## FINAL REPORT

Volume 1 of 2 (Text, Tables 1-19 and Appendix A)

STUDY TITLE

AN INHALATION PRENATAL DEVELOPMENTAL TOXICITY STUDY OF HFO-1234yf (2,3,3,3-TETRAFLUOROPROPENE) IN RABBITS

STUDY NUMBER

WIL-447022

DATA REQUIREMENT

OECD Guideline 414

OPPTS 870.3700

STUDY DIRECTOR

Tammye L. Fleeman, BS, LAT

STUDY INITIATION DATE

11 January 2008

STUDY COMPLETION DATE

14 July 2008

PERFORMING LABORATORY

WIL Research Laboratories, LLC 1407 George Road Ashland, OH 44805-8946

SPONSOR

Honeywell International Inc. P.O. Box 1139 101 Columbia Road Morristown, NJ 07962

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# COMPLIANCE STATEMENT

This study, designated WIL-447022, was conducted in compliance with the United States
Environmental Protection Agency (EPA) Good Laboratory Practice Standards (40 CFR

Part 792), 18 September 1989; the Organisation for Economic Cooperation and
Development (OECD) Principles of Good Laboratory Practice [C(97) 1 86/Final]



## , 26 November 1997; the standard operating procedures of WIL Research Laboratories,
LLC and the protocol as approved by the sponsor. A Certificate of Analysis was
provided by the sponsor (presented in Appendix 

## B); the characterization analyses were
not conducted according to Good Laboratory Practices (GLP).

The protocol was designed to be in general accordance with the United States EPA

Health Effects Test Guidelines 

## OPPTS 870.3700, Prenatal Developmental Toxicity
Study, August, 1998 and the OECD Guidelines for Testing 

## of Chemicals Guideline 414,
Prenatal Developmental Toxicity Study, 22 January 200 1.

Ta&ye 

## L. Fleeman, BS, LAT Staff Toxicologist, Developmental and Reproductive Toxicology Study Director

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# T ABLE 

# O F 

# C ONTENTS



## Volume 1 Page

Compliance Statement...............................................................................2

Table Of Contents......................................................................................3

Index Of Tables..........................................................................................6 Index Of Appendices .................................................................................8 1. Summary...................................................................................................10 1.1. Objective....................................................................................................10 1.2. Study Design..............................................................................................10

1.3. Results........................................................................................................11

1.4. Conclusions................................................................................................13

2. Introduction..............................................................................................14 2.1. General Study Information ........................................................................14 2.2. Key Study Dates ........................................................................................15

3. Study Design.............................................................................................16 4. Experimental Procedures - Materials And Methods............................17

4.1. Test Substance And Vehicle ......................................................................17

4.1.1. Test Substance Identification.....................................................................17

4.2. Exposure Methods .....................................................................................18

4.3. Test Material Generation Methods ............................................................20 4.4. Methods for Characterization of Exposure Atmospheres..........................21

4.4.1. Nominal Concentrations ............................................................................21 4.4.2. Analyzed Exposure Concentrations...........................................................21 4.4.3. Homogeneity of Vapor Test Atmospheres ................................................22

4.5. Test Substance Characterization................................................................22 4.5.1. Purity Analysis...........................................................................................22 4.5.2. Stability Analysis.......................................................................................22

4.6. Test System................................................................................................22 4.7. Animal Receipt ..........................................................................................23

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Volume 1 (continued) Page

4.8. Animal Housing (Non-Exposure Periods).................................................23 4.9. Diet, Drinking Water And Maintenance....................................................24 4.10. Environmental Conditions (Non-Exposure Periods) .................................24 4.11. Assignment Of Animals To Treatment Groups.........................................25

5. Parameters Evaluated .............................................................................26 5.1. Maternal Observations During Gestation ..................................................26

5.1.1. Clinical Observations And Survival ..........................................................26 5.1.2. Body Weights And Gravid Uterine Weights .............................................26 5.1.3. Food Consumption.....................................................................................27 5.1.4. Anatomic Pathology And Laparohysterectomy.........................................27

5.1.4.1. Unscheduled Deaths...................................................................................27 5.1.4.2. Gestation Day 29 Laparohysterectomy......................................................27 5.2. Fetal Morphological Examination .............................................................29 5.3. Statistical Analyses ....................................................................................30

5.4. Data Retention ...........................................................................................31

6. Results .......................................................................................................32 6.1. Analytical Chemistry .................................................................................32 6.2. Analyzed Exposure Concentrations...........................................................32

6.3. Maternal Clinical Observations And Survival...........................................33 6.4. Maternal Body Weights And Gravid Uterine Weights..............................34 6.5. Maternal Food Consumption .....................................................................36 6.6. Maternal Necropsy Data ............................................................................36 6.7. Gestation Day 29 Laparohysterectomy......................................................38 6.8. Fetal Morphological Data ..........................................................................38

6.8.1. External Malformations And Variations....................................................38

6.8.2. Visceral Malformations And Variations....................................................39

6.8.3. Skeletal Malformations And Variations ....................................................41 6.8.4. Summary Of External, Visceral And Skeletal Examinations ....................42

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Volume 1 (continued) Page

7. Discussion .................................................................................................44

8. Conclusions...............................................................................................46 9. Key Study Personnel And Report Submission......................................47 10. Quality Assurance Unit Statement.........................................................49 10.1. Phases Inspected ........................................................................................49 10.2. Approval ....................................................................................................51

11. References.................................................................................................52

12. Deviations From The Protocol................................................................53

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# I NDEX 

# O F 

# T ABLES 

## Note: Some table titles have been shortened due to software spacing constraints.

Volume 1 (continued) Page

1. Summary Of Maternal Survival And Pregnancy Status (Combined Phases) ...........56

2. Summary Of Clinical Findings: Total Occurrence/No. Of Animals (Phase I - Daily Examinations) ..................................................................................57

3. Summary Of Clinical Findings: Total Occurrence/No. Of Animals (Phase II - Daily Examinations) .................................................................................59

4. Summary Of Clinical Findings: Total Occurrence/No. Of Animals (Phase I - Mid-Point Of Exposure) ............................................................................61

5. Summary Of Clinical Findings: Total Occurrence/No. Of Animals (Phase II - Mid-Point Of Exposure) ...........................................................................62

6. Summary Of Clinical Findings: Total Occurrence/No. Of Animals (Phase I - 1 Hour Post-Exposure)...............................................................................63

7. Summary Of Clinical Findings: Total Occurrence/No. Of Animals (Phase II - 1 Hour Post-Exposure) .............................................................................64

8. Summary Of Body Weights During Gestation [G] (Combined Phases)...................65

9. Summary Of Body Weight Changes During Gestation [G] (Combined Phases) ........................................................................................................................ 71

10. Summary Of Gravid Uterine Weights And Net Body Weight Changes [G] (Combined Phases).....................................................................................................77

11. Summary Of Food Consumption During Gestation [G/Animal/Day] (Combined Phases).....................................................................................................78

12. Summary Of Food Consumption During Gestation [G/Kg/Day] (Combined Phases).....................................................................................................84

13. Summary Of Maternal Macroscopic Findings (Combined Phases)..........................90

14. Summary Of Fetal Data At Scheduled Necropsy (Combined Phases)......................92

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Volume 1 (continued) Page

15. Summary Of Fetal Data At Scheduled Necropsy [% Per Litter] (Combined Phases).....................................................................................................93

16. Summary Of Fetuses And Litters With Malformations [Absolute No.] (Combined Phases).....................................................................................................96

17. Summary Of Litter Proportions Of Malformations (Combined Phases)...................97

18. Summary Of Fetuses And Litters With Variations [Absolute No.] (Combined Phases)...................................................................................................101

19. Summary Of Litter Proportions Of Variations (Combined Phases)........................103

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# I NDEX 

# O F 

# A PPENDICES



## Volume 1 (continued) Page

A. Individual Animal Data............................................................................................110

A1. Individual Clinical Observations (Phase I - Daily Examinations) ..............111

A2. Individual Clinical Observations (Phase II - Daily Examinations)...................................................................118

A3. Individual Clinical Observations (Phase I - Mid-Point Of Exposure)..............................................................125

A4. Individual Clinical Observations (Phase II - Mid-Point Of Exposure).............................................................126

A5. Individual Clinical Observations (Phase II - 1 Hour Post-Exposure) .........127

A6. Individual Body Weights During Gestation [G] (Combined Phases).........128

A7. Individual Body Weight Changes During Gestation [G] (Combined Phases) ......................................................................................143

A8. Individual Gravid Uterine Weights And Net Body Weight Changes [G] (Combined Phases)................................................................................163

A9. Individual Food Consumption During Gestation [G/Animal/Day] (Combined Phases) ......................................................................................168

A10. Individual Food Consumption During Gestation [G/Kg/Day] (Combined Phases) ......................................................................................188

A11. Individual Maternal Macroscopic Findings (Combined Phases)................208

A12. Individual Fetal Data At Scheduled Necropsy (Combined Phases)............221

A13. Individual Fetal Data At Scheduled Necropsy [% Per Litter] (Combined Phases) ......................................................................................226

A14. Individual Fetal Weights [G] (Combined Phases).......................................231

A15. Individual Fetal External, Visceral And Skeletal Findings (Combined Phases) ......................................................................................236

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Volume 2 Page

B. Certificates Of Analysis (Sponsor- Or Manufacturer-Provided Data) ....................354

C. Analyses Of Test Substance Purity And Stability (WIL Research Laboratories, LLC) .........................................................................364

D. Exposure Atmosphere Generation Report (WIL Research Laboratories, LLC) .........................................................................384

E. Animal Room Environmental Conditions ...............................................................429

F. WIL Developmental Historical Control Data Version 1.1 [New Zealand White Rabbits]..................................................................................436

G. Study Protocol ..........................................................................................................448

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# 1. S UMMARY


# 1.1. O BJECTIVE 

## The objectives of the study were to determine the potential of the test article to induce
developmental toxicity after maternal exposure during the critical period of
organogenesis, to characterize maternal toxicity at the exposure levels tested and to
determine a no-observed-adverse-effect level (NOAEL) for maternal toxicity and
developmental toxicity.



# 1.2. S TUDY 

# D ESIGN 

## Five groups of time-mated female New Zealand White rabbits (12/group per phase;
approximately 5.5-6 months of age at initiation of exposure) were exposed to either clean
filtered air or vapor atmospheres of the test substance, HFO-1234yf
(2,3,3,3-tetrafluoropropene), for approximately 6 hours daily in whole-body inhalation
chambers during gestation days 6-28. Because of the limited amount of space available
in the exposure chambers, each group was divided into 2 phases, with the following
exception. The 4000 and 5500 ppm test substance concentrations were administered only
during Phase I and Phase II, respectively. Target test substance concentrations were 0,
2500, 4000, 7500 and 4000 (DuPont) parts per million (ppm) for each phase, with the
following exception. Because no toxicity was noted at 4000 ppm in Phase I, the sponsor
elected to increase the mid-exposure concentration to 5500 ppm for Phase II. In order to
determine if there were any differences in the test substance manufactured by a different
supplier, the 4000 and 5500 ppm groups were divided into 2 subgroups each, exposed to
the test substance supplied by either the sponsor or DuPont. For evaluation of the data,
the groups were combined as noted in the following table.

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Target Exposure Concentration (ppm) Group Number Test Substance Phase I Phase II Combined Phases 1 Filtered Air 0 0 0 2 HFO-1234yf 2500 (Honeywell) 2500 (Honeywell) 2500 3 HFO-1234yf 4000 (Honeywell) 5500 (Honeywell) 4000 a 

## 4 HFO-1234yf 7500 (Honeywell) 7500 (Honeywell) 5500 a 

## 5 HFO-1234yf 4000 (DuPont) 5500 (DuPont) 7500

a 

## = Data combined for test substance supplied by Honeywell and DuPont.



## Overall mean measured exposure concentrations were 2504, 3982, 7512 and 4013 ppm
for the 2500, 4000, 7500 and 4000 (DuPont) ppm groups, respectively, in Phase I and
2479, 5408, 7441 and 5479 ppm for the 2500, 5500, 7500 and 5500 (DuPont) ppm
groups, respectively, in Phase II.

All animals were observed twice daily for mortality and moribundity. Clinical
observations, body weights and food consumption were recorded at appropriate intervals.
On gestation day 29, a laparohysterectomy was performed on each surviving female. The
uteri, placentae and ovaries were examined, and the numbers of fetuses, early and late
resorptions, total implantations and corpora lutea were recorded. Gravid uterine weights
were recorded, and net body weights and net body weight changes were calculated. The
fetuses were weighed, sexed and examined for external, visceral and skeletal
malformations and developmental variations.



# 1.3. R ESULTS 

## No adverse effects were observed in fetuses or maternal animals exposed to 4000 ppm or
lower. No test substance-related developmental variations were observed at any exposure
level. Maternal toxicity was observed in animals exposed to concentrations of 5500 ppm
or higher. There were no statistically significant differences in the mean litter
proportions of malformations or developmental variations in exposed fetuses from any
exposure group when compared to concurrent control group values. A small number of
malformations occurred at a frequency above the WIL historical control data at the
maternally toxic exposure levels of 5500 ppm and higher.

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Four and 7 females in the 5500 and 7500 ppm groups, respectively, were found dead or
euthanized in extremis. Labored and/or decreased respiration and/or hypoactivity were
observed prior to death or euthanasia for 2 and 3 females in the same respective groups.
One and 3 females in the 5500 and 7500 ppm groups, respectively, aborted on gestation
day 26, 28 or 29, and 1 female in the 7500 ppm group delivered on gestation day 29. The
mortality, moribundity, abortions and premature delivery in the 5500 and 7500 ppm
groups were attributed to the test substance; no test substance-related macroscopic
findings were observed in these females. All other females survived to the scheduled

necropsy.

No test substance-related clinical findings were noted at the daily examinations or at
mid-point of or 1 hour following exposure at any concentration.

Lower mean body weight gain was noted in the 7500 ppm group during gestation
days 12-20 with corresponding occasional reductions in mean daily food consumption.
Because the most sensitive females died or were euthanized prior to the scheduled
necropsy, mean net body weight and net body weight change in this group were not
significantly different from the control group. Mean body weights in the 7500 ppm
group were similar to the control group throughout the study. A slightly lower mean
body weight gain and a mean body weight loss were observed in the 5500 ppm group
during gestation days 12-20 and 20-29, resulting in a lower mean body weight gain when
the entire exposure period (gestation days 6-29) was evaluated. A large mean net body
weight loss was observed in this group. Correspondingly lower mean food consumption
was observed in this group during gestation days 20-29. However, mean body weights
throughout the study and mean net body weight in the 5500 ppm group were similar to
the control group. Slightly lower mean body weight gains were observed in the
4000 ppm group during gestation days 12-20 and 20-29, resulting in a lower mean body
weight gain when the entire exposure period (gestation days 6-29) was evaluated.
However, because there were no test substance-related effects on mean food
consumption, mean net body weight or net body weight change, and there were no

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clinical or macroscopic findings indicative of systemic toxicity observed in this group,
the lower mean body weight gain noted in the 4000 ppm group was not considered
adverse. Mean gravid uterine weights were unaffected by exposure to the test substance

at all concentrations.

Intrauterine growth and survival were not affected by test substance exposure at any
concentration. However, test substance-related visceral malformations of the heart and/or
great vessels were observed at frequencies above the WIL historical control values in the
maternally toxic 5500 and 7500 ppm groups. These findings, which were not statistically
different from the concurrent study control group, consisted of bulbous aorta, stenotic
pulmonary arch, interventricular septal defect (absent septa), absent tricuspid valve
and/or interrupted aortic arch. No test substance-related developmental variations were
observed at any exposure level.



# 1.4. C ONCLUSIONS 

## Based on mortality, moribundity, abortions, premature delivery, lower mean body weight
gain, mean body weight loss and/or lower food consumption observed at 5500 and
7500 ppm, an exposure concentration of 4000 ppm was considered to be the
no-observed-adverse-effect level (NOAEL) for maternal toxicity. Because test
substance-related visceral malformations in the heart and/or great vessels were observed
in the 5500 and 7500 ppm groups in the presence of maternal toxicity, an exposure
concentration of 4000 ppm was considered to be the NOAEL for embryo/fetal
development when pregnant New Zealand White rabbits were exposed to HFO-1234yf
via whole-body inhalation.

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# 2. I NTRODUCTION


# 2.1. G ENERAL 

# S TUDY 

# I NFORMATION 

## This report presents the data from “An Inhalation Prenatal Developmental Toxicity Study
of HFO-1234yf (2,3,3,3-tetrafluoropropene) in Rabbits.” Due to software spacing
constraints, the study title is presented as “Inhalation Prenatal Dev Tox Study of
HFO-1234yf in Rabbits” on the report tables. Because of space limitations in the
exposure chambers, the animals in each group were divided into 2 phases. The exposures
of each group of animals were conducted separately, with the initial exposure of animals
in Phase II occurring approximately 5 weeks following the initial exposure of the animals

in Phase I. In order to determine if there were differences between the test substance
produced by Honeywell International, Inc. and that produced by E.I. DuPont, the
4000 ppm group and the 5500 ppm group were each split into 2 subgroups that were
exposed to HFO-1234yf produced by 1 manufacturer or the other. There were no
noteworthy differences between the groups exposed to the test substance produced by the
sponsor and E.I. DuPont. Statistical analyses were not conducted comparing intergroup
differences between the 2 manufacturers. For interpretation and presentation of maternal
body weight, food consumption, necropsy, laparohysterectomy and fetal morphology
data, the 4000 ppm groups (Groups 3 and 5) from Phase I were combined and the
5500 ppm groups (Groups 3 and 5) from Phase II were combined. Therefore, the
4000 and 5500 ppm groups are presented as groups 3 and 4, respectively on these data
tables. Additionally, the 7500 ppm group (Group 4 in Phases I and II) is presented as
Group 5 on the same tables.

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The following computer protocols were used for data collection during the study:

Computer Protocol Type of Data Collected

WIL-447022F......................................... Main study data (Phase I clinical observations) WIL-447022D ........................................ Main study data (Phase II clinical observations) WIL-447022C......................................... Main study data (combined maternal body weight, food consumption, necropsy, laparohysterectomy and fetal morphology data)


# 2.2. K EY 

# S TUDY 

# D ATES 1



## Date(s) Event(s)

16 January 2008...................................... Experimental starting date (first gestation day 0; Phase I) 18 January 2008...................................... Animal receipt (Phase I) 22 January 2008...................................... Experimental start date (first of Phase I test substance exposure) 22 January-14 February 2008................. Test substance administration (Phase I) 15 February 2008.................................... Last laparohysterectomy (Phase I) 19 February 2008.................................... First gestation day 0 (Phase II) 22 February 2008.................................... Animal receipt (Phase II) 25 February-19 March 2008................... Test substance administration (Phase II) 20 March 2008........................................ Last laparohysterectomy (Phase II) 9 May 2008............................................. Experimental termination/completion date (last skeletal examination)

1 

### Date ranges represent the first and last dates of evaluation.



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# 3. S TUDY 

# D ESIGN 

## Assignment of rabbits to treatment groups based on gestation day 0 body weights provided by the supplier

Receipt of time-mated rabbits on gestation days 1, 2 or 3

Maternal clinical observations recorded daily, body weights and

food consumption recorded at appropriate intervals

24 females/group (1-5) exposed to clean, filtered air or test substance for 6 hours daily via whole body inhalation from gestation days 6-28

Necropsies performed on

animals that died, were euthanized in extremis,

delivered or aborted

Laparohysterectomies performed on gestation day 29; gravid

uterine weights recorded

Fetal weights recorded; external fetal morphological examination followed by fresh dissection

Heads from all fetuses examined by a mid-coronal slice

All fetal carcasses prepared and stained for skeletal examination

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# 4. E XPERIMENTAL 

# P ROCEDURES 

# - M ATERIALS 

# A ND 

# M ETHODS


# 4.1. T EST 

# S UBSTANCE 

# A ND 

# V EHICLE


# 4.1.1. T EST 

# S UBSTANCE 

# I DENTIFICATION 

## The test substance, HFO-1234yf (2,3,3,3-tetrafluoropropene), was received from
Honeywell International Inc., Buffalo, New York (WIL log no. 7749A) and E. I. DuPont,
Wilmington, Delaware (WIL log no. 7819B), as follows:

Identification Quantity Received Physical Description Date of Receipt

HFO-1234yf Cylinder 1; Lot no. BW296A Cylinder 2; Lot no. BW305A Cylinder 3; Lot no. BW305B Cylinder 4; Lot no. BW305C Cylinder 5; Lot no. BW305D Cylinder 6; Lot no. BW305E Cylinder 7; Lot no. BW305F a 

## Cylinder 8; Lot no. BW305G a 

## Cylinder 9; Lot no. BW306A a 

## Cylinder 10; Lot no. BW306B a 

## Cylinder 11; Lot no. BW306C a 

## Cylinder 12; Lot no. BW306D a 

## Cylinder 13; Lot no. BW313A Cylinder 14; Lot no. BW313B Cylinder 15; Lot no. BW313D Cylinder 16; Lot no. BW313C CAS no. 754-12-1 [WIL log no. 7749A] 16 cylinders Total gross weight: 2189.6 kg Clear, colorless gas 14 November 2007

HFO-1234yf Cylinder no. 049918; Lot no. 049918C-110107 a 

## Cylinder no. 050064; Lot no. 050064C-102907 a 

## Cylinder no. 050432; Lot no. 050432C-102907 a 

## Cylinder no. 050483; Lot no. 050483C-102907 CAS no. 754-12-1 [WIL log no. 7819B] 4 cylinders Total gross weight: 479.9 kg Clear, colorless gas 21 December 2007

a 

## = Used on study.



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Documentation regarding the purity and stability of the test substance is on file with the
sponsor and WIL Research Laboratories, LLC. Certificates of Analysis for the test
substance were provided by the sponsor or manufacturer and are presented in
Appendix B. The purity of the test substance was > 99.9% and was confirmed by the
Analytical Chemistry Department at WIL Research Laboratories, LLC (see Section 6.1.);
the results of the purity and stability analyses are presented Appendix C. The test
substance was stored in cylinders as a gas at room temperature, and was considered stable
under these conditions. Reserve samples of the test substance (approximately 2-3 g) were
collected on 17, 18 and 30 January, 8 and 28 February and 8 and 14 March 2008, and
stored in the Archives of WIL Research Laboratories, LLC.



# 4.2. E XPOSURE 

# M ETHODS 

## Because of the limited amount of space available in the exposure chambers, animals in
each group were divided into 2 phases. The exposures of each phase were conducted
separately, with the following exception. The 4000 and 5500 ppm test substance
concentrations were administered only during Phase I and Phase II, respectively. The
initial exposure of animals in Phase II occurred approximately 5 weeks following the
initial exposure of animals in Phase I. Exposures were conducted in 5 stainless steel and
glass whole-body exposure chambers; the control group was exposed in a 2-m 3 

## (2000 L)
chamber and the test substance-exposed groups were exposed in a 1.5-m 3 

## (1500 L). One
chamber was dedicated for each group for the duration of the study. The exposure period
was approximately 6 hours per day during gestation days 6-28 for the control and test
substance-exposed groups and was defined as the time between turning the generation
system on and off, including the start equilibration time and the clearance time. The
chambers were operated under dynamic conditions at a slight negative pressure with at
least 12 air changes per hour.

All animals were housed in a normal animal colony room during non-exposure hours.
For each day of exposure, the animals were transferred from their home cages to the

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exposure chamber caging, transported to the exposure chamber room, exposed for the
requisite duration and then returned to their home cages. The cage batteries were rotated
on a daily basis through 6 battery positions for the control group chamber and 3 battery
positions for the test substance groups to help ensure similar exposure for all animals
within each group over the duration of the exposure period. Food and water were
withheld during the exposure periods. The animals were exposed to the test substance at
approximately the same time each day.

The following table presents the study group assignment:

Target Exposure Concentration (ppm) Group Number Test Substance Phase I Phase II Combined Phases Number of Females

1 Filtered Air 0 0 0 24 c 

## 2 HFO-1234yf a 

## 2500 2500 2500 24 c 

## 3 HFO-1234yf a 

## 4000 5500 4000 d 

## 24 c 

## 4 HFO-1234yf a 

## 7500 7500 5500 d 

## 24 c 

## 5 HFO-1234yf b 

## 4000 5500 7500 d 

## 24 c

a 

## = Test material manufactured by Honeywell International Inc.
b 

## = Test material manufactured by E. I. DuPont de Nemours.

c 

## = There were 12 females/group/phase.
d 

## = For the clinical observation tables, the 4000 ppm groups are designated as Groups 3 and 5 for Phase I, the 5500 ppm groups are designated as Groups 3 and 5 for Phase II and the 7500 ppm group is designated as Group 4 for both phases.

Exposure levels were provided by the sponsor representative following consultation with
the study director based on the results of a range-finding study (Fleeman, 2008; 447021).
In that study, time-mated rabbits were exposed to HFO-1234yf at target concentrations of
0, 2500, 10000 or 50000 ppm for 6 hours daily during the period of major organogenesis.
Death, moribundity, body weight losses and decreased food consumption were noted at

concentrations ≥ 10000 ppm. Microscopic evaluation of maternal animals in the
10000 ppm group revealed minimal to mild cardiomyopathy and mild renal tubular
necrosis. No test substance-related maternal findings were noted in the 2500 ppm group.
Intrauterine growth and survival were not affected by maternal exposure to HFO-1234yf

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at any concentration. Therefore, exposure levels of 2500, 4000 and 7500 ppm were
selected for this definitive prenatal developmental toxicity study in rabbits. Because no
toxicity was observed in the first exposure phase at 4000 ppm (Groups 3 and 5), the
mid-exposure level was increased to 5500 ppm for the second exposure phase.

The selected route of administration for this study was whole-body inhalation because
inhalation is a possible route of exposure to humans.



# 4.3. T EST 

# A TMOSPHERE 

# G ENERATION 

# M ETHODS 

## A gas atmosphere of the test article was generated by releasing the test article in gas form
from the original cylinders. Heat was applied to the cylinders. A regulator with pressure
gauges was used to control test article flow from the cylinders to a flow meter equipped
with a needle valve. For Chambers 2 through 4, test article was delivered from the flow
meter to a manifold system equipped with a pressure gauge to monitor manifold pressure.
From the manifold, flow meters and needle valves were used to control the test substance
delivery to each chamber. The concentrated gas from each cylinder was piped to a
mixing plenum where the concentration was reduced by mixing with chamber ventilation
air. The control group was exposed to clean, filtered air. A detailed description of the
generation method is presented in Appendix D.

Temperature, relative humidity, chamber ventilation rate and negative pressure within the
exposure chambers were monitored continuously and recorded approximately every
35 minutes. The daily mean chamber temperature ranged from 21°C to 23°C; the daily
mean chamber relative humidity ranged from 47% to 53%. The daily mean chamber
ventilation rate was 327-444 SLPM. Oxygen content within the chambers was measured
during the pre-study method development; mean oxygen content was at least 19% for all
chambers. Exposure chamber environmental conditions are summarized in Appendix D.

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# 4.4. M ETHODS 

# F OR 

# C HARACTERIZATION 

# O F 

# E XPOSURE 

# A TMOSPHERES


# 4.4.1. N OMINAL 

# C ONCENTRATIONS 

## A nominal exposure concentration was calculated daily for each chamber from the total
amount of test article used during the exposure and the total volume of air passed through
the chamber during that day’s exposure. The amount of test article used was obtained by
weighing the test article cylinders prior to and after each day’s exposure. Because
1 cylinder was used to generate into 3 chambers, a 1:1.6:3 and 1:2.2:3 ratio for Phase I
and II, respectively, (derived from the target concentrations) was used to calculate the test
article usage for Chambers 2, 3 and 4. For Chamber 5, the nominal concentration was
calculated the same as Chambers 2 through 4, but without the use of a ratio. The total
volume of air passed through each chamber was calculated from the daily average
chamber ventilation flow rate in standard liters per minute (SLPM) and the exposure
duration. . The nominal concentration of each phase was calculated as follows.

WT × MV × 10 6 

## Concentration (ppm) = GMW × CVR × DUR
Where: WT = Weight of test article used, grams MV = Molar volume at 730 mmHg and 21oC, 25.11 L/mole

10 6 

## = ppm conversion factor GMW = Test article gram molecular weight, (1) 

## 114 g/mole

CVR = Daily mean chamber ventilation rate for a given day, SLPM DUR = Duration of the daily exposure, minutes

(1) 

## = Gram Molecular Weight for Test Article Log No. 7819B was 114.06 g/mole



# 4.4.2. A NALYZED 

# E XPOSURE 

# C ONCENTRATIONS 

## Analyzed exposure concentrations were determined at approximately 35-minute intervals
using a gas chromatograph (GC). Samples were collected from the approximate
animal-breathing zone of the inhalation exposure chambers. Details of these

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concentration analyses and results are presented in Appendix D, and the results are

summarized in Section 6.2.



# 4.4.3. H OMOGENEITY 

# O F 

# V APOR 

# T EST 

# A TMOSPHERES 

## Homogeneity of exposure concentrations was evaluated during the method development
phase of the study. Four test locations and a reference location were used for these
determinations. The test locations were upper front, lower front, upper rear, and lower
rear. Samples were collected and analyzed on the GC as rapidly as possible by
alternating from the reference location to a test location. The measured concentration
was calculated as a percent difference for each position from the reference location.
Homogeneity was performed in triplicate for each test article exposure chamber. Details
of homogeneity analyses and results are presented in Appendix D, and the results are

summarized in Section 6.2.



# 4.5. T EST 

# S UBSTANCE 

# C HARACTERIZATION


# 4.5.1. P URITY 

# A NALYSIS 

## A sample of each test substance was collected from a storage cylinder prior to use for
animal exposures and were assessed for purity using GC/FID analysis of at least
duplicate injections of the undiluted sample.



# 4.5.2. S TABILITY 

# A NALYSIS 

## Test substance stability was determined using GC/FID analysis of at least duplicate
injections of the undiluted sample collected following the completion of animal

exposures.



# 4.6. T EST 

# S YSTEM 

## Time-mated female New Zealand White [Hra:(NZW):SPF] rabbits from Covance
Research Products, Kalamazoo, Michigan, were used as the test system on this study.

This species and strain of animal is recognized as appropriate for developmental toxicity
studies. WIL Research Laboratories, LLC has historical control data on the background

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incidence of fetal malformations and developmental variations in the New Zealand White
rabbit. This animal model has been proven to be susceptible to the effects of
developmental toxicants. The number of animals selected for this study was based on the
US EPA Health Effects Test Guidelines OPPTS 870.3700, Prenatal Development
Toxicity Study, August 1998 and the OECD Guidelines for Testing of Chemicals
Guideline 414, Prenatal Developmental Toxicity Study, January 2001.



# 4.7. A NIMAL 

# R ECEIPT 

## Sixty-four time-mated female New Zealand White rabbits were received in good health
from Covance Research Products, Inc., Kalamazoo, Michigan, on 18 January 2008 for
Phase I and on 22 February 2008 for Phase II. The time-mated rabbits were received on
gestation days 1, 2 or 3. The animals were approximately 5.5-6 months old upon receipt.
Each female was examined by a qualified technician on the day of receipt. Body weights
were recorded on gestation day 4 and food consumption was recorded during gestation
days 4-6. Each rabbit was uniquely identified by a color-coded plastic ear tag displaying
the animal number. The rabbits were observed twice daily for mortality and general
changes in appearance and behavior. Body weights were recorded by the supplier on
gestation day 0 under non-GLP conditions.



# 4.8. A NIMAL 

# H OUSING 

# (N ON 

# -E XPOSURE 

# P ERIODS 

# )
Upon arrival, all rabbits were housed individually in clean, stainless steel cages
suspended above ground corncob bedding (Pel-O’Cobs ® 

## ; The Andersons, Cob Products
Division, Maumee, Ohio). The bedding was changed at least twice each week. Nesting
material was not required, as the females were euthanized prior to the date of expected
parturition. Animals were maintained in accordance with the Guide for the Care and Use
of Laboratory Animals (National Research Council, 1996). The animal facilities at WIL
Research Laboratories, LLC are fully accredited by the Association for Assessment and
Accreditation of Laboratory Animal Care International (AAALAC International).

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# 4.9. D IET 

# , D RINKING 

# W ATER 

# A ND 

# M AINTENANCE 

## The basal diet used in this study, PMI Nutrition International, LLC, Certified Rabbit

LabDiet ® 

## 5322, is a certified feed with appropriate analyses performed by the
manufacturer and provided to WIL Research Laboratories, LLC. Feed lots used during
the study are documented in the study records. The feeders were changed and sanitized
once per week. Municipal water supplying the facility is regularly sampled for
contaminants according to standard operating procedures. The results of the diet and
water analyses are maintained at WIL Research Laboratories, LLC. No contaminants
were present in animal feed or water at concentrations sufficient to interfere with the
objectives of this study. The basal diet was offered in 25-g increments 3 times per day on
the day of arrival and in increased amounts over the next few days, until the animals
gradually achieved ad libitum status prior to the exposure period; basal diet was offered
ad libitum thereafter except during exposure. Beginning on 30 January 2008 (gestation
day 13 or 14), all Phase I females were supplemented with kale until euthanasia, and all
Phase II females were supplemented with kale from the onset of exposure until
euthanasia. Reverse osmosis-purified (on-site) drinking water, delivered by an automatic
watering system, was provided ad libitum during the study. Food and water were not
available during the daily exposure period.



# 4.10. E NVIRONMENTAL 

# C ONDITIONS 

# (N ON 

# -E XPOSURE 

# P ERIODS 

# )
All rabbits were housed throughout the acclimation period and during the study in an
environmentally controlled room. The room environmental controls were set to maintain
daily averages of 66 ° F ± 5 ° F (19 ° C ± 3 ° C) temperature and 50% ± 20% relative
humidity. Room temperature and relative humidity were controlled and monitored using
the Metasys ® 

## DDC Electronic Environmental control system. These data were recorded
approximately hourly and are summarized in Appendix E. Actual mean daily
temperature ranged from 65.3 ° F to 66.1 ° F (18.5 ° C to 19.0 ° C) and mean daily relative
humidity ranged from 50.0% to 58.5% during the study. Light timers were calibrated to

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provide a 12-hour light (0600 hours to 1800 hours)/12-hour dark photoperiod. Air
handling units were set to provide a minimum of 10 fresh air changes per hour.



# 4.11. A SSIGNMENT 

# O F 

# A NIMALS 

# T O 

# T REATMENT 

# G ROUPS 

## At the discretion of the study director, each animal judged to be in good health and
meeting acceptable gestation day 0 body weight requirements (2900 g to 4500 g) was
selected for use in the computerized randomization procedure. At that time, the
individual body weights and corresponding animal identification numbers were entered
into the WIL Toxicology Data Management System (WTDMS TM 

## ). A printout containing
the animal numbers, corresponding body weights and individual group assignments was
generated based on body weight stratification in a block design. The animals were then
arranged into groups according to the printout and replacement animals were arbitrarily
assigned based on body weight. Separate randomizations were conducted for Phase I and

Phase II.

The experimental design for WIL-447022 consisted of 4 test substance-exposed groups
and 1 control group, composed of 24 rabbits per group. The selected females were
approximately 5.5-6 months old at the time of mating by the supplier. Body weight
values ranged from 2892 g to 3976 g on gestation day 0.

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# 5. P ARAMETERS 

# E VALUATED


# 5.1. M ATERNAL 

# O BSERVATIONS 

# D URING 

# G ESTATION


# 5.1.1. C LINICAL 

# O BSERVATIONS 

# A ND 

# S URVIVAL 

## All rabbits were observed twice daily, once in the morning and once in the afternoon, for
moribundity and mortality. Individual detailed clinical observations were recorded from
receipt (gestation day 1, 2 or 3) through gestation day 29 (prior to exposure during the
treatment period). Animals were also observed for signs of toxicity at the mid-point of
exposure (3 hours following beginning of exposure) and approximately 1 hour following
the exposure period. The absence or presence of findings was recorded for individual
animals; however, for reporting purposes, positive findings only are presented on the

individual tables.



# 5.1.2. B ODY 

# W EIGHTS 

# A ND 

# G RAVID 

# U TERINE 

# W EIGHTS 

## Individual maternal body weights were recorded on gestation days 0 (by the supplier), 4
and 6-29 (daily). Group mean body weights were calculated for each of these days.
Mean body weight changes were calculated for each corresponding interval and also for
gestation days 6-9, 9-12, 12-20, 20-29 and 6-29. When body weights could not be
determined for an animal during a given interval (due to an unscheduled death, weighing
error, etc.), group mean values were calculated for that interval using the available data.
The time periods a given female was not weighed were designated as “NA” (Not
Applicable) on the individual report tables.

Gravid uterine weight was collected and net body weight (the gestation day 29 body
weight exclusive of the weight of the uterus and contents) and net body weight change
(the gestation day 0-29 body weight change exclusive of the weight of the uterus and
contents) were calculated and presented for each gravid female at the scheduled
laparohysterectomy.

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# 5.1.3. F OOD 

# C ONSUMPTION 

## Individual food consumption was recorded on gestation days 4-29 (daily). Food intake
was reported as g/animal/day and g/kg/day for the corresponding body weight change
intervals. When food consumption could not be determined for an animal during a given
interval (due to an unscheduled death, weighing error, food spillage, obvious erroneous
value, etc.), group mean values were calculated for that interval using the available data.
The time periods when food consumption values were unavailable for a given animal
were designated as “NA” (Not Applicable) on the individual report tables.



# 5.1.4. A NATOMIC 

# P ATHOLOGY 

# A ND 

# L APAROHYSTERECTOMY


# 5.1.4.1. U NSCHEDULED 

# D EATHS 

## A gross necropsy was performed on females that died, were euthanized in extremis,
delivered or aborted during the course of the study. Females were euthanized by an
intravenous injection of sodium pentobarbital via a marginal ear vein. Maternal tissues
with gross findings, kidneys, liver, brain, heart and lungs were retained in
10% neutral-buffered formalin for possible future histopathologic examination. The
number and location of implantation sites, corpora lutea and viable fetuses were recorded.
Recognizable fetuses (or kits delivered prior to gestation day 29) were examined
externally and preserved in 10% neutral-buffered formalin. Kits that were delivered on
gestation day 29 were examined as noted in Section 5.2. The females were then

discarded.



# 5.1.4.2. G ESTATION 

# D AY 

# 29 L APAROHYSTERECTOMY 

## The laparohysterectomies and macroscopic examinations were performed blind to
treatment group. All surviving rabbits were euthanized on gestation day 29 by an
intravenous injection of sodium pentobarbital via the marginal ear vein. The thoracic,
abdominal and pelvic cavities were opened by a ventral mid-line incision, and the
contents were examined. In all instances, the post mortem findings were correlated with
the ante mortem comments, and any abnormalities were recorded. The uterus and ovaries
were then exposed and excised. The number of corpora lutea on each ovary was

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recorded. The trimmed uterus was weighed and opened, and the number and location of
all fetuses, early and late resorptions and the total number of implantation sites were
recorded. The placentae were also examined. The individual uterine distribution of
implantation sites was documented using the following procedure. All implantation sites,
including resorptions, were numbered in consecutive order beginning with the left distal
to the left proximal uterine horn, noting the position of the cervix, and continuing from
the right proximal to the right distal uterine horn.

Uteri with no macroscopic evidence of implantation were opened and subsequently
placed in 10% ammonium sulfide solution for detection of early implantation loss
(Salewski, 1964).

Maternal tissues with gross findings, kidneys, liver, brain, heart and lungs were preserved
in 10% neutral-buffered formalin for possible future histopathologic examination.
Representative sections of corresponding organs for the gross lesions from a sufficient
number of control animals were retained for comparison. The carcass of each female was

then discarded.

Intrauterine data were summarized using 2 methods of calculation. An example of each

method of calculation follows:

1. Group Mean Litter Basis:

No. Dead Fetuses, Resorptions (Early/Late)/Group Postimplantation Loss/Litter = No. Gravid Females/Group



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2. Proportional Litter Basis:

Σ Postimplantation Loss/Litter (%) Summation Per Group (%) = No. Litters/Group

Where: No. Dead Fetuses, Resorptions (Early/Late)/Litter Postimplantation Loss/Litter (%) = No. Implantation Sites/Litter x 100



# 5.2. F ETAL 

# M ORPHOLOGICAL 

# E XAMINATION 

## Fetal examinations were performed blind to treatment group. Each viable fetus was
examined externally, individually weighed, euthanized by hypothermia followed by an
intrathoracic injection of sodium pentobarbital (if necessary) and tagged for
identification. Findings for kits delivered on gestation day 29 are included on the fetal
tables. Fetal tags contained the WIL study number, the female number and the fetus
number. The detailed external examination of each fetus included, but was not limited to,
an examination of the eyes, palate and external orifices, and each finding was recorded.
Crown-rump measurements, degrees of autolysis and gross examinations, if possible,
were recorded for late resorptions, and the tissues were discarded.

Each viable fetus was subjected to a visceral examination using a modification of the
Stuckhardt and Poppe fresh dissection technique to include the heart and major blood
vessels (Stuckhardt and Poppe, 1984). The sex of each fetus was determined by internal
examination. Fetal kidneys were examined and graded for renal papillae development
(Woo and Hoar, 1972). Heads from all fetuses were examined by a mid-coronal slice.
All carcasses were eviscerated and fixed in 100% ethyl alcohol.

Following fixation in alcohol, each fetus was macerated in potassium hydroxide and
stained with Alizarin Red S (Dawson, 1926). External, visceral and skeletal findings
were recorded as developmental variations (alterations in anatomic structure that are
considered to have no significant biological effect on animal health or body conformity

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and/or occur at high incidence, representing slight deviations from normal) or
malformations (those structural anomalies that alter general body conformity, disrupt or
interfere with normal body function, or may be incompatible with life).

The fetal developmental findings were summarized by: 1) presenting the incidence of a
given finding both as the number of fetuses and the number of litters available for
examination in the group; and 2) considering the litter as the basic unit for comparison
and calculating the number of affected fetuses in a litter on a proportional basis as

follows:

Summation per Group (%) = Viable Fetuses Affected/Litter (%) No. Litters/Group

Where:
Viable Fetuses Affected/Litter (%) = No. Viable Fetuses Affected/Litter No. Viable Fetuses/Litter x 100



# 5.3. S TATISTICAL 

# A NALYSES 

## All statistical tests were performed using appropriate computing devices or programs.
Analyses were conducted using two-tailed tests (except as noted otherwise) for minimum
significance levels of 1% and 5%, comparing each test substance-exposed group to the
control group. Each mean was presented with the standard deviation (S.D.), standard
error (S.E.) and the number of animals (N) used to calculate the mean. In addition,
percent difference from control was presented for body weights. Data obtained from
nongravid animals were excluded from statistical analyses. Due to the different rounding
conventions inherent in the types of software used, the means, standard deviations and
standard errors on the summary and individual tables may differ by ±1 in the last
significant figure. Where applicable, the litter was used as the experimental unit.

Mean maternal body weights (absolute and net), body weight changes (absolute and net)
and food consumption, gravid uterine weights, numbers of corpora lutea, implantation
sites and viable fetuses and fetal body weights (separately by sex and combined) were

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subjected to a parametric one-way analysis of variance (ANOVA) (Snedecor and
Cochran, 1980) to determine intergroup differences. If the ANOVA revealed statistically
significant (p<0.05) intergroup variance, Dunnett's test (Dunnett, 1964) was used to
compare the test substance-exposed groups to the control group. Mean litter pr oportions
(percent per litter) of prenatal data (viable and nonviable fetuses, early and late resorptions,
total resorptions, pre- and postimplantation loss and fetal sex distribution), total fetal
malformations and developmental variations (external, visceral, skeletal and combined)
and each particular external, visceral and skeletal malformation or variation were
subjected to the Kruskal-Wallis nonparametric ANOVA test (Kruskal and Wallis, 1952) to
determine intergroup differences. If the ANOVA revealed statistically significant
(p<0.05) intergroup variance, Dunn’s test (Dunn, 1964) was used to compare the test
substance-exposed groups to the control group.



# 5.4. D ATA 

# R ETENTION 

## The sponsor has title to all documentation records, raw data, specimens or other work
product generated during the performance of the study. All work product generated by
WIL Research Laboratories, LLC, including raw paper data and specimens, are retained
in the Archives at WIL Research Laboratories, LLC, as specified in the study protocol.

Reserve samples of the test article, pertinent electronic storage media and the original
final report are retained in the Archives at WIL Research Laboratories, LLC in
compliance with regulatory requirements.

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# 6. R ESULTS


# 6.1. A NALYTICAL 

# C HEMISTRY 

## Analytical Chemistry Report: Appendix C

The purity of all samples of the test substance was 100% prior to and following the
completion of use, indicating stability throughout the exposure period.



# 6.2. A NALYZED 

# E XPOSURE 

# C ONCENTRATIONS 

## Exposure Atmosphere Generation Report: Appendix D

The following table summarizes the overall mean nominal concentrations for each phase

of the test substance chamber.

Text Table 1. Mean Nominal Chamber Concentrations

Phase I
Chamber 2 Chamber 3 Chamber 4 Chamber 5 Mean Concentration (ppm): 2328 3745 7055 3635
Standard Deviation: 62.0 89.5 186.5 177.7

N: 24 24 24 24

Phase II
Chamber 2 Chamber 3 Chamber 4 Chamber 5 Mean Concentration (ppm): 2363 5203 7078 5407
Standard Deviation: 78.6 162.2 202.4 214.0

N: 24 24 24 24



## The following tables summarize the overall mean analyzed concentrations of each phase

and each chamber.

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Text Table 2. Mean Analyzed Chamber Concentrations

Phase I
Chamber 2 Chamber 3 Chamber 4 Chamber 5 Mean Concentration (ppm): 2504 3982 7512 4013
Standard Deviation: 19.4 56.5 38.1 38.4

N: 24 24 24 24
Phase II
Chamber 2 Chamber 3 Chamber 4 Chamber 5 Mean Concentration (ppm): 2479 5408 7441 5479
Standard Deviation: 69.8 194.3 189.1 233.2

N: 24 24 24 24



# 6.3. M ATERNAL 

# C LINICAL 

# O BSERVATIONS 

# A ND 

# S URVIVAL 

## Summary Data: Tables 1 through 7
Individual Data: Appendix A - Tables A1, A2, A3, A4, A5

Test substance-related effects on survival were noted in the 5500 and 7500 ppm groups as
summarized in the following table.

Text Table 3. Animals That Were Found Dead, Euthanized In Extremis, Aborted or Delivered (Gestation Day) 0 ppm 2500 ppm 4000 ppm 5500 ppm 7500 ppm Found Dead 0 0 0 3 (13, 14, 27) 6 (12, 14, 18, 20) Euthanized In Extremis 0 0 0 1 (28) 1 (16)
Aborted 0 0 0 1 (28) 3 (26, 29) Delivered 0 0 0 0 1 (29)



## On the day of or prior to death or euthanasia, 1 and 3 females in the 5500 and 7500 ppm
groups, respectively, had labored and/or decreased respiration, 2 females in the 5500 ppm
group were hypoactive, 1 female in the 7500 ppm group had clear material around the
nose and 1 female in the 7500 ppm group had red material on the left hindlimb. In
addition, the female in the 5500 ppm group had red material on the urogenital area on the
day prior to euthanasia and 1 occurrence of labored respiration several days prior to
death. Aside from a single occurrence of decreased defecation in 1 female in the

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7500 ppm group, no other noteworthy clinical findings were observed during the
exposure period for females that were found dead or euthanized in extremis. The only
noteworthy finding for the aborted females was 1 or 11 occurrences of decreased
defecation noted in 3 females in the 7500 ppm group. The abortions and premature
delivery were attributed to the test substance. All other females survived to the scheduled

necropsy.

No test substance-related clinical findings were noted females that survived to the
scheduled necropsy at the daily examinations, during mid-point of exposure or 1 hour
following exposure at any exposure concentration. Findings noted in the test
substance-treated groups, including hair loss on various body surfaces, occurred
infrequently or, at similar frequencies in the control group, and/or were observed prior to
the exposure period or in a manner that was not dose-related.



# 6.4. M ATERNAL 

# B ODY 

# W EIGHTS 

# A ND 

# G RAVID 

# U TERINE 

# W EIGHTS 

## Summary Data: Tables 8, 9, 10
Individual Data: Appendix A - Tables A6, A7, A8

Mean maternal body weight gain in the 7500 ppm group was similar to the control group
during gestation days 6-9 and 9-12. A significantly (p<0.01) lower mean body weight
gain was observed in this group during gestation days 12-20 relative to the control group.
Mean body weight gain in the 7500 ppm group was similar to the control group during
gestation days 20-29, presumably because the most sensitive animals had died. As a
result of the lower mean body weight gain during gestation days 12-20, mean body
weight gain in the 7500 ppm group was slightly lower (not statistically significant) when
the entire exposure period (gestation days 6-29) was evaluated. The decrements in mean
body weight gain in this group were not of sufficient magnitude to result in lower mean
body weights. Mean net body weight and gravid uterine weight in this group were
similar to the control group.

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Mean body weight gains in the 5500 ppm group were similar to the control group during
gestation days 6-9 and 9-12. A slightly lower mean body weight gain was observed in
this group during gestation days 12-20 (significant, p<0.05, during gestation days 12-13
only), and a significant (p<0.01) mean body weight loss was noted during gestation
days 20-29. The decrements in mean body weight gain in the 5500 ppm group resulted in
a significantly (p<0.01) lower mean body weight gain when the entire exposure period
(gestation days 6-29) was evaluated. A significant (p<0.01) mean net body weight loss
(174.8 g) was also observed in this group when compared to the control group. Although
there was no apparent exposure-related trend, the effects on mean body weights during
the last week of exposure and mean net body weight loss were considered test
substance-related because the most sensitive population in the 7500 ppm group had been
eliminated by this point. However, the mean body weight loss and lower mean body
weight gain in the 5500 ppm group were not of sufficient magnitude to result in lower
mean body weights or a lower mean net body weight. Mean gravid uterine weight in this
group was similar to the control group value.

Mean body weight gain in the 4000 ppm group was similar to the control group during
gestation days 6-9 and 9-12. Slightly (not statistically significant) lower mean body
weight gains were noted in this group during gestation days 12-20 and 20-29, resulting in
a significantly lower (p<0.05) mean body weight gain when the entire exposure period
(gestation days 6-29) was evaluated. Although the slight reduction in mean body weight
gain in the 4000 ppm group was considered test substance-related, mean body weights in
this group were similar to the control group throughout the exposure period, mean net
body weight was similar to the control group value, and only a slight (not statistically
significant) mean net body weight loss was noted. Therefore, the slightly lower mean
body weight gain in the 4000 ppm group was not considered adverse.

Mean body weights, body weight gains, net body weight, net body weight gain and
gravid uterine weight in the 2500 ppm group were unaffected by exposure to the test

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substance. Differences from the control group were slight and not statistically
significant.



# 6.5. M ATERNAL 

# F OOD 

# C ONSUMPTION 

## Summary Data: Tables 11, 12
Individual Data: Appendix A - Tables A9, A10

Mean food consumption, evaluated as g/animal/day and g/kg/day, in 7500 ppm group
was generally similar to the control group throughout the study. However, significantly
(p<0.05 or p<0.01) lower mean food consumption was observed in this group relative to
the control group during several daily intervals (gestation days 13-14 [g/kg/day only],
18-19, 22-23 and 23-24).

Mean food consumption in the 5500 ppm group was similar to the control group during
gestation days 6-9, 9-12 and 12-20, with the following exception. Significantly (p<0.05
or p<0.01) lower mean food consumption was noted compared to the control group
during gestation days 18-19. During gestation days 20-29, food consumption in the
5500 ppm group was significantly (p<0.01) lower compared to the control group; the
lower food consumption corresponded to a mean body weight loss noted during this same
period.

Mean food consumption in the 2500 and 4000 ppm groups was similar to that in the
control group throughout the exposure period. No statistically significant differences

were noted.



# 6.6. M ATERNAL 

# N ECROPSY 

# D ATA 

## Summary Data: Table 13
Individual Data: Appendix A - Table A11

Four and 7 females in the 5500 and 7500 ppm groups, respectively, were found dead or
euthanized in extremis during the study. Dark red areas or dark red discoloration in the
lungs were noted in 3 and 2 females in these respective groups, and 1 female each in the

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5500 and 7500 ppm groups had dark red areas in the thymus gland. In addition to these
findings, 1 female in the 5500 ppm group had green contents in the uterus and 1 female in
the 7500 ppm group had dark red areas in the spleen. Another female in the 7500 ppm
group had brown discoloration in the lungs, red fluid contents and white material in the
thoracic cavity, a small lobe of the liver and dark red areas in the kidneys. The lung
findings in these females were not considered test substance-related because microscopic
evaluation of lungs in the range-finding study (Fleeman, 2008; WIL-447021) did not
reveal any test substance-related findings. All of the females that were found dead or
euthanized in extremis were gravid with normally developing implantations or fetuses in
utero. In addition, 1 female in the 5500 ppm group had a late resorption, and 1 female in
the 7500 ppm had an early resorption in utero.

One and 4 females in the 5500 and 7500 ppm groups, respectively, aborted or delivered
during the study. The female in the 5500 ppm group aborted 2 viable and 5 dead fetuses
with no apparent malformations and 1 viable and 2 dead fetuses that were partially
cannibalized; 2 viable fetuses were noted in utero. This female also had dark red areas in
the lungs. Three females in the 7500 ppm group aborted late resorptions or 1 dead fetus;
2 late resorptions in the same litter had open eyelids. The female that aborted 1 dead
fetus also had 9 viable fetuses in utero. A swollen spleen and mottled liver were
observed for another of the females in this group that aborted. One female in the
7500 ppm group delivered on gestation day 29 and had dark red areas in the lungs. Other
macroscopic findings (accessory spleen, small gallbladder or cystic oviducts) noted in
females that were found dead, euthanized in extremis, aborted or delivered are common
in this species and strain. All other females survived to the scheduled necropsy.

At the scheduled necropsy on gestation day 29, no test substance-related internal findings
were observed at any exposure level. Macroscopic findings observed in the test
substance-treated groups occurred infrequently, at similar frequencies in the control
group and/or in a manner that was not dose-related.

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# 6.7. G ESTATION 

# D AY 

# 29 L APAROHYSTERECTOMY 

## Summary Data: Tables 14, 15
Individual Data: Appendix A - Tables A12, A13, A14
Historical Control Data: Appendix F

Intrauterine growth and survival were unaffected by test substance administration at
exposure concentrations of 2500, 4000, 5500 and 7500 ppm. Parameters evaluated
included postimplantation loss, live litter size, mean fetal body weights and fetal sex
ratios. No statistically significant differences from the concurrent control group were
noted, and values were within the ranges of the WIL historical control data for definitive
studies. Mean numbers of corpora lutea and implantation sites and the mean litter
proportions of preimplantation loss were similar across all groups.



# 6.8. F ETAL 

# M ORPHOLOGICAL 

# D ATA 

## Summary Data: Tables 16, 17, 18, 19
Individual Data: Appendix A - Table A15
Historical Control Data: Appendix F

The numbers of fetuses (litters) available for morphological evaluation were 206(24),
191(23), 206(24), 153(18) and 132(14) in the control, 2500, 4000, 5500 and 7500 ppm
groups, respectively. Malformations were observed in 6(4), 5(4), 2(1), 8(5) and 5(4)
fetuses (litters) in these same respective dosage groups.



# 6.8.1. E XTERNAL 

# M ALFORMATIONS 

# A ND 

# V ARIATIONS 

## External malformations were observed in 1(1), 2(1) and 1(1) fetuses (litters) in control,
2500 and 7500 ppm groups, respectively. Fetus no. 53771-01 in the 7500 ppm group had
carpal flexure (bilateral) and hyperflexion of the hindpaw (bilateral); no skeletal origin
was apparent for these malformations. Fetus nos. 53745-03 and 53745-10 in the
2500 ppm group had microphthalmia (unilateral). Skeletally, the orbit was smaller than
normal for fetus no. 53745-10; however, there was no apparent skeletal origin for
microphthalmia in the other fetus. These findings were not considered test

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substance-related because they occurred infrequently, not in an exposure-related manner,
the mean litter proportions were not statistically significantly different from the
concurrent control group and/or the values were within the ranges of the WIL historical
control data. In the control group, fetus no. 54153-08 had a short tail that consisted of
only 12 caudal vertebrae present and misshapen and fused caudal vertebrae.

No external developmental variations were noted at any exposure level. Four fetuses in
1 litter in the 2500 ppm group had white areas in the skin (dorsal neck or entire external
surface). This finding was not classified as a malformation or developmental variation
and was not included in any tabulation.



# 6.8.2. V ISCERAL 

# M ALFORMATIONS 

# A ND 

# V ARIATIONS 

## Soft tissue malformations were observed in 2(2), 0(0), 2(1), 5(4) and 3(2) fetuses (litters)
in the control, 2500, 4000, 5500 and 7500 ppm groups, respectively. In the 7500 ppm
group, fetus nos. 54108-08, 54108-10 and 54135-08 had a bulbous aorta (ascending
and/or arch), stenotic pulmonary trunk and an absent interventricular septum; fetus
nos. 54108-08 and 54135-08 also had an absent tricuspid valve. Fetus no. 54145-01 in
the 5500 ppm group also had a bulbous aorta (ascending and arch), a stenotic pulmonary
trunk and an absent interventricular septum. Fetus no. 54127-05 in the same group had
an interrupted aortic arch (the right and left subclavian and carotid arteries arose from the
ascending aorta, with no brachiocephalic trunk). The mean litter proportions of these
findings were not statistically significant compared to the concurrent control group;
however, the values for bulbous aorta (0.8% and 2.4% per litter) and stenotic pulmonary
trunk (0.8% and 2.4% per litter) in the 5500 and 7500 ppm groups, respectively,
exceeded the maximum mean values in the WIL historical control data (0.5% per litter
for both findings). Absent tricuspid valve and interrupted aortic arch have not been
observed in the WIL historical control data. Based on the mean litter proportion and the
similarity of the multiple findings (cardiovascular), the heart and great vessel anomalies
in the 5500 and 7500 ppm groups were attributed to the test substance. Fetus
no. 54170-01 in the 5500 ppm group had a diaphragmatic hernia (a portion of the liver

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protruded into the thoracic cavity through an opening in the diaphragm). Lobular
agenesis of the lungs (absent right accessory lobe) was noted in 1(1), 2(1) and
2(1) fetuses (litters) in the control, 4000 and 5500 ppm groups, respectively. These
malformations were not considered test substance-related because there was no exposureresponse relationship and/or the finding was observed similarly in the control group. A
malpositioned kidney (located more posterior than normal) was observed in fetus
no. 53735-02 in the control group. No other visceral malformations were noted.

Soft tissue developmental variations noted in all groups, including the control group,
consisted of retrocaval ureter, extra papillary muscle in the heart, major blood vessel
variations (the left carotid artery arose from the brachiocephalic trunk or retroesophageal
right subclavian artery) and accessory spleen. Other visceral developmental variations
occurred infrequently, similarly in the control group and/or not in an exposure-related
manner. No relationship to the test substance was evident.

Several visceral findings were not classified as either a malformation or developmental
variation and were not included in any tabulation. These findings are presented in the
following table.

Text Table 4. Visceral Findings Not Classified As Malformations Or Developmental Variations
Number of Fetuses Affected Finding 0 ppm 2500 ppm 4000 ppm 5500 ppm 7500 ppm Renal papilla not fully developed (Woo and Hoar grade 1) 1 1 --- Cyst(s) 1 a 

### 1 b 

### - 2 c



### - Thymus gland - dark red areas or dark red discoloration - 3 - - - Distended stomach - 1 - - - Thoracic cavity - dark red contents 1 1 - - - Thoracic cavity - fluid contents or fluid-filled - 3 - 1 d 

### 1 d 

### Abdominal cavity - fluid contents or fluid-filled - 4 - 2 d 

### 1 d


### - = Not observed.

a 

### = On gallbladder.
b 

### = On diaphragm.

c 

### = On oviduct(s).
d 

### = One fetus with heart and great vessel malformations.



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Other findings were not attributed to the test substance because they occurred
infrequently, were noted similarly in the control group or did not occur in an exposurerelated manner.



# 6.8.3. S KELETAL 

# M ALFORMATIONS 

# A ND 

# V ARIATIONS 

## Skeletal malformations were observed in 3(2), 4(4), 0(0), 3(2) and 1(1) fetuses (litters) in
the control, 2500, 4000, 5500 and 7500 ppm groups, respectively. Vertebral anomalies
with or without associated rib anomalies were noted in 1(1), 2(2), 0(0), 2(1) and 1(1)
fetuses (litters) in the same respective groups. For 1 fetus in each in the 2500, 5500 and
7500 ppm groups, this finding consisted of an extra arch, rib and/or half of centrum,
forked and/or fused ribs (5500 and 7500 ppm groups), malpositioned arches and halves of
centra (2500 and 5500 ppm groups) and costal cartilage from the extra rib associated with
the sternum (2500 and 7500 ppm groups) resulting in malpositioning of subsequent costal
cartilages (2500 ppm group). The fetus in the 7500 ppm group also had a costal cartilage
anomaly consisting of costal cartilages that fused, then bifurcated prior to associating
with the sternum normally. One fetus each in the control and 5500 ppm group had
vertebral anomalies that consisted of an absent half of a centrum and malpositioned
arches and halves of centra; the 5500 ppm group fetus also had a malproportioned arch.
One fetus in the 2500 ppm group had a vertebral anomaly consisting of a
malproportioned centrum attached to an adjacent centrum, malpositioned arches and
halves of centra and fused ribs. Also in the 2500 ppm group, 1 fetus had a vertebral
centra anomaly consisting of centra or halves of centra that were absent, attached to an
adjacent centrum or malpositioned and another fetus had a severely malaligned sternebra
resulting in fused sternebrae. Two (2) and 1(1) fetuses (litters) in the control and
5500 ppm groups, respectively, had rib anomalies consisting of bifurcated and/or fused
ribs and/or extra rib, costal cartilage from extra rib or anterior fork of bifurcated ribs that
associated with the sternum and/or malpositioned costal cartilage. Because skeletal
malformations occurred similarly in the control group, there was no exposure-response
relationship, the mean litter proportions were not statistically significantly different from

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the concurrent control group and/or the values were within the ranges of the WIL
historical control data, the malformations observed in the test substance-exposed groups
were considered spontaneous.

Skeletal developmental variations observed in all groups, including the control group,

consisted of 13 th 

## rudimentary rib(s), 13 th 

## full rib(s), sternebra(e) nos. 5 and/or 6
unossified, bent hyoid arch(es) and 27 presacral vertebrae. Other skeletal developmental
variations occurred similarly in the control group, were not observed in an
exposure-related manner, the mean litter proportions were not statistically significantly
different from the concurrent control group and/or the values were within the range of the
WIL historical control data. No relationship to the test substance was evident.



# 6.8.4. S UMMARY 

# O F 

# E XTERNAL 

# , V ISCERAL 

# A ND 

# S KELETAL 

# E XAMINATIONS 

## The numbers of fetuses (litters) available for morphological evaluation were 206(24),
191(23), 206(24), 153(18) and 132(14) in the control, 2500, 4000, 5500 and 7500 ppm
groups, respectively. Malformations were observed in 6(4), 5(4), 2(1), 8(5) and 5(4)
fetuses (litters) in these same respective dosage groups. When the total malformations
and developmental variations were evaluated on a proportional basis, no statistically
significant differences from the concurrent control group were noted. However, heart
and great vessel malformations (bulbous aorta, stenotic pulmonary trunk, interventricular
septal defects [absent septa], absent tricuspid valve and/or interrupted aortic arch) were
noted in 2(2) and 3(2) fetuses (litters) in the 5500 and 7500 ppm groups, respectively.
The mean litter proportions for these findings exceeded the maximum mean values in the
WIL historical control data for those findings that have been observed in control fetuses.
Because of this and the similarity of the findings, the malformations in the cardiovascular
system of the 5500 and 7500 ppm group fetuses were considered exposure-related. Other
fetal malformations and developmental variations, when observed in the test
substance-treated groups, occurred infrequently or at a frequency similar to that in the

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control group, did not occur in a dose-related manner and/or the values were within the
WIL historical control data ranges, and were therefore not attributed to the test substance.

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# 7. D ISCUSSION 

## The objectives of the study were to determine the potential of the test article to induce
developmental toxicity after maternal exposure during the critical period of
organogenesis, to characterize maternal toxicity at the exposure levels tested and to
determine a no-observed-adverse-effect level (NOAEL) for maternal toxicity and
developmental toxicity. The study was conducted in 2 phases due to the spatial
limitations of the exposure chambers.

Heart and great vessel malformations (bulbous aorta, stenotic pulmonary trunk,
interventricular septal defects [absent septa], absent tricuspid valve and/or interrupted
aortic arch) were noted in 2 and 3 fetuses in the 5500 and 7500 ppm groups, respectively.
The mean litter proportions for these findings exceeded the maximum mean value in the
WIL historical control data for those findings that have been observed in the historical
control data. Because of the increase compared to historical control and the similarity of
the findings, the malformations in the cardiovascular system of fetuses in the 5500 and
7500 ppm group were considered test substance-related. The malformations in these
groups were noted in the presence of maternal toxicity. No test substance-related effects
on intrauterine growth and survival were noted at any exposure level.

Four and 7 females in the 5500 and 7500 ppm groups, respectively, were found dead or
euthanized in extremis during the study. Exposure-related clinical findings, including
labored and/or decreased respiration and/or hypoactivity, were observed in 2 and
3 females in the 5500 and 7500 ppm groups, respectively, prior to death or euthanasia.
One and 3 females in the 5500 and 7500 ppm groups, respectively, aborted, and 1 female
in the 7500 ppm group delivered on gestation day 29. The mortalities, moribundity,
abortions and premature delivery in these groups were attributed to the test substance.

Lower (statistically significant) mean body weight gain was noted in the 7500 ppm group
during gestation days 12-20, with corresponding occasional reductions in mean daily
food consumption. Because the most sensitive females died or were euthanized prior to

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the scheduled necropsy, mean net body weight and net body weight change were not
significantly different from the control group. A slightly lower mean body weight gain
and a mean body weight loss were observed in the 5500 ppm group during gestation
days 12-20 and 20-29, resulting in a lower mean body weight gain when the entire
exposure period (gestation days 6-29) was evaluated and a mean net body weight loss;
the majority of the differences were statistically significant. Correspondingly lower mean
food consumption was observed in this group during gestation days 20-29 (statistically
significant). Slightly (not statistically significant) lower mean body weight gains were
observed in the 4000 ppm group during gestation days 12-20 and 20-29, resulting in a
lower mean body weight gain (statistically significant) when the entire exposure period
(gestation days 6-29) was evaluated. However, there were no test substance-related
effects on mean food consumption, mean net body weight or net body weight change in
this group. Therefore, the lower mean body weight gain noted in the 4000 ppm group

was not considered adverse.

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# 8. C ONCLUSIONS 

## Based on mortality, moribundity, abortions, premature delivery, lower mean body weight
gain, mean body weight loss and/or lower food consumption observed at 5500 and
7500 ppm, an exposure concentration of 4000 ppm was considered to be the
no-observed-adverse-effect level (NOAEL) for maternal toxicity. Because test
substance-related visceral malformations in the heart and/or great vessels were observed
in the 5500 and 7500 ppm groups in the presence of maternal toxicity, an exposure
concentration of 4000 ppm was considered to be the NOAEL for embryo/fetal
development when pregnant New Zealand White rabbits were exposed to HFO-1234yf
via whole-body inhalation.

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# 9. 

# KEY STUDY PERSONNEL AND REPORT SUBMISSION
Report Submitted By: 

# 2- 

# XAd

Tammbe L. Fleeman, 

## BS, LAT Staff Toxicologist, Developmental and Reproductive Toxicology Study Director

Report Prepared 

## By:

I 

# (lecLrzd---

Ke& J. Clevidence, 

## BS, LATG ,Senior Study Analyst

I" I/ 

## Ken L. Vargo, 

## MS Study Analyst

Director, Inhalati'on Toxicology



## \ 

# A&
XaXD. Nemec, 

## BS, DABT Director, Developmental and

Reproductive Toxicology 

# GAL %+v=+

Donald G. Stump, PhD, DABT Associate Director, Developmental and Repro duc t iv~Toxi~~~o gy

2



## gvelyn Tanchevski, BS Group Supervisor, Study Analysis and Reports 

# w
Date

Date

Date

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# K EY 

# S TUDY 

# P ERSONNEL 

# A ND 

# R EPORT 

# S UBMISSION 

# ( CONTINUED 

# )
Study Personnel:

Sally A. Keets, AS Senior Operations Manager, Vivarium Carol A. Kopp, BS, LAT Manager, Gross Pathology and Developmental Toxicology Laboratory Theresa M. Rafeld Group Manager, Formulations Laboratory Andrew J. Smith, BS Group Manager, Inhalation Toxicology Daniel W. Sved, PhD Director, Metabolism and Analytical Chemistry Bennett J. Varsho, MPH, DABT Operations Manager, Developmental and Reproductive Toxicology and the Formulations Laboratory Robert A. Wally, BS, RAC Manager, Reporting and Regulatory Technical Services

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# 10. Q UALITY 

# A SSURANCE 

# U NIT 

# S TATEMENT


# 10.1. P HASES 

# I NSPECTED

Date(s) of Inspection(s) Phase Inspected Date(s) Findings Reported to Study Director Date(s) Findings Reported to Management Auditor(s)

22-Jan-2008 Test Article Exposure 22-Jan-2008 28-Feb-2008 S.Power

14-Feb-2008 Laparohysterectomy and Fetal Examinations 14-Feb-2008 26-Mar-2008 J.Tooman

25-Feb-2008 Test Article Exposure 25-Feb-2008 26-Mar-2008 S.Power

11-Mar-2008 Gestational Body Weights/Food Weights 12-Mar-2008 24-Apr-2008 P.Weaver / A.Lowell

11-Mar-2008 Animal Care/Equipment 12-Mar-2008 24-Apr-2008 P.Weaver / A.Lowell

12-May-2008 Study Records (I-2,3) 14-May-2008 23-Jun-2008 D.Little

12-May-2008, 13-May-2008 Study Records (I-4) 13-May-2008 23-Jun-2008 D.Little

12-May-2008, 14-May-2008 Study Records (I-1) 14-May-2008 23-Jun-2008 D.Little

13-May-2008 Study Records (N-3) 13-May-2008 23-Jun-2008 D.Little

13-May-2008 Study Records (N-4) 13-May-2008 23-Jun-2008 D.Little

13-May-2008 Study Records (N-2) 13-May-2008 23-Jun-2008 D.Little

20-May-2008, 21-May-2008 Study Records (Ex-1) 23-May-2008 23-Jun-2008 S.Power

21-May-2008, 23-May-2008 Study Records (Ex-2) 23-May-2008 23-Jun-2008 S.Power

23-May-2008 Study Records (Ex-3, Ex-4, Ex-6) 23-May-2008 23-Jun-2008 S.Power

23-May-2008 Study Records (Ex-5) 23-May-2008 23-Jun-2008 S.Power

03-Jun-2008, 04-Jun-2008 Draft Report (Excluding Appendices C & D) 04-Jun-2008 14-Jul-2008 D.Little

05-Jun-2008 Study Records (A-1 and A-2) 05-Jun-2008 14-Jul-2008 N.Daniels



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Date(s) of Inspection(s) Phase Inspected Date(s) Findings Reported to Study Director Date(s) Findings Reported to Management Auditor(s)

10-Jun-2008 Draft Report (Analytical Chemistry Appendix) 10-Jun-2008 14-Jul-2008 N.Daniels

11-Jun-2008 Draft Report (Inhalation Appendix) 12-Jun-2008 14-Jul-2008 S.Power



## This study was inspected in accordance with the U.S. EPA Good Laboratory Practice
Standards (40 CFR Part 792), the OECD Principles of Good Laboratory Practice, the
standard operating procedures of WIL Research Laboratories, LLC and the sponsor's
protocol and protocol amendments with the following exceptions. The data located in
Appendix B (Certificates of Analysis) were the responsibility of the sponsor or
manufacturer. The procedures performed by Covance Research Products, Inc. were not
subject to Quality Assurance Unit inspection. Quality Assurance findings, derived from
the inspections during the conduct of the study and from the inspections of the raw data
and draft report, are documented and have been reported to the study director. A status
report is submitted to management monthly.

This report accurately reflects the data generated during the study. The methods and
procedures used in the study were those specified in the protocol, its amendments and the
standard operating procedures of WIL Research Laboratories, LLC.

The raw data, the retention samples and the final report will be stored in the Archives at
WIL Research Laboratories, LLC or another location specified by the sponsor.

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# 10.2. APPROVAL

This study was inspected according to the criteria discussed in Section 10.1.

Report Audited 

## By:



# -

Compliance Specialist

QA Consultant

Steven P. Power, Associate Compliance Specialist

Report Released 

## By:

LA LmAI I 

## eather L. Jobson,%S, RQAP-GLP HFO-1234yf



# I43LI 

# zw'b

Date

Manager, Quality Assurance

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# 11. R EFERENCES



## Dawson, A.B. A note on the staining of the skeleton of cleared specimens with Alizarin Red S. Stain Technology 1926

, 1 , 123-124.

Dunn, O.J. Multiple comparisons using rank sums. Technometrics 1964

, 6(3)

, 241-252.

Dunnett, C.W. New tables for multiple comparisons with a control. Biometrics 1964

, 20 , 482-491.

Fleeman, T.L. An Inhalation Range-Finding Prenatal Developmental Toxicity Study of HFO-1234yf (2,3,3,3-tetrafluoropropene) in Rabbits (Study No. WIL-447021). WIL Research Laboratories, LLC, Ashland, OH, 2008.

Kruskal, W.H.; Wallis, W.A. Use of ranks in one-criterion variance analysis. Journal of the American Statistical Association 1952

, 47 , 583-621.

National Research Council. Guide for the Care and Use of Laboratory Animals

, Institute of Laboratory Animal Resources, Commission on Life Sciences; National Academy Press: Washington, DC, 1996

. Salewski, E. Färbemethode zum makroskopischen Nachweis von Implantationsstellen am Uterus der Ratte. [Staining method for a macroscopic test for implantation sites in the uterus of the rat]. Naunyn - Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie 1964

, 247 , 367.

Snedecor, G.W.; Cochran, W.G. One Way Classifications; Analysis of Variance. In Statistical Methods , 7th ed.; The Iowa State University Press: Ames, IA, 1980 ; pp 215-237.

Stuckhardt, J.L.; Poppe, S.M. Fresh visceral examination of rat and rabbit fetuses used in teratogenicity testing. Teratogenesis, Carcinogenesis and Mutagenesis 1984

, 4 , 181-188.

Woo, D.C.; Hoar, R.M. Apparent hydronephrosis as a normal aspect of renal development in late gestation of rats: the effect of methyl salicylate. Teratology 1972

, 6 , 191-196.

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# 12. D EVIATIONS 

# F ROM 

# T HE 

# P ROTOCOL 

## This study was conducted in accordance with the protocol and protocol amendments,
except for the following.

• Protocol Section 5.5 states that the body weight range for females would be 2.9 kg to 4.5 kg on gestation day 0. Female no. 53748 in the 0 ppm group (Phase I) weighed 2892 g on gestation day 0.

• Protocol Section 6.4 states that all Phase I females would be supplemented with kale following the 30 January 2008 exposures and that all females in the Phase II would be supplemented beginning on the first day of exposure. In Phase I, 4000 ppm group female nos. 53723, 53724 and 53734 (gestation days 16 and 18) and 53754, 53756, 53761, 53769, 53774 and 53775 (gestation days 15 and 17) had no documentation of receiving kale supplementation. In Phase II, 5500 ppm group female nos. 54126, 54130 and 54136 (gestation day 18) and 54144, 54145, 54155, 54158, 54162, 54168 and 54170 (gestation day 17) had no documentation of receiving kale supplementation.

• Protocol Section 7.1 states that time-mated rabbits would be received by WIL Research Laboratories, LLC on gestation day 1 or 2 for each phase. Time-mated rabbits for Phase II were received on gestation day 2 or 3.

• Protocol Section 7.1 states that food consumption from gestation days 4-6 (daily) would be recorded for all rabbits (including stock). On 22 January 2008 (gestation days 5 or 6 of Phase II), food consumption was not recorded for stock female nos. 53746, 53721, 53767 and 53784.

• Protocol Section 7.5 states that the mean temperature in the inhalation chambers would be 19°C ± 3°C. The mean temperature for chambers 1 and 5 was 23°C.

• Protocol Section 7.7.2 states that the average daily exposure concentration in each chamber would be considered acceptable if within 10% of the target concentration. Due to suspect problems from the gas chromatograph on 2 March 2008 (Phase II), 2 manual bag samples were collected from each test substance chamber towards the end of animal exposure and the concentration of each was calculated using factors obtained from the 3 March 2008 calibration. These additional samples were included in the mean concentration calculation on 2 March 2008 and were found to be 2219, 4554, 6696 and 4455 ppm which was 11.2%, 17.2%, 10.6% and 19.0% from the target for chambers 2, 3, 4 and 5, respectively.

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• Protocol Section 7.7.2 states that actual test article gas concentration in the exposure atmospheres would be determined at least hourly for each chamber using an appropriate gas chromatographic method. On 3 March 2008, some samples were collected up to 1 hour 7 minutes following collection of the previous sample.

• Protocol Section 7.8.1 states that purity samples would be collected prior to use for animal exposures. A test substance sample was collected from WIL cylinder log no. 7819B #1 on 21 January 2008 prior to animal exposure. However, the sample could not be used due to leakage from the sample bag. Therefore, another sample was collected from this cylinder on 22 January 2008, which had been used for animal exposure by that time.

• Protocol Section 7.9.5 states that recognizable fetuses would be examined externally. Female no. 54107 in the 5500 ppm group (Phase II) aborted on gestation day 28. Two live fetuses were noted in the right uterine horn; however, an external examination for these fetuses was not recorded.

• Protocol Section 7.11.2 states that a mid-coronal slice would be performed on the heads of all fetuses at the time of the fresh visceral examination. A mid-coronal examination was not conducted for fetus no. 53782-03 in the 2500 ppm group (Phase I).
These deviations did not negatively impact the quality or integrity of the data or the
outcome of the study.

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# T ABLES 

# 1-19

55 of 475TABLE 1 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF MATERNAL SURVIVAL AND PREGNANCY STATUS

----------------------------------------------------------------------------------------------------------------------------------- DOSE GROUP : 1 2 3 4 5

----------------------------------------------------------------------------------------------------------------------------------- NO. % NO. % NO. % NO. % NO. %

FEMALES ON STUDY 24 24 24 24 24

FEMALES THAT ABORTED OR DELIVERED 0 0.0 0 0.0 0 0.0 1 4.2 4 16.7

FEMALES THAT DIED 0 0.0 0 0.0 0 0.0 3 12.5 6 25.0 FEMALES THAT ABORTED 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 NONGRAVID 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 GRAVID 0 0.0 0 0.0 0 0.0 3 100.0 6 100.0

FEMALES THAT WERE EUTHANIZED 0 0.0 0 0.0 0 0.0 1 4.2 1 4.2 NONGRAVID 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 GRAVID 0 0.0 0 0.0 0 0.0 1 100.0 1 100.0

FEMALES EXAMINED AT SCHEDULED NECROPSY 24 100.0 24 100.0 24 100.0 19 79.2 13 54.2 NONGRAVID 0 0.0 1 4.2 0 0.0 1 5.3 0 0.0 GRAVID 24 100.0 23 95.8 24 100.0 18 94.7 13 100.0 WITH RESORPTIONS ONLY 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 WITH VIABLE FETUSES 24 100.0 23 100.0 24 100.0 18 100.0 13 100.0

TOTAL FEMALES GRAVID 24 100.0 23 95.8 24 100.0 23 95.8 24 100.0

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM PSPSv4.01 05/20/200856of475TABLE 2 (PHASE I - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022F INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS

----- F E M A L E -----

----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 01-18-08 TO 02-15-08 GROUP: 1 2 3 4 5

-----------------------------------------------------------------------------------------------------------------------------------

NORMAL -NO SIGNIFICANT CLINICAL OBSERVATIONS 303/12 326/12 340/12 301/12 331/12

DISPOSITION -FOUND DEAD 0/ 0 0/ 0 0/ 0 2/ 2 0/ 0 -ABORTED; SENT TO NECROPSY 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 -SCHEDULED EUTHANASIA; GESTATION DAY 29 12/12 12/12 12/12 9/ 9 12/12

BODY/INTEGUMENT -HAIR LOSS LEFT HINDLIMB 11/ 1 0/ 0 0/ 0 0/ 0 0/ 0 -HAIR LOSS LEFT INGUINAL AREA 16/ 1 0/ 0 0/ 0 0/ 0 0/ 0 -HAIR LOSS RIGHT FORELIMB 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1 -HAIR LOSS LEFT FORELIMB 20/ 1 0/ 0 0/ 0 0/ 0 3/ 3 -DRIED RED MATERIAL LEFT HINDLIMB 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 -DRIED BROWN MATERIAL UROGENITAL AREA 0/ 0 0/ 0 0/ 0 0/ 0 2/ 1 -HAIR LOSS UROGENITAL AREA 0/ 0 5/ 2 0/ 0 0/ 0 0/ 0 -HAIR LOSS RIGHT INGUINAL AREA 0/ 0 2/ 1 0/ 0 0/ 0 0/ 0 -HAIR LOSS VENTRAL NECK 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 -HAIR LOSS RIGHT LATERAL ABDOMINAL AREA 0/ 0 1/ 1 0/ 0 0/ 0 0/ 0

EYES/EARS/NOSE -LACERATION NOSE 0/ 0 2/ 1 0/ 0 0/ 0 0/ 0

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 7500 PPM 5-4000 PPM DUPONT57of475TABLE 2 (PHASE I - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022F INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS

----- F E M A L E -----

----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 01-18-08 TO 02-15-08 GROUP: 1 2 3 4 5

-----------------------------------------------------------------------------------------------------------------------------------

EYES/EARS/NOSE -DRIED RED MATERIAL AROUND NOSE 0/ 0 2/ 1 0/ 0 0/ 0 0/ 0 -WET RED MATERIAL AROUND NOSE 0/ 0 1/ 1 0/ 0 0/ 0 0/ 0

EXCRETA -SOFT STOOL 2/ 2 5/ 4 0/ 0 1/ 1 2/ 2 -DECREASED DEFECATION 0/ 0 4/ 1 2/ 1 2/ 2 6/ 3 -FECES SMALL 0/ 0 1/ 1 0/ 0 0/ 0 0/ 0

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 7500 PPM 5-4000 PPM DUPONT PCSUv4.07 05/20/200858of475TABLE 3 (PHASE II - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022D INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS

----- F E M A L E -----

----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 02-22-08 TO 03-20-08 GROUP: 1 2 3 4 5

-----------------------------------------------------------------------------------------------------------------------------------

NORMAL -NO SIGNIFICANT CLINICAL OBSERVATIONS 329/12 328/12 291/12 223/12 295/12

DISPOSITION -EUTHANIZED IN EXTREMIS 0/ 0 0/ 0 0/ 0 1/ 1 1/ 1 -FOUND DEAD 0/ 0 0/ 0 1/ 1 4/ 4 2/ 2 -ABORTED; SENT TO NECROPSY 0/ 0 0/ 0 1/ 1 2/ 2 0/ 0 -DELIVERED; SENT TO NECROPSY 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 -SCHEDULED EUTHANASIA; GESTATION DAY 29 12/12 12/12 10/10 4/ 4 9/ 9

BEHAVIOR/CNS -HYPOACTIVITY 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1

BODY/INTEGUMENT -HAIR LOSS LEFT HINDLIMB 0/ 0 0/ 0 8/ 1 4/ 1 0/ 0 -HAIR LOSS RIGHT HINDLIMB 0/ 0 0/ 0 0/ 0 5/ 1 0/ 0 -HAIR LOSS UROGENITAL AREA 0/ 0 0/ 0 0/ 0 7/ 2 6/ 2 -SCABBING FACIAL AREA 0/ 0 0/ 0 10/ 1 0/ 0 0/ 0 -LACERATION FACIAL AREA 0/ 0 0/ 0 1/ 1 0/ 0 0/ 0 -HAIR LOSS RIGHT FORELIMB 0/ 0 0/ 0 0/ 0 14/ 1 0/ 0 -DRIED BROWN MATERIAL ANOGENITAL AREA 2/ 1 0/ 0 0/ 0 0/ 0 5/ 1 -HAIR LOSS LEFT FORELIMB 0/ 0 0/ 0 0/ 0 3/ 1 0/ 0

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 5500 PPM 4- 7500 PPM 5-5500 PPM DUPONT59of475TABLE 3 (PHASE II - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022D INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS

----- F E M A L E -----

----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 02-22-08 TO 03-20-08 GROUP: 1 2 3 4 5

-----------------------------------------------------------------------------------------------------------------------------------

CARDIO-PULMONARY -LABORED RESPIRATION 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1

EXCRETA -DECREASED DEFECATION 0/ 0 3/ 2 2/ 2 14/ 4 3/ 2 -SOFT STOOL 0/ 0 1/ 1 0/ 0 0/ 0 2/ 1

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 5500 PPM 4- 7500 PPM 5-5500 PPM DUPONT PCSUv4.07 05/29/200860of475TABLE 4 (PHASE I - MID-POINT OF EXPOSURE) PROJECT NO.:WIL-447022F INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS

----- F E M A L E -----

----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 01-22-08 TO 02-14-08 GROUP: 1 2 3 4 5

-----------------------------------------------------------------------------------------------------------------------------------

NORMAL -NO SIGNIFICANT CLINICAL OBSERVATIONS 276/12 276/12 276/12 240/12 276/12

BEHAVIOR/CNS -HYPOACTIVITY 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0

CARDIO-PULMONARY -INCREASED RESPIRATION 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 7500 PPM 5-4000 PPM DUPONT PCSUv4.07 05/20/2008 R:05/29/200861of475TABLE 5 (PHASE II - MID-POINT OF EXPOSURE) PROJECT NO.:WIL-447022D INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS

----- F E M A L E -----

----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 02-25-08 TO 03-19-08 GROUP: 1 2 3 4 5

-----------------------------------------------------------------------------------------------------------------------------------

NORMAL -NO SIGNIFICANT CLINICAL OBSERVATIONS 276/12 276/12 258/12 212/12 254/12

CARDIO-PULMONARY -DECREASED RESPIRATION 0/ 0 0/ 0 2/ 1 1/ 1 2/ 1 -LABORED RESPIRATION 0/ 0 0/ 0 2/ 1 1/ 1 1/ 1

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 5500 PPM 4- 7500 PPM 5-5500 PPM DUPONT PCSUv4.07 05/21/2008 R:05/29/200862of475TABLE 6 (PHASE I - 1 HOUR POST-EXPOSURE) PROJECT NO.:WIL-447022F INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS

----- F E M A L E -----

----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 01-22-08 TO 02-14-08 GROUP: 1 2 3 4 5

-----------------------------------------------------------------------------------------------------------------------------------

NORMAL -NO SIGNIFICANT CLINICAL OBSERVATIONS 276/12 276/12 276/12 241/12 276/12

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 7500 PPM 5-4000 PPM DUPONT PCSUv4.07 05/20/2008 R:05/20/200863of475TABLE 7 (PHASE II - 1 HOUR POST-EXPOSURE) PROJECT NO.:WIL-447022D INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS

----- F E M A L E -----

----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 02-25-08 TO 03-19-08 GROUP: 1 2 3 4 5

-----------------------------------------------------------------------------------------------------------------------------------

NORMAL -NO SIGNIFICANT CLINICAL OBSERVATIONS 275/12 276/12 260/12 208/12 256/12

BEHAVIOR/CNS -HYPOACTIVITY 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1

BODY/INTEGUMENT -WET RED MATERIAL UROGENITAL AREA 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1

CARDIO-PULMONARY -DECREASED RESPIRATION 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 -LABORED RESPIRATION 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 -INCREASED RESPIRATION 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0

EYES/EARS/NOSE -WET CLEAR MATERIAL AROUND NOSE 0/ 0 0/ 0 0/ 0 2/ 2 0/ 0

ORAL/DENTAL -WET CLEAR MATERIAL AROUND MOUTH 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 5500 PPM 4- 7500 PPM 5-5500 PPM DUPONT PCSUv4.07 06/19/2008 R:06/19/200864of475TABLE 8 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF BODY WEIGHTS DURING GESTATION [G]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 0 MEAN 3154. 3150. 3068. 3241. 3185. % DIFFERENCE -0.1 -2.7 2.8 1.0 S.D. 186.2 207.5 114.5 232.7 229.9 S.E. 38.0 43.3 23.4 48.5 46.9 N 24 23 24 23 24

DAY 4 MEAN 3130. 3125. 3050. 3162. 3157. % DIFFERENCE -0.2 -2.6 1.0 0.9 S.D. 161.8 184.2 134.2 209.6 226.0 S.E. 33.0 38.4 27.4 43.7 46.1 N 24 23 24 23 24

DAY 6 MEAN 3259. 3236. 3215. 3265. 3292. % DIFFERENCE -0.7 -1.4 0.2 1.0 S.D. 157.0 167.8 149.6 212.4 211.3 S.E. 32.0 35.0 30.5 44.3 43.1 N 24 23 24 23 24

DAY 7 MEAN 3258. 3253. 3209. 3302. 3300. % DIFFERENCE -0.2 -1.5 1.4 1.3 S.D. 161.7 207.3 146.1 229.5 213.1 S.E. 33.0 43.2 29.8 47.8 43.5 N 24 23 24 23 24

DAY 8 MEAN 3260. 3270. 3214. 3305. 3300. % DIFFERENCE 0.3 -1.4 1.4 1.2 S.D. 166.1 210.5 149.5 227.1 216.0 S.E. 33.9 43.9 30.5 47.4 44.1 N 24 23 24 23 24

----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN65of475TABLE 8 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL SUMMARY OF BODY WEIGHTS DURING GESTATION [G]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 9 MEAN 3278. 3286. 3229. 3316. 3314. % DIFFERENCE 0.2 -1.5 1.2 1.1 S.D. 172.1 220.0 153.5 224.9 223.5 S.E. 35.1 45.9 31.3 46.9 45.6 N 24 23 24 23 24

DAY 10 MEAN 3294. 3292. 3247. 3338. 3326. % DIFFERENCE -0.1 -1.4 1.3 1.0 S.D. 177.3 224.1 153.6 225.7 225.4 S.E. 36.2 46.7 31.4 47.1 46.0 N 24 23 24 23 24

DAY 11 MEAN 3307. 3314. 3259. 3360. 3342. % DIFFERENCE 0.2 -1.5 1.6 1.1 S.D. 171.1 231.7 151.5 236.2 234.5 S.E. 34.9 48.3 30.9 49.3 47.9 N 24 23 24 23 24

DAY 12 MEAN 3335. 3336. 3272. 3378. 3383. % DIFFERENCE 0.0 -1.9 1.3 1.4 S.D. 178.5 240.1 177.6 236.8 235.1 S.E. 36.4 50.1 36.2 49.4 49.0 N 24 23 24 23 23

DAY 13 MEAN 3365. 3360. 3298. 3388. 3399. % DIFFERENCE -0.1 -2.0 0.7 1.0 S.D. 182.4 240.9 193.1 248.7 234.0 S.E. 37.2 50.2 39.4 53.0 48.8 N 24 23 24 22 23

----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN66of475TABLE 8 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL SUMMARY OF BODY WEIGHTS DURING GESTATION [G]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 14 MEAN 3391. 3386. 3319. 3409. 3380. % DIFFERENCE -0.1 -2.1 0.5 -0.3 S.D. 182.4 245.2 199.2 284.4 259.9 S.E. 37.2 51.1 40.7 60.6 54.2 N 24 23 24 22 23

DAY 15 MEAN 3438. 3409. 3335. 3471. 3444. % DIFFERENCE -0.8 -3.0 1.0 0.2 S.D. 179.6 244.6 216.6 250.8 271.2 S.E. 36.7 51.0 44.2 54.7 60.6 N 24 23 24 21 20

DAY 16 MEAN 3470. 3434. 3359. 3503. 3451. % DIFFERENCE -1.0 -3.2 1.0 -0.5 S.D. 184.3 264.1 216.4 253.3 274.9 S.E. 37.6 55.1 44.2 55.3 61.5 N 24 23 24 21 20

DAY 17 MEAN 3493. 3460. 3378. 3512. 3457. % DIFFERENCE -0.9 -3.3 0.5 -1.0 S.D. 179.2 261.7 212.4 261.4 267.4 S.E. 36.6 54.6 43.4 57.1 61.4 N 24 23 24 21 19

DAY 18 MEAN 3508. 3479. 3386. 3518. 3439. % DIFFERENCE -0.8 -3.5 0.3 -2.0 S.D. 188.0 255.3 209.6 262.8 264.2 S.E. 38.4 53.2 42.8 57.4 62.3 N 24 23 24 21 18

----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN67of475TABLE 8 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL SUMMARY OF BODY WEIGHTS DURING GESTATION [G]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 19 MEAN 3526. 3506. 3406. 3522. 3429. % DIFFERENCE -0.6 -3.4 -0.1 -2.8 S.D. 178.8 267.4 218.7 260.4 287.6 S.E. 36.5 55.7 44.6 56.8 67.8 N 24 23 24 21 18

DAY 20 MEAN 3550. 3518. 3429. 3538. 3467. % DIFFERENCE -0.9 -3.4 -0.3 -2.3 S.D. 174.4 259.4 215.6 264.3 287.4 S.E. 35.6 54.1 44.0 57.7 69.7 N 24 23 24 21 17

DAY 21 MEAN 3575. 3543. 3449. 3560. 3484. % DIFFERENCE -0.9 -3.5 -0.4 -2.5 S.D. 178.5 265.0 211.1 269.0 292.4 S.E. 36.4 55.2 43.1 58.7 70.9 N 24 23 24 21 17

DAY 22 MEAN 3584. 3553. 3465. 3575. 3499. % DIFFERENCE -0.9 -3.3 -0.3 -2.4 S.D. 175.7 270.9 212.1 259.8 303.7 S.E. 35.9 56.5 43.3 56.7 73.7 N 24 23 24 21 17

DAY 23 MEAN 3612. 3564. 3486. 3566. 3490. % DIFFERENCE -1.3 -3.5 -1.3 -3.4 S.D. 166.7 276.1 214.7 251.9 311.4 S.E. 34.0 57.6 43.8 55.0 75.5 N 24 23 24 21 17

----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN68of475TABLE 8 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL SUMMARY OF BODY WEIGHTS DURING GESTATION [G]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 24 MEAN 3626. 3579. 3503. 3557. 3478. % DIFFERENCE -1.3 -3.4 -1.9 -4.1 S.D. 164.9 271.5 211.5 241.2 309.7 S.E. 33.7 56.6 43.2 52.6 75.1 N 24 23 24 21 17

DAY 25 MEAN 3641. 3576. 3503. 3548. 3479. % DIFFERENCE -1.8 -3.8 -2.6 -4.4 S.D. 152.7 272.9 215.0 234.5 310.3 S.E. 31.2 56.9 43.9 51.2 75.3 N 24 23 24 21 17

DAY 26 MEAN 3650. 3578. 3504. 3527. 3494. % DIFFERENCE -2.0 -4.0 -3.4 -4.3 S.D. 162.9 284.6 210.5 227.8 306.9 S.E. 33.3 59.3 43.0 49.7 76.7 N 24 23 24 21 16

DAY 27 MEAN 3652. 3572. 3491. 3524. 3527. % DIFFERENCE -2.2 -4.4 -3.5 -3.4 S.D. 171.6 278.5 208.5 221.8 200.3 S.E. 35.0 58.1 42.6 49.6 51.7 N 24 23 24 20 15

DAY 28 MEAN 3650. 3573. 3495. 3495. 3526. % DIFFERENCE -2.1 -4.2 -4.2 -3.4 S.D. 170.8 284.7 206.9 236.8 204.3 S.E. 34.9 59.4 42.2 54.3 52.7 N 24 23 24 19 15

----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN69of475TABLE 8 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 6 SPONSOR:HONEYWELL SUMMARY OF BODY WEIGHTS DURING GESTATION [G]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 29 MEAN 3667. 3589. 3500. 3493. 3578. % DIFFERENCE -2.1 -4.6 -4.7 -2.4 S.D. 173.1 291.0 207.0 247.9 198.1 S.E. 35.3 60.7 42.2 58.4 54.9 N 24 23 24 18 13

----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PGBWSUv5.09 05/21/200870of475TABLE 9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF BODY WEIGHT CHANGES DURING GESTATION [G]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 0- 4 MEAN -24. -26. -18. -78.* -28. S.D. 74.6 73.1 78.4 70.1 73.8 S.E. 15.2 15.3 16.0 14.6 15.1 N 24 23 24 23 24

DAY 4- 6 MEAN 129. 112. 164. 102. 135. S.D. 78.8 93.2 63.2 85.0 113.9 S.E. 16.1 19.4 12.9 17.7 23.2 N 24 23 24 23 24

DAY 6- 7 MEAN -1. 16. -5. 38. 8. S.D. 46.7 90.6 33.5 87.7 58.5 S.E. 9.5 18.9 6.8 18.3 11.9 N 24 23 24 23 24

DAY 7- 8 MEAN 3. 18. 5. 2. 0. S.D. 27.0 51.2 17.8 29.3 24.7 S.E. 5.5 10.7 3.6 6.1 5.1 N 24 23 24 23 24

DAY 8- 9 MEAN 18. 16. 15. 11. 14. S.D. 25.6 23.8 24.5 30.0 27.4 S.E. 5.2 5.0 5.0 6.2 5.6 N 24 23 24 23 24

----------------------------------------------------------------------------------------------------------------------------------- * = Significantly different from the control group at 0.05 using Dunnett’s test MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN71of475TABLE 9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL SUMMARY OF BODY WEIGHT CHANGES DURING GESTATION [G]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 9- 10 MEAN 15. 6. 18. 23. 11. S.D. 15.1 26.6 20.2 20.7 19.9 S.E. 3.1 5.6 4.1 4.3 4.1 N 24 23 24 23 24

DAY 10- 11 MEAN 13. 22. 11. 22. 16. S.D. 17.5 23.3 24.5 18.9 27.8 S.E. 3.6 4.9 5.0 3.9 5.7 N 24 23 24 23 24

DAY 11- 12 MEAN 28. 22. 13. 18. 25. S.D. 21.4 24.2 47.7 17.3 21.1 S.E. 4.4 5.0 9.7 3.6 4.4 N 24 23 24 23 23

DAY 12- 13 MEAN 29. 25. 27. 7.* 17. S.D. 25.4 14.5 29.5 34.7 22.2 S.E. 5.2 3.0 6.0 7.4 4.6 N 24 23 24 22 23

DAY 13- 14 MEAN 26. 26. 20. 22. -19.* S.D. 22.8 17.3 31.9 61.7 91.1 S.E. 4.7 3.6 6.5 13.2 19.0 N 24 23 24 22 23

----------------------------------------------------------------------------------------------------------------------------------- * = Significantly different from the control group at 0.05 using Dunnett’s test MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN72of475TABLE 9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL SUMMARY OF BODY WEIGHT CHANGES DURING GESTATION [G]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 14- 15 MEAN 47. 23. 17. 30. 27. S.D. 27.3 29.9 49.7 21.9 55.2 S.E. 5.6 6.2 10.2 4.8 12.3 N 24 23 24 21 20

DAY 15- 16 MEAN 32. 24. 24. 32. 7. S.D. 21.3 35.4 38.0 19.7 38.9 S.E. 4.3 7.4 7.7 4.3 8.7 N 24 23 24 21 20

DAY 16- 17 MEAN 23. 27. 19. 9. 2. S.D. 28.7 18.6 26.8 30.3 57.3 S.E. 5.9 3.9 5.5 6.6 13.2 N 24 23 24 21 19

DAY 17- 18 MEAN 15. 19. 9. 7. 9. S.D. 36.8 39.4 15.1 38.8 30.6 S.E. 7.5 8.2 3.1 8.5 7.2 N 24 23 24 21 18

DAY 18- 19 MEAN 18. 27. 20. 3. -10.* S.D. 25.5 31.8 24.0 36.0 54.8 S.E. 5.2 6.6 4.9 7.9 12.9 N 24 23 24 21 18

----------------------------------------------------------------------------------------------------------------------------------- * = Significantly different from the control group at 0.05 using Dunnett’s test MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN73of475TABLE 9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL SUMMARY OF BODY WEIGHT CHANGES DURING GESTATION [G]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 19- 20 MEAN 25. 12. 23. 17. 18. S.D. 26.7 23.2 19.9 26.0 17.6 S.E. 5.5 4.8 4.1 5.7 4.3 N 24 23 24 21 17

DAY 20- 21 MEAN 25. 25. 19. 22. 17. S.D. 23.9 21.0 22.6 29.6 37.6 S.E. 4.9 4.4 4.6 6.5 9.1 N 24 23 24 21 17

DAY 21- 22 MEAN 9. 11. 17. 15. 15. S.D. 27.2 28.6 20.3 31.1 25.9 S.E. 5.6 6.0 4.2 6.8 6.3 N 24 23 24 21 17

DAY 22- 23 MEAN 27. 11. 21. -9.* -9.* S.D. 21.3 28.4 20.4 52.5 73.5 S.E. 4.3 5.9 4.2 11.5 17.8 N 24 23 24 21 17

DAY 23- 24 MEAN 14. 15. 17. -9. -12. S.D. 29.4 25.0 21.0 69.0 61.6 S.E. 6.0 5.2 4.3 15.1 15.0 N 24 23 24 21 17

----------------------------------------------------------------------------------------------------------------------------------- * = Significantly different from the control group at 0.05 using Dunnett’s test MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN74of475TABLE 9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL SUMMARY OF BODY WEIGHT CHANGES DURING GESTATION [G]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 24- 25 MEAN 15. -4. 0. -9. 1. S.D. 33.5 31.4 30.8 29.6 46.1 S.E. 6.8 6.5 6.3 6.5 11.2 N 24 23 24 21 17

DAY 25- 26 MEAN 9. 2. 1. -21. -7. S.D. 27.6 45.6 25.0 47.9 49.8 S.E. 5.6 9.5 5.1 10.4 12.4 N 24 23 24 21 16

DAY 26- 27 MEAN 2. -5. -13. -14. -28. S.D. 37.5 28.2 27.8 58.3 56.8 S.E. 7.6 5.9 5.7 13.0 14.7 N 24 23 24 20 15

DAY 27- 28 MEAN -2. 0. 4. -16. -1. S.D. 36.7 41.0 30.2 51.7 45.0 S.E. 7.5 8.5 6.2 11.9 11.6 N 24 23 24 19 15

DAY 28- 29 MEAN 17. 16. 4. -9. 22. S.D. 38.4 37.4 31.3 57.3 37.7 S.E. 7.8 7.8 6.4 13.5 10.5 N 24 23 24 18 13

----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN75of475TABLE 9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 6 SPONSOR:HONEYWELL SUMMARY OF BODY WEIGHT CHANGES DURING GESTATION [G]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 6- 9 MEAN 20. 50. 15. 51. 23. S.D. 48.5 131.0 41.4 77.4 60.9 S.E. 9.9 27.3 8.5 16.1 12.4 N 24 23 24 23 24

DAY 9- 12 MEAN 57. 50. 43. 62. 56. S.D. 25.3 38.3 50.2 34.1 36.5 S.E. 5.2 8.0 10.2 7.1 7.6 N 24 23 24 23 23

DAY 12- 20 MEAN 215. 182. 158. 144. 110.** S.D. 65.2 64.1 85.3 92.0 184.2 S.E. 13.3 13.4 17.4 20.1 44.7 N 24 23 24 21 17

DAY 20- 29 MEAN 116. 71. 71. -31.** 97. S.D. 112.0 130.2 119.1 203.7 174.4 S.E. 22.9 27.2 24.3 48.0 48.4 N 24 23 24 18 13

DAY 6- 29 MEAN 408. 352. 285.* 235.** 324. S.D. 105.0 221.3 113.4 204.9 134.2 S.E. 21.4 46.1 23.2 48.3 37.2 N 24 23 24 18 13

----------------------------------------------------------------------------------------------------------------------------------- * = Significantly different from the control group at 0.05 using Dunnett’s test ** = Significantly different from the control group at 0.01 using Dunnett’s test MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PGBWSUv5.09 05/21/200876of475TABLE 10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF GRAVID UTERINE WTS. AND NET BODY WT. CHANGES [G]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- INITIAL BODY WT. MEAN 3154. 3150. 3068. 3218. 3099. S.D. 186.2 207.5 114.5 199.4 107.9 S.E. 38.0 43.3 23.4 47.0 29.9 N 24 23 24 18 13

TERMINAL BODY WT. MEAN 3667. 3589. 3500. 3493. 3578. S.D. 173.1 291.0 207.0 247.9 198.1 S.E. 35.3 60.7 42.2 58.4 54.9 N 24 23 24 18 13

GRAVID UTERINE WT. MEAN 491.6 475.7 460.6 449.7 506.1 S.D. 84.21 93.62 95.59 86.39 78.74 S.E. 17.19 19.52 19.51 20.36 21.84 N 24 23 24 18 13

NET BODY WT. MEAN 3175.2 3112.8 3039.1 3043.3 3071.8 S.D. 167.40 257.41 159.49 197.64 153.23 S.E. 34.17 53.67 32.56 46.58 42.50 N 24 23 24 18 13

NET BODY WT. CHANGE MEAN 21.1 -37.6 -29.4 -174.8** -27.6 S.D. 139.66 193.40 96.11 202.32 111.84 S.E. 28.51 40.33 19.62 47.69 31.02 N 24 23 24 18 13

----------------------------------------------------------------------------------------------------------------------------------- ** = Significantly different from the control group at 0.01 using Dunnett’s test PUTSUv5.06 05/20/200877of475TABLE 11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 4- 6 MEAN 170. 166. 200.* 140.* 169. S.D. 36.1 52.3 27.8 32.3 46.1 S.E. 7.4 10.9 5.7 6.7 9.4 N 24 23 24 23 24

DAY 6- 7 MEAN 165. 160. 168. 164. 167. S.D. 20.5 40.3 18.0 36.1 27.5 S.E. 4.2 8.4 3.7 7.5 5.6 N 24 23 24 23 24

DAY 7- 8 MEAN 166. 161. 165. 154. 156. S.D. 20.3 27.4 23.7 29.8 23.0 S.E. 4.2 5.7 4.8 6.2 4.7 N 24 23 24 23 24

DAY 8- 9 MEAN 163. 160. 166. 152. 156. S.D. 23.8 28.1 20.1 32.1 26.8 S.E. 4.9 5.9 4.1 6.7 5.5 N 24 23 24 23 24

DAY 9- 10 MEAN 159. 154. 163. 161. 154. S.D. 23.5 30.3 23.0 27.7 27.5 S.E. 4.8 6.5 4.7 5.8 5.6 N 24 22 24 23 24

----------------------------------------------------------------------------------------------------------------------------------- * = Significantly different from the control group at 0.05 using Dunnett’s test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN78of475TABLE 11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 10- 11 MEAN 161. 156. 163. 153. 150. S.D. 26.1 27.3 22.6 26.2 29.4 S.E. 5.3 5.7 4.6 5.5 6.0 N 24 23 24 23 24

DAY 11- 12 MEAN 160. 156. 155. 148. 146. S.D. 29.3 33.1 31.2 26.1 27.2 S.E. 6.0 6.9 6.4 5.4 5.7 N 24 23 24 23 23

DAY 12- 13 MEAN 152. 146. 143. 142. 136. S.D. 30.2 31.9 40.1 34.8 30.9 S.E. 6.2 6.7 8.2 7.4 6.5 N 24 23 24 22 23

DAY 13- 14 MEAN 151. 144. 134. 138. 116. S.D. 28.6 38.3 41.9 41.3 59.0 S.E. 5.8 8.0 8.5 8.8 12.3 N 24 23 24 22 23

DAY 14- 15 MEAN 156. 144. 138. 147. 137. S.D. 24.2 44.0 47.9 28.0 45.6 S.E. 5.0 9.2 9.8 6.1 10.2 N 23 23 24 21 20

----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN79of475TABLE 11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 15- 16 MEAN 160. 149. 146. 151. 133. S.D. 27.6 50.6 46.5 28.5 55.0 S.E. 5.7 10.5 9.5 6.2 12.3 N 23 23 24 21 20

DAY 16- 17 MEAN 165. 153. 145. 149. 136. S.D. 22.6 42.7 38.6 34.2 55.6 S.E. 4.7 8.9 7.9 7.5 12.8 N 23 23 24 21 19

DAY 17- 18 MEAN 168. 155. 148. 143. 143. S.D. 31.8 38.7 38.0 49.8 47.4 S.E. 6.6 8.1 7.7 10.9 11.2 N 23 23 24 21 18

DAY 18- 19 MEAN 171. 164. 156. 139.* 135.* S.D. 25.8 32.7 33.8 53.1 61.1 S.E. 5.4 6.8 6.9 11.6 14.4 N 23 23 24 21 18

DAY 19- 20 MEAN 166. 156. 153. 142. 139. S.D. 29.4 33.8 27.9 56.6 53.7 S.E. 6.1 7.1 5.7 12.3 13.0 N 23 23 24 21 17

----------------------------------------------------------------------------------------------------------------------------------- * = Significantly different from the control group at 0.05 using Dunnett’s test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN80of475TABLE 11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 20- 21 MEAN 162. 151. 150. 138. 138. S.D. 32.1 33.1 24.5 37.9 43.3 S.E. 6.6 6.9 5.0 8.3 10.5 N 24 23 24 21 17

DAY 21- 22 MEAN 150. 139. 141. 125. 131. S.D. 30.1 39.6 25.7 23.8 43.0 S.E. 6.1 8.4 5.2 5.2 10.4 N 24 22 24 21 17

DAY 22- 23 MEAN 140. 122. 130. 101.** 107.* S.D. 30.8 45.9 27.8 37.9 45.1 S.E. 6.3 9.6 5.7 8.3 10.9 N 24 23 24 21 17

DAY 23- 24 MEAN 125. 111. 118. 86.** 90.* S.D. 31.0 42.0 31.1 41.5 43.9 S.E. 6.3 8.8 6.3 9.1 10.6 N 24 23 24 21 17

DAY 24- 25 MEAN 111. 94. 97. 76. 81. S.D. 33.3 40.7 40.3 49.1 44.5 S.E. 6.8 8.5 8.2 10.7 10.8 N 24 23 24 21 17

----------------------------------------------------------------------------------------------------------------------------------- * = Significantly different from the control group at 0.05 using Dunnett’s test ** = Significantly different from the control group at 0.01 using Dunnett’s test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN81of475TABLE 11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 25- 26 MEAN 103. 87. 91. 62.** 75. S.D. 33.3 37.1 36.7 44.2 40.3 S.E. 6.8 7.7 7.5 9.6 10.4 N 24 23 24 21 15

DAY 26- 27 MEAN 98. 78. 81. 63.* 69. S.D. 32.0 34.7 39.7 46.7 39.5 S.E. 6.5 7.2 8.1 10.5 10.2 N 24 23 24 20 15

DAY 27- 28 MEAN 89. 77. 79. 63. 71. S.D. 35.0 40.4 36.2 43.6 38.9 S.E. 7.1 8.4 7.4 10.3 10.0 N 24 23 24 18 15

DAY 28- 29 MEAN 93. 81. 78. 61. 85. S.D. 33.7 39.9 36.7 41.9 29.5 S.E. 6.9 8.3 7.8 9.9 8.2 N 24 23 22 18 13

DAY 6- 9 MEAN 165. 160. 166. 157. 159. S.D. 19.6 28.3 19.0 28.2 23.1 S.E. 4.0 5.9 3.9 5.9 4.7 N 24 23 24 23 24

----------------------------------------------------------------------------------------------------------------------------------- * = Significantly different from the control group at 0.05 using Dunnett’s test ** = Significantly different from the control group at 0.01 using Dunnett’s test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN82of475TABLE 11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 6 SPONSOR:HONEYWELL SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 9- 12 MEAN 160. 155. 160. 154. 150. S.D. 25.3 29.3 24.1 26.0 27.3 S.E. 5.2 6.1 4.9 5.4 5.6 N 24 23 24 23 24

DAY 12- 20 MEAN 162. 152. 145. 145. 140. S.D. 24.7 36.1 33.7 32.2 43.8 S.E. 5.0 7.5 6.9 7.0 10.3 N 24 23 24 21 18

DAY 20- 29 MEAN 119. 104. 108. 89.** 100. S.D. 21.4 31.6 27.0 27.4 24.3 S.E. 4.4 6.6 5.5 6.5 6.3 N 24 23 24 18 15

DAY 6- 29 MEAN 145. 135. 135. 128. 135. S.D. 17.5 28.9 20.2 19.6 19.4 S.E. 3.6 6.0 4.1 4.6 5.0 N 24 23 24 18 15

----------------------------------------------------------------------------------------------------------------------------------- ** = Significantly different from the control group at 0.01 using Dunnett’s test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PGFWSUv5.14 06/16/200883of475TABLE 12 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 4- 6 MEAN 53. 53. 64.* 44.* 53. S.D. 11.7 17.3 8.0 10.4 14.9 S.E. 2.4 3.6 1.6 2.2 3.0 N 24 23 24 23 24

DAY 6- 7 MEAN 51. 49. 52. 50. 51. S.D. 6.0 10.4 4.7 9.6 8.2 S.E. 1.2 2.2 1.0 2.0 1.7 N 24 23 24 23 24

DAY 7- 8 MEAN 51. 49. 51. 47. 47. S.D. 5.7 7.0 6.0 8.0 7.1 S.E. 1.2 1.5 1.2 1.7 1.4 N 24 23 24 23 24

DAY 8- 9 MEAN 50. 49. 51. 46. 47. S.D. 6.8 6.8 5.1 9.3 7.7 S.E. 1.4 1.4 1.0 1.9 1.6 N 24 23 24 23 24

DAY 9- 10 MEAN 48. 46. 50. 48. 46. S.D. 6.5 6.8 5.7 7.5 7.5 S.E. 1.3 1.4 1.2 1.6 1.5 N 24 22 24 23 24

----------------------------------------------------------------------------------------------------------------------------------- * = Significantly different from the control group at 0.05 using Dunnett’s test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN84of475TABLE 12 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 10- 11 MEAN 49. 47. 50. 45. 45. S.D. 7.5 6.7 5.7 6.8 8.1 S.E. 1.5 1.4 1.2 1.4 1.7 N 24 23 24 23 24

DAY 11- 12 MEAN 48. 47. 47. 44. 44. S.D. 8.2 8.3 8.4 6.9 7.2 S.E. 1.7 1.7 1.7 1.4 1.5 N 24 23 24 23 23

DAY 12- 13 MEAN 45. 44. 43. 42. 40. S.D. 8.1 7.8 11.5 9.7 8.2 S.E. 1.7 1.6 2.3 2.1 1.7 N 24 23 24 22 23

DAY 13- 14 MEAN 45. 43. 40. 40. 34.** S.D. 7.7 9.9 11.9 11.3 16.7 S.E. 1.6 2.1 2.4 2.4 3.5 N 24 23 24 22 23

DAY 14- 15 MEAN 46. 42. 41. 42. 40. S.D. 6.4 12.0 13.3 7.0 12.5 S.E. 1.3 2.5 2.7 1.5 2.8 N 23 23 24 21 20

----------------------------------------------------------------------------------------------------------------------------------- ** = Significantly different from the control group at 0.01 using Dunnett’s test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN85of475TABLE 12 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 15- 16 MEAN 47. 43. 43. 43. 38. S.D. 7.5 13.5 12.8 7.1 15.3 S.E. 1.6 2.8 2.6 1.5 3.4 N 23 23 24 21 20

DAY 16- 17 MEAN 48. 44. 43. 42. 39. S.D. 5.7 11.3 10.6 8.6 15.2 S.E. 1.2 2.3 2.2 1.9 3.5 N 23 23 24 21 19

DAY 17- 18 MEAN 48. 45. 43. 40. 41. S.D. 8.3 10.3 10.2 13.2 12.6 S.E. 1.7 2.1 2.1 2.9 3.0 N 23 23 24 21 18

DAY 18- 19 MEAN 49. 47. 46. 39.* 39.* S.D. 6.9 8.2 8.7 14.5 16.6 S.E. 1.4 1.7 1.8 3.2 3.9 N 23 23 24 21 18

DAY 19- 20 MEAN 47. 44. 45. 40. 39. S.D. 7.9 8.5 6.9 14.8 14.2 S.E. 1.6 1.8 1.4 3.2 3.4 N 23 23 24 21 17

----------------------------------------------------------------------------------------------------------------------------------- * = Significantly different from the control group at 0.05 using Dunnett’s test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN86of475TABLE 12 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 20- 21 MEAN 45. 43. 44. 39. 39. S.D. 8.4 8.5 6.7 9.3 11.2 S.E. 1.7 1.8 1.4 2.0 2.7 N 24 23 24 21 17

DAY 21- 22 MEAN 42. 39. 41. 35. 37. S.D. 7.9 10.1 7.3 6.5 11.1 S.E. 1.6 2.2 1.5 1.4 2.7 N 24 22 24 21 17

DAY 22- 23 MEAN 39. 34. 37. 28.** 30.* S.D. 8.5 12.0 7.9 10.6 12.2 S.E. 1.7 2.5 1.6 2.3 3.0 N 24 23 24 21 17

DAY 23- 24 MEAN 35. 31. 34. 24.** 26.* S.D. 8.9 11.2 9.0 11.8 11.8 S.E. 1.8 2.3 1.8 2.6 2.9 N 24 23 24 21 17

DAY 24- 25 MEAN 31. 26. 28. 22. 23. S.D. 9.5 10.9 11.6 13.7 12.0 S.E. 1.9 2.3 2.4 3.0 2.9 N 24 23 24 21 17

----------------------------------------------------------------------------------------------------------------------------------- * = Significantly different from the control group at 0.05 using Dunnett’s test ** = Significantly different from the control group at 0.01 using Dunnett’s test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN87of475TABLE 12 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 25- 26 MEAN 28. 24. 26. 17.** 21. S.D. 9.0 9.8 10.5 12.1 11.0 S.E. 1.8 2.0 2.2 2.6 2.8 N 24 23 24 21 15

DAY 26- 27 MEAN 27. 22. 23. 18. 20. S.D. 8.8 9.5 11.4 13.1 10.9 S.E. 1.8 2.0 2.3 2.9 2.8 N 24 23 24 20 15

DAY 27- 28 MEAN 24. 21. 23. 18. 20. S.D. 9.5 11.1 10.5 12.1 11.1 S.E. 1.9 2.3 2.1 2.8 2.9 N 24 23 24 18 15

DAY 28- 29 MEAN 25. 22. 22. 17. 24. S.D. 9.0 10.8 10.5 12.0 8.4 S.E. 1.8 2.2 2.2 2.8 2.3 N 24 23 22 18 13

DAY 6- 9 MEAN 51. 49. 52. 48. 48. S.D. 5.6 6.8 4.7 7.4 6.8 S.E. 1.1 1.4 1.0 1.6 1.4 N 24 23 24 23 24

----------------------------------------------------------------------------------------------------------------------------------- ** = Significantly different from the control group at 0.01 using Dunnett’s test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN88of475TABLE 12 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 6 SPONSOR:HONEYWELL SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- DAY 9- 12 MEAN 48. 47. 49. 46. 45. S.D. 7.0 6.9 6.0 7.0 7.1 S.E. 1.4 1.4 1.2 1.5 1.5 N 24 23 24 23 23

DAY 12- 20 MEAN 47. 44. 43. 42. 41. S.D. 6.5 9.3 8.6 8.2 11.4 S.E. 1.3 1.9 1.8 1.8 2.8 N 24 23 24 21 17

DAY 20- 29 MEAN 33. 29. 31. 25.** 30. S.D. 5.9 8.3 7.8 7.6 4.9 S.E. 1.2 1.7 1.6 1.8 1.4 N 24 23 24 18 13

DAY 6- 29 MEAN 42. 39. 40. 37. 40. S.D. 4.8 7.1 4.7 4.8 4.1 S.E. 1.0 1.5 1.0 1.1 1.1 N 24 23 24 18 13

----------------------------------------------------------------------------------------------------------------------------------- ** = Significantly different from the control group at 0.01 using Dunnett’s test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PGFWSUv5.14 06/16/200889of475TABLE 13 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- GROUP : 1 2 3 4 5

-----------------------------------------------------------------------------------------------------------------------------------

NUMBER EXAMINED 24 24 24 24 24

NO SIGNIFICANT CHANGES OBSERVED 8 10 13 7 7 NONGRAVID -- AMMONIUM SULFIDE NEGATIVE 0 1 0 1 0 KIDNEYS: AREA(S), DARK RED 0 0 0 0 1 DIED GESTATION DAY 12 0 0 0 0 1 LUNGS: DISCOLORATION, DARK RED 0 0 1 1 2 SPLEEN: AREA(S), DARK RED 0 0 0 0 1 DIED GESTATION DAY 14 0 0 0 1 3 ABORTED GESTATION DAY 26 0 0 0 0 2 SKIN: MATTING, RED 0 1 0 0 1 OVIDUCTS: CYST(S) 9 5 9 6 7 LUNGS: AREA(S), DARK RED 2 3 1 5 1 ADRENAL GLANDS: NODULE(S) 0 0 0 0 1 SKIN: HAIR LOSS 0 2 0 0 1 SPLEEN: ACCESSORY 8 4 3 4 7 LIVER: SMALL 0 0 0 0 1 GALLBLADDER: ABSENT 0 1 0 0 0 OVARIES: SMALL 0 1 0 0 0 KIDNEYS: AREA(S), WHITE 1 0 0 0 0 PLACENTAE: ENLARGED 0 1 0 0 0 EUTHANIZED GESTATION DAY 16 0 0 0 0 1 GALLBLADDER: SMALL 0 0 0 0 1 THORACIC CAVITY: CONTENTS, RED FLUID 0 0 0 0 1 SKIN: MATTING, GREEN 0 0 0 0 1 THORACIC CAVITY: MATERIAL, WHITE 0 0 0 0 1 LUNGS: DISCOLORATION, BROWN 0 0 0 0 1

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM90of475TABLE 13 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL SUMMARY OF MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- GROUP : 1 2 3 4 5

-----------------------------------------------------------------------------------------------------------------------------------

NUMBER EXAMINED 24 24 24 24 24

DIED GESTATION DAY 18 0 0 0 0 1 THYMUS: AREA(S), DARK RED 0 0 0 1 1 DIED GESTATION DAY 20 0 0 0 0 1 DIED GESTATION DAY 13 0 0 0 1 0 LIVER: MOTTLED 0 1 0 0 1 GALLBLADDER: CONTENTS, DARK RED 0 0 0 1 0 LIVER: ACCESSORY LOBULE(S) 0 0 0 1 0 ORGAN DAMAGED AT NECROPSY 2 1 0 0 0 SPLEEN: SWOLLEN 1 0 0 0 1 HEART: PALE 0 0 0 1 0 ABORTED GESTATION DAY 29 0 0 0 0 1 BRAIN: HYDROCEPHALY 0 0 0 1 0 DIED GESTATION DAY 27 0 0 0 1 0 ABORTED GESTATION DAY 28 0 0 0 1 0 UTERUS: CONTENTS, GREEN 0 0 0 1 0 EUTHANIZED GESTATION DAY 28 0 0 0 1 0 DELIVERED GESTATION DAY 29 0 0 0 0 1

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM PMGSIv4.04 05/29/2008 R:05/29/200891of475TABLE 14 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF FETAL DATA AT SCHEDULED NECROPSY

----------------------------------------------------------------------------------------------------------------------------------- POST PRE FETAL NO. OF SEX VIABLE DEAD RESORPTIONS IMPLANTATION IMPLANTATION CORPORA IMPLANTATION WEIGHTS GRAVID GROUP M F FETUSES FETUSES EARLY LATE LOSS SITES LUTEA LOSS IN GRAMS FEMALES

-----------------------------------------------------------------------------------------------------------------------------------

1 TOTAL 101 105 206 0 9 1 10 216 230 14 NA 24 MEAN 4.2 4.4 8.6 0.0 0.4 0.0 0.4 9.0 9.6 0.6 41.9 S.D. 1.72 1.76 1.67 0.00 0.77 0.20 0.78 1.53 1.64 0.58 4.75 S.E. 0.35 0.36 0.34 0.00 0.16 0.04 0.16 0.31 0.33 0.12 0.97

2 TOTAL 103 88 191 0 11 13 24 215 235 20 NA 23 MEAN 4.5 3.8 8.3 0.0 0.5 0.6 1.0 9.3 10.2 0.9 39.6 S.D. 1.90 1.67 2.20 0.00 0.90 2.09 2.16 1.85 1.93 0.97 4.05 S.E. 0.40 0.35 0.46 0.00 0.19 0.43 0.45 0.39 0.40 0.20 0.84

3 TOTAL 96 110 206 0 11 1 12 218 240 22 NA 24 MEAN 4.0 4.6 8.6 0.0 0.5 0.0 0.5 9.1 10.0 0.9 39.0 S.D. 1.87 1.91 1.77 0.00 1.28 0.20 1.29 1.50 1.44 1.28 3.99 S.E. 0.38 0.39 0.36 0.00 0.26 0.04 0.26 0.31 0.29 0.26 0.82

4 TOTAL 77 76 153 0 12 1 13 166 177 11 NA 18 MEAN 4.3 4.2 8.5 0.0 0.7 0.1 0.7 9.2 9.8 0.6 38.4 S.D. 2.19 2.05 2.09 0.00 1.33 0.24 1.32 2.10 2.38 0.85 7.03 S.E. 0.52 0.48 0.49 0.00 0.31 0.06 0.31 0.50 0.56 0.20 1.66

5 TOTAL 65 67 132 0 4 4 8 140 150 10 NA 14 MEAN 4.6 4.8 9.4 0.0 0.3 0.3 0.6 10.0 10.7 0.7 37.8 S.D. 1.82 1.63 1.70 0.00 0.61 0.83 0.94 1.66 1.94 0.83 4.82 S.E. 0.49 0.43 0.45 0.00 0.16 0.22 0.25 0.44 0.52 0.22 1.29

----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group NA = NOT APPLICABLE MEAN NUMBER OF VIABLE FETUSES, MEAN NUMBER OF IMPLANTATION SITES, MEAN NUMBER OF CORPORA LUTEA, FETAL WEIGHTS COMPARED USING DUNNETT’S TEST

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM PLSUv5.10 06/16/200892of475TABLE 15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF FETAL DATA AT SCHEDULED NECROPSY [% PER LITTER]

----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- CORPORA LUTEA MEAN 9.6 10.2 10.0 9.8 10.7 S.D. 1.64 1.93 1.44 2.38 1.94 S.E. 0.33 0.40 0.29 0.56 0.52 N 24 23 24 18 14

IMPLANTATION SITES MEAN 9.0 9.3 9.1 9.2 10.0 S.D. 1.53 1.85 1.50 2.10 1.66 S.E. 0.31 0.39 0.31 0.50 0.44 N 24 23 24 18 14

VIABLE FETUSES (%) MEAN 95.3 89.9 94.9 92.8 94.6 % DIFFERENCE -5.7 -0.4 -2.6 -0.7 S.D. 9.15 18.57 12.89 12.70 9.09 S.E. 1.87 3.87 2.63 2.99 2.43 N 24 23 24 18 14

DEAD FETUSES (%) MEAN 0.0 0.0 0.0 0.0 0.0 S.D. 0.00 0.00 0.00 0.00 0.00 S.E. 0.00 0.00 0.00 0.00 0.00 N 24 23 24 18 14

EARLY RESORPTIONS (%) MEAN 4.3 5.3 4.7 6.7 2.6 S.D. 9.14 9.45 12.89 12.80 5.58 S.E. 1.87 1.97 2.63 3.02 1.49 N 24 23 24 18 14

----------------------------------------------------------------------------------------------------------------------------------- PROPORTIONAL (%) DATA COMPARED USING DUNN’S TEST CORPORA LUTEA AND IMPLANTATION SITES COMPARED USING DUNNETT’S TEST None significantly different from control group93of475TABLE 15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL SUMMARY OF FETAL DATA AT SCHEDULED NECROPSY [% PER LITTER]

----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- LATE RESORPTIONS (%) MEAN 0.4 4.7 0.4 0.5 2.8 S.D. 1.86 17.38 2.04 2.14 8.20 S.E. 0.38 3.62 0.42 0.51 2.19 N 24 23 24 18 14

TOTAL RESORPTIONS (%) MEAN 4.7 10.1 5.1 7.2 5.4 S.D. 9.15 18.57 12.89 12.70 9.09 S.E. 1.87 3.87 2.63 2.99 2.43 N 24 23 24 18 14

PRE-IMPLANTATION LOSS (%) MEAN 5.9 8.4 8.8 5.7 6.3 S.D. 5.89 8.54 12.02 7.84 6.83 S.E. 1.20 1.78 2.45 1.85 1.83 N 24 23 24 18 14

POST-IMPLANTATION LOSS (%) MEAN 4.7 10.1 5.1 7.2 5.4 S.D. 9.15 18.57 12.89 12.70 9.09 S.E. 1.87 3.87 2.63 2.99 2.43 N 24 23 24 18 14

MALES (%) MEAN 49.1 53.4 47.2 50.5 49.1 S.D. 20.65 16.18 20.89 25.54 14.62 S.E. 4.22 3.37 4.26 6.02 3.91 N 24 23 24 18 14

----------------------------------------------------------------------------------------------------------------------------------- PROPORTIONAL (%) DATA COMPARED USING DUNN’S TEST None significantly different from control group94of475TABLE 15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL SUMMARY OF FETAL DATA AT SCHEDULED NECROPSY [% PER LITTER]

----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 PPM 2500 PPM 4000 PPM 5500 PPM 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- FEMALES (%) MEAN 50.9 46.6 52.8 49.5 50.9 S.D. 20.65 16.18 20.89 25.54 14.62 S.E. 4.22 3.37 4.26 6.02 3.91 N 24 23 24 18 14

MALE FETAL WEIGHTS (g) MEAN 42.5 40.2 39.4 38.4 38.0 % DIFFERENCE -5.4 -7.3 -9.6 -10.6 S.D. 4.85 4.59 5.18 7.00 4.57 S.E. 1.01 0.96 1.08 1.70 1.22 N 23 23 23 17 14

FEMALE FETAL WEIGHTS (g) MEAN 41.3 39.1 38.4 37.5 37.4 % DIFFERENCE -5.3 -7.0 -9.2 -9.4 S.D. 5.23 4.80 3.79 7.54 6.19 S.E. 1.09 1.00 0.77 1.83 1.65 N 23 23 24 17 14

COMBINED FETAL WEIGHTS (g) MEAN 41.9 39.6 39.0 38.4 37.8 % DIFFERENCE -5.5 -6.9 -8.4 -9.8 S.D. 4.75 4.05 3.99 7.03 4.82 S.E. 0.97 0.84 0.82 1.66 1.29 N 24 23 24 18 14

----------------------------------------------------------------------------------------------------------------------------------- PROPORTIONAL (%) DATA COMPARED USING DUNN’S TEST FETAL WEIGHTS COMPARED USING DUNNETT’S TEST None significantly different from control group PLPSUv5.09 06/16/2008 R:07/08/200895of475TABLE 16 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF FETUSES AND LITTERS WITH MALFORMATIONS [ABSOLUTE NO.] DAY 29

----------------------------------------------------------------------------------------------------------------------------------- F E T U S E S L I T T E R S DOSE GROUP: 1 2 3 4 5 1 2 3 4 5

-----------------------------------------------------------------------------------------------------------------------------------

NUMBER EXAMINED EXTERNALLY 206 191 206 153 132 24 23 24 18 14 CARPAL AND/OR TARSAL FLEXURE 0 0 0 0 1 0 0 0 0 1 PAW HYPERFLEXION 0 0 0 0 1 0 0 0 0 1 MICROPHTHALMIA AND/OR ANOPHTHALMIA 0 2 0 0 0 0 1 0 0 0 SHORT TAIL 1 0 0 0 0 1 0 0 0 0

NUMBER EXAMINED VISCERALLY 206 191 206 153 132 24 23 24 18 14 KIDNEY- MALPOSITIONED 1 0 0 0 0 1 0 0 0 0 LUNGS- LOBULAR AGENESIS 1 0 2 2 0 1 0 1 1 0 BULBOUS AORTA 0 0 0 1 3 0 0 0 1 2 STENOTIC PULMONARY TRUNK 0 0 0 1 3 0 0 0 1 2 INTERRUPTED AORTIC ARCH 0 0 0 1 0 0 0 0 1 0 DIAPHRAGMATIC HERNIA 0 0 0 1 0 0 0 0 1 0 INTERVENTRICULAR SEPTAL DEFECT 0 0 0 1 3 0 0 0 1 2 TRICUSPID VALVE ABSENT 0 0 0 0 2 0 0 0 0 2

NUMBER EXAMINED SKELETALLY 206 191 206 153 132 24 23 24 18 14 RIB ANOMALY 2 0 0 1 0 2 0 0 1 0 VERTEBRAL CENTRA ANOMALY 0 1 0 0 0 0 1 0 0 0 VERTEBRAL ANOMALY WITH OR WITHOUT ASSOCIATED RIB ANOMALY 1 2 0 2 1 1 2 0 1 1 COSTAL CARTILAGE ANOMALY 0 0 0 0 1 0 0 0 0 1 STERNEBRA(E) MALALIGNED (SEVERE) 0 1 0 0 0 0 1 0 0 0

TOTAL NUMBER WITH MALFORMATIONS EXTERNAL : 1 2 0 0 1 1 1 0 0 1 SOFT TISSUE: 2 0 2 5 3 2 0 1 4 2 SKELETAL : 3 4 0 3 1 2 4 0 2 1

COMBINED : 6 5 2 8 5 4 4 1 5 4

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- PMALv5.05 07/02/200896of475TABLE 17 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF LITTER PROPORTIONS OF MALFORMATIONS % PER LITTER DAY 29

----------------------------------------------------------------------------------------------------------------------------------- DOSE GROUP: 1 2 3 4 5

----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF LITTERS EXAMINED EXTERNALLY 24 23 24 18 14

CARPAL AND/OR TARSAL FLEXURE MEAN 0.0 0.0 0.0 0.0 0.6 S.D. 0.00 0.00 0.00 0.00 2.43 S.E. 0.00 0.00 0.00 0.00 0.65

PAW HYPERFLEXION MEAN 0.0 0.0 0.0 0.0 0.6 S.D. 0.00 0.00 0.00 0.00 2.43 S.E. 0.00 0.00 0.00 0.00 0.65

MICROPHTHALMIA AND/OR ANOPHTHALMIA MEAN 0.0 0.8 0.0 0.0 0.0 S.D. 0.00 3.79 0.00 0.00 0.00 S.E. 0.00 0.79 0.00 0.00 0.00

SHORT TAIL MEAN 0.8 0.0 0.0 0.0 0.0 S.D. 4.08 0.00 0.00 0.00 0.00 S.E. 0.83 0.00 0.00 0.00 0.00

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM MODIFIED STATISTICS USED. * INDICATES PARAMETRIC ANALYSIS AND + INDICATES NON-PARAMETRIC ANALYSIS. None significantly different from control group97of475TABLE 17 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL SUMMARY OF LITTER PROPORTIONS OF MALFORMATIONS % PER LITTER DAY 29

----------------------------------------------------------------------------------------------------------------------------------- DOSE GROUP: 1 2 3 4 5

----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF LITTERS EXAMINED VISCERALLY 24 23 24 18 14

KIDNEY- MALPOSITIONED MEAN 0.8 0.0 0.0 0.0 0.0 S.D. 4.08 0.00 0.00 0.00 0.00 S.E. 0.83 0.00 0.00 0.00 0.00

LUNGS- LOBULAR AGENESIS MEAN 0.5 0.0 1.0 1.4 0.0 S.D. 2.27 0.00 5.10 5.89 0.00 S.E. 0.46 0.00 1.04 1.39 0.00

BULBOUS AORTA MEAN 0.0 0.0 0.0 0.8 2.4 S.D. 0.00 0.00 0.00 3.37 6.43 S.E. 0.00 0.00 0.00 0.79 1.72

STENOTIC PULMONARY TRUNK MEAN 0.0 0.0 0.0 0.8 2.4 S.D. 0.00 0.00 0.00 3.37 6.43 S.E. 0.00 0.00 0.00 0.79 1.72

INTERRUPTED AORTIC ARCH MEAN 0.0 0.0 0.0 1.1 0.0 S.D. 0.00 0.00 0.00 4.71 0.00 S.E. 0.00 0.00 0.00 1.11 0.00

DIAPHRAGMATIC HERNIA MEAN 0.0 0.0 0.0 0.6 0.0 S.D. 0.00 0.00 0.00 2.62 0.00 S.E. 0.00 0.00 0.00 0.62 0.00

INTERVENTRICULAR SEPTAL DEFECT MEAN 0.0 0.0 0.0 0.8 2.4 S.D. 0.00 0.00 0.00 3.37 6.43 S.E. 0.00 0.00 0.00 0.79 1.72

TRICUSPID VALVE ABSENT MEAN 0.0 0.0 0.0 0.0 1.6 S.D. 0.00 0.00 0.00 0.00 4.03 S.E. 0.00 0.00 0.00 0.00 1.08

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM MODIFIED STATISTICS USED. * INDICATES PARAMETRIC ANALYSIS AND + INDICATES NON-PARAMETRIC ANALYSIS. None significantly different from control group98of475TABLE 17 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL SUMMARY OF LITTER PROPORTIONS OF MALFORMATIONS % PER LITTER DAY 29

----------------------------------------------------------------------------------------------------------------------------------- DOSE GROUP: 1 2 3 4 5

----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF LITTERS EXAMINED SKELETALLY 24 23 24 18 14

RIB ANOMALY MEAN 0.9 0.0 0.0 0.7 0.0 S.D. 3.14 0.00 0.00 2.95 0.00 S.E. 0.64 0.00 0.00 0.69 0.00

VERTEBRAL CENTRA ANOMALY MEAN 0.0 0.4 0.0 0.0 0.0 S.D. 0.00 1.90 0.00 0.00 0.00 S.E. 0.00 0.40 0.00 0.00 0.00

VERTEBRAL ANOMALY WITH OR WITHOUT ASSOCIATED RIB ANOMALY MEAN 0.5 1.0 0.0 0.9 0.8 S.D. 2.27 3.20 0.00 3.63 2.97 S.E. 0.46 0.67 0.00 0.85 0.79

COSTAL CARTILAGE ANOMALY MEAN 0.0 0.0 0.0 0.0 0.8 S.D. 0.00 0.00 0.00 0.00 2.97 S.E. 0.00 0.00 0.00 0.00 0.79

STERNEBRA(E) MALALIGNED (SEVERE) MEAN 0.0 0.5 0.0 0.0 0.0 S.D. 0.00 2.32 0.00 0.00 0.00 S.E. 0.00 0.48 0.00 0.00 0.00

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM MODIFIED STATISTICS USED. * INDICATES PARAMETRIC ANALYSIS AND + INDICATES NON-PARAMETRIC ANALYSIS. None significantly different from control group99of475TABLE 17 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL SUMMARY OF LITTER PROPORTIONS OF MALFORMATIONS % PER LITTER DAY 29

----------------------------------------------------------------------------------------------------------------------------------- DOSE GROUP: 1 2 3 4 5

----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF LITTERS EXAMINED 24 23 24 18 14

TOTAL MALFORMATIONS

PERCENT PER LITTER WITH EXTERNAL MALFORMATIONS MEAN 0.8 0.8 0.0 0.0 0.6 S.D. 4.08 3.79 0.00 0.00 2.43 S.E. 0.83 0.79 0.00 0.00 0.65

PERCENT PER LITTER WITH SOFT TISSUE MALFORMATIONS MEAN 1.3 0.0 1.0 3.9 2.4 S.D. 4.58 0.00 5.10 7.96 6.43 S.E. 0.94 0.00 1.04 1.88 1.72

PERCENT PER LITTER WITH SKELETAL MALFORMATIONS MEAN 1.4 1.8 0.0 1.5 0.8 S.D. 4.98 4.13 0.00 4.54 2.97 S.E. 1.02 0.86 0.00 1.07 0.79

TOTAL PERCENT PER LITTER WITH MALFORMATIONS MEAN 3.5 2.2 1.0 5.5 3.8 S.D. 8.05 5.16 5.10 10.39 6.90 S.E. 1.64 1.08 1.04 2.45 1.84

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM MODIFIED STATISTICS USED. * INDICATES PARAMETRIC ANALYSIS AND + INDICATES NON-PARAMETRIC ANALYSIS. None significantly different from control group PMALKv5.06 07/02/2008100of475TABLE 18 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF FETUSES AND LITTERS WITH VARIATIONS [ABSOLUTE NO.] DAY 29

----------------------------------------------------------------------------------------------------------------------------------- F E T U S E S L I T T E R S DOSE GROUP: 1 2 3 4 5 1 2 3 4 5

-----------------------------------------------------------------------------------------------------------------------------------

NUMBER EXAMINED EXTERNALLY 206 191 206 153 132 24 23 24 18 14 NUMBER WITH FINDINGS 0 0 0 0 0 0 0 0 0 0

NUMBER EXAMINED VISCERALLY 206 191 206 153 132 24 23 24 18 14 RETROCAVAL URETER 3 3 2 2 6 3 3 2 2 4 HEART- EXTRA PAPILLARY MUSCLE 13 5 5 7 3 7 4 3 4 2 MAJOR BLOOD VESSEL VARIATION 21 13 6 10 11 10 6 4 6 6 ACCESSORY SPLEEN(S) 30 21 20 27 21 15 12 11 13 9 SPLEEN- SMALL 1 0 0 0 0 1 0 0 0 0 RENAL PAPILLA(E) NOT DEVELOPED AND/OR DISTENDED URETER(S) 1 0 0 0 2 1 0 0 0 1 GALLBLADDER- ABSENT OR SMALL 6 1 6 4 0 4 1 3 3 0 HEART- ONLY TWO PAPILLARY MUSCLES PRESENT 2 2 0 0 1 1 1 0 0 1 LUNGS- SMALL 0 0 0 1 1 0 0 0 1 1 PANCREAS- SMALL 0 0 0 1 0 0 0 0 1 0 KIDNEY(S)- PALE 1 0 0 0 0 1 0 0 0 0 SKELETAL MUSCLE- THICKENED 0 1 0 0 0 0 1 0 0 0 EXTRA FAT PADS 0 1 0 0 0 0 1 0 0 0 KIDNEY(S)- MISSHAPEN 0 1 0 0 0 0 1 0 0 0

NUMBER EXAMINED SKELETALLY 206 191 206 153 132 24 23 24 18 14 HYOID ARCH(ES) BENT 22 13 46 35 33 12 8 17 15 11 13TH RUDIMENTARY RIB(S) 31 31 36 27 24 18 17 20 14 11 STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED 25 18 21 26 16 10 9 13 11 8 13TH FULL RIB(S) 66 65 64 68 52 22 15 21 16 13 HYOID BODY AND/OR ARCH(ES) UNOSSIFIED 0 1 3 10 4 0 1 1 4 3 7TH CERVICAL RIB(S) 0 8 1 1 0 0 3 1 1 0 27 PRESACRAL VERTEBRAE 20 14 10 18 17 12 7 6 9 7 EXTRA SITE OF OSSIFICATION VENTRAL TO CERVICAL CENTRUM #2 3 0 1 0 2 2 0 1 0 2

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM

-----------------------------------------------------------------------------------------------------------------------------------101of475TABLE 18 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL SUMMARY OF FETUSES AND LITTERS WITH VARIATIONS [ABSOLUTE NO.] DAY 29

----------------------------------------------------------------------------------------------------------------------------------- F E T U S E S L I T T E R S DOSE GROUP: 1 2 3 4 5 1 2 3 4 5

-----------------------------------------------------------------------------------------------------------------------------------

NUMBER EXAMINED SKELETALLY 206 191 206 153 132 24 23 24 18 14 7TH STERNEBRA 2 0 0 0 1 2 0 0 0 1 STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) 3 2 0 0 7 3 2 0 0 4 STERNEBRAE WITH THREAD-LIKE ATTACHMENT 4 3 1 0 1 3 2 1 0 1 ACCESSORY SKULL BONE(S) 0 0 1 0 3 0 0 1 0 2 PUBIS UNOSSIFIED 0 0 1 1 0 0 0 1 1 0 EXTRA SITE OF OSSIFICATION ANTERIOR TO STERNEBRA #1 2 3 2 1 2 2 2 2 1 2 REDUCED OSSIFICATION OF THE RIB(S) 1 0 0 0 0 1 0 0 0 0 STERNEBRA(E) #1,#2,#3 AND/OR #4 UNOSSIFIED 1 0 0 0 0 1 0 0 0 0 REDUCED OSSIFICATION OF THE SKULL 0 0 0 5 1 0 0 0 1 1

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- PMALv5.05 07/02/2008102of475TABLE 19 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL SUMMARY OF LITTER PROPORTIONS OF VARIATIONS % PER LITTER DAY 29

----------------------------------------------------------------------------------------------------------------------------------- DOSE GROUP: 1 2 3 4 5

----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF LITTERS EXAMINED EXTERNALLY 24 23 24 18 14 NUMBER OF LITTERS WITH FINDINGS 0 0 0 0 0

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM MODIFIED STATISTICS USED. * INDICATES PARAMETRIC ANALYSIS AND + INDICATES NON-PARAMETRIC ANALYSIS. None significantly different from control group103of475TABLE 19 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL SUMMARY OF LITTER PROPORTIONS OF VARIATIONS % PER LITTER DAY 29

----------------------------------------------------------------------------------------------------------------------------------- DOSE GROUP: 1 2 3 4 5

----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF LITTERS EXAMINED VISCERALLY 24 23 24 18 14

RETROCAVAL URETER MEAN 1.7 1.4 1.1 1.2 4.4 S.D. 4.62 3.61 3.79 3.73 7.42 S.E. 0.94 0.75 0.77 0.88 1.98

HEART- EXTRA PAPILLARY MUSCLE MEAN 6.4 2.4 2.1 5.0 2.3 S.D. 10.96 5.62 6.65 11.04 6.32 S.E. 2.24 1.17 1.36 2.60 1.69

MAJOR BLOOD VESSEL VARIATION MEAN 11.0 6.1 3.2 6.3 7.7 S.D. 16.39 12.93 7.42 11.47 10.38 S.E. 3.35 2.70 1.51 2.70 2.77

ACCESSORY SPLEEN(S) MEAN 15.9 10.8 11.2 17.4 16.2 S.D. 17.71 14.19 16.04 15.41 19.27 S.E. 3.62 2.96 3.27 3.63 5.15

SPLEEN- SMALL MEAN 0.8 0.0 0.0 0.0 0.0 S.D. 4.08 0.00 0.00 0.00 0.00 S.E. 0.83 0.00 0.00 0.00 0.00

RENAL PAPILLA(E) NOT DEVELOPED AND/OR DISTENDED URETER(S) MEAN 0.8 0.0 0.0 0.0 1.4 S.D. 4.08 0.00 0.00 0.00 5.35 S.E. 0.83 0.00 0.00 0.00 1.43

GALLBLADDER- ABSENT OR SMALL MEAN 3.1 0.5 2.4 2.8 0.0 S.D. 7.20 2.61 7.13 7.39 0.00 S.E. 1.47 0.54 1.45 1.74 0.00

HEART- ONLY TWO PAPILLARY MUSCLES PRESENT MEAN 0.8 1.2 0.0 0.0 0.8 S.D. 4.08 5.96 0.00 0.00 2.97 S.E. 0.83 1.24 0.00 0.00 0.79

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM MODIFIED STATISTICS USED. * INDICATES PARAMETRIC ANALYSIS AND + INDICATES NON-PARAMETRIC ANALYSIS. None significantly different from control group104of475TABLE 19 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL SUMMARY OF LITTER PROPORTIONS OF VARIATIONS % PER LITTER DAY 29

----------------------------------------------------------------------------------------------------------------------------------- DOSE GROUP: 1 2 3 4 5

----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF LITTERS EXAMINED VISCERALLY 24 23 24 18 14

LUNGS- SMALL MEAN 0.0 0.0 0.0 0.8 0.8 S.D. 0.00 0.00 0.00 3.37 2.97 S.E. 0.00 0.00 0.00 0.79 0.79

PANCREAS- SMALL MEAN 0.0 0.0 0.0 0.7 0.0 S.D. 0.00 0.00 0.00 2.95 0.00 S.E. 0.00 0.00 0.00 0.69 0.00

KIDNEY(S)- PALE MEAN 0.4 0.0 0.0 0.0 0.0 S.D. 2.04 0.00 0.00 0.00 0.00 S.E. 0.42 0.00 0.00 0.00 0.00

SKELETAL MUSCLE- THICKENED MEAN 0.0 0.4 0.0 0.0 0.0 S.D. 0.00 2.09 0.00 0.00 0.00 S.E. 0.00 0.43 0.00 0.00 0.00

EXTRA FAT PADS MEAN 0.0 0.4 0.0 0.0 0.0 S.D. 0.00 2.09 0.00 0.00 0.00 S.E. 0.00 0.43 0.00 0.00 0.00

KIDNEY(S)- MISSHAPEN MEAN 0.0 2.2 0.0 0.0 0.0 S.D. 0.00 10.43 0.00 0.00 0.00 S.E. 0.00 2.17 0.00 0.00 0.00

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM MODIFIED STATISTICS USED. * INDICATES PARAMETRIC ANALYSIS AND + INDICATES NON-PARAMETRIC ANALYSIS. None significantly different from control group105of475TABLE 19 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL SUMMARY OF LITTER PROPORTIONS OF VARIATIONS % PER LITTER DAY 29

----------------------------------------------------------------------------------------------------------------------------------- DOSE GROUP: 1 2 3 4 5

----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF LITTERS EXAMINED SKELETALLY 24 23 24 18 14

HYOID ARCH(ES) BENT MEAN 11.8 6.9 25.2 24.1 24.1 S.D. 16.28 12.22 28.01 18.17 22.93 S.E. 3.32 2.55 5.72 4.28 6.13

13TH RUDIMENTARY RIB(S) MEAN 15.5 16.2 18.7 18.9 18.5 S.D. 13.02 13.99 14.84 15.86 11.83 S.E. 2.66 2.92 3.03 3.74 3.16

STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED MEAN 11.4 8.5 10.1 16.6 11.1 S.D. 22.44 13.60 11.85 21.18 13.19 S.E. 4.58 2.84 2.42 4.99 3.53

13TH FULL RIB(S) MEAN 31.9 33.2 30.4 44.1 39.3 S.D. 18.53 34.57 24.20 30.31 30.18 S.E. 3.78 7.21 4.94 7.14 8.06

HYOID BODY AND/OR ARCH(ES) UNOSSIFIED MEAN 0.0 0.5 1.3 5.2 2.8 S.D. 0.00 2.61 6.12 11.89 6.04 S.E. 0.00 0.54 1.25 2.80 1.61

7TH CERVICAL RIB(S) MEAN 0.0 3.5 0.4 0.7 0.0 S.D. 0.00 10.52 2.04 2.95 0.00 S.E. 0.00 2.19 0.42 0.69 0.00

27 PRESACRAL VERTEBRAE MEAN 9.5 6.9 4.5 13.7 13.0 S.D. 10.91 14.33 9.83 21.08 16.70 S.E. 2.23 2.99 2.01 4.97 4.46

EXTRA SITE OF OSSIFICATION VENTRAL TO CERVICAL CENTRUM #2 MEAN 1.4 0.0 0.4 0.0 1.7 S.D. 4.91 0.00 2.04 0.00 4.30 S.E. 1.00 0.00 0.42 0.00 1.15

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM MODIFIED STATISTICS USED. * INDICATES PARAMETRIC ANALYSIS AND + INDICATES NON-PARAMETRIC ANALYSIS. None significantly different from control group106of475TABLE 19 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL SUMMARY OF LITTER PROPORTIONS OF VARIATIONS % PER LITTER DAY 29

----------------------------------------------------------------------------------------------------------------------------------- DOSE GROUP: 1 2 3 4 5

----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF LITTERS EXAMINED SKELETALLY 24 23 24 18 14

7TH STERNEBRA MEAN 1.1 0.0 0.0 0.0 0.9 S.D. 3.62 0.00 0.00 0.00 3.34 S.E. 0.74 0.00 0.00 0.00 0.89

STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) MEAN 1.3 1.0 0.0 0.0 5.1 S.D. 3.63 3.41 0.00 0.00 11.02 S.E. 0.74 0.71 0.00 0.00 2.95

STERNEBRAE WITH THREAD-LIKE ATTACHMENT MEAN 2.2 1.2 0.5 0.0 1.0 S.D. 6.19 4.24 2.55 0.00 3.82 S.E. 1.26 0.88 0.52 0.00 1.02

ACCESSORY SKULL BONE(S) MEAN 0.0 0.0 0.4 0.0 2.8 S.D. 0.00 0.00 2.04 0.00 7.89 S.E. 0.00 0.00 0.42 0.00 2.11

PUBIS UNOSSIFIED MEAN 0.0 0.0 0.4 0.5 0.0 S.D. 0.00 0.00 2.04 2.14 0.00 S.E. 0.00 0.00 0.42 0.51 0.00

EXTRA SITE OF OSSIFICATION ANTERIOR TO STERNEBRA #1 MEAN 1.1 1.5 0.9 0.5 1.5 S.D. 3.89 5.21 3.20 2.14 3.84 S.E. 0.79 1.09 0.65 0.51 1.03

REDUCED OSSIFICATION OF THE RIB(S) MEAN 0.5 0.0 0.0 0.0 0.0 S.D. 2.27 0.00 0.00 0.00 0.00 S.E. 0.46 0.00 0.00 0.00 0.00

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM MODIFIED STATISTICS USED. * INDICATES PARAMETRIC ANALYSIS AND + INDICATES NON-PARAMETRIC ANALYSIS. None significantly different from control group107of475TABLE 19 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 6 SPONSOR:HONEYWELL SUMMARY OF LITTER PROPORTIONS OF VARIATIONS % PER LITTER DAY 29

----------------------------------------------------------------------------------------------------------------------------------- DOSE GROUP: 1 2 3 4 5

----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF LITTERS EXAMINED SKELETALLY 24 23 24 18 14

STERNEBRA(E) #1,#2,#3 AND/OR #4 UNOSSIFIED MEAN 0.5 0.0 0.0 0.0 0.0 S.D. 2.27 0.00 0.00 0.00 0.00 S.E. 0.46 0.00 0.00 0.00 0.00

REDUCED OSSIFICATION OF THE SKULL MEAN 0.0 0.0 0.0 2.5 0.7 S.D. 0.00 0.00 0.00 10.71 2.67 S.E. 0.00 0.00 0.00 2.53 0.71

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM MODIFIED STATISTICS USED. * INDICATES PARAMETRIC ANALYSIS AND + INDICATES NON-PARAMETRIC ANALYSIS. None significantly different from control group108of475TABLE 19 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 7 SPONSOR:HONEYWELL SUMMARY OF LITTER PROPORTIONS OF VARIATIONS % PER LITTER DAY 29

----------------------------------------------------------------------------------------------------------------------------------- DOSE GROUP: 1 2 3 4 5

----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF LITTERS EXAMINED 24 23 24 18 14

TOTAL VARIATIONS

PERCENT PER LITTER WITH EXTERNAL VARIATIONS MEAN 0.0 0.0 0.0 0.0 0.0 S.D. 0.00 0.00 0.00 0.00 0.00 S.E. 0.00 0.00 0.00 0.00 0.00

PERCENT PER LITTER WITH SOFT TISSUE VARIATIONS MEAN 29.8 22.5 17.8 28.8 29.8 S.D. 25.62 19.41 17.81 25.23 17.54 S.E. 5.23 4.05 3.64 5.95 4.69

PERCENT PER LITTER WITH SKELETAL VARIATIONS MEAN 62.0 59.8 68.0 73.5 75.3 S.D. 21.85 30.51 22.89 25.96 21.27 S.E. 4.46 6.36 4.67 6.12 5.68

TOTAL PERCENT PER LITTER WITH VARIATIONS MEAN 72.4 68.7 73.2 80.7 82.7 S.D. 21.79 22.38 21.86 21.50 15.91 S.E. 4.45 4.67 4.46 5.07 4.25

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 5500 PPM 5- 7500 PPM MODIFIED STATISTICS USED. * INDICATES PARAMETRIC ANALYSIS AND + INDICATES NON-PARAMETRIC ANALYSIS. None significantly different from control group PMALKv5.06 07/02/2008109of475

## WIL-447022 HFO-1234yf Honeywell International Inc.



# APPENDIX A

Individual Animal Data

110 of 475TABLE A1 (PHASE I - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022F INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

NO SIGNIFICANT CLINICAL OBSERVATIONS 53748 1 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 P P P 53752 1 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 P P P 53735 1 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 P P P 53742 1 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 P P P 53726 1 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 P P P 53738 1 P P P P P P P P P P P P 53739 1 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 P P 53783 1 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 P P P P 53780 1 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 P P P P 53758 1 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 P P P 53760 1 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 P P P P 53763 1 P P P P P P P P P 53736 2 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 P 53741 2 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 P 53729 2 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 P P P 53737 2 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 P P P 53745 2 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 53744 2 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 P P 53782 2 P P P P P P P P P P P P P P P P P P P P P P 53759 2 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 P P P P 53779 2 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 P P P 53757 2 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 P P P P 53753 2 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 P P P P 53778 2 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 P P P P 53747 3 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 P P P 53751 3 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 P P P 53749 3 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 P

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 7500 PPM 5-4000 PPM DUPONT111of475TABLE A1 (PHASE I - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022F INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

NO SIGNIFICANT CLINICAL OBSERVATIONS 53743 3 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 P P P 53733 3 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 P P P 53731 3 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 P P P 53768 3 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 P P P P 53762 3 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 P P P P 53766 3 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 P P P P 53755 3 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 P P P P 53765 3 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 P P P P 53764 3 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 P P P P 53730 4 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 P P P 53732 4 P P P P P P P P P 53725 4 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 P P 53727 4 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 P P 53722 4 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 P P 53770 4 P P P P P P P P P P P P P P P P P P P P P P P P 53781 4 P P P P P P P P P P P P P P 53772 4 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 P P P P 53773 4 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 P P P P 53776 4 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 P P P P 53771 4 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 P P P P 53777 4 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 P P P P 53750 5 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 P P P 53740 5 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 P P 53728 5 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 53724 5 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 P P P 53723 5 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 P P P 53734 5 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 P P P

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 7500 PPM 5-4000 PPM DUPONT112of475TABLE A1 (PHASE I - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022F INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

NO SIGNIFICANT CLINICAL OBSERVATIONS 53769 5 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 P P P 53774 5 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 P P P 53754 5 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 P 53761 5 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 P P 53775 5 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 P P P P 53756 5 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 P P P P

FOUND DEAD 53732 4 P 53781 4 P

ABORTED; SENT TO NECROPSY 53770 4 P

SCHEDULED EUTHANASIA; GESTATION DAY 29 53748 1 P 53752 1 P 53735 1 P 53742 1 P 53726 1 P 53738 1 P 53739 1 P 53783 1 P 53780 1 P 53758 1 P 53760 1 P 53763 1 P 53736 2 P 53741 2 P 53729 2 P

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 7500 PPM 5-4000 PPM DUPONT113of475TABLE A1 (PHASE I - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022F INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

SCHEDULED EUTHANASIA; GESTATION DAY 29 53737 2 P 53745 2 P 53744 2 P 53782 2 P 53759 2 P 53779 2 P 53757 2 P 53753 2 P 53778 2 P 53747 3 P 53751 3 P 53749 3 P 53743 3 P 53733 3 P 53731 3 P 53768 3 P 53762 3 P 53766 3 P 53755 3 P 53765 3 P 53764 3 P 53730 4 P 53725 4 P 53727 4 P 53722 4 P 53772 4 P 53773 4 P

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 7500 PPM 5-4000 PPM DUPONT114of475TABLE A1 (PHASE I - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022F INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

SCHEDULED EUTHANASIA; GESTATION DAY 29 53776 4 P 53771 4 P 53777 4 P 53750 5 P 53740 5 P 53728 5 P 53724 5 P 53723 5 P 53734 5 P 53769 5 P 53774 5 P 53754 5 P 53761 5 P 53775 5 P 53756 5 P

HAIR LOSS LEFT HINDLIMB 53738 1 1 1 1 1 1 1 1 1 1 1 1

HAIR LOSS LEFT INGUINAL AREA 53738 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

HAIR LOSS RIGHT FORELIMB 53754 5 1

HAIR LOSS LEFT FORELIMB 53763 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 53769 5 1 53774 5 1 53754 5 1

DRIED RED MATERIAL LEFT HINDLIMB 53732 4 1

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 7500 PPM 5-4000 PPM DUPONT115of475TABLE A1 (PHASE I - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022F INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 6 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

DRIED BROWN MATERIAL UROGENITAL AREA 53754 5 2 2

HAIR LOSS UROGENITAL AREA 53741 2 1 1 53745 2 1 1 1

HAIR LOSS RIGHT INGUINAL AREA 53741 2 1 1

HAIR LOSS VENTRAL NECK 53722 4 1

HAIR LOSS RIGHT LATERAL ABDOMINAL AREA 53782 2 1

LACERATION NOSE 53736 2 P P

DRIED RED MATERIAL AROUND NOSE 53736 2 3 1

WET RED MATERIAL AROUND NOSE 53736 2 2

SOFT STOOL 53739 1 P 53758 1 P 53736 2 P 53744 2 P 53782 2 P P 53779 2 P 53727 4 P 53740 5 P 53754 5 P

DECREASED DEFECATION 53782 2 P P P P

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 7500 PPM 5-4000 PPM DUPONT116of475TABLE A1 (PHASE I - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022F INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 7 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

DECREASED DEFECATION 53749 3 P P 53725 4 P 53770 4 P 53728 5 P P P 53754 5 P 53761 5 P P

FECES SMALL 53782 2 P

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 7500 PPM 5-4000 PPM DUPONT PCOv3.13 05/20/2008117of475TABLE A2 (PHASE II - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022D INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

NO SIGNIFICANT CLINICAL OBSERVATIONS 54169 1 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 P P P 54117 1 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 P P 54124 1 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 P P 54128 1 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 P P 54129 1 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 P P 54137 1 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 P P 54143 1 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 P P P 54147 1 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 P 54153 1 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 P P P 54157 1 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 P P P 54166 1 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 P P P 54167 1 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 P P P 54119 2 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 P P 54120 2 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 P 54123 2 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 54131 2 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 P P 54139 2 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 P P P 54141 2 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 P P P 54146 2 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 P P P 54148 2 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 P P P 54152 2 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 P P P 54156 2 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 P P 54159 2 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 P P P 54160 2 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 P P P 54107 3 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 54116 3 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 P P 54121 3 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 P P

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 5500 PPM 4- 7500 PPM 5-5500 PPM DUPONT118of475TABLE A2 (PHASE II - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022D INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

NO SIGNIFICANT CLINICAL OBSERVATIONS 54122 3 P P P P P P P P P P P P 54127 3 P P P P P P P P P P P P P P P P P P 54133 3 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 P P 54134 3 P P P P P P P P P P P P P P P P 54142 3 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 P P P 54149 3 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 P P P 54161 3 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 P P P 54163 3 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 P P 54164 3 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 P P P 54108 4 P P P P P P P P P P P P P 54111 4 P P P P P P P P P P P P 54112 4 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 P P 54114 4 P P P P P P P P P P P P P P 54115 4 P P P P P P P P P P P P 54132 4 P P P P P P P P P P P P P P 54135 4 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 P P 54138 4 P P P P P P P P P P P P 54140 4 P P P P P P P P P P P P P P P P P P P P 54150 4 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 P P P 54151 4 P P P P P P P P P P P P P P P P P P 54165 4 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 P 54113 5 P P P P P 54125 5 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 54126 5 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 P 54130 5 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 54136 5 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 P 54144 5 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

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 5500 PPM 4- 7500 PPM 5-5500 PPM DUPONT119of475TABLE A2 (PHASE II - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022D INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

NO SIGNIFICANT CLINICAL OBSERVATIONS 54145 5 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 P P P 54155 5 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 P P P 54158 5 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 P P P 54162 5 P P P P P P P P P P P P P P P P P P P P P P P 54168 5 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 P P P 54170 5 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 P P P

EUTHANIZED IN EXTREMIS 54114 4 P 54125 5 P

FOUND DEAD 54122 3 P 54115 4 P 54132 4 P 54138 4 P 54151 4 P 54113 5 P 54144 5 P

ABORTED; SENT TO NECROPSY 54107 3 P 54111 4 P 54165 4 P

DELIVERED; SENT TO NECROPSY 54140 4 P

SCHEDULED EUTHANASIA; GESTATION DAY 29 54169 1 P 54117 1 P 54124 1 P

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 5500 PPM 4- 7500 PPM 5-5500 PPM DUPONT120of475TABLE A2 (PHASE II - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022D INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

SCHEDULED EUTHANASIA; GESTATION DAY 29 54128 1 P 54129 1 P 54137 1 P 54143 1 P 54147 1 P 54153 1 P 54157 1 P 54166 1 P 54167 1 P 54119 2 P 54120 2 P 54123 2 P 54131 2 P 54139 2 P 54141 2 P 54146 2 P 54148 2 P 54152 2 P 54156 2 P 54159 2 P 54160 2 P 54116 3 P 54121 3 P 54127 3 P 54133 3 P 54134 3 P 54142 3 P

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 5500 PPM 4- 7500 PPM 5-5500 PPM DUPONT121of475TABLE A2 (PHASE II - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022D INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

SCHEDULED EUTHANASIA; GESTATION DAY 29 54149 3 P 54161 3 P 54163 3 P 54164 3 P 54108 4 P 54112 4 P 54135 4 P 54150 4 P 54126 5 P 54130 5 P 54136 5 P 54145 5 P 54155 5 P 54158 5 P 54162 5 P 54168 5 P 54170 5 P

HYPOACTIVITY 54125 5 P

HAIR LOSS LEFT HINDLIMB 54127 3 1 1 1 1 1 1 1 1 54111 4 1 1 1 1

HAIR LOSS RIGHT HINDLIMB 54140 4 1 1 1 1 1

HAIR LOSS UROGENITAL AREA 54111 4 2 2 54140 4 1 1 1 1 2

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 5500 PPM 4- 7500 PPM 5-5500 PPM DUPONT122of475TABLE A2 (PHASE II - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022D INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 6 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

HAIR LOSS UROGENITAL AREA 54113 5 1 1 1 1 1 54126 5 1

SCABBING FACIAL AREA 54134 3 P P P P P P P P P P

LACERATION FACIAL AREA 54134 3 P

HAIR LOSS RIGHT FORELIMB 54108 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1

DRIED BROWN MATERIAL ANOGENITAL AREA 54147 1 1 1 54162 5 1 1 1 1 1

HAIR LOSS LEFT FORELIMB 54108 4 1 1 1

LABORED RESPIRATION 54125 5 P

DECREASED DEFECATION 54123 2 P P 54156 2 P 54127 3 P 54163 3 P 54111 4 P P P P P P P P P P P 54132 4 P 54140 4 P 54165 4 P 54130 5 P P 54136 5 P

SOFT STOOL 54120 2 P

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 5500 PPM 4- 7500 PPM 5-5500 PPM DUPONT123of475TABLE A2 (PHASE II - DAILY EXAMINATIONS) PROJECT NO.:WIL-447022D INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 7 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

SOFT STOOL 54162 5 P P

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 5500 PPM 4- 7500 PPM 5-5500 PPM DUPONT PCOv3.13 05/29/2008124of475TABLE A3 (PHASE I - MID-POINT OF EXPOSURE) PROJECT NO.:WIL-447022F INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

HYPOACTIVITY 53770 4 P

INCREASED RESPIRATION 53773 4 P

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 4000 PPM 4- 7500 PPM 5-4000 PPM DUPONT PCOv3.13 05/20/2008 R:05/29/2008125of475TABLE A4 (PHASE II - MID-POINT OF EXPOSURE) PROJECT NO.:WIL-447022D INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

DECREASED RESPIRATION 54133 3 P P 54115 4 P 54136 5 P P

LABORED RESPIRATION 54133 3 P P 54115 4 P 54144 5 P

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 5500 PPM 4- 7500 PPM 5-5500 PPM DUPONT PCOv3.13 05/21/2008 R:05/29/2008126of475TABLE A5 (PHASE II - 1 HOUR POST-EXPOSURE) PROJECT NO.:WIL-447022D INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL CLINICAL OBSERVATIONS

----------------------------------------------------------------------------------------------------------------------------------- GESTATIONAL DAY 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 OBSERVATION ANIMAL GROUP 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

-----------------------------------------------------------------------------------------------------------------------------------

HYPOACTIVITY 54144 5 P

WET RED MATERIAL UROGENITAL AREA 54144 5 1

DECREASED RESPIRATION 54114 4 P

LABORED RESPIRATION 54151 4 P

INCREASED RESPIRATION 54143 1 P

WET CLEAR MATERIAL AROUND NOSE 54114 4 2 54132 4 1

WET CLEAR MATERIAL AROUND MOUTH 54114 4 2

----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: P = PRESENT 1 = SLIGHT 2 = MODERATE 3 = SEVERE

----------------------------------------------------------------------------------------------------------------------------------- 1- 0 PPM 2- 2500 PPM 3- 5500 PPM 4- 7500 PPM 5-5500 PPM DUPONT PCOv3.13 06/19/2008 R:06/19/2008127of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0 4 6 7 8 9 10 11 12

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 3124. 3120. 3139. 3093. 3099. 3122. 3131. 3135. 3184. 53735 G 2998. 2993. 3074. 3059. 3033. 3070. 3063. 3083. 3063. 53738 G 3317. 3197. 3352. 3347. 3347. 3357. 3400. 3405. 3408. 53739 G 3494. 3406. 3560. 3568. 3556. 3569. 3592. 3601. 3625. 53742 G 3057. 2999. 3266. 3220. 3260. 3284. 3324. 3318. 3316. 53748 G 2892. 2924. 3112. 3064. 2995. 3023. 3021. 3050. 3064. 53752 G 2962. 2927. 3106. 3103. 3097. 3130. 3158. 3182. 3188. 53758 G 3082. 3203. 3271. 3286. 3288. 3290. 3276. 3309. 3341. 53760 G 3026. 3051. 3156. 3172. 3161. 3125. 3130. 3181. 3219. 53763 G 3013. 3071. 3228. 3252. 3211. 3246. 3249. 3281. 3324. 53780 G 3141. 3294. 3402. 3395. 3413. 3474. 3486. 3472. 3522. 53783 G 3229. 3249. 3295. 3284. 3296. 3299. 3324. 3310. 3344. 54117 G 3567. 3482. 3533. 3627. 3620. 3651. 3671. 3686. 3734. 54124 G 3187. 3121. 3176. 3253. 3235. 3228. 3241. 3227. 3276. 54128 G 3313. 3202. 3258. 3317. 3301. 3304. 3314. 3348. 3380. 54129 G 3452. 3264. 3314. 3361. 3370. 3380. 3408. 3412. 3445. 54137 G 3277. 3228. 3246. 3280. 3311. 3354. 3383. 3371. 3386. 54143 G 3036. 3013. 3142. 3107. 3156. 3121. 3127. 3150. 3170. 54147 G 3330. 3296. 3541. 3481. 3493. 3527. 3530. 3536. 3558. 54153 G 2997. 2939. 3062. 3086. 3113. 3101. 3118. 3141. 3157. 54157 G 3133. 3102. 3374. 3352. 3359. 3384. 3423. 3450. 3503. 54166 G 2929. 2925. 3170. 3153. 3184. 3255. 3253. 3269. 3347. 54167 G 3199. 3228. 3437. 3318. 3354. 3382. 3403. 3410. 3436. 54169 G 2943. 2888. 2994. 3006. 2996. 3007. 3027. 3047. 3059.

MEAN 3154. 3130. 3259. 3258. 3260. 3278. 3294. 3307. 3335. S.D. 186.2 161.8 157.0 161.7 166.1 172.1 177.3 171.1 178.5 S.E. 38.0 33.0 32.0 33.0 33.9 35.1 36.2 34.9 36.4 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN128of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 13 14 15 16 17 18 19 20 21

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 3233. 3281. 3316. 3351. 3361. 3421. 3400. 3410. 3358. 53735 G 3086. 3141. 3178. 3223. 3248. 3246. 3255. 3270. 3291. 53738 G 3451. 3451. 3520. 3573. 3608. 3639. 3663. 3677. 3723. 53739 G 3648. 3655. 3685. 3718. 3719. 3768. 3737. 3763. 3787. 53742 G 3394. 3399. 3506. 3542. 3570. 3583. 3592. 3644. 3691. 53748 G 3082. 3112. 3157. 3182. 3234. 3252. 3283. 3332. 3348. 53752 G 3264. 3278. 3317. 3340. 3380. 3407. 3431. 3498. 3513. 53758 G 3334. 3359. 3424. 3441. 3452. 3458. 3501. 3511. 3528. 53760 G 3243. 3221. 3321. 3386. 3433. 3444. 3497. 3532. 3564. 53763 G 3384. 3427. 3463. 3436. 3500. 3440. 3472. 3484. 3523. 53780 G 3566. 3601. 3629. 3699. 3624. 3668. 3698. 3767. 3791. 53783 G 3346. 3412. 3482. 3484. 3490. 3495. 3526. 3536. 3559. 54117 G 3758. 3791. 3788. 3807. 3876. 3860. 3874. 3816. 3868. 54124 G 3292. 3305. 3333. 3362. 3372. 3411. 3452. 3477. 3496. 54128 G 3409. 3435. 3485. 3529. 3544. 3559. 3582. 3626. 3636. 54129 G 3476. 3498. 3541. 3577. 3590. 3616. 3581. 3612. 3610. 54137 G 3433. 3506. 3525. 3533. 3520. 3550. 3557. 3539. 3563. 54143 G 3184. 3216. 3230. 3254. 3289. 3180. 3254. 3282. 3323. 54147 G 3591. 3597. 3697. 3741. 3761. 3822. 3836. 3868. 3870. 54153 G 3163. 3187. 3229. 3254. 3284. 3319. 3311. 3324. 3360. 54157 G 3552. 3594. 3640. 3702. 3745. 3743. 3735. 3747. 3779. 54166 G 3398. 3390. 3418. 3456. 3471. 3492. 3524. 3556. 3637. 54167 G 3408. 3454. 3486. 3531. 3557. 3589. 3602. 3650. 3675. 54169 G 3060. 3080. 3140. 3156. 3194. 3225. 3249. 3288. 3314.

MEAN 3365. 3391. 3438. 3470. 3493. 3508. 3526. 3550. 3575. S.D. 182.4 182.4 179.6 184.3 179.2 188.0 178.8 174.4 178.5 S.E. 37.2 37.2 36.7 37.6 36.6 38.4 36.5 35.6 36.4 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN129of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 22 23 24 25 26 27 28 29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 3390. 3430. 3420. 3517. 3525. 3572. 3572. 3659. SCHEDULED NECROPSY DAY 29 53735 G 3308. 3329. 3368. 3384. 3387. 3339. 3317. 3375. SCHEDULED NECROPSY DAY 29 53738 G 3745. 3757. 3802. 3792. 3784. 3796. 3798. 3861. SCHEDULED NECROPSY DAY 29 53739 G 3804. 3824. 3853. 3874. 3877. 3885. 3874. 3926. SCHEDULED NECROPSY DAY 29 53742 G 3720. 3755. 3796. 3776. 3821. 3799. 3794. 3813. SCHEDULED NECROPSY DAY 29 53748 G 3347. 3415. 3429. 3469. 3501. 3471. 3434. 3454. SCHEDULED NECROPSY DAY 29 53752 G 3534. 3564. 3594. 3610. 3601. 3595. 3615. 3667. SCHEDULED NECROPSY DAY 29 53758 G 3549. 3576. 3576. 3598. 3615. 3636. 3642. 3675. SCHEDULED NECROPSY DAY 29 53760 G 3607. 3643. 3598. 3581. 3512. 3472. 3485. 3458. SCHEDULED NECROPSY DAY 29 53763 G 3517. 3559. 3547. 3573. 3619. 3642. 3645. 3593. SCHEDULED NECROPSY DAY 29 53780 G 3845. 3894. 3859. 3838. 3902. 3882. 3765. 3691. SCHEDULED NECROPSY DAY 29 53783 G 3573. 3593. 3634. 3662. 3687. 3726. 3775. 3781. SCHEDULED NECROPSY DAY 29 54117 G 3851. 3847. 3901. 3905. 3926. 3915. 3914. 3927. SCHEDULED NECROPSY DAY 29 54124 G 3510. 3563. 3583. 3626. 3657. 3660. 3683. 3714. SCHEDULED NECROPSY DAY 29 54128 G 3678. 3688. 3727. 3748. 3744. 3737. 3760. 3763. SCHEDULED NECROPSY DAY 29 54129 G 3623. 3609. 3632. 3611. 3614. 3617. 3641. 3607. SCHEDULED NECROPSY DAY 29 54137 G 3567. 3591. 3620. 3666. 3696. 3691. 3736. 3776. SCHEDULED NECROPSY DAY 29 54143 G 3305. 3334. 3352. 3388. 3383. 3392. 3443. 3448. SCHEDULED NECROPSY DAY 29 54147 G 3858. 3835. 3808. 3742. 3742. 3790. 3742. 3740. SCHEDULED NECROPSY DAY 29 54153 G 3388. 3419. 3446. 3450. 3431. 3450. 3440. 3497. SCHEDULED NECROPSY DAY 29 54157 G 3747. 3779. 3805. 3847. 3854. 3831. 3866. 3884. SCHEDULED NECROPSY DAY 29 54166 G 3576. 3633. 3614. 3596. 3573. 3508. 3468. 3447. SCHEDULED NECROPSY DAY 29 54167 G 3641. 3661. 3627. 3684. 3713. 3830. 3807. 3840. SCHEDULED NECROPSY DAY 29 54169 G 3336. 3378. 3425. 3441. 3430. 3411. 3391. 3407. SCHEDULED NECROPSY DAY 29

MEAN 3584. 3612. 3626. 3641. 3650. 3652. 3650. 3667. S.D. 175.7 166.7 164.9 152.7 162.9 171.6 170.8 173.1 S.E. 35.9 34.0 33.7 31.2 33.3 35.0 34.9 35.3 N 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN130of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0 4 6 7 8 9 10 11 12

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G 3021. 2995. 3278. 3251. 3270. 3286. 3288. 3346. 3367. 53736 G 2940. 2925. 3083. 3090. 3102. 3096. 3127. 3110. 3089. 53737 G 3054. 3090. 3163. 3141. 3191. 3186. 3183. 3192. 3203. 53741 G 2959. 3068. 3115. 3103. 3142. 3139. 3147. 3153. 3158. 53744 NG 3183. 3070. 3146. 3150. 3150. 3174. 3177. 3183. 3212. 53745 G 3082. 3093. 3296. 3308. 3361. 3362. 3333. 3374. 3408. 53753 G 2984. 3012. 3235. 3260. 3277. 3252. 3224. 3285. 3340. 53757 G 3039. 3071. 3260. 3283. 3251. 3287. 3272. 3331. 3369. 53759 G 3107. 3100. 3317. 3333. 3302. 3334. 3259. 3252. 3332. 53778 G 2971. 2996. 3130. 3096. 3060. 3061. 3097. 3094. 3122. 53779 G 3074. 3089. 3227. 3172. 3178. 3171. 3204. 3231. 3270. 53782 G 3188. 3159. 3211. 3163. 3155. 3162. 3155. 3160. 3161. 54119 G 3505. 3537. 3533. 3656. 3638. 3639. 3663. 3720. 3760. 54120 G 3371. 3296. 3296. 3358. 3387. 3403. 3414. 3448. 3439. 54123 G 3190. 3149. 3169. 3208. 3210. 3253. 3254. 3284. 3285. 54131 G 3770. 3662. 3700. 3947. 3963. 4025. 4063. 4076. 4137. 54139 G 3423. 3347. 3489. 3457. 3483. 3514. 3551. 3597. 3612. 54141 G 3319. 3042. 2921. 3202. 3428. 3450. 3446. 3458. 3466. 54146 G 2988. 2983. 3112. 3097. 3121. 3108. 3103. 3121. 3156. 54148 G 3039. 3001. 3217. 3110. 3126. 3198. 3224. 3213. 3239. 54152 G 2955. 2891. 2993. 2979. 2984. 2987. 3008. 3027. 3058. 54156 G 3255. 3215. 3266. 3247. 3244. 3264. 3270. 3277. 3275. 54159 G 3092. 3085. 3212. 3155. 3151. 3179. 3207. 3215. 3229. 54160 G 3134. 3059. 3208. 3193. 3196. 3224. 3225. 3248. 3245.

MEAN 3150. 3125. 3236. 3253. 3270. 3286. 3292. 3314. 3336. S.D. 207.5 184.2 167.8 207.3 210.5 220.0 224.1 231.7 240.1 S.E. 43.3 38.4 35.0 43.2 43.9 45.9 46.7 48.3 50.1 N 23 23 23 23 23 23 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN131of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 13 14 15 16 17 18 19 20 21

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G 3414. 3456. 3456. 3497. 3517. 3546. 3592. 3608. 3631. 53736 G 3111. 3143. 3182. 3216. 3261. 3304. 3275. 3308. 3348. 53737 G 3237. 3271. 3271. 3275. 3342. 3357. 3378. 3369. 3405. 53741 G 3190. 3249. 3247. 3290. 3318. 3350. 3329. 3384. 3390. 53744 NG 3263. 3292. 3299. 3330. 3330. 3374. 3394. 3398. 3423. 53745 G 3436. 3461. 3500. 3513. 3541. 3586. 3632. 3630. 3707. 53753 G 3374. 3381. 3415. 3447. 3493. 3494. 3527. 3577. 3579. 53757 G 3410. 3425. 3491. 3500. 3488. 3487. 3539. 3532. 3563. 53759 G 3349. 3402. 3443. 3481. 3484. 3513. 3569. 3566. 3591. 53778 G 3150. 3150. 3215. 3243. 3272. 3267. 3305. 3285. 3332. 53779 G 3273. 3320. 3370. 3361. 3402. 3430. 3448. 3470. 3500. 53782 G 3166. 3182. 3108. 3114. 3144. 3159. 3146. 3138. 3159. 54119 G 3803. 3829. 3855. 3893. 3906. 3933. 3940. 3925. 3945. 54120 G 3446. 3463. 3489. 3519. 3525. 3574. 3580. 3579. 3591. 54123 G 3313. 3301. 3310. 3210. 3225. 3269. 3324. 3364. 3419. 54131 G 4148. 4200. 4205. 4312. 4326. 4350. 4402. 4389. 4432. 54139 G 3645. 3661. 3649. 3686. 3751. 3609. 3729. 3742. 3775. 54141 G 3496. 3525. 3562. 3608. 3649. 3657. 3686. 3676. 3701. 54146 G 3200. 3229. 3252. 3285. 3312. 3332. 3348. 3372. 3393. 54148 G 3256. 3292. 3349. 3387. 3402. 3399. 3441. 3488. 3484. 54152 G 3080. 3095. 3122. 3129. 3144. 3169. 3179. 3206. 3184. 54156 G 3265. 3289. 3311. 3317. 3351. 3416. 3420. 3409. 3411. 54159 G 3260. 3281. 3304. 3340. 3361. 3400. 3431. 3462. 3476. 54160 G 3262. 3275. 3309. 3348. 3375. 3415. 3415. 3436. 3463.

MEAN 3360. 3386. 3409. 3434. 3460. 3479. 3506. 3518. 3543. S.D. 240.9 245.2 244.6 264.1 261.7 255.3 267.4 259.4 265.0 S.E. 50.2 51.1 51.0 55.1 54.6 53.2 55.7 54.1 55.2 N 23 23 23 23 23 23 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN132of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 6 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 22 23 24 25 26 27 28 29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G 3602. 3530. 3579. 3599. 3532. 3575. 3591. 3615. SCHEDULED NECROPSY DAY 29 53736 G 3350. 3353. 3366. 3412. 3396. 3378. 3423. 3435. SCHEDULED NECROPSY DAY 29 53737 G 3424. 3443. 3460. 3469. 3478. 3472. 3524. 3555. SCHEDULED NECROPSY DAY 29 53741 G 3441. 3468. 3544. 3471. 3609. 3610. 3652. 3679. SCHEDULED NECROPSY DAY 29 53744 NG 3422. 3440. 3482. 3501. 3529. 3528. 3540. 3575. SCHEDULED NECROPSY DAY 29 53745 G 3715. 3752. 3787. 3751. 3799. 3812. 3811. 3864. SCHEDULED NECROPSY DAY 29 53753 G 3625. 3657. 3667. 3697. 3696. 3714. 3735. 3788. SCHEDULED NECROPSY DAY 29 53757 G 3540. 3578. 3550. 3557. 3542. 3557. 3547. 3527. SCHEDULED NECROPSY DAY 29 53759 G 3611. 3646. 3666. 3674. 3679. 3682. 3678. 3700. SCHEDULED NECROPSY DAY 29 53778 G 3364. 3381. 3391. 3386. 3401. 3401. 3431. 3337. SCHEDULED NECROPSY DAY 29 53779 G 3531. 3559. 3564. 3506. 3409. 3428. 3482. 3483. SCHEDULED NECROPSY DAY 29 53782 G 3138. 3161. 3184. 3191. 3204. 3213. 3194. 3264. SCHEDULED NECROPSY DAY 29 54119 G 3957. 3945. 3909. 3903. 3934. 3950. 3936. 3969. SCHEDULED NECROPSY DAY 29 54120 G 3605. 3583. 3572. 3577. 3591. 3591. 3570. 3564. SCHEDULED NECROPSY DAY 29 54123 G 3360. 3319. 3316. 3314. 3322. 3309. 3279. 3276. SCHEDULED NECROPSY DAY 29 54131 G 4485. 4533. 4535. 4544. 4564. 4495. 4478. 4467. SCHEDULED NECROPSY DAY 29 54139 G 3774. 3789. 3782. 3772. 3815. 3809. 3880. 3927. SCHEDULED NECROPSY DAY 29 54141 G 3691. 3690. 3746. 3752. 3763. 3746. 3751. 3785. SCHEDULED NECROPSY DAY 29 54146 G 3407. 3439. 3451. 3427. 3385. 3334. 3317. 3341. SCHEDULED NECROPSY DAY 29 54148 G 3491. 3506. 3536. 3549. 3525. 3462. 3419. 3466. SCHEDULED NECROPSY DAY 29 54152 G 3236. 3267. 3285. 3321. 3339. 3371. 3376. 3439. SCHEDULED NECROPSY DAY 29 54156 G 3394. 3377. 3385. 3313. 3257. 3225. 3181. 3156. SCHEDULED NECROPSY DAY 29 54159 G 3489. 3494. 3513. 3536. 3521. 3495. 3375. 3337. SCHEDULED NECROPSY DAY 29 54160 G 3497. 3508. 3532. 3516. 3522. 3529. 3539. 3563. SCHEDULED NECROPSY DAY 29

MEAN 3553. 3564. 3579. 3576. 3578. 3572. 3573. 3589. S.D. 270.9 276.1 271.5 272.9 284.6 278.5 284.7 291.0 S.E. 56.5 57.6 56.6 56.9 59.3 58.1 59.4 60.7 N 23 23 23 23 23 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN133of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 7 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0 4 6 7 8 9 10 11 12

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 3144. 3026. 3220. 3215. 3212. 3233. 3277. 3291. 3275. 53724 G 3103. 3071. 3209. 3265. 3274. 3299. 3299. 3344. 3371. 53728 G 3027. 2957. 3065. 3045. 3050. 3041. 3059. 3045. 2888. 53731 G 3292. 3249. 3412. 3400. 3414. 3421. 3441. 3470. 3488. 53733 G 3089. 2972. 3221. 3204. 3228. 3244. 3276. 3312. 3326. 53734 G 3369. 3331. 3618. 3523. 3530. 3579. 3599. 3616. 3666. 53740 G 2971. 2997. 3138. 3109. 3110. 3121. 3154. 3176. 3185. 53743 G 3046. 3007. 3127. 3112. 3115. 3122. 3146. 3176. 3139. 53747 G 2917. 2775. 2985. 2954. 2918. 2915. 2949. 2972. 2960. 53749 G 2979. 2854. 3032. 3003. 3030. 3032. 3083. 3116. 3110. 53750 G 2964. 2909. 3125. 3114. 3138. 3142. 3154. 3176. 3200. 53751 G 2948. 2871. 2951. 2945. 2932. 2951. 2943. 2960. 2940. 53754 G 3063. 3123. 3298. 3308. 3340. 3326. 3321. 3308. 3308. 53755 G 3022. 3038. 3222. 3222. 3236. 3257. 3273. 3260. 3327. 53756 G 2940. 3041. 3234. 3204. 3238. 3212. 3213. 3222. 3276. 53761 G 3046. 2980. 3174. 3235. 3241. 3257. 3270. 3247. 3334. 53762 G 3136. 3111. 3335. 3351. 3347. 3370. 3376. 3380. 3432. 53764 G 2982. 3043. 3187. 3148. 3150. 3183. 3222. 3180. 3237. 53765 G 2989. 3024. 3181. 3172. 3144. 3242. 3213. 3266. 3257. 53766 G 3081. 3066. 3225. 3273. 3266. 3298. 3322. 3330. 3374. 53768 G 3226. 3188. 3430. 3423. 3411. 3422. 3484. 3445. 3464. 53769 G 3185. 3174. 3232. 3247. 3235. 3241. 3253. 3266. 3303. 53774 G 3132. 3284. 3398. 3384. 3385. 3373. 3378. 3406. 3396. 53775 G 2992. 3120. 3129. 3162. 3186. 3216. 3226. 3240. 3262.

MEAN 3068. 3050. 3215. 3209. 3214. 3229. 3247. 3259. 3272. S.D. 114.5 134.2 149.6 146.1 149.5 153.5 153.6 151.5 177.6 S.E. 23.4 27.4 30.5 29.8 30.5 31.3 31.4 30.9 36.2 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN134of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 8 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 13 14 15 16 17 18 19 20 21

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 3293. 3323. 3391. 3406. 3434. 3461. 3501. 3521. 3543. 53724 G 3397. 3417. 3442. 3469. 3490. 3495. 3530. 3551. 3583. 53728 G 2840. 2764. 2781. 2920. 3020. 3042. 3072. 3110. 3111. 53731 G 3522. 3591. 3620. 3660. 3666. 3644. 3707. 3716. 3738. 53733 G 3405. 3430. 3482. 3537. 3536. 3565. 3552. 3590. 3589. 53734 G 3745. 3711. 3716. 3741. 3767. 3776. 3819. 3841. 3884. 53740 G 3185. 3205. 3233. 3244. 3263. 3285. 3288. 3321. 3336. 53743 G 3170. 3222. 3227. 3234. 3227. 3233. 3254. 3271. 3295. 53747 G 2994. 3018. 3031. 3062. 3076. 3108. 3100. 3118. 3130. 53749 G 3134. 3182. 3006. 2920. 2914. 2931. 2909. 2978. 3061. 53750 G 3235. 3263. 3287. 3298. 3306. 3307. 3329. 3352. 3354. 53751 G 2958. 2992. 2993. 3028. 3042. 3040. 3045. 3065. 3092. 53754 G 3343. 3312. 3256. 3249. 3282. 3298. 3321. 3343. 3394. 53755 G 3377. 3382. 3356. 3409. 3458. 3442. 3456. 3493. 3544. 53756 G 3321. 3337. 3385. 3397. 3387. 3374. 3420. 3425. 3430. 53761 G 3317. 3348. 3402. 3408. 3436. 3434. 3475. 3485. 3517. 53762 G 3464. 3480. 3529. 3587. 3574. 3583. 3593. 3614. 3594. 53764 G 3287. 3299. 3337. 3341. 3364. 3378. 3396. 3427. 3447. 53765 G 3289. 3300. 3323. 3324. 3378. 3402. 3434. 3466. 3491. 53766 G 3369. 3428. 3455. 3486. 3512. 3516. 3572. 3597. 3582. 53768 G 3489. 3516. 3552. 3578. 3610. 3626. 3621. 3639. 3656. 53769 G 3311. 3318. 3333. 3366. 3329. 3316. 3356. 3360. 3369. 53774 G 3464. 3494. 3569. 3565. 3580. 3604. 3607. 3667. 3673. 53775 G 3251. 3312. 3337. 3382. 3410. 3410. 3386. 3349. 3351.

MEAN 3298. 3319. 3335. 3359. 3378. 3386. 3406. 3429. 3449. S.D. 193.1 199.2 216.6 216.4 212.4 209.6 218.7 215.6 211.1 S.E. 39.4 40.7 44.2 44.2 43.4 42.8 44.6 44.0 43.1 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN135of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 9 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 22 23 24 25 26 27 28 29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 3552. 3583. 3610. 3613. 3606. 3599. 3592. 3620. SCHEDULED NECROPSY DAY 29 53724 G 3573. 3604. 3634. 3589. 3574. 3529. 3533. 3533. SCHEDULED NECROPSY DAY 29 53728 G 3119. 3144. 3157. 3181. 3194. 3207. 3230. 3287. SCHEDULED NECROPSY DAY 29 53731 G 3753. 3752. 3770. 3769. 3794. 3785. 3782. 3779. SCHEDULED NECROPSY DAY 29 53733 G 3610. 3606. 3629. 3615. 3626. 3641. 3660. 3685. SCHEDULED NECROPSY DAY 29 53734 G 3921. 3910. 3915. 3908. 3898. 3881. 3812. 3814. SCHEDULED NECROPSY DAY 29 53740 G 3371. 3400. 3470. 3459. 3479. 3492. 3523. 3558. SCHEDULED NECROPSY DAY 29 53743 G 3307. 3324. 3363. 3362. 3384. 3369. 3393. 3419. SCHEDULED NECROPSY DAY 29 53747 G 3123. 3121. 3139. 3175. 3166. 3128. 3147. 3178. SCHEDULED NECROPSY DAY 29 53749 G 3117. 3143. 3200. 3222. 3260. 3265. 3266. 3300. SCHEDULED NECROPSY DAY 29 53750 G 3369. 3374. 3364. 3274. 3329. 3317. 3292. 3314. SCHEDULED NECROPSY DAY 29 53751 G 3093. 3104. 3095. 3052. 3043. 3071. 3077. 3053. SCHEDULED NECROPSY DAY 29 53754 G 3423. 3449. 3481. 3491. 3488. 3482. 3527. 3491. SCHEDULED NECROPSY DAY 29 53755 G 3546. 3579. 3592. 3615. 3599. 3589. 3606. 3623. SCHEDULED NECROPSY DAY 29 53756 G 3448. 3491. 3508. 3548. 3538. 3561. 3561. 3521. SCHEDULED NECROPSY DAY 29 53761 G 3516. 3516. 3509. 3465. 3464. 3414. 3404. 3414. SCHEDULED NECROPSY DAY 29 53762 G 3611. 3621. 3614. 3621. 3619. 3569. 3519. 3469. SCHEDULED NECROPSY DAY 29 53764 G 3478. 3483. 3487. 3486. 3426. 3354. 3314. 3256. SCHEDULED NECROPSY DAY 29 53765 G 3471. 3493. 3490. 3492. 3504. 3442. 3417. 3393. SCHEDULED NECROPSY DAY 29 53766 G 3651. 3717. 3721. 3753. 3721. 3691. 3724. 3688. SCHEDULED NECROPSY DAY 29 53768 G 3654. 3715. 3703. 3689. 3699. 3697. 3753. 3781. SCHEDULED NECROPSY DAY 29 53769 G 3392. 3399. 3427. 3445. 3476. 3489. 3488. 3519. SCHEDULED NECROPSY DAY 29 53774 G 3686. 3737. 3772. 3808. 3809. 3813. 3820. 3838. SCHEDULED NECROPSY DAY 29 53775 G 3380. 3406. 3424. 3434. 3396. 3406. 3447. 3459. SCHEDULED NECROPSY DAY 29

MEAN 3465. 3486. 3503. 3503. 3504. 3491. 3495. 3500. S.D. 212.1 214.7 211.5 215.0 210.5 208.5 206.9 207.0 S.E. 43.3 43.8 43.2 43.9 43.0 42.6 42.2 42.2 N 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN136of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 10 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0 4 6 7 8 9 10 11 12

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G 3830. 3616. 3631. 3793. 3793. 3719. 3802. 3840. 3869. 54113 G 3318. 3254. 3249. 3312. 3312. 3330. 3307. 3315. 3315. 54116 G 3352. 3293. 3346. 3390. 3360. 3397. 3426. 3455. 3472. 54121 G 3210. 3098. 3226. 3437. 3411. 3436. 3479. 3526. 3512. 54122 G 3139. 3079. 3139. 3099. 3094. 3077. 3093. 3088. 3101. 54125 G 3416. 3379. 3415. 3453. 3474. 3483. 3486. 3526. 3549. 54126 G 3202. 3190. 3191. 3312. 3317. 3335. 3360. 3381. 3401. 54127 G 3219. 3084. 3129. 3147. 3144. 3143. 3165. 3183. 3205. 54130 G 3558. 3274. 3329. 3512. 3473. 3495. 3532. 3535. 3591. 54133 G 3330. 3211. 3306. 3330. 3293. 3267. 3292. 3312. 3333. 54134 G 3011. 2952. 2955. 3066. 3094. 3096. 3133. 3167. 3201. 54136 G 3463. 3355. 3340. 3551. 3557. 3536. 3555. 3566. 3622. 54142 NG 3529. 3253. 3780. 3744. 3824. 3879. 3929. 3980. 4008. 54144 G 2906. 2857. 3016. 2996. 3003. 3026. 3044. 3050. 3089. 54145 G 3128. 3113. 3247. 3251. 3264. 3318. 3327. 3362. 3386. 54149 G 3064. 3084. 3354. 3316. 3359. 3390. 3408. 3435. 3451. 54155 G 2994. 2946. 3066. 3067. 3098. 3119. 3148. 3205. 3214. 54158 G 3151. 3026. 3160. 3121. 3084. 3108. 3135. 3132. 3141. 54161 G 3006. 2926. 3129. 3075. 3101. 3133. 3159. 3157. 3169. 54162 G 3598. 3529. 3747. 3666. 3740. 3752. 3745. 3784. 3780. 54163 G 2925. 2823. 2864. 2884. 2914. 2868. 2893. 2876. 2891. 54164 G 3419. 3406. 3590. 3577. 3535. 3562. 3566. 3602. 3614. 54168 G 3063. 2981. 3198. 3197. 3191. 3220. 3268. 3293. 3302. 54170 G 3232. 3257. 3460. 3405. 3403. 3447. 3456. 3489. 3483.

MEAN 3241. 3162. 3265. 3302. 3305. 3316. 3338. 3360. 3378. S.D. 232.7 209.6 212.4 229.5 227.1 224.9 225.7 236.2 236.8 S.E. 48.5 43.7 44.3 47.8 47.4 46.9 47.1 49.3 49.4 N 23 23 23 23 23 23 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN137of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 11 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 13 14 15 16 17 18 19 20 21

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G 3859. 3940. 3923. 3978. 4001. 4041. 4050. 4079. 4110. 54113 G NA NA NA NA NA NA NA NA NA 54116 G 3480. 3481. 3532. 3550. 3591. 3589. 3621. 3650. 3644. 54121 G 3522. 3547. 3579. 3657. 3708. 3725. 3731. 3757. 3796. 54122 G 2974. 2747. NA NA NA NA NA NA NA 54125 G 3557. 3587. 3616. 3642. 3636. 3656. 3576. 3507. 3602. 54126 G 3429. 3477. 3540. 3568. 3578. 3601. 3537. 3542. 3578. 54127 G 3204. 3201. 3224. 3276. 3316. 3342. 3349. 3348. 3356. 54130 G 3590. 3644. 3683. 3700. 3729. 3753. 3780. 3798. 3789. 54133 G 3380. 3389. 3421. 3418. 3317. 3274. 3257. 3251. 3302. 54134 G 3182. 3200. 3240. 3250. 3276. 3301. 3330. 3337. 3357. 54136 G 3644. 3661. 3690. 3725. 3732. 3592. 3522. 3587. 3667. 54142 NG 4021. 4076. 4073. 4128. 4072. 4190. 4190. 4249. 4274. 54144 G 3105. 3178. 3179. 3222. 3218. 3236. 3255. 3289. 3301. 54145 G 3433. 3502. 3550. 3549. 3575. 3603. 3619. 3639. 3668. 54149 G 3471. 3542. 3604. 3646. 3648. 3660. 3623. 3665. 3694. 54155 G 3196. 3207. 3229. 3260. 3276. 3306. 3345. 3352. 3361. 54158 G 3152. 3181. 3218. 3245. 3247. 3260. 3263. 3298. 3297. 54161 G 3194. 3184. 3241. 3291. 3283. 3319. 3346. 3355. 3360. 54162 G 3785. 3858. 3875. 3899. 3920. 3935. 3958. 3972. 4020. 54163 G 2922. 2955. 2939. 2966. 2966. 2945. 2959. 2984. 2991. 54164 G 3630. 3658. 3700. 3734. 3749. 3738. 3764. 3807. 3779. 54168 G 3330. 3340. 3359. 3376. 3373. 3388. 3409. 3414. 3408. 54170 G 3492. 3526. 3552. 3607. 3605. 3619. 3659. 3669. 3681.

MEAN 3388. 3409. 3471. 3503. 3512. 3518. 3522. 3538. 3560. S.D. 248.7 284.4 250.8 253.3 261.4 262.8 260.4 264.3 269.0 S.E. 53.0 60.6 54.7 55.3 57.1 57.4 56.8 57.7 58.7 N 22 22 21 21 21 21 21 21 21

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE138of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 12 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 22 23 24 25 26 27 28 29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G 4013. 3994. 4021. 3983. 3866. 3773. NA NA ABORTED DAY 28 54113 G NA NA NA NA NA NA NA NA GRAVID, DIED DAY 13 54116 G 3657. 3684. 3719. 3714. 3676. 3684. 3736. 3750. SCHEDULED NECROPSY DAY 29 54121 G 3837. 3853. 3913. 3902. 3893. 3856. 3883. 3869. SCHEDULED NECROPSY DAY 29 54122 G NA NA NA NA NA NA NA NA GRAVID, DIED DAY 14 54125 G 3668. 3695. 3665. 3646. 3560. 3444. 3363. NA GRAVID, EUTHANIZED DAY 28 54126 G 3600. 3608. 3639. 3615. 3655. 3651. 3656. 3671. SCHEDULED NECROPSY DAY 29 54127 G 3383. 3376. 3373. 3346. 3267. 3219. 3178. 3017. SCHEDULED NECROPSY DAY 29 54130 G 3809. 3675. 3554. 3503. 3479. 3370. 3321. 3260. SCHEDULED NECROPSY DAY 29 54133 G 3312. 3370. 3378. 3391. 3415. 3420. 3404. 3444. SCHEDULED NECROPSY DAY 29 54134 G 3362. 3222. 3341. 3358. 3361. 3366. 3352. 3402. SCHEDULED NECROPSY DAY 29 54136 G 3700. 3720. 3718. 3751. 3795. 3792. 3829. 3743. SCHEDULED NECROPSY DAY 29 54142 NG 4383. 4417. 4461. 4518. 4505. 4513. 4550. 4550. SCHEDULED NECROPSY DAY 29 54144 G 3344. 3338. 3374. 3397. 3301. NA NA NA GRAVID, DIED DAY 27 54145 G 3664. 3666. 3591. 3567. 3511. 3484. 3429. 3421. SCHEDULED NECROPSY DAY 29 54149 G 3723. 3655. 3440. 3404. 3441. 3589. 3620. 3690. SCHEDULED NECROPSY DAY 29 54155 G 3384. 3406. 3390. 3325. 3336. 3345. 3326. 3349. SCHEDULED NECROPSY DAY 29 54158 G 3324. 3338. 3352. 3389. 3412. 3435. 3455. 3507. SCHEDULED NECROPSY DAY 29 54161 G 3382. 3359. 3356. 3357. 3335. 3348. 3335. 3331. SCHEDULED NECROPSY DAY 29 54162 G 4011. 3941. 3860. 3818. 3741. 3664. 3708. 3714. SCHEDULED NECROPSY DAY 29 54163 G 2983. 3009. 3023. 3053. 3046. 3055. 3063. 3075. SCHEDULED NECROPSY DAY 29 54164 G 3803. 3815. 3813. 3839. 3827. 3849. 3736. 3657. SCHEDULED NECROPSY DAY 29 54168 G 3417. 3443. 3457. 3435. 3412. 3392. 3260. 3253. SCHEDULED NECROPSY DAY 29 54170 G 3694. 3723. 3723. 3715. 3732. 3749. 3750. 3721. SCHEDULED NECROPSY DAY 29

MEAN 3575. 3566. 3557. 3548. 3527. 3524. 3495. 3493. S.D. 259.8 251.9 241.2 234.5 227.8 221.8 236.8 247.9 S.E. 56.7 55.0 52.6 51.2 49.7 49.6 54.3 58.4 N 21 21 21 21 21 20 19 18

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE139of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 13 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0 4 6 7 8 9 10 11 12

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 3194. 3241. 3375. 3357. 3374. 3373. 3390. 3404. 3425. 53725 G 3072. 3102. 3417. 3374. 3353. 3394. 3434. 3469. 3506. 53727 G 3141. 2847. 3290. 3279. 3308. 3312. 3283. 3330. 3347. 53730 G 2963. 2909. 3036. 3017. 3030. 3055. 3060. 3096. 3100. 53732 G 3019. 2996. 3122. 3066. 3036. 3029. 3054. 2992. NA 53770 G 3234. 3233. 3413. 3406. 3423. 3422. 3392. 3380. 3396. 53771 G 2987. 3044. 3309. 3316. 3293. 3315. 3332. 3349. 3375. 53772 G 3175. 3153. 3343. 3300. 3310. 3343. 3345. 3339. 3372. 53773 G 3065. 3123. 3312. 3299. 3264. 3318. 3331. 3338. 3377. 53776 G 3040. 3053. 3284. 3268. 3272. 3271. 3286. 3271. 3310. 53777 G 2962. 2991. 3168. 3196. 3195. 3193. 3202. 3197. 3235. 53781 G 3214. 3210. 3288. 3248. 3239. 3231. 3240. 3258. 3250. 54108 G 3232. 3251. 3298. 3456. 3450. 3471. 3484. 3522. 3540. 54111 G 3120. 3143. 3181. 3277. 3305. 3255. 3252. 3278. 3318. 54112 G 3006. 2979. 2929. 2950. 2947. 2941. 2942. 2953. 2987. 54114 G 3368. 3275. 3312. 3422. 3420. 3394. 3404. 3472. 3464. 54115 G 3474. 3417. 3424. 3449. 3453. 3480. 3511. 3535. 3552. 54132 G 3976. 3921. 3948. 3960. 3979. 3996. 4024. 4020. 4068. 54135 G 3162. 3079. 3058. 3132. 3145. 3137. 3168. 3190. 3185. 54138 G 3214. 3111. 3137. 3234. 3238. 3286. 3256. 3268. 3286. 54140 G 3545. 3471. 3625. 3613. 3550. 3621. 3623. 3679. 3769. 54150 G 3293. 3313. 3481. 3438. 3497. 3537. 3571. 3626. 3647. 54151 G 2984. 2942. 3082. 3039. 3020. 3025. 3064. 3072. 3104. 54165 G 3007. 2964. 3170. 3109. 3109. 3144. 3167. 3171. 3190.

MEAN 3185. 3157. 3292. 3300. 3300. 3314. 3326. 3342. 3383. S.D. 229.9 226.0 211.3 213.1 216.0 223.5 225.4 234.5 235.1 S.E. 46.9 46.1 43.1 43.5 44.1 45.6 46.0 47.9 49.0 N 24 24 24 24 24 24 24 24 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE140of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 14 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 13 14 15 16 17 18 19 20 21

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 3427. 3435. 3471. 3480. 3486. 3474. 3334. 3306. 3431. 53725 G 3580. 3606. 3637. 3685. 3679. 3744. 3753. 3771. 3741. 53727 G 3362. 3364. 3437. 3466. 3512. 3475. 3435. 3485. 3529. 53730 G 3117. 3128. 3168. 3158. 3213. 3198. 3193. 3198. 3257. 53732 G NA NA NA NA NA NA NA NA NA 53770 G 3412. 3434. 3489. 3497. 3511. 3515. 3532. 3541. 3564. 53771 G 3391. 3385. 3412. 3438. 3446. 3477. 3487. 3512. 3530. 53772 G 3401. 3424. 3446. 3454. 3491. 3495. 3533. 3551. 3565. 53773 G 3439. 3443. 3474. 3522. 3566. 3612. 3577. 3622. 3656. 53776 G 3338. 3376. 3458. 3459. 3473. 3434. 3456. 3489. 3505. 53777 G 3233. 3251. 3257. 3292. 3310. 3333. 3344. 3365. 3348. 53781 G 3228. 3021. NA NA NA NA NA NA NA 54108 G 3561. 3570. 3595. 3607. 3622. 3659. 3656. 3687. 3685. 54111 G 3346. 3174. 2982. 2980. 2877. 2832. 2783. 2789. 2754. 54112 G 2994. 3028. 3066. 3078. 3084. 3091. 3113. 3122. 3118. 54114 G 3479. 3523. 3525. 3392. NA NA NA NA NA 54115 G 3548. 3317. NA NA NA NA NA NA NA 54132 G 4049. 4076. 4137. 4131. 3938. NA NA NA NA 54135 G 3217. 3222. 3266. 3242. 3275. 3289. 3281. 3304. 3295. 54138 G 3289. 3065. NA NA NA NA NA NA NA 54140 G 3786. 3855. 3878. 3883. 3891. 3938. 3982. 3996. 4031. 54150 G 3662. 3661. 3706. 3757. 3773. 3776. 3829. 3838. 3841. 54151 G 3100. 3146. 3198. 3195. 3204. 3222. 3082. NA NA 54165 G 3225. 3242. 3275. 3306. 3326. 3334. 3356. 3367. 3375.

MEAN 3399. 3380. 3444. 3451. 3457. 3439. 3429. 3467. 3484. S.D. 234.0 259.9 271.2 274.9 267.4 264.2 287.6 287.4 292.4 S.E. 48.8 54.2 60.6 61.5 61.4 62.3 67.8 69.7 70.9 N 23 23 20 20 19 18 18 17 17

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE141of475TABLE A6 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 15 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 22 23 24 25 26 27 28 29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 3441. 3505. 3565. 3567. 3611. 3605. 3619. 3658. SCHEDULED NECROPSY DAY 29 53725 G 3776. 3754. 3779. 3737. 3657. 3594. 3451. 3374. SCHEDULED NECROPSY DAY 29 53727 G 3500. 3486. 3510. 3579. 3584. 3561. 3574. 3658. SCHEDULED NECROPSY DAY 29 53730 G 3262. 3274. 3306. 3329. 3396. 3381. 3435. 3473. SCHEDULED NECROPSY DAY 29 53732 G NA NA NA NA NA NA NA NA GRAVID, DIED DAY 12 53770 G 3525. 3247. 3097. 3142. NA NA NA NA ABORTED DAY 26 53771 G 3561. 3565. 3520. 3550. 3579. 3547. 3579. 3581. SCHEDULED NECROPSY DAY 29 53772 G 3605. 3631. 3665. 3636. 3690. 3671. 3689. 3716. SCHEDULED NECROPSY DAY 29 53773 G 3690. 3666. 3679. 3714. 3750. 3777. 3777. 3773. SCHEDULED NECROPSY DAY 29 53776 G 3530. 3559. 3515. 3533. 3496. 3517. 3500. 3540. SCHEDULED NECROPSY DAY 29 53777 G 3374. 3379. 3366. 3349. 3357. 3402. 3413. 3453. SCHEDULED NECROPSY DAY 29 53781 G NA NA NA NA NA NA NA NA GRAVID, DIED DAY 14 54108 G 3707. 3739. 3742. 3772. 3726. 3706. 3702. 3703. SCHEDULED NECROPSY DAY 29 54111 G 2719. 2696. 2683. 2620. 2577. NA NA NA ABORTED DAY 26 54112 G 3132. 3160. 3170. 3173. 3181. 3190. 3200. 3223. SCHEDULED NECROPSY DAY 29 54114 G NA NA NA NA NA NA NA NA GRAVID, EUTHANIZED DAY 16 54115 G NA NA NA NA NA NA NA NA GRAVID, DIED DAY 14 54132 G NA NA NA NA NA NA NA NA GRAVID, DIED DAY 18 54135 G 3318. 3330. 3343. 3353. 3380. 3345. 3371. 3390. SCHEDULED NECROPSY DAY 29 54138 G NA NA NA NA NA NA NA NA GRAVID, DIED DAY 14 54140 G 4050. 4038. 3869. 3743. 3644. 3493. 3490. NA DELIVERED DAY 29 54150 G 3876. 3900. 3921. 3936. 3916. 3909. 3923. 3971. SCHEDULED NECROPSY DAY 29 54151 G NA NA NA NA NA NA NA NA GRAVID, DIED DAY 20 54165 G 3420. 3406. 3400. 3417. 3357. 3205. 3161. NA ABORTED DAY 29

MEAN 3499. 3490. 3478. 3479. 3494. 3527. 3526. 3578. S.D. 303.7 311.4 309.7 310.3 306.9 200.3 204.3 198.1 S.E. 73.7 75.5 75.1 75.3 76.7 51.7 52.7 54.9 N 17 17 17 17 16 15 15 13

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE PGBWv4.07 05/21/2008142of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 4 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G -4. 19. -46. 6. 23. 9. 4. 49. 49. 53735 G -5. 81. -15. -26. 37. -7. 20. -20. 23. 53738 G -120. 155. -5. 0. 10. 43. 5. 3. 43. 53739 G -88. 154. 8. -12. 13. 23. 9. 24. 23. 53742 G -58. 267. -46. 40. 24. 40. -6. -2. 78. 53748 G 32. 188. -48. -69. 28. -2. 29. 14. 18. 53752 G -35. 179. -3. -6. 33. 28. 24. 6. 76. 53758 G 121. 68. 15. 2. 2. -14. 33. 32. -7. 53760 G 25. 105. 16. -11. -36. 5. 51. 38. 24. 53763 G 58. 157. 24. -41. 35. 3. 32. 43. 60. 53780 G 153. 108. -7. 18. 61. 12. -14. 50. 44. 53783 G 20. 46. -11. 12. 3. 25. -14. 34. 2. 54117 G -85. 51. 94. -7. 31. 20. 15. 48. 24. 54124 G -66. 55. 77. -18. -7. 13. -14. 49. 16. 54128 G -111. 56. 59. -16. 3. 10. 34. 32. 29. 54129 G -188. 50. 47. 9. 10. 28. 4. 33. 31. 54137 G -49. 18. 34. 31. 43. 29. -12. 15. 47. 54143 G -23. 129. -35. 49. -35. 6. 23. 20. 14. 54147 G -34. 245. -60. 12. 34. 3. 6. 22. 33. 54153 G -58. 123. 24. 27. -12. 17. 23. 16. 6. 54157 G -31. 272. -22. 7. 25. 39. 27. 53. 49. 54166 G -4. 245. -17. 31. 71. -2. 16. 78. 51. 54167 G 29. 209. -119. 36. 28. 21. 7. 26. -28. 54169 G -55. 106. 12. -10. 11. 20. 20. 12. 1.

MEAN -24. 129. -1. 3. 18. 15. 13. 28. 29. S.D. 74.6 78.8 46.7 27.0 25.6 15.1 17.5 21.4 25.4 S.E. 15.2 16.1 9.5 5.5 5.2 3.1 3.6 4.4 5.2 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN143of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY13-14 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 48. 35. 35. 10. 60. -21. 10. -52. 32. 53735 G 55. 37. 45. 25. -2. 9. 15. 21. 17. 53738 G 0. 69. 53. 35. 31. 24. 14. 46. 22. 53739 G 7. 30. 33. 1. 49. -31. 26. 24. 17. 53742 G 5. 107. 36. 28. 13. 9. 52. 47. 29. 53748 G 30. 45. 25. 52. 18. 31. 49. 16. -1. 53752 G 14. 39. 23. 40. 27. 24. 67. 15. 21. 53758 G 25. 65. 17. 11. 6. 43. 10. 17. 21. 53760 G -22. 100. 65. 47. 11. 53. 35. 32. 43. 53763 G 43. 36. -27. 64. -60. 32. 12. 39. -6. 53780 G 35. 28. 70. -75. 44. 30. 69. 24. 54. 53783 G 66. 70. 2. 6. 5. 31. 10. 23. 14. 54117 G 33. -3. 19. 69. -16. 14. -58. 52. -17. 54124 G 13. 28. 29. 10. 39. 41. 25. 19. 14. 54128 G 26. 50. 44. 15. 15. 23. 44. 10. 42. 54129 G 22. 43. 36. 13. 26. -35. 31. -2. 13. 54137 G 73. 19. 8. -13. 30. 7. -18. 24. 4. 54143 G 32. 14. 24. 35. -109. 74. 28. 41. -18. 54147 G 6. 100. 44. 20. 61. 14. 32. 2. -12. 54153 G 24. 42. 25. 30. 35. -8. 13. 36. 28. 54157 G 42. 46. 62. 43. -2. -8. 12. 32. -32. 54166 G -8. 28. 38. 15. 21. 32. 32. 81. -61. 54167 G 46. 32. 45. 26. 32. 13. 48. 25. -34. 54169 G 20. 60. 16. 38. 31. 24. 39. 26. 22.

MEAN 26. 47. 32. 23. 15. 18. 25. 25. 9. S.D. 22.8 27.3 21.3 28.7 36.8 25.5 26.7 23.9 27.2 S.E. 4.7 5.6 4.3 5.9 7.5 5.2 5.5 4.9 5.6 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN144of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY22-23 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 40. -10. 97. 8. 47. 0. 87. -17. 62. 53735 G 21. 39. 16. 3. -48. -22. 58. -4. -7. 53738 G 12. 45. -10. -8. 12. 2. 63. 5. 51. 53739 G 20. 29. 21. 3. 8. -11. 52. 9. 56. 53742 G 35. 41. -20. 45. -22. -5. 19. 18. 32. 53748 G 68. 14. 40. 32. -30. -37. 20. -89. 41. 53752 G 30. 30. 16. -9. -6. 20. 52. 24. 58. 53758 G 27. 0. 22. 17. 21. 6. 33. 19. 51. 53760 G 36. -45. -17. -69. -40. 13. -27. -31. 94. 53763 G 42. -12. 26. 46. 23. 3. -52. 18. 78. 53780 G 49. -35. -21. 64. -20. -117. -74. 72. 48. 53783 G 20. 41. 28. 25. 39. 49. 6. 4. 45. 54117 G -4. 54. 4. 21. -11. -1. 13. 118. 83. 54124 G 53. 20. 43. 31. 3. 23. 31. 52. 48. 54128 G 10. 39. 21. -4. -7. 23. 3. 46. 76. 54129 G -14. 23. -21. 3. 3. 24. -34. 66. 65. 54137 G 24. 29. 46. 30. -5. 45. 40. 108. 32. 54143 G 29. 18. 36. -5. 9. 51. 5. -21. 49. 54147 G -23. -27. -66. 0. 48. -48. -2. -14. 31. 54153 G 31. 27. 4. -19. 19. -10. 57. 39. 56. 54157 G 32. 26. 42. 7. -23. 35. 18. 10. 119. 54166 G 57. -19. -18. -23. -65. -40. -21. 85. 92. 54167 G 20. -34. 57. 29. 117. -23. 33. -55. 54. 54169 G 42. 47. 16. -11. -19. -20. 16. 13. 52.

MEAN 27. 14. 15. 9. 2. -2. 17. 20. 57. S.D. 21.3 29.4 33.5 27.6 37.5 36.7 38.4 48.5 25.3 S.E. 4.3 6.0 6.8 5.6 7.6 7.5 7.8 9.9 5.2 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN145of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY12-20 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 226. 249. 520. SCHEDULED NECROPSY DAY 29 53735 G 207. 105. 301. SCHEDULED NECROPSY DAY 29 53738 G 269. 184. 509. SCHEDULED NECROPSY DAY 29 53739 G 138. 163. 366. SCHEDULED NECROPSY DAY 29 53742 G 328. 169. 547. SCHEDULED NECROPSY DAY 29 53748 G 268. 122. 342. SCHEDULED NECROPSY DAY 29 53752 G 310. 169. 561. SCHEDULED NECROPSY DAY 29 53758 G 170. 164. 404. SCHEDULED NECROPSY DAY 29 53760 G 313. -74. 302. SCHEDULED NECROPSY DAY 29 53763 G 160. 109. 365. SCHEDULED NECROPSY DAY 29 53780 G 245. -76. 289. SCHEDULED NECROPSY DAY 29 53783 G 192. 245. 486. SCHEDULED NECROPSY DAY 29 54117 G 82. 111. 394. SCHEDULED NECROPSY DAY 29 54124 G 201. 237. 538. SCHEDULED NECROPSY DAY 29 54128 G 246. 137. 505. SCHEDULED NECROPSY DAY 29 54129 G 167. -5. 293. SCHEDULED NECROPSY DAY 29 54137 G 153. 237. 530. SCHEDULED NECROPSY DAY 29 54143 G 112. 166. 306. SCHEDULED NECROPSY DAY 29 54147 G 310. -128. 199. SCHEDULED NECROPSY DAY 29 54153 G 167. 173. 435. SCHEDULED NECROPSY DAY 29 54157 G 244. 137. 510. SCHEDULED NECROPSY DAY 29 54166 G 209. -109. 277. SCHEDULED NECROPSY DAY 29 54167 G 214. 190. 403. SCHEDULED NECROPSY DAY 29 54169 G 229. 119. 413. SCHEDULED NECROPSY DAY 29

MEAN 215. 116. 408. S.D. 65.2 112.0 105.0 S.E. 13.3 22.9 21.4 N 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN146of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 4 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G -26. 283. -27. 19. 16. 2. 58. 21. 47. 53736 G -15. 158. 7. 12. -6. 31. -17. -21. 22. 53737 G 36. 73. -22. 50. -5. -3. 9. 11. 34. 53741 G 109. 47. -12. 39. -3. 8. 6. 5. 32. 53744 NG -113. 76. 4. 0. 24. 3. 6. 29. 51. 53745 G 11. 203. 12. 53. 1. -29. 41. 34. 28. 53753 G 28. 223. 25. 17. -25. -28. 61. 55. 34. 53757 G 32. 189. 23. -32. 36. -15. 59. 38. 41. 53759 G -7. 217. 16. -31. 32. -75. -7. 80. 17. 53778 G 25. 134. -34. -36. 1. 36. -3. 28. 28. 53779 G 15. 138. -55. 6. -7. 33. 27. 39. 3. 53782 G -29. 52. -48. -8. 7. -7. 5. 1. 5. 54119 G 32. -4. 123. -18. 1. 24. 57. 40. 43. 54120 G -75. 0. 62. 29. 16. 11. 34. -9. 7. 54123 G -41. 20. 39. 2. 43. 1. 30. 1. 28. 54131 G -108. 38. 247. 16. 62. 38. 13. 61. 11. 54139 G -76. 142. -32. 26. 31. 37. 46. 15. 33. 54141 G -277. -121. 281. 226. 22. -4. 12. 8. 30. 54146 G -5. 129. -15. 24. -13. -5. 18. 35. 44. 54148 G -38. 216. -107. 16. 72. 26. -11. 26. 17. 54152 G -64. 102. -14. 5. 3. 21. 19. 31. 22. 54156 G -40. 51. -19. -3. 20. 6. 7. -2. -10. 54159 G -7. 127. -57. -4. 28. 28. 8. 14. 31. 54160 G -75. 149. -15. 3. 28. 1. 23. -3. 17.

MEAN -26. 112. 16. 18. 16. 6. 22. 22. 25. S.D. 73.1 93.2 90.6 51.2 23.8 26.6 23.3 24.2 14.5 S.E. 15.3 19.4 18.9 10.7 5.0 5.6 4.9 5.0 3.0 N 23 23 23 23 23 23 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN147of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 6 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY13-14 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G 42. 0. 41. 20. 29. 46. 16. 23. -29. 53736 G 32. 39. 34. 45. 43. -29. 33. 40. 2. 53737 G 34. 0. 4. 67. 15. 21. -9. 36. 19. 53741 G 59. -2. 43. 28. 32. -21. 55. 6. 51. 53744 NG 29. 7. 31. 0. 44. 20. 4. 25. -1. 53745 G 25. 39. 13. 28. 45. 46. -2. 77. 8. 53753 G 7. 34. 32. 46. 1. 33. 50. 2. 46. 53757 G 15. 66. 9. -12. -1. 52. -7. 31. -23. 53759 G 53. 41. 38. 3. 29. 56. -3. 25. 20. 53778 G 0. 65. 28. 29. -5. 38. -20. 47. 32. 53779 G 47. 50. -9. 41. 28. 18. 22. 30. 31. 53782 G 16. -74. 6. 30. 15. -13. -8. 21. -21. 54119 G 26. 26. 38. 13. 27. 7. -15. 20. 12. 54120 G 17. 26. 30. 6. 49. 6. -1. 12. 14. 54123 G -12. 9. -100. 15. 44. 55. 40. 55. -59. 54131 G 52. 5. 107. 14. 24. 52. -13. 43. 53. 54139 G 16. -12. 37. 65. -142. 120. 13. 33. -1. 54141 G 29. 37. 46. 41. 8. 29. -10. 25. -10. 54146 G 29. 23. 33. 27. 20. 16. 24. 21. 14. 54148 G 36. 57. 38. 15. -3. 42. 47. -4. 7. 54152 G 15. 27. 7. 15. 25. 10. 27. -22. 52. 54156 G 24. 22. 6. 34. 65. 4. -11. 2. -17. 54159 G 21. 23. 36. 21. 39. 31. 31. 14. 13. 54160 G 13. 34. 39. 27. 40. 0. 21. 27. 34.

MEAN 26. 23. 24. 27. 19. 27. 12. 25. 11. S.D. 17.3 29.9 35.4 18.6 39.4 31.8 23.2 21.0 28.6 S.E. 3.6 6.2 7.4 3.9 8.2 6.6 4.8 4.4 6.0 N 23 23 23 23 23 23 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN148of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 7 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY22-23 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G -72. 49. 20. -67. 43. 16. 24. 8. 81. 53736 G 3. 13. 46. -16. -18. 45. 12. 13. -7. 53737 G 19. 17. 9. 9. -6. 52. 31. 23. 17. 53741 G 27. 76. -73. 138. 1. 42. 27. 24. 19. 53744 NG 18. 42. 19. 28. -1. 12. 35. 28. 38. 53745 G 37. 35. -36. 48. 13. -1. 53. 66. 46. 53753 G 32. 10. 30. -1. 18. 21. 53. 17. 88. 53757 G 38. -28. 7. -15. 15. -10. -20. 27. 82. 53759 G 35. 20. 8. 5. 3. -4. 22. 17. -2. 53778 G 17. 10. -5. 15. 0. 30. -94. -69. 61. 53779 G 28. 5. -58. -97. 19. 54. 1. -56. 99. 53782 G 23. 23. 7. 13. 9. -19. 70. -49. -1. 54119 G -12. -36. -6. 31. 16. -14. 33. 106. 121. 54120 G -22. -11. 5. 14. 0. -21. -6. 107. 36. 54123 G -41. -3. -2. 8. -13. -30. -3. 84. 32. 54131 G 48. 2. 9. 20. -69. -17. -11. 325. 112. 54139 G 15. -7. -10. 43. -6. 71. 47. 25. 98. 54141 G -1. 56. 6. 11. -17. 5. 34. 529. 16. 54146 G 32. 12. -24. -42. -51. -17. 24. -4. 48. 54148 G 15. 30. 13. -24. -63. -43. 47. -19. 41. 54152 G 31. 18. 36. 18. 32. 5. 63. -6. 71. 54156 G -17. 8. -72. -56. -32. -44. -25. -2. 11. 54159 G 5. 19. 23. -15. -26. -120. -38. -33. 50. 54160 G 11. 24. -16. 6. 7. 10. 24. 16. 21.

MEAN 11. 15. -4. 2. -5. 0. 16. 50. 50. S.D. 28.4 25.0 31.4 45.6 28.2 41.0 37.4 131.0 38.3 S.E. 5.9 5.2 6.5 9.5 5.9 8.5 7.8 27.3 8.0 N 23 23 23 23 23 23 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN149of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 8 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY12-20 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G 241. 7. 337. SCHEDULED NECROPSY DAY 29 53736 G 219. 127. 352. SCHEDULED NECROPSY DAY 29 53737 G 166. 186. 392. SCHEDULED NECROPSY DAY 29 53741 G 226. 295. 564. SCHEDULED NECROPSY DAY 29 53744 NG 186. 177. 429. SCHEDULED NECROPSY DAY 29 53745 G 222. 234. 568. SCHEDULED NECROPSY DAY 29 53753 G 237. 211. 553. SCHEDULED NECROPSY DAY 29 53757 G 163. -5. 267. SCHEDULED NECROPSY DAY 29 53759 G 234. 134. 383. SCHEDULED NECROPSY DAY 29 53778 G 163. 52. 207. SCHEDULED NECROPSY DAY 29 53779 G 200. 13. 256. SCHEDULED NECROPSY DAY 29 53782 G -23. 126. 53. SCHEDULED NECROPSY DAY 29 54119 G 165. 44. 436. SCHEDULED NECROPSY DAY 29 54120 G 140. -15. 268. SCHEDULED NECROPSY DAY 29 54123 G 79. -88. 107. SCHEDULED NECROPSY DAY 29 54131 G 252. 78. 767. SCHEDULED NECROPSY DAY 29 54139 G 130. 185. 438. SCHEDULED NECROPSY DAY 29 54141 G 210. 109. 864. SCHEDULED NECROPSY DAY 29 54146 G 216. -31. 229. SCHEDULED NECROPSY DAY 29 54148 G 249. -22. 249. SCHEDULED NECROPSY DAY 29 54152 G 148. 233. 446. SCHEDULED NECROPSY DAY 29 54156 G 134. -253. -110. SCHEDULED NECROPSY DAY 29 54159 G 233. -125. 125. SCHEDULED NECROPSY DAY 29 54160 G 191. 127. 355. SCHEDULED NECROPSY DAY 29

MEAN 182. 71. 352. S.D. 64.1 130.2 221.3 S.E. 13.4 27.2 46.1 N 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN150of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 9 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 4 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G -118. 194. -5. -3. 21. 44. 14. -16. 18. 53724 G -32. 138. 56. 9. 25. 0. 45. 27. 26. 53728 G -70. 108. -20. 5. -9. 18. -14. -157. -48. 53731 G -43. 163. -12. 14. 7. 20. 29. 18. 34. 53733 G -117. 249. -17. 24. 16. 32. 36. 14. 79. 53734 G -38. 287. -95. 7. 49. 20. 17. 50. 79. 53740 G 26. 141. -29. 1. 11. 33. 22. 9. 0. 53743 G -39. 120. -15. 3. 7. 24. 30. -37. 31. 53747 G -142. 210. -31. -36. -3. 34. 23. -12. 34. 53749 G -125. 178. -29. 27. 2. 51. 33. -6. 24. 53750 G -55. 216. -11. 24. 4. 12. 22. 24. 35. 53751 G -77. 80. -6. -13. 19. -8. 17. -20. 18. 53754 G 60. 175. 10. 32. -14. -5. -13. 0. 35. 53755 G 16. 184. 0. 14. 21. 16. -13. 67. 50. 53756 G 101. 193. -30. 34. -26. 1. 9. 54. 45. 53761 G -66. 194. 61. 6. 16. 13. -23. 87. -17. 53762 G -25. 224. 16. -4. 23. 6. 4. 52. 32. 53764 G 61. 144. -39. 2. 33. 39. -42. 57. 50. 53765 G 35. 157. -9. -28. 98. -29. 53. -9. 32. 53766 G -15. 159. 48. -7. 32. 24. 8. 44. -5. 53768 G -38. 242. -7. -12. 11. 62. -39. 19. 25. 53769 G -11. 58. 15. -12. 6. 12. 13. 37. 8. 53774 G 152. 114. -14. 1. -12. 5. 28. -10. 68. 53775 G 128. 9. 33. 24. 30. 10. 14. 22. -11.

MEAN -18. 164. -5. 5. 15. 18. 11. 13. 27. S.D. 78.4 63.2 33.5 17.8 24.5 20.2 24.5 47.7 29.5 S.E. 16.0 12.9 6.8 3.6 5.0 4.1 5.0 9.7 6.0 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN151of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 10 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY13-14 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 30. 68. 15. 28. 27. 40. 20. 22. 9. 53724 G 20. 25. 27. 21. 5. 35. 21. 32. -10. 53728 G -76. 17. 139. 100. 22. 30. 38. 1. 8. 53731 G 69. 29. 40. 6. -22. 63. 9. 22. 15. 53733 G 25. 52. 55. -1. 29. -13. 38. -1. 21. 53734 G -34. 5. 25. 26. 9. 43. 22. 43. 37. 53740 G 20. 28. 11. 19. 22. 3. 33. 15. 35. 53743 G 52. 5. 7. -7. 6. 21. 17. 24. 12. 53747 G 24. 13. 31. 14. 32. -8. 18. 12. -7. 53749 G 48. -176. -86. -6. 17. -22. 69. 83. 56. 53750 G 28. 24. 11. 8. 1. 22. 23. 2. 15. 53751 G 34. 1. 35. 14. -2. 5. 20. 27. 1. 53754 G -31. -56. -7. 33. 16. 23. 22. 51. 29. 53755 G 5. -26. 53. 49. -16. 14. 37. 51. 2. 53756 G 16. 48. 12. -10. -13. 46. 5. 5. 18. 53761 G 31. 54. 6. 28. -2. 41. 10. 32. -1. 53762 G 16. 49. 58. -13. 9. 10. 21. -20. 17. 53764 G 12. 38. 4. 23. 14. 18. 31. 20. 31. 53765 G 11. 23. 1. 54. 24. 32. 32. 25. -20. 53766 G 59. 27. 31. 26. 4. 56. 25. -15. 69. 53768 G 27. 36. 26. 32. 16. -5. 18. 17. -2. 53769 G 7. 15. 33. -37. -13. 40. 4. 9. 23. 53774 G 30. 75. -4. 15. 24. 3. 60. 6. 13. 53775 G 61. 25. 45. 28. 0. -24. -37. 2. 29.

MEAN 20. 17. 24. 19. 9. 20. 23. 19. 17. S.D. 31.9 49.7 38.0 26.8 15.1 24.0 19.9 22.6 20.3 S.E. 6.5 10.2 7.7 5.5 3.1 4.9 4.1 4.6 4.2 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN152of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 11 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY22-23 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 31. 27. 3. -7. -7. -7. 28. 13. 42. 53724 G 31. 30. -45. -15. -45. 4. 0. 90. 72. 53728 G 25. 13. 24. 13. 13. 23. 57. -24. -153. 53731 G -1. 18. -1. 25. -9. -3. -3. 9. 67. 53733 G -4. 23. -14. 11. 15. 19. 25. 23. 82. 53734 G -11. 5. -7. -10. -17. -69. 2. -39. 87. 53740 G 29. 70. -11. 20. 13. 31. 35. -17. 64. 53743 G 17. 39. -1. 22. -15. 24. 26. -5. 17. 53747 G -2. 18. 36. -9. -38. 19. 31. -70. 45. 53749 G 26. 57. 22. 38. 5. 1. 34. 0. 78. 53750 G 5. -10. -90. 55. -12. -25. 22. 17. 58. 53751 G 11. -9. -43. -9. 28. 6. -24. 0. -11. 53754 G 26. 32. 10. -3. -6. 45. -36. 28. -18. 53755 G 33. 13. 23. -16. -10. 17. 17. 35. 70. 53756 G 43. 17. 40. -10. 23. 0. -40. -22. 64. 53761 G 0. -7. -44. -1. -50. -10. 10. 83. 77. 53762 G 10. -7. 7. -2. -50. -50. -50. 35. 62. 53764 G 5. 4. -1. -60. -72. -40. -58. -4. 54. 53765 G 22. -3. 2. 12. -62. -25. -24. 61. 15. 53766 G 66. 4. 32. -32. -30. 33. -36. 73. 76. 53768 G 61. -12. -14. 10. -2. 56. 28. -8. 42. 53769 G 7. 28. 18. 31. 13. -1. 31. 9. 62. 53774 G 51. 35. 36. 1. 4. 7. 18. -25. 23. 53775 G 26. 18. 10. -38. 10. 41. 12. 87. 46.

MEAN 21. 17. 0. 1. -13. 4. 4. 15. 43. S.D. 20.4 21.0 30.8 25.0 27.8 30.2 31.3 41.4 50.2 S.E. 4.2 4.3 6.3 5.1 5.7 6.2 6.4 8.5 10.2 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN153of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 12 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY12-20 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 246. 99. 400. SCHEDULED NECROPSY DAY 29 53724 G 180. -18. 324. SCHEDULED NECROPSY DAY 29 53728 G 222. 177. 222. SCHEDULED NECROPSY DAY 29 53731 G 228. 63. 367. SCHEDULED NECROPSY DAY 29 53733 G 264. 95. 464. SCHEDULED NECROPSY DAY 29 53734 G 175. -27. 196. SCHEDULED NECROPSY DAY 29 53740 G 136. 237. 420. SCHEDULED NECROPSY DAY 29 53743 G 132. 148. 292. SCHEDULED NECROPSY DAY 29 53747 G 158. 60. 193. SCHEDULED NECROPSY DAY 29 53749 G -132. 322. 268. SCHEDULED NECROPSY DAY 29 53750 G 152. -38. 189. SCHEDULED NECROPSY DAY 29 53751 G 125. -12. 102. SCHEDULED NECROPSY DAY 29 53754 G 35. 148. 193. SCHEDULED NECROPSY DAY 29 53755 G 166. 130. 401. SCHEDULED NECROPSY DAY 29 53756 G 149. 96. 287. SCHEDULED NECROPSY DAY 29 53761 G 151. -71. 240. SCHEDULED NECROPSY DAY 29 53762 G 182. -145. 134. SCHEDULED NECROPSY DAY 29 53764 G 190. -171. 69. SCHEDULED NECROPSY DAY 29 53765 G 209. -73. 212. SCHEDULED NECROPSY DAY 29 53766 G 223. 91. 463. SCHEDULED NECROPSY DAY 29 53768 G 175. 142. 351. SCHEDULED NECROPSY DAY 29 53769 G 57. 159. 287. SCHEDULED NECROPSY DAY 29 53774 G 271. 171. 440. SCHEDULED NECROPSY DAY 29 53775 G 87. 110. 330. SCHEDULED NECROPSY DAY 29

MEAN 158. 71. 285. S.D. 85.3 119.1 113.4 S.E. 17.4 24.3 23.2 N 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN154of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 13 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 4 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G -214. 15. 162. 0. -74. 83. 38. 29. -10. 54113 G -64. -5. 63. 0. 18. -23. 8. 0. NA 54116 G -59. 53. 44. -30. 37. 29. 29. 17. 8. 54121 G -112. 128. 211. -26. 25. 43. 47. -14. 10. 54122 G -60. 60. -40. -5. -17. 16. -5. 13. -127. 54125 G -37. 36. 38. 21. 9. 3. 40. 23. 8. 54126 G -12. 1. 121. 5. 18. 25. 21. 20. 28. 54127 G -135. 45. 18. -3. -1. 22. 18. 22. -1. 54130 G -284. 55. 183. -39. 22. 37. 3. 56. -1. 54133 G -119. 95. 24. -37. -26. 25. 20. 21. 47. 54134 G -59. 3. 111. 28. 2. 37. 34. 34. -19. 54136 G -108. -15. 211. 6. -21. 19. 11. 56. 22. 54142 NG -276. 527. -36. 80. 55. 50. 51. 28. 13. 54144 G -49. 159. -20. 7. 23. 18. 6. 39. 16. 54145 G -15. 134. 4. 13. 54. 9. 35. 24. 47. 54149 G 20. 270. -38. 43. 31. 18. 27. 16. 20. 54155 G -48. 120. 1. 31. 21. 29. 57. 9. -18. 54158 G -125. 134. -39. -37. 24. 27. -3. 9. 11. 54161 G -80. 203. -54. 26. 32. 26. -2. 12. 25. 54162 G -69. 218. -81. 74. 12. -7. 39. -4. 5. 54163 G -102. 41. 20. 30. -46. 25. -17. 15. 31. 54164 G -13. 184. -13. -42. 27. 4. 36. 12. 16. 54168 G -82. 217. -1. -6. 29. 48. 25. 9. 28. 54170 G 25. 203. -55. -2. 44. 9. 33. -6. 9.

MEAN -78. 102. 38. 2. 11. 23. 22. 18. 7. S.D. 70.1 85.0 87.7 29.3 30.0 20.7 18.9 17.3 34.7 S.E. 14.6 17.7 18.3 6.1 6.2 4.3 3.9 3.6 7.4 N 23 23 23 23 23 23 23 23 22

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE155of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 14 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY13-14 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G 81. -17. 55. 23. 40. 9. 29. 31. -97. 54113 G NA NA NA NA NA NA NA NA NA 54116 G 1. 51. 18. 41. -2. 32. 29. -6. 13. 54121 G 25. 32. 78. 51. 17. 6. 26. 39. 41. 54122 G -227. NA NA NA NA NA NA NA NA 54125 G 30. 29. 26. -6. 20. -80. -69. 95. 66. 54126 G 48. 63. 28. 10. 23. -64. 5. 36. 22. 54127 G -3. 23. 52. 40. 26. 7. -1. 8. 27. 54130 G 54. 39. 17. 29. 24. 27. 18. -9. 20. 54133 G 9. 32. -3. -101. -43. -17. -6. 51. 10. 54134 G 18. 40. 10. 26. 25. 29. 7. 20. 5. 54136 G 17. 29. 35. 7. -140. -70. 65. 80. 33. 54142 NG 55. -3. 55. -56. 118. 0. 59. 25. 109. 54144 G 73. 1. 43. -4. 18. 19. 34. 12. 43. 54145 G 69. 48. -1. 26. 28. 16. 20. 29. -4. 54149 G 71. 62. 42. 2. 12. -37. 42. 29. 29. 54155 G 11. 22. 31. 16. 30. 39. 7. 9. 23. 54158 G 29. 37. 27. 2. 13. 3. 35. -1. 27. 54161 G -10. 57. 50. -8. 36. 27. 9. 5. 22. 54162 G 73. 17. 24. 21. 15. 23. 14. 48. -9. 54163 G 33. -16. 27. 0. -21. 14. 25. 7. -8. 54164 G 28. 42. 34. 15. -11. 26. 43. -28. 24. 54168 G 10. 19. 17. -3. 15. 21. 5. -6. 9. 54170 G 34. 26. 55. -2. 14. 40. 10. 12. 13.

MEAN 22. 30. 32. 9. 7. 3. 17. 22. 15. S.D. 61.7 21.9 19.7 30.3 38.8 36.0 26.0 29.6 31.1 S.E. 13.2 4.8 4.3 6.6 8.5 7.9 5.7 6.5 6.8 N 22 21 21 21 21 21 21 21 21

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE156of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 15 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY22-23 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G -19. 27. -38. -117. -93. NA NA 88. 150. 54113 G NA NA NA NA NA NA NA 81. -15. 54116 G 27. 35. -5. -38. 8. 52. 14. 51. 75. 54121 G 16. 60. -11. -9. -37. 27. -14. 210. 76. 54122 G NA NA NA NA NA NA NA -62. 24. 54125 G 27. -30. -19. -86. -116. -81. NA 68. 66. 54126 G 8. 31. -24. 40. -4. 5. 15. 144. 66. 54127 G -7. -3. -27. -79. -48. -41. -161. 14. 62. 54130 G -134. -121. -51. -24. -109. -49. -61. 166. 96. 54133 G 58. 8. 13. 24. 5. -16. 40. -39. 66. 54134 G -140. 119. 17. 3. 5. -14. 50. 141. 105. 54136 G 20. -2. 33. 44. -3. 37. -86. 196. 86. 54142 NG 34. 44. 57. -13. 8. 37. 0. 99. 129. 54144 G -6. 36. 23. -96. NA NA NA 10. 63. 54145 G 2. -75. -24. -56. -27. -55. -8. 71. 68. 54149 G -68. -215. -36. 37. 148. 31. 70. 36. 61. 54155 G 22. -16. -65. 11. 9. -19. 23. 53. 95. 54158 G 14. 14. 37. 23. 23. 20. 52. -52. 33. 54161 G -23. -3. 1. -22. 13. -13. -4. 4. 36. 54162 G -70. -81. -42. -77. -77. 44. 6. 5. 28. 54163 G 26. 14. 30. -7. 9. 8. 12. 4. 23. 54164 G 12. -2. 26. -12. 22. -113. -79. -28. 52. 54168 G 26. 14. -22. -23. -20. -132. -7. 22. 82. 54170 G 29. 0. -8. 17. 17. 1. -29. -13. 36.

MEAN -9. -9. -9. -21. -14. -16. -9. 51. 62. S.D. 52.5 69.0 29.6 47.9 58.3 51.7 57.3 77.4 34.1 S.E. 11.5 15.1 6.5 10.4 13.0 11.9 13.5 16.1 7.1 N 21 21 21 21 20 19 18 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE157of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 16 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY12-20 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G 210. NA NA ABORTED DAY 28 54113 G NA NA NA GRAVID, DIED DAY 13 54116 G 178. 100. 404. SCHEDULED NECROPSY DAY 29 54121 G 245. 112. 643. SCHEDULED NECROPSY DAY 29 54122 G NA NA NA GRAVID, DIED DAY 14 54125 G -42. NA NA GRAVID, EUTHANIZED DAY 28 54126 G 141. 129. 480. SCHEDULED NECROPSY DAY 29 54127 G 143. -331. -112. SCHEDULED NECROPSY DAY 29 54130 G 207. -538. -69. SCHEDULED NECROPSY DAY 29 54133 G -82. 193. 138. SCHEDULED NECROPSY DAY 29 54134 G 136. 65. 447. SCHEDULED NECROPSY DAY 29 54136 G -35. 156. 403. SCHEDULED NECROPSY DAY 29 54142 NG 241. 301. 770. SCHEDULED NECROPSY DAY 29 54144 G 200. NA NA GRAVID, DIED DAY 27 54145 G 253. -218. 174. SCHEDULED NECROPSY DAY 29 54149 G 214. 25. 336. SCHEDULED NECROPSY DAY 29 54155 G 138. -3. 283. SCHEDULED NECROPSY DAY 29 54158 G 157. 209. 347. SCHEDULED NECROPSY DAY 29 54161 G 186. -24. 202. SCHEDULED NECROPSY DAY 29 54162 G 192. -258. -33. SCHEDULED NECROPSY DAY 29 54163 G 93. 91. 211. SCHEDULED NECROPSY DAY 29 54164 G 193. -150. 67. SCHEDULED NECROPSY DAY 29 54168 G 112. -161. 55. SCHEDULED NECROPSY DAY 29 54170 G 186. 52. 261. SCHEDULED NECROPSY DAY 29

MEAN 144. -31. 235. S.D. 92.0 203.7 204.9 S.E. 20.1 48.0 48.3 N 21 18 18

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE158of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 17 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 4 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 47. 134. -18. 17. -1. 17. 14. 21. 2. 53725 G 30. 315. -43. -21. 41. 40. 35. 37. 74. 53727 G -294. 443. -11. 29. 4. -29. 47. 17. 15. 53730 G -54. 127. -19. 13. 25. 5. 36. 4. 17. 53732 G -23. 126. -56. -30. -7. 25. -62. NA NA 53770 G -1. 180. -7. 17. -1. -30. -12. 16. 16. 53771 G 57. 265. 7. -23. 22. 17. 17. 26. 16. 53772 G -22. 190. -43. 10. 33. 2. -6. 33. 29. 53773 G 58. 189. -13. -35. 54. 13. 7. 39. 62. 53776 G 13. 231. -16. 4. -1. 15. -15. 39. 28. 53777 G 29. 177. 28. -1. -2. 9. -5. 38. -2. 53781 G -4. 78. -40. -9. -8. 9. 18. -8. -22. 54108 G 19. 47. 158. -6. 21. 13. 38. 18. 21. 54111 G 23. 38. 96. 28. -50. -3. 26. 40. 28. 54112 G -27. -50. 21. -3. -6. 1. 11. 34. 7. 54114 G -93. 37. 110. -2. -26. 10. 68. -8. 15. 54115 G -57. 7. 25. 4. 27. 31. 24. 17. -4. 54132 G -55. 27. 12. 19. 17. 28. -4. 48. -19. 54135 G -83. -21. 74. 13. -8. 31. 22. -5. 32. 54138 G -103. 26. 97. 4. 48. -30. 12. 18. 3. 54140 G -74. 154. -12. -63. 71. 2. 56. 90. 17. 54150 G 20. 168. -43. 59. 40. 34. 55. 21. 15. 54151 G -42. 140. -43. -19. 5. 39. 8. 32. -4. 54165 G -43. 206. -61. 0. 35. 23. 4. 19. 35.

MEAN -28. 135. 8. 0. 14. 11. 16. 25. 17. S.D. 73.8 113.9 58.5 24.7 27.4 19.9 27.8 21.1 22.2 S.E. 15.1 23.2 11.9 5.1 5.6 4.1 5.7 4.4 4.6 N 24 24 24 24 24 24 24 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE159of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 18 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY13-14 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 8. 36. 9. 6. -12. -140. -28. 125. 10. 53725 G 26. 31. 48. -6. 65. 9. 18. -30. 35. 53727 G 2. 73. 29. 46. -37. -40. 50. 44. -29. 53730 G 11. 40. -10. 55. -15. -5. 5. 59. 5. 53732 G NA NA NA NA NA NA NA NA NA 53770 G 22. 55. 8. 14. 4. 17. 9. 23. -39. 53771 G -6. 27. 26. 8. 31. 10. 25. 18. 31. 53772 G 23. 22. 8. 37. 4. 38. 18. 14. 40. 53773 G 4. 31. 48. 44. 46. -35. 45. 34. 34. 53776 G 38. 82. 1. 14. -39. 22. 33. 16. 25. 53777 G 18. 6. 35. 18. 23. 11. 21. -17. 26. 53781 G -207. NA NA NA NA NA NA NA NA 54108 G 9. 25. 12. 15. 37. -3. 31. -2. 22. 54111 G -172. -192. -2. -103. -45. -49. 6. -35. -35. 54112 G 34. 38. 12. 6. 7. 22. 9. -4. 14. 54114 G 44. 2. -133. NA NA NA NA NA NA 54115 G -231. NA NA NA NA NA NA NA NA 54132 G 27. 61. -6. -193. NA NA NA NA NA 54135 G 5. 44. -24. 33. 14. -8. 23. -9. 23. 54138 G -224. NA NA NA NA NA NA NA NA 54140 G 69. 23. 5. 8. 47. 44. 14. 35. 19. 54150 G -1. 45. 51. 16. 3. 53. 9. 3. 35. 54151 G 46. 52. -3. 9. 18. -140. NA NA NA 54165 G 17. 33. 31. 20. 8. 22. 11. 8. 45.

MEAN -19. 27. 7. 2. 9. -10. 18. 17. 15. S.D. 91.1 55.2 38.9 57.3 30.6 54.8 17.6 37.6 25.9 S.E. 19.0 12.3 8.7 13.2 7.2 12.9 4.3 9.1 6.3 N 23 20 20 19 18 18 17 17 17

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE160of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 19 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY22-23 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 64. 60. 2. 44. -6. 14. 39. -2. 52. 53725 G -22. 25. -42. -80. -63. -143. -77. -23. 112. 53727 G -14. 24. 69. 5. -23. 13. 84. 22. 35. 53730 G 12. 32. 23. 67. -15. 54. 38. 19. 45. 53732 G NA NA NA NA NA NA NA -93. NA 53770 G -278. -150. 45. NA NA NA NA 9. -26. 53771 G 4. -45. 30. 29. -32. 32. 2. 6. 60. 53772 G 26. 34. -29. 54. -19. 18. 27. 0. 29. 53773 G -24. 13. 35. 36. 27. 0. -4. 6. 59. 53776 G 29. -44. 18. -37. 21. -17. 40. -13. 39. 53777 G 5. -13. -17. 8. 45. 11. 40. 25. 42. 53781 G NA NA NA NA NA NA NA -57. 19. 54108 G 32. 3. 30. -46. -20. -4. 1. 173. 69. 54111 G -23. -13. -63. -43. NA NA NA 74. 63. 54112 G 28. 10. 3. 8. 9. 10. 23. 12. 46. 54114 G NA NA NA NA NA NA NA 82. 70. 54115 G NA NA NA NA NA NA NA 56. 72. 54132 G NA NA NA NA NA NA NA 48. 72. 54135 G 12. 13. 10. 27. -35. 26. 19. 79. 48. 54138 G NA NA NA NA NA NA NA 149. 0. 54140 G -12. -169. -126. -99. -151. -3. NA -4. 148. 54150 G 24. 21. 15. -20. -7. 14. 48. 56. 110. 54151 G NA NA NA NA NA NA NA -57. 79. 54165 G -14. -6. 17. -60. -152. -44. NA -26. 46.

MEAN -9. -12. 1. -7. -28. -1. 22. 23. 56. S.D. 73.5 61.6 46.1 49.8 56.8 45.0 37.7 60.9 36.5 S.E. 17.8 15.0 11.2 12.4 14.7 11.6 10.5 12.4 7.6 N 17 17 17 16 15 15 13 24 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE161of475TABLE A7 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 20 SPONSOR:HONEYWELL INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY12-20 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G -119. 352. 283. SCHEDULED NECROPSY DAY 29 53725 G 265. -397. -43. SCHEDULED NECROPSY DAY 29 53727 G 138. 173. 368. SCHEDULED NECROPSY DAY 29 53730 G 98. 275. 437. SCHEDULED NECROPSY DAY 29 53732 G NA NA NA GRAVID, DIED DAY 12 53770 G 145. NA NA ABORTED DAY 26 53771 G 137. 69. 272. SCHEDULED NECROPSY DAY 29 53772 G 179. 165. 373. SCHEDULED NECROPSY DAY 29 53773 G 245. 151. 461. SCHEDULED NECROPSY DAY 29 53776 G 179. 51. 256. SCHEDULED NECROPSY DAY 29 53777 G 130. 88. 285. SCHEDULED NECROPSY DAY 29 53781 G NA NA NA GRAVID, DIED DAY 14 54108 G 147. 16. 405. SCHEDULED NECROPSY DAY 29 54111 G -529. NA NA ABORTED DAY 26 54112 G 135. 101. 294. SCHEDULED NECROPSY DAY 29 54114 G NA NA NA GRAVID, EUTHANIZED DAY 16 54115 G NA NA NA GRAVID, DIED DAY 14 54132 G NA NA NA GRAVID, DIED DAY 18 54135 G 119. 86. 332. SCHEDULED NECROPSY DAY 29 54138 G NA NA NA GRAVID, DIED DAY 14 54140 G 227. NA NA DELIVERED DAY 29 54150 G 191. 133. 490. SCHEDULED NECROPSY DAY 29 54151 G NA NA NA GRAVID, DIED DAY 20 54165 G 177. NA NA ABORTED DAY 29

MEAN 110. 97. 324. S.D. 184.2 174.4 134.2 S.E. 44.7 48.4 37.2 N 17 13 13

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE PGBWv4.07 05/21/2008162of475TABLE A8 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL GRAVID UTERINE WTS. AND NET BODY WT. CHANGES [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY INITIAL TERMINAL GRAVID NET BODY NET BODY STATUS BODY WT. BODY WT. UTERINE WT. WT. WT. CHANGE

----------------------------------------------------------------------------------------------------------------------------------- DAM # GROUP 1: 0 PPM

-------------------------------------------- 53726 G 3124. 3659. 588.3 3070.7 -53.3 53735 G 2998. 3375. 357.0 3018.0 20.0 53738 G 3317. 3861. 449.2 3411.8 94.8 53739 G 3494. 3926. 454.8 3471.2 -22.8 53742 G 3057. 3813. 522.3 3290.7 233.7 53748 G 2892. 3454. 446.3 3007.7 115.7 53752 G 2962. 3667. 593.7 3073.3 111.3 53758 G 3082. 3675. 499.5 3175.5 93.5 53760 G 3026. 3458. 540.3 2917.7 -108.3 53763 G 3013. 3593. 508.2 3084.8 71.8 53780 G 3141. 3691. 482.9 3208.1 67.1 53783 G 3229. 3781. 631.5 3149.5 -79.5 54117 G 3567. 3927. 560.1 3366.9 -200.1 54124 G 3187. 3714. 518.5 3195.5 8.5 54128 G 3313. 3763. 362.0 3401.0 88.0 54129 G 3452. 3607. 496.8 3110.2 -341.8 54137 G 3277. 3776. 578.3 3197.7 -79.3 54143 G 3036. 3448. 523.6 2924.4 -111.6 54147 G 3330. 3740. 499.1 3240.9 -89.1 54153 G 2997. 3497. 282.9 3214.1 217.1 54157 G 3133. 3884. 592.7 3291.3 158.3 54166 G 2929. 3447. 455.4 2991.6 62.6 54167 G 3199. 3840. 391.5 3448.5 249.5 54169 G 2943. 3407. 463.8 2943.2 0.2

MEAN 3154. 3667. 491.6 3175.2 21.1 S.D. 186.2 173.1 84.21 167.40 139.66 S.E. 38.0 35.3 17.19 34.17 28.51 N 24 24 24 24 24

G = GRAVID163of475TABLE A8 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL INDIVIDUAL GRAVID UTERINE WTS. AND NET BODY WT. CHANGES [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY INITIAL TERMINAL GRAVID NET BODY NET BODY STATUS BODY WT. BODY WT. UTERINE WT. WT. WT. CHANGE

----------------------------------------------------------------------------------------------------------------------------------- DAM # GROUP 2: 2500 PPM

-------------------------------------------- 53729 G 3021. 3615. 463.1 3151.9 130.9 53736 G 2940. 3435. 476.5 2958.5 18.5 53737 G 3054. 3555. 536.4 3018.6 -35.4 53741 G 2959. 3679. 628.9 3050.1 91.1 53744 NG 3183. 3575. NA NA NA 53745 G 3082. 3864. 587.1 3276.9 194.9 53753 G 2984. 3788. 486.1 3301.9 317.9 53757 G 3039. 3527. 403.1 3123.9 84.9 53759 G 3107. 3700. 425.5 3274.5 167.5 53778 G 2971. 3337. 377.1 2959.9 -11.1 53779 G 3074. 3483. 478.3 3004.7 -69.3 53782 G 3188. 3264. 421.6 2842.4 -345.6 54119 G 3505. 3969. 513.6 3455.4 -49.6 54120 G 3371. 3564. 428.3 3135.7 -235.3 54123 G 3190. 3276. 460.1 2815.9 -374.1 54131 G 3770. 4467. 581.3 3885.7 115.7 54139 G 3423. 3927. 520.4 3406.6 -16.4 54141 G 3319. 3785. 563.5 3221.5 -97.5 54146 G 2988. 3341. 413.0 2928.0 -60.0 54148 G 3039. 3466. 502.0 2964.0 -75.0 54152 G 2955. 3439. 665.9 2773.1 -181.9 54156 G 3255. 3156. 406.6 2749.4 -505.6 54159 G 3092. 3337. 273.8 3063.2 -28.8 54160 G 3134. 3563. 329.3 3233.7 99.7

MEAN 3150. 3589. 475.7 3112.8 -37.6 S.D. 207.5 291.0 93.62 257.41 193.40 S.E. 43.3 60.7 19.52 53.67 40.33 N 23 23 23 23 23

G = GRAVID, NG = NONGRAVID, NOT INCLUDED IN CALCULATION OF THE MEAN NA = NOT APPLICABLE164of475TABLE A8 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL INDIVIDUAL GRAVID UTERINE WTS. AND NET BODY WT. CHANGES [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY INITIAL TERMINAL GRAVID NET BODY NET BODY STATUS BODY WT. BODY WT. UTERINE WT. WT. WT. CHANGE

----------------------------------------------------------------------------------------------------------------------------------- DAM # GROUP 3: 4000 PPM

-------------------------------------------- 53723 G 3144. 3620. 396.4 3223.6 79.6 53724 G 3103. 3533. 460.5 3072.5 -30.5 53728 G 3027. 3287. 420.9 2866.1 -160.9 53731 G 3292. 3779. 405.5 3373.5 81.5 53733 G 3089. 3685. 444.8 3240.2 151.2 53734 G 3369. 3814. 578.9 3235.1 -133.9 53740 G 2971. 3558. 578.1 2979.9 8.9 53743 G 3046. 3419. 455.0 2964.0 -82.0 53747 G 2917. 3178. 426.6 2751.4 -165.6 53749 G 2979. 3300. 270.8 3029.2 50.2 53750 G 2964. 3314. 373.8 2940.2 -23.8 53751 G 2948. 3053. 268.4 2784.6 -163.4 53754 G 3063. 3491. 502.9 2988.1 -74.9 53755 G 3022. 3623. 527.0 3096.0 74.0 53756 G 2940. 3521. 490.2 3030.8 90.8 53761 G 3046. 3414. 475.7 2938.3 -107.7 53762 G 3136. 3469. 373.5 3095.5 -40.5 53764 G 2982. 3256. 370.5 2885.5 -96.5 53765 G 2989. 3393. 519.5 2873.5 -115.5 53766 G 3081. 3688. 670.3 3017.7 -63.3 53768 G 3226. 3781. 532.3 3248.7 22.7 53769 G 3185. 3519. 454.9 3064.1 -120.9 53774 G 3132. 3838. 587.0 3251.0 119.0 53775 G 2992. 3459. 470.2 2988.8 -3.2

MEAN 3068. 3500. 460.6 3039.1 -29.4 S.D. 114.5 207.0 95.59 159.49 96.11 S.E. 23.4 42.2 19.51 32.56 19.62 N 24 24 24 24 24

G = GRAVID165of475TABLE A8 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL INDIVIDUAL GRAVID UTERINE WTS. AND NET BODY WT. CHANGES [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY INITIAL TERMINAL GRAVID NET BODY NET BODY STATUS BODY WT. BODY WT. UTERINE WT. WT. WT. CHANGE

----------------------------------------------------------------------------------------------------------------------------------- DAM # GROUP 4: 5500 PPM

-------------------------------------------- 54116 G 3352. 3750. 480.3 3269.7 -82.3 54121 G 3210. 3869. 500.9 3368.1 158.1 54126 G 3202. 3671. 491.4 3179.6 -22.4 54127 G 3219. 3017. 228.0 2789.0 -430.0 54130 G 3558. 3260. 368.2 2891.8 -666.2 54133 G 3330. 3444. 394.3 3049.7 -280.3 54134 G 3011. 3402. 477.7 2924.3 -86.7 54136 G 3463. 3743. 635.1 3107.9 -355.1 54142 NG 3529. 4550. NA NA NA 54145 G 3128. 3421. 402.2 3018.8 -109.2 54149 G 3064. 3690. 529.4 3160.6 96.6 54155 G 2994. 3349. 402.3 2946.7 -47.3 54158 G 3151. 3507. 459.7 3047.3 -103.7 54161 G 3006. 3331. 468.6 2862.4 -143.6 54162 G 3598. 3714. 468.3 3245.7 -352.3 54163 G 2925. 3075. 358.8 2716.2 -208.8 54164 G 3419. 3657. 424.7 3232.3 -186.7 54168 G 3063. 3253. 529.1 2723.9 -339.1 54170 G 3232. 3721. 476.2 3244.8 12.8

MEAN 3218. 3493. 449.7 3043.3 -174.8 S.D. 199.4 247.9 86.39 197.64 202.32 S.E. 47.0 58.4 20.36 46.58 47.69 N 18 18 18 18 18

G = GRAVID, NG = NONGRAVID, NOT INCLUDED IN CALCULATION OF THE MEAN NA = NOT APPLICABLE166of475TABLE A8 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL INDIVIDUAL GRAVID UTERINE WTS. AND NET BODY WT. CHANGES [G]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY INITIAL TERMINAL GRAVID NET BODY NET BODY STATUS BODY WT. BODY WT. UTERINE WT. WT. WT. CHANGE

----------------------------------------------------------------------------------------------------------------------------------- DAM # GROUP 5: 7500 PPM

-------------------------------------------- 53722 G 3194. 3658. 610.7 3047.3 -146.7 53725 G 3072. 3374. 443.1 2930.9 -141.1 53727 G 3141. 3658. 617.4 3040.6 -100.4 53730 G 2963. 3473. 528.6 2944.4 -18.6 53771 G 2987. 3581. 502.4 3078.6 91.6 53772 G 3175. 3716. 541.5 3174.5 -0.5 53773 G 3065. 3773. 589.0 3184.0 119.0 53776 G 3040. 3540. 499.6 3040.4 0.4 53777 G 2962. 3453. 464.9 2988.1 26.1 54108 G 3232. 3703. 448.6 3254.4 22.4 54112 G 3006. 3223. 333.9 2889.1 -116.9 54135 G 3162. 3390. 457.2 2932.8 -229.2 54150 G 3293. 3971. 543.0 3428.0 135.0

MEAN 3099. 3578. 506.1 3071.8 -27.6 S.D. 107.9 198.1 78.74 153.23 111.84 S.E. 29.9 54.9 21.84 42.50 31.02 N 13 13 13 13 13

G = GRAVID PUTv4.05 05/20/2008167of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13 13-14

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 162. 169. 148. 148. 130. 133. 135. 154. 152. 53735 G 179. 132. 139. 149. 142. 149. 142. 128. 128. 53738 G 188. 177. 171. 161. 171. 176. 156. 183. 163. 53739 G 189. 177. 185. 181. 167. 174. 178. 179. 170. 53742 G 206. 149. 186. 181. 200. 185. 176. 192. 183. 53748 G 179. 131. 129. 127. 112. 121. 122. 105. 110. 53752 G 197. 172. 172. 169. 173. 172. 171. 174. 162. 53758 G 204. 174. 174. 165. 143. 153. 152. 130. 123. 53760 G 201. 174. 182. 152. 172. 183. 180. 169. 162. 53763 G 213. 168. 163. 156. 151. 154. 147. 138. 138. 53780 G 220. 184. 188. 192. 178. 185. 186. 197. 182. 53783 G 149. 121. 124. 113. 127. 114. 103. 89. 79. 54117 G 113. 179. 148. 147. 158. 137. 143. 142. 139. 54124 G 116. 175. 163. 162. 144. 145. 153. 149. 140. 54128 G 117. 178. 155. 140. 139. 150. 143. 140. 153. 54129 G 104. 172. 175. 163. 180. 174. 178. 166. 165. 54137 G 108. 177. 170. 161. 145. 140. 125. 122. 132. 54143 G 173. 164. 171. 165. 149. 158. 165. 141. 154. 54147 G 191. 161. 183. 185. 172. 180. 188. 170. 181. 54153 G 142. 146. 146. 137. 146. 133. 146. 134. 149. 54157 G 202. 210. 204. 217. 214. 207. 218. 202. 214. 54166 G 191. 180. 195. 209. 176. 220. 233. 194. 187. 54167 G 181. 132. 164. 172. 173. 175. 164. 136. 135. 54169 G 160. 168. 154. 158. 145. 147. 146. 124. 129.

MEAN 170. 165. 166. 163. 159. 161. 160. 152. 151. S.D. 36.1 20.5 20.3 23.8 23.5 26.1 29.3 30.2 28.6 S.E. 7.4 4.2 4.2 4.9 4.8 5.3 6.0 6.2 5.8 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN168of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22 22-23

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 153. 162. 141. 179. 178. 155. 114. 122. 135. 53735 G 128. 145. 139. 138. 153. 141. 139. 137. 132. 53738 G 172. 185. 181. 243. NA NA 227. 213. 194. 53739 G 168. 174. 159. 171. 168. 177. 157. 159. 151. 53742 G 189. 190. 192. 190. 190. 189. 192. 195. 179. 53748 G 124. 143. 144. 153. 165. 159. 153. 123. 149. 53752 G 162. 165. 162. 168. 172. 176. 173. 166. 149. 53758 G 152. 137. 159. 164. 171. 151. 151. 137. 119. 53760 G 161. 184. 196. 197. 193. 195. 200. 191. 175. 53763 G 154. 135. 174. 152. 160. 140. 149. 136. 113. 53780 G NA NA NA NA 205. 201. 195. 193. 182. 53783 G 100. 98. 121. 128. 133. 129. 122. 104. 85. 54117 G 140. 132. 157. 145. 141. 116. 139. 99. 80. 54124 G 147. 159. 152. 157. 162. 177. 166. 157. 140. 54128 G 158. 168. 156. 153. 156. 175. 163. 164. 149. 54129 G 173. 175. 167. 162. 121. 112. 86. 105. 101. 54137 G 129. 135. 143. 151. 144. 140. 135. 129. 117. 54143 G 158. 146. 156. 92. 155. 143. 136. 130. 132. 54147 G 192. 199. 202. 202. 207. 195. 178. 159. 116. 54153 G 152. 136. 153. 146. 157. 170. 163. 160. 158. 54157 G 206. 214. 208. 217. 217. 209. 194. 152. 159. 54166 G 186. 203. 200. 198. 213. 215. 200. 174. 162. 54167 G 147. 152. 169. 182. 195. 200. 187. 134. 112. 54169 G 141. 153. 163. 172. 173. 162. 167. 161. 179.

MEAN 156. 160. 165. 168. 171. 166. 162. 150. 140. S.D. 24.2 27.6 22.6 31.8 25.8 29.4 32.1 30.1 30.8 S.E. 5.0 5.7 4.7 6.6 5.4 6.1 6.6 6.1 6.3 N 23 23 23 23 23 23 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE169of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12 12-20

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 116. 126. 121. 129. 129. 140. 155. 133. 159. 53735 G 135. 111. 99. 68. 46. 97. 140. 144. 138. 53738 G 177. 124. 102. 106. 83. 118. 170. 168. 188. 53739 G 138. 128. 113. 114. 108. 117. 181. 173. 171. 53742 G 169. 152. 152. 128. 115. 111. 172. 187. 189. 53748 G 137. 135. 129. 93. 66. 64. 129. 118. 138. 53752 G 135. 129. 119. 112. 129. 116. 171. 172. 168. 53758 G 107. 109. 111. 118. 110. 104. 171. 149. 148. 53760 G 145. 95. 17. 20. 61. 67. 169. 178. 182. 53763 G 92. 103. 129. 137. 124. 61. 162. 151. 149. 53780 G 77. 104. 117. 109. 7. 2. 188. 183. 196. 53783 G 86. 81. 76. 85. 86. 81. 119. 115. 110. 54117 G 79. 81. 85. 78. 80. 83. 158. 146. 139. 54124 G 151. 143. 121. 116. 103. 96. 167. 147. 155. 54128 G 152. 132. 116. 108. 106. 113. 158. 144. 157. 54129 G 84. 37. 49. 53. 57. 71. 170. 177. 155. 54137 G 106. 100. 109. 95. 101. 105. 169. 137. 137. 54143 G 132. 118. 115. 126. 117. 127. 167. 157. 143. 54147 G 75. 13. 34. 62. 65. 55. 176. 180. 194. 54153 G 151. 132. 118. 117. 116. 124. 143. 142. 150. 54157 G 153. 146. 145. 122. 107. 121. 210. 213. 211. 54166 G 122. 90. 68. 33. 25. 38. 195. 210. 200. 54167 G 112. 128. 128. 138. 144. 138. 156. 171. 165. 54169 G 163. 143. 88. 81. 56. 78. 160. 146. 152.

MEAN 125. 111. 103. 98. 89. 93. 165. 160. 162. S.D. 31.0 33.3 33.3 32.0 35.0 33.7 19.6 25.3 24.7 S.E. 6.3 6.8 6.8 6.5 7.1 6.9 4.0 5.2 5.0 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN170of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 126. 142. SCHEDULED NECROPSY DAY 29 53735 G 107. 127. SCHEDULED NECROPSY DAY 29 53738 G 149. 166. SCHEDULED NECROPSY DAY 29 53739 G 132. 157. SCHEDULED NECROPSY DAY 29 53742 G 155. 173. SCHEDULED NECROPSY DAY 29 53748 G 117. 126. SCHEDULED NECROPSY DAY 29 53752 G 136. 156. SCHEDULED NECROPSY DAY 29 53758 G 118. 140. SCHEDULED NECROPSY DAY 29 53760 G 108. 151. SCHEDULED NECROPSY DAY 29 53763 G 116. 138. SCHEDULED NECROPSY DAY 29 53780 G 110. 152. SCHEDULED NECROPSY DAY 29 53783 G 90. 104. SCHEDULED NECROPSY DAY 29 54117 G 89. 123. SCHEDULED NECROPSY DAY 29 54124 G 133. 147. SCHEDULED NECROPSY DAY 29 54128 G 134. 146. SCHEDULED NECROPSY DAY 29 54129 G 71. 127. SCHEDULED NECROPSY DAY 29 54137 G 111. 131. SCHEDULED NECROPSY DAY 29 54143 G 126. 141. SCHEDULED NECROPSY DAY 29 54147 G 84. 147. SCHEDULED NECROPSY DAY 29 54153 G 138. 143. SCHEDULED NECROPSY DAY 29 54157 G 144. 185. SCHEDULED NECROPSY DAY 29 54166 G 101. 162. SCHEDULED NECROPSY DAY 29 54167 G 136. 153. SCHEDULED NECROPSY DAY 29 54169 G 124. 141. SCHEDULED NECROPSY DAY 29

MEAN 119. 145. S.D. 21.4 17.5 S.E. 4.4 3.6 N 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN171of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13 13-14

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G 213. 186. 194. 199. 161. 185. 190. 199. 195. 53736 G 189. 168. 163. 157. 156. 149. 139. 131. 126. 53737 G 174. 148. 163. 149. 140. 139. 125. 126. 123. 53741 G 189. 167. 179. 155. 160. 144. 161. 154. 164. 53744 NG 170. 157. 152. 150. 144. 137. 157. 163. 155. 53745 G 219. 212. 210. 186. 165. 173. 170. 161. 172. 53753 G 262. 185. 182. 175. 173. 197. 205. 181. 175. 53757 G 220. 177. 175. 176. 163. 187. 179. 160. 157. 53759 G 224. 178. 165. 160. 137. 137. 151. 133. 139. 53778 G 205. 156. 147. 127. 126. 135. 142. 131. 128. 53779 G 201. 164. 155. 157. 156. 173. 171. 149. 161. 53782 G 147. 114. 105. 107. 84. 106. 77. 71. 52. 54119 G 108. 221. 179. 182. 185. 186. 182. 184. 167. 54120 G 109. 148. 137. 147. 155. 149. 140. 128. 128. 54123 G 111. 158. 132. 129. NA 140. 133. 123. 81. 54131 G 108. 266. 220. 220. 240. 218. 231. 218. 219. 54139 G 177. 158. 181. 186. 179. 183. 186. 171. 189. 54141 G 20. 68. 167. 201. 183. 165. 171. 163. 171. 54146 G 163. 151. 162. 143. 139. 143. 160. 151. 155. 54148 G 166. 123. 142. 167. 141. 140. 141. 134. 139. 54152 G 164. 146. 146. 141. 144. 155. 148. 133. 129. 54156 G 137. 122. 126. 113. 115. 116. 105. 100. 87. 54159 G 159. 121. 136. 148. 145. 141. 148. 138. 147. 54160 G 160. 137. 138. 153. 132. 134. 130. 127. 116.

MEAN 166. 160. 161. 160. 154. 156. 156. 146. 144. S.D. 52.3 40.3 27.4 28.1 30.3 27.3 33.1 31.9 38.3 S.E. 10.9 8.4 5.7 5.9 6.5 5.7 6.9 6.7 8.0 N 23 23 23 23 22 23 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE172of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 6 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22 22-23

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G 171. 195. 169. 175. 201. 189. 185. NA 53. 53736 G 134. 153. 162. 165. 158. 146. 153. 137. 116. 53737 G 128. 144. 146. 157. 148. 144. 142. 143. 125. 53741 G 158. 159. 157. 158. 151. 158. 150. 142. 154. 53744 NG 147. 157. 148. 165. 169. 158. 152. 149. 154. 53745 G 173. 189. 183. 184. 200. 194. 187. 189. 158. 53753 G 169. 179. 192. 194. 211. 200. 198. 193. 185. 53757 G 167. 162. 147. 164. 165. 154. 150. 136. 126. 53759 G 156. 139. 152. 167. 176. 158. 162. 157. 152. 53778 G 133. 135. 151. 156. 167. 148. 167. 169. 159. 53779 G 163. 167. 159. 194. 175. 164. 166. 160. 142. 53782 G 1. 11. 45. 68. 68. 47. 57. 59. 56. 54119 G 173. 174. 181. 176. 165. 159. 126. 116. 81. 54120 G 136. 145. 144. 158. 140. 141. 132. 103. 77. 54123 G 63. 22. 39. 89. 132. 146. 144. 95. 47. 54131 G 211. 232. 220. 214. 213. 216. 209. 219. 212. 54139 G 177. 185. 186. 58. 187. 179. 160. 152. 136. 54141 G 172. 189. 192. 191. 186. 136. 136. 115. 99. 54146 G 153. 172. 170. 163. 168. 162. 162. 149. 149. 54148 G 169. 169. 181. 155. 178. 174. 158. 133. 122. 54152 G 139. 138. 155. 158. 161. 149. 138. 136. 132. 54156 G 86. 90. 102. 118. 113. 108. 88. 54. 36. 54159 G 145. 151. 163. 158. 172. 178. 169. 171. 163. 54160 G 124. 125. 125. 139. 137. 136. 127. 129. 132.

MEAN 144. 149. 153. 155. 164. 156. 151. 139. 122. S.D. 44.0 50.6 42.7 38.7 32.7 33.8 33.1 39.6 45.9 S.E. 9.2 10.5 8.9 8.1 6.8 7.1 6.9 8.4 9.6 N 23 23 23 23 23 23 23 22 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE173of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 7 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12 12-20

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G 80. 60. 30. 81. 94. 124. 193. 179. 187. 53736 G 115. 112. 87. 87. 100. 39. 163. 148. 147. 53737 G 119. 116. 102. 100. 91. 92. 153. 135. 140. 53741 G 153. 109. 121. 105. 136. 127. 167. 155. 157. 53744 NG 170. 159. 165. 162. 158. 163. 153. 146. 158. 53745 G 146. 100. 118. 104. 81. 106. 203. 169. 182. 53753 G 161. 164. 139. 137. 145. 160. 181. 192. 188. 53757 G 114. 106. 89. 104. 98. 99. 176. 176. 160. 53759 G 151. 139. 113. 122. 122. 127. 168. 142. 153. 53778 G 159. 125. 124. 112. 138. 97. 143. 134. 144. 53779 G 115. 54. 13. 32. 74. 79. 159. 167. 167. 53782 G 70. 76. 66. 64. 52. 82. 109. 89. 45. 54119 G 72. 55. 81. 100. 80. 70. 194. 184. 172. 54120 G 53. 44. 70. 53. 60. 48. 144. 148. 140. 54123 G 33. 51. 54. 46. 40. 39. 140. 137. 87. 54131 G 186. 167. 144. 79. 63. 51. 235. 230. 218. 54139 G 92. 56. 110. 93. 103. 127. 175. 183. 167. 54141 G 104. 101. 89. 81. 79. 93. 145. 173. 175. 54146 G 131. 103. 65. 38. 29. 46. 152. 147. 162. 54148 G 103. 71. 81. 8. 1. 71. 144. 141. 162. 54152 G 110. 109. 102. 105. 89. 97. 144. 149. 145. 54156 G 25. 2. 2. 7. 3. 7. 120. 112. 101. 54159 G 152. 142. 116. 61. 16. 2. 135. 145. 157. 54160 G 119. 94. 89. 72. 72. 71. 143. 132. 129.

MEAN 111. 94. 87. 78. 77. 81. 160. 155. 152. S.D. 42.0 40.7 37.1 34.7 40.4 39.9 28.3 29.3 36.1 S.E. 8.8 8.5 7.7 7.2 8.4 8.3 5.9 6.1 7.5 N 23 23 23 23 23 23 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN174of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 8 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G 88. 151. SCHEDULED NECROPSY DAY 29 53736 G 105. 133. SCHEDULED NECROPSY DAY 29 53737 G 114. 131. SCHEDULED NECROPSY DAY 29 53741 G 133. 149. SCHEDULED NECROPSY DAY 29 53744 NG 159. 156. SCHEDULED NECROPSY DAY 29 53745 G 132. 164. SCHEDULED NECROPSY DAY 29 53753 G 165. 178. SCHEDULED NECROPSY DAY 29 53757 G 114. 146. SCHEDULED NECROPSY DAY 29 53759 G 138. 148. SCHEDULED NECROPSY DAY 29 53778 G 139. 141. SCHEDULED NECROPSY DAY 29 53779 G 93. 137. SCHEDULED NECROPSY DAY 29 53782 G 65. 67. SCHEDULED NECROPSY DAY 29 54119 G 87. 143. SCHEDULED NECROPSY DAY 29 54120 G 71. 115. SCHEDULED NECROPSY DAY 29 54123 G 61. 88. SCHEDULED NECROPSY DAY 29 54131 G 148. 194. SCHEDULED NECROPSY DAY 29 54139 G 114. 149. SCHEDULED NECROPSY DAY 29 54141 G 100. 141. SCHEDULED NECROPSY DAY 29 54146 G 97. 133. SCHEDULED NECROPSY DAY 29 54148 G 83. 126. SCHEDULED NECROPSY DAY 29 54152 G 113. 133. SCHEDULED NECROPSY DAY 29 54156 G 25. 75. SCHEDULED NECROPSY DAY 29 54159 G 110. 134. SCHEDULED NECROPSY DAY 29 54160 G 101. 120. SCHEDULED NECROPSY DAY 29

MEAN 104. 135. S.D. 31.6 28.9 S.E. 6.6 6.0 N 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN175of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 9 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13 13-14

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 205. 174. 186. 186. 181. 175. 150. 160. 160. 53724 G 179. 183. 179. 185. 168. 191. 169. 162. 159. 53728 G 186. 164. 147. 151. 142. 144. 63. 1. 5. 53731 G 190. 175. 176. 176. 190. 186. 183. 164. 157. 53733 G 190. 161. 174. 172. 167. 168. 170. 183. 156. 53734 G 210. 163. 191. 194. 197. 198. 194. 192. 179. 53740 G 205. 172. 165. 175. 166. 169. 165. 162. 152. 53743 G 161. 136. 121. 119. 127. 117. 102. 80. 99. 53747 G 185. 159. 140. 138. 142. 135. 127. 132. 116. 53749 G 167. 145. 134. 147. 158. 161. 152. 127. 106. 53750 G 185. 152. 167. 161. 155. 176. 169. 159. 155. 53751 G 146. 124. 116. 123. 111. 113. 103. 105. 110. 53754 G 221. 180. 177. 152. 122. 132. 126. 113. 37. 53755 G 233. 166. 165. 179. 179. 176. 186. 164. 163. 53756 G 237. 177. 173. 174. 161. 157. 171. 161. 155. 53761 G 244. 194. 197. 165. 192. 171. 185. 165. 155. 53762 G 215. 176. 157. 165. 169. 170. 163. 157. 150. 53764 G 202. 162. 157. 169. 169. 157. 159. 143. 142. 53765 G 201. 162. 128. 177. 164. 174. 164. 141. 134. 53766 G 233. 198. 199. 197. 195. 193. 182. 165. 173. 53768 G 214. 192. 183. 171. 190. 163. 168. 158. 167. 53769 G 176. 158. 154. 146. 150. 140. 145. 129. 132. 53774 G 251. 192. 193. 176. 174. 177. 178. 184. 157. 53775 G 165. 165. 171. 175. 154. 159. 156. 123. 101.

MEAN 200. 168. 165. 166. 163. 163. 155. 143. 134. S.D. 27.8 18.0 23.7 20.1 23.0 22.6 31.2 40.1 41.9 S.E. 5.7 3.7 4.8 4.1 4.7 4.6 6.4 8.2 8.5 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN176of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 10 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22 22-23

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 166. 188. 169. 169. 185. 176. 165. 160. 146. 53724 G 165. 186. 174. 166. 180. 178. 168. 156. 136. 53728 G 37. 109. 150. 166. 177. 165. 150. 145. 138. 53731 G 164. 184. 162. 152. 182. 168. 149. 132. 125. 53733 G 165. 166. 157. 165. 164. 160. 152. 140. 131. 53734 G 182. 202. 163. 178. 185. 192. 174. 155. 141. 53740 G 146. 159. 146. 147. 151. 146. 148. 135. 128. 53743 G 103. 108. 110. 109. 112. 108. 100. 94. 89. 53747 G 118. 136. 125. 133. 133. 124. 113. 102. 88. 53749 G 16. 1. 18. 33. 61. 128. 172. 180. 185. 53750 G 155. 158. 145. 141. 148. 147. 135. 124. 113. 53751 G 105. 120. 106. 100. 110. 120. 115. 106. 95. 53754 G 46. 58. 99. 121. 153. 151. 158. 160. 138. 53755 G 169. 174. 184. 177. 166. 174. 176. 129. 160. 53756 G 174. 171. 137. 144. 168. 173. 179. 172. 168. 53761 G 183. 180. 174. 168. 179. 164. 155. 137. 110. 53762 G 153. 166. 156. 161. 164. 141. 127. 132. 108. 53764 G 152. 148. 157. 177. 169. 173. 164. 161. 137. 53765 G 127. 152. 163. 177. 175. 164. 166. 134. 106. 53766 G 186. 185. 197. 192. 205. 195. 181. 187. 186. 53768 G 174. 173. 187. 192. 176. 168. 161. 159. 127. 53769 G 124. 116. 101. 96. 118. 115. 122. 128. 117. 53774 G 181. 165. 170. 181. 180. 168. 167. 162. 154. 53775 G 109. 98. 119. 103. 102. 83. 104. 92. 92.

MEAN 138. 146. 145. 148. 156. 153. 150. 141. 130. S.D. 47.9 46.5 38.6 38.0 33.8 27.9 24.5 25.7 27.8 S.E. 9.8 9.5 7.9 7.7 6.9 5.7 5.0 5.2 5.7 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN177of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 11 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12 12-20

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 119. 112. 102. 95. 93. 102. 182. 169. 172. 53724 G 104. 75. 43. 28. 71. 63. 182. 176. 171. 53728 G 120. 126. 120. 127. 120. NA 154. 116. 101. 53731 G 119. 114. 106. 95. 75. 84. 176. 186. 167. 53733 G 112. 88. 98. 105. 114. 117. 169. 168. 165. 53734 G 108. 86. 61. 56. 38. 44. 183. 196. 184. 53740 G 116. 111. 96. 83. 89. 93. 171. 167. 151. 53743 G 90. 76. 89. 81. 83. 92. 125. 115. 104. 53747 G 73. 66. 60. 50. 70. 86. 146. 135. 127. 53749 G 183. 175. 169. 160. 146. 145. 142. 157. 61. 53750 G 157. 28. 90. 62. 34. 51. 160. 167. 151. 53751 G 75. 14. 52. 76. 56. 58. 121. 109. 110. 53754 G 112. 112. 92. 87. 79. 79. 170. 127. 97. 53755 G 146. 126. 106. 107. 85. 83. 170. 180. 171. 53756 G 163. 157. 144. 136. 121. 93. 175. 163. 160. 53761 G 89. 27. 7. 9. 69. 58. 185. 183. 171. 53762 G 82. 86. 66. 31. 2. 3. 166. 167. 156. 53764 G 118. 89. 55. 12. 1. 0. 163. 162. 158. 53765 G 85. 92. 78. 59. 44. 32. 156. 167. 154. 53766 G 165. 142. 120. 83. 93. NA 198. 190. 187. 53768 G 143. 113. 115. 122. 112. 94. 182. 174. 174. 53769 G 98. 92. 101. 88. 86. 134. 153. 145. 116. 53774 G 158. 155. 153. 137. 111. 102. 187. 176. 173. 53775 G 94. 75. 69. 58. 103. 95. 170. 156. 105.

MEAN 118. 97. 91. 81. 79. 78. 166. 160. 145. S.D. 31.1 40.3 36.7 39.7 36.2 36.7 19.0 24.1 33.7 S.E. 6.3 8.2 7.5 8.1 7.4 7.8 3.9 4.9 6.9 N 24 24 24 24 24 22 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE178of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 12 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 122. 153. SCHEDULED NECROPSY DAY 29 53724 G 94. 143. SCHEDULED NECROPSY DAY 29 53728 G 131. 121. SCHEDULED NECROPSY DAY 29 53731 G 111. 149. SCHEDULED NECROPSY DAY 29 53733 G 117. 147. SCHEDULED NECROPSY DAY 29 53734 G 96. 151. SCHEDULED NECROPSY DAY 29 53740 G 111. 140. SCHEDULED NECROPSY DAY 29 53743 G 88. 102. SCHEDULED NECROPSY DAY 29 53747 G 79. 112. SCHEDULED NECROPSY DAY 29 53749 G 168. 126. SCHEDULED NECROPSY DAY 29 53750 G 88. 130. SCHEDULED NECROPSY DAY 29 53751 G 72. 96. SCHEDULED NECROPSY DAY 29 53754 G 113. 117. SCHEDULED NECROPSY DAY 29 53755 G 124. 154. SCHEDULED NECROPSY DAY 29 53756 G 148. 158. SCHEDULED NECROPSY DAY 29 53761 G 73. 136. SCHEDULED NECROPSY DAY 29 53762 G 71. 125. SCHEDULED NECROPSY DAY 29 53764 G 82. 129. SCHEDULED NECROPSY DAY 29 53765 G 88. 130. SCHEDULED NECROPSY DAY 29 53766 G 145. 174. SCHEDULED NECROPSY DAY 29 53768 G 127. 157. SCHEDULED NECROPSY DAY 29 53769 G 107. 121. SCHEDULED NECROPSY DAY 29 53774 G 144. 164. SCHEDULED NECROPSY DAY 29 53775 G 87. 113. SCHEDULED NECROPSY DAY 29

MEAN 108. 135. S.D. 27.0 20.2 S.E. 5.5 4.1 N 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN179of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 13 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13 13-14

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G 115. 225. 180. 116. 191. 171. 157. 162. 172. 54113 G 85. 165. 137. 102. 111. 122. 109. NA NA 54116 G 112. 169. 149. 156. 169. 162. 159. 145. 141. 54121 G 108. 227. 179. 181. 198. 192. 171. 178. 179. 54122 G 113. 90. 76. 82. 104. 95. 73. 14. 1. 54125 G 138. 148. 137. 129. 138. 141. 139. 130. 111. 54126 G 114. 206. 188. 165. 189. 168. 169. 165. 170. 54127 G 111. 150. 147. 124. 152. 130. 133. 127. 112. 54130 G 115. 196. 136. 152. 162. 150. 158. 139. 150. 54133 G 118. 160. 151. 132. 151. 129. 141. 135. 119. 54134 G 113. 162. 152. 144. 158. 152. 143. 139. 117. 54136 G 111. 230. 199. 174. 187. 178. 173. 160. 154. 54142 NG 142. 152. 192. 210. 216. 215. 229. 226. 225. 54144 G 168. 156. 145. 156. 167. 140. 145. 143. 156. 54145 G 166. 167. 159. 178. 175. 171. 163. 170. 172. 54149 G 190. 172. 193. 218. 208. 206. 197. 197. 207. 54155 G 166. 136. 158. 168. 164. 176. 163. 139. 126. 54158 G 153. 122. 110. 120. 116. 119. 113. 121. 120. 54161 G 176. 132. 153. 175. 164. 150. 153. 131. 116. 54162 G 184. 137. 181. 183. 166. 151. 146. 143. 177. 54163 G 137. 108. 106. 119. 124. 117. 118. 117. 99. 54164 G 174. 177. 153. 167. 155. 162. 159. 160. 147. 54168 G 174. 172. 181. 182. 184. 172. 167. 168. 154. 54170 G 187. 171. 179. 178. 172. 159. 144. 133. 132.

MEAN 140. 164. 154. 152. 161. 153. 148. 142. 138. S.D. 32.3 36.1 29.8 32.1 27.7 26.2 26.1 34.8 41.3 S.E. 6.7 7.5 6.2 6.7 5.8 5.5 5.4 7.4 8.8 N 23 23 23 23 23 23 23 22 22

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE180of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 14 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22 22-23

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G 145. 152. 175. 186. 184. 189. 191. 108. 41. 54113 G NA NA NA NA NA NA NA NA NA 54116 G 153. 166. 177. 170. 162. 159. 137. 119. 115. 54121 G 188. 211. 204. 210. 206. 295. 229. 133. 134. 54122 G NA NA NA NA NA NA NA NA NA 54125 G 121. 128. 117. 126. 46. 24. 70. 107. 87. 54126 G 184. 178. 185. 183. 126. 107. 139. 137. 145. 54127 G 109. 117. 116. 125. 130. 114. 121. 114. 102. 54130 G 146. 166. 171. 167. 165. 149. 144. 120. 5. 54133 G 124. 119. 65. 21. 14. 48. 55. 56. 82. 54134 G 137. 149. 142. 151. 154. 137. 147. 123. 26. 54136 G 160. 160. 136. 18. 16. 65. 133. 146. 130. 54142 NG 223. 222. 188. 169. 214. 227. 219. 225. 249. 54144 G 157. 166. 158. 142. 161. 153. 147. 148. 129. 54145 G 188. 175. 176. 182. 189. 188. 172. 137. 117. 54149 G 207. 210. 205. 203. 194. 196. 180. 184. 137. 54155 G 124. 123. 131. 147. 147. 146. 131. 132. 119. 54158 G 126. 121. 134. 123. 130. 141. 129. 127. 123. 54161 G 126. 144. 146. 155. 163. 153. 133. 115. 97. 54162 G 165. 165. 168. 165. 166. 163. 153. 136. 83. 54163 G 99. 107. 101. 90. 110. 111. 105. 106. 97. 54164 G 148. 150. 156. 156. 157. 162. 138. 133. 123. 54168 G 145. 128. 128. 135. 139. 130. 104. 112. 93. 54170 G 132. 145. 140. 143. 150. 151. 139. 137. 142.

MEAN 147. 151. 149. 143. 139. 142. 138. 125. 101. S.D. 28.0 28.5 34.2 49.8 53.1 56.6 37.9 23.8 37.9 S.E. 6.1 6.2 7.5 10.9 11.6 12.3 8.3 5.2 8.3 N 21 21 21 21 21 21 21 21 21

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE181of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 15 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12 12-20

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G 53. 3. 3. 0. NA NA 174. 173. 171. 54113 G NA NA NA NA NA NA 135. 114. NA 54116 G 112. 105. 74. 82. 97. 93. 158. 163. 159. 54121 G 154. 167. 106. 78. 60. 61. 196. 187. 209. 54122 G NA NA NA NA NA NA 83. 91. NA 54125 G 61. 44. 3. 0. NA NA 138. 139. 100. 54126 G 147. 129. 122. 116. 111. 102. 186. 175. 162. 54127 G 86. 62. 26. 0. 2. 0. 140. 138. 119. 54130 G 1. 0. 1. 0. 1. 0. 161. 157. 157. 54133 G 120. 124. 117. 120. 114. 122. 148. 140. 81. 54134 G 100. 100. 82. 99. 79. 89. 153. 151. 141. 54136 G 91. 127. 137. 139. 123. 39. 201. 179. 109. 54142 NG 231. 240. 244. 220. 227. 214. 185. 220. 212. 54144 G 119. 103. 37. NA NA NA 152. 151. 155. 54145 G 57. 28. 31. 7. 28. 39. 168. 170. 180. 54149 G 1. 0. 39. 99. 102. 124. 194. 204. 202. 54155 G 95. 100. 46. 63. 50. 61. 154. 168. 135. 54158 G 106. 110. 117. 113. 114. 110. 117. 116. 127. 54161 G 78. 58. 40. 43. 50. 54. 153. 156. 142. 54162 G 26. 5. 0. 3. 22. 33. 167. 154. 164. 54163 G 92. 89. 73. 71. 73. 80. 111. 120. 104. 54164 G 106. 102. 98. 80. 8. 2. 166. 159. 155. 54168 G 81. 40. 48. 55. 3. 7. 178. 174. 141. 54170 G 123. 95. 93. 87. 89. 76. 176. 158. 141.

MEAN 86. 76. 62. 63. 63. 61. 157. 154. 145. S.D. 41.5 49.1 44.2 46.7 43.6 41.9 28.2 26.0 32.2 S.E. 9.1 10.7 9.6 10.5 10.3 9.9 5.9 5.4 7.0 N 21 21 21 20 18 18 23 23 21

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE182of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 16 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G NA NA ABORTED DAY 28 54113 G NA NA GRAVID, DIED DAY 13 54116 G 104. 138. SCHEDULED NECROPSY DAY 29 54121 G 125. 171. SCHEDULED NECROPSY DAY 29 54122 G NA NA GRAVID, DIED DAY 14 54125 G NA NA GRAVID, EUTHANIZED DAY 28 54126 G 128. 154. SCHEDULED NECROPSY DAY 29 54127 G 57. 100. SCHEDULED NECROPSY DAY 29 54130 G 30. 108. SCHEDULED NECROPSY DAY 29 54133 G 101. 105. SCHEDULED NECROPSY DAY 29 54134 G 94. 125. SCHEDULED NECROPSY DAY 29 54136 G 118. 134. SCHEDULED NECROPSY DAY 29 54142 NG 230. 216. SCHEDULED NECROPSY DAY 29 54144 G NA NA GRAVID, DIED DAY 27 54145 G 68. 133. SCHEDULED NECROPSY DAY 29 54149 G 96. 160. SCHEDULED NECROPSY DAY 29 54155 G 89. 124. SCHEDULED NECROPSY DAY 29 54158 G 117. 120. SCHEDULED NECROPSY DAY 29 54161 G 74. 119. SCHEDULED NECROPSY DAY 29 54162 G 51. 119. SCHEDULED NECROPSY DAY 29 54163 G 87. 101. SCHEDULED NECROPSY DAY 29 54164 G 88. 130. SCHEDULED NECROPSY DAY 29 54168 G 60. 119. SCHEDULED NECROPSY DAY 29 54170 G 109. 135. SCHEDULED NECROPSY DAY 29

MEAN 89. 128. S.D. 27.4 19.6 S.E. 6.5 4.6 N 18 18

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE183of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 17 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13 13-14

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 205. 183. 177. 166. 150. 153. 141. 124. 124. 53725 G 213. 208. 175. 206. 208. 195. 191. 209. 199. 53727 G 121. 166. 166. 179. 156. 175. 148. 172. 143. 53730 G 171. 152. 147. 147. 139. 147. 128. 121. 100. 53732 G 191. 142. 129. 122. 126. 82. NA NA NA 53770 G 201. 161. 167. 148. 127. 132. 148. 138. 126. 53771 G 238. 185. 165. 165. 170. 163. 157. 132. 127. 53772 G 208. 157. 174. 170. 150. 153. 150. 127. 135. 53773 G 221. 174. 180. 179. 182. 181. 187. 176. 172. 53776 G 235. 172. 175. 167. 167. 157. 149. 143. 134. 53777 G 234. 201. 190. 179. 172. 169. 166. 145. 146. 53781 G 171. 124. 120. 126. 112. 117. 113. 93. 4. 54108 G 117. 230. 157. 173. 193. 185. 176. 172. 165. 54111 G 114. 168. 165. 115. 111. 124. 104. 99. 7. 54112 G 112. 115. 98. 100. 100. 96. 103. 99. 97. 54114 G 116. 199. 152. 148. 150. 170. 146. 131. 122. 54115 G 113. 132. 125. 124. 150. 130. 110. 102. 1. 54132 G 112. 135. 131. 135. 144. 130. 141. 118. 112. 54135 G 115. 174. 160. 145. 158. 147. 130. 127. 131. 54138 G 124. 160. 148. 144. 153. 134. 128. 106. 3. 54140 G 184. 182. 150. 174. 176. 161. 175. 157. 189. 54150 G 194. 173. 190. 204. 203. 207. 202. 188. 184. 54151 G 174. 165. 143. 153. 147. 146. 135. 109. 124. 54165 G 183. 140. 160. 169. 162. 145. 139. 135. 131.

MEAN 169. 167. 156. 156. 154. 150. 146. 136. 116. S.D. 46.1 27.5 23.0 26.8 27.5 29.4 27.2 30.9 59.0 S.E. 9.4 5.6 4.7 5.5 5.6 6.0 5.7 6.5 12.3 N 24 24 24 24 24 24 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE184of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 18 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22 22-23

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 138. 140. 130. 117. 22. 25. 125. 98. 122. 53725 G 188. 205. 203. 197. 195. 200. 135. 156. 105. 53727 G 154. 170. 165. 159. 141. 139. 148. 121. 89. 53730 G 93. 97. 105. 98. 120. 123. 125. 125. 113. 53732 G NA NA NA NA NA NA NA NA NA 53770 G 136. 133. 120. 124. 147. 138. 137. 126. 5. 53771 G 132. 136. 147. 170. 166. 166. 160. 154. 123. 53772 G 148. 135. 149. 157. 165. 159. 141. 140. 135. 53773 G 192. 193. 192. 203. 187. 190. 192. 196. 135. 53776 G 145. 134. 149. 149. 158. 143. 142. 137. 123. 53777 G 151. 150. 139. 150. 152. 141. 134. 132. 104. 53781 G NA NA NA NA NA NA NA NA NA 54108 G 175. 176. 169. 170. 168. 165. 156. 147. 131. 54111 G 1. 1. 0. 1. 1. 4. 0. 1. 1. 54112 G 94. 99. 103. 115. 121. 127. 117. 110. 106. 54114 G 93. 1. NA NA NA NA NA NA NA 54115 G NA NA NA NA NA NA NA NA NA 54132 G 117. 100. 1. NA NA NA NA NA NA 54135 G 132. 129. 141. 140. 136. 133. 121. 113. 103. 54138 G NA NA NA NA NA NA NA NA NA 54140 G 197. 190. 192. 174. 195. 176. 181. 161. 126. 54150 G 195. 192. 192. 197. 199. 209. 201. 193. 192. 54151 G 136. 136. 150. 102. 16. NA NA NA NA 54165 G 129. 141. 146. 152. 147. 130. 124. 119. 104.

MEAN 137. 133. 136. 143. 135. 139. 138. 131. 107. S.D. 45.6 55.0 55.6 47.4 61.1 53.7 43.3 43.0 45.1 S.E. 10.2 12.3 12.8 11.2 14.4 13.0 10.5 10.4 10.9 N 20 20 19 18 18 17 17 17 17

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE185of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 19 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12 12-20

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 104. 109. 105. 95. 107. 106. 175. 148. 103. 53725 G 102. 58. 3. 0. 1. 0. 196. 198. 200. 53727 G 84. 115. 93. 79. 73. 99. 170. 160. 155. 53730 G 109. 100. 106. 85. 95. 98. 149. 138. 107. 53732 G NA NA NA NA NA NA 131. 104. NA 53770 G 20. 1. NA NA NA NA 159. 136. 133. 53771 G 94. 104. 97. 82. 100. 92. 172. 163. 147. 53772 G 131. 110. 101. 88. 89. 85. 167. 151. 147. 53773 G 139. 120. 100. 97. 76. 65. 178. 183. 188. 53776 G 98. 102. 84. 78. 71. 80. 171. 158. 144. 53777 G 87. 71. 69. 106. 118. 114. 190. 169. 147. 53781 G NA NA NA NA NA NA 123. 114. NA 54108 G 118. 103. 70. 43. 67. 72. 187. 185. 170. 54111 G 0. 2. NA NA NA NA 149. 113. 14. 54112 G 92. 75. 73. 76. 79. 89. 104. 100. 107. 54114 G NA NA NA NA NA NA 166. 155. NA 54115 G NA NA NA NA NA NA 127. 130. NA 54132 G NA NA NA NA NA NA 134. 138. NA 54135 G 96. 83. 76. 85. 87. 95. 160. 145. 134. 54138 G NA NA NA NA NA NA 151. 138. NA 54140 G 11. 0. 0. 2. 2. NA 169. 171. 184. 54150 G 166. 156. 140. 124. 102. 114. 189. 204. 195. 54151 G NA NA NA NA NA NA 154. 143. 110. 54165 G 84. 71. 15. 0. 1. NA 156. 149. 139.

MEAN 90. 81. 75. 69. 71. 85. 159. 150. 140. S.D. 43.9 44.5 40.3 39.5 38.9 29.5 23.1 27.3 43.8 S.E. 10.6 10.8 10.4 10.2 10.0 8.2 4.7 5.6 10.3 N 17 17 15 15 15 13 24 24 18

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE186of475TABLE A9 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 20 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 108. 120. SCHEDULED NECROPSY DAY 29 53725 G 62. 145. SCHEDULED NECROPSY DAY 29 53727 G 100. 136. SCHEDULED NECROPSY DAY 29 53730 G 106. 116. SCHEDULED NECROPSY DAY 29 53732 G NA NA GRAVID, DIED DAY 12 53770 G NA NA ABORTED DAY 26 53771 G 112. 139. SCHEDULED NECROPSY DAY 29 53772 G 113. 137. SCHEDULED NECROPSY DAY 29 53773 G 124. 161. SCHEDULED NECROPSY DAY 29 53776 G 102. 133. SCHEDULED NECROPSY DAY 29 53777 G 104. 139. SCHEDULED NECROPSY DAY 29 53781 G NA NA GRAVID, DIED DAY 14 54108 G 101. 147. SCHEDULED NECROPSY DAY 29 54111 G NA NA ABORTED DAY 26 54112 G 91. 99. SCHEDULED NECROPSY DAY 29 54114 G NA NA GRAVID, EUTHANIZED DAY 16 54115 G NA NA GRAVID, DIED DAY 14 54132 G NA NA GRAVID, DIED DAY 18 54135 G 95. 124. SCHEDULED NECROPSY DAY 29 54138 G NA NA GRAVID, DIED DAY 14 54140 G 60. 135. SCHEDULED NECROPSY DAY 29 54150 G 154. 179. SCHEDULED NECROPSY DAY 29 54151 G NA NA GRAVID, DIED DAY 20 54165 G 65. 116. ABORTED DAY 29

MEAN 100. 135. S.D. 24.3 19.4 S.E. 6.3 5.0 N 15 15

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE PGFWv4.09 06/16/2008187of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13 13-14

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 52. 54. 48. 48. 42. 42. 43. 48. 47. 53735 G 59. 43. 46. 49. 46. 48. 46. 42. 41. 53738 G 57. 53. 51. 48. 51. 52. 46. 53. 47. 53739 G 54. 50. 52. 51. 47. 48. 49. 49. 47. 53742 G 66. 46. 57. 55. 61. 56. 53. 57. 54. 53748 G 59. 42. 43. 42. 37. 40. 40. 34. 36. 53752 G 65. 55. 55. 54. 55. 54. 54. 54. 50. 53758 G 63. 53. 53. 50. 44. 46. 46. 39. 37. 53760 G 65. 55. 57. 48. 55. 58. 56. 52. 50. 53763 G 68. 52. 50. 48. 46. 47. 45. 41. 41. 53780 G 66. 54. 55. 56. 51. 53. 53. 56. 51. 53783 G 46. 37. 38. 34. 38. 34. 31. 27. 23. 54117 G 32. 50. 41. 40. 43. 37. 39. 38. 37. 54124 G 37. 54. 50. 50. 45. 45. 47. 45. 42. 54128 G 36. 54. 47. 42. 42. 45. 43. 41. 45. 54129 G 32. 52. 52. 48. 53. 51. 52. 48. 47. 54137 G 33. 54. 52. 48. 43. 41. 37. 36. 38. 54143 G 56. 52. 55. 53. 48. 50. 52. 44. 48. 54147 G 56. 46. 52. 53. 49. 51. 53. 48. 50. 54153 G 47. 47. 47. 44. 47. 42. 46. 42. 47. 54157 G 62. 62. 61. 64. 63. 60. 63. 57. 60. 54166 G 63. 57. 62. 65. 54. 67. 70. 58. 55. 54167 G 54. 39. 49. 51. 51. 51. 48. 40. 39. 54169 G 54. 56. 51. 53. 48. 48. 48. 41. 42.

MEAN 53. 51. 51. 50. 48. 49. 48. 45. 45. S.D. 11.7 6.0 5.7 6.8 6.5 7.5 8.2 8.1 7.7 S.E. 2.4 1.2 1.2 1.4 1.3 1.5 1.7 1.7 1.6 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN188of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22 22-23

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 46. 49. 42. 53. 52. 46. 34. 36. 40. 53735 G 41. 45. 43. 43. 47. 43. 42. 42. 40. 53738 G 49. 52. 50. 67. NA NA 61. 57. 52. 53739 G 46. 47. 43. 46. 45. 47. 42. 42. 40. 53742 G 55. 54. 54. 53. 53. 52. 52. 53. 48. 53748 G 40. 45. 45. 47. 50. 48. 46. 37. 44. 53752 G 49. 50. 48. 49. 50. 51. 49. 47. 42. 53758 G 45. 40. 46. 47. 49. 43. 43. 39. 33. 53760 G 49. 55. 57. 57. 56. 55. 56. 53. 48. 53763 G 45. 39. 50. 44. 46. 40. 43. 39. 32. 53780 G NA NA NA NA 56. 54. 52. 51. 47. 53783 G 29. 28. 35. 37. 38. 37. 34. 29. 24. 54117 G 37. 35. 41. 37. 36. 30. 36. 26. 21. 54124 G 44. 47. 45. 46. 47. 51. 48. 45. 40. 54128 G 46. 48. 44. 43. 44. 49. 45. 45. 40. 54129 G 49. 49. 47. 45. 34. 31. 24. 29. 28. 54137 G 37. 38. 41. 43. 41. 39. 38. 36. 33. 54143 G 49. 45. 48. 28. 48. 44. 41. 39. 40. 54147 G 53. 54. 54. 53. 54. 51. 46. 41. 30. 54153 G 47. 42. 47. 44. 47. 51. 49. 47. 46. 54157 G 57. 58. 56. 58. 58. 56. 52. 40. 42. 54166 G 55. 59. 58. 57. 61. 61. 56. 48. 45. 54167 G 42. 43. 48. 51. 54. 55. 51. 37. 31. 54169 G 45. 49. 51. 54. 53. 50. 51. 48. 53.

MEAN 46. 47. 48. 48. 49. 47. 45. 42. 39. S.D. 6.4 7.5 5.7 8.3 6.9 7.9 8.4 7.9 8.5 S.E. 1.3 1.6 1.2 1.7 1.4 1.6 1.7 1.6 1.7 N 23 23 23 23 23 23 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE189of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12 12-20

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 34. 36. 34. 36. 36. 39. 50. 42. 48. 53735 G 40. 33. 29. 20. 14. 29. 46. 47. 43. 53738 G 47. 33. 27. 28. 22. 31. 51. 50. 53. 53739 G 36. 33. 29. 29. 28. 30. 51. 48. 46. 53742 G 45. 40. 40. 34. 30. 29. 53. 56. 54. 53748 G 40. 39. 37. 27. 19. 19. 42. 39. 43. 53752 G 38. 36. 33. 31. 36. 32. 55. 54. 50. 53758 G 30. 30. 31. 33. 30. 28. 52. 45. 43. 53760 G 40. 26. 5. 6. 18. 19. 54. 56. 54. 53763 G 26. 29. 36. 38. 34. 17. 50. 46. 43. 53780 G 20. 27. 30. 28. 2. 1. 55. 52. 54. 53783 G 24. 22. 21. 23. 23. 21. 36. 35. 32. 54117 G 20. 21. 22. 20. 20. 21. 44. 40. 36. 54124 G 42. 40. 33. 32. 28. 26. 52. 45. 46. 54128 G 41. 35. 31. 29. 28. 30. 48. 43. 45. 54129 G 23. 10. 14. 15. 16. 20. 51. 52. 44. 54137 G 29. 27. 30. 26. 27. 28. 51. 41. 39. 54143 G 39. 35. 34. 37. 34. 37. 53. 50. 44. 54147 G 20. 3. 9. 16. 17. 15. 50. 51. 52. 54153 G 44. 38. 34. 34. 34. 36. 46. 45. 46. 54157 G 40. 38. 38. 32. 28. 31. 62. 62. 58. 54166 G 34. 25. 19. 9. 7. 11. 61. 64. 58. 54167 G 31. 35. 35. 37. 38. 36. 46. 50. 47. 54169 G 48. 42. 26. 24. 16. 23. 53. 48. 48.

MEAN 35. 31. 28. 27. 24. 25. 51. 48. 47. S.D. 8.9 9.5 9.0 8.8 9.5 9.0 5.6 7.0 6.5 S.E. 1.8 1.9 1.8 1.8 1.9 1.8 1.1 1.4 1.3 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN190of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- 53726 G 36. 43. SCHEDULED NECROPSY DAY 29 53735 G 32. 39. SCHEDULED NECROPSY DAY 29 53738 G 39. 46. SCHEDULED NECROPSY DAY 29 53739 G 34. 42. SCHEDULED NECROPSY DAY 29 53742 G 41. 49. SCHEDULED NECROPSY DAY 29 53748 G 34. 39. SCHEDULED NECROPSY DAY 29 53752 G 38. 46. SCHEDULED NECROPSY DAY 29 53758 G 33. 41. SCHEDULED NECROPSY DAY 29 53760 G 30. 45. SCHEDULED NECROPSY DAY 29 53763 G 32. 40. SCHEDULED NECROPSY DAY 29 53780 G 29. 42. SCHEDULED NECROPSY DAY 29 53783 G 25. 30. SCHEDULED NECROPSY DAY 29 54117 G 23. 32. SCHEDULED NECROPSY DAY 29 54124 G 37. 43. SCHEDULED NECROPSY DAY 29 54128 G 36. 41. SCHEDULED NECROPSY DAY 29 54129 G 20. 36. SCHEDULED NECROPSY DAY 29 54137 G 30. 37. SCHEDULED NECROPSY DAY 29 54143 G 37. 43. SCHEDULED NECROPSY DAY 29 54147 G 22. 40. SCHEDULED NECROPSY DAY 29 54153 G 40. 44. SCHEDULED NECROPSY DAY 29 54157 G 38. 51. SCHEDULED NECROPSY DAY 29 54166 G 28. 47. SCHEDULED NECROPSY DAY 29 54167 G 37. 43. SCHEDULED NECROPSY DAY 29 54169 G 37. 44. SCHEDULED NECROPSY DAY 29

MEAN 33. 42. S.D. 5.9 4.8 S.E. 1.2 1.0 N 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN191of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13 13-14

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G 68. 57. 59. 61. 49. 56. 57. 59. 57. 53736 G 63. 54. 53. 51. 50. 48. 45. 42. 40. 53737 G 56. 47. 51. 47. 44. 44. 39. 39. 38. 53741 G 61. 54. 57. 49. 51. 46. 51. 49. 51. 53744 NG 55. 50. 48. 47. 45. 43. 49. 50. 47. 53745 G 69. 64. 63. 55. 49. 52. 50. 47. 50. 53753 G 84. 57. 56. 54. 53. 61. 62. 54. 52. 53757 G 69. 54. 54. 54. 50. 57. 53. 47. 46. 53759 G 70. 54. 50. 48. 42. 42. 46. 40. 41. 53778 G 67. 50. 48. 41. 41. 44. 46. 42. 41. 53779 G 64. 51. 49. 49. 49. 54. 53. 46. 49. 53782 G 46. 36. 33. 34. 27. 34. 24. 22. 16. 54119 G 31. 61. 49. 50. 51. 50. 49. 49. 44. 54120 G 33. 44. 41. 43. 45. 43. 41. 37. 37. 54123 G 35. 50. 41. 40. NA 43. 40. 37. 24. 54131 G 29. 70. 56. 55. 59. 54. 56. 53. 52. 54139 G 52. 45. 52. 53. 51. 51. 52. 47. 52. 54141 G 7. 22. 50. 58. 53. 48. 49. 47. 49. 54146 G 53. 49. 52. 46. 45. 46. 51. 48. 48. 54148 G 53. 39. 46. 53. 44. 43. 44. 41. 42. 54152 G 56. 49. 49. 47. 48. 51. 49. 43. 42. 54156 G 42. 37. 39. 35. 35. 35. 32. 31. 27. 54159 G 50. 38. 43. 47. 45. 44. 46. 43. 45. 54160 G 51. 43. 43. 48. 41. 41. 40. 39. 35.

MEAN 53. 49. 49. 49. 46. 47. 47. 44. 43. S.D. 17.3 10.4 7.0 6.8 6.8 6.7 8.3 7.8 9.9 S.E. 3.6 2.2 1.5 1.4 1.4 1.4 1.7 1.6 2.1 N 23 23 23 23 22 23 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE192of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 6 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22 22-23

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G 49. 56. 48. 50. 56. 53. 51. NA 15. 53736 G 42. 48. 50. 50. 48. 44. 46. 41. 35. 53737 G 39. 44. 44. 47. 44. 43. 42. 42. 36. 53741 G 49. 49. 48. 47. 45. 47. 44. 42. 45. 53744 NG 45. 47. 44. 49. 50. 47. 45. 44. 45. 53745 G 50. 54. 52. 52. 55. 53. 51. 51. 42. 53753 G 50. 52. 55. 56. 60. 56. 55. 54. 51. 53757 G 48. 46. 42. 47. 47. 44. 42. 38. 35. 53759 G 46. 40. 44. 48. 50. 44. 45. 44. 42. 53778 G 42. 42. 46. 48. 51. 45. 50. 50. 47. 53779 G 49. 50. 47. 57. 51. 47. 48. 46. 40. 53782 G 0. 4. 14. 22. 22. 15. 18. 19. 18. 54119 G 45. 45. 46. 45. 42. 40. 32. 29. 21. 54120 G 39. 41. 41. 45. 39. 39. 37. 29. 21. 54123 G 19. 7. 12. 27. 40. 44. 42. 28. 14. 54131 G 50. 54. 51. 49. 49. 49. 47. 49. 47. 54139 G 48. 50. 50. 16. 51. 48. 43. 40. 36. 54141 G 49. 53. 53. 52. 51. 37. 37. 31. 27. 54146 G 47. 53. 52. 49. 50. 48. 48. 44. 44. 54148 G 51. 50. 53. 46. 52. 50. 45. 38. 35. 54152 G 45. 44. 49. 50. 51. 47. 43. 42. 41. 54156 G 26. 27. 31. 35. 33. 32. 26. 16. 11. 54159 G 44. 45. 49. 47. 50. 52. 49. 49. 47. 54160 G 38. 38. 37. 41. 40. 40. 37. 37. 38.

MEAN 42. 43. 44. 45. 47. 44. 43. 39. 34. S.D. 12.0 13.5 11.3 10.3 8.2 8.5 8.5 10.1 12.0 S.E. 2.5 2.8 2.3 2.1 1.7 1.8 1.8 2.2 2.5 N 23 23 23 23 23 23 23 22 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE193of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 7 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12 12-20

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G 23. 17. 8. 23. 26. 34. 59. 54. 54. 53736 G 34. 33. 26. 26. 29. 11. 53. 48. 46. 53737 G 34. 33. 29. 29. 26. 26. 48. 42. 42. 53741 G 44. 31. 34. 29. 37. 35. 53. 49. 48. 53744 NG 49. 46. 47. 46. 45. 46. 48. 46. 48. 53745 G 39. 27. 31. 27. 21. 28. 61. 50. 52. 53753 G 44. 45. 38. 37. 39. 43. 56. 59. 54. 53757 G 32. 30. 25. 29. 28. 28. 54. 53. 46. 53759 G 41. 38. 31. 33. 33. 34. 51. 43. 44. 53778 G 47. 37. 37. 33. 40. 29. 46. 43. 45. 53779 G 32. 15. 4. 9. 21. 23. 50. 52. 50. 53782 G 22. 24. 21. 20. 16. 25. 34. 28. 14. 54119 G 18. 14. 21. 25. 20. 18. 54. 50. 44. 54120 G 15. 12. 20. 15. 17. 13. 43. 43. 40. 54123 G 10. 15. 16. 14. 12. 12. 44. 42. 26. 54131 G 41. 37. 32. 17. 14. 11. 60. 56. 51. 54139 G 24. 15. 29. 24. 27. 33. 50. 51. 45. 54141 G 28. 27. 24. 22. 21. 25. 45. 50. 49. 54146 G 38. 30. 19. 11. 9. 14. 49. 47. 49. 54148 G 29. 20. 23. 2. 0. 21. 46. 44. 48. 54152 G 34. 33. 31. 31. 26. 28. 48. 49. 46. 54156 G 7. 1. 1. 2. 1. 2. 37. 34. 30. 54159 G 43. 40. 33. 17. 5. 1. 43. 45. 47. 54160 G 34. 27. 25. 20. 20. 20. 45. 41. 39.

MEAN 31. 26. 24. 22. 21. 22. 49. 47. 44. S.D. 11.2 10.9 9.8 9.5 11.1 10.8 6.8 6.9 9.3 S.E. 2.3 2.3 2.0 2.0 2.3 2.2 1.4 1.4 1.9 N 23 23 23 23 23 23 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN194of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 8 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- 53729 G 25. 43. SCHEDULED NECROPSY DAY 29 53736 G 31. 41. SCHEDULED NECROPSY DAY 29 53737 G 33. 39. SCHEDULED NECROPSY DAY 29 53741 G 38. 45. SCHEDULED NECROPSY DAY 29 53744 NG 46. 47. SCHEDULED NECROPSY DAY 29 53745 G 35. 46. SCHEDULED NECROPSY DAY 29 53753 G 45. 51. SCHEDULED NECROPSY DAY 29 53757 G 32. 42. SCHEDULED NECROPSY DAY 29 53759 G 38. 42. SCHEDULED NECROPSY DAY 29 53778 G 41. 43. SCHEDULED NECROPSY DAY 29 53779 G 27. 41. SCHEDULED NECROPSY DAY 29 53782 G 20. 21. SCHEDULED NECROPSY DAY 29 54119 G 22. 37. SCHEDULED NECROPSY DAY 29 54120 G 20. 33. SCHEDULED NECROPSY DAY 29 54123 G 18. 27. SCHEDULED NECROPSY DAY 29 54131 G 33. 45. SCHEDULED NECROPSY DAY 29 54139 G 30. 40. SCHEDULED NECROPSY DAY 29 54141 G 27. 39. SCHEDULED NECROPSY DAY 29 54146 G 29. 41. SCHEDULED NECROPSY DAY 29 54148 G 24. 37. SCHEDULED NECROPSY DAY 29 54152 G 34. 42. SCHEDULED NECROPSY DAY 29 54156 G 8. 23. SCHEDULED NECROPSY DAY 29 54159 G 32. 40. SCHEDULED NECROPSY DAY 29 54160 G 29. 36. SCHEDULED NECROPSY DAY 29

MEAN 29. 39. S.D. 8.3 7.1 S.E. 1.7 1.5 N 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN195of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 9 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13 13-14

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 66. 54. 58. 58. 56. 53. 46. 49. 48. 53724 G 57. 57. 55. 56. 51. 57. 50. 48. 47. 53728 G 62. 54. 48. 50. 47. 47. 21. 0. 2. 53731 G 57. 51. 52. 51. 55. 54. 53. 47. 44. 53733 G 61. 50. 54. 53. 51. 51. 51. 54. 46. 53734 G 60. 46. 54. 55. 55. 55. 53. 52. 48. 53740 G 67. 55. 53. 56. 53. 53. 52. 51. 48. 53743 G 52. 44. 39. 38. 41. 37. 32. 25. 31. 53747 G 64. 54. 48. 47. 48. 46. 43. 44. 39. 53749 G 57. 48. 44. 48. 52. 52. 49. 41. 34. 53750 G 61. 49. 53. 51. 49. 56. 53. 49. 48. 53751 G 50. 42. 39. 42. 38. 38. 35. 36. 37. 53754 G 69. 54. 53. 46. 37. 40. 38. 34. 11. 53755 G 74. 52. 51. 55. 55. 54. 56. 49. 48. 53756 G 76. 55. 54. 54. 50. 49. 53. 49. 47. 53761 G 79. 61. 61. 51. 59. 52. 56. 50. 47. 53762 G 67. 53. 47. 49. 50. 50. 48. 46. 43. 53764 G 65. 51. 50. 53. 53. 49. 50. 44. 43. 53765 G 65. 51. 41. 55. 51. 54. 50. 43. 41. 53766 G 74. 61. 61. 60. 59. 58. 54. 49. 51. 53768 G 65. 56. 54. 50. 55. 47. 49. 45. 48. 53769 G 55. 49. 48. 45. 46. 43. 44. 39. 40. 53774 G 75. 57. 57. 52. 52. 52. 52. 54. 45. 53775 G 53. 52. 54. 55. 48. 49. 48. 38. 31.

MEAN 64. 52. 51. 51. 50. 50. 47. 43. 40. S.D. 8.0 4.7 6.0 5.1 5.7 5.7 8.4 11.5 11.9 S.E. 1.6 1.0 1.2 1.0 1.2 1.2 1.7 2.3 2.4 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN196of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 10 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22 22-23

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 49. 55. 49. 49. 53. 50. 47. 45. 41. 53724 G 48. 54. 50. 48. 51. 50. 47. 44. 38. 53728 G 13. 38. 51. 55. 58. 53. 48. 47. 44. 53731 G 45. 51. 44. 42. 50. 45. 40. 35. 33. 53733 G 48. 47. 44. 46. 46. 45. 42. 39. 36. 53734 G 49. 54. 43. 47. 49. 50. 45. 40. 36. 53740 G 45. 49. 45. 45. 46. 44. 44. 40. 38. 53743 G 32. 33. 34. 34. 35. 33. 30. 28. 27. 53747 G 39. 45. 41. 43. 43. 40. 36. 33. 28. 53749 G 5. 0. 6. 11. 21. 43. 57. 58. 59. 53750 G 47. 48. 44. 43. 45. 44. 40. 37. 34. 53751 G 35. 40. 35. 33. 36. 39. 37. 34. 31. 53754 G 14. 18. 30. 37. 46. 45. 47. 47. 40. 53755 G 50. 51. 54. 51. 48. 50. 50. 36. 45. 53756 G 52. 50. 40. 43. 49. 51. 52. 50. 48. 53761 G 54. 53. 51. 49. 52. 47. 44. 39. 31. 53762 G 44. 47. 44. 45. 46. 39. 35. 37. 30. 53764 G 46. 44. 47. 53. 50. 51. 48. 46. 39. 53765 G 38. 46. 49. 52. 51. 48. 48. 38. 30. 53766 G 54. 53. 56. 55. 58. 54. 50. 52. 50. 53768 G 49. 49. 52. 53. 49. 46. 44. 44. 34. 53769 G 37. 35. 30. 29. 35. 34. 36. 38. 34. 53774 G 51. 46. 48. 50. 50. 46. 46. 44. 41. 53775 G 33. 29. 35. 30. 30. 25. 31. 27. 27.

MEAN 41. 43. 43. 43. 46. 45. 44. 41. 37. S.D. 13.3 12.8 10.6 10.2 8.7 6.9 6.7 7.3 7.9 S.E. 2.7 2.6 2.2 2.1 1.8 1.4 1.4 1.5 1.6 N 24 24 24 24 24 24 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN197of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 11 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12 12-20

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 33. 31. 28. 26. 26. 28. 57. 52. 51. 53724 G 29. 21. 12. 8. 20. 18. 56. 53. 49. 53728 G 38. 40. 38. 40. 37. NA 50. 39. 34. 53731 G 32. 30. 28. 25. 20. 22. 52. 54. 46. 53733 G 31. 24. 27. 29. 31. 32. 52. 51. 47. 53734 G 28. 22. 16. 14. 10. 12. 51. 54. 49. 53740 G 34. 32. 28. 24. 25. 26. 55. 53. 47. 53743 G 27. 23. 26. 24. 25. 27. 40. 37. 32. 53747 G 23. 21. 19. 16. 22. 27. 50. 46. 42. 53749 G 58. 55. 52. 49. 45. 44. 47. 51. 20. 53750 G 47. 8. 27. 19. 10. 15. 51. 53. 46. 53751 G 24. 5. 17. 25. 18. 19. 41. 37. 37. 53754 G 32. 32. 26. 25. 23. 23. 51. 38. 29. 53755 G 41. 35. 29. 30. 24. 23. 53. 55. 50. 53756 G 47. 45. 41. 38. 34. 26. 54. 50. 47. 53761 G 25. 8. 2. 3. 20. 17. 57. 56. 50. 53762 G 23. 24. 18. 9. 1. 1. 50. 49. 44. 53764 G 34. 26. 16. 4. 0. 0. 51. 51. 47. 53765 G 24. 26. 22. 17. 13. 9. 49. 51. 46. 53766 G 44. 38. 32. 22. 25. NA 61. 57. 54. 53768 G 39. 31. 31. 33. 30. 25. 53. 50. 49. 53769 G 29. 27. 29. 25. 25. 38. 47. 44. 35. 53774 G 42. 41. 40. 36. 29. 27. 55. 52. 49. 53775 G 28. 22. 20. 17. 30. 28. 54. 48. 31.

MEAN 34. 28. 26. 23. 23. 22. 52. 49. 43. S.D. 9.0 11.6 10.5 11.4 10.5 10.5 4.7 6.0 8.6 S.E. 1.8 2.4 2.2 2.3 2.1 2.2 1.0 1.2 1.8 N 24 24 24 24 24 22 24 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE198of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 12 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- 53723 G 34. 45. SCHEDULED NECROPSY DAY 29 53724 G 26. 41. SCHEDULED NECROPSY DAY 29 53728 G 41. 40. SCHEDULED NECROPSY DAY 29 53731 G 29. 41. SCHEDULED NECROPSY DAY 29 53733 G 32. 42. SCHEDULED NECROPSY DAY 29 53734 G 25. 40. SCHEDULED NECROPSY DAY 29 53740 G 32. 42. SCHEDULED NECROPSY DAY 29 53743 G 26. 31. SCHEDULED NECROPSY DAY 29 53747 G 25. 37. SCHEDULED NECROPSY DAY 29 53749 G 53. 41. SCHEDULED NECROPSY DAY 29 53750 G 26. 40. SCHEDULED NECROPSY DAY 29 53751 G 23. 32. SCHEDULED NECROPSY DAY 29 53754 G 33. 35. SCHEDULED NECROPSY DAY 29 53755 G 35. 45. SCHEDULED NECROPSY DAY 29 53756 G 42. 47. SCHEDULED NECROPSY DAY 29 53761 G 21. 40. SCHEDULED NECROPSY DAY 29 53762 G 20. 36. SCHEDULED NECROPSY DAY 29 53764 G 24. 39. SCHEDULED NECROPSY DAY 29 53765 G 25. 39. SCHEDULED NECROPSY DAY 29 53766 G 39. 50. SCHEDULED NECROPSY DAY 29 53768 G 34. 44. SCHEDULED NECROPSY DAY 29 53769 G 31. 36. SCHEDULED NECROPSY DAY 29 53774 G 38. 46. SCHEDULED NECROPSY DAY 29 53775 G 26. 34. SCHEDULED NECROPSY DAY 29

MEAN 31. 40. S.D. 7.8 4.7 S.E. 1.6 1.0 N 24 24

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN199of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 13 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13 13-14

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G 32. 61. 47. 31. 51. 45. 41. 42. 44. 54113 G 26. 50. 41. 31. 33. 37. 33. NA NA 54116 G 34. 50. 44. 46. 50. 47. 46. 42. 41. 54121 G 34. 68. 52. 53. 57. 55. 49. 51. 51. 54122 G 36. 29. 25. 27. 34. 31. 24. 5. 0. 54125 G 41. 43. 40. 37. 40. 40. 39. 37. 31. 54126 G 36. 63. 57. 50. 56. 50. 50. 48. 49. 54127 G 36. 48. 47. 39. 48. 41. 42. 40. 35. 54130 G 35. 57. 39. 44. 46. 42. 44. 39. 41. 54133 G 36. 48. 46. 40. 46. 39. 42. 40. 35. 54134 G 38. 54. 49. 47. 51. 48. 45. 44. 37. 54136 G 33. 67. 56. 49. 53. 50. 48. 44. 42. 54142 NG 40. 40. 51. 55. 55. 54. 57. 56. 56. 54144 G 57. 52. 48. 52. 55. 46. 47. 46. 50. 54145 G 52. 51. 49. 54. 53. 51. 48. 50. 50. 54149 G 59. 52. 58. 65. 61. 60. 57. 57. 59. 54155 G 55. 44. 51. 54. 52. 55. 51. 43. 39. 54158 G 49. 39. 35. 39. 37. 38. 36. 38. 38. 54161 G 58. 43. 50. 56. 52. 47. 48. 41. 36. 54162 G 51. 37. 49. 49. 44. 40. 39. 38. 46. 54163 G 48. 38. 37. 41. 43. 41. 41. 40. 34. 54164 G 50. 49. 43. 47. 43. 45. 44. 44. 40. 54168 G 56. 54. 57. 57. 57. 52. 51. 51. 46. 54170 G 56. 50. 53. 52. 50. 46. 41. 38. 38.

MEAN 44. 50. 47. 46. 48. 45. 44. 42. 40. S.D. 10.4 9.6 8.0 9.3 7.5 6.8 6.9 9.7 11.3 S.E. 2.2 2.0 1.7 1.9 1.6 1.4 1.4 2.1 2.4 N 23 23 23 23 23 23 23 22 22

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE200of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 14 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22 22-23

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G 37. 38. 44. 46. 45. 46. 47. 27. 10. 54113 G NA NA NA NA NA NA NA NA NA 54116 G 44. 47. 50. 47. 45. 44. 38. 33. 31. 54121 G 53. 58. 55. 56. 55. 79. 61. 35. 35. 54122 G NA NA NA NA NA NA NA NA NA 54125 G 34. 35. 32. 35. 13. 7. 20. 29. 24. 54126 G 52. 50. 52. 51. 35. 30. 39. 38. 40. 54127 G 34. 36. 35. 38. 39. 34. 36. 34. 30. 54130 G 40. 45. 46. 45. 44. 39. 38. 32. 1. 54133 G 36. 35. 19. 6. 4. 15. 17. 17. 25. 54134 G 43. 46. 44. 46. 46. 41. 44. 37. 8. 54136 G 44. 43. 36. 5. 4. 18. 37. 40. 35. 54142 NG 55. 54. 46. 41. 51. 54. 51. 52. 57. 54144 G 49. 52. 49. 44. 50. 47. 45. 45. 39. 54145 G 53. 49. 49. 51. 52. 52. 47. 37. 32. 54149 G 58. 58. 56. 56. 53. 54. 49. 50. 37. 54155 G 39. 38. 40. 45. 44. 44. 39. 39. 35. 54158 G 39. 37. 41. 38. 40. 43. 39. 38. 37. 54161 G 39. 44. 44. 47. 49. 46. 40. 34. 29. 54162 G 43. 42. 43. 42. 42. 41. 38. 34. 21. 54163 G 34. 36. 34. 30. 37. 37. 35. 35. 32. 54164 G 40. 40. 42. 42. 42. 43. 36. 35. 32. 54168 G 43. 38. 38. 40. 41. 38. 30. 33. 27. 54170 G 37. 41. 39. 40. 41. 41. 38. 37. 38.

MEAN 42. 43. 42. 40. 39. 40. 39. 35. 28. S.D. 7.0 7.1 8.6 13.2 14.5 14.8 9.3 6.5 10.6 S.E. 1.5 1.5 1.9 2.9 3.2 3.2 2.0 1.4 2.3 N 21 21 21 21 21 21 21 21 21

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE201of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 15 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12 12-20

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G 13. 1. 1. 0. NA NA 47. 45. 43. 54113 G NA NA NA NA NA NA 41. 34. NA 54116 G 30. 28. 20. 22. 26. 25. 47. 47. 45. 54121 G 40. 43. 27. 20. 16. 16. 58. 54. 57. 54122 G NA NA NA NA NA NA 27. 29. NA 54125 G 17. 12. 1. 0. NA NA 40. 40. 28. 54126 G 41. 36. 34. 32. 30. 28. 57. 52. 46. 54127 G 25. 18. 8. 0. 1. 0. 45. 43. 36. 54130 G 0. 0. 0. 0. 0. 0. 47. 44. 42. 54133 G 36. 37. 34. 35. 33. 36. 45. 42. 24. 54134 G 30. 30. 24. 29. 24. 26. 50. 48. 43. 54136 G 24. 34. 36. 37. 32. 10. 57. 50. 30. 54142 NG 52. 53. 54. 49. 50. 47. 49. 56. 52. 54144 G 35. 30. 11. NA NA NA 50. 49. 48. 54145 G 16. 8. 9. 2. 8. 11. 51. 51. 51. 54149 G 0. 0. 11. 28. 28. 34. 58. 60. 56. 54155 G 28. 30. 14. 19. 15. 18. 50. 53. 41. 54158 G 32. 33. 34. 33. 33. 32. 38. 37. 39. 54161 G 23. 17. 12. 13. 15. 16. 49. 49. 43. 54162 G 7. 1. 0. 1. 6. 9. 45. 41. 42. 54163 G 31. 29. 24. 23. 24. 26. 39. 42. 35. 54164 G 28. 27. 26. 21. 2. 1. 47. 44. 42. 54168 G 23. 12. 14. 16. 1. 2. 56. 53. 42. 54170 G 33. 26. 25. 23. 24. 20. 51. 46. 39.

MEAN 24. 22. 17. 18. 18. 17. 48. 46. 42. S.D. 11.8 13.7 12.1 13.1 12.1 12.0 7.4 7.0 8.2 S.E. 2.6 3.0 2.6 2.9 2.8 2.8 1.6 1.5 1.8 N 21 21 21 20 18 18 23 23 21

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE202of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 16 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- 54107 G NA NA ABORTED DAY 28 54113 G NA NA GRAVID, DIED DAY 13 54116 G 28. 39. SCHEDULED NECROPSY DAY 29 54121 G 32. 47. SCHEDULED NECROPSY DAY 29 54122 G NA NA GRAVID, DIED DAY 14 54125 G NA NA GRAVID, EUTHANIZED DAY 28 54126 G 35. 44. SCHEDULED NECROPSY DAY 29 54127 G 17. 31. SCHEDULED NECROPSY DAY 29 54130 G 8. 30. SCHEDULED NECROPSY DAY 29 54133 G 30. 31. SCHEDULED NECROPSY DAY 29 54134 G 28. 38. SCHEDULED NECROPSY DAY 29 54136 G 32. 37. SCHEDULED NECROPSY DAY 29 54142 NG 52. 52. SCHEDULED NECROPSY DAY 29 54144 G NA NA GRAVID, DIED DAY 27 54145 G 19. 38. SCHEDULED NECROPSY DAY 29 54149 G 27. 45. SCHEDULED NECROPSY DAY 29 54155 G 27. 38. SCHEDULED NECROPSY DAY 29 54158 G 35. 37. SCHEDULED NECROPSY DAY 29 54161 G 22. 36. SCHEDULED NECROPSY DAY 29 54162 G 13. 31. SCHEDULED NECROPSY DAY 29 54163 G 29. 34. SCHEDULED NECROPSY DAY 29 54164 G 23. 35. SCHEDULED NECROPSY DAY 29 54168 G 18. 36. SCHEDULED NECROPSY DAY 29 54170 G 29. 38. SCHEDULED NECROPSY DAY 29

MEAN 25. 37. S.D. 7.6 4.8 S.E. 1.8 1.1 N 18 18

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE203of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 17 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 4- 6 6- 7 7- 8 8- 9 9-10 10-11 11-12 12-13 13-14

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 62. 54. 53. 49. 44. 45. 41. 36. 36. 53725 G 65. 61. 52. 61. 61. 56. 55. 59. 55. 53727 G 39. 51. 50. 54. 47. 53. 44. 51. 43. 53730 G 58. 50. 49. 48. 45. 48. 41. 39. 32. 53732 G 62. 46. 42. 40. 41. 27. NA NA NA 53770 G 60. 47. 49. 43. 37. 39. 44. 41. 37. 53771 G 75. 56. 50. 50. 51. 49. 47. 39. 37. 53772 G 64. 47. 53. 51. 45. 46. 45. 37. 40. 53773 G 69. 53. 55. 54. 55. 54. 56. 52. 50. 53776 G 74. 53. 54. 51. 51. 48. 45. 43. 40. 53777 G 76. 63. 59. 56. 54. 53. 52. 45. 45. 53781 G 53. 38. 37. 39. 35. 36. 35. 29. 1. 54108 G 36. 68. 45. 50. 55. 53. 50. 48. 46. 54111 G 36. 52. 50. 35. 34. 38. 32. 30. 2. 54112 G 38. 39. 33. 34. 34. 33. 35. 33. 32. 54114 G 35. 59. 44. 43. 44. 49. 42. 38. 35. 54115 G 33. 38. 36. 36. 43. 37. 31. 29. 0. 54132 G 28. 34. 33. 34. 36. 32. 35. 29. 28. 54135 G 37. 56. 51. 46. 50. 46. 41. 40. 41. 54138 G 40. 50. 46. 44. 47. 41. 39. 32. 1. 54140 G 52. 50. 42. 49. 49. 44. 47. 42. 49. 54150 G 57. 50. 55. 58. 57. 58. 56. 51. 50. 54151 G 58. 54. 47. 51. 48. 48. 44. 35. 40. 54165 G 60. 45. 51. 54. 51. 46. 44. 42. 41.

MEAN 53. 51. 47. 47. 46. 45. 44. 40. 34. S.D. 14.9 8.2 7.1 7.7 7.5 8.1 7.2 8.2 16.7 S.E. 3.0 1.7 1.4 1.6 1.5 1.7 1.5 1.7 3.5 N 24 24 24 24 24 24 23 23 23

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE204of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 18 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 14-15 15-16 16-17 17-18 18-19 19-20 20-21 21-22 22-23

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 40. 40. 37. 34. 6. 8. 37. 29. 35. 53725 G 52. 56. 55. 53. 52. 53. 36. 42. 28. 53727 G 45. 49. 47. 46. 41. 40. 42. 34. 25. 53730 G 30. 31. 33. 31. 38. 38. 39. 38. 35. 53732 G NA NA NA NA NA NA NA NA NA 53770 G 39. 38. 34. 35. 42. 39. 39. 36. 1. 53771 G 39. 40. 43. 49. 48. 47. 45. 43. 35. 53772 G 43. 39. 43. 45. 47. 45. 40. 39. 37. 53773 G 56. 55. 54. 57. 52. 53. 53. 53. 37. 53776 G 42. 39. 43. 43. 46. 41. 41. 39. 35. 53777 G 46. 46. 42. 45. 46. 42. 40. 39. 31. 53781 G NA NA NA NA NA NA NA NA NA 54108 G 49. 49. 47. 47. 46. 45. 42. 40. 35. 54111 G 0. 0. 0. 0. 0. 1. 0. 0. 0. 54112 G 31. 32. 33. 37. 39. 41. 38. 35. 34. 54114 G 26. 0. NA NA NA NA NA NA NA 54115 G NA NA NA NA NA NA NA NA NA 54132 G 28. 24. 0. NA NA NA NA NA NA 54135 G 41. 40. 43. 43. 41. 40. 37. 34. 31. 54138 G NA NA NA NA NA NA NA NA NA 54140 G 51. 49. 49. 44. 49. 44. 45. 40. 31. 54150 G 53. 51. 51. 52. 52. 55. 52. 50. 49. 54151 G 43. 43. 47. 32. 5. NA NA NA NA 54165 G 40. 43. 44. 46. 44. 39. 37. 35. 30.

MEAN 40. 38. 39. 41. 39. 39. 39. 37. 30. S.D. 12.5 15.3 15.2 12.6 16.6 14.2 11.2 11.1 12.2 S.E. 2.8 3.4 3.5 3.0 3.9 3.4 2.7 2.7 3.0 N 20 20 19 18 18 17 17 17 17

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE205of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 19 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 23-24 24-25 25-26 26-27 27-28 28-29 6- 9 9-12 12-20

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 29. 31. 29. 26. 30. 29. 52. 44. 30. 53725 G 27. 15. 1. 0. 0. 0. 58. 57. 55. 53727 G 24. 32. 26. 22. 20. 27. 52. 48. 45. 53730 G 33. 30. 32. 25. 28. 28. 49. 45. 34. 53732 G NA NA NA NA NA NA 43. NA NA 53770 G 6. 0. NA NA NA NA 47. 40. 38. 53771 G 27. 29. 27. 23. 28. 26. 52. 49. 43. 53772 G 36. 30. 28. 24. 24. 23. 50. 45. 42. 53773 G 38. 32. 27. 26. 20. 17. 54. 55. 53. 53776 G 28. 29. 24. 22. 20. 23. 52. 48. 42. 53777 G 26. 21. 21. 31. 35. 33. 60. 53. 45. 53781 G NA NA NA NA NA NA 38. 35. NA 54108 G 32. 27. 19. 12. 18. 19. 55. 53. 47. 54111 G 0. 1. NA NA NA NA 46. 34. 5. 54112 G 29. 24. 23. 24. 25. 28. 35. 34. 35. 54114 G NA NA NA NA NA NA 49. 45. NA 54115 G NA NA NA NA NA NA 37. 37. NA 54132 G NA NA NA NA NA NA 34. 34. NA 54135 G 29. 25. 23. 25. 26. 28. 51. 46. 41. 54138 G NA NA NA NA NA NA 47. 42. NA 54140 G 3. 0. 0. 1. 1. NA 47. 47. 47. 54150 G 42. 40. 36. 32. 26. 29. 54. 57. 52. 54151 G NA NA NA NA NA NA 51. 47. NA 54165 G 25. 21. 4. 0. 0. NA 50. 47. 42.

MEAN 26. 23. 21. 20. 20. 24. 48. 45. 41. S.D. 11.8 12.0 11.0 10.9 11.1 8.4 6.8 7.1 11.4 S.E. 2.9 2.9 2.8 2.8 2.9 2.3 1.4 1.5 2.8 N 17 17 15 15 15 13 24 23 17

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE206of475TABLE A10 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 20 SPONSOR:HONEYWELL INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]

----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 20-29 6-29

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- 53722 G 31. 35. SCHEDULED NECROPSY DAY 29 53725 G 17. 40. SCHEDULED NECROPSY DAY 29 53727 G 28. 39. SCHEDULED NECROPSY DAY 29 53730 G 32. 36. SCHEDULED NECROPSY DAY 29 53732 G NA NA GRAVID, DIED DAY 12 53770 G NA NA ABORTED DAY 26 53771 G 32. 40. SCHEDULED NECROPSY DAY 29 53772 G 31. 39. SCHEDULED NECROPSY DAY 29 53773 G 33. 45. SCHEDULED NECROPSY DAY 29 53776 G 29. 39. SCHEDULED NECROPSY DAY 29 53777 G 31. 42. SCHEDULED NECROPSY DAY 29 53781 G NA NA GRAVID, DIED DAY 14 54108 G 27. 41. SCHEDULED NECROPSY DAY 29 54111 G NA NA ABORTED DAY 26 54112 G 29. 32. SCHEDULED NECROPSY DAY 29 54114 G NA NA GRAVID, EUTHANIZED DAY 16 54115 G NA NA GRAVID, DIED DAY 14 54132 G NA NA GRAVID, DIED DAY 18 54135 G 28. 38. SCHEDULED NECROPSY DAY 29 54138 G NA NA GRAVID, DIED DAY 14 54140 G NA NA SCHEDULED NECROPSY DAY 29 54150 G 39. 48. SCHEDULED NECROPSY DAY 29 54151 G NA NA GRAVID, DIED DAY 20 54165 G NA NA ABORTED DAY 29

MEAN 30. 40. S.D. 4.9 4.1 S.E. 1.4 1.1 N 13 13

G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE PGFWv4.09 06/16/2008207of475TABLE A11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM MATERNAL GROSS OBSERVATION

----------------------------------------------------------------------------------------------------------------------------------- 53726 OVIDUCTS: CYST(S) FEW, 1 TO 4 MM IN DIAMETER, BILATERAL 53735 NO SIGNIFICANT CHANGES OBSERVED 53738 OVIDUCTS: CYST(S) ONE, 2 MM IN DIAMETER, RIGHT SPLEEN: ACCESSORY TWO, 1 AND 2 MM IN DIAMETER 53739 NO SIGNIFICANT CHANGES OBSERVED 53742 LUNGS: AREA(S), DARK RED MULTIPLE, PINPOINT, RIGHT APICAL, RIGHT INTERMEDIATE AND RIGHT DIAPHRAGMATIC LOBES 53748 KIDNEYS: AREA(S), WHITE ONE, 2 MM IN DIAMETER, IN CORTEX, LEFT 53752 NO SIGNIFICANT CHANGES OBSERVED 53758 SPLEEN: ACCESSORY ONE, 2 X 2 X 1 MM 53760 OVIDUCTS: CYST(S) ONE, 4 MM IN DIAMETER, RIGHT 53763 SPLEEN: ACCESSORY ONE, 4 MM IN DIAMETER 53780 OVIDUCTS: CYST(S) MULTIPLE, 1 TO 3 MM IN DIAMETER, BILATERAL SPLEEN: ACCESSORY TWO, 2 X 1 X 1 AND 3 X 2 X 1 MM 53783 OVIDUCTS: CYST(S) TWO, PINPOINT, BILATERAL 54117 OVIDUCTS: CYST(S) ONE, 3 MM IN DIAMETER, RIGHT ORGAN DAMAGED AT NECROPSY BRAIN 54124 LUNGS: AREA(S), DARK RED FEW, IRREGULARLY SHAPED, ALL LOBES SPLEEN: ACCESSORY208of475TABLE A11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL INDIVIDUAL MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM MATERNAL GROSS OBSERVATION

----------------------------------------------------------------------------------------------------------------------------------- 54124 ONE, 2 MM IN DIAMETER 54128 OVIDUCTS: CYST(S) MULTIPLE, 1 TO 5 MM IN DIAMETER, BILATERAL SPLEEN: ACCESSORY ONE, 3 MM IN DIAMETER ORGAN DAMAGED AT NECROPSY BRAIN 54129 SPLEEN: ACCESSORY ONE, 2 MM IN DIAMETER 54137 OVIDUCTS: CYST(S) ONE, 2 MM IN DIAMETER, RIGHT SPLEEN: SWOLLEN 54143 NO SIGNIFICANT CHANGES OBSERVED 54147 NO SIGNIFICANT CHANGES OBSERVED 54153 NO SIGNIFICANT CHANGES OBSERVED 54157 OVIDUCTS: CYST(S) FEW, 2 TO 3 MM IN DIAMETER, BILATERAL 54166 SPLEEN: ACCESSORY ONE, 5 MM IN DIAMETER 54167 NO SIGNIFICANT CHANGES OBSERVED 54169 NO SIGNIFICANT CHANGES OBSERVED209of475TABLE A11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL INDIVIDUAL MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM MATERNAL GROSS OBSERVATION

----------------------------------------------------------------------------------------------------------------------------------- 53729 SPLEEN: ACCESSORY ONE, 2 MM IN DIAMETER LUNGS: AREA(S), DARK RED MULTIPLE, IRREGULARLY SHAPED, ALL LOBES 53736 SKIN: MATTING, RED NASAL 53737 LUNGS: AREA(S), DARK RED MULTIPLE, IRREGULARLY SHAPED, ALL LOBES OVIDUCTS: CYST(S) ONE, 10 MM IN DIAMETER, LEFT PLACENTAE: ENLARGED SITE #1 53741 SKIN: HAIR LOSS INGUINAL, RIGHT OVIDUCTS: CYST(S) FEW, 1 TO 2 MM IN DIAMETER, BILATERAL 53744 OVIDUCTS: CYST(S) FEW, PINPOINT TO 1 MM IN DIAMETER, BILATERAL GALLBLADDER: ABSENT OVARIES: SMALL BILATERAL NONGRAVID -- AMMONIUM SULFIDE NEGATIVE 53745 LUNGS: AREA(S), DARK RED MULTIPLE, PINPOINT TO 2 MM IN DIAMETER, ALL LOBES 53753 NO SIGNIFICANT CHANGES OBSERVED 53757 NO SIGNIFICANT CHANGES OBSERVED 53759 NO SIGNIFICANT CHANGES OBSERVED 53778 NO SIGNIFICANT CHANGES OBSERVED 53779 NO SIGNIFICANT CHANGES OBSERVED 53782 SKIN: HAIR LOSS INGUINAL, RIGHT 54119 LIVER: MOTTLED ALL LOBES210of475TABLE A11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL INDIVIDUAL MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM MATERNAL GROSS OBSERVATION

----------------------------------------------------------------------------------------------------------------------------------- 54120 NO SIGNIFICANT CHANGES OBSERVED 54123 OVIDUCTS: CYST(S) TWO, 2 MM IN DIAMETER, RIGHT 54131 ORGAN DAMAGED AT NECROPSY
BRAIN 54139 NO SIGNIFICANT CHANGES OBSERVED 54141 SPLEEN: ACCESSORY TWO, 3 AND 5 MM IN DIAMETER 54146 SPLEEN: ACCESSORY ONE, 3 MM IN DIAMETER 54148 NO SIGNIFICANT CHANGES OBSERVED 54152 SPLEEN: ACCESSORY ONE, 5 X 2 X 1 MM 54156 NO SIGNIFICANT CHANGES OBSERVED 54159 NO SIGNIFICANT CHANGES OBSERVED 54160 OVIDUCTS: CYST(S) FEW, 1 TO 4 MM IN DIAMETER, LEFT211of475TABLE A11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL INDIVIDUAL MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM MATERNAL GROSS OBSERVATION

----------------------------------------------------------------------------------------------------------------------------------- 53723 NO SIGNIFICANT CHANGES OBSERVED 53724 NO SIGNIFICANT CHANGES OBSERVED 53728 NO SIGNIFICANT CHANGES OBSERVED 53731 NO SIGNIFICANT CHANGES OBSERVED 53733 OVIDUCTS: CYST(S) FEW, 1 TO 3 MM IN DIAMETER, BILATERAL 53734 SPLEEN: ACCESSORY ONE, 2 MM IN DIAMETER LUNGS: DISCOLORATION, DARK RED ALL LOBES 53740 NO SIGNIFICANT CHANGES OBSERVED 53743 OVIDUCTS: CYST(S) FEW, 1 TO 3 MM IN DIAMETER, BILATERAL 53747 NO SIGNIFICANT CHANGES OBSERVED 53749 NO SIGNIFICANT CHANGES OBSERVED 53750 NO SIGNIFICANT CHANGES OBSERVED 53751 OVIDUCTS: CYST(S) MULTIPLE, 1 TO 2 MM IN DIAMETER, BILATERAL 53754 SPLEEN: ACCESSORY ONE, 4 X 2 X 1 MM 53755 NO SIGNIFICANT CHANGES OBSERVED 53756 OVIDUCTS: CYST(S) MULTIPLE, 1 TO 6 MM IN DIAMETER, BILATERAL LUNGS: AREA(S), DARK RED TWO, IRREGULARLY SHAPED, LEFT DIAPHRAGMATIC LOBE 53761 OVIDUCTS: CYST(S) FEW, 1 TO 2 MM IN DIAMETER, LEFT 53762 OVIDUCTS: CYST(S) FEW, PINPOINT TO 2 MM IN DIAMETER, BILATERAL 53764 OVIDUCTS: CYST(S) ONE, 3 MM IN DIAMETER, RIGHT SPLEEN: ACCESSORY ONE, 1 MM IN DIAMETER212of475TABLE A11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 6 SPONSOR:HONEYWELL INDIVIDUAL MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM MATERNAL GROSS OBSERVATION

----------------------------------------------------------------------------------------------------------------------------------- 53765 NO SIGNIFICANT CHANGES OBSERVED 53766 NO SIGNIFICANT CHANGES OBSERVED 53768 NO SIGNIFICANT CHANGES OBSERVED 53769 OVIDUCTS: CYST(S) MULTIPLE, 1 MM IN DIAMETER, BILATERAL 53774 NO SIGNIFICANT CHANGES OBSERVED 53775 OVIDUCTS: CYST(S) ONE, 3 MM IN DIAMETER, RIGHT213of475TABLE A11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 7 SPONSOR:HONEYWELL INDIVIDUAL MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM MATERNAL GROSS OBSERVATION

----------------------------------------------------------------------------------------------------------------------------------- 54107 LUNGS: AREA(S), DARK RED MULTIPLE, IRREGULARLY SHAPED, ALL LOBES ABORTED GESTATION DAY 28 UTERUS: LEFT- 5 FORMER IMPLANTATION SITES; RIGHT- 5 FORMER IMPLANTATION SITES, 2 FETUSES OVARIES: CORPORA LUTEA- 5, LEFT; 9, RIGHT FETUS GROSS OBSERVATIONS DELIVERED: 2 LIVE FETUSES WITH NO APPARENT MALFORMATIONS, 1 LIVE FETUS PARTIALLY CANNIBALIZED (FORELIMB, BILATERAL; EAR, BILATERAL; TAIL); 5 DEAD FETUSES, CROWN-RUMP LENGTHS: 6.5 TO 7.5 CM, NO APPARENT MALFORMATIONS; 1 DEAD FETUS PARTIALLY CANNIBALIZED (EAR, BILATERAL), CROWN-RUMP LENGTH: 7.2 CM, NO APPARENT MALFORMATIONS; 1 DEAD FETUS PARTIALLY CANNIBALIZED (ONLY HEAD AND TORSO PRESENT) FETAL GROSS OBSERVATIONS IN UTERO: 2 LIVE FETUSES 54113 THYMUS: AREA(S), DARK RED MULTIPLE, IRREGULARLY SHAPED LUNGS: AREA(S), DARK RED MULTIPLE, IRREGULARLY SHAPED, ALL LOBES DIED GESTATION DAY 13 UTERUS: LEFT- 9 NORMALLY DEVELOPING IMPLANTATIONS; RIGHT-3 NORMALLY DEVELOPING IMPLANTATIONS OVARIES: CORPORA LUTEA- 9, LEFT; 3, RIGHT 54116 NO SIGNIFICANT CHANGES OBSERVED 54121 OVIDUCTS: CYST(S) FEW, 1 TO 2 MM IN DIAMETER, RIGHT 54122 DIED GESTATION DAY 14 UTERUS: LEFT- 8 NORMALLY DEVELOPING IMPLANTATIONS; RIGHT- 3 NORMALLY DEVELOPING IMPLANTATIONS OVARIES: CORPORA LUTEA- 10, LEFT; 3, RIGHT LUNGS: DISCOLORATION, DARK RED ALL LOBES214of475TABLE A11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 8 SPONSOR:HONEYWELL INDIVIDUAL MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM MATERNAL GROSS OBSERVATION

----------------------------------------------------------------------------------------------------------------------------------- 54125 UTERUS: CONTENTS, GREEN SURROUNDS ALL SITES LUNGS: AREA(S), DARK RED MULTIPLE, IRREGULARLY SHAPED, ALL LOBES EUTHANIZED GESTATION DAY 28 UTERUS: LEFT- 3 FETUSES; RIGHT- 6 FETUSES OVARIES: CORPORA LUTEA- 3, LEFT; 6, RIGHT FETAL GROSS OBSERVATIONS IN UTERO: 9 LIVE FETUSES WITH NO APPARENT MALFORMATIONS 54126 NO SIGNIFICANT CHANGES OBSERVED 54127 SPLEEN: ACCESSORY ONE, 5 X 1 X 1 MM BRAIN: HYDROCEPHALY INCREASED CAVITATION OF THE LATERAL, BILATERAL VENTRICLES; A 3 MM IN DIAMETER OPENING IN THE LEFT CEREBRAL HEMISPHERE 54130 GALLBLADDER: CONTENTS, DARK RED LIVER: ACCESSORY LOBULE(S) ONE, 7 X 5 X 2 MM, ATTACHED TO MEDIAN LOBE 54133 NO SIGNIFICANT CHANGES OBSERVED 54134 SPLEEN: ACCESSORY ONE, 3 MM IN DIAMETER 54136 OVIDUCTS: CYST(S) FEW, 1 TO 3 MM IN DIAMETER, LEFT 54142 OVIDUCTS: CYST(S) ONE, 4 MM IN DIAMETER, LEFT NONGRAVID -- AMMONIUM SULFIDE NEGATIVE SPLEEN: ACCESSORY ONE, 4 MM IN DIAMETER 54144 DIED GESTATION DAY 27 UTERUS: LEFT- 2 DEAD FETUSES, 1 LATE RESORPTION; RIGHT- 5 DEAD FETUSES OVARIES: CORPORA LUTEA- 3, LEFT; 5, RIGHT FETAL GROSS OBSERVATIONS215of475TABLE A11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 9 SPONSOR:HONEYWELL INDIVIDUAL MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM MATERNAL GROSS OBSERVATION

----------------------------------------------------------------------------------------------------------------------------------- 54144 IN UTERO: 7 DEAD FETUSES, CROWN-RUMP LENGTHS: 9.0 TO 9.5 CM, NO APPARENT MALFORMATIONS, 1 LATE RESORPTION, CROWN-RUMP LENGTH: 8.0 CM, SLIGHT AUTOLYSIS, NO APPARENT MALFORMATIONS 54145 HEART: PALE ALL CHAMBERS 54149 LUNGS: AREA(S), DARK RED MULTIPLE, IRREGULARLY SHAPED, ALL LOBES 54155 LUNGS: AREA(S), DARK RED MULTIPLE, PINPOINT, ALL LOBES OVIDUCTS: CYST(S) FEW, PINPOINT, RIGHT 54158 SPLEEN: ACCESSORY ONE, 3 MM IN DIAMETER 54161 NO SIGNIFICANT CHANGES OBSERVED 54162 NO SIGNIFICANT CHANGES OBSERVED 54163 NO SIGNIFICANT CHANGES OBSERVED 54164 OVIDUCTS: CYST(S) FEW, 1 MM IN DIAMETER, BILATERAL 54168 OVIDUCTS: CYST(S) FEW, PINPOINT TO 1 MM IN DIAMETER, RIGHT 54170 NO SIGNIFICANT CHANGES OBSERVED216of475TABLE A11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 10 SPONSOR:HONEYWELL INDIVIDUAL MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM MATERNAL GROSS OBSERVATION

----------------------------------------------------------------------------------------------------------------------------------- 53722 SKIN: HAIR LOSS VENTRAL NECK SPLEEN: ACCESSORY ONE, 2 MM IN DIAMETER 53725 OVIDUCTS: CYST(S) MULTIPLE, 1 TO 2 MM IN DIAMETER, BILATERAL SPLEEN: ACCESSORY ONE, 2 X 2 X 1 MM 53727 NO SIGNIFICANT CHANGES OBSERVED 53730 OVIDUCTS: CYST(S) TWO, 1 MM IN DIAMETER, LEFT ADRENAL GLANDS: NODULE(S) ONE, 3 MM IN DIAMETER, LEFT 53732 DIED GESTATION DAY 12 UTERUS: LEFT- 2 NORMALLY DEVELOPING IMPLANTATIONS; RIGHT- 7 NORMALLY DEVELOPING IMPLANTATIONS OVARIES: CORPORA LUTEA- 2, LEFT; 7, RIGHT 53770 ABORTED GESTATION DAY 26 UTERUS: LEFT- 6 FORMER IMPLANTATION SITES; RIGHT- 3 FORMER IMPLANTATION SITES OVARIES: CORPORA LUTEA- 6, LEFT; 3, RIGHT FETAL GROSS OBSERVATIONS ABORTED: 5 LATE RESORPTIONS, MODERATE AUTOLYSIS, NO APPARENT MALFORMATIONS, CROWN-RUMP LENGTHS: 5.0 TO 6.0 CM; 2 LATE RESORPTIONS, SEVERE AUTOLYSIS, OPEN EYELID, BILATERAL, CROWN-RUMP LENGTHS: 5.0 AND 6.0 CM 53771 NO SIGNIFICANT CHANGES OBSERVED 53772 SPLEEN: ACCESSORY ONE, 10 X 3 X 2 MM 53773 NO SIGNIFICANT CHANGES OBSERVED 53776 NO SIGNIFICANT CHANGES OBSERVED 53777 OVIDUCTS: CYST(S) ONE, 2 MM IN DIAMETER, RIGHT217of475TABLE A11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 11 SPONSOR:HONEYWELL INDIVIDUAL MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM MATERNAL GROSS OBSERVATION

----------------------------------------------------------------------------------------------------------------------------------- 53777 SPLEEN: ACCESSORY THREE, 3 MM IN DIAMETER TO 10 X 4 X 1 MM 53781 LUNGS: DISCOLORATION, DARK RED ALL LOBES SPLEEN: AREA(S), DARK RED FEW, IRREGULARLY SHAPED DIED GESTATION DAY 14 UTERUS: LEFT- 5 NORMALLY DEVELOPING IMPLANTATIONS; RIGHT- 4 NORMALLY DEVELOPING IMPLANTATIONS, 1 EARLY RESORPTION OVARIES: CORPORA LUTEA- 5, LEFT; 7, RIGHT 54108 NO SIGNIFICANT CHANGES OBSERVED 54111 SPLEEN: ACCESSORY ONE, 3 MM IN DIAMETER ABORTED GESTATION DAY 26 UTERUS: LEFT- 1 FORMER IMPLANTATION SITE, 4 FETUSES; RIGHT- 1 FORMER IMPLANTATION SITE, 5 FETUSES FETAL GROSS OBSERVATIONS ABORTED: 1 DEAD FETUS WITH NO APPARENT MALFORMATIONS, CROWN- RUMP LENGTH: 5.6 CM IN UTERO: 9 LIVE FETUSES WITH NO APPARENT MALFORMATIONS 54112 NO SIGNIFICANT CHANGES OBSERVED 54114 OVIDUCTS: CYST(S) ONE, 2 MM IN DIAMETER, LEFT; FEW, 1 TO 3 MM IN DIAMETER, RIGHT EUTHANIZED GESTATION DAY 16 UTERUS: LEFT- 4 NORMALLY DEVELOPING IMPLANTATIONS; RIGHT- 9 NORMALLY DEVELOPING IMPLANTATIONS OVARIES CORPORA LUTEA- 5, LEFT; 9, RIGHT 54115 SPLEEN: ACCESSORY ONE, 2 MM IN DIAMETER GALLBLADDER: SMALL DIED GESTATION DAY 14 UTERUS: LEFT- 6 NORMALLY DEVELOPING IMPLANTATIONS; RIGHT- 5 NORMALLY DEVELOPING IMPLANTATIONS218of475TABLE A11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 12 SPONSOR:HONEYWELL INDIVIDUAL MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM MATERNAL GROSS OBSERVATION

----------------------------------------------------------------------------------------------------------------------------------- 54115 OVARIES: CORPORA LUTEA- 6, LEFT; 6, RIGHT 54132 THORACIC CAVITY: CONTENTS, RED FLUID APPROXIMATELY 40.0 ML SKIN: MATTING, GREEN BUCCAL THORACIC CAVITY: MATERIAL, WHITE ATTACHED TO SURFACE OF ALL THORACIC WALLS AND VISCERA LUNGS: DISCOLORATION, BROWN ALL LOBES LIVER: SMALL RIGHT LOBE KIDNEYS: AREA(S), DARK RED SEVERAL, PINPOINT TO 3 MM IN DIAMETER, IN CORTEX, BILATERAL DIED GESTATION DAY 18 UTERUS: LEFT- 4 NORMALLY DEVELOPING IMPLANTATIONS; RIGHT- 7 NORMALLY DEVELOPING IMPLANTATIONS OVARIES: CORPORA LUTEA- 5, LEFT; 9, RIGHT 54135 OVIDUCTS: CYST(S) ONE, 2 MM IN DIAMETER, LEFT 54138 LUNGS: DISCOLORATION, DARK RED ALL LOBES DIED GESTATION DAY 14 UTERUS: LEFT- 4 NORMALLY DEVELOPING IMPLANTATIONS; RIGHT- 5 NORMALLY DEVELOPING IMPLANTATIONS OVARIES: CORPORA LUTEA- 6, LEFT; 6, RIGHT 54140 OVIDUCTS: CYST(S) MULTIPLE, 1 TO 3 MM IN DIAMETER, BILATERAL LUNGS: AREA(S), DARK RED TWO, 4 MM IN DIAMETER, LEFT DIAPHRAGMATIC LOBE DELIVERED GESTATION DAY 29 54150 NO SIGNIFICANT CHANGES OBSERVED 54151 THYMUS: AREA(S), DARK RED MULTIPLE, PINPOINT TO 2 MM IN DIAMETER219of475TABLE A11 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 13 SPONSOR:HONEYWELL INDIVIDUAL MATERNAL MACROSCOPIC FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM MATERNAL GROSS OBSERVATION

----------------------------------------------------------------------------------------------------------------------------------- 54151 DIED GESTATION DAY 20 UTERUS: LEFT- 4 NORMALLY DEVELOPING IMPLANTATIONS; RIGHT- 3 NORMALLY DEVELOPING IMPLANTATIONS OVARIES: CORPORA LUTEA- 5, LEFT; 4, RIGHT 54165 SKIN: MATTING, RED HINDLIMB, BILATERAL; UROGENITAL OVIDUCTS: CYST(S) FEW, 2 MM IN DIAMETER, BILATERAL SPLEEN: SWOLLEN LIVER: MOTTLED ALL LOBES SPLEEN: ACCESSORY ONE, 7 X 5 X 2 MM ABORTED GESTATION DAY 29 UTERUS: LEFT- 2 LATE RESORPTIONS, 5 FORMER IMPLANTATION SITES; RIGHT- 2 FORMER IMPLANTATION SITES OVARIES: CORPORA LUTEA- 7, RIGHT; 2, LEFT FETAL GROSS OBSERVATIONS ABORTED: 7 LATE RESORPTIONS, CROWN-RUMP LENGTHS: 7.5 TO 9.0 CM, MUMMIFIED IN UTERO: 2 LATE RESORPTIONS, CROWN-RUMP LENGTHS: 8.5 CM, MUMMIFIED PMFGRDv4.16 05/29/2008220of475TABLE A12 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL FETAL DATA AT SCHEDULED NECROPSY

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

--------------------------------------- VIABLE FETUSES DEAD FETUSES EARLY RESORPTIONS LATE RESORPTIONS IMPLANTATION SITES CORPORA LUTEA

-------------------------- ---------------- ---------------- ---------------- ---------------- ---------------- SEX LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT DAM# M F HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL OVARY TOTAL

------ ------- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- 53726 6 4 4 6 10 0 0 0 0 0 0 0 0 0 4 6 10 4 6 10 53735 0 5 3 2 5 0 0 0 0 1 1 0 0 0 3 3 6 3 3 6 53738 2 5 5 2 7 0 0 0 0 0 0 0 0 0 5 2 7 5 3 8 53739 6 3 4 5 9 0 0 0 0 1 1 0 0 0 4 6 10 4 7 11 53742 6 3 5 4 9 0 0 0 1 0 1 0 0 0 6 4 10 6 4 10 53748 4 3 5 2 7 0 0 0 0 0 0 0 0 0 5 2 7 6 2 8 53752 2 8 3 7 10 0 0 0 0 0 0 0 0 0 3 7 10 3 7 10 53758 4 6 6 4 10 0 0 0 0 0 0 0 1 1 6 5 11 6 5 11 53760 5 4 5 4 9 0 0 0 0 0 0 0 0 0 5 4 9 5 4 9 53763 5 5 9 1 10 0 0 0 0 0 0 0 0 0 9 1 10 9 1 10 53780 3 6 6 3 9 0 0 0 0 0 0 0 0 0 6 3 9 6 5 11 53783 6 4 7 3 10 0 0 0 0 0 0 0 0 0 7 3 10 8 3 11 54117 3 6 2 7 9 0 0 0 0 0 0 0 0 0 2 7 9 2 8 10 54124 4 4 7 1 8 0 0 0 0 2 2 0 0 0 7 3 10 7 4 11 54128 3 3 1 5 6 0 0 0 0 0 0 0 0 0 1 5 6 1 5 6 54129 5 4 5 4 9 0 0 0 0 0 0 0 0 0 5 4 9 6 4 10 54137 4 6 4 6 10 0 0 0 0 1 1 0 0 0 4 7 11 5 7 12 54143 3 6 4 5 9 0 0 0 0 0 0 0 0 0 4 5 9 4 5 9 54147 7 3 8 2 10 0 0 0 0 0 0 0 0 0 8 2 10 9 2 11 54153 5 0 2 3 5 0 0 0 2 1 3 0 0 0 4 4 8 4 4 8 54157 5 5 6 4 10 0 0 0 0 0 0 0 0 0 6 4 10 6 4 10 54166 3 7 6 4 10 0 0 0 0 0 0 0 0 0 6 4 10 7 4 11 54167 3 3 3 3 6 0 0 0 0 0 0 0 0 0 3 3 6 4 3 7 54169 7 2 3 6 9 0 0 0 0 0 0 0 0 0 3 6 9 4 6 10

TOTAL 101 105 113 93 206 0 0 0 3 6 9 0 1 1 116 100 216 124 106 230 MEAN 4.2 4.4 4.7 3.9 8.6 0.0 0.0 0.0 0.1 0.3 0.4 0.0 0.0 0.0 4.8 4.2 9.0 5.2 4.4 9.6 S.D. 1.72 1.76 1.97 1.75 1.67 0.00 0.00 0.00 0.45 0.53 0.77 0.00 0.20 0.20 1.90 1.71 1.53 2.01 1.77 1.64 S.E. 0.35 0.36 0.40 0.36 0.34 0.00 0.00 0.00 0.09 0.11 0.16 0.00 0.04 0.04 0.39 0.35 0.31 0.41 0.36 0.33 N = 24221of475TABLE A12 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL INDIVIDUAL FETAL DATA AT SCHEDULED NECROPSY

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

--------------------------------------- VIABLE FETUSES DEAD FETUSES EARLY RESORPTIONS LATE RESORPTIONS IMPLANTATION SITES CORPORA LUTEA

-------------------------- ---------------- ---------------- ---------------- ---------------- ---------------- SEX LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT DAM# M F HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL OVARY TOTAL

------ ------- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- 53729 5 4 5 4 9 0 0 0 2 1 3 0 0 0 7 5 12 7 5 12 53736 6 3 5 4 9 0 0 0 0 0 0 0 0 0 5 4 9 6 4 10 53737 7 3 5 5 10 0 0 0 0 1 1 1 0 1 6 6 12 6 7 13 53741 4 7 6 5 11 0 0 0 0 0 0 0 0 0 6 5 11 8 7 15 53744 NONGRAVID 53745 6 5 3 8 11 0 0 0 0 0 0 0 0 0 3 8 11 3 8 11 53753 5 4 6 3 9 0 0 0 0 0 0 0 0 0 6 3 9 7 3 10 53757 3 5 2 6 8 0 0 0 0 0 0 0 0 0 2 6 8 2 6 8 53759 3 4 4 3 7 0 0 0 0 1 1 0 0 0 4 4 8 4 4 8 53778 2 4 4 2 6 0 0 0 2 1 3 0 0 0 6 3 9 6 3 9 53779 5 5 5 5 10 0 0 0 0 0 0 0 0 0 5 5 10 5 5 10 53782 6 2 3 5 8 0 0 0 0 0 0 0 0 0 3 5 8 3 6 9 54119 6 4 5 5 10 0 0 0 0 0 0 0 0 0 5 5 10 5 5 10 54120 5 3 4 4 8 0 0 0 0 0 0 0 0 0 4 4 8 4 5 9 54123 6 2 5 3 8 0 0 0 0 0 0 0 0 0 5 3 8 5 4 9 54131 5 4 5 4 9 0 0 0 0 0 0 0 0 0 5 4 9 5 5 10 54139 1 8 5 4 9 0 0 0 1 0 1 0 0 0 6 4 10 7 4 11 54141 3 6 5 4 9 0 0 0 0 0 0 0 0 0 5 4 9 5 5 10 54146 5 2 1 6 7 0 0 0 0 0 0 0 0 0 1 6 7 1 7 8 54148 8 3 9 2 11 0 0 0 0 0 0 1 0 1 10 2 12 10 3 13 54152 6 4 6 4 10 0 0 0 0 0 0 1 0 1 7 4 11 7 5 12 54156 1 1 2 0 2 0 0 0 0 0 0 3 7 10 5 7 12 5 7 12 54159 3 2 2 3 5 0 0 0 1 0 1 0 0 0 3 3 6 3 6 9 54160 2 3 2 3 5 0 0 0 0 1 1 0 0 0 2 4 6 2 5 7

TOTAL 103 88 99 92 191 0 0 0 6 5 11 6 7 13 111 104 215 116 119 235 MEAN 4.5 3.8 4.3 4.0 8.3 0.0 0.0 0.0 0.3 0.2 0.5 0.3 0.3 0.6 4.8 4.5 9.3 5.0 5.2 10.2 S.D. 1.90 1.67 1.79 1.62 2.20 0.00 0.00 0.00 0.62 0.42 0.90 0.69 1.46 2.09 1.97 1.41 1.85 2.14 1.40 1.93 S.E. 0.40 0.35 0.37 0.34 0.46 0.00 0.00 0.00 0.13 0.09 0.19 0.14 0.30 0.43 0.41 0.29 0.39 0.45 0.29 0.40 N = 23222of475TABLE A12 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL INDIVIDUAL FETAL DATA AT SCHEDULED NECROPSY

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

--------------------------------------- VIABLE FETUSES DEAD FETUSES EARLY RESORPTIONS LATE RESORPTIONS IMPLANTATION SITES CORPORA LUTEA

-------------------------- ---------------- ---------------- ---------------- ---------------- ---------------- SEX LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT DAM# M F HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL OVARY TOTAL

------ ------- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- 53723 1 7 6 2 8 0 0 0 0 0 0 0 0 0 6 2 8 6 3 9 53724 2 6 3 5 8 0 0 0 1 0 1 0 0 0 4 5 9 4 6 10 53728 3 5 2 6 8 0 0 0 0 0 0 0 0 0 2 6 8 4 6 10 53731 5 4 2 7 9 0 0 0 0 0 0 0 0 0 2 7 9 2 7 9 53733 4 3 3 4 7 0 0 0 0 0 0 0 0 0 3 4 7 3 5 8 53734 5 7 4 8 12 0 0 0 0 0 0 0 0 0 4 8 12 6 9 15 53740 3 7 2 8 10 0 0 0 0 0 0 0 0 0 2 8 10 2 8 10 53743 5 5 3 7 10 0 0 0 0 0 0 0 0 0 3 7 10 3 7 10 53747 0 8 4 4 8 0 0 0 1 1 2 0 0 0 5 5 10 7 5 12 53749 3 1 2 2 4 0 0 0 3 3 6 0 0 0 5 5 10 5 5 10 53750 4 3 5 2 7 0 0 0 0 0 0 0 0 0 5 2 7 5 3 8 53751 4 1 3 2 5 0 0 0 0 0 0 0 0 0 3 2 5 6 4 10 53754 5 5 4 6 10 0 0 0 0 0 0 0 0 0 4 6 10 4 6 10 53755 6 3 4 5 9 0 0 0 0 1 1 0 0 0 4 6 10 4 6 10 53756 3 5 3 5 8 0 0 0 0 0 0 0 0 0 3 5 8 4 7 11 53761 6 3 2 7 9 0 0 0 0 0 0 0 0 0 2 7 9 2 7 9 53762 2 6 3 5 8 0 0 0 0 0 0 0 0 0 3 5 8 3 6 9 53764 2 6 5 3 8 0 0 0 0 1 1 0 0 0 5 4 9 5 5 10 53765 5 5 5 5 10 0 0 0 0 0 0 0 0 0 5 5 10 5 5 10 53766 5 6 5 6 11 0 0 0 0 0 0 0 0 0 5 6 11 5 6 11 53768 6 3 6 3 9 0 0 0 0 0 0 1 0 1 7 3 10 7 3 10 53769 6 4 4 6 10 0 0 0 0 0 0 0 0 0 4 6 10 5 6 11 53774 8 2 3 7 10 0 0 0 0 0 0 0 0 0 3 7 10 3 7 10 53775 3 5 5 3 8 0 0 0 0 0 0 0 0 0 5 3 8 5 3 8

TOTAL 96 110 88 118 206 0 0 0 5 6 11 1 0 1 94 124 218 105 135 240 MEAN 4.0 4.6 3.7 4.9 8.6 0.0 0.0 0.0 0.2 0.3 0.5 0.0 0.0 0.0 3.9 5.2 9.1 4.4 5.6 10.0 S.D. 1.87 1.91 1.27 1.95 1.77 0.00 0.00 0.00 0.66 0.68 1.28 0.20 0.00 0.20 1.35 1.81 1.50 1.47 1.61 1.44 S.E. 0.38 0.39 0.26 0.40 0.36 0.00 0.00 0.00 0.13 0.14 0.26 0.04 0.00 0.04 0.28 0.37 0.31 0.30 0.33 0.29 N = 24223of475TABLE A12 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL INDIVIDUAL FETAL DATA AT SCHEDULED NECROPSY

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

--------------------------------------- VIABLE FETUSES DEAD FETUSES EARLY RESORPTIONS LATE RESORPTIONS IMPLANTATION SITES CORPORA LUTEA

-------------------------- ---------------- ---------------- ---------------- ---------------- ---------------- SEX LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT DAM# M F HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL OVARY TOTAL

------ ------- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- 54107 ABORTED DAY 28 54113 GRAVID, DIED DAY 13 54116 3 5 5 3 8 0 0 0 1 0 1 0 0 0 6 3 9 6 3 9 54121 6 1 4 3 7 0 0 0 3 2 5 0 0 0 7 5 12 7 5 12 54122 GRAVID, DIED DAY 14 54125 GRAVID, EUTHANIZED DAY 28 54126 8 3 5 6 11 0 0 0 0 0 0 0 0 0 5 6 11 5 7 12 54127 4 1 3 2 5 0 0 0 2 1 3 0 0 0 5 3 8 5 3 8 54130 7 4 8 3 11 0 0 0 0 0 0 0 0 0 8 3 11 8 3 11 54133 6 0 1 5 6 0 0 0 0 0 0 0 0 0 1 5 6 2 6 8 54134 2 6 2 6 8 0 0 0 0 0 0 0 0 0 2 6 8 3 6 9 54136 4 6 6 4 10 0 0 0 0 0 0 1 0 1 7 4 11 7 5 12 54142 NONGRAVID 54144 GRAVID, DIED DAY 27 54145 4 3 4 3 7 0 0 0 0 0 0 0 0 0 4 3 7 4 3 7 54149 5 5 3 7 10 0 0 0 0 0 0 0 0 0 3 7 10 4 7 11 54155 2 5 6 1 7 0 0 0 0 0 0 0 0 0 6 1 7 6 2 8 54158 0 7 4 3 7 0 0 0 1 0 1 0 0 0 5 3 8 5 3 8 54161 5 3 3 5 8 0 0 0 0 1 1 0 0 0 3 6 9 3 6 9 54162 7 4 6 5 11 0 0 0 0 0 0 0 0 0 6 5 11 7 7 14 54163 1 6 3 4 7 0 0 0 0 0 0 0 0 0 3 4 7 3 4 7 54164 3 5 2 6 8 0 0 0 0 0 0 0 0 0 2 6 8 2 6 8 54168 6 7 8 5 13 0 0 0 0 1 1 0 0 0 8 6 14 8 7 15 54170 4 5 5 4 9 0 0 0 0 0 0 0 0 0 5 4 9 5 4 9

TOTAL 77 76 78 75 153 0 0 0 7 5 12 1 0 1 86 80 166 90 87 177 MEAN 4.3 4.2 4.3 4.2 8.5 0.0 0.0 0.0 0.4 0.3 0.7 0.1 0.0 0.1 4.8 4.4 9.2 5.0 4.8 9.8 S.D. 2.19 2.05 1.97 1.58 2.09 0.00 0.00 0.00 0.85 0.57 1.33 0.24 0.00 0.24 2.10 1.58 2.10 1.94 1.72 2.38 S.E. 0.52 0.48 0.46 0.37 0.49 0.00 0.00 0.00 0.20 0.14 0.31 0.06 0.00 0.06 0.50 0.37 0.50 0.46 0.41 0.56 N = 18224of475TABLE A12 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL INDIVIDUAL FETAL DATA AT SCHEDULED NECROPSY

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

--------------------------------------- VIABLE FETUSES DEAD FETUSES EARLY RESORPTIONS LATE RESORPTIONS IMPLANTATION SITES CORPORA LUTEA

-------------------------- ---------------- ---------------- ---------------- ---------------- ---------------- SEX LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT DAM# M F HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL HORN HORN TOTAL OVARY TOTAL

------ ------- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- ---- ---- ----- 53722 9 3 4 8 12 0 0 0 0 0 0 0 0 0 4 8 12 4 8 12 53725 4 5 4 5 9 0 0 0 0 0 0 0 0 0 4 5 9 4 6 10 53727 6 6 5 7 12 0 0 0 0 0 0 0 0 0 5 7 12 6 8 14 53730 4 3 1 6 7 0 0 0 0 0 0 0 3 3 1 9 10 1 9 10 53732 GRAVID, DIED DAY 12 53770 ABORTED DAY 26 53771 7 4 6 5 11 0 0 0 1 0 1 0 0 0 7 5 12 7 5 12 53772 5 4 4 5 9 0 0 0 1 1 2 0 0 0 5 6 11 6 7 13 53773 3 7 4 6 10 0 0 0 0 0 0 0 0 0 4 6 10 5 6 11 53776 4 6 2 8 10 0 0 0 0 0 0 0 0 0 2 8 10 2 8 10 53777 5 3 5 3 8 0 0 0 0 0 0 0 0 0 5 3 8 5 3 8 53781 GRAVID, DIED DAY 14 54108 3 6 4 5 9 0 0 0 1 0 1 0 0 0 5 5 10 5 5 10 54111 ABORTED DAY 26 54112 3 3 0 6 6 0 0 0 0 0 0 0 0 0 0 6 6 1 6 7 54114 GRAVID, EUTHANIZED DAY 16 54115 GRAVID, DIED DAY 14 54132 GRAVID, DIED DAY 18 54135 5 4 5 4 9 0 0 0 0 0 0 0 0 0 5 4 9 5 5 10 54138 GRAVID, DIED DAY 14 54140 5 5 5 5 10 0 0 0 0 0 0 1 0 1 6 5 11 6 7 13 54150 2 8 4 6 10 0 0 0 0 0 0 0 0 0 4 6 10 4 6 10 54151 GRAVID, DIED DAY 20 54165 ABORTED DAY 29

TOTAL 65 67 53 79 132 0 0 0 3 1 4 1 3 4 57 83 140 61 89 150 MEAN 4.6 4.8 3.8 5.6 9.4 0.0 0.0 0.0 0.2 0.1 0.3 0.1 0.2 0.3 4.1 5.9 10.0 4.4 6.4 10.7 S.D. 1.82 1.63 1.67 1.39 1.70 0.00 0.00 0.00 0.43 0.27 0.61 0.27 0.80 0.83 1.90 1.64 1.66 1.86 1.60 1.94 S.E. 0.49 0.43 0.45 0.37 0.45 0.00 0.00 0.00 0.11 0.07 0.16 0.07 0.21 0.22 0.51 0.44 0.44 0.50 0.43 0.52 N = 14 PLRDv4.08 06/16/2008225of475TABLE A13 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL FETAL DATA AT SCHEDULED NECROPSY [% PER LITTER]

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM

----------------------------------------------------------------------------------------------------------------------------------- PRE- POST- CORPORA IMPLANTATION FETUSES RESORPTIONS IMPLANTATION IMPLANTATION DAM # LUTEA SITES VIABLE DEAD EARLY LATE TOTAL LOSS LOSS MALES FEMALES

----------------------------------------------------------------------------------------------------------------------------------- # # % % % % % % % % %

----------------------------------------------------------------------------------------------------------------------------------- 53726 10.0 10.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 60.0 40.0 53735 6.0 6.0 83.3 0.0 16.7 0.0 16.7 0.0 16.7 0.0 100.0 53738 8.0 7.0 100.0 0.0 0.0 0.0 0.0 12.5 0.0 28.6 71.4 53739 11.0 10.0 90.0 0.0 10.0 0.0 10.0 9.1 10.0 66.7 33.3 53742 10.0 10.0 90.0 0.0 10.0 0.0 10.0 0.0 10.0 66.7 33.3 53748 8.0 7.0 100.0 0.0 0.0 0.0 0.0 12.5 0.0 57.1 42.9 53752 10.0 10.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 20.0 80.0 53758 11.0 11.0 90.9 0.0 0.0 9.1 9.1 0.0 9.1 40.0 60.0 53760 9.0 9.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 55.6 44.4 53763 10.0 10.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 50.0 50.0 53780 11.0 9.0 100.0 0.0 0.0 0.0 0.0 18.2 0.0 33.3 66.7 53783 11.0 10.0 100.0 0.0 0.0 0.0 0.0 9.1 0.0 60.0 40.0 54117 10.0 9.0 100.0 0.0 0.0 0.0 0.0 10.0 0.0 33.3 66.7 54124 11.0 10.0 80.0 0.0 20.0 0.0 20.0 9.1 20.0 50.0 50.0 54128 6.0 6.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 50.0 50.0 54129 10.0 9.0 100.0 0.0 0.0 0.0 0.0 10.0 0.0 55.6 44.4 54137 12.0 11.0 90.9 0.0 9.1 0.0 9.1 8.3 9.1 40.0 60.0 54143 9.0 9.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 33.3 66.7 54147 11.0 10.0 100.0 0.0 0.0 0.0 0.0 9.1 0.0 70.0 30.0 54153 8.0 8.0 62.5 0.0 37.5 0.0 37.5 0.0 37.5 100.0 0.0 54157 10.0 10.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 50.0 50.0 54166 11.0 10.0 100.0 0.0 0.0 0.0 0.0 9.1 0.0 30.0 70.0 54167 7.0 6.0 100.0 0.0 0.0 0.0 0.0 14.3 0.0 50.0 50.0 54169 10.0 9.0 100.0 0.0 0.0 0.0 0.0 10.0 0.0 77.8 22.2

----------------------------------------------------------------------------------------------------------------------------------- MEAN 9.6 9.0 95.3 0.0 4.3 0.4 4.7 5.9 4.7 49.1 50.9 S.D. 1.64 1.53 9.15 0.00 9.14 1.86 9.15 5.89 9.15 20.65 20.65 S.E. 0.33 0.31 1.87 0.00 1.87 0.38 1.87 1.20 1.87 4.22 4.22 N 24 24 24 24 24 24 24 24 24 24 24226of475TABLE A13 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL INDIVIDUAL FETAL DATA AT SCHEDULED NECROPSY [% PER LITTER]

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM

----------------------------------------------------------------------------------------------------------------------------------- PRE- POST- CORPORA IMPLANTATION FETUSES RESORPTIONS IMPLANTATION IMPLANTATION DAM # LUTEA SITES VIABLE DEAD EARLY LATE TOTAL LOSS LOSS MALES FEMALES

----------------------------------------------------------------------------------------------------------------------------------- # # % % % % % % % % %

----------------------------------------------------------------------------------------------------------------------------------- 53729 12.0 12.0 75.0 0.0 25.0 0.0 25.0 0.0 25.0 55.6 44.4 53736 10.0 9.0 100.0 0.0 0.0 0.0 0.0 10.0 0.0 66.7 33.3 53737 13.0 12.0 83.3 0.0 8.3 8.3 16.7 7.7 16.7 70.0 30.0 53741 15.0 11.0 100.0 0.0 0.0 0.0 0.0 26.7 0.0 36.4 63.6 53745 11.0 11.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 54.5 45.5 53753 10.0 9.0 100.0 0.0 0.0 0.0 0.0 10.0 0.0 55.6 44.4 53757 8.0 8.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 37.5 62.5 53759 8.0 8.0 87.5 0.0 12.5 0.0 12.5 0.0 12.5 42.9 57.1 53778 9.0 9.0 66.7 0.0 33.3 0.0 33.3 0.0 33.3 33.3 66.7 53779 10.0 10.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 50.0 50.0 53782 9.0 8.0 100.0 0.0 0.0 0.0 0.0 11.1 0.0 75.0 25.0 54119 10.0 10.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 60.0 40.0 54120 9.0 8.0 100.0 0.0 0.0 0.0 0.0 11.1 0.0 62.5 37.5 54123 9.0 8.0 100.0 0.0 0.0 0.0 0.0 11.1 0.0 75.0 25.0 54131 10.0 9.0 100.0 0.0 0.0 0.0 0.0 10.0 0.0 55.6 44.4 54139 11.0 10.0 90.0 0.0 10.0 0.0 10.0 9.1 10.0 11.1 88.9 54141 10.0 9.0 100.0 0.0 0.0 0.0 0.0 10.0 0.0 33.3 66.7 54146 8.0 7.0 100.0 0.0 0.0 0.0 0.0 12.5 0.0 71.4 28.6 54148 13.0 12.0 91.7 0.0 0.0 8.3 8.3 7.7 8.3 72.7 27.3 54152 12.0 11.0 90.9 0.0 0.0 9.1 9.1 8.3 9.1 60.0 40.0 54156 12.0 12.0 16.7 0.0 0.0 83.3 83.3 0.0 83.3 50.0 50.0 54159 9.0 6.0 83.3 0.0 16.7 0.0 16.7 33.3 16.7 60.0 40.0 54160 7.0 6.0 83.3 0.0 16.7 0.0 16.7 14.3 16.7 40.0 60.0

----------------------------------------------------------------------------------------------------------------------------------- MEAN 10.2 9.3 89.9 0.0 5.3 4.7 10.1 8.4 10.1 53.4 46.6 S.D. 1.93 1.85 18.57 0.00 9.45 17.38 18.57 8.54 18.57 16.18 16.18 S.E. 0.40 0.39 3.87 0.00 1.97 3.62 3.87 1.78 3.87 3.37 3.37 N 23 23 23 23 23 23 23 23 23 23 23227of475TABLE A13 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL INDIVIDUAL FETAL DATA AT SCHEDULED NECROPSY [% PER LITTER]

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM

----------------------------------------------------------------------------------------------------------------------------------- PRE- POST- CORPORA IMPLANTATION FETUSES RESORPTIONS IMPLANTATION IMPLANTATION DAM # LUTEA SITES VIABLE DEAD EARLY LATE TOTAL LOSS LOSS MALES FEMALES

----------------------------------------------------------------------------------------------------------------------------------- # # % % % % % % % % %

----------------------------------------------------------------------------------------------------------------------------------- 53723 9.0 8.0 100.0 0.0 0.0 0.0 0.0 11.1 0.0 12.5 87.5 53724 10.0 9.0 88.9 0.0 11.1 0.0 11.1 10.0 11.1 25.0 75.0 53728 10.0 8.0 100.0 0.0 0.0 0.0 0.0 20.0 0.0 37.5 62.5 53731 9.0 9.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 55.6 44.4 53733 8.0 7.0 100.0 0.0 0.0 0.0 0.0 12.5 0.0 57.1 42.9 53734 15.0 12.0 100.0 0.0 0.0 0.0 0.0 20.0 0.0 41.7 58.3 53740 10.0 10.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 30.0 70.0 53743 10.0 10.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 50.0 50.0 53747 12.0 10.0 80.0 0.0 20.0 0.0 20.0 16.7 20.0 0.0 100.0 53749 10.0 10.0 40.0 0.0 60.0 0.0 60.0 0.0 60.0 75.0 25.0 53750 8.0 7.0 100.0 0.0 0.0 0.0 0.0 12.5 0.0 57.1 42.9 53751 10.0 5.0 100.0 0.0 0.0 0.0 0.0 50.0 0.0 80.0 20.0 53754 10.0 10.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 50.0 50.0 53755 10.0 10.0 90.0 0.0 10.0 0.0 10.0 0.0 10.0 66.7 33.3 53756 11.0 8.0 100.0 0.0 0.0 0.0 0.0 27.3 0.0 37.5 62.5 53761 9.0 9.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 66.7 33.3 53762 9.0 8.0 100.0 0.0 0.0 0.0 0.0 11.1 0.0 25.0 75.0 53764 10.0 9.0 88.9 0.0 11.1 0.0 11.1 10.0 11.1 25.0 75.0 53765 10.0 10.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 50.0 50.0 53766 11.0 11.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 45.5 54.5 53768 10.0 10.0 90.0 0.0 0.0 10.0 10.0 0.0 10.0 66.7 33.3 53769 11.0 10.0 100.0 0.0 0.0 0.0 0.0 9.1 0.0 60.0 40.0 53774 10.0 10.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 80.0 20.0 53775 8.0 8.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 37.5 62.5

----------------------------------------------------------------------------------------------------------------------------------- MEAN 10.0 9.1 94.9 0.0 4.7 0.4 5.1 8.8 5.1 47.2 52.8 S.D. 1.44 1.50 12.89 0.00 12.89 2.04 12.89 12.02 12.89 20.89 20.89 S.E. 0.29 0.31 2.63 0.00 2.63 0.42 2.63 2.45 2.63 4.26 4.26 N 24 24 24 24 24 24 24 24 24 24 24228of475TABLE A13 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL INDIVIDUAL FETAL DATA AT SCHEDULED NECROPSY [% PER LITTER]

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM

----------------------------------------------------------------------------------------------------------------------------------- PRE- POST- CORPORA IMPLANTATION FETUSES RESORPTIONS IMPLANTATION IMPLANTATION DAM # LUTEA SITES VIABLE DEAD EARLY LATE TOTAL LOSS LOSS MALES FEMALES

----------------------------------------------------------------------------------------------------------------------------------- # # % % % % % % % % %

----------------------------------------------------------------------------------------------------------------------------------- 54116 9.0 9.0 88.9 0.0 11.1 0.0 11.1 0.0 11.1 37.5 62.5 54121 12.0 12.0 58.3 0.0 41.7 0.0 41.7 0.0 41.7 85.7 14.3 54126 12.0 11.0 100.0 0.0 0.0 0.0 0.0 8.3 0.0 72.7 27.3 54127 8.0 8.0 62.5 0.0 37.5 0.0 37.5 0.0 37.5 80.0 20.0 54130 11.0 11.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 63.6 36.4 54133 8.0 6.0 100.0 0.0 0.0 0.0 0.0 25.0 0.0 100.0 0.0 54134 9.0 8.0 100.0 0.0 0.0 0.0 0.0 11.1 0.0 25.0 75.0 54136 12.0 11.0 90.9 0.0 0.0 9.1 9.1 8.3 9.1 40.0 60.0 54145 7.0 7.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 57.1 42.9 54149 11.0 10.0 100.0 0.0 0.0 0.0 0.0 9.1 0.0 50.0 50.0 54155 8.0 7.0 100.0 0.0 0.0 0.0 0.0 12.5 0.0 28.6 71.4 54158 8.0 8.0 87.5 0.0 12.5 0.0 12.5 0.0 12.5 0.0 100.0 54161 9.0 9.0 88.9 0.0 11.1 0.0 11.1 0.0 11.1 62.5 37.5 54162 14.0 11.0 100.0 0.0 0.0 0.0 0.0 21.4 0.0 63.6 36.4 54163 7.0 7.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 14.3 85.7 54164 8.0 8.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 37.5 62.5 54168 15.0 14.0 92.9 0.0 7.1 0.0 7.1 6.7 7.1 46.2 53.8 54170 9.0 9.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 44.4 55.6

----------------------------------------------------------------------------------------------------------------------------------- MEAN 9.8 9.2 92.8 0.0 6.7 0.5 7.2 5.7 7.2 50.5 49.5 S.D. 2.38 2.10 12.70 0.00 12.80 2.14 12.70 7.84 12.70 25.54 25.54 S.E. 0.56 0.50 2.99 0.00 3.02 0.51 2.99 1.85 2.99 6.02 6.02 N 18 18 18 18 18 18 18 18 18 18 18229of475TABLE A13 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL INDIVIDUAL FETAL DATA AT SCHEDULED NECROPSY [% PER LITTER]

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM

----------------------------------------------------------------------------------------------------------------------------------- PRE- POST- CORPORA IMPLANTATION FETUSES RESORPTIONS IMPLANTATION IMPLANTATION DAM # LUTEA SITES VIABLE DEAD EARLY LATE TOTAL LOSS LOSS MALES FEMALES

----------------------------------------------------------------------------------------------------------------------------------- # # % % % % % % % % %

----------------------------------------------------------------------------------------------------------------------------------- 53722 12.0 12.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 75.0 25.0 53725 10.0 9.0 100.0 0.0 0.0 0.0 0.0 10.0 0.0 44.4 55.6 53727 14.0 12.0 100.0 0.0 0.0 0.0 0.0 14.3 0.0 50.0 50.0 53730 10.0 10.0 70.0 0.0 0.0 30.0 30.0 0.0 30.0 57.1 42.9 53771 12.0 12.0 91.7 0.0 8.3 0.0 8.3 0.0 8.3 63.6 36.4 53772 13.0 11.0 81.8 0.0 18.2 0.0 18.2 15.4 18.2 55.6 44.4 53773 11.0 10.0 100.0 0.0 0.0 0.0 0.0 9.1 0.0 30.0 70.0 53776 10.0 10.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 40.0 60.0 53777 8.0 8.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 62.5 37.5 54108 10.0 10.0 90.0 0.0 10.0 0.0 10.0 0.0 10.0 33.3 66.7 54112 7.0 6.0 100.0 0.0 0.0 0.0 0.0 14.3 0.0 50.0 50.0 54135 10.0 9.0 100.0 0.0 0.0 0.0 0.0 10.0 0.0 55.6 44.4 54140 13.0 11.0 90.9 0.0 0.0 9.1 9.1 15.4 9.1 50.0 50.0 54150 10.0 10.0 100.0 0.0 0.0 0.0 0.0 0.0 0.0 20.0 80.0

----------------------------------------------------------------------------------------------------------------------------------- MEAN 10.7 10.0 94.6 0.0 2.6 2.8 5.4 6.3 5.4 49.1 50.9 S.D. 1.94 1.66 9.09 0.00 5.58 8.20 9.09 6.83 9.09 14.62 14.62 S.E. 0.52 0.44 2.43 0.00 1.49 2.19 2.43 1.83 2.43 3.91 3.91 N 14 14 14 14 14 14 14 14 14 14 14 PILPv4.02 06/16/2008230of475TABLE A14 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL FETAL WEIGHTS [G]

----------------------------------------------------------------------------------------------------------------------------------- FETUS # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

----------------------------------------------------------------------------------------------------------------------------------- DAM # MEAN GROUP 1: 0 PPM

-------------------------------------------- 53726 43.2 48.9 44.8 45.8 44.2/39.7 39.1 40.5 43.0 46.4 39.5 53735 49.8 54.2 42.7 50.7/ E 50.2 51.1 53738 45.5 50.1 45.1 43.2 45.5 44.2/44.2 46.4 53739 35.4 35.7 33.9 35.6 35.7/32.5 30.0 38.6 E 41.1 35.1 53742 41.2 39.9 43.3 43.4 40.4 E 35.1/37.0 46.4 44.1 41.1 53748 44.9 46.8 40.4 45.1 40.4 47.7/47.1 47.1 53752 43.1 51.3 36.5 45.1/47.1 39.7 37.4 33.7 47.6 46.1 46.4 53758 35.4 40.5 36.0 35.4 32.2 27.3 36.0/34.5 L 36.1 38.0 37.9 53760 44.6 46.8 46.0 44.0 42.3 43.9/43.2 40.1 42.3 52.4 53763 37.6 42.7 40.3 44.1 34.5 37.1 40.4 30.0 27.0 38.8/41.0 53780 38.8 39.1 39.5 36.7 33.0 34.9 40.0/45.9 35.7 44.5 53783 48.1 50.3 48.8 48.4 48.4 43.9 39.1 52.5/48.7 49.8 51.4 54117 48.2 50.9 49.5/44.2 45.3 50.2 49.3 46.6 47.3 50.6 54124 45.8 52.2 50.9 49.5 45.0 42.6 42.4 37.1/46.5 E E 54128 43.7 42.9/41.5 41.4 43.2 46.1 46.8 54129 40.0 45.5 39.3 39.1 40.5 36.2/40.2 39.4 37.6 41.8 54137 43.0 46.2 42.6 37.0 47.6/45.0 38.2 41.6 43.7 44.2 43.5 E 54143 42.9 49.6 43.3 40.8 41.4/40.4 36.8 46.6 39.0 48.5 54147 34.7 39.5 38.5 34.6 32.1 32.4 30.7 28.0 36.5/37.3 37.1 54153 38.8 41.1 38.0 E E /34.8 36.5 E 43.5 54157 43.8 45.7 45.9 39.8 40.1 40.1 42.3/48.9 42.8 43.9 48.3 54166 32.3 40.6 23.2 33.8 27.4 26.9 30.7/33.3 37.5 35.0 34.5 54167 47.7 52.1 49.1 43.5/47.3 46.9 47.1 54169 37.8 42.0 41.1 41.3/39.0 31.3 33.3 33.6 39.4 39.2

MEAN 41.9 S.D. 4.75 S.E. 0.97 N 24

E = EARLY RESORPTION L = LATE RESORPTION D = DEAD FETUS ’/’ DENOTES POSITION OF CERVIX231of475TABLE A14 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL INDIVIDUAL FETAL WEIGHTS [G]

----------------------------------------------------------------------------------------------------------------------------------- FETUS # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

----------------------------------------------------------------------------------------------------------------------------------- DAM # MEAN GROUP 2: 2500 PPM

-------------------------------------------- 53729 36.5 E 25.7 E 40.4 23.7 33.2 41.2/44.2 38.8 39.5 42.0 E 53736 38.5 41.4 36.7 36.0 35.2 36.1/36.8 39.3 44.6 40.7 53737 34.4 L 34.9 36.0 32.3 32.5 33.3/35.0 27.3 33.0 35.5 E 44.4 53741 42.7 45.7 37.7 42.1 46.9 38.3 36.5/42.2 42.9 48.7 40.2 48.1 53745 37.9 41.3 45.5 36.4/38.1 30.0 26.2 34.5 43.9 38.2 38.7 43.7 53753 39.5 43.2 36.4 39.8 36.8 34.8 39.1/41.3 41.2 43.2 53757 35.0 39.7 36.9/33.3 26.8 29.8 37.6 36.5 39.6 53759 43.7 42.0 46.0 43.4 37.1/44.3 42.1 E 51.3 53778 43.7 46.3 43.2 E 42.4 39.3 E / E 45.2 46.0 53779 35.0 40.2 28.2 29.8 30.5 32.3/40.8 35.6 37.8 35.2 39.2 53782 37.7 40.2 35.2 38.8/32.3 31.8 40.1 37.0 46.4 54119 38.0 39.5 34.1 34.6 33.5 35.1/39.6 32.7 45.5 41.9 43.3 54120 37.0 46.5 39.1 37.3 35.7/33.3 26.1 36.3 41.8 54123 41.5 38.8 28.8 40.2 45.1 45.2/46.1 42.5 45.1 54131 45.3 48.6 48.0 44.6 37.1 46.6/48.0 35.8 46.8 52.1 54139 43.0 48.4 41.2 42.7 37.8 40.1 E /38.8 47.5 44.2 46.5 54141 44.6 48.3 43.4 43.5 45.1 42.3/43.0 47.3 47.1 41.4 54146 41.3 47.5/40.2 39.3 35.1 41.0 43.5 42.4 54148 31.7 32.9 34.2 30.3 28.8 30.1 31.7 22.0 L 25.2 37.8/33.1 42.9 54152 43.5 51.2 40.0 L 41.3 46.3 35.6 40.9/45.5 41.9 42.7 50.0 54156 35.2 32.3 38.0 L L L / L L L L L L L 54159 38.3 42.4 E 35.5/34.6 36.9 41.9 54160 46.5 49.2 46.2/47.5 45.2 44.4 E

MEAN 39.6 S.D. 4.05 S.E. 0.84 N 23

E = EARLY RESORPTION L = LATE RESORPTION D = DEAD FETUS ’/’ DENOTES POSITION OF CERVIX232of475TABLE A14 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL INDIVIDUAL FETAL WEIGHTS [G]

----------------------------------------------------------------------------------------------------------------------------------- FETUS # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

----------------------------------------------------------------------------------------------------------------------------------- DAM # MEAN GROUP 3: 4000 PPM

-------------------------------------------- 53723 36.4 41.8 37.7 37.0 35.2 29.5 31.4/34.8 44.1 53724 41.4 E 40.0 41.3 41.8/37.9 42.8 40.2 43.5 43.8 53728 38.5 47.4 41.6/36.3 31.1 30.9 36.3 40.3 43.7 53731 33.6 39.0 36.0/29.4 27.1 35.0 33.9 32.7 30.8 38.5 53733 45.8 45.7 46.7 45.9/44.8 40.8 46.4 50.3 53734 35.0 45.5 42.3 38.1 37.6/30.3 24.6 29.1 27.0 35.6 35.7 34.6 40.1 53740 42.8 46.8 46.0/44.5 41.7 42.1 40.5 42.3 37.1 41.1 45.5 53743 33.3 38.0 33.9 32.3/28.9 25.7 29.1 30.5 36.5 36.6 41.4 53747 38.7 43.1 39.5 E 31.1 34.2/40.6 E 43.8 37.8 39.1 53749 43.3 47.2 43.7 E E E / E E E 43.1 39.1 53750 39.8 46.8 31.2 35.8 37.8 42.2/41.8 43.0 53751 39.0 42.8 35.4 36.1/38.0 42.8 53754 37.5 42.3 38.3 38.8 32.5/40.1 34.8 33.6 33.8 39.7 41.3 53755 41.2 45.6 41.7 40.1 43.0/35.7 34.7 41.2 E 43.3 45.4 53756 45.3 50.2 43.9 48.8/46.3 41.4 44.0 45.0 43.0 53761 38.2 38.1 36.6/35.8 31.5 37.3 37.4 37.1 43.2 46.7 53762 33.3 37.9 35.7 27.8/32.4 25.5 33.4 38.0 35.6 53764 33.0 39.6 33.0 33.4 30.8 34.2/28.7 E 30.4 33.8 53765 37.5 39.9 39.7 39.2 26.7 32.5/35.0 36.2 39.5 42.7 43.6 53766 43.8 49.9 47.2 46.0 32.5 49.6/44.6 33.2 38.7 48.8 45.6 46.1 53768 40.4 48.4 39.6 L 39.3 38.4 32.5 36.4/44.0 47.6 37.7 53769 33.4 42.2 37.8 27.6 39.0/29.6 26.2 23.1 29.3 38.3 40.8 53774 42.9 49.0 45.1 38.7/35.1 36.7 42.2 42.5 42.7 44.5 52.5 53775 41.6 40.7 42.8 42.6 35.6 38.2/39.3 47.7 45.5

MEAN 39.0 S.D. 3.99 S.E. 0.82 N 24

E = EARLY RESORPTION L = LATE RESORPTION D = DEAD FETUS ’/’ DENOTES POSITION OF CERVIX233of475TABLE A14 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL INDIVIDUAL FETAL WEIGHTS [G]

----------------------------------------------------------------------------------------------------------------------------------- FETUS # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

----------------------------------------------------------------------------------------------------------------------------------- DAM # MEAN GROUP 4: 5500 PPM

-------------------------------------------- 54116 42.3 48.2 44.6 E 38.0 37.3 37.1/42.2 46.1 44.6 54121 48.0 48.7 E 50.1 E E 42.7 49.1/51.3 48.5 E 45.4 E 54126 33.6 40.5 36.4 33.7 36.0 34.9/28.6 31.0 34.6 32.6 23.6 37.3 54127 31.0 35.4 E 31.1 E 29.6/30.0 E 28.7 54130 22.2 31.8 25.5 15.2 15.0 14.4 15.9 18.2 26.6/25.6 25.6 30.7 54133 48.6 51.7/46.2 40.0 49.7 49.6 54.3 54134 44.3 41.8 42.5/51.7 42.4 38.3 44.9 45.5 46.9 54136 41.7 43.9 42.5 41.6 38.8 L 31.6 42.3/42.2 42.9 42.2 48.7 54145 40.9 45.9 41.3 37.9 42.9/39.1 36.7 42.2 54149 37.3 45.5 40.6 38.4/39.1 32.5 25.6 17.5 39.0 43.3 51.3 54155 40.3 40.2 38.9 37.9 39.5 35.8 43.5/46.3 54158 47.1 E 44.2 47.4 46.6 44.1/47.2 51.2 49.2 54161 41.3 43.9 41.5 40.5/ E 37.9 36.5 40.1 43.1 46.7 54162 29.8 31.6 35.1 31.1 13.6 20.9 30.8/28.3 33.6 35.4 32.7 34.9 54163 37.8 46.1 37.3 33.5/33.2 35.8 37.3 41.2 54164 37.3 37.8 33.7/36.5 35.5 39.1 35.8 37.9 41.9 54168 30.0 40.3 27.0 27.5 23.5 24.0 22.8 26.7 31.5/29.9 27.6 34.0 35.0 39.9 E 54170 37.1 40.8 40.2 34.8 27.1 31.4/33.4 37.7 41.9 46.5

MEAN 38.4 S.D. 7.03 S.E. 1.66 N 18

E = EARLY RESORPTION L = LATE RESORPTION D = DEAD FETUS ’/’ DENOTES POSITION OF CERVIX234of475TABLE A14 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL INDIVIDUAL FETAL WEIGHTS [G]

----------------------------------------------------------------------------------------------------------------------------------- FETUS # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

----------------------------------------------------------------------------------------------------------------------------------- DAM # MEAN GROUP 5: 7500 PPM

-------------------------------------------- 53722 35.9 42.6 37.3 42.4 40.7/34.3 33.0 26.7 29.7 28.6 34.7 39.2 41.5 53725 35.0 37.9 35.3 36.1 35.4/32.5 29.8 31.2 35.9 40.5 53727 37.2 46.9 43.1 39.6 30.3 34.9/37.1 23.9 26.2 35.3 44.4 40.2 44.9 53730 43.7 48.7/40.5 L L 51.0 41.3 L 34.1 41.3 48.8 53771 32.8 34.9 35.9 32.9 28.1 18.4 25.9 E /34.6 34.3 36.5 39.0 40.1 53772 43.2 38.9 42.7 39.7 44.9 E /37.6 43.5 43.2 E 46.7 51.9 53773 42.9 48.5 49.9 40.2 41.3/41.8 32.7 35.5 41.6 45.9 51.7 53776 35.9 43.5 39.1/33.3 30.2 35.1 33.7 31.3 34.7 37.3 40.8 53777 42.7 47.5 45.9 40.7 34.1 40.1/44.5 42.4 46.0 54108 36.1 35.9 34.4 35.1 35.2 E /38.9 32.8 37.0 33.6 42.2 54112 40.8 /36.2 38.9 38.0 42.1 42.3 47.0 54135 37.8 44.4 37.0 36.2 37.4 34.9/29.3 36.1 41.2 43.5 54140 26.2 28.6 22.1 24.5 25.9 22.9 L /20.9 25.0 26.5 31.4 34.3 54150 39.0 45.0 43.9 39.3 36.8/33.8 34.7 27.2 41.1 42.2 45.9

MEAN 37.8 S.D. 4.82 S.E. 1.29 N 14

E = EARLY RESORPTION L = LATE RESORPTION D = DEAD FETUS ’/’ DENOTES POSITION OF CERVIX PFWTv4.15 06/16/2008235of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

-----------------------------------------------------------------------------------------------------------------------------------

53726 1 2 3 4 5 6 7 8 9 10 A A A A/ A A A A A A SEX: F M M M M M M F F F

SKELETAL 1 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 VISCERAL 6 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL 7 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT SKELETAL 8 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 9 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 10 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,4,5,7,8,9,10 SKELETAL 2,3,4,5,6

53735 1 2 3 4 5 6 A A A/ E A A SEX: F F F - F F

SKELETAL 1 V 13TH FULL RIB(S) P
BILATERAL

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE236of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53735 (CONTINUED) SKELETAL 1 V 27 PRESACRAL VERTEBRAE P VISCERAL 2 M KIDNEY- MALPOSITIONED P LEFT LOCATED MORE POSTERIOR THAN NORMAL V SPLEEN- SMALL P V ACCESSORY SPLEEN(S) P TWO, PINPOINT V RENAL PAPILLA(E) NOT DEVELOPED AND/OR DISTENDED URETER(S) 1 URETER, RIGHT RENAL PAPILLA(E) NOT FULLY DEVELOPED (WOO AND HOAR GRADE 1) P RIGHT V GALLBLADDER- ABSENT OR SMALL P SMALL V MAJOR BLOOD VESSEL VARIATION P RETROESOPHAGEAL RIGHT SUBCLAVIAN: RIGHT SUBCLAVIAN COURSES RETROESOPHAGEAL AND JOINS AORTIC ARCH ADJACENT TO DUCTUS ARTERIOSUS (NO BRACHIOCEPHALIC TRUNK) SKELETAL V HYOID ARCH(ES) BENT 1 RIGHT V 13TH RUDIMENTARY RIB(S) P
BILATERAL EXTERNAL 4 EARLY RESORPTION VISCERAL 5 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 6 V MAJOR BLOOD VESSEL VARIATION P RETROESOPHAGEAL RIGHT SUBCLAVIAN: RIGHT SUBCLAVIAN COURSES RETROESOPHAGEAL AND JOINS AORTIC ARCH ADJACENT TO DUCTUS

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE237of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53735 (CONTINUED) ARTERIOSUS (NO BRACHIOCEPHALIC TRUNK) NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,5,6 VISCERAL 1,3 SKELETAL 3,6

53738 1 2 3 4 5 6 7 A A A A A/ A A SEX: M F F F F M F

VISCERAL 1 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 2 V 7TH STERNEBRA P LOCATED BETWEEN #5 AND #6, WITH THREAD-LIKE ATTACHMENT TO #5 V EXTRA SITE OF OSSIFICATION VENTRAL TO CERVICAL CENTRUM #2 P VISCERAL 3 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
LEFT V 27 PRESACRAL VERTEBRAE P SKELETAL 5 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 6 V 13TH RUDIMENTARY RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE238of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53738 (CONTINUED) RIGHT VISCERAL 7 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7 VISCERAL 2,5,6 SKELETAL

53739 1 2 3 4 5 6 7 8 9 10 A A A A/ A A A E A A SEX: F M F M M F M - M M

VISCERAL 3 V GALLBLADDER- ABSENT OR SMALL P SMALL SKELETAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 4 V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 5 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 6 V 13TH FULL RIB(S) P
BILATERAL EXTERNAL 8 EARLY RESORPTION SKELETAL 10 V 13TH RUDIMENTARY RIB(S) P
BILATERAL

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE239of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53739 (CONTINUED) NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,9,10 VISCERAL 1,2,4,5,6,7,9,10 SKELETAL 1,2,7,9

53742 1 2 3 4 5 6 7 8 9 10 A A A A E A/ A A A A SEX: M M M F - F M M F M

VISCERAL 1 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL 2 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 3 V 13TH FULL RIB(S) P
LEFT SKELETAL 4 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P EXTERNAL 5 EARLY RESORPTION SKELETAL 6 M VERTEBRAL ANOMALY WITH OR WITHOUT ASSOCIATED RIB ANOMALY P RIGHT HALF OF LUMBAR CENTRUM #1 ABSENT; RIGHT THORACIC ARCH AND HALF OF THORACIC CENTRUM #12 LOCATED MORE POSTERIOR THAN NORMAL; RIGHT LUMBAR ARCH AND HALF OF LUMBAR CENTRUM #2 LOCATED MORE ANTERIOR THAN NORMAL V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE240of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 6 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53742 (CONTINUED)
BILATERAL VISCERAL 7 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 8 V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 10 M RIB ANOMALY P RIB #7 FORKED, MEDIAL, BILATERAL; COSTAL CARTILAGE ARISING FROM ANTERIOR PORTION OF FORKED RIB #7, BILATERAL ASSOCIATES WITH STERNUM IN NORMAL #7 POSITION V REDUCED OSSIFICATION OF THE RIB(S) P RIB #12, MODERATE, RIGHT; RIB #12, SLIGHT, LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,6,7,8,9,10 VISCERAL 2,3,4,6,8,9,10 SKELETAL 1,9

53748 1 2 3 4 5 6 7 A A A A A/ A A SEX: M F M F F M M

SKELETAL 1 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT VISCERAL 2 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE241of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 7 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53748 (CONTINUED) #5 SKELETAL V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 4 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 5 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 7 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7 VISCERAL 1,3,4,5,6,7 SKELETAL 3,6

53752 1 2 3 4 5 6 7 8 9 10 A A A/ A A A A A A A SEX: M F F F F F F F M F

SKELETAL 2 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 3 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 4 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 5 V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 6 V 13TH RUDIMENTARY RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE242of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 8 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53752 (CONTINUED)
BILATERAL SKELETAL 8 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 10 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,4,5,6,7,8,9,10 SKELETAL 1,7,9

53758 1 2 3 4 5 6 7 8 9 10 11 A A A A A A/ A L A A A SEX: F M F M F M M - F F F

VISCERAL 5 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER EXTERNAL 8 LATE RESORPTION CROWN-RUMP LENGTH: 5.3 CM, MUMMIFIED SKELETAL 10 V 13TH RUDIMENTARY RIB(S) P RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,9,10,11 VISCERAL 1,2,3,4,6,7,9,10,11 SKELETAL 1,2,3,4,5,6,7,9,11

53760 1 2 3 4 5 6 7 8 9 A A A A A/ A A A A SEX: M M M F M F F F M

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE243of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 9 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53760 (CONTINUED) SKELETAL 1 V HYOID ARCH(ES) BENT 1
LEFT V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 2 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 4 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL 5 V 13TH RUDIMENTARY RIB(S) P
LEFT VISCERAL 6 V RETROCAVAL URETER P RIGHT SKELETAL V HYOID ARCH(ES) BENT 2
LEFT V 13TH FULL RIB(S) P
BILATERAL SKELETAL 7 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 8 V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 1,2,3,5,7,8,9 SKELETAL 3,4,9

53763 1 2 3 4 5 6 7 8 9 10 A A A A A A A A A/ A SEX: F M F F M M M F M F

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE244of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 10 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53763 (CONTINUED) SKELETAL 3 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 4 V HYOID ARCH(ES) BENT 2 RIGHT V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 6 V 13TH FULL RIB(S) P
LEFT SKELETAL 7 V 13TH FULL RIB(S) P RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,4,5,6,7,8,9,10 SKELETAL 1,2,5,8,9,10

53780 1 2 3 4 5 6 7 8 9 A A A A A A/ A A A SEX: F F F F F M M F M

SKELETAL 1 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 2 V STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) 1 #3 AND #4; RIGHT HALF OF #3 ATTACHED TO LEFT HALF OF #4; RIGHT HALF OF #4 ATTACHED TO #5 SKELETAL 3 V HYOID ARCH(ES) BENT 1
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 1,2,3,4,5,6,7,8,9 SKELETAL 4,5,6,7,8,9

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE245of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 11 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

-----------------------------------------------------------------------------------------------------------------------------------

53783 1 2 3 4 5 6 7 8 9 10 A A A A A A A/ A A A SEX: M M F F M M F F M M

SKELETAL 1 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 2 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 3 V 13TH FULL RIB(S) P
BILATERAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 4 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 5 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V HYOID ARCH(ES) BENT 2 RIGHT SKELETAL 6 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 VISCERAL 7 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE246of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 12 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53783 (CONTINUED) #5 SKELETAL 8 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 9 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V HYOID ARCH(ES) BENT 1
LEFT SKELETAL 10 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,4,5,6,8,9,10 SKELETAL

54117 1 2 3 4 5 6 7 8 9 A A/ A A A A A A A SEX: F F F F F F M M M

SKELETAL 3 V 13TH RUDIMENTARY RIB(S) P
LEFT V STERNEBRAE WITH THREAD-LIKE ATTACHMENT P #4 ATTACHED TO #5 SKELETAL 4 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT V STERNEBRAE WITH THREAD-LIKE ATTACHMENT P #4 ATTACHED TO #5 SKELETAL 6 V 13TH RUDIMENTARY RIB(S) P
LEFT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE247of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 13 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54117 (CONTINUED) SKELETAL 7 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT VISCERAL 8 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL 9 V 13TH RUDIMENTARY RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 1,2,3,4,5,6,7,9 SKELETAL 1,2,5,8

54124 1 2 3 4 5 6 7 8 9 10 A A A A A A A/ A E E SEX: M F M M F F F M - -

VISCERAL 1 V ACCESSORY SPLEEN(S) P TWO, PINPOINT SKELETAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 3 V RETROCAVAL URETER P RIGHT V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, LEFT VISCERAL 5 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK VISCERAL 6 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH RUDIMENTARY RIB(S) P
LEFT VISCERAL 7 V MAJOR BLOOD VESSEL VARIATION P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE248of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 14 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54124 (CONTINUED) LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V HYOID ARCH(ES) BENT 2
BILATERAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 VISCERAL 8 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, LEFT SKELETAL V HYOID ARCH(ES) BENT 2
LEFT EXTERNAL 9 EARLY RESORPTION EXTERNAL 10 EARLY RESORPTION NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8 VISCERAL 2,4 SKELETAL 2,3,4,5

54128 1 2 3 4 5 6 A/ A A A A A SEX: M F F F M M

VISCERAL 1 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V HYOID ARCH(ES) BENT 2
BILATERAL SKELETAL 2 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 3 V HYOID ARCH(ES) BENT 3
BILATERAL SKELETAL 4 V 13TH RUDIMENTARY RIB(S) P
LEFT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE249of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 15 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54128 (CONTINUED) SKELETAL 4 V HYOID ARCH(ES) BENT 3
BILATERAL SKELETAL 5 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT V HYOID ARCH(ES) BENT 2
BILATERAL VISCERAL 6 V ACCESSORY SPLEEN(S) P ONE, PINPOINT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6 VISCERAL 2,3,4,5 SKELETAL 6

54129 1 2 3 4 5 6 7 8 9 A A A A A/ A A A A SEX: M F F F M M M F M

VISCERAL 1 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 2 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT VISCERAL 3 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT VISCERAL 4 V ACCESSORY SPLEEN(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE250of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 16 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54129 (CONTINUED) ONE, PINPOINT SKELETAL V HYOID ARCH(ES) BENT P SEVERE, RIGHT; SLIGHT, LEFT V 13TH FULL RIB(S) P
BILATERAL VISCERAL 5 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 7TH STERNEBRA P LOCATED BETWEEN #5 AND #6 V STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) 1 #3 THROUGH #5 V STERNEBRA(E) #1,#2,#3 AND/OR #4 UNOSSIFIED P #2 M RIB ANOMALY P EXTRA RIB LOCATED BETWEEN LEFT THORACIC ARCHES #3 AND #4; RIGHT RIB #1 FORKED, MEDIAL; LEFT COSTAL CARTILAGE ARISING FROM EXTRA RIB ASSOCIATES WITH STERNUM IN NORMAL #4 POSITION; ALL SUBSEQUENT LEFT COSTAL CARTILAGES ASSOCIATE WITH STERNUM ONE NUMBER POSITION HIGHER THAN NORMAL; RIGHT COSTAL CARTILAGE ARISING FROM ANTERIOR PORTION OF FORKED RIB #1 FUSED TO RIGHT COSTAL CARTILAGE ARISING FROM POSTERIOR PORTION OF FORKED RIB #1 PROXIMAL AND ASSOCIATES WITH STERNUM IN NORMAL #1 POSITION; ALL OTHER RIGHT COSTAL CARTILAGES NOT AFFECTED VISCERAL 6 V GALLBLADDER- ABSENT OR SMALL P SMALL M LUNGS- LOBULAR AGENESIS P RIGHT ACCESSORY LOBE ABSENT V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 27 PRESACRAL VERTEBRAE P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE251of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 17 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54129 (CONTINUED) SKELETAL 6 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 7 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V HYOID ARCH(ES) BENT 2
LEFT VISCERAL 8 V GALLBLADDER- ABSENT OR SMALL P SMALL SKELETAL V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P
LEFT SKELETAL 9 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 2,9 SKELETAL 3

54137 1 2 3 4 5 6 7 8 9 10 11 A A A A/ A A A A A A E SEX: F M F M M F F F M F -

SKELETAL 1 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 2 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 3 V HEART- EXTRA PAPILLARY MUSCLE P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE252of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 18 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54137 (CONTINUED) VENTRICLE, RIGHT VISCERAL V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL 5 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT VISCERAL 6 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 7 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL 8 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 9 V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 10 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V 13TH RUDIMENTARY RIB(S) P RIGHT EXTERNAL 11 EARLY RESORPTION

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE253of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 19 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54137 (CONTINUED) NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,5,8,9 SKELETAL 4,7

54143 1 2 3 4 5 6 7 8 9 A A A A/ A A A A A SEX: F M F F M M F F F

VISCERAL 1 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V HYOID ARCH(ES) BENT 1 RIGHT VISCERAL 2 GALLBLADDER- CYST(S) P ONE, 1 MM IN DIAMETER VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 5 V ACCESSORY SPLEEN(S) P TWO, PINPOINT V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE254of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 20 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54143 (CONTINUED)
BILATERAL SKELETAL V 27 PRESACRAL VERTEBRAE P VISCERAL 6 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT VISCERAL 7 V ACCESSORY SPLEEN(S) P ONE, 1 MM IN DIAMETER VISCERAL 8 V ACCESSORY SPLEEN(S) P TWO, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 9 V 13TH RUDIMENTARY RIB(S) P
LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 3,9 SKELETAL 2,3,6,7

54147 1 2 3 4 5 6 7 8 9 10 A A A A A A A A/ A A SEX: M M F M M F M F M M

SKELETAL 2 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 4 V GALLBLADDER- ABSENT OR SMALL P SMALL SKELETAL 5 V 13TH FULL RIB(S) P
LEFT VISCERAL 7 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER V GALLBLADDER- ABSENT OR SMALL P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE255of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 21 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54147 (CONTINUED) SMALL SKELETAL V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 8 V STERNEBRAE WITH THREAD-LIKE ATTACHMENT P #4 ATTACHED TO #5 NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,5,6,8,9,10 SKELETAL 1,3,4,6,9,10

54153 1 2 3 4 5 6 7 8 A A E E/ A A E A SEX: M M - - M M - M

SKELETAL 1 V HYOID ARCH(ES) BENT 2 RIGHT V 13TH FULL RIB(S) P
BILATERAL EXTERNAL 3 EARLY RESORPTION EXTERNAL 4 EARLY RESORPTION SKELETAL 5 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 6 V ACCESSORY SPLEEN(S) P ONE, 1 MM IN DIAMETER SKELETAL V 13TH FULL RIB(S) P
LEFT V STERNEBRAE WITH THREAD-LIKE ATTACHMENT P #4 ATTACHED TO #5 EXTERNAL 7 EARLY RESORPTION EXTERNAL 8 M SHORT TAIL

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE256of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 22 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54153 (CONTINUED) 5 MM IN LENGTH VISCERAL CONFIRMATION OF SHORT TAIL P SKELETAL CONFIRMATION OF SHORT TAIL P ONLY 12 CAUDAL VERTEBRAE PRESENT; CAUDAL VERTEBRAE #7 THROUGH #9 MISSHAPEN AND/OR FUSED NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,5,6 VISCERAL 1,2,5 SKELETAL 2

54157 1 2 3 4 5 6 7 8 9 10 A A A A A A/ A A A A SEX: M F F F F M M F M M

VISCERAL 1 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK VISCERAL 2 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V HEART- ONLY TWO PAPILLARY MUSCLES PRESENT P VENTRICLE, RIGHT SKELETAL V 13TH RUDIMENTARY RIB(S) P RIGHT V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 VISCERAL 3 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) 1 #4 AND #5

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE257of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 23 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54157 (CONTINUED) VISCERAL 4 V KIDNEY(S)- PALE P RIGHT SKELETAL V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 5 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 SKELETAL 6 V EXTRA SITE OF OSSIFICATION ANTERIOR TO STERNEBRA #1 P VISCERAL 7 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 8 V HEART- ONLY TWO PAPILLARY MUSCLES PRESENT P VENTRICLE, RIGHT SKELETAL V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 5,6,9,10 SKELETAL 1,9,10

54166 1 2 3 4 5 6 7 8 9 10 A A A A A A/ A A A A SEX: M M F F F F F M F F

SKELETAL 1 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 2 V 13TH FULL RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE258of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 24 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54166 (CONTINUED)
BILATERAL SKELETAL V 27 PRESACRAL VERTEBRAE P SKELETAL 3 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 4 V 13TH FULL RIB(S) P
BILATERAL V EXTRA SITE OF OSSIFICATION VENTRAL TO CERVICAL CENTRUM #2 P V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 SKELETAL 5 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 7 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 9 V EXTRA SITE OF OSSIFICATION VENTRAL TO CERVICAL CENTRUM #2 P SKELETAL 10 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,4,5,6,7,8,9,10 SKELETAL 6,8

54167 1 2 3 4 5 6 A A A/ A A A SEX: F F M M F M

SKELETAL 1 V EXTRA SITE OF OSSIFICATION ANTERIOR TO STERNEBRA #1 P SKELETAL 2 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT VISCERAL 3 V ACCESSORY SPLEEN(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE259of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 25 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54167 (CONTINUED) ONE, PINPOINT VISCERAL 4 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK VISCERAL 6 V RETROCAVAL URETER P RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6 VISCERAL 1,2,5 SKELETAL 3,4,5,6

54169 1 2 3 4 5 6 7 8 9 A A A/ A A A A A A SEX: M M M M F M M F M

VISCERAL 2 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL 4 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 5 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 7 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 8 V HYOID ARCH(ES) BENT 1
BILATERAL VISCERAL 9 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE260of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 26 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54169 (CONTINUED) VISCERAL 9 THORACIC CAVITY- CONTENTS, DARK RED P SKELETAL V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 1,3,4,6,7,8 SKELETAL 1,2,3,6

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE261of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 27 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

-----------------------------------------------------------------------------------------------------------------------------------

53729 1 2 3 4 5 6 7 8 9 10 11 12 E A E A A A A/ A A A A E SEX: - F - M F M F M F M M -

EXTERNAL 1 EARLY RESORPTION VISCERAL 2 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P
BILATERAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 EXTERNAL 3 EARLY RESORPTION VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, PINPOINT VISCERAL 5 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 AND #6 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 6 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 7 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V MAJOR BLOOD VESSEL VARIATION P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE262of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 28 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53729 (CONTINUED) LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 8 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 9 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 10 V ACCESSORY SPLEEN(S) P TWO, PINPOINT SKELETAL V STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) P #4 AND #5, MODERATE; #2 AND #3, SLIGHT V 13TH FULL RIB(S) P
BILATERAL VISCERAL 11 V ACCESSORY SPLEEN(S) P FOUR, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL EXTERNAL 12 EARLY RESORPTION NO REMARKABLE OBSERVATIONS EXTERNAL 2,4,5,6,7,8,9,10,11 VISCERAL 6,8,9 SKELETAL 4

53736 1 2 3 4 5 6 7 8 9 A A A A A/ A A A A SEX: F F M M M F M M M

SKELETAL 1 V 13TH FULL RIB(S) P
LEFT SKELETAL 2 V 13TH FULL RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE263of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 29 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53736 (CONTINUED)
LEFT SKELETAL 3 V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 4 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 5 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 6 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT VISCERAL 7 ABDOMINAL CAVITY- CONTENTS, CLEAR FLUID P APPROXIMATELY 1.0 ML SKELETAL V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT VISCERAL 8 ABDOMINAL CAVITY- CONTENTS, CLEAR FLUID P APPROXIMATELY 0.5 ML SKELETAL V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT VISCERAL 9 ABDOMINAL CAVITY- CONTENTS, CLEAR FLUID P APPROXIMATELY 1.0 ML SKELETAL V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 1,2,3,4,5,6 SKELETAL

53737 1 2 3 4 5 6 7 8 9 10 11 12 L A A A A A/ A A A A E A SEX: - M M F M F M M M F - M

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE264of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 30 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53737 (CONTINUED) EXTERNAL 1 LATE RESORPTION CROWN-RUMP LENGTH: 10.0 CM, MODERATE AUTOLYSIS, NO APPARENT MALFORMATIONS SKELETAL 4 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 6 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 SKELETAL 10 V 13TH FULL RIB(S) P
LEFT EXTERNAL 11 EARLY RESORPTION SKELETAL 12 V 13TH RUDIMENTARY RIB(S) P
LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 2,3,4,5,6,7,8,9,10,12 VISCERAL 2,3,4,5,6,7,8,9,10,12 SKELETAL 2,3,5,7,8,9

53741 1 2 3 4 5 6 7 8 9 10 11 A A A A A A/ A A A A A SEX: F F M M M F M F F F F

SKELETAL 1 V 7TH CERVICAL RIB(S) P PINPOINT, RIGHT SKELETAL 2 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 7TH CERVICAL RIB(S) P PINPOINT, BILATERAL SKELETAL 3 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 VISCERAL 4 V MAJOR BLOOD VESSEL VARIATION P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE265of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 31 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53741 (CONTINUED) LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL 5 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 6 V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 7 V 7TH CERVICAL RIB(S) P PINPOINT, RIGHT SKELETAL 8 V 7TH CERVICAL RIB(S) P INTERMEDIATE, LEFT V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 10 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 11 V 7TH CERVICAL RIB(S) P PINPOINT, BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10,11 VISCERAL 1,2,3,5,6,7,8,9,10,11 SKELETAL 4,9

53745 1 2 3 4 5 6 7 8 9 10 11 A A A/ A A A A A A A A SEX: F M F M F M F M M F M

EXTERNAL 1 SKIN: AREA(S), WHITE TWO, PINPOINT AND 2 MM IN DIAMETER, DORSAL NECK SKELETAL V HYOID ARCH(ES) BENT 1
LEFT V STERNEBRAE WITH THREAD-LIKE ATTACHMENT P #3 ATTACHED TO #4; #4 ATTACHED TO #5

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE266of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 32 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53745 (CONTINUED) SKELETAL 1 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT SKELETAL 2 V 13TH FULL RIB(S) P
BILATERAL EXTERNAL 3 SKIN: AREA(S), WHITE MULTIPLE, PINPOINT TO 3 MM IN DIAMETER, ALL EXTERNAL SURFACES M MICROPHTHALMIA AND/OR ANOPHTHALMIA MICROPHTHALMIA, LEFT VISCERAL CONFIRMATION OF MICROPHTHALMIA P SKELETAL V 13TH FULL RIB(S) P
BILATERAL M VERTEBRAL CENTRA ANOMALY P RIGHT HALF OF CERVICAL CENTRUM #4 ABSENT; CERVICAL CENTRUM #2 ATTACHED TO CERVICAL CENTRUM #3; RIGHT HALF OF CERVICAL CENTRUM #5 LOCATED MORE ANTERIOR THAN NORMAL MICROPHTHALMIA- NO APPARENT SKELETAL ORIGIN P SKELETAL 4 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 5 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 6 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 7 V 13TH RUDIMENTARY RIB(S) P
BILATERAL EXTERNAL 9 SKIN: AREA(S), WHITE MULTIPLE, PINPOINT TO 3 MM IN DIAMETER, ALL EXTERNAL SURFACES SKELETAL V 13TH FULL RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE267of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 33 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53745 (CONTINUED)
BILATERAL SKELETAL V 27 PRESACRAL VERTEBRAE P V STERNEBRAE WITH THREAD-LIKE ATTACHMENT P #3 ATTACHED TO #4; #4 ATTACHED TO #5 EXTERNAL 10 SKIN: AREA(S), WHITE FEW, PINPOINT TO 2 MM IN DIAMETER, DORSAL NECK M MICROPHTHALMIA AND/OR ANOPHTHALMIA MICROPHTHALMIA, LEFT VISCERAL V RETROCAVAL URETER P RIGHT CONFIRMATION OF MICROPHTHALMIA P SKELETAL V 13TH FULL RIB(S) P
BILATERAL CONFIRMATION OF MICROPHTHALMIA P ORBIT APPEARS SMALLER THAN NORMAL, LEFT SKELETAL 11 V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 2,4,5,6,7,8,11 VISCERAL 1,2,4,5,6,7,8,9,11 SKELETAL 8

53753 1 2 3 4 5 6 7 8 9 A A A A A A/ A A A SEX: F F M F M M M F M

VISCERAL 1 V RETROCAVAL URETER P RIGHT SKELETAL V 13TH RUDIMENTARY RIB(S) P
LEFT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE268of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 34 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53753 (CONTINUED) VISCERAL 3 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER SKELETAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 5 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 AND #6 SKELETAL 6 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 SKELETAL 7 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 AND #6 SKELETAL 8 M VERTEBRAL ANOMALY WITH OR WITHOUT ASSOCIATED RIB ANOMALY P RIGHT HALF OF THORACIC CENTRUM #9 SMALLER THAN NORMAL AND ATTACHED TO RIGHT HALF OF THORACIC CENTRUM #8; RIGHT THORACIC ARCH AND RIGHT HALF OF THORACIC CENTRUM #8 LOCATED MORE POSTERIOR THAN NORMAL; RIGHT THORACIC ARCH AND RIGHT HALF OF THORACIC CENTRUM #10 LOCATED MORE ANTERIOR THAN NORMAL; LEFT RIBS #4 AND #5 FUSED, PROXIMAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 2,4,5,6,7,8,9 SKELETAL 2,4,9

53757 1 2 3 4 5 6 7 8 A A/ A A A A A A SEX: M F F M M F F F

SKELETAL 1 V STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) 1 #3 AND #4 SKELETAL 3 V HYOID ARCH(ES) BENT 1
LEFT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE269of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 35 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53757 (CONTINUED) SKELETAL 3 V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY VISCERAL 6 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER VISCERAL 7 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8 VISCERAL 1,2,3,4,5,8 SKELETAL 2,4,5,6,7,8

53759 1 2 3 4 5 6 7 8 A A A A/ A A E A SEX: F M F M M F - F

SKELETAL 1 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT SKELETAL 2 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 3 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 5 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 6 V 13TH FULL RIB(S) P
BILATERAL EXTERNAL 7 EARLY RESORPTION SKELETAL 8 V 13TH FULL RIB(S) P
BILATERAL

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE270of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 36 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53759 (CONTINUED) NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,8 VISCERAL 1,2,3,4,5,6,8 SKELETAL 4

53778 1 2 3 4 5 6 7 8 9 A A E A A E/ E A A SEX: M F - M F - - F F

VISCERAL 1 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER SKELETAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 2 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P EXTERNAL 3 EARLY RESORPTION VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER SKELETAL V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 5 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P EXTERNAL 6 EARLY RESORPTION EXTERNAL 7 EARLY RESORPTION SKELETAL 8 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 9 V 13TH FULL RIB(S) P
BILATERAL

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE271of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 37 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53778 (CONTINUED) NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,4,5,8,9 VISCERAL 2,5,8,9 SKELETAL

53779 1 2 3 4 5 6 7 8 9 10 A A A A A/ A A A A A SEX: F F F M F M F M M M

VISCERAL 1 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL 2 V STERNEBRAE WITH THREAD-LIKE ATTACHMENT P #4 ATTACHED TO #5 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 3 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 5 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT VISCERAL 6 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT VISCERAL 8 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL 9 V 13TH RUDIMENTARY RIB(S) P
LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 2,3,4,5,7,9,10 SKELETAL 1,4,6,7,8,10

53782 1 2 3 4 5 6 7 8 A A A/ A A A A A SEX: F M M M M M M F

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE272of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 38 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53782 (CONTINUED) VISCERAL 1 DIAPHRAGM- CYST(S) P ONE, 5 MM IN DIAMETER SKELETAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 3 V ACCESSORY SPLEEN(S) P ONE, 1 MM IN DIAMETER SKELETAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 5 V GALLBLADDER- ABSENT OR SMALL P SMALL SKELETAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 6 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 7 V HYOID ARCH(ES) BENT 1 RIGHT V 13TH FULL RIB(S) P
BILATERAL SKELETAL 8 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8 VISCERAL 2,4,6,7,8 SKELETAL 2,4

54119 1 2 3 4 5 6 7 8 9 10 A A A A A/ A A A A A SEX: M M M M M F F M F F

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE273of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 39 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54119 (CONTINUED) SKELETAL 1 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 SKELETAL 3 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 VISCERAL 4 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P
BILATERAL SKELETAL 5 V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P
BILATERAL VISCERAL 6 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P
BILATERAL VISCERAL 7 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V HYOID ARCH(ES) BENT 1 RIGHT V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P
BILATERAL VISCERAL 8 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 27 PRESACRAL VERTEBRAE P V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 V 13TH FULL RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE274of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 40 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54119 (CONTINUED)
BILATERAL VISCERAL 9 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 SKELETAL 10 V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,5,10 SKELETAL 2

54120 1 2 3 4 5 6 7 8 A A A A/ A A A A SEX: M F F M M F M M

SKELETAL 1 V 13TH FULL RIB(S) P
BILATERAL V 7TH CERVICAL RIB(S) P PINPOINT, BILATERAL SKELETAL 2 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 4 V 13TH RUDIMENTARY RIB(S) P
LEFT V HYOID ARCH(ES) BENT 1
BILATERAL VISCERAL 5 V MAJOR BLOOD VESSEL VARIATION P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE275of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 41 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54120 (CONTINUED) LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL 8 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8 VISCERAL 1,2,3,4,6,7,8 SKELETAL 3,5,6,7

54123 1 2 3 4 5 6 7 8 A A A A A/ A A A SEX: M F F M M M M M

VISCERAL 3 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V HYOID ARCH(ES) BENT P SEVERE, LEFT; MODERATE, RIGHT VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL 5 V EXTRA SITE OF OSSIFICATION ANTERIOR TO STERNEBRA #1 P TWO OSSIFICATION CENTERS PRESENT VISCERAL 6 THYMUS- AREA(S), DARK RED P MULTIPLE, PINPOINT SKELETAL 7 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 8 V HYOID ARCH(ES) BENT 1 RIGHT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE276of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 42 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54123 (CONTINUED) NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8 VISCERAL 1,2,5,7,8 SKELETAL 1,2,4,6

54131 1 2 3 4 5 6 7 8 9 A A A A A/ A A A A SEX: F F M M M F F M M

VISCERAL 1 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL M VERTEBRAL ANOMALY WITH OR WITHOUT ASSOCIATED RIB ANOMALY P EXTRA RIB, ARCH AND HALF OF THORACIC CENTRUM LOCATED BETWEEN RIGHT THORACIC ARCHES #4 AND #5; RIGHT THORACIC ARCH AND RIGHT HALF OF THORACIC CENTRUM #4 LOCATED MORE ANTERIOR THAN NORMAL; RIGHT THORACIC ARCH AND RIGHT HALF OF THORACIC CENTRUM #5 LOCATED MORE POSTERIOR THAN NORMAL; RIGHT COSTAL CARTILAGE ARISING FROM EXTRA RIB ASSOCIATES WITH STERNUM IN NORMAL #5 POSITION; ALL SUBSEQUENT RIGHT COSTAL CARTILAGES ASSOCIATE WITH STERNUM ONE NUMBER POSITION HIGHER THAN NORMAL VISCERAL 2 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 7TH CERVICAL RIB(S) P PINPOINT, LEFT SKELETAL 4 V 7TH CERVICAL RIB(S) P PINPOINT, LEFT VISCERAL 7 V HEART- EXTRA PAPILLARY MUSCLE P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE277of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 43 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54131 (CONTINUED) VENTRICLE, RIGHT SKELETAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH RUDIMENTARY RIB(S) P RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 3,4,5,6,8,9 SKELETAL 3,5,6,8,9

54139 1 2 3 4 5 6 7 8 9 10 A A A A A E/ A A A A SEX: F F F F F - F M F F

SKELETAL 1 V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 2 M STERNEBRA(E) MALALIGNED (SEVERE) P #2; LEFT HALF OF #2 FUSED TO LEFT HALF OF #1 SKELETAL 3 V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 4 V HYOID ARCH(ES) BENT 1 RIGHT V EXTRA SITE OF OSSIFICATION ANTERIOR TO STERNEBRA #1 P VISCERAL 5 THYMUS- DISCOLORATION, DARK RED P EXTERNAL 6 EARLY RESORPTION SKELETAL 7 V HYOID ARCH(ES) BENT P MODERATE, RIGHT; SLIGHT, LEFT V 13TH FULL RIB(S) P
LEFT SKELETAL 8 V 13TH RUDIMENTARY RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE278of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 44 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54139 (CONTINUED)
LEFT VISCERAL 9 THYMUS- DISCOLORATION, DARK RED P SKELETAL 10 V EXTRA SITE OF OSSIFICATION ANTERIOR TO STERNEBRA #1 P NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,7,8,9,10 VISCERAL 1,2,3,4,7,8,10 SKELETAL 5,9

54141 1 2 3 4 5 6 7 8 9 A A A A A/ A A A A SEX: M F F M F F F M F

VISCERAL 2 V ACCESSORY SPLEEN(S) P TWO, 1 MM IN DIAMETER VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER VISCERAL 5 V RETROCAVAL URETER P RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 1,3,6,7,8,9 SKELETAL 1,2,3,4,5,6,7,8,9

54146 1 2 3 4 5 6 7 A/ A A A A A A SEX: M M F M F M M

SKELETAL 1 V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 2 V HYOID ARCH(ES) BENT 1

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE279of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 45 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54146 (CONTINUED)
BILATERAL SKELETAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 3 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V HEART- ONLY TWO PAPILLARY MUSCLES PRESENT P VENTRICLE, RIGHT V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 4 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 5 V HYOID ARCH(ES) BENT P MODERATE, LEFT; SLIGHT, RIGHT V 13TH RUDIMENTARY RIB(S) P RIGHT VISCERAL 7 V HEART- ONLY TWO PAPILLARY MUSCLES PRESENT P VENTRICLE, RIGHT STOMACH- DISTENDED P SKELETAL V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE280of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 46 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54146 (CONTINUED) NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7 VISCERAL 1,2,5,6 SKELETAL 6

54148 1 2 3 4 5 6 7 8 9 10 11 12 A A A A A A A L A A/ A A SEX: M M M M M M F - M M F F

SKELETAL 2 V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL 5 V 13TH RUDIMENTARY RIB(S) P
LEFT EXTERNAL 8 LATE RESORPTION CROWN-RUMP LENGTH: 7.6 CM, SEVERE AUTOLYSIS, NO APPARENT MALFORMATIONS SKELETAL 9 V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 12 THORACIC CAVITY- CONTENTS, DARK RED P NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,9,10,11,12 VISCERAL 1,2,3,5,6,7,9,10,11 SKELETAL 1,3,4,6,7,10,11,12

54152 1 2 3 4 5 6 7 8 9 10 11 A A L A A A A/ A A A A SEX: F M - F M M M F M M F

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE281of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 47 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54152 (CONTINUED) VISCERAL 1 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 2 V SKELETAL MUSCLE- THICKENED P ENTIRE LUMBAR REGION V EXTRA FAT PADS P SURROUNDING VENTRAL AND LEFT LATERAL NECK RENAL PAPILLA(E) NOT FULLY DEVELOPED (WOO AND HOAR GRADE 1) P
LEFT SKELETAL V 13TH FULL RIB(S) P
BILATERAL EXTERNAL 3 LATE RESORPTION CROWN-RUMP LENGTH: 6.5 CM, SEVERE AUTOLYSIS, NO APPARENT MALFORMATIONS SKELETAL 4 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 5 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 6 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 8 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 9 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 10 V 13TH FULL RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE282of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 48 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54152 (CONTINUED)
BILATERAL VISCERAL 11 ABDOMINAL CAVITY- FLUID FILLED P APPROXIMATELY 1.0 ML SKELETAL V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,4,5,6,7,8,9,10,11 VISCERAL 4,5,6,7,10 SKELETAL 7

54156 1 2 3 4 5 6 7 8 9 10 11 12 A A L L L/ L L L L L L L SEX: F M - - - - - - - - - -

VISCERAL 1 V KIDNEY(S)- MISSHAPEN P
BILATERAL EXTERNAL 3 LATE RESORPTION CROWN-RUMP LENGTH: 7.5 CM, MUMMIFIED EXTERNAL 4 LATE RESORPTION CROWN-RUMP LENGTH: 8.0 CM, SEVERE AUTOLYSIS, NO APPARENT MALFORMATIONS EXTERNAL 5 LATE RESORPTION CROWN-RUMP LENGTH: 7.1 CM, MUMMIFIED EXTERNAL 6 LATE RESORPTION CROWN-RUMP LENGTH: 6.2 CM, MUMMIFIED EXTERNAL 7 LATE RESORPTION CROWN-RUMP LENGTH: 5.9 CM, MUMMIFIED EXTERNAL 8 LATE RESORPTION CROWN-RUMP LENGTH: 6.5 CM, MUMMIFIED

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE283of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 49 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54156 (CONTINUED) EXTERNAL 9 LATE RESORPTION CROWN-RUMP LENGTH: 6.6 CM, MUMMIFIED EXTERNAL 10 LATE RESORPTION CROWN-RUMP LENGTH: 7.1 CM, MUMMIFIED EXTERNAL 11 LATE RESORPTION CROWN-RUMP LENGTH: 8.0 CM, MUMMIFIED EXTERNAL 12 LATE RESORPTION CROWN-RUMP LENGTH: 7.5 CM, MUMMIFIED NO REMARKABLE OBSERVATIONS EXTERNAL 1,2 VISCERAL 2 SKELETAL 1,2

54159 1 2 3 4 5 6 A E A/ A A A SEX: M - M F M F

SKELETAL 1 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT EXTERNAL 2 EARLY RESORPTION SKELETAL 3 V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 4 V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,3,4,5,6 VISCERAL 1,3,4,5,6 SKELETAL 5,6

54160 1 2 3 4 5 6 A A/ A A A E SEX: M F M F F -

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE284of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 50 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 2500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54160 (CONTINUED) SKELETAL 2 V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 3 V 13TH RUDIMENTARY RIB(S) P
BILATERAL EXTERNAL 6 EARLY RESORPTION NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5 VISCERAL 1,2,3,4,5 SKELETAL 1,4,5

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE285of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 51 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

-----------------------------------------------------------------------------------------------------------------------------------

53723 1 2 3 4 5 6 7 8 A A A A A A/ A A SEX: F F F F M F F F

SKELETAL 1 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 3 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 4 V HYOID ARCH(ES) BENT 1
LEFT SKELETAL 6 V HYOID ARCH(ES) BENT 3
LEFT V 13TH FULL RIB(S) P RIGHT SKELETAL 7 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 8 V 13TH RUDIMENTARY RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8 VISCERAL 1,2,3,4,5,6,7,8 SKELETAL 2,5

53724 1 2 3 4 5 6 7 8 9 E A A A/ A A A A A SEX: - F F M F F F F M

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE286of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 52 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53724 (CONTINUED) EXTERNAL 1 EARLY RESORPTION SKELETAL 2 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 3 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 4 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 6 V HYOID ARCH(ES) BENT 1
LEFT SKELETAL 7 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 8 V HYOID ARCH(ES) BENT 1
LEFT V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 9 V HYOID ARCH(ES) BENT 1
LEFT V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 2,3,4,5,6,7,8,9 VISCERAL 2,3,4,5,6,7,8,9 SKELETAL 5

53728 1 2 3 4 5 6 7 8 A A/ A A A A A A SEX: F M F M F M F F

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE287of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 53 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53728 (CONTINUED) SKELETAL 2 V EXTRA SITE OF OSSIFICATION ANTERIOR TO STERNEBRA #1 P SKELETAL 3 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8 VISCERAL 1,2,3,4,5,6,7,8 SKELETAL 1,4,5,6,7,8

53731 1 2 3 4 5 6 7 8 9 A A/ A A A A A A A SEX: F M M M M F F F M

VISCERAL 3 V GALLBLADDER- ABSENT OR SMALL P SMALL SKELETAL 4 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 6 V GALLBLADDER- ABSENT OR SMALL P SMALL SKELETAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 7 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 8 V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 9 V 13TH RUDIMENTARY RIB(S) P RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 1,2,4,5,7,8,9 SKELETAL 1,2,3,5

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE288of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 54 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

-----------------------------------------------------------------------------------------------------------------------------------

53733 1 2 3 4 5 6 7 A A A/ A A A A SEX: M M F M F F M

VISCERAL 3 V ACCESSORY SPLEEN(S) P TWO, PINPOINT V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 5 V 13TH RUDIMENTARY RIB(S) P RIGHT VISCERAL 6 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V HYOID ARCH(ES) BENT 1
LEFT V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 7 V 13TH RUDIMENTARY RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7 VISCERAL 1,2,5,7 SKELETAL 1,2

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE289of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 55 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

-----------------------------------------------------------------------------------------------------------------------------------

53734 1 2 3 4 5 6 7 8 9 10 11 12 A A A A/ A A A A A A A A SEX: F F M M F F F F M M F M

SKELETAL 1 V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 2 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT VISCERAL 7 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 9 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK VISCERAL 10 V GALLBLADDER- ABSENT OR SMALL P SMALL VISCERAL 11 V ACCESSORY SPLEEN(S) P ONE, PINPOINT VISCERAL 12 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V 13TH FULL RIB(S) P
LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10,11,12 VISCERAL 1,2,3,4,5,6,8 SKELETAL 3,4,5,6,8,9,10,11

53740 1 2 3 4 5 6 7 8 9 10 A A/ A A A A A A A A SEX: F F M M F F M F F F

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE290of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 56 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53740 (CONTINUED) SKELETAL 1 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 2 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 3 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 5 V ACCESSORY SKULL BONE(S) P ONE, 3 X 2 MM, IN SAGITTAL SUTURE V HYOID ARCH(ES) BENT P MODERATE, LEFT; SLIGHT, RIGHT V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 6 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 7 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 8 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 9 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 10 V HYOID ARCH(ES) BENT 1
LEFT V 13TH FULL RIB(S) P
BILATERAL

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE291of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 57 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53740 (CONTINUED) NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,4,5,6,7,8,9,10 SKELETAL 4

53743 1 2 3 4 5 6 7 8 9 10 A A A/ A A A A A A A SEX: F M M F M M F M F F

VISCERAL 1 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 3 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 4 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT VISCERAL 5 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 6 V HYOID ARCH(ES) BENT P MODERATE, RIGHT; SLIGHT, LEFT V 13TH FULL RIB(S) P
BILATERAL SKELETAL 7 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 VISCERAL 8 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE292of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 58 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53743 (CONTINUED) SKELETAL 8 V 13TH FULL RIB(S) P
LEFT V EXTRA SITE OF OSSIFICATION ANTERIOR TO STERNEBRA #1 P SKELETAL 9 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 10 V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 2,3,4,6,7,9,10 SKELETAL 2

53747 1 2 3 4 5 6 7 8 9 10 A A E A A/ A E A A A SEX: F F - F F F - F F F

SKELETAL 1 V HYOID ARCH(ES) BENT P MODERATE, LEFT; SLIGHT, RIGHT SKELETAL 2 V HYOID ARCH(ES) BENT 1 RIGHT V 13TH FULL RIB(S) P
BILATERAL EXTERNAL 3 EARLY RESORPTION SKELETAL 4 V HYOID ARCH(ES) BENT 1
LEFT SKELETAL 5 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 6 V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH RUDIMENTARY RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE293of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 59 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53747 (CONTINUED)
BILATERAL EXTERNAL 7 EARLY RESORPTION SKELETAL 9 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 10 V HYOID ARCH(ES) BENT P MODERATE, LEFT; SLIGHT, RIGHT V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,4,5,6,8,9,10 VISCERAL 1,2,4,5,6,8,9,10 SKELETAL 8

53749 1 2 3 4 5 6 7 8 9 10 A A E E E/ E E E A A SEX: M M - - - - - - M F

SKELETAL 1 V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 2 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH RUDIMENTARY RIB(S) P RIGHT EXTERNAL 3 EARLY RESORPTION EXTERNAL 4 EARLY RESORPTION EXTERNAL 5 EARLY RESORPTION

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE294of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 60 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53749 (CONTINUED) EXTERNAL 6 EARLY RESORPTION EXTERNAL 7 EARLY RESORPTION EXTERNAL 8 EARLY RESORPTION SKELETAL 9 V HYOID ARCH(ES) BENT 2
BILATERAL VISCERAL 10 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,9,10 VISCERAL 1,9 SKELETAL

53750 1 2 3 4 5 6 7 A A A A A/ A A SEX: M M M F M F F

VISCERAL 1 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER VISCERAL 2 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER V RETROCAVAL URETER P RIGHT SKELETAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE295of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 61 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53750 (CONTINUED) SKELETAL 4 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 5 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 7 V 13TH RUDIMENTARY RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7 VISCERAL 3,4,5,6,7 SKELETAL 1,3,6

53751 1 2 3 4 5 A A A/ A A SEX: M M M F M

SKELETAL 1 V HYOID ARCH(ES) BENT 1
BILATERAL SKELETAL 3 V HYOID ARCH(ES) BENT 1
BILATERAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 4 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 5 V 13TH RUDIMENTARY RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5 VISCERAL 1,2,3,4,5 SKELETAL 2

53754 1 2 3 4 5 6 7 8 9 10 A A A A/ A A A A A A SEX: F F M M M F F M M F

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE296of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 62 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53754 (CONTINUED) SKELETAL 1 V HYOID ARCH(ES) BENT 2
BILATERAL SKELETAL 2 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 3 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 7 V HYOID ARCH(ES) BENT 1
BILATERAL V 7TH CERVICAL RIB(S) P PINPOINT, RIGHT SKELETAL 8 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT SKELETAL 9 V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 10 V HYOID ARCH(ES) BENT 2
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,4,5,6,7,8,9,10 SKELETAL 4,5,6

53755 1 2 3 4 5 6 7 8 9 10 A A A A/ A A A E A A SEX: F M M M F M M - F M

SKELETAL 1 V HYOID ARCH(ES) BENT 3
BILATERAL VISCERAL 2 V ACCESSORY SPLEEN(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE297of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 63 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53755 (CONTINUED) ONE, LESS THAN 1 MM IN DIAMETER SKELETAL V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 7 V 13TH FULL RIB(S) P RIGHT EXTERNAL 8 EARLY RESORPTION SKELETAL 10 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,9,10 VISCERAL 1,3,4,5,6,7,9,10 SKELETAL 3,4,5,6,9

53756 1 2 3 4 5 6 7 8 A A A/ A A A A A SEX: M F M F F F M F

SKELETAL 1 V HYOID ARCH(ES) BENT 3 RIGHT V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT SKELETAL 2 V HYOID ARCH(ES) BENT 3
BILATERAL V 13TH RUDIMENTARY RIB(S) P
LEFT VISCERAL 3 V RETROCAVAL URETER P RIGHT SKELETAL V HYOID ARCH(ES) BENT 2
BILATERAL SKELETAL 4 V HYOID ARCH(ES) BENT 3

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE298of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 64 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53756 (CONTINUED)
BILATERAL SKELETAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 5 V HYOID ARCH(ES) BENT 1
BILATERAL SKELETAL 6 V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 7 V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 8 V HYOID ARCH(ES) BENT 2
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8 VISCERAL 1,2,4,5,6,7,8 SKELETAL

53761 1 2 3 4 5 6 7 8 9 A A/ A A A A A A A SEX: F M F M M M F M M

SKELETAL 1 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT V HYOID ARCH(ES) BENT P MODERATE, RIGHT; SLIGHT, LEFT SKELETAL 2 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 3 V HYOID ARCH(ES) BENT 1
BILATERAL

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE299of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 65 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53761 (CONTINUED) SKELETAL 3 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 6 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT VISCERAL 8 V ACCESSORY SPLEEN(S) P ONE, 1 MM IN DIAMETER SKELETAL V HYOID ARCH(ES) BENT 1
BILATERAL SKELETAL 9 V HYOID ARCH(ES) BENT 1
LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 1,2,3,4,5,6,7,9 SKELETAL 4,5,7

53762 1 2 3 4 5 6 7 8 A A A/ A A A A A SEX: F M F F F F M F

SKELETAL 3 V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 4 V 13TH RUDIMENTARY RIB(S) P
LEFT VISCERAL 5 M LUNGS- LOBULAR AGENESIS P RIGHT ACCESSORY LOBE ABSENT VISCERAL 6 V ACCESSORY SPLEEN(S) P ONE, 1 MM IN DIAMETER M LUNGS- LOBULAR AGENESIS P RIGHT ACCESSORY LOBE ABSENT SKELETAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE300of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 66 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53762 (CONTINUED) #5 SKELETAL V HYOID ARCH(ES) BENT 3 RIGHT SKELETAL 8 V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8 VISCERAL 1,2,3,4,7,8 SKELETAL 1,2,5,7

53764 1 2 3 4 5 6 7 8 9 A A A A A/ A E A A SEX: F F F M M F - F F

VISCERAL 1 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 2 V 13TH FULL RIB(S) P RIGHT VISCERAL 3 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 5 V 13TH FULL RIB(S) P
LEFT EXTERNAL 7 EARLY RESORPTION VISCERAL 8 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, LEFT SKELETAL V 13TH FULL RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE301of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 67 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53764 (CONTINUED) FULL, LEFT; RUDIMENTARY, RIGHT VISCERAL 9 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V HYOID ARCH(ES) BENT 3
LEFT V 13TH FULL RIB(S) P
LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,8,9 VISCERAL 2,4,5,6 SKELETAL 4,6

53765 1 2 3 4 5 6 7 8 9 10 A A A A A/ A A A A A SEX: M F M F M M F M F F

SKELETAL 1 V HYOID ARCH(ES) BENT 2
LEFT SKELETAL 2 V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 3 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 4 V 13TH FULL RIB(S) P RIGHT SKELETAL 5 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 6 V HYOID ARCH(ES) BENT 2
BILATERAL SKELETAL 7 V EXTRA SITE OF OSSIFICATION VENTRAL TO CERVICAL CENTRUM #2 P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE302of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 68 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53765 (CONTINUED) SKELETAL 7 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 8 V 13TH FULL RIB(S) P
LEFT VISCERAL 9 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK VISCERAL 10 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,4,5,6,7,8 SKELETAL 9

53766 1 2 3 4 5 6 7 8 9 10 11 A A A A A/ A A A A A A SEX: M M M F M F F F F F M

VISCERAL 2 V GALLBLADDER- ABSENT OR SMALL P SMALL VISCERAL 3 V GALLBLADDER- ABSENT OR SMALL P SMALL SKELETAL 4 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 6 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE303of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 69 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53766 (CONTINUED) #5 SKELETAL 8 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 9 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 10 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER SKELETAL V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P VISCERAL 11 V GALLBLADDER- ABSENT OR SMALL P SMALL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10,11 VISCERAL 1,4,5,6,7,8,9 SKELETAL 1,2,3,5,7,11

53768 1 2 3 4 5 6 7 8 9 10 A A L A A A A/ A A A SEX: M F - M M M F M M F

SKELETAL 2 V HYOID ARCH(ES) BENT 1 RIGHT EXTERNAL 3 LATE RESORPTION CROWN-RUMP LENGTH: 7.0 CM, SEVERE AUTOLYSIS, NO APPARENT MALFORMATIONS

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE304of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 70 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53768 (CONTINUED) SKELETAL 5 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 6 V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 7 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 9 V HYOID ARCH(ES) BENT 1 RIGHT SKELETAL 10 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,4,5,6,7,8,9,10 VISCERAL 1,2,4,5,6,7,8,9,10 SKELETAL 1,4,8

53769 1 2 3 4 5 6 7 8 9 10 A A A A/ A A A A A A SEX: M M F F F F M M M M

SKELETAL 1 V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 2 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT SKELETAL 3 V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, 1 MM IN DIAMETER SKELETAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 5 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE305of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 71 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53769 (CONTINUED) #6 SKELETAL V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY V 13TH RUDIMENTARY RIB(S) P
LEFT V PUBIS UNOSSIFIED P BILATERAL SKELETAL 6 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 7 V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY SKELETAL 8 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 AND #6 V 13TH RUDIMENTARY RIB(S) P RIGHT V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY VISCERAL 9 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER SKELETAL 10 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,5,6,7,8,10 SKELETAL 9

53774 1 2 3 4 5 6 7 8 9 10 A A A/ A A A A A A A SEX: M F M M M M F M M M

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE306of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 72 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53774 (CONTINUED) SKELETAL 4 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 7 V HYOID ARCH(ES) BENT 1 RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,4,5,6,7,8,9,10 SKELETAL 1,2,3,5,6,8,9,10

53775 1 2 3 4 5 6 7 8 A A A A A/ A A A SEX: F M M F F F M F

SKELETAL 1 V 13TH RUDIMENTARY RIB(S) P
LEFT VISCERAL 2 V ACCESSORY SPLEEN(S) P ONE, PINPOINT VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT V 27 PRESACRAL VERTEBRAE P V STERNEBRAE WITH THREAD-LIKE ATTACHMENT P #4 ATTACHED TO #5 SKELETAL 5 V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 6 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL 7 V 13TH RUDIMENTARY RIB(S) P RIGHT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE307of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 73 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 4000 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53775 (CONTINUED) SKELETAL 8 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT V 27 PRESACRAL VERTEBRAE P NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8 VISCERAL 1,3,5,7,8 SKELETAL 2,3,6

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE308of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 74 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

-----------------------------------------------------------------------------------------------------------------------------------

54116 1 2 3 4 5 6 7 8 9 A A E A A A/ A A A SEX: F M - F F M F M F

SKELETAL 1 V 13TH FULL RIB(S) P
BILATERAL V HYOID ARCH(ES) BENT 2
BILATERAL EXTERNAL 3 EARLY RESORPTION VISCERAL 5 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER SKELETAL V 13TH RUDIMENTARY RIB(S) P RIGHT VISCERAL 7 V PANCREAS- SMALL P SKELETAL 9 V 13TH FULL RIB(S) P
BILATERAL V HYOID ARCH(ES) BENT 2
BILATERAL V 7TH CERVICAL RIB(S) P INTERMEDIATE, RIGHT; PINPOINT, LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,4,5,6,7,8,9 VISCERAL 1,2,4,6,8,9 SKELETAL 2,4,6,7,8

54121 1 2 3 4 5 6 7 8 9 10 11 12 A E A E E A A/ A A E A E SEX: M - M - - M F M M - M -

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE309of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 75 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54121 (CONTINUED) EXTERNAL 2 EARLY RESORPTION VISCERAL 3 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P
BILATERAL EXTERNAL 4 EARLY RESORPTION EXTERNAL 5 EARLY RESORPTION SKELETAL 6 V 13TH RUDIMENTARY RIB(S) P
LEFT V HYOID ARCH(ES) BENT 1
BILATERAL SKELETAL 7 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 8 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 9 V 13TH RUDIMENTARY RIB(S) P RIGHT EXTERNAL 10 EARLY RESORPTION SKELETAL 11 V HYOID ARCH(ES) BENT 1
BILATERAL EXTERNAL 12 EARLY RESORPTION NO REMARKABLE OBSERVATIONS EXTERNAL 1,3,6,7,8,9,11 VISCERAL 1,6,7,8,9,11 SKELETAL 1

54126 1 2 3 4 5 6 7 8 9 10 11 A A A A A/ A A A A A A SEX: F M M M F M M M M M F

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE310of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 76 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54126 (CONTINUED) SKELETAL 1 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH FULL RIB(S) P
LEFT VISCERAL 3 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL 4 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 6 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 7 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 8 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 VISCERAL 9 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 10 V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 11 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V EXTRA SITE OF OSSIFICATION ANTERIOR TO STERNEBRA #1 P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE311of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 77 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54126 (CONTINUED) NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10,11 VISCERAL 1,2,4,5,6,7,8,10,11 SKELETAL 2,3,5

54127 1 2 3 4 5 6 7 8 A E A E A/ A E A SEX: M - M - M M - F

SKELETAL 1 V HYOID ARCH(ES) BENT 2
LEFT V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P RIGHT EXTERNAL 2 EARLY RESORPTION SKELETAL 3 V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P
BILATERAL EXTERNAL 4 EARLY RESORPTION VISCERAL 5 M INTERRUPTED AORTIC ARCH P RIGHT CAROTID AND RIGHT SUBCLAVIAN ARISE INDEPENDENTLY FROM THE ASCENDING AORTA (NO BRACHIOCEPHALIC TRUNK); LEFT CAROTID AND LEFT SUBCLAVIAN ARISE FROM THE ASCENDING AORTA SKELETAL V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P
BILATERAL SKELETAL 6 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 V 13TH RUDIMENTARY RIB(S) P
LEFT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE312of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 78 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54127 (CONTINUED) EXTERNAL 7 EARLY RESORPTION SKELETAL 8 V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P
BILATERAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 NO REMARKABLE OBSERVATIONS EXTERNAL 1,3,5,6,8 VISCERAL 1,3,6,8 SKELETAL

54130 1 2 3 4 5 6 7 8 9 10 11 A A A A A A A A/ A A A SEX: M F F M F M M M M F M

SKELETAL 1 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 2 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 SKELETAL 3 V REDUCED OSSIFICATION OF THE SKULL P ONE AREA, 1 MM IN DIAMETER, FRONTAL, BILATERAL; TWO AREAS, 2 X 1 MM, PARIETAL, BILATERAL V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 AND #6 SKELETAL 4 V REDUCED OSSIFICATION OF THE SKULL P ONE AREA, 1 MM IN DIAMETER, FRONTAL, BILATERAL; TWO AREAS,

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE313of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 79 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54130 (CONTINUED) 2 X 1 MM, PARIETAL, LEFT; ONE AREA, 1 MM IN DIAMETER, PARIETAL, LEFT; ONE AREA, 3 X 1 MM, PARIETAL, RIGHT SKELETAL V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 SKELETAL 5 V REDUCED OSSIFICATION OF THE SKULL P ONE AREA, 1 MM IN DIAMETER, FRONTAL, BILATERAL; ONE AREA, 2 X 1 MM, PARIETAL, BILATERAL V PUBIS UNOSSIFIED P BILATERAL V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 AND #6 VISCERAL 6 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 AND #6 SKELETAL 7 V REDUCED OSSIFICATION OF THE SKULL P TWO AREAS, 1 MM IN DIAMETER, PARIETAL, LEFT; ONE AREA, 1 MM IN DIAMETER, PARIETAL, RIGHT V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY V 13TH RUDIMENTARY RIB(S) P
LEFT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE314of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 80 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54130 (CONTINUED) SKELETAL 7 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 AND #6 SKELETAL 8 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 SKELETAL 9 V REDUCED OSSIFICATION OF THE SKULL P ONE AREA, 3 X 1 MM, PARIETAL, LEFT; ONE AREA, 2 X 1 MM, PARIETAL, RIGHT SKELETAL 10 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 AND #6 NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10,11 VISCERAL 1,2,3,4,5,7,8,9,10,11 SKELETAL 11

54133 1 2 3 4 5 6 A/ A A A A A SEX: M M M M M M

SKELETAL 1 V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 2 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 3 V 13TH FULL RIB(S) P
BILATERAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 SKELETAL 4 V HYOID ARCH(ES) BENT 2 RIGHT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE315of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 81 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54133 (CONTINUED) SKELETAL 4 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 5 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 6 V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6 VISCERAL 1,2,3,4,5,6 SKELETAL

54134 1 2 3 4 5 6 7 8 A A/ A A A A A A SEX: F F M M F F F F

VISCERAL 1 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER SKELETAL V 13TH RUDIMENTARY RIB(S) P RIGHT VISCERAL 2 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER SKELETAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 3 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 4 V 13TH RUDIMENTARY RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE316of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 82 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54134 (CONTINUED) RIGHT SKELETAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 SKELETAL 5 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 6 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P VISCERAL 7 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER SKELETAL V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 8 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT V 27 PRESACRAL VERTEBRAE P NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8 VISCERAL 3,4,5,6,8 SKELETAL

54136 1 2 3 4 5 6 7 8 9 10 11 A A A A L A A/ A A A A SEX: M F M F - F F M M F F

VISCERAL 1 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL 2 V HYOID ARCH(ES) BENT 1
LEFT SKELETAL 4 V 13TH RUDIMENTARY RIB(S) P
LEFT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE317of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 83 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54136 (CONTINUED) EXTERNAL 5 LATE RESORPTION CROWN-RUMP LENGTH: 9.5 CM, SEVERE AUTOLYSIS, NO APPARENT MALFORMATIONS SKELETAL 6 V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 7 V 13TH FULL RIB(S) P
BILATERAL V HYOID ARCH(ES) BENT 2
BILATERAL VISCERAL 8 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL 9 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT VISCERAL 11 V ACCESSORY SPLEEN(S) P TWO, PINPOINT SKELETAL V HYOID ARCH(ES) BENT 1 RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,6,7,8,9,10,11 VISCERAL 2,3,4,6,7,9,10 SKELETAL 1,3,8,10

54145 1 2 3 4 5 6 7 A A A A/ A A A SEX: M F M M M F F

VISCERAL 1 ABDOMINAL CAVITY- CONTENTS, RED FLUID P APPROXIMATELY 1.0 ML M INTERVENTRICULAR SEPTAL DEFECT P ENTIRE SEPTUM ABSENT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE318of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 84 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54145 (CONTINUED) VISCERAL 1 M STENOTIC PULMONARY TRUNK P THORACIC CAVITY- FLUID FILLED P APPROXIMATELY 3.5 ML V LUNGS- SMALL P ALL LOBES M BULBOUS AORTA P ASCENDING AND AORTIC ARCH V ACCESSORY SPLEEN(S) P THREE, LESS THAN 1 MM IN DIAMETER SKELETAL 2 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V HYOID ARCH(ES) BENT 3
LEFT V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 4 V HYOID ARCH(ES) BENT 1
LEFT VISCERAL 6 V RETROCAVAL URETER P RIGHT SKELETAL V HYOID ARCH(ES) BENT 2
LEFT SKELETAL 7 V HYOID ARCH(ES) BENT 3
BILATERAL V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7 VISCERAL 2,3,4,5,7 SKELETAL 1,3,5

54149 1 2 3 4 5 6 7 8 9 10 A A A/ A A A A A A A SEX: F F F M F F M M M M

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE319of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 85 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54149 (CONTINUED) SKELETAL 1 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 2 V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 3 V 13TH RUDIMENTARY RIB(S) P RIGHT VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 5 V 13TH RUDIMENTARY RIB(S) P RIGHT VISCERAL 6 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY VISCERAL 7 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V GALLBLADDER- ABSENT OR SMALL P SMALL SKELETAL V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 8 V 13TH FULL RIB(S) P
BILATERAL

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE320of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 86 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54149 (CONTINUED) VISCERAL 9 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 10 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH RUDIMENTARY RIB(S) P RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,5,8 SKELETAL

54155 1 2 3 4 5 6 7 A A A A A A/ A SEX: F F F F F M M

SKELETAL 1 V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 3 V 13TH RUDIMENTARY RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 6 V 13TH RUDIMENTARY RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7 VISCERAL 1,2,3,4,5,6,7 SKELETAL 2,4,5,7

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE321of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 87 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

-----------------------------------------------------------------------------------------------------------------------------------

54158 1 2 3 4 5 6 7 8 E A A A A/ A A A SEX: - F F F F F F F

EXTERNAL 1 EARLY RESORPTION SKELETAL 2 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 V 13TH FULL RIB(S) P
BILATERAL V HYOID ARCH(ES) BENT 2
BILATERAL SKELETAL 3 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 4 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 5 V ACCESSORY SPLEEN(S) P FEW, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL V HYOID ARCH(ES) BENT 1
BILATERAL VISCERAL 6 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK V ACCESSORY SPLEEN(S) P FEW, PINPOINT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE322of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 88 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54158 (CONTINUED) SKELETAL 6 V 13TH RUDIMENTARY RIB(S) P RIGHT VISCERAL 7 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 VISCERAL 8 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK NO REMARKABLE OBSERVATIONS EXTERNAL 2,3,4,5,6,7,8 VISCERAL 2,3 SKELETAL 8

54161 1 2 3 4 5 6 7 8 9 A A A/ E A A A A A SEX: F M M - M M F M F

SKELETAL 1 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 VISCERAL 2 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER EXTERNAL 4 EARLY RESORPTION VISCERAL 5 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER VISCERAL 7 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE323of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 89 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54161 (CONTINUED) SKELETAL 9 V HYOID ARCH(ES) BENT 2
LEFT V 13TH RUDIMENTARY RIB(S) P RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,5,6,7,8,9 VISCERAL 1,3,6,8,9 SKELETAL 2,3,5,6,7,8

54162 1 2 3 4 5 6 7 8 9 10 11 A A A A A A/ A A A A A SEX: F M F F M M M M F M M

SKELETAL 1 V HYOID ARCH(ES) BENT 1
LEFT V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 2 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 3 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 4 V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 5 V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE324of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 90 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54162 (CONTINUED) BODY SKELETAL V HYOID ARCH(ES) BENT 2
LEFT SKELETAL 6 V HYOID ARCH(ES) BENT 1 RIGHT V 13TH RUDIMENTARY RIB(S) P
LEFT V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 SKELETAL 7 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 8 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 10 V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10,11 VISCERAL 1,2,3,4,5,6,7,8,9,10,11 SKELETAL 9,11

54163 1 2 3 4 5 6 7 A A A/ A A A A SEX: F F F F F M F

VISCERAL 1 V ACCESSORY SPLEEN(S) P TWO, PINPOINT SKELETAL V HYOID ARCH(ES) BENT 1 RIGHT V 13TH FULL RIB(S) P
BILATERAL

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE325of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 91 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54163 (CONTINUED) SKELETAL 1 V 27 PRESACRAL VERTEBRAE P VISCERAL 2 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT VISCERAL 3 V GALLBLADDER- ABSENT OR SMALL P ABSENT SKELETAL V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P VISCERAL 5 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P VISCERAL 6 V GALLBLADDER- ABSENT OR SMALL P SMALL V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7 VISCERAL 4,7 SKELETAL 2,4,7

54164 1 2 3 4 5 6 7 8 A A/ A A A A A A SEX: F F M F M M F F

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE326of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 92 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54164 (CONTINUED) VISCERAL 1 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V 13TH FULL RIB(S) P
BILATERAL M RIB ANOMALY P LEFT RIB #5 FORKED, MEDIAL; LEFT RIBS #4 AND #5 FUSED, MEDIAL; LEFT COSTAL CARTILAGE ARISING FROM ANTERIOR PORTION OF FORKED RIB #5 ASSOCIATES WITH STERNUM IN NORMAL #5 POSITION; LEFT COSTAL CARTILAGE ARISING FROM POSTERIOR PORTION OF FORKED RIB #5 ASSOCIATES WITH STERNUM IN NORMAL #6 POSITION; ALL SUBSEQUENT LEFT COSTAL CARTILAGES ASSOCIATE WITH STERNUM ONE NUMBER POSITION HIGHER THAN NORMAL VISCERAL 2 V GALLBLADDER- ABSENT OR SMALL P SMALL OVIDUCTS- CYST(S) P ONE, 1 MM IN DIAMETER, RIGHT SKELETAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 3 V ACCESSORY SPLEEN(S) P ONE, 1 MM IN DIAMETER SKELETAL V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 4 OVIDUCTS- CYST(S) P FEW, PINPOINT, LEFT V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE327of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 93 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54164 (CONTINUED) VISCERAL 5 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 6 M LUNGS- LOBULAR AGENESIS P RIGHT ACCESSORY LOBE ABSENT V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT SKELETAL V HYOID ARCH(ES) BENT 1 RIGHT V 13TH FULL RIB(S) P
BILATERAL VISCERAL 7 M LUNGS- LOBULAR AGENESIS P RIGHT ACCESSORY LOBE ABSENT SKELETAL V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 8 V HYOID ARCH(ES) BENT 1
LEFT V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8 VISCERAL 8 SKELETAL

54168 1 2 3 4 5 6 7 8 9 10 11 12 13 14 A A A A A A A A/ A A A A A E SEX: F F M F F F F M F M M M M -

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE328of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 94 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54168 (CONTINUED) SKELETAL 1 V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 2 V RETROCAVAL URETER P RIGHT SKELETAL M VERTEBRAL ANOMALY WITH OR WITHOUT ASSOCIATED RIB ANOMALY P EXTRA RIB, ARCH AND HALF OF THORACIC CENTRUM LOCATED BETWEEN LEFT THORACIC ARCHES #9 AND #10; LEFT THORACIC ARCH AND LEFT HALF OF THORACIC CENTRUM #9 LOCATED MORE ANTERIOR THAN NORMAL; LEFT THORACIC ARCH AND LEFT HALF OF THORACIC CENTRUM #10 LOCATED MORE POSTERIOR THAN NORMAL; RIGHT RIBS #8 AND #9 FUSED, PROXIMAL THROUGH MEDIAL VISCERAL 3 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
LEFT SKELETAL 4 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 5 ABDOMINAL CAVITY- CONTENTS, RED FLUID P APPROXIMATELY 1.0 ML V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 6 M VERTEBRAL ANOMALY WITH OR WITHOUT ASSOCIATED RIB ANOMALY P LEFT HALF OF LUMBAR CENTRUM #2 ABSENT; LEFT LUMBAR ARCH #1 SMALLER THAN NORMAL; LEFT LUMBAR ARCH AND LEFT HALF LUMBAR CENTRUM #1 LOCATED MORE ANTERIOR THAN NORMAL; LEFT LUMBAR ARCH AND LEFT HALF OF LUMBAR CENTRUM #3 LOCATED MORE

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE329of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 95 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54168 (CONTINUED) ANTERIOR THAN NORMAL SKELETAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 7 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 8 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT VISCERAL 9 V MAJOR BLOOD VESSEL VARIATION P RIGHT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P
BILATERAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 10 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT VISCERAL 11 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK V ACCESSORY SPLEEN(S) P ONE, 1 MM IN DIAMETER SKELETAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 12 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 13 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT EXTERNAL 14 EARLY RESORPTION

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE330of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 96 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54168 (CONTINUED) NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10,11,12,13 VISCERAL 1,4,6,7,8,10,12,13 SKELETAL

54170 1 2 3 4 5 6 7 8 9 A A A A A/ A A A A SEX: M F M M F M F F F

VISCERAL 1 M DIAPHRAGMATIC HERNIA P PORTION OF LEFT LOBE OF LIVER PROTRUDES INTO THORACIC CAVITY THROUGH AN OPENING IN THE DIAPHRAGM SKELETAL 2 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 VISCERAL 5 V ACCESSORY SPLEEN(S) P TWO, PINPOINT SKELETAL V HYOID ARCH(ES) BENT 1
LEFT V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 7 V 13TH FULL RIB(S) P
BILATERAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE331of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 97 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 5500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54170 (CONTINUED) NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 2,3,4,6,7,8,9 SKELETAL 1,3,4,6,8,9

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE332of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 98 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

-----------------------------------------------------------------------------------------------------------------------------------

53722 1 2 3 4 5 6 7 8 9 10 11 12 A A A A/ A A A A A A A A SEX: M F M M M M F F M M M M

SKELETAL 1 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 2 V HYOID ARCH(ES) BENT 1
LEFT V 13TH RUDIMENTARY RIB(S) P
BILATERAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 3 V HYOID ARCH(ES) BENT 1
BILATERAL SKELETAL 4 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 5 V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 6 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 7 V 13TH RUDIMENTARY RIB(S) P RIGHT V 27 PRESACRAL VERTEBRAE P SKELETAL 8 V 13TH FULL RIB(S) P RIGHT V 27 PRESACRAL VERTEBRAE P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE333of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 99 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53722 (CONTINUED) VISCERAL 9 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 10 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P VISCERAL 11 V ACCESSORY SPLEEN(S) P ONE, 1 MM IN DIAMETER SKELETAL V STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) 1 #4; #3 WITH THREAD-LIKE ATTACHMENT TO LEFT HALF OF #4; RIGHT HALF OF #4 ATTACHED TO #5 SKELETAL 12 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10,11,12 VISCERAL 1,2,3,4,5,6,7,8,10,12 SKELETAL

53725 1 2 3 4 5 6 7 8 9 A A A A/ A A A A A SEX: F F F M M F F M M

SKELETAL 1 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 2 V ACCESSORY SPLEEN(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE334of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 100 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53725 (CONTINUED) TWO, IRREGULARLY SHAPED SKELETAL V EXTRA SITE OF OSSIFICATION VENTRAL TO CERVICAL CENTRUM #2 P V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 3 V 13TH FULL RIB(S) P
BILATERAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, 1 MM IN DIAMETER SKELETAL V 13TH RUDIMENTARY RIB(S) P
LEFT M COSTAL CARTILAGE ANOMALY P RIGHT COSTAL CARTILAGES #1 AND #2 FUSED, PROXIMAL AND BIFURCATES PRIOR TO JOINING STERNUM IN NORMAL #1 AND #2 POSITIONS, RESPECTIVELY M VERTEBRAL ANOMALY WITH OR WITHOUT ASSOCIATED RIB ANOMALY P EXTRA ARCH AND RIB LOCATED BETWEEN LEFT THORACIC ARCHES #6 AND #7; EXTRA RIB FUSED TO LEFT RIB #7, PROXIMAL; RIGHT RIB #8 FORKED, PROXIMAL; COSTAL CARTILAGE ARISING FROM EXTRA RIB ASSOCIATES WITH STERNUM IN NORMAL #7 POSITION VISCERAL 5 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 VISCERAL 6 V ACCESSORY SPLEEN(S) P TWO, PINPOINT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE335of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 101 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53725 (CONTINUED) SKELETAL 6 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P VISCERAL 7 V ACCESSORY SPLEEN(S) P TWO, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P VISCERAL 8 V ACCESSORY SPLEEN(S) P TWO, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL V STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) P #5, MODERATE; #2 THROUGH #4, SLIGHT; RIGHT HALF OF #2 ATTACHED TO LEFT HALF OF #3; RIGHT HALF OF #3 ATTACHED TO LEFT HALF OF #4; RIGHT HALF OF #4 ATTACHED TO LEFT HALF OF #5 SKELETAL 9 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 1,3,9 SKELETAL

53727 1 2 3 4 5 6 7 8 9 10 11 12 A A A A A/ A A A A A A A SEX: M M F F M M F F F M F M

VISCERAL 2 V RETROCAVAL URETER P RIGHT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE336of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 102 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53727 (CONTINUED) SKELETAL 2 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 4 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 6 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V HYOID ARCH(ES) BENT 1
LEFT SKELETAL 8 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 9 V 13TH RUDIMENTARY RIB(S) P
LEFT VISCERAL 10 V RETROCAVAL URETER P RIGHT VISCERAL 12 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10,11,12 VISCERAL 1,3,4,5,7,8,9,11 SKELETAL 1,3,5,7,10,11,12

53730 1 2 3 4 5 6 7 8 9 10 A/ A L L A A L A A A SEX: M M - - F F - M F M

SKELETAL 1 V 13TH RUDIMENTARY RIB(S) P RIGHT V STERNEBRAE WITH THREAD-LIKE ATTACHMENT P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE337of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 103 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53730 (CONTINUED) #3 ATTACHED TO #4; #4 ATTACHED TO #5 EXTERNAL 3 LATE RESORPTION CROWN-RUMP LENGTH: 8.4 CM, SEVERE AUTOLYSIS, NO APPARENT MALFORMATIONS EXTERNAL 4 LATE RESORPTION CROWN-RUMP LENGTH: 6.9 CM, MUMMIFIED SKELETAL 5 V ACCESSORY SKULL BONE(S) P ONE, 3 X 1 MM, IN SAGITTAL SUTURE SKELETAL 6 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P EXTERNAL 7 LATE RESORPTION CROWN-RUMP LENGTH: 8.2 CM, SEVERE AUTOLYSIS, NO APPARENT MALFORMATIONS SKELETAL 8 V ACCESSORY SKULL BONE(S) P ONE, 3 X 2 MM, IN SAGITTAL SUTURE SKELETAL 9 V 13TH RUDIMENTARY RIB(S) P RIGHT VISCERAL 10 V RETROCAVAL URETER P RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,5,6,8,9,10 VISCERAL 1,2,5,6,8,9 SKELETAL 2,10

53771 1 2 3 4 5 6 7 8 9 10 11 12 A A A A A A E/ A A A A A SEX: F M M F F M - M M M F M

EXTERNAL 1 M CARPAL AND/OR TARSAL FLEXURE

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE338of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 104 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53771 (CONTINUED) CARPAL, BILATERAL EXTERNAL M PAW HYPERFLEXION HINDPAW, BILATERAL VISCERAL CONFIRMATION OF CARPAL FLEXURE P CONFIRMATION OF HYPERFLEXION P SKELETAL CARPAL FLEXURE- NO APPARENT SKELETAL ORIGIN P PAW HYPERFLEXION- NO APPARENT SKELETAL ORIGIN P V 13TH FULL RIB(S) P
BILATERAL V HYOID ARCH(ES) BENT 1
LEFT SKELETAL 2 V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT VISCERAL 3 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL 5 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT VISCERAL 6 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P
BILATERAL EXTERNAL 7 EARLY RESORPTION SKELETAL 8 V 13TH RUDIMENTARY RIB(S) P
LEFT VISCERAL 9 V ACCESSORY SPLEEN(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE339of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 105 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53771 (CONTINUED) TWO, 1 MM IN DIAMETER SKELETAL V 13TH RUDIMENTARY RIB(S) P
LEFT VISCERAL 10 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P RIGHT SKELETAL 11 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 2,3,4,5,6,8,9,10,11,12 VISCERAL 2,4,5,8,11,12 SKELETAL 3,4,12

53772 1 2 3 4 5 6 7 8 9 10 11 A A A A E/ A A A E A A SEX: M M M F - M M F - F F

SKELETAL 2 V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 3 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 4 V 13TH RUDIMENTARY RIB(S) P
BILATERAL EXTERNAL 5 EARLY RESORPTION SKELETAL 7 V 13TH FULL RIB(S) P
BILATERAL

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE340of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 106 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53772 (CONTINUED) SKELETAL 7 V 27 PRESACRAL VERTEBRAE P VISCERAL 8 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P EXTERNAL 9 EARLY RESORPTION SKELETAL 10 V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 11 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V 13TH RUDIMENTARY RIB(S) P RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,6,7,8,10,11 VISCERAL 1,2,3,4,6,7,10,11 SKELETAL 1,6

53773 1 2 3 4 5 6 7 8 9 10 A A A A/ A A A A A A SEX: F F F M F F M F M F

VISCERAL 1 V RETROCAVAL URETER P RIGHT SKELETAL V HYOID ARCH(ES) BENT P SEVERE, RIGHT; MODERATE, LEFT V 13TH FULL RIB(S) P
BILATERAL V 27 PRESACRAL VERTEBRAE P SKELETAL 2 V HYOID ARCH(ES) BENT 1

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE341of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 107 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53773 (CONTINUED)
BILATERAL SKELETAL V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT SKELETAL 3 V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 4 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT SKELETAL 5 V HYOID ARCH(ES) BENT 3
BILATERAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 6 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER V RETROCAVAL URETER P RIGHT SKELETAL V 13TH FULL RIB(S) P
BILATERAL VISCERAL 7 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER SKELETAL V 13TH RUDIMENTARY RIB(S) P RIGHT SKELETAL 9 V HYOID ARCH(ES) BENT P MODERATE, RIGHT; SLIGHT, LEFT VISCERAL 10 V ACCESSORY SPLEEN(S) P ONE, LESS THAN 1 MM IN DIAMETER SKELETAL V HYOID ARCH(ES) BENT 3
BILATERAL V 13TH FULL RIB(S) P
BILATERAL

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE342of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 108 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53773 (CONTINUED) NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 2,3,4,5,8,9 SKELETAL 8

53776 1 2 3 4 5 6 7 8 9 10 A A/ A A A A A A A A SEX: F M M M F M F F F F

SKELETAL 1 V HYOID ARCH(ES) BENT 3
BILATERAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 2 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT SKELETAL 3 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #6 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 5 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 AND #6 V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH RUDIMENTARY RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT SKELETAL 6 V 13TH FULL RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE343of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 109 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53776 (CONTINUED)
BILATERAL SKELETAL 7 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 AND #6 V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY V HYOID ARCH(ES) BENT 3
LEFT SKELETAL 8 V HYOID ARCH(ES) BENT 1
BILATERAL SKELETAL 9 V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 10 V HYOID ARCH(ES) BENT 2
BILATERAL V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,2,3,4,5,6,7,8,9,10 SKELETAL 4

53777 1 2 3 4 5 6 7 8 A A A A A/ A A A SEX: M F F M M M F M

SKELETAL 1 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 2 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE344of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 110 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 53777 (CONTINUED) SKELETAL 2 V EXTRA SITE OF OSSIFICATION VENTRAL TO CERVICAL CENTRUM #2 P V 7TH STERNEBRA P LOCATED BETWEEN #5 AND #6 V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P
BILATERAL SKELETAL 3 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 4 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH FULL RIB(S) P
BILATERAL V STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) 1 #5 V 27 PRESACRAL VERTEBRAE P SKELETAL 5 V 13TH FULL RIB(S) P FULL, RIGHT; RUDIMENTARY, LEFT SKELETAL 6 V 27 PRESACRAL VERTEBRAE P V 13TH FULL RIB(S) P
BILATERAL SKELETAL 7 V 13TH FULL RIB(S) P
BILATERAL SKELETAL 8 V HYOID ARCH(ES) BENT 1 RIGHT V 13TH FULL RIB(S) P
BILATERAL NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8 VISCERAL 1,3,5,6,7,8 SKELETAL

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE345of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 111 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

-----------------------------------------------------------------------------------------------------------------------------------

54108 1 2 3 4 5 6 7 8 9 10 A A A A E/ A A A A A SEX: M F F M - F M F F F

VISCERAL 2 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK V HEART- ONLY TWO PAPILLARY MUSCLES PRESENT P VENTRICLE, RIGHT SKELETAL V EXTRA SITE OF OSSIFICATION ANTERIOR TO STERNEBRA #1 P SKELETAL 3 V HYOID ARCH(ES) BENT 1
LEFT V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT SKELETAL 4 V HYOID ARCH(ES) BENT 2
LEFT EXTERNAL 5 EARLY RESORPTION VISCERAL 6 V ACCESSORY SPLEEN(S) P FEW, PINPOINT SKELETAL V HYOID ARCH(ES) BENT 1
BILATERAL SKELETAL 7 V HYOID ARCH(ES) BENT 3
BILATERAL VISCERAL 8 M INTERVENTRICULAR SEPTAL DEFECT P ENTIRE SEPTUM ABSENT V LUNGS- SMALL P ALL LOBES V ACCESSORY SPLEEN(S) P FEW, PINPOINT M TRICUSPID VALVE ABSENT P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE346of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 112 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54108 (CONTINUED) RIGHT VISCERAL M STENOTIC PULMONARY TRUNK P M BULBOUS AORTA P ASCENDING AND AORTIC ARCH THORACIC CAVITY- FLUID FILLED P ABDOMINAL CAVITY- FLUID FILLED P SKELETAL V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH FULL RIB(S) P
LEFT VISCERAL 10 M INTERVENTRICULAR SEPTAL DEFECT P ENTIRE SEPTUM ABSENT M STENOTIC PULMONARY TRUNK P M BULBOUS AORTA P ASCENDING AND AORTIC ARCH SKELETAL V HYOID ARCH(ES) BENT 3
BILATERAL V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,6,7,8,9,10 VISCERAL 1,3,4,7,9 SKELETAL 1,9

54112 1 2 3 4 5 6 / A A A A A A SEX: M M F F M F

SKELETAL 3 V HYOID ARCH(ES) BENT 3 RIGHT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE347of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 113 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54112 (CONTINUED) SKELETAL 3 V 13TH RUDIMENTARY RIB(S) P
BILATERAL VISCERAL 4 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P
BILATERAL SKELETAL 5 V 13TH RUDIMENTARY RIB(S) P
LEFT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6 VISCERAL 1,2,3,5,6 SKELETAL 1,2,6

54135 1 2 3 4 5 6 7 8 9 A A A A A/ A A A A SEX: F F M M F M F M M

SKELETAL 2 V HYOID ARCH(ES) BENT 1
BILATERAL V 13TH RUDIMENTARY RIB(S) P
BILATERAL SKELETAL 3 V 13TH FULL RIB(S) P
BILATERAL VISCERAL 5 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT VISCERAL 6 V ACCESSORY SPLEEN(S) P TWO, PINPOINT VISCERAL 7 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH RUDIMENTARY RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE348of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 114 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54135 (CONTINUED)
LEFT VISCERAL 8 M STENOTIC PULMONARY TRUNK P M BULBOUS AORTA P AORTIC ARCH M INTERVENTRICULAR SEPTAL DEFECT P ENTIRE SEPTUM ABSENT M TRICUSPID VALVE ABSENT P RIGHT VISCERAL 9 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9 VISCERAL 1,2,3,4 SKELETAL 1,4,5,6,8,9

54140 1 2 3 4 5 6 7 8 9 10 11 A A A A A L/ A A A A A SEX: F M F M F - F M M F M

VISCERAL 1 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK SKELETAL V 13TH RUDIMENTARY RIB(S) P
LEFT SKELETAL 2 V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY VISCERAL 3 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL V 13TH FULL RIB(S) P

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE349of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 115 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54140 (CONTINUED)
LEFT SKELETAL V HYOID ARCH(ES) BENT 2
BILATERAL SKELETAL 4 V REDUCED OSSIFICATION OF THE SKULL P ONE AREA, 2 MM IN DIAMETER, FRONTAL, RIGHT SKELETAL 5 V 13TH RUDIMENTARY RIB(S) P
BILATERAL V HYOID ARCH(ES) BENT 2
BILATERAL V HYOID BODY AND/OR ARCH(ES) UNOSSIFIED P BODY EXTERNAL 6 LATE RESORPTION CROWN-RUMP LENGTH: 8.5 CM, SLIGHT AUTOLYSIS, NO APPARENT MALFORMATIONS SKELETAL 7 V 13TH FULL RIB(S) P FULL, LEFT; RUDIMENTARY, RIGHT VISCERAL 8 V MAJOR BLOOD VESSEL VARIATION P LEFT CAROTID ARISES FROM THE BRACHIOCEPHALIC TRUNK VISCERAL 9 V ACCESSORY SPLEEN(S) P ONE, PINPOINT SKELETAL 10 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 V HYOID ARCH(ES) BENT 2
BILATERAL VISCERAL 11 V ACCESSORY SPLEEN(S) P ONE, PINPOINT V RETROCAVAL URETER P RIGHT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE350of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 116 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54140 (CONTINUED) NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,7,8,9,10,11 VISCERAL 2,4,5,7,10 SKELETAL 8,9,11

54150 1 2 3 4 5 6 7 8 9 10 A A A A/ A A A A A A SEX: M F F F F F F M F F

SKELETAL 1 V HYOID ARCH(ES) BENT 1 RIGHT VISCERAL 2 V RENAL PAPILLA(E) NOT DEVELOPED AND/OR DISTENDED URETER(S) P KIDNEY, RIGHT (WOO AND HOAR GRADE 0) SKELETAL V EXTRA SITE OF OSSIFICATION ANTERIOR TO STERNEBRA #1 P V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 VISCERAL 3 V RENAL PAPILLA(E) NOT DEVELOPED AND/OR DISTENDED URETER(S) P KIDNEY, RIGHT (WOO AND HOAR GRADE 0) SKELETAL V HYOID ARCH(ES) BENT 1 RIGHT V STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) 1 #4 SKELETAL 4 V STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) 1 #4 SKELETAL 5 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 SKELETAL 6 V STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) 1 #4 AND #5; RIGHT HALF OF #4 ATTACHED TO LEFT HALF OF #5 VISCERAL 7 V HEART- EXTRA PAPILLARY MUSCLE P VENTRICLE, RIGHT

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE351of475TABLE A15 (COMBINED PHASES) PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 117 SPONSOR:HONEYWELL INDIVIDUAL FETAL EXTERNAL, VISCERAL AND SKELETAL FINDINGS

----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 5: 7500 PPM FETUS # GRADE

----------------------------------------------------------------------------------------------------------------------------------- 54150 (CONTINUED) SKELETAL 7 V ACCESSORY SKULL BONE(S) P ONE, 3 X 1 MM, IN SAGITTAL SUTURE V STERNEBRA(E) MALALIGNED(SLIGHT OR MODERATE) 1 #4 AND #5 SKELETAL 9 V STERNEBRA(E) #5 AND/OR #6 UNOSSIFIED P #5 NO REMARKABLE OBSERVATIONS EXTERNAL 1,2,3,4,5,6,7,8,9,10 VISCERAL 1,4,5,6,8,9,10 SKELETAL 8,10

A = VIABLE FETUS, E = EARLY RESORPTION, L = LATE RESORPTION, D = DEAD FETUS, "/" DENOTES CERVIX POSITION OBSERVATION CODE: M = MALFORMATION, V = VARIATION GRADE CODE: 1 = SLIGHT, 2 = MODERATE, 3 = MARKED, P = PRESENT SEX CODE: M = MALE, F = FEMALE, - = NOT APPLICABLE PFETv4.14 07/02/2008352of475

## FINAL REPORT

Volume 2 of 2 (Appendices B-G)

STUDY TITLE

AN INHALATION PRENATAL DEVELOPMENTAL TOXICITY STUDY OF HFO-1234yf (2,3,3,3-TETRAFLUOROPROPENE) IN RABBITS

STUDY NUMBER

WIL-447022

DATA REQUIREMENT

OECD Guideline 414

OPPTS 870.3700

STUDY DIRECTOR

Tammye L. Fleeman, BS, LAT

STUDY INITIATION DATE

11 January 2008

STUDY COMPLETION DATE

14 July 2008

PERFORMING LABORATORY

WIL Research Laboratories, LLC 1407 George Road Ashland, OH 44805-8946

SPONSOR

Honeywell International Inc. P.O. Box 1139 101 Columbia Road Morristown, NJ 07962

353 of 475

## WIL-447022 HFO-1234yf Honeywell International Inc.



# APPENDIX B

Certificates Of Analysis (Sponsor- Or Manufacturer-Provided Data)

354 of 475

## 355 of 475

## 356 of 475

## 357 of 475

## 358 of 475

## 359 of 475

## 360 of 475

## " HFO 1234yf (2,3,3,3-tetrafluoroprop-1-ene)” CERTIFICATE OF ANALYSIS CAS Number 754-12-1

This is to advise you that the product listed below has been classified BY GC/FID, GC/MSD Data are provided below.

LOT Number: 049918c-110107

GROSS 225.0 lbs. TARE 78.3 lbs.

NET 146.7 lbs.

Nonflammable Gas

ANALYSIS: HFO 1234yf 99.9997 v% Possible Impurities

Total fluorolefins 0.0001 v% Total saturated Fluorocarbons 0.0001 v%

Acetone, THF, Toluene 0.0001 v% Unknowns 0.0000 v%

1. Analysis done using Gc-MSD SIM for impurities 2. Compound Id verified by Gc-MSD. 3. N.D. = non-detect: detection limit by GC-MSD SIM is 1ppm.

Larry C. Hirsch DuET/ CPD / APDL Advanced Process Development Lab DuPont Experimental station Wilmington, DE 19880-0269 (302) 695-9367 FAX: (302)695-1799



## 361 of 475

## " HFO 1234yf (2,3,3,3-tetrafluoroprop-1-ene)” CERTIFICATE OF ANALYSIS CAS Number 754-12-1

This is to advise you that the product listed below has been classified BY GC/FID, GC/MSD Data are provided below.

LOT Number: 050064c-102907

GROSS 276.0 lbs. TARE 86.0 lbs.

NET 193.0 lbs.

Nonflammable Gas

ANALYSIS: HFO 1234yf 99.9923 v% Possible Impurities

Total fluorolefins 0.0005 v% Total saturated Fluorocarbons 0.0033 v%

Acetone, THF, Toluene 0.0039 v% Unknowns 0.0000 v%

1. Analysis done using Gc-MSD SIM for impurities 2. Compound Id verified by Gc-MSD. 3. N.D. = non-detect: detection limit by GC-MSD SIM is 1ppm.

Larry C. Hirsch DuET/ CPD / APDL Advanced Process Development Lab DuPont Experimental station Wilmington, DE 19880-0269 (302) 695-9367 FAX: (302)695-1799



## 362 of 475

## " HFO 1234yf (2,3,3,3-tetrafluoroprop-1-ene)” CERTIFICATE OF ANALYSIS CAS Number 754-12-1

This is to advise you that the product listed below has been classified BY GC/FID, GC/MSD Data are provided below.

LOT Number: 050432c-102907

GROSS 280 lbs. TARE 79 lbs. NET 201 lbs.

Nonflammable Gas

ANALYSIS: HFO 1234yf 99.9977 v% Possible Impurities

Total fluorolefins 0.0016 v% Total saturated Fluorocarbons 0.0006 v%

Acetone, THF, Toluene 0.0001 v% Unknowns 0.0000 v%

1. Analysis done using Gc-MSD SIM for impurities 2. Compound Id verified by Gc-MSD. 3. N.D. = non-detect: detection limit by GC-MSD SIM is 1ppm.

Larry C. Hirsch DuET/ CPD / APDL Advanced Process Development Lab DuPont Experimental station Wilmington, DE 19880-0269 (302) 695-9367 FAX: (302)695-1799



## 363 of 475

## WIL-447022 HFO-1234yf Honeywell International Inc.



# APPENDIX C

Analyses Of Test Substance Purity And Stability (WIL Research Laboratories, LLC)

364 of 475

## AN INHALATION PRENATAL DEVELOPMENTAL TOXICITY STUDY OF HFO-1234yf (2,3,3,3-TETRAFLUOROPROPENE) IN RABBITS

Analyses Of Test Substance Purity And Stability

Analytical Chemistry Department

WIL Research Laboratories, LLC WIL-447022 Honeywell International, Inc. HFO-1234yf

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# T ABLE 

# O F 

# C ONTENTS 

## Page

Table Of Contents......................................................................................2 Index Of Figures ........................................................................................2

Index Of Tables..........................................................................................3

1. Introduction................................................................................................4 2. Experimental ..............................................................................................4 2.1. Gas Chromatography ...................................................................................4 2.2. Preparation Of Samples For Purity And Stability Analyses........................4 2.3. Purity And Stability Assessments................................................................5

3. Results And Discussion..............................................................................5 3.1. Test Substance Purity Assessment.............................................................10

4. Conclusion ................................................................................................10 5. Key Study Personnel And Report Submission......................................12



# I NDEX 

# O F 

# F IGURES



## Figure 1: Representative Chromatogram Of A Honeywell International, Inc., HFO-1234yf Sample From The Storage Cylinder Prior To Use For Animal Exposures ....................................................................6

Figure 2: Representative Chromatogram Of A E.I. du Pont de Nemours And Company HFO-1234yf Sample From The Storage Cylinder Prior To Use For Animal Exposures.......................................7

Figure 3: Representative Chromatogram Of A Honeywell International, Inc., HFO-1234yf Sample From The Storage Cylinder After Completion Of Animal Exposures.........................................................8

Figure 4: Representative Chromatogram Of A E.I. du Pont de Nemours And Company HFO-1234yf Sample From The Storage Cylinder After Completion Of Animal Exposures ................................9

Figure 5: Representative Chromatogram Of A Blank Air Injection ...................10 WIL-447022 Honeywell International, Inc. HFO-1234yf

- 2 -
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# I NDEX 

# O F 

# T ABLES 

## Page

Table 1: Purity Prior To Use ..............................................................................14

Table 2: Purity After Completion ......................................................................16

Table 3: Stability................................................................................................18

Table 4: Stability................................................................................................19 WIL-447022 Honeywell International, Inc. HFO-1234yf

- 3 -
367 of 475

# 1. I NTRODUCTION 

## This report provides a detailed description of a method using gas chromatography (GC)
with flame ionization detection (FID) for the determination of test substance
(HFO-1234yf) purity. Test substance purity was assessed as the area percent of the
HFO-1234yf GC/FID peak. Test substance samples were collected and analyzed from
the storage cylinder prior to use for animal exposures (100% pure) and from the storage
cylinder after completion of use for animal exposures 57 days later (100% pure).
Comparison of these purity data indicated that the test substance was stable for the
duration of use on the study.



# 2. E XPERIMENTAL


# 2.1. G AS 

# C HROMATOGRAPHY



## Instrument: Varian CP-3800 gas chromatograph equipped with a flame ionization detector and Varian MS Workstation data system or equivalent system
Column: J&W DB-Wax column, 30 m × 0.25 mm ID, 0.25 μm film thickness
Temperature Program: Initial temperature 50oC, hold for 2 minutes Ramp at 30oC:minute to 260oC, hold for 1 minute

Flow: 0.8 mL/minute
Injector Temperature: 260°C
Injection Volume: 1.0 mL, by hand using glass gastight syringe
Split Ratio: 25:1
Detector Temperature: 300°C
Retention Time: Approximately 2.3 minutes

Run Time: 10 minutes



# 2.2. P REPARATION 

# O F 

# S AMPLES 

# F OR 

# P URITY 

# A ND 

# S TABILITY 

# A NALYSES 

## Individual samples of the test substance (HFO-1234yf collected in a gas bag)
manufactured by Honeywell International, Inc., and E.I. du Pont de Nemours and WIL-447022 Honeywell International, Inc. HFO-1234yf

- 4 -
368 of 475

## Company were received from the WIL Inhalation Department for determination of test
substance purity by GC/FID. Approximately 1.0 mL of each test substance was injected
for GC/FID analysis using a glass, gastight syringe.



# 2.3. P URITY 

# A ND 

# S TABILITY 

# A SSESSMENTS 

## Test substance samples were collected from the storage cylinder prior to use for animal
exposures and from the storage cylinder after completion of animal exposures. The
samples were transferred to the WIL Analytical Chemistry Department for GC/FID
analysis to assess test substance purity. Comparison of these purity data was used to
assess test substance stability over the duration of use on the study. Typically, three
1.0-mL injections were made from each sample, with the area percent results from the
last two injections used to assess purity and stability.



# 3. R ESULTS 

# A ND 

# D ISCUSSION 

## Under the described chromatographic conditions, the retention time for HFO-1234yf was
approximately 2.3 minutes. Figures 1 through 5 are typical chromatograms of test
substance samples from the storage cylinder prior to use for animal exposures (Figures 1
and 2), test substance samples from the storage cylinder after completion of animal
exposures (Figures 3 and 4) and a blank air injection (Figure 5). The total analysis time
required for each run was 10 minutes. WIL-447022 Honeywell International, Inc. HFO-1234yf

- 5 -
369 of 475

## Figure 1: Representative Chromatogram Of A Honeywell International, Inc., HFO-1234yf Sample From The Storage Cylinder Prior To Use For Animal Exposures WIL-447022 Honeywell International, Inc. HFO-1234yf

- 6 -
370 of 475

## Figure 2: Representative Chromatogram Of A E.I. du Pont de Nemours And Company HFO-1234yf Sample From The Storage Cylinder Prior To Use For Animal Exposures WIL-447022 Honeywell International, Inc. HFO-1234yf

- 7 -
371 of 475

## Figure 3: Representative Chromatogram Of A Honeywell International, Inc., HFO-1234yf Sample From The Storage Cylinder After Completion Of Animal Exposures WIL-447022 Honeywell International, Inc. HFO-1234yf

- 8 -
372 of 475

## Figure 4: Representative Chromatogram Of A E.I. du Pont de Nemours And Company HFO-1234yf Sample From The Storage Cylinder After Completion Of Animal Exposures WIL-447022 Honeywell International, Inc. HFO-1234yf

- 9 -
373 of 475

## Figure 5: Representative Chromatogram Of A Blank Air Injection



# 3.1. T EST 

# S UBSTANCE 

# P URITY 

# A SSESSMENT 

## As shown in Figures 1 through 4, one major peak (retention time at approximately
2.3 minutes) was present in the GC/FID chromatograms resulting from injection of the
test substance. Figure 5 represents a blank air injection and potential impurities present
in the chromatographic system. The peak area percent data from the analysis of the
samples are summarized in Tables 1 and 2. The mean area percent (purity) of test
substance samples collected from the storage cylinder prior to use for animal exposures
and from the storage cylinder after completion of animal exposures were 100% and
100%, respectively. Comparison of these data indicated that the test substance was stable
for the duration of use on the study (57 days) as summarized in Tables 3 and 4.



# 4. C ONCLUSION 

## Test substance purity was assessed using GC/FID and expressed as the area percent of the
HFO-1234yf chromatographic peak. Test substance samples were collected and analyzed
from the storage cylinder prior to use for animal exposures (100% pure) and from the WIL-447022 Honeywell International, Inc. HFO-1234yf

- 10 -
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## storage cylinder after completion of animal exposures 57 days later (100% pure).
Comparison of these purity data indicated that the test substance was stable for the
duration of use on the study. WIL-447022 Honeywell International, Inc. HFO-1234yf

- 11 -
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## WIL-4-4-7022 Honeywell International, Inc. 

## HFO- 1234yf



# 5. 

# KEY STUDY PERSONNEL AND REPORT SUBMISSION

Report Submitted By:

Tamhye 

## L. Fleeman, BS, LAT Staff Toxicologist, Developmental and Reproductive Toxicology Study Director bate 

# '

Report Prepared By:

Research Chemist



## , Analytical Chemistry

Report Reviewed By: *4



## Study Personnel:

Joshua J. Hiller, AA John E. Essex 111, BA Melissa A. Hull, BS Associate Chemist I Publishing Specialist, Study Analysis and Reports Group Supervisor, Regulatory Technical Services

-12-

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## 475

# TABLES 1 - 4 WIL-447022 Honeywell International, Inc. HFO-1234yf

- 13 -
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Test Substance Mean Date Date Ref. Sample Run Retention Percent Percent Percent Collected Analyzed # ID # Time Area Area Area Area ( 447022 - ) (WIL log no-) (%) (%) (%)

NA 1/23/08 1-1 blank 1 NA NA NA NA

1/21/08 1/23/08 1-2 7749A#7-2 2 2.21 176111 100 100 1-3 7749A#7-2 3 2.21 169970 100 100 1-4 7749A#7-2 4 2.23 125859 100 100 100

447022.xls Pre study purity

Printed: 12Jun2008 11:19 AM AN INHALATION PRENATAL DEVELOPMENTAL TOXICITY

Table 1: Purity Prior To Use STUDY OF HFO-1234yf (2,3,3,3-TETRAFLUOROPROPENE) IN RABBITS 

## WIL-447022 Honeywell International, Inc. HFO-1234yf

- 14 -
378 of 475Honeywell International Inc.

Test Substance Mean Date Date Ref. Sample Run Retention Percent Percent Percent Collected Analyzed # ID # Time Area Area Area Area ( 447022 - ) (WIL log no-) (%) (%) (%)

NA 1/23/08 2-1 blank 5 NA NA NA NA

1/22/08 1/23/08 2-2 7819B#1-3 6 2.21 161141 100 100 2-3 7819B#1-3 7 2.22 129626 100 100 2-4 7819B#1-3 8 2.22 96281 100 100 100

447022.xls Pre study purity (2)

Printed: 12Jun2008 11:19 AM AN INHALATION PRENATAL DEVELOPMENTAL TOXICITY

Table 1 (continued): Purity Prior To Use STUDY OF HFO-1234yf (2,3,3,3-TETRAFLUOROPROPENE) IN RABBITS 

## WIL-447022 Honeywell International, Inc. HFO-1234yf

- 15 -
379 of 475Honeywell International Inc.

Test Substance Mean Date Date Ref. Sample Run Retention Percent Percent Percent Collected Analyzed # ID # Time Area Area Area Area (447022) (WIL log no-) (%) (%) (%)

After Completion NA 3/20/08 8-1 blank 9 NA NA NA NA

3/20/08 3/20/08 8-2 7749A#12-2 10 2.23 48133 100 100

3/20/08 3/20/08 8-3 7749A#12-2 11 2.22 68772 100 100 100
8-4 7749A#12-2 12 2.23 32611 100 100

447022.xls Post study purity

Printed: 12Jun2008 11:19 AM AN INHALATION PRENATAL DEVELOPMENTAL TOXICITY STUDY OF HFO-1234yf (2,3,3,3-TETRAFLUOROPROPENE) IN RABBITS Table 2: Purity After Completion 

## WIL-447022 Honeywell International, Inc. HFO-1234yf

- 16 -
380 of 475Honeywell International Inc.

Test Substance Mean Date Date Ref. Sample Run Retention Percent Percent Percent Collected Analyzed # ID # Time Area Area Area Area (447022) (WIL log no-) (%) (%) (%)

After Completion NA 3/20/08 9-1 blank 13 NA NA NA NA

3/20/08 3/20/08 9-2 7819B#3-2 14 2.22 62468 100 100

3/20/08 3/20/08 9-3 7819B#3-2 15 2.22 23583 100 100 100
9-4 7819B#3-2 16 2.22 54163 100 100

447022.xls Post study purity (2)

Printed: 12Jun2008 11:19 AM AN INHALATION PRENATAL DEVELOPMENTAL TOXICITY STUDY OF HFO-1234yf (2,3,3,3-TETRAFLUOROPROPENE) IN RABBITS Table 2 (continued): Purity After Completion 

## WIL-447022 Honeywell International, Inc. HFO-1234yf

- 17 -
381 of 475Test Substance MeanPercentDate Date Ref. Sample Run Retention Percent Percent ofCollectedAnalyzed#ID#TimeAreaAreaAreaTime Zero(447022-) (WIL log no-) (%) (%) (%)Prior to Use1/21/08 1/23/08 1-3 7749A#7-23 2.21 169970 100 1001/21/08 1/23/08 1-4 7749A#7-24 2.23 125859 100After Completion3/20/08 3/20/08 8-3 7749A#12-211 2.22 68772 100 1001003/20/08 3/20/08 8-4 7749A#12-212 2.23 32611 100447022.xls StabilityPrinted: 12Jun2008 11:19 AMTable 3: StabilityAN INHALATION PRENATAL DEVELOPMENTAL TOXICITYSTUDY OF HFO-1234yf (2,3,3,3-TETRAFLUOROPROPENE) IN RABBITS 

## WIL-447022 Honeywell International, Inc. HFO-1234yf

- 18 -
382 of 475Test Substance MeanPercentDate Date Ref. Sample Run Retention Percent Percent ofCollectedAnalyzed#ID#TimeAreaAreaAreaTime Zero(447022-) (WIL log no-) (%) (%) (%)Prior to Use1/21/08 1/23/08 2-3 7819B#1-37 2.22 129626 100 1001/21/08 1/23/08 2-4 7819B#1-38 2.22 96281 100After Completion3/20/08 3/20/08 9-3 7819B#3-215 2.22 23583 100 1001003/20/08 3/20/08 9-4 7819B#3-216 2.22 54163 100447022.xls Stability (2)Printed: 12Jun2008 11:19 AMTable 4: StabilityAN INHALATION PRENATAL DEVELOPMENTAL TOXICITYSTUDY OF HFO-1234yf (2,3,3,3-TETRAFLUOROPROPENE) IN RABBITS 

## WIL-447022 Honeywell International, Inc. HFO-1234yf

- 19 -
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## WIL-447022 HFO-1234yf Honeywell International Inc.



# APPENDIX D

Exposure Atmosphere Generation Report (WIL Research Laboratories, LLC)

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## AN INHALATION PRENATAL DEVELOPMENTAL TOXICITY STUDY OF HFO-1234yf (2,3,3,3-TETRAFLUOROPROPENE) IN RABBITS

Exposure Atmosphere Generation Report

Inhalation Department

WIL Research Laboratories, LLC WIL-447022 Honeywell International Inc. HFO-1234yf

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# T ABLE 

# O F 

# C ONTENTS 

## Page

Table Of Contents......................................................................................2 Index Of Figures ........................................................................................2

Index Of Tables..........................................................................................3 1. Exposure Methods .....................................................................................4 1.1. Exposure Regimen.......................................................................................4 1.2. Inhalation Exposure System Description.....................................................4 1.3. Animal Transport And Placement ...............................................................5 1.4. Exposure Environmental Conditions ...........................................................5

2. Test Atmosphere Generation Methods ....................................................7 3. Methods For Characterization Of Exposure Atmospheres ...................8

3.1. Nominal Concentrations ..............................................................................8 3.2. Analyzed Exposure Concentrations.............................................................9 3.2.1. Analytical Methods......................................................................................9 3.2.2. Gas Chromatograph Calibration ................................................................10

3.3. Determination Of Homogeneity Of Exposure Atmospheres.....................13

4. Results Of Characterization Of Actual Exposure Concentrations .........................................................................................14 4.1. Nominal Exposure Concentrations ............................................................14 4.2. Analyzed Exposure Concentrations...........................................................15

5. Key Study Personnel And Report Submission......................................16



# I NDEX 

# O F 

# F IGURES



## 1. Atmosphere Generation And Exposure System (Chambers 2, 3 And 4) ..................18

2. Atmosphere Generation And Exposure System (Chamber 5)...................................19 WIL-447022 Honeywell International Inc. HFO-1234yf

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# I NDEX 

# O F 

# T ABLES 

## Page

1. Daily Mean Chamber Temperature [Degrees Celsius] Phase I.................................21

2. Daily Mean Chamber Temperature [Degrees Celsius] Phase II................................22

3. Daily Mean Chamber Relative Humidity [%] Phase I...............................................23

4. Daily Mean Chamber Relative Humidity [%] Phase II .............................................24

5. Daily Mean Chamber Ventilation Rate [SLPM] Phase I...........................................25

6. Daily Mean Chamber Ventilation Rate [SLPM] Phase II .........................................26

7. Daily Oxygen Content Determination [%] Phase I....................................................27

8. Daily Oxygen Content Determination [%] Phase II ..................................................28

9. Test Atmosphere Homogeneity Determination .........................................................29

10. Daily Nominal Concentration [PPM] Phase I............................................................33

11. Daily Nominal Concentration [PPM] Phase II...........................................................34

12. Daily Mean Test Atmosphere Concentrations [PPM] Phase I ..................................35

13. Daily Mean Test Atmosphere Concentrations [PPM] Phase II.................................40 WIL-447022 Honeywell International Inc. HFO-1234yf

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# 1. E XPOSURE 

# M ETHODS


# 1.1. E XPOSURE 

# R EGIMEN 

## The test article or filtered air (control group) was administered in 2 phases as a daily
6-hour whole-body inhalation exposure. Each phase was conducted 7 days per week at
approximately the same time each day for 24 days. A detailed description of the study
design and exposure schedule is presented in the main report. The following table
presents the overall schedule for inhalation exposures:

Phase I Study Day Date First Exposure 0 22 January 2008 Last Exposure 23 14 February 2008

Phase II Study Day Date First Exposure 0 25 February 2008 Last Exposure 23 19 March 2008



# 1.2. I NHALATION 

# E XPOSURE 

# S YSTEM 

# D ESCRIPTION 

## Exposures were conducted in one 2.0-m 3 

## (2000-L) and four 1.5-m 3 

## (1500-L) stainless
steel and glass whole-body inhalation exposure chambers for control group and test
article groups, respectively. One chamber was dedicated to each group for the duration
of the study as follows:

Phase I Group Number 1 2 3 4 5
Chamber Number 1 2 3 4 5 Target Exposure Concentration (ppm) 0 2500 4000 7500 4000

Phase II Group Number 1 2 3 4 5
Chamber Number 1 2 3 4 5 Target Exposure Concentration (ppm) 0 2500 5500 7500 5500 WIL-447022 Honeywell International Inc. HFO-1234yf

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## Chamber supply air was provided from a HEPA- and charcoal-filtered, temperature- and
humidity-controlled source. Treatment of exhaust air consisted of charcoal and HEPA

filtration.



# 1.3. A NIMAL 

# T RANSPORT 

# A ND 

# P LACEMENT 

## Animals were individually housed in stainless steel wire-mesh caging. Food and water
were withheld during the exposure periods. Animals were housed in a normal animal
colony room during non-exposure hours. For the exposure each day, the animals were
transferred to exposure caging, transported to the exposure chamber room, exposed for
the requisite duration and returned to their home cages in the animal colony room.

The cage batteries were rotated on a daily basis between 6 battery positions in the control
chamber and 3 battery positions in the test article chambers to help ensure a similar
exposure for all animals within each group over the duration of the exposure period.



# 1.4. E XPOSURE 

# E NVIRONMENTAL 

# C ONDITIONS 

## Chamber temperature, relative humidity, ventilation rate and negative pressure within
each chamber were continually monitored and recorded at approximately 35-minute
intervals through the use of LabVIEW ® 

## for Windows Data Acquisition Software
(National Instruments, Inc., Austin, TX) and a personal computer with appropriate
hardware. For each 6-hour exposure period, at least 10 data points were collected per
chamber. Chamber temperature and relative humidity were monitored with an Omega
Model No. HX94C Humidity and Temperature transmitter probe (Omega Engineering,
Inc., Stamford, CT). The mean temperature and mean relative humidity were to be
between 16°C to 22°C and 30% to 70%, respectively.

All chambers were operated under dynamic conditions, at least 12 air changes per hour
(400 liters per minute [LPM] for Chamber 1 and 300 LPM for Chambers 2 through 5) at
a slight negative pressure. Chamber airflow was monitored by a sharp edge orifice plate
and Dwyer Magnehelic ® 

## Indicating Transmitter pressure gauge (Michigan City, IN). WIL-447022 Honeywell International Inc. HFO-1234yf

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## Each gauge was calibrated under the conditions of exposure for conversion from pressure
to airflow in standard liters per minute (SLPM) through the use of a Fox Gas Mass
Flowmeter Transmitter (Model FT2, Fox Thermal Instruments, Marina, CA). Daily
means for chamber temperature, relative humidity and ventilation rate over the study
period are presented in Tables 1 through 6 of this appendix. The following table
summarizes the grand mean environmental conditions for each phase in all chambers:

Phase I
Chamber: 1 2 3 4 5 Temperature (oC): 23 22 22 22 23

Standard Deviation: 0.7 0.5 0.6 0.6 0.6
Relative Humidity (%): 53 51 53 52 53

Standard Deviation: 5.0 2.7 2.0 2.5 4.6
Chamber Ventilation Rate (SLPM): 443 330 329 327 327

Standard Deviation: 4.7 3.9 4.1 4.5 4.7 Exposure Days: 24 24 24 24 24

Phase II
Chamber: 1 2 3 4 5 Temperature (oC): 23 22 21 21 23

Standard Deviation: 0.4 0.4 0.4 0.6 0.6
Relative Humidity (%): 50 49 52 47 52

Standard Deviation: 1.7 1.9 1.2 1.7 1.6
Chamber Ventilation Rate (SLPM): 444 332 332 333 332

Standard Deviation: 5.3 3.6 4.7 4.0 5.0 Exposure Days: 24 24 24 24 24

Oxygen content was measured during the method development phase of the study and on
each exposure day using a Drager Pac III equipped with a calibrated oxygen sensor
(Draeger Safety, Inc., Pittsburgh, PA) or an AMI Oxygen Analyzer (Model 201RSP,
Advanced Micro Instruments, Inc., Huntington Beach, CA). Oxygen content of each WIL-447022 Honeywell International Inc. HFO-1234yf

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## phase was at least 19% for all chambers and is presented in Tables 7 and 8 of this
appendix.



# 2. T EST 

# A TMOSPHERE 

# G ENERATION 

# M ETHODS 

## The test atmosphere generation and exposure systems are shown schematically in
Figures 1 and 2. A gas atmosphere of the test article was generated by releasing the test
article in gas form from the original cylinders. One cylinder was used to deliver test
article (WIL log no. 7749A) to Chambers 2, 3 and 4 and one cylinder was used to deliver
test article (WIL log no. 7819B) to Chamber 5. Heat was applied to the cylinders using a
heated blanket controlled by a J-type thermocouple and CN370 Omega temperature
controller set to 30°C to 40°C. A Matheson regulator (model no. M3126-660,
Montgomeryville, PA) with Ashcroft pressure gauges (0 to 100 psi at the inlet side of the
regulator and 0 to 30 psi at outlet side of the regulator, Stratford, CT) were used to
control test article flow from the cylinders to a Top Trak Mass Flow Meter (model
no. 822S-M-2-OK2-PV1-V1, Sierra Instruments, Inc. Monterey, CA) equipped with a
needle valve. For Chambers 2 through 4, test article was delivered from the Top Trak
flow meter to a manifold system equipped with an Ashcroft pressure gauge (0 to 30 psi)
to monitor manifold pressure. Attached to the manifold, Top Trak Mass Flow Meters and

needle valves were used to control the test article delivered to each chamber. Chamber 5
test article was delivered through a Top Trak Mass Flow Meter, and needle valve was
used to control test article delivered to the chamber. The concentrated gas from each
cylinder was piped to a mixing plenum where the concentration was reduced by mixing
with chamber ventilation air. The following table summarizes the Top Trak readings for
each phase: WIL-447022 Honeywell International Inc. HFO-1234yf

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## Phase I

Chamber Top Trak Top Trak Reading Number Model No. (indicated)
2 8225-L-2-OK1-PV1-V1 3.07-3.37
3 8225-L-2-OK1-PV1-V1 4.85-5.80
4 8225-M-2-OK1-PV1-V1 08.6-09.9
5 8225-M-2-OK1-PV1-V1 4.73-5.39

Phase II

Chamber Top Trak Top Trak Reading Number Model No. (indicated)
2 8225-L-2-OK1-PV1-V1 3.10-3.61
3 8225-L-2-OK1-PV1-V1 7.43-8.54
4 8225-M-2-OK1-PV1-V1 08.5-10.7
5 8225-M-2-OK1-PV1-V1 6.97-7.95



# 3. M ETHODS 

# F OR 

# C HARACTERIZATION 

# O F 

# E XPOSURE 

# A TMOSPHERES


# 3.1. N OMINAL 

# C ONCENTRATIONS 

## A nominal exposure concentration was calculated daily for each chamber from the total
amount of test article used during the exposure and the total volume of air passed through
the chamber during that day’s exposure. The amount of test article used was obtained by
weighing the test article cylinders prior to and after each day’s exposure. Because
1 cylinder was used to generate into 3 chambers, a 5:8:15 and 5:11:15 ratio for Phase I
and II, respectively, (derived from the target concentrations) was used to calculate the test
article usage for Chambers 2, 3 and 4, respectively. The total volume of air passed
through each chamber was calculated from the daily average chamber ventilation flow
rate in standard liters per minute (SLPM) and the exposure duration. The nominal
concentration of each phase was calculated as follows. WIL-447022 Honeywell International Inc. HFO-1234yf

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## WT × MV × 10 6 

## Concentration (ppm) = GMW × CVR × DUR
Where: WT = Weight of test article used, grams MV = Molar volume at 730 mmHg and 21oC, 25.11 L/mole

10 6 

## = ppm conversion factor GMW = Test article gram molecular weight, (1) 

## 114 g/mole

CVR = Daily mean chamber ventilation rate for a given day, SLPM DUR = Duration of the daily exposure, minutes

(1) 

## = Gram Molecular Weight for WIL Log No. 7819B was 114.06 g/mole



# 3.2. A NALYZED 

# E XPOSURE 

# C ONCENTRATIONS


# 3.2.1. A NALYTICAL 

# M ETHODS 

## Analyzed exposure concentrations were determined at approximately 35-minute intervals
using a gas chromatograph (GC). Samples were collected from the approximate
animal-breathing zone of the inhalation exposure chambers via 1/8-inch Teflon tubing.

Under the control of the LabVIEW ® 

## data acquisition software application, sampling and
analyses were performed as follows. The program controls an external multi-position
valve (Model E16, Valco Instruments Co., Inc., Houston, TX) that permits sequential
sampling from the exposure room and each exposure chamber. Using an event controller
and a Hewlett Packard Model 3396 Series II integrator (with BASIC program), gas
sample injection onto the chromatography column occurs via an internal gas-sampling
valve with a sample loop. The chromatograph is displayed and the area under the sample
peak is calculated and stored. The LabVIEW ® 

## application then acquires the stored peak
area data and uses a linear equation based on the GC calibration curve to calculate the
measured concentrations in parts per million (ppm). The following table summarizes the
operational parameters used for the GC methods:

Instrument: Hewlett Packard 5890 Series II Detector: Flame Ionization (FID) WIL-447022 Honeywell International Inc. HFO-1234yf

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## Column: J&W Scientific, DB-624, 30m × 0.53mm ID, 3.0-micron film thickness

Gases Pressure (psig) Flow Rate (mL/minute)
Carrier - Helium: 10 13 Fuel - Hydrogen: 18 37
Air: 34 277 Temperatures (oC)
Column: 100

Detector: 200 Auxiliary: 86

Integrator: Hewlett Packard Model 3396 Series II

Run Parameters
Chart Zero Offset: 0
Chart Attenuation: 8 Chart Speed: 1.5 cm/minute Peak Area Rejection Value: 0
Peak Threshold: 7
Peak Width: 0.02 Retention Time (Minutes): Approximately 0.68 minutes



# 3.2.2. G AS 

# C HROMATOGRAPH 

# C ALIBRATION 

## The GC was calibrated using gas-phase standards prepared to contain known gas
concentrations of the test article. Concentrated test article was drawn from each cylinder

into a 1-L Tedlar ® 

## (SKC Inc., Eighty Four, PA) gas bag. A known amount of test article
from each 1-L sample bag was pulled into an air-tight glass syringe and injected into a

5- or 10-L Tedlar ® 

## gas bag filled with compressed air. A dry test meter (DTM-200A,
Elster American Meter Co., Nebraska City, NE) was used to measure the total volume of
air in a standard bag. The standard bag was manually agitated and run on the GC.
Concentrations of the gas-phase standards are calculated as follows: WIL-447022 Honeywell International Inc. HFO-1234yf

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## 10 6 

## × VOL Concentration (ppm) = mL + VOL

Where: VOL = Volume of gaseous test article injected into bag, mL
10 6 

## = ppm conversion factor mL = Volume of air used to prepare bag, mL

Prior to initiation of animal exposures, the GC was calibrated with standards prepared
and analyzed in triplicate. Three calibration curves were prepared for Phase I, including
calibration curve No. 1 for Chambers 2 and 3, No. 2 for Chamber 4 and No. 3 for
Chamber 5. Four calibration curves were prepared for Phase II, including calibration
curves No. 1, 2, 3 and 4 for Chambers 2, 3, 4 and 5, respectively. The calibration curves
were defined by using standards prepared at 5 gas concentrations for WIL log no. 7749A
and 3 gas concentrations for WIL log no. 7819B. The prime calibration curves were
prepared for all chambers using linear regression formulas and was used to calculate
exposure concentrations.

Prior to the initiation of each day’s exposure, 1 of the 5 standards was prepared and
analyzed for WIL log no. 7749A and 1 of the 3 standards was prepared and analyzed for
WIL log no. 7819B, and the appropriate linear regression curve was used to perform a
calibration check of the GC. The GC was considered to be in calibration if the analyzed
concentration of the prepared standards were within ± 10% of the known concentration.
The following table summarizes the standard parameters of each phase:

Phase I
Calibration Curve 1

Test Article Standard Volume of Test Article Total Dilution Air Volume (log no.) (ppm) (mL) (mL)

7749A 1189 9.5 8000

7749A 2991 24 8000
7749A 5470 44 8000 WIL-447022 Honeywell International Inc. HFO-1234yf

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## Calibration Curve 2

Test Article Standard Volume of Test Article Total Dilution Air Volume (log no.) (ppm) (mL) (mL)

7749A 5470 44 8000
7749A 7937 40 5000

7749A 9901 20 2000

Calibration Curve 3

Test Article Standard Volume of Test Article Total Dilution Air Volume (log no.) (ppm) (mL) (mL)

7819B 1189 9.5 8000
7819B 2991 24 8000
7819B 5470 44 8000

Phase II

Calibration Curve 1

Test Article Standard Volume of Test Article Total Dilution Air Volume (log no.) (ppm) (mL) (mL)

7749A 1189 9.5 8000

7749A 2991 24 8000
7749A 5470 44 8000

Calibration Curve 2

Test Article Standard Volume of Test Article Total Dilution Air Volume (log no.) (ppm) (mL) (mL)

7749A 1189 9.5 8000
7749A 5470 44 8000

7749A 7937 40 5000 WIL-447022 Honeywell International Inc. HFO-1234yf

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## Calibration Curve 3

Test Article Standard Volume of Test Article Total Dilution Air Volume (log no.) (ppm) (mL) (mL)

7749A 5470 44 8000
7749A 7937 40 5000
7749A 9901 20 2000

Calibration Curve 4

Test Article Standard Volume of Test Article Total Dilution Air Volume (log no.) (ppm) (mL) (mL)

7819B 1189 9.5 8000
7819B 5470 44 8000
7819B 7937 40 5000



# 3.3. D ETERMINATION 

# O F 

# H OMOGENEITY 

# O F 

# E XPOSURE 

# A TMOSPHERES 

## Homogeneity of exposure concentrations was evaluated during the method development
phase of the study. Four test locations and a reference location were used for these
determinations. The test locations were Upper Front, Lower Front, Upper Rear, and
Lower Rear. Samples were collected and analyzed on the GC as rapidly as possible by
alternating from the reference location to a test location. The measured concentration
was calculated as a percent difference for each position from the reference location.
Homogeneity was performed in triplicate for each test article exposure chamber. The
results are presented in Table 9 of this appendix. The following table summarizes the
mean data of the replicates for each test article chamber: WIL-447022 Honeywell International Inc. HFO-1234yf

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## Chamber Number Test Location Mean % From Reference 2 Upper Front -1.1

Lower Front -0.9 Upper Rear -1.3
Lower Rear -0.8

3 Upper Front -0.8
Lower Front -0.7 Upper Rear -0.7
Lower Rear -0.8

4 Upper Front -1.7

Lower Front -1.9 Upper Rear -2.0
Lower Rear -1.6

5 Upper Front -1.4
Lower Front -1.3 Upper Rear -1.8
Lower Rear -1.5

These data indicate that the homogeneity of each exposure chamber atmosphere was
within ± 10% of the reference port and was adequate for the purpose of this study.



# 4. R ESULTS 

# O F 

# C HARACTERIZATION 

# O F 

# A CTUAL 

# E XPOSURE 

# C ONCENTRATIONS


# 4.1. N OMINAL 

# E XPOSURE 

# C ONCENTRATIONS 

## Daily nominal concentrations for the test article chamber are presented in Tables 10
and 11 of this appendix for Phase I and Phase II, respectively. Due to the relatively small
amount of test article used each day for Chambers 2, 3 and 4 and the large scale needed
to weigh the cylinder, an inconsistency was noted among each day’s nominal WIL-447022 Honeywell International Inc. HFO-1234yf

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## concentration. The following table summarizes the overall mean nominal concentrations
for each phase:

Phase I
Chamber: 2 3 4 5 Mean Concentration (ppm): 2328 3745 7055 3635
Standard Deviation: 62.0 89.5 186.5 177.7

N: 24 24 24 24

Phase II
Chamber: 2 3 4 5 Mean Concentration (ppm): 2363 5203 7078 5407
Standard Deviation: 78.6 162.2 202.4 214.0

N: 24 24 24 24



# 4.2. A NALYZED 

# E XPOSURE 

# C ONCENTRATIONS 

## Daily mean analyzed concentrations for each test article chamber are presented in Tables
12 and 13 of this appendix for Phase I and II, respectively. The following table
summarizes the overall mean analyzed concentrations of each phase and each chamber:

Phase I
Chamber: 1 2 3 4 5 Mean Concentration (ppm): 0 2504 3982 7512 4013
Standard Deviation: 0.0 19.4 56.5 38.1 38.4

N: 24 24 24 24 24

Phase II
Chamber: 1 2 3 4 5 Mean Concentration (ppm): 0 2479 5408 7441 5479
Standard Deviation: 0.0 69.8 194.3 189.1 233.2

N: 24 24 24 24 24 WIL-447022 Honeywell International Inc. HFO-1234yf

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## WIL-447022 Honeywell International Inc. HFO- 1234yf



# 5. 

# KEY STUDY PERSONNEL AND REPORT SUBMISSION



## Report Submitted By: 

# 3 2bJ

Tahmye 

## L. Fleeman, BS, LAT Staff Toxicologist, Developmental

And Reproductive Toxicology Study Director 

# m

Project Leader, e Inhalation S.Cock urn Toxicology Report Prepared By:



# ll-I SAIL! 

## zc-iq 

## Date

Report Reviewed By:
\



## Study Personnel:

Christine A. Heston, BA John 

## E. Essex 111, BA Quality Control Coordinator, Inhalation Toxicology Publishing Specialist, Study Analysis and Reports

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# FIGURES 1 - 2 WIL-447022 Honeywell International Inc. HFO-1234yf

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## Figure 1: Atmosphere Generation and Exposure System (Chambers 2, 3 and 4)

Supply Air

1500-L Chamber



### Orifice Meter

To Exhaust Mixing Chamber 

### Mass Flow Meter Manifold

and Gauge 1 2 3



### To other Chambers 1 2 3



### TA Cylinder with Heat Blanket Temperature

Controller 

### Mass Flow Meter

0123

0 1 2 3 

# WIL-447022 Honeywell International Inc. HFO-1234yf

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## Figure 2: Atmosphere Generation and Exposure System (Chamber 5)

Supply Air

1500-L Chamber



### Orifice Meter

To Exhaust Mixing Chamber 1 2 3



### Mass Flow Meter

0123 

### Temperature

Controller

0 1 2 3



### TA Cylinder with Heat Blanket 

# WIL-447022 Honeywell International Inc. HFO-1234yf

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# TABLES 1 - 13 WIL-447022 Honeywell International Inc. HFO-1234yf

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404 of 475INHALATION TABLE 1 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL DAILY MEAN CHAMBER TEMPERATURE [DEGREES CELSIUS] PHASE I

----------------------------------------------------------------------------------------------------------------------------------- DATE GROUP: 0 PPM 2500 PPM 4000 PPM 7500 PPM 4000 PPM

----------------------------------------------------------------------------------------------------------------------------------- 01/22/08 23. 22. 21. 21. 22. 01/23/08 23. 23. 22. 23. 24. 01/24/08 23. 23. 22. 22. 23. 01/25/08 22. 22. 21. 22. 22. 01/26/08 22. 22. 21. 22. 23. 01/27/08 22. 22. 22. 22. 23. 01/28/08 22. 22. 21. 22. 23. 01/29/08 23. 23. 22. 22. 23. 01/30/08 23. 22. 22. 22. 23. 01/31/08 22. 22. 21. 21. 22. 02/01/08 22. 22. 21. 21. 22. 02/02/08 22. 22. 21. 21. 22. 02/03/08 22. 22. 22. 21. 23. 02/04/08 23. 22. 22. 22. 23. 02/05/08 24. 23. 22. 22. 23. 02/06/08 23. 23. 22. 22. 23. 02/07/08 23. 22. 22. 22. 23. 02/08/08 23. 22. 22. 22. 23. 02/09/08 23. 23. 22. 22. 23. 02/10/08 23. 22. 22. 22. 23. 02/11/08 22. 22. 21. 21. 23. 02/12/08 22. 22. 21. 21. 22. 02/13/08 22. 22. 21. 21. 23. 02/14/08 21. 21. 20. 20. 21.

----------------------------------------------------------------------------------------------------------------------------------- GRAND MEAN 23. 22. 22. 22. 23. S.D. 0.7 0.5 0.6 0.6 0.6 C.V.(%) 2.9 2.3 2.7 3.0 2.7 N 24 24 24 24 24 PINHv4.05 03/24/2008 R:03/24/2008WIL-447022Honeywell International Inc.HFO-1234yf-21-405of475INHALATION TABLE 2 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL DAILY MEAN CHAMBER TEMPERATURE [DEGREES CELSIUS] PHASE II

----------------------------------------------------------------------------------------------------------------------------------- DATE GROUP: 0 PPM 2500 PPM 5500 PPM 7500 PPM 5500 PPM

----------------------------------------------------------------------------------------------------------------------------------- 02/25/08 22. 21. 20. 21. 21. 02/26/08 22. 22. 21. 22. 23. 02/27/08 22. 22. 21. 22. 22. 02/28/08 23. 22. 21. 22. 23. 02/29/08 23. 22. 21. 22. 23. 03/01/08 23. 22. 21. 22. 23. 03/02/08 23. 22. 21. 22. 23. 03/03/08 23. 23. 22. 22. 23. 03/04/08 23. 22. 21. 22. 22. 03/05/08 22. 22. 21. 21. 22. 03/06/08 23. 22. 22. 22. 22. 03/07/08 22. 22. 21. 21. 22. 03/08/08 23. 22. 21. 20. 22. 03/09/08 23. 22. 21. 21. 22. 03/10/08 23. 22. 21. 21. 23. 03/11/08 23. 22. 21. 21. 23. 03/12/08 23. 23. 21. 21. 23. 03/13/08 23. 22. 21. 21. 23. 03/14/08 23. 23. 22. 21. 23. 03/15/08 23. 22. 22. 21. 23. 03/16/08 23. 22. 21. 21. 23. 03/17/08 23. 22. 21. 21. 23. 03/18/08 23. 22. 21. 21. 22. 03/19/08 22. 22. 21. 20. 22.

----------------------------------------------------------------------------------------------------------------------------------- GRAND MEAN 23. 22. 21. 21. 23. S.D. 0.4 0.4 0.4 0.6 0.6 C.V.(%) 1.9 1.8 2.1 2.9 2.6 N 24 24 24 24 24 PINHv4.05 03/24/2008 R:03/24/2008WIL-447022Honeywell International Inc.HFO-1234yf-22-406of475INHALATION TABLE 3 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL DAILY MEAN CHAMBER RELATIVE HUMIDITY [%] PHASE I

----------------------------------------------------------------------------------------------------------------------------------- DATE GROUP: 0 PPM 2500 PPM 4000 PPM 7500 PPM 4000 PPM

----------------------------------------------------------------------------------------------------------------------------------- 01/22/08 49. 48. 52. 50. 47. 01/23/08 52. 52. 55. 55. 48. 01/24/08 48. 50. 51. 53. 40. 01/25/08 52. 51. 52. 54. 42. 01/26/08 50. 50. 52. 53. 52. 01/27/08 50. 50. 53. 53. 51. 01/28/08 49. 49. 51. 52. 52. 01/29/08 53. 52. 54. 54. 55. 01/30/08 55. 52. 55. 55. 54. 01/31/08 68. 53. 56. 57. 55. 02/01/08 56. 53. 56. 55. 57. 02/02/08 49. 49. 51. 50. 49. 02/03/08 50. 48. 51. 50. 51. 02/04/08 49. 48. 51. 49. 52. 02/05/08 50. 49. 51. 49. 54. 02/06/08 55. 51. 54. 53. 55. 02/07/08 53. 55. 56. 53. 56. 02/08/08 54. 54. 54. 52. 56. 02/09/08 54. 54. 55. 52. 57. 02/10/08 52. 53. 55. 52. 57. 02/11/08 53. 54. 56. 51. 57. 02/12/08 65. 53. 56. 51. 56. 02/13/08 60. 59. 55. 51. 56. 02/14/08 55. 48. 51. 45. 51.

----------------------------------------------------------------------------------------------------------------------------------- GRAND MEAN 53. 51. 53. 52. 53. S.D. 5.0 2.7 2.0 2.5 4.6 C.V.(%) 9.3 5.3 3.8 4.9 8.8 N 24 24 24 24 24 PINHv4.05 03/24/2008 R:03/24/2008WIL-447022Honeywell International Inc.HFO-1234yf-23-407of475INHALATION TABLE 4 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL DAILY MEAN CHAMBER RELATIVE HUMIDITY [%] PHASE II

----------------------------------------------------------------------------------------------------------------------------------- DATE GROUP: 0 PPM 2500 PPM 5500 PPM 7500 PPM 5500 PPM

----------------------------------------------------------------------------------------------------------------------------------- 02/25/08 51. 48. 51. 46. 51. 02/26/08 48. 46. 51. 46. 51. 02/27/08 52. 47. 51. 45. 50. 02/28/08 51. 48. 52. 46. 51. 02/29/08 50. 49. 53. 47. 52. 03/01/08 50. 48. 52. 46. 51. 03/02/08 50. 49. 52. 46. 51. 03/03/08 52. 50. 52. 48. 53. 03/04/08 49. 49. 51. 47. 51. 03/05/08 50. 48. 50. 45. 51. 03/06/08 50. 48. 50. 46. 53. 03/07/08 49. 49. 51. 45. 51. 03/08/08 48. 55. 51. 50. 56. 03/09/08 48. 49. 51. 45. 51. 03/10/08 52. 50. 52. 48. 53. 03/11/08 54. 51. 53. 49. 55. 03/12/08 54. 53. 55. 51. 55. 03/13/08 50. 50. 52. 47. 53. 03/14/08 51. 50. 52. 47. 52. 03/15/08 50. 49. 51. 47. 52. 03/16/08 49. 49. 52. 45. 52. 03/17/08 49. 50. 52. 45. 51. 03/18/08 52. 51. 54. 48. 54. 03/19/08 52. 49. 53. 49. 54.

----------------------------------------------------------------------------------------------------------------------------------- GRAND MEAN 50. 49. 52. 47. 52. S.D. 1.7 1.9 1.2 1.7 1.6 C.V.(%) 3.4 3.8 2.3 3.6 3.1 N 24 24 24 24 24 PINHv4.05 03/24/2008 R:03/24/2008WIL-447022Honeywell International Inc.HFO-1234yf-24-408of475INHALATION TABLE 5 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL DAILY MEAN CHAMBER VENTILATION RATE [SLPM] PHASE I

----------------------------------------------------------------------------------------------------------------------------------- DATE GROUP: 0 PPM 2500 PPM 4000 PPM 7500 PPM 4000 PPM

----------------------------------------------------------------------------------------------------------------------------------- 01/22/08 457. 339. 329. 323. 331. 01/23/08 448. 332. 332. 320. 330. 01/24/08 447. 325. 325. 327. 330. 01/25/08 442. 332. 334. 333. 336. 01/26/08 440. 328. 330. 328. 327. 01/27/08 439. 327. 328. 337. 329. 01/28/08 452. 330. 337. 329. 334. 01/29/08 447. 328. 332. 331. 326. 01/30/08 447. 328. 327. 327. 328. 01/31/08 442. 325. 329. 324. 320. 02/01/08 440. 334. 326. 329. 332. 02/02/08 442. 329. 326. 329. 327. 02/03/08 441. 328. 330. 326. 328. 02/04/08 439. 334. 331. 330. 328. 02/05/08 438. 331. 328. 326. 323. 02/06/08 443. 330. 329. 333. 325. 02/07/08 448. 326. 326. 326. 329. 02/08/08 445. 327. 328. 322. 323. 02/09/08 443. 326. 326. 318. 316. 02/10/08 441. 334. 329. 323. 328. 02/11/08 441. 336. 327. 324. 322. 02/12/08 437. 333. 324. 326. 320. 02/13/08 439. 332. 318. 328. 323. 02/14/08 443. 337. 337. 333. 325.

----------------------------------------------------------------------------------------------------------------------------------- GRAND MEAN 443. 330. 329. 327. 327. S.D. 4.7 3.9 4.1 4.5 4.7 C.V.(%) 1.1 1.2 1.2 1.4 1.4 N 24 24 24 24 24

SLPM = STANDARD LITERS PER MINUTE PINHv4.05 03/24/2008 R:03/24/2008WIL-447022Honeywell International Inc.HFO-1234yf-25-409of475INHALATION TABLE 6 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL DAILY MEAN CHAMBER VENTILATION RATE [SLPM] PHASE II

----------------------------------------------------------------------------------------------------------------------------------- DATE GROUP: 0 PPM 2500 PPM 5500 PPM 7500 PPM 5500 PPM

----------------------------------------------------------------------------------------------------------------------------------- 02/25/08 445. 338. 334. 330. 329. 02/26/08 441. 336. 329. 321. 328. 02/27/08 438. 335. 327. 337. 337. 02/28/08 439. 333. 324. 334. 333. 02/29/08 437. 337. 323. 336. 338. 03/01/08 436. 335. 322. 334. 335. 03/02/08 436. 335. 337. 334. 329. 03/03/08 436. 333. 336. 329. 325. 03/04/08 437. 333. 337. 330. 328. 03/05/08 452. 332. 336. 331. 325. 03/06/08 451. 331. 334. 334. 334. 03/07/08 450. 336. 335. 333. 329. 03/08/08 449. 337. 334. 338. 341. 03/09/08 449. 331. 334. 334. 332. 03/10/08 446. 330. 332. 336. 333. 03/11/08 444. 328. 330. 335. 334. 03/12/08 442. 326. 328. 330. 328. 03/13/08 441. 325. 327. 327. 325. 03/14/08 449. 330. 334. 330. 334. 03/15/08 447. 328. 337. 336. 335. 03/16/08 448. 329. 333. 338. 345. 03/17/08 448. 329. 333. 337. 330. 03/18/08 444. 334. 337. 330. 332. 03/19/08 447. 335. 337. 334. 333.

----------------------------------------------------------------------------------------------------------------------------------- GRAND MEAN 444. 332. 332. 333. 332. S.D. 5.3 3.6 4.7 4.0 5.0 C.V.(%) 1.2 1.1 1.4 1.2 1.5 N 24 24 24 24 24

SLPM = STANDARD LITERS PER MINUTE PINHv4.05 03/24/2008 R:03/24/2008WIL-447022Honeywell International Inc.HFO-1234yf-26-410of475INHALATION TABLE 7 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL DAILY OXYGEN CONTENT DETERMINATION [%] PHASE I

----------------------------------------------------------------------------------------------------------------------------------- DATE GROUP: 0 PPM 2500 PPM 4000 PPM 7500 PPM 4000 PPM

----------------------------------------------------------------------------------------------------------------------------------- 01/22/08 20.9 20.9 20.9 20.9 20.9 01/23/08 20.9 20.9 20.9 20.9 20.9 01/24/08 20.9 20.9 20.6 20.5 20.6 01/25/08 20.9 20.6 20.6 20.6 20.5 01/26/08 20.9 20.9 20.9 20.9 20.9 01/27/08 20.9 20.9 20.9 20.9 20.9 01/28/08 20.9 20.9 20.9 20.9 20.9 01/29/08 20.9 20.9 20.9 20.9 20.9 01/30/08 20.9 20.9 20.9 20.9 20.9 01/31/08 20.9 20.9 20.9 20.9 20.9 02/01/08 20.9 20.9 20.9 20.9 20.9 02/02/08 20.9 20.9 20.9 20.9 20.9 02/03/08 20.9 20.9 20.9 20.9 20.9 02/04/08 20.9 20.9 20.9 20.9 20.9 02/05/08 20.9 20.9 20.9 20.9 20.9 02/06/08 20.9 20.9 20.9 20.6 20.9 02/07/08 20.9 20.9 20.9 20.9 20.9 02/08/08 20.9 20.9 20.9 20.9 20.9 02/09/08 20.9 20.9 20.9 20.9 20.9 02/10/08 20.9 20.9 20.9 20.9 20.9 02/11/08 20.9 20.9 20.6 20.6 20.6 02/12/08 20.9 20.9 20.9 20.9 20.6 02/13/08 20.9 20.6 20.5 20.5 20.9 02/14/08 20.9 20.9 20.9 20.9 20.9

----------------------------------------------------------------------------------------------------------------------------------- GRAND MEAN 20.9 20.9 20.8 20.8 20.8 S.D. 0.00 0.08 0.13 0.14 0.13 C.V.(%) 0.000 0.383 0.625 0.673 0.625 N 24 24 24 24 24

MANUALv1.0 03/24/2008 R:03/25/2008WIL-447022Honeywell International Inc.HFO-1234yf-27-411of475INHALATION TABLE 8 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL DAILY OXYGEN CONTENT DETERMINATION [%] PHASE II

----------------------------------------------------------------------------------------------------------------------------------- DATE GROUP: 0 PPM 2500 PPM 5500 PPM 7500 PPM 5500 PPM

----------------------------------------------------------------------------------------------------------------------------------- 02/25/08 20.9 20.9 20.6 20.6 20.6 02/26/08 20.9 20.9 20.9 20.9 20.6 02/27/08 20.8 20.7 20.6 20.5 20.5 02/28/08 20.6 20.3 20.2 20.1 20.1 02/29/08 20.8 20.8 20.9 20.5 20.5 03/01/08 20.8 20.8 20.5 20.4 20.4 03/02/08 20.4 20.2 20.1 20.0 20.1 03/03/08 20.7 20.4 20.3 20.1 20.1 03/04/08 20.7 19.54 19.42 19.44 19.39 03/05/08 20.9 20.9 20.9 20.9 20.9 03/06/08 20.9 20.9 20.9 20.9 20.9 03/07/08 20.5 20.4 20.4 20.4 20.4 03/08/08 20.5 20.5 20.5 20.5 20.5 03/09/08 20.6 20.6 20.5 20.5 20.5 03/10/08 20.5 20.5 20.5 20.5 20.5 03/11/08 20.5 20.5 20.5 20.5 20.4 03/12/08 20.5 20.5 20.5 20.4 20.4 03/13/08 20.4 20.4 20.4 20.4 20.4 03/14/08 20.4 20.4 20.4 20.4 20.4 03/15/08 20.4 20.3 20.3 20.3 20.3 03/16/08 20.4 20.3 20.3 20.3 20.3 03/17/08 20.3 20.3 20.3 20.3 20.3 03/18/08 20.3 20.2 20.2 20.2 20.2 03/19/08 20.1 20.1 20.2 20.2 20.1

----------------------------------------------------------------------------------------------------------------------------------- GRAND MEAN 20.6 20.5 20.4 20.4 20.4 S.D. 0.23 0.32 0.32 0.31 0.30 C.V.(%) 1.117 1.561 1.569 1.520 1.471 N 24 24 24 24 24

MANUALv1.0 03/24/2008 R:06/18/2008WIL-447022Honeywell International Inc.HFO-1234yf-28-412of475INHALATION TABLE 9 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL TEST ATMOSPHERE HOMOGENEITY DETERMINATION

--------------------------------------------------------------------------------------------------------------------------------- TARGET: 2500 PPM CHAMBER #2

--------------------------------------------------------------------------------------------------------------------------------- DATE SAMPLING LOCATION CONCENTRATION (PPM) % FROM REFERENCE MEAN %

--------------------------------------------------------------------------------------------------------------------------------- 01/15/08 REFERENCE PORT 2498.7 UPPER FRONT 2472.7 -1.0

REFERENCE PORT 2516.0 UPPER FRONT 2487.0 -1.2

REFERENCE PORT 2504.3 UPPER FRONT 2479.3 -1.0 -1.1

REFERENCE PORT 2520.7 LOWER FRONT 2488.6 -1.3

REFERENCE PORT 2509.5 LOWER FRONT 2491.2 -0.7

REFERENCE PORT 2508.5 LOWER FRONT 2488.2 -0.8 -0.9

REFERENCE PORT 2531.6 UPPER REAR 2491.4 -1.6

REFERENCE PORT 2511.1 UPPER REAR 2485.7 -1.0

REFERENCE PORT 2512.7 UPPER REAR 2480.7 -1.3 -1.3

REFERENCE PORT 2520.2 LOWER REAR 2501.6 -0.7

REFERENCE PORT 2518.5 LOWER REAR 2487.2 -1.2

REFERENCE PORT 2500.4 LOWER REAR 2487.6 -0.5 -0.8

-------------------------------------------------------------------------------------------------------------------------------- PPM = PARTS PER MILLIONWIL-447022Honeywell International Inc.HFO-1234yf-29-413of475INHALATION TABLE 9 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL TEST ATMOSPHERE HOMOGENEITY DETERMINATION

--------------------------------------------------------------------------------------------------------------------------------- TARGET: 4000 PPM CHAMBER #3

--------------------------------------------------------------------------------------------------------------------------------- DATE SAMPLING LOCATION CONCENTRATION (PPM) % FROM REFERENCE MEAN %

--------------------------------------------------------------------------------------------------------------------------------- 01/15/08 REFERENCE PORT 4011.1 UPPER FRONT 3981.8 -0.7

REFERENCE PORT 3969.6 UPPER FRONT 3950.1 -0.5

REFERENCE PORT 3968.8 UPPER FRONT 3924.6 -1.1 -0.8

REFERENCE PORT 3999.0 LOWER FRONT 3980.1 -0.5

REFERENCE PORT 3973.3 LOWER FRONT 3934.7 -1.0

REFERENCE PORT 3934.7 LOWER FRONT 3913.8 -0.5 -0.7

REFERENCE PORT 3991.9 UPPER REAR 3956.8 -0.9

REFERENCE PORT 3956.1 UPPER REAR 3923.1 -0.8

REFERENCE PORT 3931.9 UPPER REAR 3914.8 -0.4 -0.7

REFERENCE PORT 3976.0 LOWER REAR 3934.4 -1.0

REFERENCE PORT 3958.4 LOWER REAR 3918.7 -1.0

REFERENCE PORT 3945.1 LOWER REAR 3913.1 -0.8 -0.9

-------------------------------------------------------------------------------------------------------------------------------- PPM = PARTS PER MILLIONWIL-447022Honeywell International Inc.HFO-1234yf-30-414of475INHALATION TABLE 9 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL TEST ATMOSPHERE HOMOGENEITY DETERMINATION

--------------------------------------------------------------------------------------------------------------------------------- TARGET: 7500 PPM CHAMBER #4

--------------------------------------------------------------------------------------------------------------------------------- DATE SAMPLING LOCATION CONCENTRATION (PPM) % FROM REFERENCE MEAN %

--------------------------------------------------------------------------------------------------------------------------------- 01/16/08 REFERENCE PORT 7560.6 UPPER FRONT 7440.8 -1.6

REFERENCE PORT 7545.5 UPPER FRONT 7401.8 -1.9

REFERENCE PORT 7503.2 UPPER FRONT 7390.5 -1.5 -1.7

REFERENCE PORT 7587.8 LOWER FRONT 7432.7 -2.0

REFERENCE PORT 7540.5 LOWER FRONT 7395.2 -1.9

REFERENCE PORT 7540.1 LOWER FRONT 7411.2 -1.7 -1.9

REFERENCE PORT 7545.9 UPPER REAR 7412.1 -1.8

REFERENCE PORT 7491.3 UPPER REAR 7343.9 -2.0

REFERENCE PORT 7546.2 UPPER REAR 7379.6 -2.2 -2.0

REFERENCE PORT 7555.4 LOWER REAR 7463.0 -1.2

REFERENCE PORT 7477.7 LOWER REAR 7321.5 -2.1

REFERENCE PORT 7543.4 LOWER REAR 7426.2 -1.6 -1.6

-------------------------------------------------------------------------------------------------------------------------------- PPM = PARTS PER MILLIONWIL-447022Honeywell International Inc.HFO-1234yf-31-415of475INHALATION TABLE 9 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL TEST ATMOSPHERE HOMOGENEITY DETERMINATION

--------------------------------------------------------------------------------------------------------------------------------- TARGET: 4000 PPM CHAMBER #5

--------------------------------------------------------------------------------------------------------------------------------- DATE SAMPLING LOCATION CONCENTRATION (PPM) % FROM REFERENCE MEAN %

--------------------------------------------------------------------------------------------------------------------------------- 01/18/08 REFERENCE PORT 4032.5 UPPER FRONT 3957.3 -1.9

REFERENCE PORT 3958.8 UPPER FRONT 3913.5 -1.1

REFERENCE PORT 3972.5 UPPER FRONT 3919.9 -1.3 -1.4

REFERENCE PORT 4012.8 LOWER FRONT 3951.3 -1.5

REFERENCE PORT 3979.4 LOWER FRONT 3917.4 -1.6

REFERENCE PORT 3964.3 LOWER FRONT 3930.4 -0.9 -1.3

REFERENCE PORT 3984.4 UPPER REAR 3914.4 -1.8

REFERENCE PORT 3968.5 UPPER REAR 3886.9 -2.1

REFERENCE PORT 3987.4 UPPER REAR 3929.9 -1.4 -1.8

REFERENCE PORT 3989.2 LOWER REAR 3912.7 -1.9

REFERENCE PORT 3958.4 LOWER REAR 3906.6 -1.3

REFERENCE PORT 3992.6 LOWER REAR 3945.9 -1.2 -1.5

-------------------------------------------------------------------------------------------------------------------------------- PPM = PARTS PER MILLION

MANUALv1.0 02/15/2008 R:06/18/2008WIL-447022Honeywell International Inc.HFO-1234yf-32-416of475INHALATION TABLE 10 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL DAILY NOMINAL CONCENTRATION [PPM] PHASE I

----------------------------------------------------------------------------------------------------------------------------------- DATE GROUP: 2500 PPM 4000 PPM 7500 PPM 4000 PPM

----------------------------------------------------------------------------------------------------------------------------------- 01/22/08 2337 3852 7357 3418 01/23/08 2402 3844 7477 3243 01/24/08 2387 3819 7117 3706 01/25/08 2468 3925 7382 3640 01/26/08 2332 3708 6995 3834 01/27/08 2339 3731 6808 3810 01/28/08 2384 3735 7173 3753 01/29/08 2332 3686 6932 3658 01/30/08 2382 3822 7167 3636 01/31/08 2404 3799 7233 3631 02/01/08 2290 3754 6974 3408 02/02/08 2308 3727 6924 3647 02/03/08 2315 3682 6988 3636 02/04/08 2257 3644 6853 3729 02/05/08 2278 3677 6938 3597 02/06/08 2400 3852 7136 3669 02/07/08 2313 3700 6938 3346 02/08/08 2289 3651 6973 3881 02/09/08 2229 3566 6854 3774 02/10/08 2273 3693 7053 3636 02/11/08 2244 3689 6980 3703 02/12/08 2379 3912 7289 3344 02/13/08 2238 3738 6795 3976 02/14/08 2302 3683 6989 3575

----------------------------------------------------------------------------------------------------------------------------------- GRAND MEAN 2328 3745 7055 3635 S.D. 62.0 89.5 186.5 177.7 C.V.(%) 2.66 2.39 2.64 4.89 N 24 24 24 24

MANUALv1.0 03/24/2008 R:06/18/2008WIL-447022Honeywell International Inc.HFO-1234yf-33-417of475INHALATION TABLE 11 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL DAILY NOMINAL CONCENTRATION [PPM] PHASE II

----------------------------------------------------------------------------------------------------------------------------------- DATE GROUP: 2500 PPM 5500 PPM 7500 PPM 5500 PPM

----------------------------------------------------------------------------------------------------------------------------------- 02/25/08 2277 5070 6998 5390 02/26/08 2173 4883 6825 4847 02/27/08 2312 5212 6896 5444 02/28/08 2297 5193 6869 5417 02/29/08 2343 5377 7049 5066 03/01/08 2401 5495 7224 5476 03/02/08 2622 5734 7889 5576 03/03/08 2341 5105 7109 5268 03/04/08 2371 5154 7177 5686 03/05/08 2378 5169 7155 5363 03/06/08 2400 5233 7135 5493 03/07/08 2306 5087 6979 5576 03/08/08 2313 5135 6920 5559 03/09/08 2400 5233 7135 5434 03/10/08 2422 5297 7137 5601 03/11/08 2415 5281 7094 5477 03/12/08 2361 5163 6998 5407 03/13/08 2368 5179 7062 5551 03/14/08 2392 5200 7177 5310 03/15/08 2407 5154 7049 5841 03/16/08 2385 5183 6963 5406 03/17/08 2385 5183 6984 5281 03/18/08 2334 5089 7087 5249 03/19/08 2312 5057 6958 5050

----------------------------------------------------------------------------------------------------------------------------------- GRAND MEAN 2363 5203 7078 5407 S.D. 78.6 162.2 202.4 214.0 C.V.(%) 3.33 3.12 2.86 3.96 N 24 24 24 24

MANUALv1.0 03/24/2008 R:06/18/2008WIL-447022Honeywell International Inc.HFO-1234yf-34-418of475INHALATION TABLE 12 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL DAILY MEAN TEST ATMOSPHERE CONCENTRATIONS [PPM] PHASE I

----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 PPM 2500 PPM 4000 PPM 7500 PPM 4000 PPM

----------------------------------------------------------------------------------------------------------------------------------- CH. NO. 1 2.0M3 CH. NO. 2 1.5M3 CH. NO. 3 1.5M3 CH. NO. 4 1.5M3 CH. NO. 5 1.5M3 CONC. CONC. CONC. CONC. CONC.

-----------------------------------------------------------------------------------------------------------------------------------

STUDY DAY: 0 MEAN 0. 2517. 4019. 7551. 4014. SD 0.0 40.9 75.9 72.4 42.9 CV(%) 0.00 1.62 1.89 0.96 1.07 N 10 10 10 10 10

STUDY DAY: 1 MEAN 0. 2518. 4023. 7535. 4027. SD 0.0 11.9 79.5 101.3 46.2 CV(%) 0.00 0.47 1.98 1.34 1.15 N 10 10 10 10 10

STUDY DAY: 2 MEAN 0. 2506. 3980. 7469. 4000. SD 0.0 51.5 123.8 103.6 112.4 CV(%) 0.00 2.05 3.11 1.39 2.81 N 10 10 10 10 10

STUDY DAY: 3 MEAN 0. 2501. 3976. 7477. 4003. SD 0.0 25.5 45.0 100.6 105.1 CV(%) 0.00 1.02 1.13 1.35 2.63 N 10 10 10 10 10

STUDY DAY: 4 MEAN 0. 2499. 3983. 7531. 4041. SD 0.0 29.2 101.4 134.2 55.6 CV(%) 0.00 1.17 2.55 1.78 1.38 N 10 10 10 10 10

CV (%) = COEFFICIENT OF VARIATION, CH. = CHAMBER, NO. = NUMBER, CONC. = CONCENTRATION CONCENTRATION IN: PPMWIL-447022Honeywell International Inc.HFO-1234yf-35-419of475INHALATION TABLE 12 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL DAILY MEAN TEST ATMOSPHERE CONCENTRATIONS [PPM] PHASE I

----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 PPM 2500 PPM 4000 PPM 7500 PPM 4000 PPM

----------------------------------------------------------------------------------------------------------------------------------- CH. NO. 1 2.0M3 CH. NO. 2 1.5M3 CH. NO. 3 1.5M3 CH. NO. 4 1.5M3 CH. NO. 5 1.5M3 CONC. CONC. CONC. CONC. CONC.

-----------------------------------------------------------------------------------------------------------------------------------

STUDY DAY: 5 MEAN 0. 2512. 3930. 7476. 4018. SD 0.0 21.8 108.2 114.8 85.0 CV(%) 0.00 0.87 2.75 1.54 2.11 N 10 10 10 10 10

STUDY DAY: 6 MEAN 0. 2485. 3995. 7490. 4031. SD 0.0 22.4 76.4 154.9 29.3 CV(%) 0.00 0.90 1.91 2.07 0.73 N 10 10 10 10 10

STUDY DAY: 7 MEAN 0. 2495. 4007. 7571. 4035. SD 0.0 37.4 66.9 53.7 30.6 CV(%) 0.00 1.50 1.67 0.71 0.76 N 10 10 10 10 10

STUDY DAY: 8 MEAN 0. 2507. 4011. 7536. 3974. SD 0.0 19.9 72.4 70.4 41.1 CV(%) 0.00 0.79 1.80 0.93 1.03 N 10 10 10 10 10

STUDY DAY: 9 MEAN 0. 2525. 4051. 7473. 3995. SD 0.0 24.0 54.8 37.0 42.0 CV(%) 0.00 0.95 1.35 0.50 1.05 N 10 10 10 10 10

CV (%) = COEFFICIENT OF VARIATION, CH. = CHAMBER, NO. = NUMBER, CONC. = CONCENTRATION CONCENTRATION IN: PPMWIL-447022Honeywell International Inc.HFO-1234yf-36-420of475INHALATION TABLE 12 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL DAILY MEAN TEST ATMOSPHERE CONCENTRATIONS [PPM] PHASE I

----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 PPM 2500 PPM 4000 PPM 7500 PPM 4000 PPM

----------------------------------------------------------------------------------------------------------------------------------- CH. NO. 1 2.0M3 CH. NO. 2 1.5M3 CH. NO. 3 1.5M3 CH. NO. 4 1.5M3 CH. NO. 5 1.5M3 CONC. CONC. CONC. CONC. CONC.

-----------------------------------------------------------------------------------------------------------------------------------

STUDY DAY: 10 MEAN 0. 2473. 4038. 7553. 3938. SD 0.0 22.8 114.6 130.7 54.3 CV(%) 0.00 0.92 2.84 1.73 1.38 N 10 10 10 10 10

STUDY DAY: 11 MEAN 0. 2489. 4069. 7553. 3981. SD 0.0 16.2 54.4 36.6 76.5 CV(%) 0.00 0.65 1.34 0.48 1.92 N 10 10 10 10 10

STUDY DAY: 12 MEAN 0. 2518. 3996. 7556. 4004. SD 0.0 40.0 71.3 33.8 58.7 CV(%) 0.00 1.59 1.78 0.45 1.47 N 10 10 10 10 10

STUDY DAY: 13 MEAN 0. 2483. 4004. 7487. 3964. SD 0.0 21.4 73.5 48.3 28.2 CV(%) 0.00 0.86 1.83 0.64 0.71 N 10 10 10 10 10

STUDY DAY: 14 MEAN 0. 2479. 4068. 7477. 4019. SD 0.0 48.4 85.8 113.2 35.7 CV(%) 0.00 1.95 2.11 1.51 0.89 N 10 10 10 10 10

CV (%) = COEFFICIENT OF VARIATION, CH. = CHAMBER, NO. = NUMBER, CONC. = CONCENTRATION CONCENTRATION IN: PPMWIL-447022Honeywell International Inc.HFO-1234yf-37-421of475INHALATION TABLE 12 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL DAILY MEAN TEST ATMOSPHERE CONCENTRATIONS [PPM] PHASE I

----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 PPM 2500 PPM 4000 PPM 7500 PPM 4000 PPM

----------------------------------------------------------------------------------------------------------------------------------- CH. NO. 1 2.0M3 CH. NO. 2 1.5M3 CH. NO. 3 1.5M3 CH. NO. 4 1.5M3 CH. NO. 5 1.5M3 CONC. CONC. CONC. CONC. CONC.

-----------------------------------------------------------------------------------------------------------------------------------

STUDY DAY: 15 MEAN 0. 2525. 4005. 7503. 4006. SD 0.0 40.1 133.8 87.8 18.8 CV(%) 0.00 1.59 3.34 1.17 0.47 N 10 10 10 10 10

STUDY DAY: 16 MEAN 0. 2510. 3972. 7488. 3978. SD 0.0 25.2 75.1 163.5 31.9 CV(%) 0.00 1.00 1.89 2.18 0.80 N 10 10 10 10 10

STUDY DAY: 17 MEAN 0. 2488. 3944. 7507. 4003. SD 0.0 12.9 43.2 32.7 52.0 CV(%) 0.00 0.52 1.10 0.44 1.30 N 10 10 10 10 10

STUDY DAY: 18 MEAN 0. 2463. 3951. 7538. 4101. SD 0.0 33.6 53.5 197.1 39.3 CV(%) 0.00 1.36 1.35 2.61 0.96 N 10 10 10 10 10

STUDY DAY: 19 MEAN 0. 2495. 3992. 7513. 4037. SD 0.0 52.0 86.2 186.6 37.7 CV(%) 0.00 2.08 2.16 2.48 0.93 N 10 10 10 10 10

CV (%) = COEFFICIENT OF VARIATION, CH. = CHAMBER, NO. = NUMBER, CONC. = CONCENTRATION CONCENTRATION IN: PPMWIL-447022Honeywell International Inc.HFO-1234yf-38-422of475INHALATION TABLE 12 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL DAILY MEAN TEST ATMOSPHERE CONCENTRATIONS [PPM] PHASE I

----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 PPM 2500 PPM 4000 PPM 7500 PPM 4000 PPM

----------------------------------------------------------------------------------------------------------------------------------- CH. NO. 1 2.0M3 CH. NO. 2 1.5M3 CH. NO. 3 1.5M3 CH. NO. 4 1.5M3 CH. NO. 5 1.5M3 CONC. CONC. CONC. CONC. CONC.

-----------------------------------------------------------------------------------------------------------------------------------

STUDY DAY: 20 MEAN 0. 2512. 3916. 7581. 3988. SD 0.0 51.7 31.0 114.4 89.4 CV(%) 0.00 2.06 0.79 1.51 2.24 N 10 10 10 10 10

STUDY DAY: 21 MEAN 0. 2524. 3891. 7514. 4103. SD 0.0 26.6 49.6 55.2 38.0 CV(%) 0.00 1.05 1.28 0.73 0.93 N 10 10 10 10 10

STUDY DAY: 22 MEAN 0. 2542. 3906. 7454. 4055. SD 0.0 34.5 31.6 68.3 44.2 CV(%) 0.00 1.36 0.81 0.92 1.09 N 10 10 10 10 10

STUDY DAY: 23 MEAN 0. 2526. 3837. 7450. 3988. SD 0.0 20.8 143.0 43.0 102.7 CV(%) 0.00 0.82 3.73 0.58 2.58 N 10 10 10 10 10

STUDY DAYS 0 THROUGH 23 MEAN 0. 2504. 3982. 7512. 4013. SD 0.0 19.4 56.5 38.1 38.4 CV(%) 0.00 0.78 1.42 0.51 0.96 N 24 24 24 24 24

-----------------------------------------------------------------------------------------------------------------------------------

CV (%) = COEFFICIENT OF VARIATION, CH. = CHAMBER, NO. = NUMBER, CONC. = CONCENTRATION CONCENTRATION IN: PPM PCHCSUv4.06 03/25/2008 R:06/19/2008WIL-447022Honeywell International Inc.HFO-1234yf-39-423of475INHALATION TABLE 13 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 1 SPONSOR:HONEYWELL DAILY MEAN TEST ATMOSPHERE CONCENTRATIONS [PPM] PHASE II

----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 PPM 2500 PPM 5500 PPM 7500 PPM 5500 PPM

----------------------------------------------------------------------------------------------------------------------------------- CH. NO. 1 2.0M3 CH. NO. 2 1.5M3 CH. NO. 3 1.5M3 CH. NO. 4 1.5M3 CH. NO. 5 1.5M3 CONC. CONC. CONC. CONC. CONC.

-----------------------------------------------------------------------------------------------------------------------------------

STUDY DAY: 0 MEAN 0. 2484. 5529. 7529. 5527. SD 0.0 25.8 94.3 57.8 139.9 CV(%) 0.00 1.04 1.71 0.77 2.53 N 10 10 10 10 10

STUDY DAY: 1 MEAN 0. 2521. 5412. 7630. 5486. SD 0.0 18.3 99.7 144.8 82.9 CV(%) 0.00 0.73 1.84 1.90 1.51 N 10 10 10 10 10

STUDY DAY: 2 MEAN 0. 2497. 5472. 7393. 5508. SD 0.0 51.9 98.7 256.6 146.6 CV(%) 0.00 2.08 1.80 3.47 2.66 N 10 10 10 10 10

STUDY DAY: 3 MEAN 0. 2536. 5449. 7465. 5640. SD 0.0 25.9 121.3 60.9 74.5 CV(%) 0.00 1.02 2.23 0.82 1.32 N 10 10 10 10 10

STUDY DAY: 4 MEAN 0. 2400. 5360. 7261. 5592. SD 0.0 61.6 190.6 172.7 221.4 CV(%) 0.00 2.57 3.56 2.38 3.96 N 10 10 10 10 10

CV (%) = COEFFICIENT OF VARIATION, CH. = CHAMBER, NO. = NUMBER, CONC. = CONCENTRATION CONCENTRATION IN: PPMWIL-447022Honeywell International Inc.HFO-1234yf-40-424of475INHALATION TABLE 13 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 2 SPONSOR:HONEYWELL DAILY MEAN TEST ATMOSPHERE CONCENTRATIONS [PPM] PHASE II

----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 PPM 2500 PPM 5500 PPM 7500 PPM 5500 PPM

----------------------------------------------------------------------------------------------------------------------------------- CH. NO. 1 2.0M3 CH. NO. 2 1.5M3 CH. NO. 3 1.5M3 CH. NO. 4 1.5M3 CH. NO. 5 1.5M3 CONC. CONC. CONC. CONC. CONC.

-----------------------------------------------------------------------------------------------------------------------------------

STUDY DAY: 5 MEAN 0. 2492. 5482. 7153. 5652. SD 0.0 299.2 470.2 439.4 410.0 CV(%) 0.00 12.01 8.58 6.14 7.25 N 10 10 10 10 10

STUDY DAY: 6 MEAN 0. 2219. 4554. 6696. 4455. SD 0.0 157.2 522.7 467.7 479.8 CV(%) 0.00 7.08 11.48 6.99 10.77 N 10 12 12 12 12

STUDY DAY: 7 MEAN 0. 2486. 5307. 7575. 5470. SD 0.0 62.6 144.2 81.1 93.9 CV(%) 0.00 2.52 2.72 1.07 1.72 N 9 6 6 6 6

STUDY DAY: 8 MEAN 0. 2415. 5328. 7377. 5263. SD 0.0 63.9 190.3 40.7 142.7 CV(%) 0.00 2.64 3.57 0.55 2.71 N 10 10 9 9 9

STUDY DAY: 9 MEAN 0. 2450. 5431. 7435. 5434. SD 0.0 23.7 131.7 46.7 121.8 CV(%) 0.00 0.97 2.42 0.63 2.24 N 10 10 10 10 10

CV (%) = COEFFICIENT OF VARIATION, CH. = CHAMBER, NO. = NUMBER, CONC. = CONCENTRATION CONCENTRATION IN: PPMWIL-447022Honeywell International Inc.HFO-1234yf-41-425of475INHALATION TABLE 13 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 3 SPONSOR:HONEYWELL DAILY MEAN TEST ATMOSPHERE CONCENTRATIONS [PPM] PHASE II

----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 PPM 2500 PPM 5500 PPM 7500 PPM 5500 PPM

----------------------------------------------------------------------------------------------------------------------------------- CH. NO. 1 2.0M3 CH. NO. 2 1.5M3 CH. NO. 3 1.5M3 CH. NO. 4 1.5M3 CH. NO. 5 1.5M3 CONC. CONC. CONC. CONC. CONC.

-----------------------------------------------------------------------------------------------------------------------------------

STUDY DAY: 10 MEAN 0. 2493. 5383. 7412. 5419. SD 0.0 15.0 69.8 40.5 50.4 CV(%) 0.00 0.60 1.30 0.55 0.93 N 10 10 10 10 10

STUDY DAY: 11 MEAN 0. 2400. 5311. 7469. 5558. SD 0.0 25.3 54.2 78.4 101.1 CV(%) 0.00 1.05 1.02 1.05 1.82 N 10 10 10 10 10

STUDY DAY: 12 MEAN 0. 2468. 5504. 7496. 5496. SD 0.0 33.0 147.0 112.8 123.6 CV(%) 0.00 1.34 2.67 1.50 2.25 N 10 10 10 10 10

STUDY DAY: 13 MEAN 0. 2509. 5552. 7549. 5532. SD 0.0 46.5 46.7 70.4 64.8 CV(%) 0.00 1.85 0.84 0.93 1.17 N 10 10 10 10 10

STUDY DAY: 14 MEAN 0. 2546. 5536. 7578. 5510. SD 0.0 18.0 82.5 164.7 109.0 CV(%) 0.00 0.71 1.49 2.17 1.98 N 10 10 10 10 10

CV (%) = COEFFICIENT OF VARIATION, CH. = CHAMBER, NO. = NUMBER, CONC. = CONCENTRATION CONCENTRATION IN: PPMWIL-447022Honeywell International Inc.HFO-1234yf-42-426of475INHALATION TABLE 13 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 4 SPONSOR:HONEYWELL DAILY MEAN TEST ATMOSPHERE CONCENTRATIONS [PPM] PHASE II

----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 PPM 2500 PPM 5500 PPM 7500 PPM 5500 PPM

----------------------------------------------------------------------------------------------------------------------------------- CH. NO. 1 2.0M3 CH. NO. 2 1.5M3 CH. NO. 3 1.5M3 CH. NO. 4 1.5M3 CH. NO. 5 1.5M3 CONC. CONC. CONC. CONC. CONC.

-----------------------------------------------------------------------------------------------------------------------------------

STUDY DAY: 15 MEAN 0. 2525. 5475. 7506. 5529. SD 0.0 12.7 82.0 46.0 87.0 CV(%) 0.00 0.50 1.50 0.61 1.57 N 10 10 10 10 10

STUDY DAY: 16 MEAN 0. 2506. 5494. 7502. 5506. SD 0.0 28.3 147.0 63.3 58.9 CV(%) 0.00 1.13 2.68 0.84 1.07 N 10 10 10 10 10

STUDY DAY: 17 MEAN 0. 2557. 5519. 7547. 5562. SD 0.0 9.1 120.8 120.6 63.0 CV(%) 0.00 0.36 2.19 1.60 1.13 N 10 10 10 10 10

STUDY DAY: 18 MEAN 0. 2516. 5475. 7525. 5522. SD 0.0 8.7 60.6 77.8 67.1 CV(%) 0.00 0.34 1.11 1.03 1.22 N 10 10 10 10 10

STUDY DAY: 19 MEAN 0. 2539. 5413. 7516. 5674. SD 0.0 15.8 60.6 87.7 47.8 CV(%) 0.00 0.62 1.12 1.17 0.84 N 10 10 10 10 10

CV (%) = COEFFICIENT OF VARIATION, CH. = CHAMBER, NO. = NUMBER, CONC. = CONCENTRATION CONCENTRATION IN: PPMWIL-447022Honeywell International Inc.HFO-1234yf-43-427of475INHALATION TABLE 13 PROJECT NO.:WIL-447022I INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 5 SPONSOR:HONEYWELL DAILY MEAN TEST ATMOSPHERE CONCENTRATIONS [PPM] PHASE II

----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 PPM 2500 PPM 5500 PPM 7500 PPM 5500 PPM

----------------------------------------------------------------------------------------------------------------------------------- CH. NO. 1 2.0M3 CH. NO. 2 1.5M3 CH. NO. 3 1.5M3 CH. NO. 4 1.5M3 CH. NO. 5 1.5M3 CONC. CONC. CONC. CONC. CONC.

-----------------------------------------------------------------------------------------------------------------------------------

STUDY DAY: 20 MEAN 0. 2516. 5427. 7470. 5519. SD 0.0 18.1 36.0 47.9 101.4 CV(%) 0.00 0.72 0.66 0.64 1.84 N 10 10 10 10 10

STUDY DAY: 21 MEAN 0. 2455. 5447. 7456. 5503. SD 0.0 22.0 75.4 53.5 119.9 CV(%) 0.00 0.89 1.38 0.72 2.18 N 10 10 10 10 10

STUDY DAY: 22 MEAN 0. 2483. 5442. 7562. 5550. SD 0.0 15.9 49.7 96.1 150.3 CV(%) 0.00 0.64 0.91 1.27 2.71 N 10 10 10 10 10

STUDY DAY: 23 MEAN 0. 2484. 5482. 7472. 5584. SD 0.0 9.6 120.0 29.4 126.0 CV(%) 0.00 0.38 2.19 0.39 2.26 N 10 10 10 10 10

STUDY DAYS 0 THROUGH 23 MEAN 0. 2479. 5408. 7441. 5479. SD 0.0 69.8 194.3 189.1 233.2 CV(%) 0.00 2.82 3.59 2.54 4.26 N 24 24 24 24 24

-----------------------------------------------------------------------------------------------------------------------------------

CV (%) = COEFFICIENT OF VARIATION, CH. = CHAMBER, NO. = NUMBER, CONC. = CONCENTRATION CONCENTRATION IN: PPM PCHCSUv4.06 04/08/2008 R:06/19/2008WIL-447022Honeywell International Inc.HFO-1234yf-44-428of475

## WIL-447022 HFO-1234yf Honeywell International Inc.



# APPENDIX E

Animal Room Environmental Conditions

429 of 475TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY447022HONEYWELLINHALATION PRENATAL DEV TOX STUDY OF HFO-1234YF IN RABBITSSPONSOR:PROJECT NO.:WILPAGE 144702201/18/0810:0010:0003/20/08STUDY SPECIFICATIONS:DATE IN:TIME IN:DATE OUT:TIME OUT:B ROOM 43RABBITLOW TEMPERATURE oF:61.0 HIGH TEMPERATURE oF:71.0LOW HUMIDITY:30.0HIGH HUMIDITY:70.0ROOM SPECIFICATIONS:SPECIES:TEMPERATURE HUMIDITYMEAN (oF)DATEMEAN (%RH)LOW TEMPERATURE oC:16.1 HIGH TEMPERATURE oC:21.7MEAN (oC)65.5 51.818-Jan-08 18.665.4 52.719-Jan-08 18.665.5 53.020-Jan-08 18.665.4 53.621-Jan-08 18.665.5 53.122-Jan-08 18.665.4 53.323-Jan-08 18.565.6 53.524-Jan-08 18.765.6 52.925-Jan-08 18.665.5 53.526-Jan-08 18.665.5 53.627-Jan-08 18.665.4 54.328-Jan-08 18.565.6 54.129-Jan-08 18.765.6 53.830-Jan-08 18.665.5 54.031-Jan-08 18.665.5 54.201-Feb-08 18.665.7 53.602-Feb-08 18.765.8 54.403-Feb-08 18.865.5 55.904-Feb-08 18.665.4 58.505-Feb-08 18.665.7 54.506-Feb-08 18.765.3 54.507-Feb-08 18.565.7 53.208-Feb-08 18.765.7 54.709-Feb-08 18.74/29/2008 15:06REPORT 4VERSION 1.09NOTE: + = VALUE WAS GREATER THAN HIGH RANGE- = VALUE WAS LESS THAN LOW RANGENOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES



## 430 of 475TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY447022HONEYWELLINHALATION PRENATAL DEV TOX STUDY OF HFO-1234YF IN RABBITSSPONSOR:PROJECT NO.:WILPAGE 244702201/18/0810:0010:0003/20/08STUDY SPECIFICATIONS:DATE IN:TIME IN:DATE OUT:TIME OUT:B ROOM 43RABBITLOW TEMPERATURE oF:61.0 HIGH TEMPERATURE oF:71.0LOW HUMIDITY:30.0HIGH HUMIDITY:70.0ROOM SPECIFICATIONS:SPECIES:TEMPERATURE HUMIDITYMEAN (oF)DATEMEAN (%RH)LOW TEMPERATURE oC:16.1 HIGH TEMPERATURE oC:21.7MEAN (oC)65.7 50.810-Feb-08 18.765.6 53.811-Feb-08 18.765.4 52.812-Feb-08 18.565.9 52.913-Feb-08 18.865.6 53.114-Feb-08 18.765.9 54.215-Feb-08 18.865.9 50.416-Feb-08 18.866.1 51.317-Feb-08 19.065.6 52.018-Feb-08 18.765.9 50.119-Feb-08 18.865.9 50.020-Feb-08 18.865.8 51.121-Feb-08 18.865.7 51.822-Feb-08 18.765.6 52.523-Feb-08 18.765.5 53.024-Feb-08 18.665.7 53.325-Feb-08 18.765.5 52.026-Feb-08 18.665.3 52.727-Feb-08 18.565.6 52.228-Feb-08 18.665.5 52.529-Feb-08 18.665.8 52.001-Mar-08 18.865.6 52.302-Mar-08 18.665.5 53.003-Mar-08 18.64/29/2008 15:06REPORT 4VERSION 1.09NOTE: + = VALUE WAS GREATER THAN HIGH RANGE- = VALUE WAS LESS THAN LOW RANGENOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES



## 431 of 475TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY447022HONEYWELLINHALATION PRENATAL DEV TOX STUDY OF HFO-1234YF IN RABBITSSPONSOR:PROJECT NO.:WILPAGE 344702201/18/0810:0010:0003/20/08STUDY SPECIFICATIONS:DATE IN:TIME IN:DATE OUT:TIME OUT:B ROOM 43RABBITLOW TEMPERATURE oF:61.0 HIGH TEMPERATURE oF:71.0LOW HUMIDITY:30.0HIGH HUMIDITY:70.0ROOM SPECIFICATIONS:SPECIES:TEMPERATURE HUMIDITYMEAN (oF)DATEMEAN (%RH)LOW TEMPERATURE oC:16.1 HIGH TEMPERATURE oC:21.7MEAN (oC)65.6 51.804-Mar-08 18.665.8 51.405-Mar-08 18.865.7 52.506-Mar-08 18.765.7 51.807-Mar-08 18.765.8 51.908-Mar-08 18.865.7 50.709-Mar-08 18.765.7 51.810-Mar-08 18.765.6 53.111-Mar-08 18.665.7 52.512-Mar-08 18.765.7 51.613-Mar-08 18.765.3 52.814-Mar-08 18.565.7 52.315-Mar-08 18.765.7 51.816-Mar-08 18.765.5 51.717-Mar-08 18.665.6 51.618-Mar-08 18.765.5 53.919-Mar-08 18.665.7 54.720-Mar-08 18.74/29/2008 15:06REPORT 4VERSION 1.09NOTE: + = VALUE WAS GREATER THAN HIGH RANGE- = VALUE WAS LESS THAN LOW RANGENOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES



## 432 of 475TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY447022HONEYWELLINHALATION PRENATAL DEV TOX STUDY OF HFO-1234YF IN RABBITSSPONSOR:PROJECT NO.:WILPAGE 444702201/18/0810:0010:0003/20/08STUDY SPECIFICATIONS:DATE IN:TIME IN:DATE OUT:TIME OUT:B ROOM 43RABBITLOW TEMPERATURE oF:61.0 HIGH TEMPERATURE oF:71.0LOW HUMIDITY:30.0HIGH HUMIDITY:70.0ROOM SPECIFICATIONS:SPECIES:TEMPERATURE HUMIDITYMEAN (oF)DATEMEAN (%RH)LOW TEMPERATURE oC:16.1 HIGH TEMPERATURE oC:21.7MEAN (oC)65.6TEMPERATURE oF 65.3 66.158.550.052.863MEAN MINMAX18.7TEMPERATURE oC 18.5 19.0HUMIDITY (%RH)**GRAND STATS**N DAYS4/29/2008 15:06REPORT 4VERSION 1.09NOTE: + = VALUE WAS GREATER THAN HIGH RANGE- = VALUE WAS LESS THAN LOW RANGENOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES



## 433 of 475TEMPERATURE/HUMIDITY - END OF STUDY SUMMARY REPORT447022HONEYWELLINHALATION PRENATAL DEV TOX STUDY OF HFO-1234YF IN RABBITSSPONSOR:PROJECT NO.:WIL-15:0829-Apr-08PAGE 1B ROOM 43RABBITLOW TEMPERATURE: 61.0HIGH TEMPERATURE: 71.0LOW HUMIDITY: 30.0HIGH HUMIDITY: 70.0ROOM SPECIFICATIONS:SPECIES:TEMPERATURE HUMIDITY01/18/0810:0010:0003/20/08DATE IN:TIME IN:DATE OUT:TIME OUT:**ROOM B ROOM 43 SUMMARY**MEANMINMAX65.664.268.052.812.287.20.633.07SDNSAMPLES14851485NDAYSFIRST DAYLAST DAY01/18/0803/20/08634/29/2008 15:08REPORT 5VERSION 1.10NOTE: TEMPERATURE UNITS = DEGREES FAHRENHEITHUMIDITY UNITS = % RELATIVE HUMIDITYNOTE: MEANS REPRESENT THE MEAN OF ALL VALUES



## 434 of 475TEMPERATURE/HUMIDITY - END OF STUDY SUMMARY REPORT447022HONEYWELLINHALATION PRENATAL DEV TOX STUDY OF HFO-1234YF IN RABBITSSPONSOR:PROJECT NO.:WIL-15:0829-Apr-08PAGE 2**STUDY 447022 SUMMARY**MEANMINMAX65.664.268.052.812.287.20.633.07SDNSAMPLES14851485FIRST DAYLAST DAY01/18/0803/20/08NDAYS634/29/2008 15:08REPORT 5VERSION 1.10NOTE: TEMPERATURE UNITS = DEGREES FAHRENHEITHUMIDITY UNITS = % RELATIVE HUMIDITYNOTE: MEANS REPRESENT THE MEAN OF ALL VALUES



## 435 of 475

## WIL-447022 HFO-1234yf Honeywell International Inc.



# APPENDIX F

WIL Developmental Historical Control Data

Version 1.1 [New Zealand White Rabbits]

436 of 475Mean MaxSEMS.D. Median MinTotal75thQuartile25thQuartileMean of StudyMeansEndpointMean Gravid Uterine Weight (g)Total No. of Animals in the Control GroupTotal No. Viable FetusesMean No. Viable Fetuses/DamMean No. Postimplantation Loss/DamViable Fetuses (%/Litter)Postimplantation Loss (%/Litter)Total No. of Postimplantation LossesLate Resorptions (%/Litter)Early Resorptions (%/Litter)Mean No. Implantations/DamDead Fetuses (%/Litter)Mean No. Preimplantation Loss/DamMean No. Corpora Lutea/DamPreimplantation Loss (%/Litter)Total No. Preimplantation LossesTotal No. Female FetusesTotal No. Male FetusesMean Male Body Weight (g)Mean Fetal Body Weight (g)Mean Female Body Weight (g)325496.98.8263695.80.41174.22.61.50.19.210.00.72187.31339129741.240.140.624.480.461.400.131.401.360.710.390.470.370.353.531.561.751.65443.18.092.70.11.10.50.50.08.49.30.32.538.837.438.0532.89.698.90.67.35.72.81.510.210.61.312.443.642.743.0NO. OF DATASETSNo. of Animals Examined at LaparohysterectomyNo. of Animals That DiedNo. of Animals That AbortedPercent PregnantNo. GravidNo. With Only ResorptionsNo. of Dams With Live FetusesNo. Nongravid% Females/Litter% Males/Litter95.5 92.0 96.06.540.120.370.030.370.360.100.130.100.090.940.190.440.420.47503.2 478.3 512.28.9 8.6 9.195.9 95.3 96.30.4 0.3 0.44.1 3.7 4.72.4 1.9 2.70.0 0.0 0.09.3 8.9 9.59.9 9.7 10.30.6 0.5 1.05.8 4.4 10.51.5 0.9 1.941.1 39.3 42.041.4 40.2 42.140.6 38.6 41.41441305029820318No. of Animals That Delivered293.8 4.601.2385.0100.050.7 4.49 1.2049.3 4.49 1.20 42.8 55.544.5 57.250.149.947.0 54.445.6 53.0WIL Developmental Historical ControlHra:(NZW)SPF RabbitPage 1 of 11New Zealand Rabbit Time-Mated [Kalamazoo] EFD v.1.1



## 437 of 475Mean of StudyMeansMALFORMATIONS (% Per Litter)Mean MaxSEMS.D. Median Min75thQuartile25thQuartileNO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally26362636263629829829814TOTAL EXTERNAL MALFORMATIONS 0.4 0.43 0.00.11 0.2 0.00.71.1TOTAL VISCERAL MALFORMATIONS 1.2 0.98 0.00.26 1.0 0.51.73.0TOTAL SKELETAL MALFORMATIONS 1.1 0.60 0.00.16 1.1 0.81.32.2EXTERNAL2Carpal and/or Tarsal Flexure 0.0 0.14 0.00.04 0.0 0.00.00.5Cleft Palate 0.1 0.18 0.00.05 0.0 0.00.00.6Ectrodactyly 0.0 0.12 0.00.03 0.0 0.00.00.4Exencephaly with or without Open Eyelid(s) 0.1 0.18 0.00.05 0.0 0.00.00.5Gastroschisis 0.1 0.21 0.00.06 0.0 0.00.00.6Microphthalmia and/or Anophthalmia 0.1 0.24 0.00.06 0.0 0.00.00.9Tail- Short 0.1 0.21 0.00.06 0.0 0.00.00.6VISCERAL3Bulbous Aorta 0.1 0.17 0.00.05 0.0 0.00.00.5Diaphragmatic Hernia 0.1 0.21 0.00.06 0.0 0.00.00.8Heart- Misshapen 0.0 0.11 0.00.03 0.0 0.00.00.4Hydrocephaly 0.1 0.33 0.00.09 0.0 0.00.00.9Lung(s)- Lobular Agenesis 0.5 0.75 0.00.20 0.0 0.00.82.4Lung(s)- Lobular Dysgenesis 0.0 0.17 0.00.04 0.0 0.00.00.6Persistent Truncus Arteriosus 0.2 0.59 0.00.16 0.0 0.00.02.1Stenotic Pulmonary Trunk 0.0 0.14 0.00.04 0.0 0.00.00.5Thyroid Gland(s)- Absent 0.2 0.79 0.00.21 0.0 0.00.02.9Transposition of the Great Vessels 0.0 0.17 0.00.04 0.0 0.00.00.6SKELETAL4Costal Cartilage Anomaly 0.1 0.32 0.00.08 0.0 0.00.01.1WIL Developmental Historical ControlHra:(NZW)SPF RabbitPage 2 of 11New Zealand Rabbit Time-Mated [Kalamazoo] EFD v.1.1



## 438 of 475Mean of StudyMeansMALFORMATIONS (% Per Litter)Mean MaxSEMS.D. Median Min75thQuartile25thQuartileNO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally26362636263629829829814SKELETAL4Rib Anomaly 0.2 0.34 0.00.09 0.0 0.00.31.2Skull Anomaly 0.1 0.24 0.00.06 0.0 0.00.00.8Sternebra(e)- Fused 0.2 0.26 0.00.07 0.0 0.00.30.7Sternebra(e)- Malaligned (Severe) 0.1 0.30 0.00.08 0.0 0.00.01.0Vertebral Anomaly with or without Associated Rib Anomaly 0.5 0.42 0.00.11 0.4 0.00.81.3Vertebral Centra Anomaly 0.1 0.23 0.00.06 0.0 0.00.00.7WIL Developmental Historical ControlHra:(NZW)SPF RabbitPage 3 of 11New Zealand Rabbit Time-Mated [Kalamazoo] EFD v.1.1



## 439 of 475Mean of StudyMeans2VARIATIONS (% Per Litter)Mean MaxSEMS.D. Median Min75thQuartile25thQuartileNO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally26362636263629829829814TOTAL EXTERNAL VARIATIONS 0.0 0.00 0.00.00 0.0 0.00.00.0TOTAL VISCERAL VARIATIONS 25.4 5.12 17.31.37 23.7 22.527.935.4TOTAL SKELETAL VARIATIONS 61.6 6.24 52.91.67 63.0 56.265.371.1VISCERAL3Gallbladder- Absent or Small 2.5 1.43 0.00.38 2.4 1.53.35.4Gallbladder- Bilobed 0.0 0.12 0.00.03 0.0 0.00.00.4Heart- Extra Papillary Muscle 2.7 1.74 0.00.46 2.7 2.03.17.8Heart- Small 0.1 0.21 0.00.06 0.0 0.00.00.8Hemorrhagic Ring Around the Iris 0.2 0.47 0.00.13 0.0 0.00.01.4Liver- Pale 0.1 0.23 0.00.06 0.0 0.00.00.9Major Blood Vessel Variation 7.7 2.66 3.00.71 7.8 5.69.712.5Pancreas- Small 0.1 0.21 0.00.06 0.0 0.00.00.8Retrocaval Ureter(s) 1.6 1.39 0.00.37 1.3 0.52.64.0Spleen- Accessory 13.1 4.01 8.41.07 12.4 10.114.521.9Spleen- Pale 0.4 0.56 0.00.15 0.0 0.00.51.6Spleen- Small 0.1 0.14 0.00.04 0.0 0.00.00.4Thymus- Hemorrhagic 0.6 0.76 0.00.20 0.0 0.01.12.1Thyroid Gland(s)- Enlarged 0.1 0.33 0.00.09 0.0 0.00.01.3SKELETAL413th Full Rib(s) 33.4 8.63 16.52.31 33.7 28.141.045.713th Rudimentary Rib(s) 18.4 4.18 10.31.12 17.8 16.518.827.825 Presacral Vertebrae 0.3 0.71 0.00.19 0.0 0.00.42.527 Presacral Vertebrae 8.6 2.98 4.80.80 7.5 6.810.515.628 Presacral Vertebrae 0.0 0.11 0.00.03 0.0 0.00.00.47th Cervical Rib(s) 1.9 1.06 0.50.28 1.7 1.02.73.7WIL Developmental Historical ControlHra:(NZW)SPF RabbitPage 4 of 11New Zealand Rabbit Time-Mated [Kalamazoo] EFD v.1.1



## 440 of 475Mean of StudyMeans2VARIATIONS (% Per Litter)Mean MaxSEMS.D. Median Min75thQuartile25thQuartileNO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally26362636263629829829814SKELETAL47th Sternebra 0.0 0.17 0.00.04 0.0 0.00.00.6Extra Site of Ossification Anterior to Sternebra #1 1.3 0.75 0.00.20 1.2 0.91.52.8Extra Site of Ossification Ventral to Cervical Centrum #2 0.0 0.13 0.00.03 0.0 0.00.00.5Hyoid Arch(es) Bent 5.2 1.63 1.30.43 5.3 5.06.07.6Hyoid Body and/or Arch(es) Unossified 0.3 0.41 0.00.11 0.0 0.00.41.3Reduced Ossification of the Skull 0.2 0.28 0.00.08 0.0 0.00.30.9Skull Bone(s)- Accessory 0.3 0.34 0.00.09 0.2 0.00.50.9Sternebra(e) #5 and/or #6 Unossified 8.6 4.69 3.91.25 6.8 5.210.518.5Sternebra(e)- Malaligned (Slight or Moderate) 0.7 0.51 0.00.14 0.7 0.50.92.1Sternebrae with Thread-Like Attachment 1.1 0.95 0.00.25 0.8 0.51.93.2Vertebral Centra Not Fully Ossified 0.0 0.17 0.00.04 0.0 0.00.00.6WIL Developmental Historical ControlHra:(NZW)SPF RabbitPage 5 of 11New Zealand Rabbit Time-Mated [Kalamazoo] EFD v.1.1



## 441 of 475Modal Distribution of Fetal Body Weights40.0-40.9No. of Datasets in Historical ControlRange of Study DatesNo. of Dams in Historical ControlNo. of Dams with Live FetusesMean Fetal Body Weight Range (g)41.0-41.9 42.0-42.9 43.0-43.938.0-38.9 39.0-39.1Mean Fetal Body Weight (g)32529843.038.0 -146/10/20078/22/2006 -2Total No. DatasetsMean Litter SizeLitter Size Range8.98.98.8 -49.19.68.1 -18.78.78.7 -39.09.38.9 -38.69.18.0 -18.48.4 8.4-WIL Developmental Historical ControlHra:(NZW)SPF RabbitPage 6 of 11New Zealand Rabbit Time-Mated [Kalamazoo] EFD v.1.1



## 442 of 475Distribution of Spontaneous Litter ComplicationsNo. ofSitesDistribution ofImplantation SitesNo. ofAnimals PercentNo. ofAnimals PercentNo. ofAnimals PercentNo. ofAnimalsFemales with CompleteLitter ResorptionFemales thatDelivered/AbortedTotal AbnormalReproductive Outcomes2 0 0.0 50.01 1 50.021 0 0.0 0.00 0 0.033 0 0.0 0.00 0 0.045 0 0.0 0.00 0 0.057 0 0.0 0.00 0 0.0623 0 0.0 0.00 0 0.0759 0 0.0 0.00 0 0.0871 0 0.0 0.00 0 0.0959 0 0.0 0.00 0 0.01037 0 0.0 2.71 1 2.71121 0 0.0 4.81 1 4.81211 0 0.0 0.00 0 0.0132 0 0.0 0.00 0 0.014Total No. Gravid Does:Total No. Datasets:Years:Average Litter Size:146/10/20078/22/2006 -3058.8WIL Developmental Historical ControlHra:(NZW)SPF RabbitPage 7 of 11New Zealand Rabbit Time-Mated [Kalamazoo] EFD v.1.1



## 443 of 475Summary Incidence Malformations and Variations(Total Number Fetuses/Litters Affected)Ranked Uppermost to NethermostMALFORMATIONSNO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally263626362636298298298Fetuses LittersNumber14EXTERNAL2Tail- Short 3 3Cleft Palate 2 2Exencephaly with or without Open Eyelid(s) 2 2Gastroschisis 2 2Carpal and/or Tarsal Flexure 1 1Ectrodactyly 1 1Microphthalmia and/or Anophthalmia 1 1VISCERAL3Lung(s)- Lobular Agenesis 13 9Hydrocephaly 3 2Bulbous Aorta 2 2Persistent Truncus Arteriosus 2 2Diaphragmatic Hernia 1 1Heart- Misshapen 1 1Lung(s)- Lobular Dysgenesis 1 1Stenotic Pulmonary Trunk 1 1Thyroid Gland(s)- Absent 1 1Transposition of the Great Vessels 1 1SKELETAL4Vertebral Anomaly with or without Associated Rib Anomaly 12 12Rib Anomaly 5 5Sternebra(e)- Fused 4 4Sternebra(e)- Malaligned (Severe) 4 4WIL Developmental Historical ControlHra:(NZW)SPF RabbitPage 8 of 11New Zealand Rabbit Time-Mated [Kalamazoo] EFD v.1.1



## 444 of 475Summary Incidence Malformations and Variations(Total Number Fetuses/Litters Affected)Ranked Uppermost to NethermostMALFORMATIONSNO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally263626362636298298298Fetuses LittersNumber14SKELETAL4Costal Cartilage Anomaly 3 3Skull Anomaly 2 2Vertebral Centra Anomaly 2 2WIL Developmental Historical ControlHra:(NZW)SPF RabbitPage 9 of 11New Zealand Rabbit Time-Mated [Kalamazoo] EFD v.1.1



## 445 of 475Summary Incidence Malformations and Variations(Total Number Fetuses/Litters Affected)Ranked Uppermost to Nethermost2VARIATIONSNO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally263626362636298298298Fetuses LittersNumber14VISCERAL3Spleen- Accessory 327 164Major Blood Vessel Variation 199 100Heart- Extra Papillary Muscle 72 49Gallbladder- Absent or Small 64 42Retrocaval Ureter(s) 41 24Thymus- Hemorrhagic 13 8Spleen- Pale 11 8Hemorrhagic Ring Around the Iris 5 4Spleen- Small 2 2Liver- Pale 2 1Thyroid Gland(s)- Enlarged 2 1Gallbladder- Bilobed 1 1Heart- Small 1 1Lung(s)- Small 1 1Pancreas- Small 1 1SKELETAL413th Full Rib(s) 897 24413th Rudimentary Rib(s) 485 23427 Presacral Vertebrae 233 107Sternebra(e) #5 and/or #6 Unossified 226 123Hyoid Arch(es) Bent 129 937th Cervical Rib(s) 47 32Extra Site of Ossification Anterior to Sternebra #1 30 25WIL Developmental Historical ControlHra:(NZW)SPF RabbitPage 10 of 11New Zealand Rabbit Time-Mated [Kalamazoo] EFD v.1.1



## 446 of 475Summary Incidence Malformations and Variations(Total Number Fetuses/Litters Affected)Ranked Uppermost to Nethermost2VARIATIONSNO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally263626362636298298298Fetuses LittersNumber14SKELETAL4Sternebrae with Thread-Like Attachment 30 25Sternebra(e)- Malaligned (Slight or Moderate) 21 19Hyoid Body and/or Arch(es) Unossified 8 8Skull Bone(s)- Accessory 8 725 Presacral Vertebrae 6 6Reduced Ossification of the Skull 4 428 Presacral Vertebrae 1 17th Sternebra 1 1Extra Site of Ossification Ventral to Cervical Centrum #2 1 1Vertebral Centra Not Fully Ossified 1 1WIL Developmental Historical ControlHra:(NZW)SPF RabbitPage 11 of 11New Zealand Rabbit Time-Mated [Kalamazoo] EFD v.1.1



## 447 of 475

## WIL-447022 HFO-1234yf Honeywell International Inc.



# APPENDIX G

Study Protocol

448 of 475

## Study Number: WIL-447022

PROTOCOL AMENDMENT IV

Sponsor: Honeywell International Inc.

A. Title of Study : An Inhalation Prenatal Developmen tal Toxicity Study of HFO-1234yf (2,3,3,3- Tetrafluoropropene) in Rabbits

B. Protocol Modifications :

1) 3 STUDY SCHEDULE:

Proposed Animal Receipt Date:

Phase I: 18 January 2008 (Experimental Starting Date) Phase II: 22 February 2008

Proposed Experimental Start Date:

Phase I: 22 January 2008 Phase II: 25 February 2008

Proposed Date of Last Data Collection:

Phase I: 2 April 2008 Phase II: 1 May 2008 (Experimental Termination/Completion Date)

Proposed Audited Report Date: 19 June 2008

2) 4.1.2 Cylinder/Lot Numbers:

Cylinder/lot number BW296B was not received from Honeywell; the correct number of the cylinder/lot number received was BW296A. All other cylinder/lot numbe rs listed in the protocol are

correct.

449 of 475

## WIL-447022 Protocol Amendment 

## IV Page 2



## C. Reasons for the Protocol Modification:

1) Correction of study schedule for OECD and EPA regulations.

2) Correction of one cylinder/lot number.

Approval:

Honeywell International Inc.



## / Sponsor Representative

WIL Research Laboratories, LLC



## ~am$~e 

## L. Fleeman, BS, LAT Study Director



# r 6 5iLK-q

Date Director, Developmental and

Reproductive Toxicology



## ,... 

## .... .sz. !, ::I, !% I.... :::r,.;:::;. :::r 

### ,:::::..



## ..... 

## ....... , 

## ....,........ .:: ::::::I:::!: :::::L': :::'I:: :



# yii3jc7!i:,K-:;k
:I:; ji 71 i;;; I: ;! 

# g.9

450 of 475

## Study Number: WIL-447022

PROTOCOL AMENDMENT III

Sponsor: Honeywell International Inc.

A. Title of Study : An Inhalation Prenatal Developmen tal Toxicity Study of HFO-1234yf (2,3,3,3- Tetrafluoropropene) in Rabbits

B. Protocol Modifications :

1) 13 Reports:

The following is added to this Section: For reporting purposes, the data fr om Phase I (Computer Protocol Number: WIL-447022D) and the data from Phase II (Computer Protocol Number: WIL-447022F) will be combined under Computer Protocol Number: WIL-447022C. The exception to this will be the Clinical Observation tables. Any notable clinical observation will be addressed in the text of the repor t and the individual tables will be presented under their respective protocol numbers.
In addition, within Phase I, the data for the two 4,000 ppm groups will be combined into one group of 24 anim als and in Phase II, the data for the two 5,500 ppm groups will be co mbined into one group of 24 animals. The group arrangement for the Final Report will be:

a 

## This group is a combination of the same exposure level of the Honeywell and

DuPont manufactured test articles from each phase. Group Number Test Article Target Exposure Concentration (ppm) Number of Females

1 Filtered Air 0 24 2 HFO-1234yf 2, 500 24 3 HFO-1234yf 4,000 a 

## 24 4 HFO-1234yf 5,500 a 

## 24 5 HFO-1234yf 7, 500 24



## 451 of 475

# WlL-447022 Protocol Amendment 

# 111 Page 2



# C. Reasons for the Protocol Modification:

1) Data combined at the request of the Sponsor for reporting purposes.

Approval:

Honeywell Internaqonal Inc.



# $

Date Sponsor Representative



# WIL Research Laboratories, LLC

7 

# /aL; 

# ^. 

# db 9% 7~ot ~h~e 

# L. Fleeman, BS, LAT 

# *

Study Director



# 2 

# z&qar

Mark D. Nemec, 

# BS, DABT Date Director, Developmental and

Reproductive Toxicology

452 of 475

## Study Number: WIL-447022

PROTOCOL AMENDMENT II

Sponsor: Honeywell International Inc.

A. Title of Study : An Inhalation Prenatal Developmen tal Toxicity Study of HFO-1234yf (2,3,3,3- Tetrafluoropropene) in Rabbits

B. Protocol Modifications :

1) 7.4.1 Organization of Test Groups:

The following section is changed to the following to adjust the Group 3 and 5 exposure levels to 5,500 ppm for Phase II.

The dosage levels were provided by the Sponsor Representative after consultation with the WIL Study Director. The following table presents the study group arrangement.

a 

## Test material manufactured by Honeywell International, Inc. Target Exposure Concentration (ppm) Number of Females Group Number Test Article Phase I Phase II Phase I Phase II
1 Filtered Air 0 0 12 12 2 HFO-1234yf a 

## 2,500 2,500 12 12 3 HFO-1234yf a 

## 4,000 5,500 12 12 4 HFO-1234yf a 

## 7,500 7,500 12 12

5 HFO-1234yf (DuPont Manufactured) 4,000 5,500 12 12



## 453 of 475

## WZL-447022 Protocol Amendment 11 Page 2



## C. Reasons for the Protocol Modification:

1) 

## Due to the lack of toxicity noted at 4000 ppm, an exposure level of 5,500 ppm will be used for Group 3 

## and 5 for Phase 

## I1 of the study at the Sponsor's request.

Approval:

Honeywell International Inc.



# / Sponsor Representative



## WIL Research Laboratories, LLC



# 20 L3 20of, f'ammye 

## L. Fleeman, BS Date Study Director 

# b SC;~ 4,: a( Lib 

# a~s
Mark D. Nemec, BS, DABT Date Director, Developmental and

Reproductive Toxicology



## 454 of 475d191m *am. mnmo,

,sz. 

### ::::; AZE. !EEE! 1sllmm .mP' mm.111 7.6- 1.mm. r.m,.. l.11.f 4LImIIt.. smmr .dmmmmun. -mmv ammmsmn. ..rn.rammmmm~mm ~~P~.III~I~IIOS ~DBSDIII~PIPIMl~'III~II~ ImUKSml8I ruwmna vmsmmrmpm~nl ammasalla 1s.m.u~s .am r,.lm~.~l 

# ..... YII. #rimmma mm81nmmm 11111101 Imnameml~m ar.-T.m am.ar-.ssm-~nmb~nmr-~rr~~a 

### ~i yr nt(r 8.110 w11m ,lb--&!!!h. 

### ,jE b--d $a:L ,:I!' '.m.m.' mmm~ bm di ins 

## .i 18

, 

# 61 1;;;

, 

# oe
.,In, 

### ., .m 

### ., IB. Iw dl 1u 

## Study Number: WIL-447022

PROTOCOL AMENDMENT 

## I Sponsor: Honeywell International Inc.

A. Title of Study:



## An Inhalation Prenatal Developmental Toxicity Study of HFO-1234yf (2,3,3,3- Tetrafluoropropene) in Rabbits

B. Protocol Modifications:

1) 6.4 Basal Diet:

The following is added to this section per Study Director Notification dated January 30,2008:

Kale will be provided once daily to all the rabbits in Phase 

## I beginning on January 30, 2008 and continue until the scheduled euthanasia. In addition, all Phase 

## II females on study will be provided with kale supplementation once daily beginning on the first day of exposure and continuing until the schedule euthanasia.

C. 

## Reasons for the Protocol Modification:

1) Due to a few females with evidence of reduced food consumption, kale supplementation will be provided.

Approval:

2-25 

# 64 4

Date 

## / Sponsor Representative



## WIL Research Laboratories. LLC

?ammye 

## L. Fleeman, BS Study Director Date 

# '

- 

# 56d.dc~B

Date Director, Developmental and

Reproductive Toxicology



## WIL 

## RESEARCH LABORATORIES, LLC 1407 

### GEORGE ROAD ASHLAND, OH 44805-9281 (419) 289-8700 FAX (419) 289-3650 

# - Improving human health and protecting the environment through scientific research services.@


## 455 of 475Page 1 of 20 WIL-447022 January 11,2008



## PROTOCOL

AN INHALATION PRENATAL DEVELOPMENTAL TOXICITY STUDY OF HFO-1234~4 

## (2,3,3,3-TETRAFLUOROPROPENE) IN RABBITS

(U.S. EPA OPPTS and OECD Guidelines)

Submitted To:

Honeywell International Inc. P.O. Box 1139 10 1 Columbia Road Morristown, 

## NJ 07962

WIL Research Laboratories, LLC 1407 George Road Ashland, OH 44805-8946



## WIL 

## RESEARCH LABORATORIES, 

### LLC 1407 GEORGE ROAD ASHLAND, OH 44805-9281 (419) 289-8700 FAX (419) 289-3650 

# -- Improving human health and protecting the environment through scientific research services.@


## 456 of 475Paee 2 of 20 WIL47022 January 11,2008



## 1 OBJECTIVE:

The objective this study is to determine the potential of the test article to induce developmental toxicity after maternal exposure during the critical period of organogenesis, to characterize maternal toxicity at the exposure levels tested and to determine a NOAEL (no-observed-adverse-effect level) for maternal toxicity and developmental toxicity. The study will be conducted in 2 Phases due to limitations of the exposure chambers.

This study is subject to the applicable regulations of the United States Environmental Protection Agency (EPA) Health Effects Test Guidelines OPPTS 870.3700, Prenatal Developmental Toxicity Study, August, 1998 and the Organisation of Economic Cooperation and Development (OECD) Guidelines for Testing of Chemicals Guideline 4 14, Prenatal Developmental Toxicity Study, January, 200 1, and will be conducted in accordance with the EPA (40 CFR Part 792) and OECD Good Laboratory Practice Regulations.

2 PERSONNEL INVOLVED 

## IN THE STUDY:

2.1 Sponsor Representatives:

George Rusch, PhD, DABT Director of Toxicology and Risk Assessment 1 0 1 Columbia Road Morristown, NJ 07962 Tel: (973)-455-3672 Email: george.rusch@honeywell.com

Gary 

## W. Jepson, PhD Senior.Toxicologist & 

## Manager, Applied Toxicology and Technology Development DuPont Haskell Global Centers for Health and Environmental Sciences H11626A 1090 Elkton, Rd. Newark, DE 1971 1 Tel: (302) 45 1-0010 Fax: (302) 366-5003 Email: Gary.W.Jepson- 1 @USA.dupont.com



## 457 of 475WIL-447022 Page 3 of 20 Janualy 1 1,2008



## 2.2 

## WIL Study 

### Director:



## Tammye 

## L. Fleeman, BS Staff Toxicologist, Developmental

and Reproductive Toxicology Tel: (419) 289-8700 Fax: (419) 289-3650 Email: tfleeman@wilresearch.com

2.3 

## WIL Deputy Director:



## Daniel T. Kirkpatrick, PhD, DABT Director, Inhalation Toxicology Tel: (419) 289-8700 Fax: (419) 289-3650 Email: dkirkpatrick@wilresearch.com

2.4 

## WIL Departmental Responsibilities:



## Joseph F. 

## Holson, PhD President, Director

Mark D. Nemec, BS, DABT Director, Developmental and

Reproductive Toxicology

Donald G. Stump, PhD, DABT Associate Director, Developmental

and Reproductive Toxicology

George A. Parker, DVM, PhD, DACVP, DABT Director, Pathology

Melissa J. Beck, PhD Assistant Director, Neurosciences

Daniel W. Sved, PhD Director, Metabolism and Analytical Chemistry

Walter R. Miller, DVM Clinical Veterinarian and Head of Surgery

and Experimental Medicine



## 458 of 475WIL-447022 Page 4 of 20 January 11,2008



## Ronald 

## E. Wilson, BS Director, Informational Systems

Carol A. Kopp, BS, LAT Manager, Gross Pathology and

Developmental Toxicology Laboratory

Heather L. Johnson, BS, RQAP-GLP Manager, Quality Assurance

Bennett J. Varsho, MPH, DABT Operations Manager, Developmental and

Reproductive Toxicology and the Formulations Laboratory

Robert A. Wally, BS, RAC Manager, Reporting and Regulatory

Technical Services

3 

### STUDY SCHEDULE:



## Proposed Animal Receipt Date: Phase I: Phase 11: 18 January 2008 22 February 2008

Proposed Experimental Start Date: Phase I: 22 January 2008 Phase 11: 25 February 2008

-. 

## Proposed Experimental Termination Date: Phase I: 15 February 2008 Phase 11: 20 March 2008

Proposed Audited Report Date: 19 

## June 2008

4 TEST ARTICLE DATA:

4.1 Test Article 

## 1

4.1.1 Identification:

HFO-1234yf 

## (2,3,3,3-tet~afluoropropene); manufactured at Honeywell International, Inc.



## 459 of 475Page 5 of 20 WIL-447022 January 11,2008



## 4.1.2 CylinderLot Numbers:

Not all of the listed cylindersllots will be used on this study. Those that

are used on study will be clearly identified 

## in the study records and the final report.

BW296B; BW305E; BW305F; BW305G; BW306A; BW306B; BW306C; BW306D; BW313A; BW313B; BW313C and BW313D

4.1.3 Purity:

All cylinderllot numbers are > 99.9%

4.1.4 Lot Number and Purity:

Each cylinder of test material has a unique lot number and Certificate of Analyses for purity.

4.1.5 Stability:

The test article is considered to be stable under the storage conditions provided by the Sponsor. No expiration date appears on the Certificate of Analyses; however, the stability of the test article will be assessed in this study, see Section 7.8, Test Article Characterization.

4.1.6 Physical Description:

The test article is a clear, colorless gas at standard temperature and
pressure. This will not be confirmed by 

## WIL Research Laboratories, LLC.

4.1.7 Storage Conditions:

Ambient (less than 25°C) as a liquefied gas in appropriate cylinders.

4.2 Test Article 2

4.2.1 Identification:



## HFO- 1234yf (2,3,3,3-tetrafluoropropene); manufactured at E. 

## I du Pont de Nemours

4.2.2 CylinderLot Number:



## 460 of 475Page 6 of 20 WIL-447022 January 11,2008

-

. 

### 4.2.3 Purity:



## All cylindersllot numbers are 

## > 99.9%

4.2.4 Stability:



## The test article is considered to be stable under the storage conditions provided by the Sponsor. No expiration date appears on the Certificate of Analyses; however, the stability of the test article will be assessed in this study, see Section 7.8, Test Article Characterization.

4.2.5 Physical Description:



## The test article is a clear, colorless gas at standard temperature and
pressure. This will not be confirmed by 

## WIL Research Laboratories, LLC.

4.2.6 Storage Conditions:



## Ambient (less than 25°C) as a liquefied gas in appropriate cylinders.

4.3 Reserve Samples:



## Reserve samples of each test article will be taken fiom each lot number used on study and stored in the Archives at 

## WLL Research Laboratories, LLC indefinitely, unless otherwise specified.

4.4 Personnel Safety Information:



## It is the responsibility of the Sponsor to notify the testing.facility of any special handling requirements for the test article. A Material Safety Data Sheet (MSDS) should accompany the test article upon arrival at the laboratory.

At a minimum, technical staff will wear safety glasses, appropriate gloves, and facility clothing when handling or working with the test article. Additional personal protective equipment, such as a respirator, protective coveralls or sleeve covers, may be required. Specific equipment and its use will be defined by study management and communicated to technical staff, as appropriate .



### 4.5 Test Article Disposition:



## With the exception of the reserve samples taken fiom each test article, all test article remaining at study completion will be returned to the Sponsor.



## 461 of 475Page 7 of 20 WIL-447022 January 1 1,2008



## 5 TEST SYSTEM:

5.1 Species:

Rabbit

5.2 Strain:

New Zealand White [Hra:(NZW)SPF]

5.3 Source:

Covance Research Products, Inc. Kalamazoo, Michigan

5.4 Number of Study:

120 time-mated females (maximum of 128) purchased. For each phase of the study, 64 females will be ordered and 60 will be placed on study. Animals not assigned to the study will be transferred to the stock animal colony or will be euthanized by intravenous administration of sodium pentobarbital and discarded.

The number of animals selected for this study is based on the US EPA Health Effects Test Guidelines OPPTS 870.3700, Prenatal Development Toxicity Study, August 1998 and the OECD Guidelines for Testing of Chemicals Guideline 4 14, Prenatal Developmental Toxicity Study, January 200 1.

5.5 Body Weight Range:

2.9 

## - 4.5 kg on Gestation Day 0.

5.6 Approximate Age:

5 to 9 months on Gestation Day 0.

5.7 Identification System:

Each rabbit will be uniquely identified by number using a plastic ear tag. Individual cage cards will be affixed to each cage and will display the animal number, group number, study number, dosage level, and sex of the animal.

5.8 Justification for Selection:

This species and strain of rabbit has been recognized as appropriate for developmental toxicity studies. 

## WIL Research Laboratories, LLC has historical



## 462 of 475Page 8 of 20 Wn-447022 January 11,2008



## data on the background incidence of fetal malformations and developmental variations in this species from the same strain and source. This animal model has been proven to be susceptible to the effects of developmental toxicants.



## 6 SPECIFIC MAINTENANCE SCHEDULE:

6.1 Animal Housing:

The rabbits will be individually housed in clean suspended stainless steel cages in an environmentally controlled room during the study. The cages will be elevated above ground corncob bedding (Pel-0' cobs@) or other suitable material, which will be changed at least two times each week. Nesting material will not be provided, as euthanasia is scheduled prior to anticipated parturition. The cages will be subjected to routine cleaning at a frequency consistent with maintaining good animal health and WIL Standard Operating Procedures. The facilities at WIL Research Laboratories, LLC are fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International).

6.2 

## Environmental Conditions:

Controls will be set to maintain an average daily temperature of 66 i 

## 5°F (19 f 

## 3°C) and an average daily relative humidity of 50 i 

## 20%. Temperature and relative humidity will be monitored continuously. Data for these two parameters will be scheduled for automatic collection on an hourly basis. Fluorescent lighting controlled by light timers will provide illumination for a 12-hour lighudark photoperiod. The ventilation rate will be set at a minimum of 10 room air changes per hour, 100% fresh air.

6.3 Drinking Water:

Reverse osmosis-purified water will be available 

## ad libitum 

## while the females

are in their home cage. No water will be available during the exposure periods. Filters servicing the automatic watering system are changed regularly according
to WIL Standard Operating Procedures. The municipal water supplying the laboratory is analyzed according to WIL 

## Standard Operating Procedures on a routine basis to ensure that contaminants are not present in concentrations that would be expected to affect the outcome of the study.

6.4 

## Basal Diet:

PMI Nutrition International, LLC Certified Rabbit ~ab~iet@ 5322 will be offered in gradual increments during the period prior to dosing according to 

## WIL SOPS and ad 

### libitum 

## during the study while the females are in their home
cage. No food will be available during the exposure periods. Periodic analyses



## 463 of 475Page 9 of 20 WIL-447022 January 11,2008



## of the certified feed are performed by the manufacturer to ensure that heavy metals and pesticides are not present at concentrations that would be expected to affect the outcome of the study. Results of the analyses are provided to WIL Research Laboratories, LLC by the manufacturer. Feeders will be changed and sanitized once per week.

7 EXPERIMENTAL DESIGN:



## 7.1 Animal Receipt and Quarantine:

Time-mated rabbits will be received by 

## WIL Research Laboratories, LLC on gestation day 1 and 2 for each Phase. Each rabbit will be inspected by a qualified technician upon receipt and permanently identified with an ear tag. Each rabbit will be observed twice daily for changes in general appearance and behavior. Prior to the start of the in-life phase, those animals judged to be suitable test subjects will be identified. Body weights on gestation day 4 and food consumption from gestation days 

## 4-6 (daily) will be recorded for all rabbits (including stock).

7.2 

## Randomization:

The gestation day 

## 0 body weight of each doe will be recorded by the supplier (gestation day 0 

## weights not collected under GLP conditions). The day on which confirmation of mating is made will be designated gestation day 0. 

## Rabbits judged to be suitabIe test subjects and meeting acceptable body weight requirements will be assigned to the study at random using a computer program. Gestation day 0 

## body weights will be used for randomization. At that time, the animal numbers and corresponding body weights will be entered into the WIL Toxicology Data Management System (WTDMS~). Aprintout containing the animal numbers and individual group assignments will be generated based on body weight stratification into a block design. The rabbits will then be arranged into the groups according to the printout. Each Phase will have a control group and four test article groups that consist of 12 rabbits each.

Any animal assigned to the study that is found dead, euthanized in 

### extremis 

## or exhibits abnormal clinical signs, reduced food consumption or body weight losses prior to the start of dosing may be replaced by 

## an animal of appropriate gestation age when possible. Replacement animals will be arbitrarily assigned (not computer randomized) to the study based on comparable body weights (if possible) with respect to the animal that was replaced.



## 7.3 Route of 

## Test Article Administration:

The route of administration will be whole-body inhalation, since this is a possible route of exposure for humans.



## 464 of 475Paee 10 of 20 WIL-447022 January 1 1,2008



### 7.4 Organization of Test Groups, Dosa~e Levels and Treatment Regimen:

7.4.1 Organization of Test Groups:



## The dosage levels were provided by the Sponsor Representative after consultation with the WIL Study Director.

The following table presents the study group arrangement.

'Test material manufactured by Honeywell International, Inc.



### 7.4.2 Vehicle Control Article:



## Filtered Air

7.4.3 Treatment Regimen:



## The test materials in filtered air atmospheres will be administered to the test groups as 6-hour, daily whole-body exposure during the period of major organogenesis, gestation days 6 through 28. 

## All rabbits will be exposed at approximately the same time each day.

7.5 Exposure Methods:



## Exposures will be conducted in stainless steel and glass whole-body exposure chambers. The control group will be exposed in a 2000 

## L chamber and the test article-exposed groups will be exposed in 1500 

## L chambers. One chamber will be dedicated for each group for the duration of the study. The chambers will be operated under dynamic conditions from a HEPA and charcoal filtered air source. Airflow rate through the chamber will be such that there will be at least 12 air changes per hour. Mean chamber temperature and relative humidity will be 19 3°C and 30-70%, respectively. These parameters will be monitored continuously and recorded approximately every 30 minutes during each day's exposure. Oxygen content of the exposure atmosphere will be measured during the methods developmental phase of the study and daily during the exposure phase of the study, and will be at least 19% in each chamber. All animals will be caged individually during the exposures. All animals will be housed in a



## 465 of 475Wn-447022 Page 11 of 20 January 11,2008



## normal animal colony room during non-exposure hours. For each day's
exposure, the animals will be placed in exposure batteries, transported to the exposure room, exposed for the requisite duration, and returned to their home cages. Food and water will not be available during the exposures.



## 7.6 Test Material Generation Methods:



## The test articles will be received as a liquefied gas in cylinders. Test atmospheres will be generated by metering gas fkom the headspace of the storage cylinders. Metering of gas will be controlled using appropriate valves and flow meters as determined during pre-study method development. If
necessary, to .maintain the rate of vaporization of liquefied gas within the cylinders, heat will be applied to the outside of the cylinders using a thermostatically-controlled heating blanket. Details of generation systems and methodologies, including the operating conditions for each system, will be defined during pre-study method development and included in a description of
exposure, test atmosphere generation and monitoring methods, which will be approved by the study director or management of the Inhalation Department. If modifications of methods or operating conditions are required during the study, study director approval is required (preferably before or at the time a change is implem&ted).

7.7 Methods for Characterization of Exposure Atmospheres:

Nominal concentrations:



## If possible.(based on ability to determine daily weight changes for liquefied gas cylinders), nominal exposure concentrations will be calculated for each exposure using the following-formula:

ppm Test Article (TA) = 

## Wt. TA Mol. Vol. lo6 MW Ch. Flow Exp. Dur. Where: Wt. TA 

## - Weight of test article used during exposure, in
grams Mol. Vol. 

## - Molar volume at 730 mmHg and 21°C, 25.1 1 Llmole lo6 

## - ppm conversion factor MW- 

## Test article molecular weight, in gramslmole Ch. Flow 

## - Average chamber flow rate, in liters per minute (LPM) Exp. Dur. 

## - Duration of exposure, in minutes



## 466 of 475Page 12 of 20 WIL-447022 January 11,2008



## 7.7.2 Analyzed Exposure Concentrations:

Actual test article gas concentrations in the exposure atmospheres will be determined at least at hourly intervals for each chamber using an appropriate gas chromatographic method. Analytical methods will be defined during pre-study method development and included in a description of exposure, test atmosphere generation and monitoring methods, which will be approved by the study director or management of the Inhalation Department. If modifications of methods or operating conditions are required during the study, study director approval is required (preferably before or at the time a change is implemented). The
average daily concentrations in each chamber will be considered acceptable if they are within 10% 

## of their target concentrations.

7.7.3 Temporal Stability and Homogeneity of Vapor Test Atmospheres:

During pre-study method development trials, the stability of the test article gas concentrations over time and the spatial homogeneity of the
test article gas concentrations within each test chamber will be evaluated. Methods and results of these evaluations will be documented in the study records and described in the study report.

7.8 Test Article Characterization:

7.8.1 Purity Analysis:

A sample of each test article, collected from an original storage cylinder prior to use for animal exposures, will be assessed for purity using GC/FID analysis of at least duplicate injections 

## of the undiluted sample. The test article purity will be expressed as "area.percent."

7.8.2 Stability Analysis:

The same procedure used for the purity analysis will be followed for the stability analysis of a sample collected after completion of animal
exposures. The resulting "area percent" values will be compared to the original purity values.

7.9 Maternal Observations During; Gestation:

7.9.1 Appearance and Behavior:

Each rabbit will be observed twice daily for moribundity and mortality,

once in the morning and once in the afternoon from the day after animal receipt until euthanasia. Detailed physical examinations will be



## 467 of 475WIL-447022 Page 13 of 20 January 11,2008



## recorded daily. Mortality and all signs of overt toxicity will be recorded on the day observed. The observations shall include, but are not limited to, evaluations for changes in appearance of skin and 

## fur, eyes, mucous membranes, respiratory and circulatory system, autonomic and central

nervous systems, somatomotor activity and behavior. During the
treatment period, the rabbits will also be observed in the chambers at approximately the mid-point of the exposure (3 

## hours following the beginning of exposure) and then approximately one hour following
exposure for findings that are potentially related to treatment or that might change before the next scheduled observation. Additional postdosing observation periods may be necessary and will be documented in the study records.

7.9.2 Body Weights:

Individual body weights will be recorded on gestation days 0 (by supplier), 4 and 6-29 (daily).

7.9.3 Food Consumption:

Individual food consumption will be recorded daily from gestation days 4-29. Food intake will be reported as glanimallday and g/kg/day for each corresponding body weight interval during gestation.

7.9.4 Deaths and Animals Euthanized in 

## Extremis:

Females not surviving until the scheduled euthanasia will be necropsied as described below and cause of death recorded, if possible. Rabbits not expected to survive to the next observation pefiod (moribund) will be euthanized by an intravenous injection of sodium pentobarbital via a marginal ear vein or other suitable site. The cranial, thoracic, abdominal and pelvic cavities will be opened and the organs examined. The number and location of implantation sites, corpora lutea and the number of viable fetuses will be recorded. Uteri which appear nongravid by macroscopic examination will be opened and placed in a 10% ammonium sulfide solution (Salewski, 1964) for detection of early implantation loss. The kidneys (bilateral), liver, brain, heart, lungs and all gross lesions will be preserved in 10% neutral-buffered formalin for possible future histopathological evaluation. Recognizable fetuses will be examined externally and preserved in 10% neutral-buffered formalin. Carcasses from adult animals will be discarded. Viable fetuses will be euthanized by hypothermia followed by intrathoracic injection of sodium pentobarbital, if necessary. Recognizable fetuses will be examined externally and preserved in 10% neutral-buffered formalin.



## 468 of 475WIL-447022 Page 14 of 20 January 11,2008



### 7.9.5 Abortion and Premature Deliveries:



## Females with evidence of abortion or premature delivery will be euthanized by an intravenous injection of sodium pentobarbital via a marginal ear vein or other suitable site. The thoracic, abdominal and pelvic cavities will be opened and the organs examined. The number and location of implantation sites and viable fetuses will be recorded. Carcasses fiom adult animals will be discarded. Corpora lutea will also be counted and recorded. The kidneys (bilateral), liver, brain, heart, lungs and all gross lesions will be preserved in 10% neutral-buffered formalin for possible future histopathological evaluation. Viable fetuses will be euthanized by hypothermia followed by an intrathoracic injection of sodium pentobarbital, if necessary. Viable kits will be euthanized by

an intraperitoneal injection of sodium pentobarbital. Recognizable fetuses or kits will be examined externally and preserved in 10% neutral-buffered formalin. Recognizable fetuses or kits fiom premature deliveries or abortions on gestation day 29 will be examined as described in section 7.1 1.

7.10 Laparohvsterectomv and Macroscopic Examination:



## Laparohysterectomies and macroscopic examinations will be performed blind to treatment group. All surviving rabbits will be euthanized by an intravenous injection of sodium pentobarbital via a marginal ear vein or other suitable site

on gestation day 29. The thoracic, abdominal and pelvic cavities will be opened and the organs examined. The uterus of each doe will be excised and its adnexa trimmed. Corpora lutea will be counted and recorded. Gravid uterine weights will be obtained and recorded. The uterus of each doe will be opened and the number of viable and nonviable fetuses and early and late resorptions recorded. The total number of implantation sites will be recorded, and the placentae examined. The individual uterine distribution will be documented using the following procedure: all implantation sites, including early and late resorpGons, will be numbered in consecutive fashion beginning with the left distal uterine horn, noting the position of the cervix and continuing fiom the proximal to the distal right uterine horn. Uteri which appear nongravid by macroscopic examination will be opened and placed in a 10% ammonium sulfide solution (Salewski, 1964) for detection of early implantation loss. The kidneys (bilateral), liver, brain, heart, lungs and all gross lesions will be preserved in 10% neutral-buffered formalin for possible future histopathological evaluation. Representative sections of corresponding organs for the gross lesions fiom a sufficient number of controls will be retained for comparison. Carcasses of the adult animals will be discarded.



## 469 of 475WIL-447022 Page 15 of 20 January 11,2008



## 7.1 1 Fetal Morpholog;ical Examination:

External, internal and skeletal findings will be recorded as developmental variations or malformations. Representative photographs of all malformations,

as appropriate, will be included in the study records. Corresponding low magnification photographs, depicting both the malformed fetus and a comparison control fetus, or normal littermate, will also be included in the study records as needed, and as appropriate, for comparison. Prenatal data (viable and nonviable fetuses, early and late resorptions, pre- and postimplantation loss and the fetal sex distribution) will be presented on a group mean basis and additionally as proportional data (% 

## per litter).

7.11.1 External:

Each viable fetus will be examined in 

## detail, weighed, euthanized by hypothermia followed by an intrathoracic injection of sodium pentobarbital, if necessary, and tagged. Nonviable fetuses (the degree of autolysis is minimal or absent) will be examined, crown-rump length measured, weighed and tagged individually. The crown-rump length of late resorptions (advanced degree of autolysis) will be measured, the degree of autolysis recorded, a gross external examination performed (if possible) and the tissue will be discarded.

7.1 1.2 Visceral (Internal):

Fetuses will be examined for visceral anomalies by dissection in the fresh (non-fixed) state. The thoracic and abdominal cavities will be opened and dissected using a technique described by Stuckhardt and Poppe (1984). This examination will include the heart and major vessels. Fetal kidneys will be examined and graded for renal papillae development (Woo and Hoar, 1972). The heads from all fetuses will be examined by a mid-coronal slice. The sex of all fetuses will be determined by internal examination.

All carcasses will be eviscerated, skinned and fixed in 100% ethyl alcohol for subsequent examination of skeletons.

7.11.3 Skeletal:

Each eviscerated fetus, following fixation in alcohol, will be stained with Alizarin Red S by a method similar to that described by Dawson (1926). The skeletal examination will be made following this procedure.



## 470 of 475Page 16 of 20 WIL-447022 January 1 1,2008



### 8 

## DURATION OF STUDY:

Due to the multiple phases, this study will require approximately three months for the in-life activities through the laparohysterectomy phase. The processing and evaluation of the fetal specimens will require approximately six weeks.



## 9 STATISTICAL METHODS:

All analyses will be two-tailed for minimum significance levels of 5% and 1%. All means will be presented with standard deviations. All statistical tests will be performed using a computer with appropriate programming as referenced below. The litter, rather than the fetus, will be considered as the experimental unit.



## 9.1 Maternal In-Life Data:

Continuous data variables [mean maternal body weights (absolute and net), body weight gains (absolute and net) and food consumption of each interval] will be subjected to a parametric one-way analysis of variance (ANOVA) (Snedecor, 1980) to determine intergroup difference. If the results of the ANOVA are significant (p<0.05), Dunnett's test (Dunnett, 1964) will be applied
to the data.

9.2 

## Laparohvsterectomv Data:

The group mean numbers of corpora lutea, implantation sites, viable fetuses, maternal gravid uterine weights and mean fetal weight (separately by sex, and combined) will be subjected to a parametric one-way analysis of variance (ANOVA) (Snedecor, 1980) and Dunnett's test (Dunnett, 1964) as described above. The mean litter proportions of prenatal data (% 

## per litter of viable and nonviable fetuses, early and late resorptions, total - 

## resorptions, pre- and post-implantation loss and the fetal sex distribution) 'will be subjected to the Kruskal-Wallis nonparametic ANOVA test (Kruskal, 1952) to determine intergroup difference. If the result of the ANOVA are significant (p<0.05), the Dunn's Test (Dunn, 1964) will be applied to the data.

9.3 

## Fetal Morpholo(ry Data:

The mean litter proportion (% 

## per litter) of total fetal malformations and developmental variations (external, visceral, skeletal and combined) and of each particular external, visceral and skeletal malformation or variation will be tabulated. The mean litter proportions of fetal malformations and developmental variations will be subjected to the Kruskal-Wallis nonparametic ANOVA (Kruskal, 1952) test followed by the Dunn's Test (Dunn, 1964) (if appropriate) as described above.



## 471 of 475WIL-447022 Page 17 of 20 January 1 1,2008



### 10 

## QUALITY ASSURANCE:

The study will be audited by the WIL Quality Assurance Unit while in progress to

assure compliance with the study protocol and protocol amendments, WIL Standard Operating Procedures and the appropriate provisions of the EPA TSCA (40 CFR,Part 792) Good Laboratory Practice Standards and the OECD Principles of Good Laboratory Practice November 26, 1997 [C(97)186/Final]. The raw data and draft report will be audited by the WIL Quality Assurance Unit prior to submission to the Sponsor's Representative to assure that the final report accurately describes the conduct and the findings of the study.

This study will be included on the WIL master list of regulated studies.

11 RECORDS TO BE MAINTAINED:

All original raw data records, as defined by WIL SOPs and the applicable GLPs, will be stored as described in Section 12 in the Archives at WIL Research Laboratories, LLC.

12 

## WORK PRODUCT:

The Sponsor will have title to all documentation records, raw data, slides, specimens and other work product generated during the performance of the study. All work product, including raw paper data, pertinent electronic storage media and specimens, will be retained for 10 years following issuance of the final report in the Archives at WIL Research Laboratories, LLC. Thereafter, WIL Research Laboratories, LLC will charge a monthly archiving fee for retention of all work product. All work product will be stored in compliance with regulatory requirements.

Any work product, including documents, specimens, and samples, that are required by this protocol, its amendments, or other written instructions of the Sponsor, to be shipped by 

## WIL Research Laboratories, LLC to another location will be appropriately packaged and labeled as defined by WIL's SOPs and delivered to a common carrier for shipment. WIL Research Laboratories, LLC will not be responsible for shipment following delivery to the common carrier.

13 

## REPORTS:

The final report will contain a summary, test article data, methods and procedures, maternal and fetal data, WIL Historical Control Data (New Zealand White Rabbits), the analytical chemistry report and an interpretation and discussion of the study results. The final report will be comprehensive and shall define levels inducing toxic effects under the condition of this investigation. The report will contain all information necessary to conform to current EPA OPPTS and OECD specifications.



## 472 of 475Page 18 of 20 WIL-447022 January 1 1,2008



## WIL Research Laboratories, LLC will submit one electronic copy of an audited draft report to each Sponsor Representative in a timely manner upon completion of data collection prior to issuance of the final report. One revision will be permitted as part of the cost of the study, from which 'the Sponsor's reasonable revisions and suggestions will be incorporated into the final report, as appropriate. Additional changes or revisions may be made, at extra cost. It is expected that the Sponsor will review the draft report and provide comments to 

## WIL Research Laboratories, LLC within a two-month time fiame following submission. WIL Research Laboratories, LLC will submit the final report within one month following receipt of comments. If the Sponsor's comments and/or authorization to finalize the report have not been received at WIL Research Laboratories, LLC within one year following submission of the draft report, 

## WlL Research Laboratories, LLC may elect to finalize the report following appropriate written notification to the Sponsor. One electronic copy (PDF) of the final report on CD-R and one bound hard copy will be provided to each Sponsor Representative.

14 ANIMAL WELFARE ACT COMPLIANCE:

This study will comply with all applicable sections of the Final Rules of the Animal Welfare Act (AWA) regulations (9 

## CFR Parts 1,2 and 3). 

## The Sponsor should make particular note of the following:

The Sponsor Representative's signature on this protocol documents for the Study Director the Sponsor's assurance that the study described in this protocol does not unnecessarily duplicate previous experiments.

Whenever possible, procedures used in this study have been designed to avoid or minimize discomfort, distress or pain to animals. All methods are described in this study protocol or in 

## written laboratory Standard Operating Procedures.

Animals that experience severe or chronic pain or distress that cannot be relieved will be painlessly euthanized as deemed appropriate by the veterinary staff and Study Director. The Sponsor will be advised by the Study Director of all circumstances which could lead to this action in as timely a manner as possible.

Methods of euthanasia used during this study are in conformance with the abovereferenced regulation.

The SponsorIStudy Director has considered altematives to procedures that may

cause more than momentary or slight pain or distress to the 

## animals and has provided a written narrative description (AWA covered species) of the methods and sources used to determine that altematives are not available.



## 473 of 475WIL-447022 Page 19 of 20 January 11,2008



### 15 

## PROTOCOL MODIFICATION:

Modification of the protocol may be accomplished during the course of this investigation. However, no changes will be made in the study design without the verbal or written permission of the Sponsor. 

## In the event that the Sponsor verbally requests or approves a change in the protocol, such changes will be made by appropriate documentation in the form of a protocol amendment. All alterations of the protocol and reasons for the modification(s) will be signed by the Study Director and the Sponsor Representative.

16 REFERENCES:

Dawson, A.B. A note on the staining of the skeleton of cleared specimens with Alizarin Red S. Stain Technology 1926,1, 123-124



## Dunn, 0. 

## J. Multiple comparisons using rank sums. Technometrics, 1964 6(3):24 1-252.



## Dunnett, C.W. New tables for multiple comparisons with a control. Biometries 

## 1964, 20, 

### 482-49 1.



## Kruskal, W.H.; Wallis, W.A. Use of ranks in one-criterion variance analysis. Journal of the American Statistical Association 1952,47, 583-621



## Salewski, 

## E. FSirbemethode 

## zum makroskopischen Nachweis von Implantationsstellen am Uterus der Ratte. [Staining method for a macroscopic test for implantation sites 

## in the uterus of the rat]. Naunyn 

## - Schmiedebergs ArchivJirr Experimentelle Pathologie und Pharmakologie 1964,247, 367.



## Snedecor, G.W.; Cochran, W.G. One Way Classifications; Analysis of Variance. 

## In Statistical Methods, 7th ed.; The Iowa State University Press: hes, 

## IA, 1980; pp 2 15- 237.



## Stuckhardt, 

## J.L.; Poppe, 

## S.M. Fresh visceral examination of rat and rabbit fetuses used in teratogenicity testing. Teratogenesis, Carcinogenesis and Mutagenesis 1984,4, 18 

## 1- 188.



## 474 of 475WIL-447022 Page 20 of 20 January 1 1,2008



## Woo, D.C.; Hoar, 

## R.M. Apparent hydronephrosis as a normal aspect of renal development 

## in late gestation of rats: the effect of methyl salicylate. Teratology 

## 1972; 6, 

## 191-196.

17 PROTOCOL APPROVAL:



## Sponsor approval received via P1~161 

# I on 

# 1 0 

# 4,~u~ 2009



# . Date

Honeywell International Inc.



# ' Sponsor Representative



## WIL Research Laboratories, LLC



# II Qwby 

# 6?

~bmm~e 

## L. Fleeman, BS Date Study Director 

# .~a8

Date \ 

## Director, Developmental and Reproductive Toxicology



## 475 of 475

## AMENDMENT TO THE FINAL REPORT

STUDY TITLE

AN INHALATION PRENATAL DE VELOPMENTAL TOXICITY STUDY OF HFO-1234yf (2,3,3,3-TETRAF LUOROPROPENE) IN RABBITS

STUDY NUMBER

WIL-447022

DATA REQUIREMENT

OECD Guideline 414 OPPTS 870.3700

STUDY DIRECTOR

Tammye L. Fleeman, BS, LAT

DATE FINAL REPORT ISSUED

14 July 2008

DATE AMENDMENT ISSUED

12 August 2008

PERFORMING LABORATORY

WIL Research Laboratories, LLC 1407 George Road Ashland, OH 44805-8946

SPONSOR

Honeywell International Inc. P.O. Box 1139 101 Columbia Road Morristown, NJ 07962

Page 1 of 5

## WIL-447022 Honeywell International Inc. 

## HFO- 1234yf



# AMENDMENT 

# To THE FINAL REPORT

Section 10.1 

## Phases Inspected Original Report Page: 50 

## Amendment to Final Report Page: 5
Change: Documentation of inspection 

## of Study Records (N-1) was added to the text

table.

Reason for Change: The Quality Assurance Unit audit for this phase was not issued
prior to issuance of the final report. The original data audit was conducted on
13 May 2008, but an audit report was not issued. Data were audited again on

30 July 2008, and the audit was released indicating that there were no findings.

The changes to this report had no impact on the scientific validity or interpretation of 

## the

results 

## of this study.

The amendment did not entail generation of new data, revision of calculations or

modification of previously submitted data and did not change the conclusion of the study.

The signature below certifies that the revised page has been reviewed and approved by
the study director.



# 12- 

# L-tZooq Tamhye L. Fleeman, 

## BS, LAT Staff Toxicologist, Developmental and Reproductive Toxicology Study Director Date 

# '

-2-

## WIL-447022 Honeywell International Inc. HFO-1234yf

Date(s) of 

# QUALITY ASSURANCE UNIT STATEMENT

Date( s) 

### Date( s) 

### Findings Findings Reported to Reported to Inspect ion(s) 

# -

dv Director Management 

### Auditom 05-Aug-2008 Final Report Amendment 05-Aug-2008 12-Aug-2008 H.Johnson



## This amendment was inspected in accordance with the U.S. EPA Good Laboratory

Practice Standards (40 CFR Part 792), the OECD Principles of Good Laboratory Practice,
the standard operating procedures of WIL Research Laboratories, LLC and the sponsor’s
protocol and protocol amendments. Quality Assurance findings, derived from the review

of the amendment to the final report, are documented and have been reported to the study

director. A status report is submitted to management monthly.

This amendment accurately reflects the data generated during the study. The methods
and procedures used in the study were those specified in the protocol, its amendments
and the standard operating procedures of WIL Research Laboratories, LLC.

This amendment to the final report will be stored in the Archives at WIL Research
Laboratories, LLC, or another location specified by the sponsor.

Amendment Audited and Reviewed 

## By:



# - W bk\ 

## Heather 

## L. Johson, BS, RQAP-GLP Manager, Quality Assurance

-3-

## WIL-447022 HFO-1234yf
Hone ywell International Inc.

-4- 

# R EVISED 

# P AGE

## WIL-447022 HFO-1234yf Honeywell International Inc.

-5- Date(s) of Inspection(s) Phase Inspected Date(s) Findings Reported to Study Director Date(s) Findings Reported to Management Auditor(s)

10-Jun-2008 Draft Report (Analytical Chemistry Appendix) 10-Jun-2008 14-Jul-2008 N.Daniels

11-Jun-2008 Draft Report (Inhalation Appendix) 12-Jun-2008 14-Jul-2008 S.Power

13-May-2008 30-Jul-2008 Study Records (N-1) 30-Jul-2008 12-Aug-2008 D.Little



## This study was inspected in accordance wi th the U.S. EPA Good Laboratory Practice
Standards (40 CFR Part 792), the OECD Prin ciples of Good Laboratory Practice, the
standard operating procedures of WIL Research Laboratories, LLC and the sponsor's
protocol and protocol amendments with the following exceptions. The data located in
Appendix B (Certificates of Analysis) were the responsibility of the sponsor or
manufacturer. The procedures performed by Covance Research Products, Inc. were not
subject to Quality Assurance Unit inspection. Quality Assurance findings, derived from
the inspections during the conduct of the study and from the inspections of the raw data
and draft report, are documented and have b een reported to the study director. A status
report is submitted to management monthly.

This report accurately reflects the data ge nerated during the study. The methods and
procedures used in the study we re those specified in the prot ocol, its amendments and the
standard operating procedures of WIL Research Laboratories, LLC.

The raw data, the retention samples and the fina l report will be stored in the Archives at
WIL Research Laboratories, LLC or a nother location specified by the sponsor.