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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TABLE OF CONTENTS

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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INDEX OF TABLES

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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INDEX OF APPENDICES

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. SUMMARY

1.1. OBJECTIVE

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. STUDY DESIGN

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) 4000a

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

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. RESULTS

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. CONCLUSIONS

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. INTRODUCTION

2.1. GENERAL STUDY INFORMATION

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. KEY STUDY DATES1

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. STUDY DESIGN

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. EXPERIMENTAL PROCEDURES - MATERIALS AND METHODS

4.1. TEST SUBSTANCE AND VEHICLE

4.1.1. TEST SUBSTANCE IDENTIFICATION

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. BW305Fa

Cylinder 8; Lot no. BW305Ga

Cylinder 9; Lot no. BW306Aa

Cylinder 10; Lot no. BW306Ba

Cylinder 11; Lot no. BW306Ca

Cylinder 12; Lot no. BW306Da

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-110107a

Cylinder no. 050064;

Lot no. 050064C-102907a

Cylinder no. 050432;

Lot no. 050432C-102907a

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. EXPOSURE METHODS

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-m3

 (2000 L)

chamber and the test substance-exposed groups were exposed in a 1.5-m3

 (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 24c

2 HFO-1234yfa 2500 2500 2500 24c

3 HFO-1234yfa 4000 5500 4000d 24c

4 HFO-1234yfa 7500 7500 5500d 24c

5 HFO-1234yfb 4000 5500 7500d 24c

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. TEST ATMOSPHERE GENERATION METHODS

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. METHODS FOR CHARACTERIZATION OF EXPOSURE ATMOSPHERES

4.4.1. NOMINAL CONCENTRATIONS

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 × 106

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

106 = 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. ANALYZED EXPOSURE CONCENTRATIONS

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. HOMOGENEITY OF VAPOR TEST ATMOSPHERES

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. TEST SUBSTANCE CHARACTERIZATION

4.5.1. PURITY ANALYSIS

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. STABILITY ANALYSIS

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. TEST SYSTEM

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. ANIMAL RECEIPT

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. ANIMAL HOUSING (NON-EXPOSURE PERIODS)

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. DIET, DRINKING WATER AND MAINTENANCE

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. ENVIRONMENTAL CONDITIONS (NON-EXPOSURE PERIODS)

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. ASSIGNMENT OF ANIMALS TO TREATMENT GROUPS

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 (WTDMSTM). 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. PARAMETERS EVALUATED

5.1. MATERNAL OBSERVATIONS DURING GESTATION

5.1.1. CLINICAL OBSERVATIONS AND SURVIVAL

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. BODY WEIGHTS AND GRAVID UTERINE WEIGHTS

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. FOOD CONSUMPTION

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. ANATOMIC PATHOLOGY AND LAPAROHYSTERECTOMY

5.1.4.1. UNSCHEDULED DEATHS

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. GESTATION DAY 29 LAPAROHYSTERECTOMY

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. FETAL MORPHOLOGICAL EXAMINATION

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. STATISTICAL ANALYSES

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 proportions

(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. DATA RETENTION

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. RESULTS

6.1. ANALYTICAL CHEMISTRY

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. ANALYZED EXPOSURE CONCENTRATIONS

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. MATERNAL CLINICAL OBSERVATIONS AND SURVIVAL

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. MATERNAL BODY WEIGHTS AND GRAVID UTERINE WEIGHTS

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. MATERNAL FOOD CONSUMPTION

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. MATERNAL NECROPSY DATA

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. GESTATION DAY 29 LAPAROHYSTERECTOMY

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. FETAL MORPHOLOGICAL DATA

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. EXTERNAL MALFORMATIONS AND VARIATIONS

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. VISCERAL MALFORMATIONS AND VARIATIONS

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) 1a 1b - 2c -

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 - 1d 1d

Abdominal cavity - fluid contents or

fluid-filled - 4 - 2d 1d

- = 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. SKELETAL MALFORMATIONS AND VARIATIONS

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 13th rudimentary rib(s), 13th 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. SUMMARY OF EXTERNAL, VISCERAL AND SKELETAL

EXAMINATIONS

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. DISCUSSION

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. CONCLUSIONS

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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HFO-1234yf 

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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KEY STUDY PERSONNEL AND REPORT SUBMISSION (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. QUALITY ASSURANCE UNIT STATEMENT

10.1. PHASES INSPECTED

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. 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, 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. DEVIATIONS FROM THE PROTOCOL

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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TABLES 1-19

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 TABLE 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 

 05/20/2008 

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 TABLE 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 DUPONT 

 

57 of 475
 TABLE 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 

 05/20/2008 

58 of 475
 TABLE 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 DUPONT 

 

59 of 475
 TABLE 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 

 05/29/2008 

60 of 475
 TABLE 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:05/29/2008 

61 of 475
 TABLE 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:05/29/2008 

62 of 475
 TABLE 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:05/20/2008 

63 of 475
 TABLE 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:06/19/2008 

64 of 475
 TABLE 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 MEAN 

 

65 of 475
 TABLE 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 MEAN 

 

66 of 475
 TABLE 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 MEAN 

 

67 of 475
 TABLE 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 MEAN 

 

68 of 475
 TABLE 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 MEAN 

 

69 of 475
 TABLE 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 

 05/21/2008 

 

70 of 475
 TABLE 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 MEAN 

 

71 of 475
 TABLE 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 MEAN 

 

72 of 475
 TABLE 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 MEAN 

 

73 of 475
 TABLE 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 MEAN 

 

74 of 475
 TABLE 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 MEAN 

 

75 of 475
 TABLE 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 

 05/21/2008 

 

76 of 475
 TABLE 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 

 05/20/2008 

77 of 475
 TABLE 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 MEAN 

 

78 of 475
 TABLE 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 MEAN 

 

79 of 475
 TABLE 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 MEAN 

 

80 of 475
 TABLE 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 MEAN 

 

81 of 475
 TABLE 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 MEAN 

 

82 of 475
 TABLE 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 

 06/16/2008 

 

83 of 475
 TABLE 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 MEAN 

 

84 of 475
 TABLE 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 MEAN 

 

85 of 475
 TABLE 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 MEAN 

 

86 of 475
 TABLE 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 MEAN 

 

87 of 475
 TABLE 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 MEAN 

 

88 of 475
 TABLE 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 

 06/16/2008 

 

89 of 475
 TABLE 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 PPM 

 

90 of 475
 TABLE 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:05/29/2008 

91 of 475
 TABLE 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 

 06/16/2008 

92 of 475
 TABLE 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 group 

 

93 of 475
 TABLE 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 group 

 

94 of 475
 TABLE 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:07/08/2008 

95 of 475
 TABLE 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 

 07/02/2008 

96 of 475
 TABLE 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 group 

 

97 of 475
 TABLE 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 group 

 

98 of 475
 TABLE 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 group 

 

99 of 475
 TABLE 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 

 07/02/2008 

100 of 475
 TABLE 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 

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

 

101 of 475
 TABLE 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 

102

 07/02/2008 

 of 475
 TABLE 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 group 

 

103 of 475
 TABLE 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 group 

 

104 of 475
 TABLE 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 group 

 

105 of 475
 TABLE 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 group 

 

106 of 475
 TABLE 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 group 

 

107 of 475
 TABLE 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 group 

 

108 of 475
 TABLE 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 

 07/02/2008 

109 of 475
WIL-447022 HFO-1234yf

Honeywell International Inc.

APPENDIX A

Individual Animal Data

110 of 475
 TABLE 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 DUPONT 

 

111 of 475
 TABLE 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 DUPONT 

 

112 of 475
 TABLE 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 DUPONT 

 

113 of 475
 TABLE 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 DUPONT 

 

114 of 475
 TABLE 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 DUPONT 

 

115 of 475
 TABLE 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 DUPONT 

 

116 of 475
 TABLE 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 

117

 05/20/2008 

 of 475
 TABLE 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 DUPONT 

 

118 of 475
 TABLE 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 DUPONT 

 

119 of 475
 TABLE 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 DUPONT 

 

120 of 475
 TABLE 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 DUPONT 

 

121 of 475
 TABLE 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 DUPONT 

 

122 of 475
 TABLE 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 DUPONT 

 

123 of 475
 TABLE 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 

 05/29/2008 

124 of 475
 TABLE 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:05/29/2008 

125 of 475
 TABLE 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 

126

 R:05/29/2008 

 of 475
 TABLE 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:06/19/2008 

127 of 475
 TABLE 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 MEAN 

 

128 of 475
 TABLE 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 MEAN 

 

129 of 475
 TABLE 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 MEAN 

 

130 of 475
 TABLE 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 MEAN 

 

131 of 475
 TABLE 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 MEAN 

 

132 of 475
 TABLE 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 MEAN 

 

133 of 475
 TABLE 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 MEAN 

 

134 of 475
 TABLE 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 MEAN 

 

135 of 475
 TABLE 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 MEAN 

 

136 of 475
 TABLE 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 MEAN 

 

137 of 475
 TABLE 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 APPLICABLE 

 

138 of 475
 TABLE 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 APPLICABLE 

 

139 of 475
 TABLE 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 APPLICABLE 

 

140 of 475
 TABLE 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 APPLICABLE 

 

141 of 475
 TABLE 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 

 05/21/2008 

142 of 475
 TABLE 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 MEAN 

 

143 of 475
 TABLE 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 MEAN 

 

144 of 475
 TABLE 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 MEAN 

 

145 of 475
 TABLE 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 MEAN 

 

146 of 475
 TABLE 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 MEAN 

 

147 of 475
 TABLE 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 MEAN 

 

148 of 475
 TABLE 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 MEAN 

 

149 of 475
 TABLE 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 MEAN 

 

150 of 475
 TABLE 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 MEAN 

 

151 of 475
 TABLE 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 MEAN 

 

152 of 475
 TABLE 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 MEAN 

 

153 of 475
 TABLE 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 MEAN 

 

154 of 475
 TABLE 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 APPLICABLE 

 

155 of 475
 TABLE 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 APPLICABLE 

 

156 of 475
 TABLE 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 APPLICABLE 

 

157 of 475
 TABLE 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 APPLICABLE 

 

158 of 475
 TABLE 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 APPLICABLE 

 

159 of 475
 TABLE 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 APPLICABLE 

 

160 of 475
 TABLE 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 APPLICABLE 

 

161 of 475
 TABLE 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 

 05/21/2008 

162 of 475
 TABLE 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 = GRAVID 

 

163 of 475
 TABLE 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 APPLICABLE 

 

164 of 475
 TABLE 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 = GRAVID 

 

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 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 APPLICABLE 

 

166 of 475
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 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 

 05/20/2008 

167 of 475
 TABLE A9 (COMBINED PHASES) 

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 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 MEAN 

 

168 of 475
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 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 APPLICABLE 

 

169 of 475
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 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 MEAN 

 

170 of 475
 TABLE 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 MEAN 

 

171 of 475
 TABLE 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 APPLICABLE 

 

172 of 475
 TABLE 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 APPLICABLE 

 

173 of 475
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 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 MEAN 

 

174 of 475
 TABLE 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 MEAN 

 

175 of 475
 TABLE A9 (COMBINED PHASES) 

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 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 MEAN 

 

176 of 475
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 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 MEAN 

 

177 of 475
 TABLE 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 APPLICABLE 

 

178 of 475
 TABLE 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 MEAN 

 

179 of 475
 TABLE 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 APPLICABLE 

 

180 of 475
 TABLE 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 APPLICABLE 

 

181 of 475
 TABLE 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 APPLICABLE 

 

182 of 475
 TABLE 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 APPLICABLE 

 

183 of 475
 TABLE 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 APPLICABLE 

 

184 of 475
 TABLE 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 APPLICABLE 

 

185 of 475
 TABLE A9 (COMBINED PHASES) 

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 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 APPLICABLE 

 

186 of 475
 TABLE 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 

 06/16/2008 

187 of 475
 TABLE A10 (COMBINED PHASES) 

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 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 MEAN 

 

188 of 475
 TABLE 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 APPLICABLE 

 

189 of 475
 TABLE 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 MEAN 

 

190 of 475
 TABLE 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 MEAN 

 

191 of 475
 TABLE 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 APPLICABLE 

 

192 of 475
 TABLE 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 APPLICABLE 

 

193 of 475
 TABLE 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 MEAN 

 

194 of 475
 TABLE 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 MEAN 

 

195 of 475
 TABLE 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 MEAN 

 

196 of 475
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 ----------------------------------------------------------------------------------------------------------------------------------- 

 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 MEAN 

 

197 of 475
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 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 APPLICABLE 

 

198 of 475
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 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 MEAN 

 

199 of 475
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 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 APPLICABLE 

 

200 of 475
 TABLE 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 APPLICABLE 

 

201 of 475
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 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 APPLICABLE 

 

202 of 475
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 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 APPLICABLE 

 

203 of 475
 TABLE 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 APPLICABLE 

 

204 of 475
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 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 APPLICABLE 

 

205 of 475
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 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 APPLICABLE 

 

206 of 475
 TABLE A10 (COMBINED PHASES) 

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 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 

 06/16/2008 

207 of 475
 TABLE A11 (COMBINED PHASES) 

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

 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: ACCESSORY 

 

208 of 475
 TABLE A11 (COMBINED PHASES) 

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

 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 OBSERVED 

 

209 of 475
 TABLE A11 (COMBINED PHASES) 

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 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 LOBES 

 

210 of 475
 TABLE A11 (COMBINED PHASES) 

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 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, LEFT 

 

211 of 475
 TABLE A11 (COMBINED PHASES) 

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

 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 DIAMETER 

 

212 of 475
 TABLE 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, RIGHT 

 

213 of 475
 TABLE 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 LOBES 

 

214 of 475
 TABLE 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 OBSERVATIONS 

 

215 of 475
 TABLE A11 (COMBINED PHASES) 

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 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 OBSERVED 

 

216 of 475
 TABLE 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, RIGHT 

 

217 of 475
 TABLE 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 IMPLANTATIONS 

 

218 of 475
 TABLE A11 (COMBINED PHASES) 

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 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 DIAMETER 

 

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 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 

 05/29/2008 

 

220 of 475
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 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 = 24 

 

221 of 475
 TABLE 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 = 23 

 

222 of 475
 TABLE 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 = 24 

 

223 of 475
 TABLE 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 = 18 

 

224 of 475
 TABLE 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 

 06/16/2008 

225 of 475
 TABLE 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 24 

 

226 of 475
 TABLE 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 23 

 

227 of 475
 TABLE 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 24 

 

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 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 18 

 

229 of 475
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 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 

 06/16/2008 

230 of 475
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 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 CERVIX 

 

231 of 475
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 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 CERVIX 

 

232 of 475
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 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 CERVIX 

 

233 of 475
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 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 CERVIX 

 

234 of 475
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 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 

 06/16/2008 

235 of 475
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 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 APPLICABLE 

 

236 of 475
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 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 APPLICABLE 

 

237 of 475
 TABLE 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 APPLICABLE 

 

238 of 475
 TABLE 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 APPLICABLE 

 

239 of 475
 TABLE 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 APPLICABLE 

 

240 of 475
 TABLE 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 APPLICABLE 

 

241 of 475
 TABLE 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 APPLICABLE 

 

242 of 475
 TABLE 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 APPLICABLE 

 

243 of 475
 TABLE 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 APPLICABLE 

 

244 of 475
 TABLE 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 APPLICABLE 

 

245 of 475
 TABLE 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 APPLICABLE 

 

246 of 475
 TABLE 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 APPLICABLE 

 

247 of 475
 TABLE 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 APPLICABLE 

 

248 of 475
 TABLE 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 APPLICABLE 

 

249 of 475
 TABLE 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 APPLICABLE 

 

250 of 475
 TABLE 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 APPLICABLE 

 

251 of 475
 TABLE A15 (COMBINED PHASES) 

 PROJECT NO.:WIL-447022C INHALATION PRENATAL DEV TOX STUDY OF HFO-1234yf IN RABBITS PAGE 17 

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

 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 APPLICABLE 

 

252 of 475
 TABLE 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 APPLICABLE 

 

253 of 475
 TABLE 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 APPLICABLE 

 

254 of 475
 TABLE 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 APPLICABLE 

 

255 of 475
 TABLE 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 APPLICABLE 

 

256 of 475
 TABLE 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 APPLICABLE 

 

257 of 475
 TABLE 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 APPLICABLE 

 

258 of 475
 TABLE 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 APPLICABLE 

 

259 of 475
 TABLE 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 APPLICABLE 

 

260 of 475
 TABLE 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 APPLICABLE 

 

261 of 475
 TABLE 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 APPLICABLE 

 

262 of 475
 TABLE 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 APPLICABLE 

 

263 of 475
 TABLE 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 APPLICABLE 

 

264 of 475
 TABLE 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 APPLICABLE 

 

265 of 475
 TABLE 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 APPLICABLE 

 

266 of 475
 TABLE 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 APPLICABLE 

 

267 of 475
 TABLE 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 APPLICABLE 

 

268 of 475
 TABLE 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 APPLICABLE 

 

269 of 475
 TABLE 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 APPLICABLE 

 

270 of 475
 TABLE 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 APPLICABLE 

 

271 of 475
 TABLE 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 APPLICABLE 

 

272 of 475
 TABLE 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 APPLICABLE 

 

273 of 475
 TABLE 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 APPLICABLE 

 

274 of 475
 TABLE 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 APPLICABLE 

 

275 of 475
 TABLE 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 APPLICABLE 

 

276 of 475
 TABLE 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 APPLICABLE 

 

277 of 475
 TABLE 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 APPLICABLE 

 

278 of 475
 TABLE 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 APPLICABLE 

 

279 of 475
 TABLE 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 APPLICABLE 

 

280 of 475
 TABLE 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 APPLICABLE 

 

281 of 475
 TABLE 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 APPLICABLE 

 

282 of 475
 TABLE 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 APPLICABLE 

 

283 of 475
 TABLE 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 APPLICABLE 

 

284 of 475
 TABLE 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 APPLICABLE 

 

285 of 475
 TABLE 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 APPLICABLE 

 

286 of 475
 TABLE 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 APPLICABLE 

 

287 of 475
 TABLE 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 APPLICABLE 

 

288 of 475
 TABLE 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 APPLICABLE 

 

289 of 475
 TABLE 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 APPLICABLE 

 

290 of 475
 TABLE 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 APPLICABLE 

 

291 of 475
 TABLE 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 APPLICABLE 

 

292 of 475
 TABLE 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 APPLICABLE 

 

293 of 475
 TABLE 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 APPLICABLE 

 

294 of 475
 TABLE 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 APPLICABLE 

 

295 of 475
 TABLE 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 APPLICABLE 

 

296 of 475
 TABLE 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 APPLICABLE 

 

297 of 475
 TABLE 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 APPLICABLE 

 

298 of 475
 TABLE 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 APPLICABLE 

 

299 of 475
 TABLE 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 APPLICABLE 

 

300 of 475
 TABLE 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 APPLICABLE 

 

301 of 475
 TABLE 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 APPLICABLE 

 

302 of 475
 TABLE 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 APPLICABLE 

 

303 of 475
 TABLE 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 APPLICABLE 

 

304 of 475
 TABLE 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 APPLICABLE 

 

305 of 475
 TABLE 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 APPLICABLE 

 

306 of 475
 TABLE 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 APPLICABLE 

 

307 of 475
 TABLE 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 APPLICABLE 

 

308 of 475
 TABLE 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 APPLICABLE 

 

309 of 475
 TABLE 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 APPLICABLE 

 

310 of 475
 TABLE 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 APPLICABLE 

 

311 of 475
 TABLE 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 APPLICABLE 

 

312 of 475
 TABLE 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 APPLICABLE 

 

313 of 475
 TABLE 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 APPLICABLE 

 

314 of 475
 TABLE 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 APPLICABLE 

 

315 of 475
 TABLE 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 APPLICABLE 

 

316 of 475
 TABLE 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 APPLICABLE 

 

317 of 475
 TABLE 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 APPLICABLE 

 

318 of 475
 TABLE 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 APPLICABLE 

 

319 of 475
 TABLE 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 APPLICABLE 

 

320 of 475
 TABLE 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 APPLICABLE 

 

321 of 475
 TABLE 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 APPLICABLE 

 

322 of 475
 TABLE 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 APPLICABLE 

 

323 of 475
 TABLE 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 APPLICABLE 

 

324 of 475
 TABLE 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 APPLICABLE 

 

325 of 475
 TABLE 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 APPLICABLE 

 

326 of 475
 TABLE 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 APPLICABLE 

 

327 of 475
 TABLE 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 APPLICABLE 

 

328 of 475
 TABLE 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 APPLICABLE 

 

329 of 475
 TABLE 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 APPLICABLE 

 

330 of 475
 TABLE 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 APPLICABLE 

 

331 of 475
 TABLE 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 APPLICABLE 

 

332 of 475
 TABLE 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 APPLICABLE 

 

333 of 475
 TABLE 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 APPLICABLE 

 

334 of 475
 TABLE 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 APPLICABLE 

 

335 of 475
 TABLE 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 APPLICABLE 

 

336 of 475
 TABLE 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 APPLICABLE 

 

337 of 475
 TABLE 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 APPLICABLE 

 

338 of 475
 TABLE 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 APPLICABLE 

 

339 of 475
 TABLE 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 APPLICABLE 

 

340 of 475
 TABLE 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 APPLICABLE 

 

341 of 475
 TABLE 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 APPLICABLE 

 

342 of 475
 TABLE 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 APPLICABLE 

 

343 of 475
 TABLE 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 APPLICABLE 

 

344 of 475
 TABLE 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 APPLICABLE 

 

345 of 475
 TABLE 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 APPLICABLE 

 

346 of 475
 TABLE 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 APPLICABLE 

 

347 of 475
 TABLE 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 APPLICABLE 

 

348 of 475
 TABLE 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 APPLICABLE 

 

349 of 475
 TABLE 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 APPLICABLE 

 

350 of 475
 TABLE 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 APPLICABLE 

 

351 of 475
 TABLE 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 

352

 07/02/2008 

 of 475
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 99.9923v% 

 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 

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APPENDIX C

Analyses Of Test Substance Purity And Stability

(WIL Research Laboratories, LLC)

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Analyses Of Test Substance Purity And Stability

Analytical Chemistry Department

WIL Research Laboratories, LLC

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TABLE OF CONTENTS

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

INDEX OF FIGURES

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

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INDEX OF TABLES

Page

Table 1: Purity Prior To Use ..............................................................................14

Table 2: Purity After Completion ......................................................................16

Table 3: Stability................................................................................................18

Table 4: Stability................................................................................................19

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1. INTRODUCTION

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. EXPERIMENTAL

2.1. GAS CHROMATOGRAPHY

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. PREPARATION OF SAMPLES FOR PURITY AND STABILITY ANALYSES

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

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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. PURITY AND STABILITY ASSESSMENTS

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. RESULTS AND DISCUSSION

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.

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Figure 1: Representative Chromatogram Of A Honeywell International, Inc.,

HFO-1234yf Sample From The Storage Cylinder Prior To Use

 For Animal Exposures

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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

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Figure 3: Representative Chromatogram Of A Honeywell International, Inc.,

HFO-1234yf Sample From The Storage Cylinder After Completion Of

Animal Exposures

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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

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Figure 5: Representative Chromatogram Of A Blank Air Injection

3.1. TEST SUBSTANCE PURITY ASSESSMENT

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. CONCLUSION

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

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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.

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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 

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TABLES 1 - 4

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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 

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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 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 

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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-) (%) (%) (%)

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

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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-) (%) (%) (%)

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

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Test Substance Mean 

Date Date Ref. Sample Run Retention Percent Percent 

 Collected Analyzed # ID # Time Area Area Area 

(447022-) (WIL log no-) (%) (%) 

Prior to Use

1/21/08 1/23/08 1-3 7749A#7-2 3 2.21 169970 100 1001/21/08 1/23/08 1-4 7749A#7-2 4 2.23 125859 100

After Completion

3/20/08 3/20/08 8-3 7749A#12-2 11 2.22 68772 100 100 

3/20/08 3/20/08 8-4 7749A#12-2 12 2.23 32611 100

447022

Printed: 12Jun2

Table 3: Stability

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Test Substance Mean 

Date Date Ref. Sample Run Retention Percent Percent 

 Collected Analyzed # ID # Time Area Area Area 

(447022-) (WIL log no-) (%) (%) 

Prior to Use

1/21/08 1/23/08 2-3 7819B#1-3 7 2.22 129626 100 1001/21/08 1/23/08 2-4 7819B#1-3 8 2.22 96281 100

After Completion

3/20/08 3/20/08 9-3 7819B#3-2 15 2.22 23583 100 100 

3/20/08 3/20/08 9-4 7819B#3-2 16 2.22 54163 100

447022.x

Printed: 12Jun

Table 4: Stability

AN INHALATION PRENATAL DEVELOPMENTAL TOXICITY 

STUDY OF HFO-1234yf (2,3,3,3-TETRAFLUOROPROPENE) IN RABBITS 

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APPENDIX D

Exposure Atmosphere Generation Report

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Exposure Atmosphere Generation Report

Inhalation Department

WIL Research Laboratories, LLC

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TABLE OF CONTENTS

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

INDEX OF FIGURES

1. Atmosphere Generation And Exposure System (Chambers 2, 3 And 4) ..................18

2. Atmosphere Generation And Exposure System (Chamber 5)...................................19

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INDEX OF TABLES

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

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1. EXPOSURE METHODS

1.1. EXPOSURE REGIMEN

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. INHALATION EXPOSURE SYSTEM DESCRIPTION

Exposures were conducted in one 2.0-m3 (2000-L) and four 1.5-m3 (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

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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. ANIMAL TRANSPORT AND PLACEMENT

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. EXPOSURE ENVIRONMENTAL CONDITIONS

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).

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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

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phase was at least 19% for all chambers and is presented in Tables 7 and 8 of this

appendix.

2. TEST ATMOSPHERE GENERATION METHODS

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:

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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. METHODS FOR CHARACTERIZATION OF EXPOSURE ATMOSPHERES

3.1. NOMINAL CONCENTRATIONS

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.

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WT × MV × 106

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

106 = 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. ANALYZED EXPOSURE CONCENTRATIONS

3.2.1. ANALYTICAL METHODS

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)

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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. GAS CHROMATOGRAPH CALIBRATION

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:

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106

 × VOL Concentration (ppm) = mL + VOL

Where:

VOL = Volume of gaseous test article injected into bag, mL

106 = 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

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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

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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. DETERMINATION OF HOMOGENEITY OF EXPOSURE ATMOSPHERES

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:

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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. RESULTS OF CHARACTERIZATION OF ACTUAL EXPOSURE

CONCENTRATIONS

4.1. NOMINAL EXPOSURE CONCENTRATIONS

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

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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. ANALYZED EXPOSURE CONCENTRATIONS

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

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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 

-16- 

400 of 475 
FIGURES 1 - 2

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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

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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

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HFO-1234yf

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TABLES 1 - 13

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Honeywell International Inc.

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 INHALATION 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:03/24/2008 

Honeywell International Inc.WIL-447022 HFO-1234yf -21- 

405 of 475
 INHALATION 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:03/24/2008 

Honeywell International Inc.WIL-447022 HFO-1234yf -22- 

406 of 475
 INHALATION 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:03/24/2008 

Honeywell International Inc.WIL-447022 HFO-1234yf -23- 

407 of 475
 INHALATION 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:03/24/2008 

Honeywell International Inc.WIL-447022 HFO-1234yf -24- 

408 of 475
 INHALATION 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:03/24/2008 

Honeywell International Inc.WIL-447022 HFO-1234yf -25- 

409 of 475
 INHALATION 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:03/24/2008 

Honeywell International Inc.WIL-447022 HFO-1234yf -26- 

410 of 475
 INHALATION 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:03/25/2008 

Honeywell International Inc.WIL-447022 HFO-1234yf -27- 

411 of 475
 INHALATION 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:06/18/2008 

Honeywell International Inc.WIL-447022 HFO-1234yf -28- 

412 of 475
 INHALATION 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 MILLION 

 

 

Honeywell International Inc.WIL-447022 HFO-1234yf -29- 

413 of 475
 INHALATION 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 MILLION 

 

 

Honeywell International Inc.WIL-447022 HFO-1234yf -30- 

414 of 475
 INHALATION 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 MILLION 

 

 

Honeywell International Inc.WIL-447022 HFO-1234yf -31- 

415 of 475
 INHALATION 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:06/18/2008 

Honeywell International Inc.WIL-447022 HFO-1234yf -32- 

416 of 475
 INHALATION 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:06/18/2008 

Honeywell International Inc.WIL-447022 HFO-1234yf -33- 

417 of 475
 INHALATION 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:06/18/2008 

Honeywell International Inc.WIL-447022 HFO-1234yf -34- 

418 of 475
 INHALATION 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: PPM 

 

Honeywell International Inc.WIL-447022 HFO-1234yf -35- 

419 of 475
 INHALATION 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: PPM 

 

Honeywell International Inc.WIL-447022 HFO-1234yf -36- 

420 of 475
 INHALATION 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: PPM 

 

Honeywell International Inc.WIL-447022 HFO-1234yf -37- 

421 of 475
 INHALATION 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: PPM 

 

Honeywell International Inc.WIL-447022 HFO-1234yf -38- 

422 of 475
 INHALATION 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:06/19/2008 

Honeywell International Inc.WIL-447022 HFO-1234yf -39- 

423 of 475
 INHALATION 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: PPM 

 

Honeywell International Inc.WIL-447022 HFO-1234yf -40- 

424 of 475
 INHALATION 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: PPM 

 

Honeywell International Inc.WIL-447022 HFO-1234yf -41- 

425 of 475
 INHALATION 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: PPM 

 

Honeywell International Inc.WIL-447022 HFO-1234yf -42- 

426 of 475
 INHALATION 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: PPM 

 

Honeywell International Inc.WIL-447022 HFO-1234yf -43- 

427 of 475
 INHALATION 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:06/19/2008 

Honeywell International Inc.WIL-447022 HFO-1234yf -44- 

428 of 475
WIL-447022 HFO-1234yf

Honeywell International Inc.

APPENDIX E

Animal Room Environmental Conditions

429 of 475
447022 TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY

HONEYWELL

INHALATION PRENATAL DEV TOX STUDY OF HFO-1234YF IN RABBITS

SPONSOR:PROJECT NO.:WIL

447022 01/18/08 1

03/20/08 1

STUDY SPECIFICATIONS: DATE IN: TIME IN:

DATE OUT: TIME OUT:

B ROOM 43RABBIT

LOW TEMPERATURE oF: 61.0 HIGH TEMPERATURE oF: 71.0 L

H

ROOM SPECIFICATIONS:SPECIES:

TEMPERATURE HUMIDITY

MEAN (oF)DATE MEAN (%RH)

LOW TEMPERATURE oC: 16.1 HIGH TEMPERATURE oC: 21.7

MEAN (oC)

18-Jan-08 18.6 65.5 51.8

19-Jan-08 18.6 65.4 52.7

20-Jan-08 18.6 65.5 53.0

21-Jan-08 18.6 65.4 53.6

22-Jan-08 18.6 65.5 53.1

23-Jan-08 18.5 65.4 53.3

24-Jan-08 18.7 65.6 53.5

25-Jan-08 18.6 65.6 52.9

26-Jan-08 18.6 65.5 53.5

27-Jan-08 18.6 65.5 53.6

28-Jan-08 18.5 65.4 54.3

29-Jan-08 18.7 65.6 54.1

30-Jan-08 18.6 65.6 53.8

31-Jan-08 18.6 65.5 54.0

01-Feb-08 18.6 65.5 54.2

02-Feb-08 18.7 65.7 53.6

03-Feb-08 18.8 65.8 54.4

04-Feb-08 18.6 65.5 55.9

05-Feb-08 18.6 65.4 58.5

06-Feb-08 18.7 65.7 54.5

07-Feb-08 18.5 65.3 54.5

08-Feb-08 18.7 65.7 53.2

09-Feb-08 18.7 65.7 54.7

4

NOTE: + = VALUE WAS GREATER THAN HIGH RANGE - = VALUE WAS LESS THAN LOW RANGENOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES

430 of 475
447022 TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY

HONEYWELL

INHALATION PRENATAL DEV TOX STUDY OF HFO-1234YF IN RABBITS

SPONSOR:PROJECT NO.:WIL

447022 01/18/08 1

03/20/08 1

STUDY SPECIFICATIONS: DATE IN: TIME IN:

DATE OUT: TIME OUT:

B ROOM 43RABBIT

LOW TEMPERATURE oF: 61.0 HIGH TEMPERATURE oF: 71.0 L

H

ROOM SPECIFICATIONS:SPECIES:

TEMPERATURE HUMIDITY

MEAN (oF)DATE MEAN (%RH)

LOW TEMPERATURE oC: 16.1 HIGH TEMPERATURE oC: 21.7

MEAN (oC)

10-Feb-08 18.7 65.7 50.8

11-Feb-08 18.7 65.6 53.8

12-Feb-08 18.5 65.4 52.8

13-Feb-08 18.8 65.9 52.9

14-Feb-08 18.7 65.6 53.1

15-Feb-08 18.8 65.9 54.2

16-Feb-08 18.8 65.9 50.4

17-Feb-08 19.0 66.1 51.3

18-Feb-08 18.7 65.6 52.0

19-Feb-08 18.8 65.9 50.1

20-Feb-08 18.8 65.9 50.0

21-Feb-08 18.8 65.8 51.1

22-Feb-08 18.7 65.7 51.8

23-Feb-08 18.7 65.6 52.5

24-Feb-08 18.6 65.5 53.0

25-Feb-08 18.7 65.7 53.3

26-Feb-08 18.6 65.5 52.0

27-Feb-08 18.5 65.3 52.7

28-Feb-08 18.6 65.6 52.2

29-Feb-08 18.6 65.5 52.5

01-Mar-08 18.8 65.8 52.0

02-Mar-08 18.6 65.6 52.3

03-Mar-08 18.6 65.5 53.0

4

NOTE: + = VALUE WAS GREATER THAN HIGH RANGE - = VALUE WAS LESS THAN LOW RANGENOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES

431 of 475
447022 TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY

HONEYWELL

INHALATION PRENATAL DEV TOX STUDY OF HFO-1234YF IN RABBITS

SPONSOR:PROJECT NO.:WIL

447022 01/18/08 1

03/20/08 1

STUDY SPECIFICATIONS: DATE IN: TIME IN:

DATE OUT: TIME OUT:

B ROOM 43RABBIT

LOW TEMPERATURE oF: 61.0 HIGH TEMPERATURE oF: 71.0 L

H

ROOM SPECIFICATIONS:SPECIES:

TEMPERATURE HUMIDITY

MEAN (oF)DATE MEAN (%RH)

LOW TEMPERATURE oC: 16.1 HIGH TEMPERATURE oC: 21.7

MEAN (oC)

04-Mar-08 18.6 65.6 51.8

05-Mar-08 18.8 65.8 51.4

06-Mar-08 18.7 65.7 52.5

07-Mar-08 18.7 65.7 51.8

08-Mar-08 18.8 65.8 51.9

09-Mar-08 18.7 65.7 50.7

10-Mar-08 18.7 65.7 51.8

11-Mar-08 18.6 65.6 53.1

12-Mar-08 18.7 65.7 52.5

13-Mar-08 18.7 65.7 51.6

14-Mar-08 18.5 65.3 52.8

15-Mar-08 18.7 65.7 52.3

16-Mar-08 18.7 65.7 51.8

17-Mar-08 18.6 65.5 51.7

18-Mar-08 18.7 65.6 51.6

19-Mar-08 18.6 65.5 53.9

20-Mar-08 18.7 65.7 54.7

4

NOTE: + = VALUE WAS GREATER THAN HIGH RANGE - = VALUE WAS LESS THAN LOW RANGENOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES

432 of 475
447022 TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY

HONEYWELL

INHALATION PRENATAL DEV TOX STUDY OF HFO-1234YF IN RABBITS

SPONSOR:PROJECT NO.:WIL

447022 01/18/08 1

03/20/08 1

STUDY SPECIFICATIONS: DATE IN: TIME IN:

DATE OUT: TIME OUT:

B ROOM 43RABBIT

LOW TEMPERATURE oF: 61.0 HIGH TEMPERATURE oF: 71.0 L

H

ROOM SPECIFICATIONS:SPECIES:

TEMPERATURE HUMIDITY

MEAN (oF)DATE MEAN (%RH)

LOW TEMPERATURE oC: 16.1 HIGH TEMPERATURE oC: 21.7

MEAN (oC)

65.6TEMPERATURE oF 65.3 66.1

58.550.052.8

63MEAN MIN MAX

18.7TEMPERATURE oC 18.5 19.0

HUMIDITY (%RH)GRAND STATSN DAYS

4

NOTE: + = VALUE WAS GREATER THAN HIGH RANGE - = VALUE WAS LESS THAN LOW RANGENOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES

433 of 475
447022 TEMPERATURE/HUMIDITY - END OF STUDY SUMMARY REPORT

HONEYWELL

INHALATION PRENATAL DEV TOX STUDY OF HFO-1234YF IN RABBITS

SPONSOR:PROJECT NO.:WIL- 15:08 29-Apr-0

B ROOM 43RABBIT

LOW TEMPERATURE: 61.0HIGH TEMPERATURE: 71.0LOW HUMIDITY: 30.0HIGH HUMIDITY: 70.0ROOM SPECIFICATIONS:SPECIES:

TEMPERATURE HUMIDITY

01/18/0810:0010:0003/20/08

DATE IN:TIME IN:DATE OUT:TIME OUT:

ROOM B ROOM 43 SUMMARY

MEANMINMAX

65.664.268.0

52.812.287.2

SD 0.63 3.07N SAMPLES 1485 1485N DAYSFIRST DAYLAST DAY

01/18/0803/20/08

63

4/

NOTE: TEMPERATURE UNITS = DEGREES FAHRENHEIT HUMIDITY UNITS = % RELATIVE HUMIDITYNOTE: MEANS REPRESENT THE MEAN OF ALL VALUES

434 of 475
447022 TEMPERATURE/HUMIDITY - END OF STUDY SUMMARY REPORT

HONEYWELL

INHALATION PRENATAL DEV TOX STUDY OF HFO-1234YF IN RABBITS

SPONSOR:PROJECT NO.:WIL- 15:08 29-Apr-0

STUDY 447022 SUMMARY

MEANMINMAX

65.664.268.0

52.812.287.2

SD 0.63 3.07N SAMPLES 1485 1485FIRST DAYLAST DAY

01/18/0803/20/08

N DAYS 63

4/

NOTE: TEMPERATURE UNITS = DEGREES FAHRENHEIT HUMIDITY 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 475
Total Mean Max S.D. Median Min SEM

25th

Quartile

Mean of Study Means

EndpointMean Gravid Uterine Weight (g)Total No. of Animals in the Control Group Total No. Viable FetusesMean No. Viable Fetuses/DamMean No. Postimplantation Loss/Dam Viable Fetuses (%/Litter) Postimplantation Loss (%/Litter) Total No. of Postimplantation Losses Late Resorptions (%/Litter) Early Resorptions (%/Litter)Mean No. Implantations/Dam Dead Fetuses (%/Litter)Mean No. Preimplantation Loss/DamMean No. Corpora Lutea/Dam Preimplantation Loss (%/Litter) Total No. Preimplantation LossesTotal No. Female FetusesTotal No. Male Fetuses Mean Male Body Weight (g)Mean Fetal Body Weight (g) Mean Female Body Weight (g)

325

496.9

8.8

2636

95.8

0.4

117

4.22.61.50.19.2

10.0

0.7

218

7.3

13391297

41.240.140.6

24.48

0.461.400.131.401.360.710.390.470.370.353.531.561.751.65

443.1

8.0

92.7

0.11.10.50.50.08.49.30.32.5

38.837.438.0

532.8

9.6

98.9

0.67.35.72.81.5

10.210.6

1.3

12.443.642.743.0

NO. OF DATASETSNo. of Animals Examined at Laparohysterectomy No. of Animals That Died No. of Animals That Aborted Percent Pregnant No. Gravid No. With Only Resorptions No. of Dams With Live Fetuses No. Nongravid% Females/Litter% Males/Litter

95.5 92.0 

6.540.120.370.030.370.360.100.130.100.090.940.190.440.420.47

503.2 478.3 

8.9 8.6 

95.9 95.3 

0.4 0.3 4.1 3.7 2.4 1.9 0.0 0.0 9.3 8.9 9.9 9.7 0.6 0.5 5.8 4.4 1.5 0.9 

41.1 39.3 41.4 40.2 40.6 38.6 

14

41

305

0

298

20

318

 No. of Animals That Delivered 2

93.8 4.60 1.23 85.0 100.0

50.7 4.49 1.2049.3 4.49 1.20 42.8 55.5

50.1 44.5 57.249.9

47.0 45.6 

WIL Developmental Historical ControlHra:(NZW)SPF Rabbit

New Zealand Rabbit Time-Mated [Ka

437 of 475
Mean of Study Means

MALFORMATIONS (% Per Litter) Mean Max S.D. Median Min SEM

25th

Quar

NO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally

263626362636

298298298

14

TOTAL EXTERNAL MALFORMATIONS 0.4 0.43 0.0 0.11 0.2 0.0 1.1 

TOTAL VISCERAL MALFORMATIONS 1.2 0.98 0.0 0.26 1.0 0.5 3.0 TOTAL SKELETAL MALFORMATIONS 1.1 0.60 0.0 0.16 1.1 0.8 2.2 

EXTERNAL 2

Carpal and/or Tarsal Flexure 0.0 0.14 0.0 0.04 0.0 0.0 0.5 

Cleft Palate 0.1 0.18 0.0 0.05 0.0 0.0 0.6 Ectrodactyly 0.0 0.12 0.0 0.03 0.0 0.0 0.4 Exencephaly with or without Open Eyelid(s) 0.1 0.18 0.0 0.05 0.0 0.0 0.5 Gastroschisis 0.1 0.21 0.0 0.06 0.0 0.0 0.6 Microphthalmia and/or Anophthalmia 0.1 0.24 0.0 0.06 0.0 0.0 0.9 Tail- Short 0.1 0.21 0.0 0.06 0.0 0.0 0.6 

VISCERAL 3

Bulbous Aorta 0.1 0.17 0.0 0.05 0.0 0.0 0.5 

Diaphragmatic Hernia 0.1 0.21 0.0 0.06 0.0 0.0 0.8 Heart- Misshapen 0.0 0.11 0.0 0.03 0.0 0.0 0.4 Hydrocephaly 0.1 0.33 0.0 0.09 0.0 0.0 0.9 Lung(s)- Lobular Agenesis 0.5 0.75 0.0 0.20 0.0 0.0 2.4 Lung(s)- Lobular Dysgenesis 0.0 0.17 0.0 0.04 0.0 0.0 0.6 Persistent Truncus Arteriosus 0.2 0.59 0.0 0.16 0.0 0.0 2.1 Stenotic Pulmonary Trunk 0.0 0.14 0.0 0.04 0.0 0.0 0.5 Thyroid Gland(s)- Absent 0.2 0.79 0.0 0.21 0.0 0.0 2.9 Transposition of the Great Vessels 0.0 0.17 0.0 0.04 0.0 0.0 0.6 

SKELETAL 4

Costal Cartilage Anomaly 0.1 0.32 0.0 0.08 0.0 0.0 1.1 

WIL Developmental Historical ControlHra:(NZW)SPF Rabbit

New Zealand Rabbit Time-Mated [Ka

438 of 475
Mean of Study Means

MALFORMATIONS (% Per Litter) Mean Max S.D. Median Min SEM

25th

Quar

NO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally

263626362636

298298298

14

SKELETAL 4

Rib Anomaly 0.2 0.34 0.0 0.09 0.0 0.0 1.2 

Skull Anomaly 0.1 0.24 0.0 0.06 0.0 0.0 0.8 Sternebra(e)- Fused 0.2 0.26 0.0 0.07 0.0 0.0 0.7 Sternebra(e)- Malaligned (Severe) 0.1 0.30 0.0 0.08 0.0 0.0 1.0 Vertebral Anomaly with or without Associated Rib Anomaly 0.5 0.42 0.0 0.11 0.4 0.0 1.3 Vertebral Centra Anomaly 0.1 0.23 0.0 0.06 0.0 0.0 0.7 

WIL Developmental Historical ControlHra:(NZW)SPF Rabbit

New Zealand Rabbit Time-Mated [Ka

439 of 475
Mean of Study Means

2

VARIATIONS (% Per Litter) Mean Max S.D. Median Min SEM

25th

Quar

NO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally

263626362636

298298298

14

TOTAL EXTERNAL VARIATIONS 0.0 0.00 0.0 0.00 0.0 0.0 0.0 

TOTAL VISCERAL VARIATIONS 25.4 5.12 17.3 1.37 23.7 22.5 35.4 

TOTAL SKELETAL VARIATIONS 61.6 6.24 52.9 1.67 63.0 56.2 71.1 

VISCERAL 3

Gallbladder- Absent or Small 2.5 1.43 0.0 0.38 2.4 1.5 5.4 

Gallbladder- Bilobed 0.0 0.12 0.0 0.03 0.0 0.0 0.4 Heart- Extra Papillary Muscle 2.7 1.74 0.0 0.46 2.7 2.0 7.8 Heart- Small 0.1 0.21 0.0 0.06 0.0 0.0 0.8 Hemorrhagic Ring Around the Iris 0.2 0.47 0.0 0.13 0.0 0.0 1.4 Liver- Pale 0.1 0.23 0.0 0.06 0.0 0.0 0.9 Major Blood Vessel Variation 7.7 2.66 3.0 0.71 7.8 5.6 12.5 

Pancreas- Small 0.1 0.21 0.0 0.06 0.0 0.0 0.8 

Retrocaval Ureter(s) 1.6 1.39 0.0 0.37 1.3 0.5 4.0 Spleen- Accessory 13.1 4.01 8.4 1.07 12.4 10.1 21.9 

Spleen- Pale 0.4 0.56 0.0 0.15 0.0 0.0 1.6 

Spleen- Small 0.1 0.14 0.0 0.04 0.0 0.0 0.4 Thymus- Hemorrhagic 0.6 0.76 0.0 0.20 0.0 0.0 2.1 Thyroid Gland(s)- Enlarged 0.1 0.33 0.0 0.09 0.0 0.0 1.3 

SKELETAL 4

13th Full Rib(s) 33.4 8.63 16.5 2.31 33.7 28.1 45.7 

13th Rudimentary Rib(s) 18.4 4.18 10.3 1.12 17.8 16.5 27.8 25 Presacral Vertebrae 0.3 0.71 0.0 0.19 0.0 0.0 2.5 

27 Presacral Vertebrae 8.6 2.98 4.8 0.80 7.5 6.8 15.6 

28 Presacral Vertebrae 0.0 0.11 0.0 0.03 0.0 0.0 0.4 

7th Cervical Rib(s) 1.9 1.06 0.5 0.28 1.7 1.0 3.7 

WIL Developmental Historical ControlHra:(NZW)SPF Rabbit

New Zealand Rabbit Time-Mated [Ka

440 of 475
Mean of Study Means

2

VARIATIONS (% Per Litter) Mean Max S.D. Median Min SEM

25th

Quar

NO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally

263626362636

298298298

14

SKELETAL 4

7th Sternebra 0.0 0.17 0.0 0.04 0.0 0.0 0.6 

Extra Site of Ossification Anterior to Sternebra #1 1.3 0.75 0.0 0.20 1.2 0.9 2.8 Extra Site of Ossification Ventral to Cervical Centrum #2 0.0 0.13 0.0 0.03 0.0 0.0 0.5 Hyoid Arch(es) Bent 5.2 1.63 1.3 0.43 5.3 5.0 7.6 Hyoid Body and/or Arch(es) Unossified 0.3 0.41 0.0 0.11 0.0 0.0 1.3 Reduced Ossification of the Skull 0.2 0.28 0.0 0.08 0.0 0.0 0.9 Skull Bone(s)- Accessory 0.3 0.34 0.0 0.09 0.2 0.0 0.9 Sternebra(e) #5 and/or #6 Unossified 8.6 4.69 3.9 1.25 6.8 5.2 18.5 

Sternebra(e)- Malaligned (Slight or Moderate) 0.7 0.51 0.0 0.14 0.7 0.5 2.1 

Sternebrae with Thread-Like Attachment 1.1 0.95 0.0 0.25 0.8 0.5 3.2 Vertebral Centra Not Fully Ossified 0.0 0.17 0.0 0.04 0.0 0.0 0.6 

WIL Developmental Historical ControlHra:(NZW)SPF Rabbit

New Zealand Rabbit Time-Mated [Ka

441 of 475
Modal Distribution of Fetal Body Weights 

40.0-40.9

No. of Datasets in Historical ControlRange of Study DatesNo. of Dams in Historical ControlNo. of Dams with Live FetusesMean Fetal Body Weight Range (g)

Mean Fetal Body Weight (g) 38.0-38.9 39.0-39.1 41.0-41.9 42.0-42.9 43

325298

38.0 - 43.0

14

8/22/2006 - 6/10/2007

Total No. Datasets 2Mean Litter SizeLitter Size Range

8.9

8.98.8 -

4

9.1

9.68.1 -

1

8.7

8.78.7 -

3

9.0

9.38.9 -

3

8.6

9.18.0 -

8.

WIL Developmental Historical ControlHra:(NZW)SPF Rabbit

New Zealand Rabbit Time-Mated [Ka

442 of 475
Distribution of Spontaneous Litter Complications

No. of 

Sites

Distribution of

Implantation Sites

No. of

Animals Percent

No. of

Animals Percent

No. of

Animals Percent

No. of

Animals

Females with Complete

Litter Resorption

Females that

Delivered/Aborted

Total Abnormal

Reproductive Outcomes

2 2 0 0.0 50.01 1 50.0

3 1 0 0.0 0.0 0 0 0.0

4 3 0 0.0 0.0 0 0 0.0

5 5 0 0.0 0.0 0 0 0.0

6 7 0 0.0 0.0 0 0 0.0

7 23 0 0.0 0.0 0 0 0.0

8 59 0 0.0 0.0 0 0 0.0

9 71 0 0.0 0.0 0 0 0.0

10 59 0 0.0 0.0 0 0 0.0

11 37 0 0.0 2.7 1 1 2.7

12 21 0 0.0 4.8 1 1 4.8

13 11 0 0.0 0.0 0 0 0.0

14 2 0 0.0 0.0 0 0 0.0

Total No. Gravid Does:

Total No. Datasets:

Years:

Average Litter Size:

14

8/22/2006 - 6/10/2007

305

8.8

WIL Developmental Historical ControlHra:(NZW)SPF Rabbit

New Zealand Rabbit Time-Mated [Ka

443 of 475
Summary Incidence Malformations and Variations

(Total Number Fetuses/Litters Affected)

Ranked Uppermost to Nethermost

MALFORMATIONS

NO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally

263626362636

298298298

Fetuses Litters

Number

14

EXTERNAL 2

Tail- 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 1

VISCERAL 3

Lung(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 1

SKELETAL 4

Vertebral Anomaly with or without Associated Rib Anomaly 12 12Rib Anomaly 5 5Sternebra(e)- Fused 4 4Sternebra(e)- Malaligned (Severe) 4 4

WIL Developmental Historical ControlHra:(NZW)SPF Rabbit

New Zealand Rabbit Time-Mated [Ka

444 of 475
Summary Incidence Malformations and Variations

(Total Number Fetuses/Litters Affected)

Ranked Uppermost to Nethermost

MALFORMATIONS

NO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally

263626362636

298298298

Fetuses Litters

Number

14

SKELETAL 4

Costal Cartilage Anomaly 3 3Skull Anomaly 2 2Vertebral Centra Anomaly 2 2

WIL Developmental Historical ControlHra:(NZW)SPF Rabbit

New Zealand Rabbit Time-Mated [Ka

445 of 475
Summary Incidence Malformations and Variations

(Total Number Fetuses/Litters Affected)

Ranked Uppermost to Nethermost

2

VARIATIONSNO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally

263626362636

298298298

Fetuses Litters

Number

14

VISCERAL 3

Spleen- 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 1

SKELETAL 4

13th 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 25

WIL Developmental Historical ControlHra:(NZW)SPF Rabbit

New Zealand Rabbit Time-Mated [Ka

446 of 475
Summary Incidence Malformations and Variations

(Total Number Fetuses/Litters Affected)

Ranked Uppermost to Nethermost

2

VARIATIONSNO. OF DATASETSTotal No. of Fetuses/Litters Examined ExternallyTotal No. of Fetuses/Litters Examined ViscerallyTotal No. of Fetuses/Litters Examined Skeletally

263626362636

298298298

Fetuses Litters

Number

14

SKELETAL 4

Sternebrae 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 1

WIL Developmental Historical ControlHra:(NZW)SPF Rabbit

New Zealand Rabbit Time-Mated [Ka

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 Developmental 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 numbers 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 g.9 :I:; ji 71 i;;; I: ;! 

450 of 475
Study Number: WIL-447022 

PROTOCOL AMENDMENT III 

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) 13 Reports: 

The following is added to this Section: 

For reporting purposes, the data from 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 report 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 animals and in Phase II, the data for 

the two 5,500 ppm groups will be combined 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 4,000a 24 

4 HFO-1234yf 5,500a 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 

Study Director 

L. Fleeman, BS, LAT * 

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 Developmental 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.

Group Target Exposure Concentration (ppm) Number of Females 

Number Test Article Phase I Phase II Phase I Phase II 

1 Filtered Air 0 0 12 12 

2 HFO-1234yfa 2,500 2,500 12 12 

3 HFO-1234yfa 4,000 5,500 12 12 

4 HFO-1234yfa 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 475
d191m mnmo, *am. 

,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 475
Page 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 475
Paee 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 475
WIL-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 475
WIL-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 475
Page 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 475
Page 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 475
Page 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 475
Page 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 475
Page 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 475
Paee 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 475
Wn-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 475
Page 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 

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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. 

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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. 

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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. 

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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 475
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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 475
Page 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. 

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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 475
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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 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 

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: 

- bk\ W 

Heather L. Johson, BS, RQAP-GLP 

Manager, Quality Assurance 

-3- 
WIL-447022 HFO-1234yf 

Honeywell International Inc. 

-4- 

REVISED PAGE
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 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.