Group 4 Group 5 Note: 2-Bromo-3,3,3-Trifluoropropene (26,580 ppm) E-1-Bromo-3,3,3-Trifluoropropene (25,650 ppm) 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene (24,800 ppm) 2-Bromo-3,3,3-Trifluoropropene (5, 173 ppm) E-1-Bromo-3,3,3-Trifluoropropene (45,850 ppm)

Unless otherwise specified in a histopathology note, the organ/tissue examined was the required (routine) section.02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations Page: 1

STATUS: Humane/Otherwise Specified PHASE DAY OF DEATH: 1 SEX: Male PHASE: Dosing phase ANIMAL: _1046 GROUP: 1 Tissue Gross Observations/Comments Lungs
. ....... No gross observations on tissue. Microscopic Observations/Comments
ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. BRONCHIOLAR EPITHELIUM: DEQUAMATED, Moderate. BRONCHIOLAR/PERIBRONCHIOLAR ACUTE/SUBACUTE INFLAMMATION, Slight. SUBACUTE (CHRONIC ACTIVE)/CHRONIC INFLAMMATION, Multifocal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

"1J ll> (Q CD <0 002-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations Page: 2

STATUS: Humane/Otherwise Specified PHASE DAY OF DEATH: l SEX: Male PHASE: Dosing phase ANIMAL: 1047 GROUP·; 1 Tissue Lungs
. · · · · · · · ·Gross Observations/Comments Discolored, All lobes, Red, Foci, 0.2

- 0.5 em, Moderate Microscopic Observations/Comments Examined; 1 correlation found:

HEMORRHAGE(S), Multifocal, Slight. ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. BRONCHIOLAR EPITHELIUM: DEQUAMATED, Moderate. BRONCHIOLAR/PERIBRONCHIOLAR ACUTE/SUBACUTE INFLAMMATION, Slight. BRONCHIOLAR LUMENS: DESQUAMATED EPITHELIAL CELLS/INFLAMMATORY CELLS/CELL DEBRIS, Moderate. LYMPHOID CELL AGGREGATE(S), Focal, Minimal. SUBACUTE (CHRONIC ACTIVE)/CHRONIC INFLAMMATION, Multifocal, Minimal.

Tissues without comment under Gross observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

""0 PJ (Q <D <0

.......**02-Jan~03;** 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations Page: 3

STATUS: Humane/Otherwise Specified PHASE DAY OF DEATH: 1 SEX: Male PHASE: Dosing phase ANIMAL(; 1048 GROUP: 1 Tissue Lungs
........ .Gross Observations/Comments Discolored, All lobes, Red, Moderate Discolored, Right lobes, Red, Foci, 0.2

- 0.5 em, Moderate Microscopic Observations/Comments Examined; 1 correlation found:

CONGESTION, Slight. Examined; 1 correlation found:

HEMORRHAGE(S), Multifocal, Slight. ARTERIES: MEDIAL HYPERTROPHY, Slight. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Moderate. BRONCHIOLAR EPITHELIUM: DEQUAMATED, Moderate. BRONCHIOLAR/PERIBRONCHIOLAR ACUTE/SUBACUTE INFLAMMATION, Slight. BRONCHIOLAR LUMENS: DESQUAMATED EPITHELIAL CELLS/INFLAMMATORY CELLS/CELL DEBRIS, Moderate.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



### -o lJ) (.Q <D 

### c.o 1\)02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations Page: 4

STATUS: Humane/Otherwise Specified PHASE DAY OF DEATH: 1 SEX: Male PHASE: Dosing phase ANIMAL: _1049 GROUP: 1 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. Microscopic Observations/Comments
ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Moderate. BRONCHIOLAR EPITHELIUM: DEQUAMATED, Slight. BRONCHIOLAR/PERIBRONCHIOLAR ACUTE/SUBACUTE INFLAMMATION, Slight. SUBACUTE (CHRONIC ACTIVE)/CHRONIC INFLAMMATION, Multifocal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



## -a PJ (Cl <D <D 

### w02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations Page: 5

STATUS: .Found Dead PHASE DAY OF DEATH: 1 SEX: Male PHASE: Dosing phase ANIMAL;. 1050 GROUP: 1 Tissue Lungs
. · · · · · · · ·

Trachea
. . . . . . . . Gross Observations/Comments Discolored, All lobes, Red, Severe
Abnormal Contents, All lobes, Fluid, Moderate

Abnormal Contents, Lumen, Clear, Frothy fluid, Moderate Microscopic Observations/Comments Examined; 1 correlation found:

CONGESTION, Moderate. Examined; 1 correlation found:

EDEMA, Slight. ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Moderate. BRONCHIOLAR EPITHELIUM: DEQUAMATED, Moderate. BRONCHIOLAR/PERIBRONCHIOLAR ACUTE/SUBACUTE INFLAMMATION, Slight. BRONCHIOLAR LUMENS: DESQUAMATED EPITHELIAL CELLS/INFLAMMATORY CELLS/CELL DEBRIS, Moderate. No micropathology observations on tissue.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined. 

### -u !l> co <D co**~**02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An**Acu~e** (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs •........ No gross observations on tissue. SEX: Male PHASE: Dosing phase

Microscopic Observations/Comments Page: 6

ANIMAL: .2046

GROUP: 2

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. LYMPHOID CELL AGGREGATE(S), Focal, Minimal. SUBACUTE (CHRONIC ACTIVE)/CHRONIC INFLAMMATION, Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

"1J Pl 

### co CD <0 0102-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Lungs
........ .Gross Observations/Comments Discolored, All lobes, Red, Foci, 0.2

- 0.5 em, Slight SEX: Male PHASE: Dosing phase

Microscopic Observations/Comments

Examined; 1 correlation found:

HEMORRHAGE(S), Multifocal, Slight. ARTERIES: MEDIAL HYPERTROPHY, Minimal. Page: 7

ANIMAL:,, 2047

GROUP: 2

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. VESSEL(S): MINERAL DEPOSIT(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



### -u m c.o CD <.o 0)02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Male PHASE: Dosing phase

Microscopic Observations/Comments Page: 8

ANIMAL: "2048

GROUP: 2

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. LYMPHOID CELL AGGREGATE(S), Focal, Minimal. SUBACUTE (CHRONIC ACTIVE)/CHRONIC INFLAMMATION, Multifocal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



### -o 0> (Q <D (0 -....)02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations Page: 9**--------~---------------------------------------------;------------------------------~---------------------------------------------** STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Male PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined. ANIMAL: 20.49 GROUP: 2

""0 Po> 

### co CD 

### c.o (X)02-Jan-03; 16:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs .....•... No gross observations on tissue. SEX: Male PHASE: Dosing phase

Microscopic Observations/Comments

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. SUBACUTE (CHRONIC ACTIVE)/CHRONIC INFLAMMATION, Multifocal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined. Page: 10

ANIMAL:.,2050

GROUP: 2



### -o s:u co CD <0 <002-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449

STATUS: Found Dead PHASE DAY OF DEATH: 0 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations SEX: Male PHASE: Dosing phase Tissue Gross Observations/Comments Microscopic Observations/Comments Lungs
. . . . . . . . . Discolored, All lobes, Red, Slight Examined; l correlation found.: CONGESTION, Slight. Page: 11

ANIMAL.: 3046

GROUP: 3

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



## -u Ol 

### co CD



### ...... 0 002-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449

STATUS: Found Dead PHASE DAY OF DEATH: 0 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure ·Individual Animal Gross and Microscopic Observations SEX: Male PHASE: Dosing phase Tissue Gross Observations/Comments Microscopic Observations/Comments Lungs
. . . . . . . · · Discolored, All lobes, Red, Moderate Examined; 1 correlation found: CONGESTION, Moderate. HEMORRHAGE(S), Multifocal, Slight. ARTERIES: MEDIAL HYPERTROPHY, Slight. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. Page: 12

ANIMAL·:. 3047

GROUP: 3

LYMPHOID CELL AGGREGATE(S), Focal, Minimal. INTERSTITIUM: OSSEOUS METAPLASIA, Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

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## ..... 0



## .....02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449

STATUS: Found Dead PHASE DAY OF DEATH; 0 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations SEX: Male PHASE: Dosing phase Tissue Gross Observations/Comments Microscopic Observations/Comments Lungs
. · · · · · · · · Discolored, Right lobes, Red, Moderate Examined; 1 correlation found: CONGESTION, Moderate. ARTERIES: MEDIAL HYPERTROPHY, Minimal. Page: 13

ANIMAL: .3048

GROUP: 3

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

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## ..... 0 [\)02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449

STATUS: Found Dead PHASE DAY OF DEATH; 0 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations SEX: Male PHASE: Dosing phase Tissue Gross Observations/Comments Microscopic Observations/Comments Lungs
........ . Discolored, All lobes, Red, Slight Examined; 1 correlation found: CONGESTION, Slight. ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. Page: 14

ANIMAL:, 3049

GROUP: 3

LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



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__. 0 

### c.v02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449

STATUS: Found Dead PHASE DAY OF DEATH: 0 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations SEX: Male PHASE: Dosing phase Tissue Gross Observations/Comments Microscopic Observations/Comments Lungs
. . · · · · · · · Discolored, All lobes, Red, Slight Examined; 1 correlation found: CONGESTION, Slight. ARTERIES: MEDIAL HYPERTROPHY, Minimal. Page: 15

ANIMAL:
.. 3050

GROUP: 3

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



### -u m c.o <D



### ...... 0 ..j::.02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE .DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
. . No gross observations on tissue. SEX: Male PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined. Page: 16

ANIMAL:. 4046

GROUP: 4

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### ...... 0 ()102-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Male PHASE: Dosing phase

Microscopic Observations/Comments

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. Page: 17

ANIMAL_: 4047

GROUP: 4

LYMPHOID CELL AGGREGATE(S), Focal, Minimal. INTERSTITIUM: OSSEOUS METAPLASIA, Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



## -u p) (.Q CD
__,_ 0 (J')**----~--** -----**~----~---·-**02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS:· Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Male PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. Page: 18

ANIMAL: 4048

GROUP: 4

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



### -u s:u (Q CD 

### _.. 0 -....,J02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs ...•..... No gross observations on tissue. SEX: Male PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. LYMPHOID CELL AGGREGATE(S), Multifocal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined. Page: 19

ANIMAL:_,4049

GROUP: 4

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### ...... 0 ())02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) InhalaUon Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Male PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. Page: 20

ANIMAL.: 4050

GROUP: 4

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

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### ...... 0 (002-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Male PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. Page: 21

ANIMAL; 5046

GROUP: 5

LYMPHOID CELL AGGREGATE(S), Focal, Minimal. INTERSTITIUM: OSSEOUS METAPLASIA, Multifocal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

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## ..... 

## ..... 002-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449

STATUS: Found Dead PHASE DAY OF DEATH: 0 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic observations SEX: Male PHASE: Dosing phase Tissue Gross Observations/Comments Microscopic Observations/Comments Lungs
..... , ... Abnormal.Contents, All lobes, Fluid CONGESTION, Moderate. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. Page: 22**ANIMA~,:** 5047 GROUP: 5

LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



### -u P> (Q CD



### ......

......


### ......02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Male PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. Page: 23**ANIMA~:** 5048 GROUP: 5

LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

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.......

....... 1\)\.-**~~'**
02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449

STATUS: Found Dead PHASE DAY OF DEATH: 0 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations SEX: Male PHASE: Dosing phase Tissue Gross Observations/Comments Microscopic Observations/Comments Lungs
........ . Abnormal Contents, All lobes, Fluid Examined; no correlation found ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined. Page: 24

ANIMAL: 5Q49

GROUP: 5



## -u P> (Q <D



### ......
...... c.v02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Male PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined. Page: 25

ANIMAL: 5050

GROUP: 5



### -a Pl (.Q <D



# .....

...... +:>.02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations Page: 26

STATUS: Humane/Otherwise Specified PHASE DAY OF DEATH: 1 SEX: Female PHASE: Dosing phase ANIMAL:. 1546 GROUP: 1 Tissue Gross Observations/Comments Lungs ....•.... No gross observations on tissue. Microscopic Observations/Comments HEMORRHAGE(S), Multifocal, Slight. ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. BRONCHIOLAR EPITHELIUM: DEQUAMATED, Slight. BRONCHIOLAR/PERIBRONCHIOLAR ACUTE/SUBACUTE INFLAMMATION, Slight. BRONCHIOLAR LUMENS; DESQUAMATED EPITHELIAL CELLS/INFLAMMATORY CELLS/CELL DEBRIS, Slight. SUBACUTE (CHRONIC ACTIVE)/CHRONIC INFLAMMATION, Multifocal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

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### _., _., CJl02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449**~',**

An Acute (4-Hour) Inhalation Toxicity study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations Page: 27

STATUS: Humane/Otherwise Specified PHASE DAY OF DEATH: 1 SEX: Female PHASE: Dosing phase ANIMA!;; 1547 GROUP: 1 Tissue Gross Observations/Comments Lungs ........• No gross observations on tissue. Microscopic Observations/Comments CONGESTION, Slight. ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. BRONCHIOLAR EPITHELIUM: DEQUAMATED, Moderate. BRONCHIOLAR/PERIBRONCHIOLAR ACUTE/SUBACUTE INFLAMMATION, Slight. BRONCHIOLAR LUMENS: DESQUAMATED EPITHELIAL CELLS/INFLAMMATORY CELLS/CELL DEBRIS, Slight.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

'"'0 A> <0 <D

.......

....... (j)02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations Page: 28

STATUS: Found Dead PHASE DAY OF DEATH: 1 SEX: Female PHASE: Dosing phase**ANIMAL~** 1548 GROUP: l Tissue G'ross Observations/Comments Lungs
........ . Discolored, All lobes,**R~d,** Moderate Microscopic Observations/Comments Examined; 1 correlation found:

CONGESTION, Slight. ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. BRONCHIOLAR EPITHELIUM: DEQUAMATED, Slight. BRONCHIOLAR/PERIBRONCHIOLAR ACUTE/SUBACUTE INFLAMMATION, Slight. BRONCHIOLAR LUMENS: DESQUAMATED EPITHELIAL CELLS/INFLAMMATORY CELLS/CELL DEBRIS, Slight. INTERSTITIUM: OSSEOUS METAPLASIA, Focal, Minimal.

Tissues without ·comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

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### ......

...... -....j02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations Page: 29

STATUS: Humane/Otherwise Specified PHASE DAY OF DEATH: 1 SEX: Female PHASE: Dosing phase ANIMAL,: 1549 GROUP: 1 Tissue Gross Observations/Comments Lungs
........ . Discolored, All lobes, Red, Slight Microscopic Observations/Comments Examined; 1 correlation found:

CONGESTION, Slight. ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Moderate. BRONCHIOLAR EPITHELIUM: DEQUAMATED, Slight. BRONCHIOLAR/PERIBRONCHIOLAR ACUTE/SUBACUTE INFLAMMATION, Slight. BRONCHIOLAR LUMENS: DESQUAMATED EPITHELIAL CELLS/INFLAMMATORY CELLS/CELL DEBRIS, Slight. SUBACUTE (CHRONIC ACTIVE)/CHRONIC INFLAMMATION, Multifocal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

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### ......


### ...... CXl02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449' An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic observations Page: 30

STATUS: Humane/Otherwise Specified PHASE DAY OF DEATH: 1 SEX: Female PHASE: Dosing phase ANIMAL: 1550 GROUP,; l Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. Microscopic Observations/Comments CONGESTION, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. BRONCHIOLAR EPITHELIUM: DEQUAMATED, Slight. BRONCHIOLAR/PERIBRONCHIOLAR ACUTE/SUBACUTE INFLAMMATION, Slight. BRONCHIOLAR LUMENS: DESQUAMATED EPITHELIAL CELLS/INFLAMMATORY CELLS/CELL DEBRIS, Slight.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

'1J 

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### _... _... <.o02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs ......•.. No gross observations on tissue. SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. Page: 31

ANIMAL;_ 2546

GROUP: 2

LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

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# ..... [\) 002-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Lungs
........ .Gross Observations/Comments Adhesion, Left lobe(s), Moderate/ To thoracic wall SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments

Examined; 1 correlation found:

VISCERAL PLEURA/CAPSULE: FIBROSIS, Focal, Minimal. HEMORRHAGE(S), Multifocal, Slight. Page; 32

ANIMAL:,,2547

GROUP: 2

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. LYMPHOID CELL AGGREGATE(S), Focal, Minimal. SUBACUTE (CHRONIC ACTIVE)/CHRONIC INFLAMMATION, Multifocal, Slight.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

"'1J Po> <0 <D


### _. 1\) 

### _.02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs .......•. No gross observations on tissue. SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. Page: 33

ANIMAL.: 2548

GROUP: 2

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

"U Ol co <D

....... 1\:) 1\:)02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs ....•.... No gross observations on tissue. SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments
ARTERIES: MEDIAL HYPERTROPHY, Minimal. Page: 34

ANIMAL.t 2549

GROUP: 2

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

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### w02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. Page: 35

ANIMAL: 2550

GROUP: 2

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



### -o Ol (Q CD


### _. )\) ,J:::..02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449

STATUS: Found Dead PHASE DAY OF DEATH: 0 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations SEX: Female PHASE: Dosing phase Tissue Gross Observations/Comments Microscopic Observations/Comments Lungs
. · · · · · · · · Discolored, All lobes, Red, Slight Examined; 1 correlation found: CONGESTION, Slight. ALVEOLAR/!NTRAALVEOLAR MACROPHAGES, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined. Page: 36

AN!Mb.L: 3546

GROUP: 3

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### _. 1\) ()102-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449

STATUS: Found Dead PHASE DAY OF DEATH: 0 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations SEX: Female PHASE: Dosing phase Tissue Gross Observations/Comments Microscopic Observations/Comments Lungs
........ . Discolored, All lobes, Red, Slight Examined; 1 correlation found: CONGESTION, Slight. ARTERIES: MEDIAL HYPERTROPHY, Minimal. Page: 37

ANIMAL!
..3547

GROUP: 3

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



### -o m 

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### ...... (\) (J)02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449

STATUS : ·Found Dead PHASE DAY OF DEATH: 0 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations SEX: Female PHASE: Dosing phase Tissue Gross Observations/Comments Microscopic Observations/Comments Lungs
........ . Discolored, Right lobes, Red, Slight Examined; 1 correlation found: CONGESTION, Slight. HEMORRHAGE(S), Multifocal, Minimal. ARTERIES: MEDIAL HYPERTROPHY, Minimal. Page: 38

ANIMAL;. 3548

GROUP: 3

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



## -o Pl co <D

....... 1\) -.....j02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449

STATUS: Found Dead PHASE DAY OF DEATH: 0 ..------... ,

An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations SEX: Female PHASE: Dosing phase Tissue Gross Observations/Comments Microscopic Observations/Comments Lungs
....... . Discolored, All lobes, Red, Slight CONGESTION, Slight. ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined. Page: 39

ANIMAL.: 3549

GROUP: 3



### -o P> 

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### ...... 1\) (X)02-Jan-03; 18:30 Huntingdon Life sciences, Inc. 025449

STATUS: Found Dead PHASE DAY OF DEATH: 0 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations SEX: Female PHASE: Dosing phase Tissue Gross Observations/Comments Microscopic Observations/Comments Lungs
. . . . . . . .. Discolored, All lobes, Red, Moderate Examined; 1 correlation found: CONGESTION, Moderate. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. Page: 40

ANIMAL;, 3550

GROUP: 3

LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



### -o p.) (Q <D



## ..... 1\) (002-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. Page: 41

ANIMAL,: 4546

GROUP: 4

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight. LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

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....... 

### w 002-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. Page: 42

ANIMAL: 4547

GROUP: 4

LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

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### _.. (.r.) 

### _..02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. LYMPHOID CELL AGGREGATE(S), Multifocal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined. Page: 43

ANIMAL: 4548

GROUP: 4



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02-Jan-03; 18:30 Huntingdon Life ,sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/comments Lungs
......... No gross observations on tissue. SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. Page: 44

ANIMAL: 4549

GROUP: 4

LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

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### co CD ...,.\, 

### w 

### w02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Lungs
........ .Gross Observations/Comments Discolored, All lobes, Red,. Foci, 0.2

- 0.5 em SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments

Examined; 1 correlation found:

HEMORRHAGE(S), Multifocal, Slight. CONGESTION, Slight. Page: 45

ANIMAL: 4550

GROUP: 4

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

""'0 P> 

### co <D
_, 

### w +::-02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue, SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. INTERSTITIUM: OSSEOUS METAPLASIA, Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined. Page: 46

ANIMAL; 5546

GROUP: 5

"1J 

### m (Q <D


### __.. 

### c.v (}102-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/comments Lungs
......... No gross observations on tissue. SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments
ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined. Page: 47

ANIMAL_; 5547

GROUP: 5

""0 lll (Q <D



### ...... (.U (J)02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments Page: 48

ANIMAL_:_ 5548

GROUP: 5

ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Slight.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.



## -a P> <0 <D
_., 

### c.u -.....j02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Observations STATUS: Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal. Page: 49

ANIW\L: 5549

GROUP: 5

LYMPHOID CELL AGGREGATE(S), Focal, Minimal.

Tissues without comment under Gross Observations were within normal limits at necropsy. The following tissues were unremarkable microscopically: No tissues examined.

"'U P.> 

### co CD 

### _.. 

### w co02-Jan-03; 18:30 Huntingdon Life Sciences, Inc. 025449 An Acute (4-Hour) Inhalation Toxicity Study in the Rat via Nose-Only Exposure Individual Animal Gross and Microscopic Ooservations STATUS: ·Final phase sacrifice PHASE DAY OF DEATH: 14 Tissue Gross Observations/Comments Lungs
......... No gross observations on tissue. SEX: Female PHASE: Dosing phase

Microscopic Observations/Comments

ARTERIES: MEDIAL HYPERTROPHY, Minimal. ALVEOLAR/INTRAALVEOLAR MACROPHAGES, Minimal.

Tissues without comment under Gross Observations were within normal limits at.necropsy. The following tissues were unremarkable microscopically: No tissues examined. Page: 50

ANIMA4; 5550

GROUP: 5



## -u p.) (Q <D



### ...... 

### w c.o

### Huntingdon Life Sciences 02-5449
Equipment List Exposure Chamber 

### Page 140 Final Report AppendixA
Flow-past nose-onlychamberwith polycarbonate nose-onlytubes (CR Equipment, SA). 

### Compound Generator Glass Bubbler (Crown Glass Co., Inc.). 

### Flowmeter Dwyer®, sizes 0-0.24, 0-1, 0-4, 0-10 and 0-20 Lpm (Dwyer® Instruments), calibrated prestudy with

a Sierra Instruments Top Trak Mass Flowmeter, Modei822-13-0VI-PVI-VI. 

### Pressure Gauges Norgreen backpressure gauge, P/N 9892K23. Dwyer® Magnehelic® gauge, Model N/A. U.S. Gauge backpressure gauge, P/N 12672-1. 

### Regulators Norgreen, P/N 9892KO and 9892K23. Union Carbide, P/N SG380030. 

### Metering Valve Nupro® Co., Model SS-4L Series. 

### Tubing Clear plastic size 1/4",1/2", 1" (Norton). Teflon® size 1/8", 1/4". Stainless steel size 1/2". Stainless steel "T" tube, 

### W' AirAnalyzer MIRAN® 1A Ambient Air Analyzer (Wilks) with a Cole Parmer Strip Chart Recorder, Model 201,

and a Micronta® LCD Benchtop Digital Multimeter No. 22-195. Balston® MicrofibreTM Disposable Filter Units were attached in-line. 

### Particle Sizer TSI Aerodynamic Particle Sizer, Model 330000, and a DELL computer, Model 486P/25, equipped

with an Epson LQ-500 Dot matrix printer, Model P78PA. 

### Thermometer and Humidity Gauge Springfield and Sunbeam Temperature and Humidity Gauges, calibrated prestudywith a VWR

Digital Hygrometer and Thermometer. 

### Balances AND EP12KA. AND FX 6000. Mettler PE11.

### Huntingdon Life Sciences 02-5449

MIRAN® Calibration Methodologyfor 2-Bromo-3,3,3-Trifluoropropene 

### Page 141 Final Report Appendix 8
Settings: The instrument settings for the unit are summarized below: Wavelength, microns 3.42 Pathlength, dial setting 14.00 Slit width, mm 1 Range,absorbance 1 Response,seconds 1 Gain High Chart speed, em/min 1 Chart volts 1 Calibrations: The MIRAN® was turned on and allowed to warm up for approximately 10 minutes. The cell was flushed with room air for approximately one minute. The loop was closed, the unit was zeroed and the calibration series was performed as shown below. The resultant data were plotted to obtain a calibration curve. Each observer used a separate syringe for calibration.

Injection Calculated Absorbance Volume Concentration1**O~erator** 

### 1**O~erator** 

### 2 Average (til) (ppm) (volts) (volts) (volts) Group 1 510 20,000 0.433 0.474 0.454 640 25,120 0.553 0.571 0.562 760 29,830 0.634 0.661 0.648 Group 4 100 3,925 0.1292 0.1221 0.1257 130 5,102 0.1386 0.1390 0.1388 160 6,280 0.1658 0.1686 0.1672
1

### Calculated Cone. (ppm)= Volume**(~L)** 

### x Density**(mg/~L)** 

### x (1000**~g/mg)** 

### x (22.4**~U~mole)** 

### x (295K/273K} MW (pg/Jlmole) x 5.64L 

### where: 5.64L =volume of MIRAN® closed-loop Density (mg/JIL) = 1.60 MW (tig/Jimole) = 174.95

### Huntingdon Life Sciences 

## 02-5449

MIRAN® Calibration Page 

## 142 Final Report Appendix B Calibration Checks: A one-point calibration check of the MIRAN®was performed prior to each exposure. The parameters are shown below: Injection Volume 

## (pl) Group 1 

## 640 Group 4 

## 130 Calculated Concentration (ppm) 

## 25,120 5,102 Expected Acceptable Absorbance Absorbance Reading Range

(volts) (volts)


## 0.562 0.478- 0.646
0.1388 0.1180-0.1596 The absorbance was recorded after each injection. The absorbance was considered satisfactory if it was within 

## 15% of the original calibration series. If the absorbance value fell outside the 

## 15% range, the injection was rechecked as follows. The volume for the value that was out of range was reinjected twice. The closer pair of the three injections were averaged and the results were compared to the original curve. If the average of the pair was within the 

## 15% range, the original was accepted. If the value of the average was outside the 

## 15% range, the Study Director decided if a new graph was to be prepared.

### Huntingdon Life Sciences 02-5449

MIRAN® Calibration
Calibration CuNe for 2-Bromo-3,3,3-Trifluoropropene Group 1 Page 143 Final Report Appendix 

## B**31000~--------------------------------------~**



## ,.... 30000 29000 28000 

# a. 27000 c. 

### ';;" 26000 0 

# 'i 25000



# ... 

# - § 24000 (.) 

# 823000 22000 21000 3 2 

### y=65107x

-64586x 

### +60360x R2 

### =0.9666



# •**19000+-------+-------4-------~-------+-------4** 

### 0.430 0.480 0.530 0.580 0.630 0.680 Absorbance (Volts)

### Huntingdon Life Sciences 02-5449 Page 144 Final Report
MIRAN® Calibration Appendix B 

# I
Calibration Curve for 2-Bromo-3,3,3-Trifluoropropene Group 4**6500~------------------------------------~**


### 6000

,......., 

# a. 5500 

### c. "'-" c 0 

# 'i 5000



### .... 

# - c Q) (..) 

## § 4500 

## u
4000 • y 

### =-6142817.5944i 

### + 1933968.2043l-114025.3737x R2 

### =0.9636**3500+-----------~-------------r----------~** 

### 0.1200 0.1400 0.1600 0.1800 Absorbance (Volts)

### Huntingdon Life Sciences 02-5449

MIRAN® Calibration Methodologyfor E-1-Bromo-3,3,3-Trifluoropropene 

### Page 145 Final Report Appendix B
Settings: The instrument settings for the unit are summarized below: Wavelength, microns 3.44 Pathlength, dial setting 8.17 Slit width, mm 1 Range,absorbance 1 Response,seconds 1 Gain High Chart speed, em/min 1 Chart volts 1 Calibrations: The MIRAN® was turned on and allowed to warm up for approximately 10 minutes. The cell was flushed with room air for approximately one minute. The loop was closed, the unit was zeroed and the calibration series was performed as shown below. The resultant data were plotted to obtain a calibration curve. Each observer used a separate syringe for calibration.

Injection Volume (/JL) Group 2 490 620 740 Group 5

1100 1250 1400 Calculated Concentration1 

### (ppm) 19,830 25,100 29,950 44,524 50,595 56,666
1

### Calculated Cone. (ppm)= 

### OQerator 1 (volts)
0.586 0.691 0.765
0.662 0.726 0.770 Absorbance OQerator 2 (volts)
0.605 0.710 0.785
0.667 0.719 0.766 Average (volts)
0.596 0.701 0.775
0.665 0.723 0.768

Volume (yl) x Density (mg/yl) x (1000 yg/mg) x (22.4yUymole) x (295K/273K) MW (.ug/,umole) x 5.64L 

### where: 5.64L =volume of MIRAN® closed-loop Density (mg/pL) = 1.65 MW (/Jg/pmole) = 174.95(**·~** .. \:· .·· 

### Huntingdon Life Sciences 02-5449



### MIRAN® Calibration Page 146 

### Final Report Appendix B Calibration Checks: A one-point calibration check of the MIRAN®was performed prior to each exposure. The parameters are shown below: Expected Acceptable Injection Calculated Absorbance Absorbance Volume Concentration Reading Range 

## {til) (ppm) (volts) (volts) Group 2 620 25,100 0.701 0.596- 0.806 

### Group 5

1250 50,595 0.723 0.615- 0.831 

### The absorbance was recorded after each injection. The absorbance was considered satisfactory if it was within 15% 

### of the original calibration series. If the absorbance value fell outside the 15% 

### range, the injection was rechecked as follows. The volume for the value that was out of range was reinjected twice. The closer pair of the three injections were averaged and the results were compared to the original curve. If the average of the pair was within the 15% 

### range, the original was accepted. If the value of the average was within the 15% 

### range, the original was accepted. If the value of the average was outside the 15% 

### range, the Study Director decided if a new graph was to be prepared.

### Huntingdon Life Sciences 02-5449

MIRAN® Calibration Page 147 Final Report Appendix B
Calibration Curve for E-1-Bromo-3,3,3-Trifluoropropene Group 2**31000~---------------------------------------,**



### ,...., 30000 29000 28000 

# a. 27000 

### c. "';; 26000 0 

# 'i 25000



## .... 

# -**~** 24000 (.) c 0 

### 23000 

### u 22000 21000 3 2 y

# = 47108x

- 36268x 

### +38259x R2 

### =0.9813

20000**19000+-------+-------~-------r-------+------~** 

### 0.550 0.600 0.650 0.700 0.750 0.800 Absorbance (Volts)

### ( Huntingdon Life Sciences 02-5449

MlRAN®·calibration Page 148 Final Report Appendix B
Calibration Curve for E-1-Bromo-3,3,3-Trifluoropropene Group 5

60000,--------------------------------------, 59000 58000 57000 56000 

# E' 55ooo 0. 

### 54000 

# a 53ooo 

# 5 52000 

# 'i 51000 

# -E 50000**~** 

### 49000 

# 5 48000 (.) 47000 46000 45000 44000 3 2 

### y =287208x

-346602x 

### + 170531x R2 

### =0.9958

43000**42000+-------+-------r-------r-------~----~** 

### 0.550 0.600 0.650 0.700 0.750 0.800 Absorbanee (Volts)

### Huntingdon Life Sciences 02-5449

MIRAN® Calibration Page 149 Final Report Appendix B Methodologyfor 1-Bromo-2- Trifluoromethyl-3,3,3-Trifluoropropene 

### Settings: The instrument settings for the unit are summarized below: Wavelength, microns Pathlength, dial setting Slit width, mm Range, absorbance Response, seconds Gain Chart speed, em/min Chart volts 3.42 12.86 

## 1 1 1 

### High 1 1 

### Calibrations: The MIRAN® was turned on and allowed to warm up for approximately 10 minutes. The cell was flushed with room air for approximately one minute. The loop was closed, the unit was zeroed and the calibration series was performed as shown below. The resultant data were plotted to obtain a calibration cuNe. Each obseNer used a separate syringe for calibration.

Injection Calculated Absorbance Volume Concentration1**O~erator** 

### 1**O~erator** 

### 2 Average (pl) (ppm) (volts) (volts) (volts) Group 3 620 19,820 0.581 0.583 0.582 780 24,940 0.706 0.685 0.696 940 30,060 0.796 0.782 0.789
1

### Calculated Cone. (ppm)= Volume (yl) x Density (mg/yl) x (1000 yg/mg) x (22.4 yUymole) 

### x (295K/273K) MW (pg/,umole) x 5.64L 

### where: 5.64L =volume of MIRAN® closed-loop Density (mg/,ul) = 1.81 MW (pg/,umole) = 242.95

### Huntingdon Life Sciences 02-5449

MIRAN® Calibration Page 150 Final Report Appendix 

## 8 Calibration Checks: A one-point calibration check of the MIRAN®was performed prior to the exposure. The parameters are shown below: Expected Acceptable Injection Calculated Absorbance Absorbance Volume Concentration Reading Range 

### {til) (ppm) (volts) (volts) Group 3 780 24,940 0.696 0.592 - 0.800 The absorbance was recorded after each injection. The absorbance was considered satisfactory if it was within 15% of the original calibration series. If the absorbance value fell outside the 15% range, the injection was rechecked as follows. The volume for the value that was out of range was reinjected twice. The closer pair of the three injections were averaged and the results were compared to the original curve. If the average of the pair was within the 15% range, the original was accepted. If the value of the average was outside the 15% range, the Study Director decided if a new graph was to be prepared.

### Huntingdon Life Sciences 02-5449

MIRAN® Calibration Page 151 Final Report Appendix B
Calibration Curve for 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene Group 3**31000~------------------------------------~**



# - 30000 29000 28000 

# a. 27000 

### c.**~** 

### 26000 0 

# 'i 25000



# ... 

# -**~** 

### 24000 (.) 

# 823000 22000 21000 3 2 y 

### =26543x

- 17422x 

### +35223x R2 

### =0.9916

20000**19000+----+----+----r----+----+----+----+--~** 

### 0.430 0.480 0.530 0.580 0.630 0.680 0.730 0.780 0.830 Absorbance (Volts)

### Appendix C



# PROTOCOL 2-Bromo-3,3,3-Trifluoropropene, 1-Bromo-3,3,3-Trifluoropropeneand Page 152



### 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene
ANACUTE (4-HOUR) INHALATIONTOXICITYSTUDY INTHERAT VIA NOSE-ONLYEXPOSURE

HLSStudyNo.: ProtocolNo.: Date: 02-5449 Final 10July2002

### ·PROTOCOLSIGNATURES

### IPREFACE (ConfidentialInformation- to bedistributed on aneed-to-knowbasis)

StudyTitle: 2-Bromo-3,3,3-Trifluoropropene, 1-Bromo-3,3,3-Trifluoropropeneand 

### Page 153

1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene: AnAcute (4-Hour)InhalationToxicityStudyinthe

### Rat viaNose-OnlyExposure 

### HLS StudyNo.: 02-5449 This is theFinalProtocol. It

### hasbeenreviewed and approvedby:

Gary
.Ho an, 

### .A., DABT StudyDirect r HuntingdonLife Sciences MettlersRoad EastMillstone, NJ 08875-2360 PhoneNo.: 1-732-873-2550x2920 FaxNo.: 1-732-873-3992 Email: hoffmang@princeton.huntingdon.com

# B~- SponsorRepresentative

. AmericanPacificCorporation

3770HowardHughesParkway Suite300 

### LasVegas,NV 89109 PhoneNo.: 1-702-699-4131 FaxNo.: 1-702-735-4876 

### Email: bcolton@apfc.com 

# !3**~** 

# 2002.. Date

### Page 154 

### TABLE OFCONTENTS 

### 1.. INTRODUCTION...............................-......................................................................1 2. STUDYPERSONNEL
...........................................................................................l 

### 3. PROPOSED STUDYDATES...............................................................................l 4.
. EXPERIMENTALDESIGN
.................................................................................2 4.1. 

### JUSTIFICATIONFORROUTE, DURATIONANDFREQUENCY
....................2 4.2. JUSTIFICATIONFORTESTANIMAL SELECTION
.........................................

### .3 4.3. JUSTIFICATIONFORNUMBER OFANIMALS
................................................

### .3 4.4. JUSTIFICATIONFOREXPOSURELEVELSELECTION
.................................

### .3 5. TEST SUBSTANCES
............................................................................................3 5.1. TEST SUBSTANCES:
............................................................................................3 5.2. IDENTIFICATION OFTEST SUBSTANCES
.......................................................3 

### 5.3. ARCHIVAL SAMPLES
..........................................................................................

### 3 5.4. ADMINISTRATION OFTESTSUBSTANCES
.....:..............................................4 

### 5.5. EXPOSURE CONCENTRATIONDETERMINATION
........................................4 

### 5.6. PARTICLE SIZEDISTRIBUTIONANALYSIS:
...................................................4 

### 5.7. CHAMBERENVIRONMENT:
..............................................................................5 5.8. SUMMARY OF CHAMBERACTIVITY:
.............................................................5 5.9. FREQUENCYAND DURATION OFADMINISTRATION
.................................5 5.10. UNUSEDTEST SUBSTANCES
..........................................................................5 

### 6. TESTANIMALS
.....................................................................................................5 6.1. SPECIES
..................................................................................................................5 6.2. SUPPLIER
...............................................................................................................6 6.3. ANIMALREQUIREMENTS/SPECIFICATIONS
.................................................6 6.4. ACCLIMATIONPERIOD
.......................................;..............................................6 6.5. ANIMALCAREANDIIUSBANDRY
...................................................................6 

### 7. IN-LIFE EVALUATIONS......................................................................................9 7.1. CLINICAL OBSERVATIONS
................................................................................9 7.2. BODYWEIGHTS
.................................................................................................10 8. POSTMORTEMEV ALUATIONS
....................................................................lO 

### 8.1. MACROSCOPICPATHOLOGY
..........................................................................

### lO 8.2. METHOD OFEUTHANASIA
..............................................................................10 8.3. TISSUEPRESERVATION
...................................................................................10 8.4. ORGANWEIGHTS
..............................................................................................10 8.5. MICROSCOPICPATHOLOGYEVALUATIONS
..............................................11 

### 9. ARCHIVING OFRECORDSAND SPECIMENS
...........................................ll

### Page 155 

### 10. STATISTICALANALYSIS
...............................................................................12

. 11. REPORTING
.......................................................................................................12 

### 11.1. STATUS REPORTS
...........................................................................................12 11.2. FINALREPORT
.................................................................................................12 12. REGULATORYREFERENCES
.......................................................................13 

### 12.1. TESTWG GUIDELWES
....................................................................................13 12.2. GOOD LABORATORYPRACTICES
...............................................................13 12.3. ANIMALWELFAREACT COMPLIANCE
.....................................................13 12.4. INSTITUTIONALANIMAL CARE AND USE COMMITTEE (IACUC)
.......14 13. QUALITYASSURANCE MONITORING
.......................................................14 

### 14. ALTERATIONIN STUDYDESIGN................................................................

### 14

### Huntingdon Life Sciences StudyNo. 02-5449 

### 1. INTRODUCTION HLS StudyNo.



## 2. Protocol StudyTitle

TestingFacility

Purpose



### STUDYPERSONNEL StudyDirector Alternate Contact Page 156 

### Page 1 

### FinalProtocol
02-5449 Final 2-Bromo-3,3,3-Trifluoropropene, 1-Bromo-3,3,3-Trifluoropropene and 1-Bromo-2-Trifluoromethyl-3,3,3- Trifluoropropene: AnAcute (4-Hour) InhalationToxicityStudyintheRatvia Nose-OnlyExposure HuntingdonLife Sciences Mettlers Road P.O. Box 2360 EastMillstone,NJ 08875-2360 This study is designed to assess the potential and comparative acute inhalation toxicity of 3 test substances when administered for 4 hours via nose-only exposure. GaryM. Hoffman, B.A.,DABT Carol S. Auletta, M.B.A.,DABTx2960 Additional personnel will be documented in the study file and presented in the final report. 

### 3. PROPOSED STUDYDATES StudyInitiation Receipt ofTestAnimals FirstDayofTreatment Last DayofTreatment Necropsy- Termination Submission ofAudited DraftReport Experimental TerminationDate StudyCompletion DateStudyDirector signsprotocol September2002 September2002 (experimental start date) October2002 October2002 December2002 January2003 (dateoflastdatacollection) Date final report is signed by Study Director

### HuntingdonLife Sciences StudyNo. 02-5449 

### 4. EXPERIMENTALDESIGN Page 157 

### Page2 Final Protocol
Initially, one group per test substance (consisting of five per sex per group of Sprague-Dawley rats) will be exposed to an atmosphere containing the test substance for four hours at a measured concentration ofapproximately 2.5% which is equivalent to 25,000 ppm (parts per million of test substance in air) or at a maximum attainable concentration, whicheveris lower. These animals will then be heldfor a 14-daypost-exposure observationperiod. Ifsigns ofapparentlyreversible toxicity still persist, they will be held for one additional 7-day observation period. At the end ofthe observation period or upon spontaneous death, a macroscopic necropsy examination, measurement ofselected organ weights and a microscopic examinationofthelungswillbeperformed onall animals. If

### any compound-relatedmortalityoccursinthe initial group(s), additional testing to estimatethe medianlethal concentrationmaybeperformed (Sponsorconsulted). At leastone additional group consisting offive ofthe more sensitive sex as determined bythe initialtest group ofSprague-Dawleyrats each will be exposed to atmosphere containing the test substance for four hours. Ifthe more sensitive sex cannot be determined, thenfivepersex willbeexposedfor the additional group(s). The target concentration(s) will be selected to try to produce at least two groups with partial mortality. Exposure levels for the additional group(s) will be documented in the rawdata and final report. The animals will then beheld for a 14-daypost-exposure observation period. Ifsigns ofapparently reversible toxicity still persist, they will beheld for one additional 7-day observation period. At the end ofthe observation period or upon spontaneous death, a macroscopic necropsy examination, measurement ofselected organweights and amicroscopic examination ofthe lungs willbeperformedon all animals. Estimates ofthemedian lethal concentration, with 95% confidence limits, will be calculated where appropriate. A control exposure group is consideredunnecessary unless a vehicle (other thanwater) is used for test substance administration. Where adequate information is available to demonstrate that animals ofthe sex tested are markedlymore sensitive, testing in animals ofthe othersexisnotrequired. 

### 4.1. JUSTIFICATiONFORROUTE,DURATIONAND FREQUENCY The inhalationroute is one ofthe potential routes ofhuman exposure to this test substance and is the route as perthe regulatoryrequirements of the OECD and EPA as indicated in 

### Section 12.1. The duration of the study and frequency ofexposures are as perthe regulatoryrequirements of the OECD andEPA as indicated in Section 12.1.1/ 

### Page 158 

### HuntingdonLife Sciences Page 3 StudyNo. 02-5449 Final Protocol 4.2. JUSTIFICATIONFORTESTANIMAL SELECTION Therat is arodent animal model commonly utilized in toxicity testing as per the regulatory requirements ofthe OECD and EPA as indicated in Section 12.1. ill 

### addition, a historical database is available for comparative evaluation. 4.3. JUSTIFICATIONFORNUMBEROFANIMALS Thenumber ofanimals in the protocol is considered to be the minimum necessary for scientific and statistical reasons in order to evaluate the data with sufficient confidence levels as per the regulatory requirements ofthe OECD andEPA as indicatedin Section 12.1. 4.4. JUSTIFICATIONFOREXPOSURELEVEL SELECTION The exposure levels are as specifiedbythe Sponsorbased on prior testing ofthese or similarchemicals. 5. TESTSUBSTANCES 5.1. 

### TESTSUBSTANCES:

. 2-Bromo-3,3,3-Trifluoropropene,

1-Bromo-3,3,3-Trifluoropropene and 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene TestSubstances Category: industrial gases Description, lot number, storage, expiration date (if available) and handling procedures, as well as other pertinent information will be documentedinthe studydata. 5.2. IDENTIFICATION OFTESTSUBSTANCES Unless otherwise noted, the identity, strength, purity, composition, stability and method ofsynthesis, fabrication and/or derivation of each batch ofthetest substances willbe documentedbythe Sponsorbeforeits useinthe study. This documentationwillbemaintainedbythe Sponsor. 5.3. ARCHlY AL SAMPLES An 

### archival sample from each lot oftest substance will NOT be taken and storedinthe Archives ofthe TestingFacility.

### HuntingdonLife Sciences StudyNo. 02-5449 5.4. ADMINISTRATION OFTESTSUBSTANCES Page 159 

### Page4 FinalProtocol The test substances will be administered by nose-only inhalation exposure. Thetest substanceswillbe administered as avapor (depending on thephysicalproperties ofthe test substance) inthebreathing air ofthe animals. The test atmospheres will be generated by an appropriate procedure determined during pre-study trials. The trials will be performed to evaluate the optimal set of conditions and equipment to generate stable atmospheres at the target exposure level(s). The method willbedescribed intheraw data ofthe studyand in thereport. · The flow-past nose-only exposure chambers will be operated at a minimum flow rate of8litersperminute. The final airflow willbe setto provide at least one air change in 5.0minutes (12 air changes/hour) and a T99 

### equilibrium time ofat most 23 minutes. The T99 

### equilibrium time will be added to the 4 hours; i.e., the atmosphere will be generated for 4 hours and T99 

### minutes. This chamber size and airflow rate is considered adequate to maintain the oxygen level at least 19%. At the end ofthe exposure, all animals will remain in the chamber for a minimum of30 minutes. Duringthis time the chamberwill be operated at approximately the same flowrateusingclean air only. 5.5. EXPOSURE CONCENTRATIONDETERMINATION A nominal exposure concentration will be calculated ifpossible. The flow of air through the chamber will be monitored using appropriate calibrated equipment. The test substance consumed during the exposure will be divided by the total volume ofair passing through the chamber (volumetric flow rate times total exposure time) to give the nominal concentration. During each exposure, measurements ofairborne concentrations oftest substance will be performed each hour using an infrared (IR) spectrophotometric samplingprocedure. Ifmore than the normal amount oftrial time is required because oftest substance generation or monitoring problems (40 technician hours), the Sponsorwillbeconsultedpriorto additionaltrials (additionalcost). 5.6. PARTICLE SIZEDISTRIBUTIONANALYSIS: During each exposure, particle size determinations willbe performed each hour using a cascade impactor orother appropriate device, to characterize the aerodynamicparticle sizedistribution ofany aerosolpresent.

### HuntingdonLife Sciences StudyNo. 02-5449 

### 5.7. CHAMBERENVIRONMENT: Paqe 160 ¥age5 FinalProtocol Temperature, humidity and airflowratewillberecorded every 30minutes during exposure. Chamber temperature and relative humidity will be maintained, to the extent possible, between 20 to 24

# oc and 30 to 70%, respectively. 

### 5.8. SUMMARY OFCHAMBERACTIVITY: Theminimumfrequencyofchamberactivityis summarizedbelow: Activity MeasuredTestSubstance Concentration Particle Size Temperature RelativeHumidity AirflowRate NominalTestSubstanceConcentration Loading/UnloadingVerification Frequency/Exposure 4X 

### lX 9X 9X 9X 

### IX lX


### 5.9. FREQUENCYAND DURATION OFADMINISTRATION Thetest substanceswillbe administered for4hoursfor 1 day. 

### 5.10. UNUSED TESTSUBSTANCES The unused portion of the test substances as well as any erilpty test substance containers will be returned to the Sponsor following completion ofthe in-life phase ofthe study. 

### In the event the Sponsor wishes the TestingFacilityto arrange for disposal, a cost for this service willbeprovided. 

### 6. TESTANIMALS 6.1. SPECIES Albino Rats (Outbred)Va:f/Plus® Sprague-Dawley- derived (CD®) Crl: CD (SD) IGS BR

### Page 161 

### Page 6 HuntingdonLife Sciences StudyNo. 02-5449 FinalProtocol 

### 6.2. SUPPLIER CharlesRiverLaboratories Documentation ofthe specific breedingfacilitywillbe maintained inthe studyfile. 

### 6.3. ANIMALREQUIREMENTS/SPECIFICATIONS 6.3.1. NUMBER OFANIMALS ON STUDY 5per sexpertest substance forthe initial groups and 5persexper test substance or 5 ofone sex per test substance, as determined, for the subsequent groups with a minimum of 1 group and a maximum of6 groups willbeused. Should additional groups be required, they will be added following consultation with the Sponsor. 

### 6.3.2. AGE Young adults (approximately 7-11 weeks old at receipt and between 8-12 weeks old at exposureinitiation). 

### 6.3.3. WEIGHT Males: Approximately200-360 grams atinitiation Females: Approximately 180-260 grams atinitiation Individual weight should not exceed ± 20% ofthe mean weight for each sex. Animals outside ofthese ranges maybe used at the discretion ofthe StudyDirector. Note: Femaleswillbenulliparous andnonpregnant. 

### 6.4. ACCLIMATIONPERIOD Approximately 1 week; all animals will be checked for viability twice daily. Prior to assignment to study, all animals will be examined to ascertain suitabilityfor study. 

### 6.5. ANIMAL CAREANDHUSBANDRY 6.5.1. FACILITIES MANAGEMENT/ANIMALHUSBANDRY Currently acceptablepractices ofgood animal husbandrywill be followed, e.g., Guidefor the Care and Use ofLaboratory Animals; National Academy Press, 1996. Huntingdon Life Sciences Inc. is fully accredited by the Association for

### Huntingdon LifeSciences StudyNo. 02-5449 Page 162 

### Page7 FinalProtocol Assessment and Accreditation of Laboratory Animal Care International (AAALAC). 6.5.2. VETERINARY CARE Animals will be monitored by the technical staff for any conditions requiring possible veterinary care. If any such conditions are identified, a staffveterinarian will benotified for an examination and evaluation. Animals will be treated as outlined in the Animal Welfare Act Compliance section ofthis protocol. 6.5.3. ENVIRONMENTAL CONDITIONS Light/DarkCycle 

### Twelvehourlight/dark cycleprovidedvia automatictimer. Temperature Temperature will be monitored in accordance with Testing Facility SOPs to ensure that the desired range of 18 to 26°C is maintained to themaximum extentpossible
.

.Humidity Humiditywill bemonitored in accordance with Testing Facility SOPs to ensure that the desired range of 30 to 70% IS 

### maintainedto themaximum extentpossible. 6.5.4. HOUSING Group housed (2-6/cage) during acclimation, then individually

### in suspended stainless steelwiremesh cages during study. 6.5.5. FEED Certified Rodent Diet, No. 5002; (Meal) (PMI Nutrition International, St. Louis, MO) adlibitum. 

### 6.5.6. WATER Elizabethtown Water Company, Westfield, NJ; ad libitum, 

### via automatedwatering system.

### HuntingdonLife Sciences StudyNo. 02-5449 6.5.7. FEEDANALYSIS Page 163 

### PageS FinalProtocol Analytical certification of batches of feed provided by the manufacturer will be maintained on file by the manufacturer. There are no known contaminants in the feed which are expectedto interferewiththe objectives ofthis study. 6.5.8. WATERANALYSIS 

### Water analyses are conducted by Elizabethtown Water Company to assure that water meets standards specified under the EPA Federal SafeDrinkingWater ActRegulations (40 CFR Part 141). Water analysis, provided by the supplier, will be maintained on file at the TestingFacility. In 

### addition, chemical and microbiological analyses are conducted biannually on water samples collected from representative rooms in this facility. Results are maintained on file. There are no known ·contaminantswhich are expected to interferewiththe objectives ofthis study. 6.5.9. ANIMALASSIGNMENT 

### More animals than required for the study will bepurchased and acclimated. Animals will·be arbitrarily placed in 

### cages upon receipt and will beplaced on study as available at time ofstudy initiation. Animals considered unsuitable for study on the basis ofpretest physical examinations and outlying body weights will be excluded. Disposition ofall animals not utilized in the study willbemaintained onfile atthe TestingFacility. 6.5.10. IDENTIFICATION 

### Each animalwill be assigned a temporaryidentificationnumber uponreceipt. After selection for study, each animal willbe eartagged with a number assigned by the Testing Facility. This numberplus the studynumber will comprise the unique animal number for each animal. Ifthe tag is lost, it will be replaced. Eachcage will beprovidedwith a cage cardwhichwillbe color coded for exposure level identification and will contain the studynumber and animal number. 6.5.11. ANIMAL HUSBANDRY/EXPOSURE Housing: 

### Individuallyintubes.

### HuntingdonLife Sciences StudyNo. 02-5449 Food: Water: 7. IN-LIFEEVALUATIONS 7.1. CLINICAL OBSERVATIONS None. None. Page 164 

### Page 9 Final Protocol

NOTE: Animals showing severe and enduring signs ofdistress and pain may need to behumanelyeuthanized as perOECD andEPAtest guidelines. 7.1.1. VIABILITY CHECKS (CAGE-SIDE) Observations for mortality and general condition will bemade at least twice daily (once in the morning and once in the afternoon). Animals in poor health or in a possible moribund condition will be identified for further monitoring and possible euthanasia. 7.1.2. PHYSICALEXAMINATIONS Day0 (Day ofExposure): Animals willbe observed individually priorto exposure, as a group at fifteen minuteintervals duringthe first hour of exposure, and hourly for the remainder of the exposure. Theywillbeobservedindividuallyuponremoval from the chainberandhourlyfor twohourspost-exposure. Days 1-14: Detailed general observations will berecorded once daily. Iftheanimals areheld for an additional one-weekrecovery period, theywillbe observedfrom Day 15 throughDay21. Examinations will include but not be limited to, evaluation of skinand fur, 

### eyes and mucous membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects, including tremors and convulsions, changes in the level ofmotor activity, gait and posture, reactivity to handling or sensory stimuli, grip strength, and stereotypies or bizarrebehavior (e.g., self- mutilation, walkingbackwards). Detailedobservationswillberecorded at eachinterval.

### HuntingdonLife Sciences StudyNo. 02-5449 

### 7.2. BODYWEIGHTS Page 165 

### Page 10 FinalProtocol Day 0 (prior to exposure), Days 7 and 14 (termination). Ifthe animals are heldfor an additional oneweekrecoveryperiod, theywill also beweighed onDay21 (Termination). 

### 8. POSTMORTEMEVALUATIONS 8.1. MACROSCOPICPATHOLOGY A complete macroscopic examination will be performed on all animals, including animals euthanized in a moribund condition or found dead; all abnormal observations will be recorded. The necropsy will include examination ofthe external surface and all orifices; the organs and tissues ofthe cranial, thoracic, abdominal and pelvic cavities and neck; and the remainder ofthe carcass. Tissues and lesions will be saved as indicated in Section 8.3. 

### 8.2. METHOD OFEUTHANASIA Exsanguinationfollowing carbon dioxideinhalation. 

### 8.3. TISSUEPRESERVATION All weighed organs as listed in Section 8.4 will be preserved in 10% neutral buffered formalin. The lungs will be infused with 10% neutral buffered formalin to ensure fixation and preserved for all animals. Additionally, if macroscopically observed pathological lesions are observed in animals which survive more than 24hours, the lesion will be taken at necropsy and preserved in 10% neutral buffered formalin. A pathologist will review the data to determine which lesions appear to be due to the test substance. Lesions which appear to be due to the test substance will be archived, or examined microscopically (additional cost), as determinedbytheSponsor 

### 8.4. ORGANWEIGHTS Organs indicatedbelow willbetaken from all survivors at the scheduled necropsies, weighed, recorded and organ/body and organ/brain weight ratios calculated. Organs will notbe weighed for animals found dead or euthanized in amoribund condition duringthe course ofthe study. Prior to weighing, all organs will be carefully dissected and properly trimmed to remove fat and other contiguous tissues in a uniform manner. Organs will be weighed as soon as possible after dissection to avoid drying. Paired organs willbeweighedtogether.

### ( 

### HuntingdonLife Sciences StudyNo. 02-5449 Page 166 

### Page 11 Final Protocol



## 9. adrenals brain kidneys lungs liver ovanes testes


### 8.5. MICROSCOPICPATHOLOGYEVALUATIONS Forall animals in all groups, thelungswillbeexaminedmicroscopically. Tissues with macroscopic lesions and target organs may be examined in all animals (additional cost, Sponsor consulted). Target organs will be designated by the Study Director, pathologist and/or Sponsor based on experimental findings. Authorizationwill be obtained from the Sponsor prior to performing additional examinations. Any abnormalities not noted during macroscopic postmortem examinations which are seen duringhistologicalprocessingwillberecorded. Additional examinations will be made only after consultation with the Sponsor and receipt of authorization from the Sponsor. Stains Standard stainswillbeused (hematoxylin and eosin). Special stains may be employed on selected tissues in making a diagnosis at the discretion ofthe StudyPathologist. Special stains maybe employed at the request ofthe Sponsor (additional cost). 

### ARCHIVING OFRECORDSAND SPECIMENS All data documenting experimental details and studyprocedures and observations willberecorded and maintained as raw data. Atthe completion ofthe study, all reports, raw data, preserved archival specimens and retained samples will be maintained in the Testing Facility's Archives for a period of 1 year after submissionofthe signed final report. The Sponsor will be contacted in order to determine the fmal disposition ofthese materials. The Sponsorisresponsiblefor all cost associatedwiththe storage ofthese materials beyond one year from the issuance ofthe final report and for any costs associated with the shipment ofthese materials to the Sponsor or to any other facilitydesignatedbytheSponsor.

### HuntingdonLife Sciences StudyNo. 02-5449 

### 10. STATISTICALANALYSIS Page 167 

### Page 12 FinalProtocol Ifappropriate, a calculation ofan estimate ofthemedian lethal concentration, with 95% confidence limits, using the method ofMaximum Likelihood Estimation1 

### or Litchfield and Wilcoxon2 

### willbeperformed for the combined sexes, the males and the females.

1

### Finney,D.J. ProbitAnalysis, 3rdEdition, CambridgeUniversityPress,London, 1971. 2

### Litchfield, J.T., Jr. andF. Wilcoxon, 1949, J.Pharma. Exp. Therap., 96:99-113. 

### 11. REPORTING 11.1. STATUS REPORTS Periodic verbal and written updates on study progress will be provided bythe StudyDirector. 

### 11.2. FINALREPORT One copy of an audited draft report will be submitted following termination of the study. After receipt and review of the Sponsor's comments, appropriate changes will be made and 2 paper copies of a signed, audited final report will beissued. (Additional copies ofreports will be provided at additional cost). The report willinclude, butnot be limited to: Compliance Statement QualityAssurance Statement Summary Introduction ExperimentalDesign Materials andMethods Discussion ofStudyResults Conclusion TablesofExposureData MortalityDatawithLC50 

### (ifapplicable) Tables ofindividual and summarydailyphysical examinations Tables ofindividualbodyweights andbodyweight changes Tableofindividualmacroscopicpostmortemfmdings (lesionswhich appearto bedue to test substancewillbenoted) Tableofindividual organweights and organ weightratios Tableofindividual microscopicpostmortemfindings (as appropriate) Listofseniorpersonnelparticipating inthe study Copyofstudyprotocol and associated amendments

### HuntingdonLife Sciences StudyNo. 02-5449 12. REGULATORYREFERENCES 12.1. TESTING GUIDELINES Page 168 

### Page 13 FinalProtocol

This studyis designedto meetorexceedtherequirements of: The Organization for Economic Cooperation and Development (OECD) Guidelines: AcuteInhalation (12 May 1981), Part403. HealthEffects Test Guidelines, Office ofPrevention, Pesticides and Toxic Substances, U.S. Environmental Protection Agency (OPPTS), August, 1998; OPPTS 870.1300, AcuteInhalationToxicity. 12.2. GOODLABORATORYPRACTICES This studywillbeconductedincompliancewith: OECD Principles ofGoodLaboratoryPractices ENV/MC/CHEM (98)17 EPA GoodLaboratoryPractices as setforth in40 CFRPart792 (TSCA) 12.3. ANIMALWELFAREACT COMPLIANCE This study will complywith all appropriate parts ofthe Animal Welfare Act Regulations: 9 CFR Parts 1 and 2 Final Rules, Federal Register, Volume 54, No. 168, August 31, 1989, pp. 36112-36163 effective October 30, 1989 and 9 CFR Part 3 Animal Welfare Standards; Final Rule, FederalRegister, Volume 56, No. 32,February 15, 1991, pp. 6426- 6505 effective March 18, 1991. The Sponsor should make particular note ofthefollowing: 1. The Sponsor's signature on this protocol documents that, for the study described, there are no generally accepted non-animal alternatives and the study does not unnecessarily duplicate previous experiments in regard to species, test substance, route of administration orduration oftreatment. 2. All procedures used in this study have been designed to avoid discomfort, distress and pain to the animals. All methods are described in this study protocol or written laboratory standard operatingprocedures. 3. Any procedures outlined in this study which cause more than momentaryor slight pain or distress to the animals will beperformed with appropriate sedatives, analgesics or anesthetics unless the withholding of these agents is justified for scientific reasons, in

### HuntingdonLife Sciences StudyNo. 02-5449 Page 169 

### Page 14 FinalProtocol

12.4. 

### writing by the Sponsor and the Study Director, in which case the procedure will continue for the minimum time necessary. Documentation ofthejustificationfor withholding treatment for pain or distress and IACUC approval ofthe procedures willbemadeprior to studyinitiation onthe IACUCProtocolReviewForm. 4. Animals experiencingmorethan momentaryorslightpain ordistress due to test substance or injury or illness may be euthanized by the Testing Facility's veterinary staff to relieve pain after consultation with the Study Director and Sponsor. However, in emergency situations, the veterinary staffis authorized to administer emergency treatment as necessary. Any subsequent treatment or euthanasia will be administered after consultation with the Study Director. The Sponsor will be advised by the Study Director of all emergency situations inas timelyamanner as possible. 5. Methods of euthanasia used during this study are in conformance with the above-referencedregulations. INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) The IACUC Protocol Review Subcommittee has reviewed this protocol and found itto beincompliancewith all appropriateregulations. 13.
.QUALITYASSURANCEMONITORING TheHuntingdon Life Sciences QualityAssurance Unit will monitor the facilities, equipment, personnel, methods, practices, records and controls used in this study to assure that they are inconformance withthis protocol, company SOPs, and the appropriate GoodLaboratoryPracticerequirements. 14. ALTERATIONIN STUDYDESIGN Alterations ofthis protocol maybe made as the studyprogresses. No changes in the protocol will bemade without the consent ofthe Sponsor. In the event that the Sponsor authorizes a protocol change verbally, such changes will behonored bytheTestingFacility andwillbefollowed byawrittenverification. Allprotocol modifications willbe signed bythe Study Director and a Sponsor representative. Any modifications potentially affecting animal welfare will also be signed by 2 members of the Institutional Animal Care and Use Committee prior to the modification's implementation.

### HuntingdonLife Sciences StudyNo. 02-5449 ProtocolAmendmentNo. 1 

### Page 170 Page 1ofl FinalProtocol


### StudyTitle: 2-Bronio-3,3,3-Trifluoropropene, 1-Bromo-3,3,3-Trifluoropropene and 1-Bromo-2-Trifluoromethyl-3,3,3-Trifluoropropene: AnAcute (4-Hour)Inhalation ToxicityStudyintheRatviaNose-OnlyExposure Changes 1. Page4, AdministrationofTest Substances: Revise:
......The flow-past nose-only exposure chambers will be operated at a minimumflow rate of6 &

### litersper**minute~**

### .... 2. Page5, SummaryofChamberActivity: Revise: Theminimumfrequencyofchamberactivityis summarizedbelow: Activity Particle Size
3. Page 10, TissuePreservation: Frequency !Exposure 4-!--X

Revise: All weighed organs as listed in Section 8.4 will be preserved in 10% neutral buffered formalin. The lungs will be infused with 10% neutral buffered formalin to ensure fixation and preserved for all animals. The testes 

### will be fixed in modified Davidson's solutionfor atleast48 hourspriortopermanentstorageinNBF
..:" Reasonsfor Changes 1. Thetotalflowratewasreducedto reducethe consumptionofthetest substance
.

.2. Errorinoriginalprotocol.

3. Omissioninoriginalprotocol. Additional CostRequired: No
. Amendment approvedby:
GaryM. Hoffin:t B.A.,D.A.B.T.

# s~ BradfordF. Colton SponsorRepresentative 

# 3/oslo3 I I 

### Date**(~** 

### . . . . 

### Huntingdon Life Sciences 02-5449 Page 171 Final Report Testing Facility Personnel Appendix D 

### TITLE/DEPARTMENT SENIOR VICE PRESIDENT,

SAFETYASSESSMENT SENIOR DIRECTOR, SAFETY

ASSESSMENT DIRECTOR, TOXICOLOGY

OPERATIONS DIRECTOR, QUALITYASSURANCE STUDY DIRECTOR PATHOLOGIST STUDY MONITOR VETERINARIAN MANAGER/SUPERVISOR

Inhalation Toxicology Histology 

### NAME/DEGREE Sylvie J. Gosselin, D.V.M., Ph.D.,

Diplomate A.C.V.P. CarolS. Auletta, M.B.A., D.A.B.T.,

R.A.C.

lan Vanterpool, F.I.A.T. Nicki S. Iacono, B.S. Gary M. Hoffman, B.A., D.A.B.T. Henry F. Bolte, D.V.M., Ph.D. Tara A. Gankiewicz, B.A. Teresa S. Kusznir, V.M.D.

Robert Faust, B.S. Janet Kusisto, B.S., H.T. (ASCP)

### Huntingdon Life Sciences 02-5449
Report Amendments There are no amendments for this report at this time. Page 172 Final Report Appendix E