Page 1 of 77

REVISED FINAL REPORT

STUDY TITLE

ACUTE INHALATION TOXICITY STUDY OF

 IN ALBINO RATS

STUDY NUMBER

DATA REQUIREMENT

U.S. EPA Health Effects Test Guidelines OPPTS Guideline 870.1300 (1998)

OECD Guideline For Testing Chemicals Section 4: Health Effects, Number 403

STUDY DIRECTOR

STUDY INITIATION DATE

December 27, 2007

STUDY COMPLETION DATE

October 9, 2008

DATE REVISED FINAL ISSUED

January 12, 2009

PERFORMING LABORATORY

SPONSOR STUDY NUMBER

SPONSOR


QUALITY ASSURANCE UNIT STATEMENT

Date(s) of

Inspection(s)

Phase

Inspected

Date(s) Findings

Reported

to Study Director

Date(s) Findings

Reported to 

Management Auditor(s)

23-Jan-2008 Test Article Exposure 23-Jan-2008 28-Feb-2008

09-May-2008 Study Records (Ex-1) 09-May-2008 23-Jun-2008

09-May-2008 Draft Report 09-May-2008 23-Jun-2008

10-Nov-2008 Final Report Amendment 10-Nov-2008 11-Nov-2008

12-Jan-2009 Revised Final Report 12-Jan-2009 12-Jan-2009

This study was inspected in accordance with the U.S. EPA Good Laboratory Practice

Regulations (40 CFR Part 160), the OECD Principles of Good Laboratory Practice, the standard

operating procedures of and the sponsor's protocol and

protocol amendments with the following exception. The data located in Appendix A (Certificate

Of Analysis) were the responsibility of the sponsor. Quality Assurance findings, derived from

the inspections during the conduct of the study and from the inspections of the raw data and draft

report (including the final report amendment and the revised final 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 

The raw data, the retention sample and the final report will be stored in the Archives at 

or another location specified by the sponsor.

Acute Inhalation Toxicity

Study of in Albino Rats

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TABLE OF CONTENTS

Page

REVISED FINAL REPORT.........................................................................................................2

GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT...................................3

QUALITY ASSURANCE UNIT STATEMENT ........................................................................4

KEY STUDY PERSONNEL AND REPORT SUBMISSION ...................................................5

Approval ....................................................................................................................................6

Table Of Contents..........................................................................................................................7

Index Of Figures ............................................................................................................................8

Index Of Tables..............................................................................................................................8

Index Of Attachments....................................................................................................................9

STUDY INFORMATION ...........................................................................................................10

SUMMARY ..................................................................................................................................11

A. Objective............................................................................................................................11

B. Test Guidelines ..................................................................................................................11

C. Study Design......................................................................................................................11

D. Results................................................................................................................................11

E. Conclusions........................................................................................................................11

Introduction..................................................................................................................................12

A. General Study Information ................................................................................................12

B. Key Study Dates ................................................................................................................12

C. Experimental Design..........................................................................................................12

EXPERIMENTAL PROCEDURES - MATERIALS AND METHODS................................13

A. Test Substance Identification.............................................................................................13

B. Exposure Methods .............................................................................................................13

C. Test Atmosphere Generation Methods ..............................................................................14

D. Methods Of Characterization Of Exposure Atmospheres .................................................15

1. Nominal Concentrations.........................................................................................................................15

2. Analyzed Concentrations .......................................................................................................................15

E. Route And Rationale Of Test Substance Administration ..................................................17

F. Animal Receipt And Acclimation......................................................................................17

G. Animal Housing.................................................................................................................17

H. Diet, Drinking Water And Maintenance............................................................................17

I. Environmental Conditions .................................................................................................18

J. Assignment Of Animals To Treatment Groups.................................................................18

K. Data Retention ...................................................................................................................18

PARAMETERS EVALUATED .................................................................................................19

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A. Mortality ............................................................................................................................19

B. Clinical Observations.........................................................................................................19

C. Body Weights.....................................................................................................................19

D. Necropsy ............................................................................................................................19

RESULTS AND DISCUSSION ..................................................................................................20

A. Characterization Of Exposure Atmospheres......................................................................20

1. Environmental Conditions......................................................................................................................20

2. Nominal Concentrations.........................................................................................................................20

3. Analyzed Concentrations .......................................................................................................................20

B. Mortality ............................................................................................................................20

C. Clinical Observations.........................................................................................................21

D. Body Weights.....................................................................................................................21

E. Necropsy ............................................................................................................................21

CONCLUSIONS ..........................................................................................................................22

DEVIATIONS FROM THE PROTOCOL................................................................................23

INDEX OF FIGURES

1. Atmosphere Generation And Exposure System...................................................................................25

INDEX OF TABLES

1. Individual Test Atmosphere Concentrations........................................................................................27

2. Summary Of Clinical Findings: Total Occurrence/No. Of Animals ..................................................28

3. Summary Of Body Weights [G]...........................................................................................................32

4. Summary Of Body Weight Changes [G] .............................................................................................34

5. Summary Of Macroscopic Findings ....................................................................................................36

6. Individual Clinical Observations..........................................................................................................38

7. Individual Body Weights [G] ...............................................................................................................42

8. Individual Body Weight Changes [G]..................................................................................................44

9. Individual Macroscopic Findings.........................................................................................................46

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INDEX OF ATTACHMENTS

Page

A. Certificate Of Analysis (Sponsor-Provided Data)..................................................................56

B. Animal Room Environmental Conditions..............................................................................58

C. Study Protocol.........................................................................................................................63

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STUDY INFORMATION

Test Material:

 Number:

Composition:

Purity: 99.9932%

CAS Registry Number:

Physical Characteristics: Clear, colorless liquid

Sponsor:

Study Initiated/Completed: December 27, 2007 / October 9, 2008

Experimental Start/Termination: January 23, 2008 / February 6, 2008

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SUMMARY

A. Objective

The objective of this study was to determine the acute inhalation toxicity of when

administered as a vapor for a single, 4-hour, nose-only exposure to rats.

B. Test Guidelines

The protocol was designed to be in compliance with the Environmental Protection Agency

(EPA) Office of Prevention, Pesticides and Toxic Substances (OPPTS) Guideline 870.1300 and

the Organisation for Economic Cooperation and Development (OECD) Guidelines for Testing

Chemicals, Section 403.

C. Study Design

The acute inhalation toxicity of was evaluated in this 4-hour, single-exposure study in

rats. The test substance was administered to 1 group of 5 male and 5 female Crl:CD(SD) albino

rats via nose-only exposure as a vapor at a concentration of 102,900 ppm, the highest achievable

vapor concentration.

Mortality, clinical observations, body weights and body weight changes were evaluated over a

14-day post-exposure observation period. Necropsies were conducted on all animals.

D. Results

None of the animals died during the exposure or the 14-day post-exposure observation period.

Clinical observations immediately following exposure included tremors and rales. There were

no toxicologically significant clinical signs during the 14-day post-exposure observation period,

and all animals were considered clinically normal by study day 1. There were no remarkable

changes in body weight. All animals surpassed their initial (study day 0) body weight by study

day 14 and were considered normal. The only macroscopic finding noted during the scheduled

necropsy was clear fluid contents in the uterus for 1 female. This macroscopic finding is

considered spurious and not related to test material exposure.

E. Conclusions

Based on the results of this study, the LC50 of was greater than 102,900 ppm, the

highest achievable vapor concentration, when male and female albino rats were exposed to a

vapor of the test substance as a single, 4-hour, nose-only exposure.

Acute Inhalation Toxicity

Study of in Albino Rats

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INTRODUCTION

A. General Study Information

This study presents the data from an “Acute Inhalation Toxicity Study of in Albino

Rats”.

The following computer protocol was used for data collection during the study:

Computer Protocol(s) Type of Data Collected

..............................................Main study data

B. Key Study Dates

Date(s) Event(s)

January 22, 2008........................................Experimental starting date

 (acclimation to nose-only tubes)

January 23, 2008........................................Experimental start date

 (day of exposure)

February 6, 2008........................................Experimental completion/termination date

 (gross necropsy)

C. Experimental Design

The following table presents the animal exposure conducted for the study:

Exposure Number of Animals

Number

Target Exposure

Concentration (ppm)

Analyzed Exposure

Concentration (ppm) Males Females

1 100,000 102,900a 5 5

a

 = Rounded value (actual value presented on tables is 102,878 ppm)

The target exposure concentration for this limit test was selected by the Sponsor based upon the

physical characteristics (boiling point) of the test article and exposure atmosphere specifications

from acute inhalation study guidelines. As determined during the method development phase of

the study, the mean temperature of the exposure atmosphere at concentrations greater than

approximately 100,000 ppm was above the guideline limit of 24°C due to the amount of heated

air required to completely vaporize the liquid test article.

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EXPERIMENTAL PROCEDURES - MATERIALS AND METHODS

A. Test Substance Identification

The test substance, [ was received from

on December 3, 2007, as follows:

Identification

No. of Containers

Received Description

1 cylinder

Gross weight: Clear, colorless

liquid

Purity and stability data were the responsibility of the sponsor. A Certificate of Analysis is

presented in Appendix A. The purity of the test substance was 99.9932%. The test substance

was stored at room temperature. A reserve sample of the test substance (approximately 6 g) was

collected on December 27, 2007, and stored in the Archives of 

B. Exposure Methods

The exposure was conducted using a 7.9-L conventional nose-only exposure system (designed

and fabricated by . Animals were restrained in nose-only

exposure holding tubes during exposure. Food and water were withheld during the exposure.

Exposure atmosphere environmental conditions were recorded at approximately 60-minute

intervals during the exposure. An Omega model no. HX94C temperature and humidity

transmitter probe (Omega Engineering, Inc., Stamford, Connecticut, U.S.A.) provided

monitoring of temperature and percent relative humidity. Oxygen content was measured on

January 17, 2008 during the pre-exposure method development phase using a Drager PAC III

equipped with a calibrated oxygen sensor (Draeger Safety, Inc., Pittsburgh, Pennsylvania,

U.S.A.). The oxygen content was 20.0%.

The time required to attain 99% of the equilibrium concentration (or clearance time for the

concentration to decrease from the equilibrium concentration) was calculated by the following

formula:

V × K t99 = F

Where:

V = volume of the conventional nose-only exposure system, L

K = constant for 99%, 4.60

F = flow rate of air through the chamber, L/minute

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The calculated t99 equilibrium time for this study was 1.4 minutes. Prior to the animal exposure,

the test substance atmosphere was generated to reach the approximate target concentration as

defined by the t99 equilibrium time. The animals were loaded on the nose-only exposure system

while the system was running. The start of the 4-hour animal exposure began when the last

animal was placed on the system.

C. Test Atmosphere Generation Methods

A vapor atmosphere of the test substance was generated using a system similar to that shown in

Figure 1. The system operated as follows: The test substance was metered at a known flow rate

by a liquid metering pump (Model QG50, 3/8-inch piston, Fluid Metering Inc., Syosset, New

York, U.S.A.) to the top of a glass bead vaporization column (2-inch I.D. × 26-inch length) filled

with 6-, 12- and 16-mm glass beads. The bead column was wrapped with an Omega electric

heating tape (model no. SRT101-100) controlled using a J-type thermocouple and digital

temperature controller set to maintain a temperature of 126-135°C. Using a Coilhose

Pneumatics Regulator (model no. 8802K, East Brunswick, New Jersey, U.S.A) and a Linde

rotameter-type flowmeter (Union Carbide Corp., Danbury, Connecticut, U.S.A.), compressed air

was metered to the bottom of the vaporization column. Vaporization occurred as the liquid test

substance coated the surface of the heated beads and air flowed up through the column. The test

substance vapors were piped to a tee prior to the nose-only system where the concentration

mixed with oxygen and humidified air. Oxygen was added from a compressed oxygen cylinder

(5.0 research grade, Praxair Inc., Danbury, Connecticut, U.S.A.) using a regulator (model no.

3051301-01-MIB, Concoa, Virginia Beach, Virginia, U.S.A.) and an Omega rotameter-type

flowmeter (model no. FL-3905G-HRV). Humidified air was added using a Coilhose Pneumatics

Regulator (model no. 8802K). A rotameter-type flowmeter (model no. VFB-69-BV, Dwyer

Instruments, Inc., Michigan City, Indiana, U.S.A.) was use to control the compressed air that

passed through a muffler-type bubbler submerged in a 2-L Erlenmeyer flask filled with

deionized water. The aerosol atmosphere was delivered to the nose-only exposure system

through 3/4-inch Tygon® tubing. The exhaust atmosphere passed through the in-house exhaust

system before being released from the facility. The parameters used for this study are

summarized in the following table:

Group

(ppm)

Generation

Airflow Rate

(mL/minute)

Oxygen

Flow Rate

(mL/minute)

Humidified

Airflow Rate

(L/minute)

Total

Airflow Rate

(L/minute)

Test Substance

Delivery Rate

(mL/minute)

102,900 15.0 1031 9.3 25.3 8.6

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D. Methods Of Characterization Of Exposure Atmospheres

1. Nominal Concentrations

The nominal exposure concentration was calculated for the exposure as the total amount of test

substance used during the exposure divided by the total volume of air that passed through the

chamber during the exposure, using the following equation:

Test Substance Used (g) × MV × 106

Nominal Concentration (ppm) = TAV × GMW

Where

MV = Molar volume at 

GMW = Gram molecular weight of the test substance, 

TAV = Total air volume of exposure, L

106 = ppm conversion

2. Analyzed Concentrations

Analyzed exposure concentrations were determined at approximately 60-minute intervals using a

gas chromatograph (GC). Samples of the exposure atmosphere were collected from the chamber

using an internal gas-sampling valve and sample loop. The chromatograph was displayed and

the area under the sample peak was calculated and stored. The concentration in parts per

million (ppm) was calculated using a ln-quadratic formula based on the GC calibration curve.

The following table summarizes the gas chromatograph conditions:

Gas Chromatograph: Hewlett Packard 5890 Series II

Detector: Flame ionization

Column: J&W Scientific, DB-5, 30 m × 0.530 mm, 0.5 micron film thickness

Gases

Carrier-Helium: 14 mL/minute

Fuel-Hydrogen: 32 mL/minute

Air: 303 mL/minute

Temperatures (°C)

Column: 100

Detector: 275

Auxiliary: 119

Retention Time: Approximately 0.7 minutes

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Study of in Albino Rats

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Integrator: Hewlett Packard 3396 Series II

Run Parameters

Zero Offset: 0

Attenuation: 13

Chart Speed: 2.0 cm/minute

Peak Area Rejection: 0

Peak Threshold: 6

Peak Width: 0.04

The GC was calibrated using gas-phase standards prepared to contain known vapor

concentrations of the test substance prepared in 10-L Tedlar® gas bags (SKC, Inc., Eighty Four,

Pennsylvania, U.S.A.). Standard bags were prepared by metering a known amount of air into the

bag using a dry test meter (Model DTM-200A, Elster American Meter Co., Nebraska City,

Nebraska, U.S.A.) and injecting a known volume of test substance. Using a hand-held heated

blower, the bag was warmed until total volatilization of the test substance was visually observed.

A sample was collected from the bag for approximately 8 minutes prior to being run through the

GC. The concentrations of the gas-phase standards were calculated as follows:

VOL × R × T × D × 10-3 × 106

Concentration (ppm) = L × GMW × P

Where:

VOL = Volume of test substance vaporized into bag, μL

R = Universal constant, 

T = Nominal laboratory temperature in K (273 + 21°C = 294 K)

D = Density of the test substance, 

L = Volume of air used to prepare bag, 

GMW = Gram molecular weight, 

P = Nominal laboratory barometric pressure,

10-3 = μL to mL conversion factor

106 = Conversion factor to ppm

Prior to initiating animal exposure, the GC was calibrated with standards prepared and analyzed

in triplicate. The calibration curve was defined using standards prepared at 4 vapor

concentrations spanning an appropriate range relative to the target exposure concentrations for

the study. The prime calibration curve was prepared for the target concentration using the

quadratic formula. The integrated peak area (y) and the theoretical concentrations of the

calibration standards (x) were fit with least-squares regression analysis to the ln-quadratic

formula:

ln (y) = a × [ln(x)]2

+ b × ln (x) + c

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Study of in Albino Rats

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On the day of exposure, 1 of the 4 standards was prepared and analyzed, and the prime

calibration curve was used to perform a calibration check of the GC. The following table

summarizes the standards used for this study:

Standard

Concentration (ppm)

Volume of Test

Substance (μL)

Volume of

Air (L)

84533 2000 5

101439 2400 5

118346 2800 5

126799 3000 5

E. Route And Rationale Of Test Substance Administration

The selected route of administration for this study was inhalation exposure since this is a reliable

and accurate method of evaluating toxicity and is the possible route of human exposure. The

nose-only exposure method was selected to reduce test substance requirements and minimize

dermal absorption. The animal model, the albino rat, is generally recognized as appropriate for

acute inhalation toxicity studies.

F. Animal Receipt And Acclimation

The Crl:CD(SD) rats used for this study were received in good health from Charles River

Laboratories, Raleigh, North Carolina, U.S.A., on January 15, 2007. The rats were uniquely

identified by ear tags displaying the animal number and were acclimated to the laboratory for a

minimum of 7 days. During the acclimation period, the rats were observed twice daily for

mortality and moribundity. The animals were subjected to restraint in the nose-only exposure

holding tubes for 1 hour on January 22, 2008 prior to test substance exposure.

G. Animal Housing

Upon arrival, all animals were housed in individual suspended wire-mesh cages. The animals

were maintained by the Animal Husbandry staff of in

accordance with standard operating procedures (SOP). On the day of exposure, the animals were

placed in nose-only exposure holding tubes in the animal room, transported to the exposure

room, exposed for the requisite duration then returned to their home cages.

H. Diet, Drinking Water And Maintenance

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

LabDiet® 5002, is a certified feed with appropriate analyses performed by the manufacturer and

provided to Municipal water supplying the facility is

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Study of in Albino Rats

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analyzed for contaminants according to SOP. The results of the diet and water analyses are

maintained at No contaminants were present in animal feed

or water at concentrations sufficient to interfere with the objectives of this study. The basal diet

and municipal water, delivered by an automatic watering system, were provided ad libitum,

except during the exposure period.

I. Environmental Conditions

The animal room was maintained with controlled temperature, humidity and light (12 hours

light/12 hours dark). The room temperature and humidity controls were set to maintain daily

averages of 71 ± 5°F (22 ± 3°C) and 50 ± 20% relative humidity. Room temperature and relative

humidity were monitored using the Metasys DDC Electronic Environmental control system and

were scheduled for data collection on an hourly basis. These data are summarized in

Appendix B. Actual mean daily temperature ranged from 70.4°F to 70.6°F (21.3°C to 21.5°C)

and mean daily relative humidity ranged from 35.9% to 48.1% during the study.

J. Assignment Of Animals To Treatment Groups

Animals used in the study were selected from available stock and assigned to groups using an

arbitrary assignment. The animals were selected based on body weight requirements and on the

appearance of general good health. The selected animals were approximately 8 weeks old at

initiation of exposure; body weight values ranged from 276 g to 294 g for males and from 207 g

to 226 g for females. Individual body weights at assignment were within ± 20% of the mean for

each sex.

K. 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 

including the original final report, raw paper data, specimens and pertinent

electronic storage media will be returned to the sponsor within 15 days of the issuance of the

final report, as specified in the study protocol.

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PARAMETERS EVALUATED

A. Mortality

Each animal was observed for mortality at the approximate midpoint of exposure, immediately

following exposure on study day 0 and twice daily thereafter for 14 days.

B. Clinical Observations

Each animal was observed immediately following exposure on study day 0 and once daily

thereafter for 14 days.

C. Body Weights

Body weights were obtained immediately prior to exposure on study day 0 and on post-exposure

days 7 and 14.

D. Necropsy

Animals at the scheduled necropsy were euthanized by isoflurane anesthesia followed by

exsanguination. The major organ systems of the cranial, thoracic and abdominal cavities were

examined for all animals.

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RESULTS AND DISCUSSION

A. Characterization Of Exposure Atmospheres

1. Environmental Conditions

Mean temperature and relative humidity of the animal exposure atmosphere was summarized in

the following table:

Group Temperature (°C) Relative Humidity (%)

(ppm) Mean S.D. N Mean S.D. N

102,900 25 1.3 4 41 6.8 4

2. Nominal Concentrations

The following table summarizes the nominal exposure concentration data for the atmosphere

generation period for the animal exposure:

Group

(ppm)

Test Substance

Used (g)

Generation

Time (minutes)

Total Volume of

Chamber Air (L)

Nominal Exposure

Concentration (ppm)

102,900 4141 245 6199 102,279

3. Analyzed Concentrations

Individual Data: Table 1

The following table summarizes the actual exposure concentration data for the animal exposure:

Group

(ppm)

Mean Concentration

(ppm)

Standard

Deviation

Number of

Samples

102,900 102,900 5549 4

B. Mortality

Summary Data: Table 2

Individual Data: Table 6

None of the animals died during exposure or during the 14-day post-exposure observation

period. Based on the data obtained, the LC50 of was found to be greater than

102,900 ppm.

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C. Clinical Observations

Summary Data: Table 2

Individual Data: Table 6

Immediately following exposure, tremors were observed for 2 males and 1 female, and rales was

observed for 2 females. There were no other toxicologically significant clinical signs

immediately following exposure. Several animals were noted with clear material on the facial

area, eyes, forelimbs, trunk, rump and urogenital area and/or yellow material on the urogenital

area immediately following exposure. These findings are typical for animals restrained in

nose-only exposure holding tubes for 4 hours. There were no toxicologically significant clinical

signs during the 14-day post-exposure observation period, and all animals were considered

clinically normal by study day 1.

D. Body Weights

Summary Data: Tables 3, 4

Individual Data: Tables 7, 8

There were no remarkable changes in body weight. All animals surpassed their initial (study

day 0) body weight by study day 14 and were considered normal.

E. Necropsy

Summary Data: Table 5

Individual Data: Table 9

The only macroscopic finding noted during the scheduled necropsy was clear fluid contents in

the uterus for 1 female. This finding was considered spurious and not related to test material

exposure. There were no other macroscopic findings for animals as the scheduled necropsy.

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Study of in Albino Rats

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CONCLUSIONS

Based on the results of this study, the LC50 of was greater than 102,900 ppm when

male and female albino rats were exposed to a vapor of the test substance as a single, 4-hour,

nose-only exposure.

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Study of in Albino Rats

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DEVIATIONS FROM THE PROTOCOL

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

the following.

• Protocol Section 7.5 states that the daily average temperature of the exposure

atmosphere will be 22 ± 2°C. On January 23, 2008, the average temperature of the

exposure atmosphere was 25°C.

This deviation was a result of the amount of heat required to completely vaporize the test

substance and did not negatively impact the quality or integrity of the data nor the outcome of

the study.

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Study of in Albino Rats

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FIGURE 1

Acute Inhalation Toxicity

Study of in Albino Rats

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Figure 1. Atmosphere Generation And Exposure System

Compressed

Oxygen

To Facility

Exhaust

7.9-L Nose-Only

System

Regulator and

Rotameter

Compressed

Air

Erlenmeyer

Flask Glass Bead

Column

Temp.

Controller

123

Test Article

Reservoir

FMI

Pump

Rotameter and

Regulator

Compressed

Air

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Study of in Albino Rats

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TABLES 1-9

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 TABLE 1 

 ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 1 INDIVIDUAL TEST ATMOSPHERE CONCENTRATIONS 

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

 CONCENTRATIONS FOR STUDY DAY: 0 EXPOSURE DATE:23-JAN-08 

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

 GROUP: 102,878 PPM 

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

 TIME INTO CONCENTRATION 

 EXPOSURE (HH:MM) (PPM) 

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

 00:30 94566. 

 01:30 105496. 

 02:30 105405. 

 03:32 106046. 

 

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

 MEAN 102878. 

 SD 5548.7 

 CV(%) 5.39 

 N 4 

 

 

 

Study of in Albino RatsAcute Inhalation Toxicity

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 TABLE 2 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 1 

 SPONSOR SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS 

 SPONSOR NO 

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

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

 DAY 0 POST-EXPOSURE 

 GROUP: 1 

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

 

 BEHAVIOR/CNS 

 -TREMORS 2/ 2 

 

 BODY/INTEGUMENT 

 -WET YELLOW MATERIAL UROGENITAL AREA 2/ 2 

 -WET CLEAR MATERIAL VENTRAL TRUNK 5/ 5 

 -WET CLEAR MATERIAL LEFT LATERAL TRUNK 4/ 4 

 -WET CLEAR MATERIAL UROGENITAL AREA 3/ 3 

 -WET CLEAR MATERIAL FORELIMB(S) 1/ 1 

 

 EYES/EARS/NOSE 

 -WET CLEAR MATERIAL LEFT EYE 1/ 1 

 -WET CLEAR MATERIAL RIGHT EYE 1/ 1 

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

 1- 102,878 PPM 

 

Study of in Albino RatsAcute Inhalation Toxicity

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 TABLE 2 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 2 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS SPONSOR NO.: 

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

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

 DAY 0 POST-EXPOSURE 

 GROUP: 1 

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

 

 BEHAVIOR/CNS 

 -TREMORS 1/ 1 

 

 BODY/INTEGUMENT 

 -WET YELLOW MATERIAL UROGENITAL AREA 2/ 2 

 -WET CLEAR MATERIAL VENTRAL TRUNK 5/ 5 

 -WET CLEAR MATERIAL UROGENITAL AREA 3/ 3 

 -WET CLEAR MATERIAL FORELIMB(S) 3/ 3 

 -WET CLEAR MATERIAL DORSAL RUMP 2/ 2 

 -WET CLEAR MATERIAL FACIAL AREA 2/ 2 

 -WET CLEAR MATERIAL RIGHT LATERAL TRUNK 1/ 1 

 

 CARDIO-PULMONARY 

 -RALES 2/ 2 

 

 EYES/EARS/NOSE 

 -WET CLEAR MATERIAL LEFT EYE 1/ 1 

 -WET CLEAR MATERIAL RIGHT EYE 4/ 4 

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

 1- 102,878 PPM 

 

Study of in Albino RatsAcute Inhalation Toxicity

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 TABLE 2 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 3 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS SPONSOR NO 

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

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

 TABLE RANGE: DAY 1 TO DAY 14 

 GROUP: 1 

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

 

 NORMAL 

 -NO SIGNIFICANT CLINICAL OBSERVATIONS 70/ 5 

 

 DISPOSITION 

 -SCHEDULED NECROPSY 5/ 5 

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

 1- 102,878 PPM 

 

Study of in Albino RatsAcute Inhalation Toxicity

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 TABLE 2 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 4 

 SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS SPONSOR NO.: 

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

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

 TABLE RANGE: DAY 1 TO DAY 14 

 GROUP: 1 

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

 

 NORMAL 

 -NO SIGNIFICANT CLINICAL OBSERVATIONS 68/ 5 

 

 DISPOSITION 

 -SCHEDULED NECROPSY 5/ 5 

 

 BODY/INTEGUMENT 

 -DRIED YELLOW MATERIAL UROGENITAL AREA 2/ 2 

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

 1- 102,878 PPM 

 

Study of in Albino RatsAcute Inhalation Toxicity

-31-
 TABLE 3 

 PROJECT NO ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 1 SPONSOR SUMMARY OF BODY WEIGHTS [G] SPONSOR NO 

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

 MALES 

 GROUP: 102,878 PPM 

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

 DAY 0 

 MEAN 282. 

 S.D. 7.4 

 N 5 

 

 7 

 MEAN 311. 

 S.D. 16.8 

 N 5 

 

 14 

 MEAN 362. 

 S.D. 16.8 

 N 5 

 

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

 

Study of in Albino RatsAcute Inhalation Toxicity

-32-
 TABLE 3 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 2 

 SUMMARY OF BODY WEIGHTS [G] SPONSOR NO 

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

 FEMALES 

 GROUP: 102,878 PPM 

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

 DAY 0 

 MEAN 212. 

 S.D. 8.0 

 N 5 

 

 7 

 MEAN 232. 

 S.D. 11.7 

 N 5 

 

 14 

 MEAN 250. 

 S.D. 15.7 

 N 5 

 

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

 

Study of in Albino RatsAcute Inhalation Toxicity

-33-
 TABLE 4 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 1 

 SUMMARY OF BODY WEIGHT CHANGES [G] SPONSOR 

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

 MALES 

 GROUP: 102,878 PPM 

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

 DAY 0 TO 7 

 MEAN 30. 

 S.D. 13.5 

 N 5 

 

 7 TO 14 

 MEAN 51. 

 S.D. 7.4 

 N 5 

 

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

 

Study of in Albino RatsAcute Inhalation Toxicity

-34-
 TABLE 4 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 2 

 SPONSOR SUMMARY OF BODY WEIGHT CHANGES [G] 

 SPONSOR 

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

 FEMALES 

 GROUP: 102,878 PPM 

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

 DAY 0 TO 7 

 MEAN 19. 

 S.D. 5.4 

 N 5 

 

 7 TO 14 

 MEAN 18. 

 S.D. 5.6 

 N 5 

 

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

 

Study of in Albino RatsAcute Inhalation Toxicity

-35-
 TABLE 5 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 1 . SUMMARY OF MACROSCOPIC FINDINGS SPONSOR 

 SCHEDULED NECROPSY 

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

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

 GROUP: 1 

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

 NUMBER OF ANIMALS IN DOSE GROUP 5 

 NUMBER OF ANIMALS TERMINALLY EUTHANIZED 5 

 

 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 5 

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

 1- 102,878 PPM 

 

Study of in Albino RatsAcute Inhalation Toxicity

-36-
 TABLE 5 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 2 SPONSOR SUMMARY OF MACROSCOPIC FINDINGS SPONSOR 

 SCHEDULED NECROPSY 

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

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

 GROUP: 1 

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

 NUMBER OF ANIMALS IN DOSE GROUP 5 

 NUMBER OF ANIMALS TERMINALLY EUTHANIZED 5 

 

 

 UTERUS 

 -CONTENTS, CLEAR FLUID 1 

 

 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 4 

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

 1- 102,878 PPM 

 

 

Study of in Albino RatsAcute Inhalation Toxicity

-37-
 TABLE 6 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 1 INDIVIDUAL CLINICAL OBSERVATIONS SPONSOR

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

 DURING POST- DAY POST-EXPOSURE 1 1 1 1 1 

 OBSERVATION NO. SEX GRP EXPOSURE EXPOSURE 1 2 3 4 5 6 7 8 9 0 1 2 3 4 

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

 

 NO SIGNIFICANT CLINICAL OBSERVATIONS 95086 M 1 - - P P P P P P P P P P P P P P 

 95087 M 1 - - P P P P P P P P P P P P P P 

 95089 M 1 - - P P P P P P P P P P P P P P 

 95090 M 1 - - P P P P P P P P P P P P P P 

 95094 M 1 - - P P P P P P P P P P P P P P 

 95099 F 1 - - P P P P P P P P P P P P P P 

 95101 F 1 - - P P P P P P P P P P P P P P 

 95110 F 1 - - - P P P P P P P P P P P P P 

 95113 F 1 - - P P P P P P P P P P P P P P 

 95114 F 1 - - - P P P P P P P P P P P P P 

 

 SCHEDULED NECROPSY 95086 M 1 - - - - - - - - - - - - - - - P 

 95087 M 1 - - - - - - - - - - - - - - - P 

 95089 M 1 - - - - - - - - - - - - - - - P 

 95090 M 1 - - - - - - - - - - - - - - - P 

 95094 M 1 - - - - - - - - - - - - - - - P 

 95099 F 1 - - - - - - - - - - - - - - - P 

 95101 F 1 - - - - - - - - - - - - - - - P 

 95110 F 1 - - - - - - - - - - - - - - - P 

 95113 F 1 - - - - - - - - - - - - - - - P 

 95114 F 1 - - - - - - - - - - - - - - - P 

 

 TREMORS 95089 M 1 - P - - - - - - - - - - - - - - 

 95094 M 1 - P - - - - - - - - - - - - - - 

 

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

 1- 102,878 PPM 

 GRP = GROUP 

 GRADE CODE: P = PRESENT S = SLIGHT M = MODERATE V = SEVERE - = NOT SEEN AT THAT INTERVAL 

 SEX CODE: M = MALE F = FEMALE 

 

Study of in Albino RatsAcute Inhalation Toxicity

-38-
 TABLE 6 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 2 SPONSOR INDIVIDUAL CLINICAL OBSERVATIONS SPONSOR NO 

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

 DURING POST- DAY POST-EXPOSURE 1 1 1 1 1 

 OBSERVATION NO. SEX GRP EXPOSURE EXPOSURE 1 2 3 4 5 6 7 8 9 0 1 2 3 4 

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

 

 TREMORS 95114 F 1 - P - - - - - - - - - - - - - - 

 

 WET YELLOW MATERIAL UROGENITAL AREA 95086 M 1 - P - - - - - - - - - - - - - - 

 95089 M 1 - P - - - - - - - - - - - - - - 

 95101 F 1 - P - - - - - - - - - - - - - - 

 95113 F 1 - P - - - - - - - - - - - - - - 

 

 WET CLEAR MATERIAL VENTRAL TRUNK 95086 M 1 - P - - - - - - - - - - - - - - 

 95087 M 1 - P - - - - - - - - - - - - - - 

 95089 M 1 - P - - - - - - - - - - - - - - 

 95090 M 1 - P - - - - - - - - - - - - - - 

 95094 M 1 - P - - - - - - - - - - - - - - 

 95099 F 1 - P - - - - - - - - - - - - - - 

 95101 F 1 - P - - - - - - - - - - - - - - 

 95110 F 1 - P - - - - - - - - - - - - - - 

 95113 F 1 - P - - - - - - - - - - - - - - 

 95114 F 1 - P - - - - - - - - - - - - - - 

 

 WET CLEAR MATERIAL LEFT LATERAL TRUNK 95086 M 1 - P - - - - - - - - - - - - - - 

 95087 M 1 - P - - - - - - - - - - - - - - 

 95089 M 1 - P - - - - - - - - - - - - - - 

 95094 M 1 - P - - - - - - - - - - - - - - 

 

 WET CLEAR MATERIAL UROGENITAL AREA 95087 M 1 - P - - - - - - - - - - - - - - 

 95090 M 1 - P - - - - - - - - - - - - - - 

 95094 M 1 - P - - - - - - - - - - - - - - 

 

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

 1- 102,878 PPM 

 GRP = GROUP 

 GRADE CODE: P = PRESENT S = SLIGHT M = MODERATE V = SEVERE - = NOT SEEN AT THAT INTERVAL 

 SEX CODE: M = MALE F = FEMALE 

 

Study of in Albino RatsAcute Inhalation Toxicity

-39-
 TABLE 6 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 3 INDIVIDUAL CLINICAL OBSERVATIONS SPONSOR 

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

 DURING POST- DAY POST-EXPOSURE 1 1 1 1 1 

 OBSERVATION NO. SEX GRP EXPOSURE EXPOSURE 1 2 3 4 5 6 7 8 9 0 1 2 3 4 

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

 

 WET CLEAR MATERIAL UROGENITAL AREA 95099 F 1 - P - - - - - - - - - - - - - - 

 95110 F 1 - P - - - - - - - - - - - - - - 

 95114 F 1 - P - - - - - - - - - - - - - - 

 

 WET CLEAR MATERIAL FORELIMB(S) 95089 M 1 - P - - - - - - - - - - - - - - 

 95110 F 1 - P - - - - - - - - - - - - - - 

 95113 F 1 - P - - - - - - - - - - - - - - 

 95114 F 1 - P - - - - - - - - - - - - - - 

 

 WET CLEAR MATERIAL DORSAL RUMP 95101 F 1 - P - - - - - - - - - - - - - - 

 95113 F 1 - P - - - - - - - - - - - - - - 

 

 WET CLEAR MATERIAL FACIAL AREA 95110 F 1 - P - - - - - - - - - - - - - - 

 95113 F 1 - P - - - - - - - - - - - - - - 

 

 WET CLEAR MATERIAL RIGHT LATERAL TRUNK 95114 F 1 - P - - - - - - - - - - - - - - 

 

 DRIED YELLOW MATERIAL UROGENITAL AREA 95110 F 1 - - P - - - - - - - - - - - - - 

 95114 F 1 - - P - - - - - - - - - - - - - 

 

 RALES 95113 F 1 - P - - - - - - - - - - - - - - 

 95114 F 1 - P - - - - - - - - - - - - - - 

 

 WET CLEAR MATERIAL LEFT EYE 95089 M 1 - P - - - - - - - - - - - - - - 

 95101 F 1 - P - - - - - - - - - - - - - - 

 

 WET CLEAR MATERIAL RIGHT EYE 95089 M 1 - P - - - - - - - - - - - - - - 

 95099 F 1 - P - - - - - - - - - - - - - - 

 95101 F 1 - P - - - - - - - - - - - - - - 

 95110 F 1 - P - - - - - - - - - - - - - - 

 

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

 1- 102,878 PPM 

 GRP = GROUP 

 GRADE CODE: P = PRESENT S = SLIGHT M = MODERATE V = SEVERE - = NOT SEEN AT THAT INTERVAL 

 SEX CODE: M = MALE F = FEMALE 

 

Study of in Albino RatsAcute Inhalation Toxicity

-40-
 TABLE 6 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 4 INDIVIDUAL CLINICAL OBSERVATIONS SPONSOR

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

 DURING POST- DAY POST-EXPOSURE 1 1 1 1 1 

 OBSERVATION NO. SEX GRP EXPOSURE EXPOSURE 1 2 3 4 5 6 7 8 9 0 1 2 3 4 

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

 

 WET CLEAR MATERIAL RIGHT EYE 95113 F 1 - P - - - - - - - - - - - - - - 

 

 ALIVE AT MIDPOINT 95086 M 1 P - - - - - - - - - - - - - - - 

 95087 M 1 P - - - - - - - - - - - - - - - 

 95089 M 1 P - - - - - - - - - - - - - - - 

 95090 M 1 P - - - - - - - - - - - - - - - 

 95094 M 1 P - - - - - - - - - - - - - - - 

 95099 F 1 P - - - - - - - - - - - - - - - 

 95101 F 1 P - - - - - - - - - - - - - - - 

 95110 F 1 P - - - - - - - - - - - - - - - 

 95113 F 1 P - - - - - - - - - - - - - - - 

 95114 F 1 P - - - - - - - - - - - - - - - 

 

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

 1- 102,878 PPM 

 GRP = GROUP 

 GRADE CODE: P = PRESENT S = SLIGHT M = MODERATE V = SEVERE - = NOT SEEN AT THAT INTERVAL 

 SEX CODE: M = MALE F = FEMALE 

 

Study of in Albino RatsAcute Inhalation Toxicity

-41-
 TABLE 7 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 1 SPONSOR INDIVIDUAL BODY WEIGHTS [G] SPONSOR NO 

 MALE GROUP: 102,878 PPM 

 DAY 0 7 14 

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

 ANIMAL 

 95086 280. 313. 376. 

 95087 283. 333. 376. 

 95089 276. 289. 337. 

 95090 294. 320. 369. 

 95094 276. 302. 354. 

 

 

 MEAN 282. 311. 362. 

 S.D. 7.4 16.8 16.8 

 N 5 5 5 

 

Study of in Albino RatsAcute Inhalation Toxicity

-42-
 TABLE 7 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 2 SPONSOR INDIVIDUAL BODY WEIGHTS [G] SPONSOR NO 

 FEMALE GROUP: 102,878 PPM 

 DAY 0 7 14 

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

 ANIMAL 

 95099 209. 231. 250. 

 95101 207. 217. 231. 

 95110 207. 227. 238. 

 95113 226. 249. 270. 

 95114 212. 234. 259. 

 

 

 MEAN 212. 232. 250. 

 S.D. 8.0 11.7 15.7 

 N 5 5 5 

 

Study of in Albino RatsAcute Inhalation Toxicity

-43-
 TABLE 8 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 1 SPONSOR INDIVIDUAL BODY WEIGHT CHANGES [G] SPONSOR 

 MALE GROUP: 102,878 PPM 

 DAY 0 TO 7 7 TO 14 

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

 ANIMAL 

 95086 33. 63. 

 95087 50. 43. 

 95089 13. 48. 

 95090 26. 49. 

 95094 26. 52. 

 

 

 MEAN 30. 51. 

 S.D. 13.5 7.4 

 N 5 5 

 

Study of in Albino RatsAcute Inhalation Toxicity

-44-
 TABLE 8 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 2 SPONSOR INDIVIDUAL BODY WEIGHT CHANGES [G] SPONSOR 

 FEMALE GROUP: 102,878 PPM 

 DAY 0 TO 7 7 TO 14 

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

 ANIMAL 

 95099 22. 19. 

 95101 10. 14. 

 95110 20. 11. 

 95113 23. 21. 

 95114 22. 25. 

 

 

 MEAN 19. 18. 

 S.D. 5.4 5.6 

 N 5 5 

 

Study of in Albino RatsAcute Inhalation Toxicity

-45-
 TABLE 9 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 1 INDIVIDUAL MACROSCOPIC FINDINGS SPONSOR NO 

 

 ANIMAL NO. 95086 GROUP 1: 102,878 PPM MALE SCHEDULED EUTH 02/06/08 DATE OF DEATH: 02/06/08 STUDY DAY: 14 

 GRADE 

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

 NO SIGNIFICANT 

 CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS 

 EYES HEART INTESTINE KIDNEYS 

 LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND 

 PANCREAS PITUITARY PROSTATE SPINAL CORD 

 SAL. GLAND MAND SKIN SPLEEN STOMACH 

 SEMINAL VESICLES TESTES THYMUS THYROID GLANDS 

 TRACHEA URINARY BLADDER DIAPHRAGM 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

Study of in Albino RatsAcute Inhalation Toxicity

-46-
 TABLE 9 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 2 SPONSOR . INDIVIDUAL MACROSCOPIC FINDINGS 

 SPONSOR NO 

 

 ANIMAL NO. 95087 GROUP 1: 102,878 PPM MALE SCHEDULED EUTH 02/06/08 DATE OF DEATH: 02/06/08 STUDY DAY: 14 

 GRADE 

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

 NO SIGNIFICANT 

 CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS 

 EYES HEART INTESTINE KIDNEYS 

 LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND 

 PANCREAS PITUITARY PROSTATE SPINAL CORD 

 SAL. GLAND MAND SKIN SPLEEN STOMACH 

 SEMINAL VESICLES TESTES THYMUS THYROID GLANDS 

 TRACHEA URINARY BLADDER DIAPHRAGM 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

Study of in Albino RatsAcute Inhalation Toxicity

-47-
 TABLE 9 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 3 SPONSOR INDIVIDUAL MACROSCOPIC FINDINGS 

 SPONSOR NO 

 

 ANIMAL NO. 95089 GROUP 1: 102,878 PPM MALE SCHEDULED EUTH 02/06/08 DATE OF DEATH: 02/06/08 STUDY DAY: 14 

 GRADE 

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

 NO SIGNIFICANT 

 CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS 

 EYES HEART INTESTINE KIDNEYS 

 LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND 

 PANCREAS PITUITARY PROSTATE SPINAL CORD 

 SAL. GLAND MAND SKIN SPLEEN STOMACH 

 SEMINAL VESICLES TESTES THYMUS THYROID GLANDS 

 TRACHEA URINARY BLADDER DIAPHRAGM 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

Study of in Albino RatsAcute Inhalation Toxicity

-48-
 TABLE 9 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 4 SPONSOR INDIVIDUAL MACROSCOPIC FINDINGS 

 SPONSOR NO 

 

 ANIMAL NO. 95090 GROUP 1: 102,878 PPM MALE SCHEDULED EUTH 02/06/08 DATE OF DEATH: 02/06/08 STUDY DAY: 14 

 GRADE 

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

 NO SIGNIFICANT 

 CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS 

 EYES HEART INTESTINE KIDNEYS 

 LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND 

 PANCREAS PITUITARY PROSTATE SPINAL CORD 

 SAL. GLAND MAND SKIN SPLEEN STOMACH 

 SEMINAL VESICLES TESTES THYMUS THYROID GLANDS 

 TRACHEA URINARY BLADDER DIAPHRAGM 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

Study of in Albino RatsAcute Inhalation Toxicity

-49-
 TABLE 9 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 5 SPONSOR INDIVIDUAL MACROSCOPIC FINDINGS 

 SPONSOR NO 

 

 ANIMAL NO. 95094 GROUP 1: 102,878 PPM MALE SCHEDULED EUTH 02/06/08 DATE OF DEATH: 02/06/08 STUDY DAY: 14 

 GRADE 

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

 NO SIGNIFICANT 

 CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS 

 EYES HEART INTESTINE KIDNEYS 

 LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND 

 PANCREAS PITUITARY PROSTATE SPINAL CORD 

 SAL. GLAND MAND SKIN SPLEEN STOMACH 

 SEMINAL VESICLES TESTES THYMUS THYROID GLANDS 

 TRACHEA URINARY BLADDER DIAPHRAGM 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

Study of in Albino RatsAcute Inhalation Toxicity

-50-
 TABLE 9 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 6 INDIVIDUAL MACROSCOPIC FINDINGS SPONSOR NO 

 

 ANIMAL NO. 95099 GROUP 1: 102,878 PPM FEMALE SCHEDULED EUTH 02/06/08 DATE OF DEATH: 02/06/08 STUDY DAY: 14 

 GRADE 

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

 NO SIGNIFICANT 

 CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES 

 HEART INTESTINE KIDNEYS LIVER 

 LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS 

 OVARIES PANCREAS PITUITARY SPINAL CORD 

 SAL. GLAND MAND SKIN SPLEEN STOMACH 

 THYMUS THYROID GLANDS TRACHEA URINARY BLADDER 

 UTERUS CERVIX VAGINA DIAPHRAGM 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

Study of in Albino RatsAcute Inhalation Toxicity

-51-
 TABLE 9 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 7 SPONSOR INDIVIDUAL MACROSCOPIC FINDINGS SPONSOR 

 

 ANIMAL NO. 95101 GROUP 1: 102,878 PPM FEMALE SCHEDULED EUTH 02/06/08 DATE OF DEATH: 02/06/08 STUDY DAY: 14 

 GRADE 

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

 UTERUS GROSS: CONTENTS, CLEAR FLUID P 

 BOTH HORNS 

 NO SIGNIFICANT 

 CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES 

 HEART INTESTINE KIDNEYS LIVER 

 LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS 

 OVARIES PANCREAS PITUITARY SPINAL CORD 

 SAL. GLAND MAND SKIN SPLEEN STOMACH 

 THYMUS THYROID GLANDS TRACHEA URINARY BLADDER 

 CERVIX VAGINA DIAPHRAGM 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

Study of in Albino RatsAcute Inhalation Toxicity

-52-
 TABLE 9 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 8 SPONSOR INDIVIDUAL MACROSCOPIC FINDINGS SPONSOR NO 

 

 ANIMAL NO. 95110 GROUP 1: 102,878 PPM FEMALE SCHEDULED EUTH 02/06/08 DATE OF DEATH: 02/06/08 STUDY DAY: 14 

 GRADE 

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

 NO SIGNIFICANT 

 CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES 

 HEART INTESTINE KIDNEYS LIVER 

 LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS 

 OVARIES PANCREAS PITUITARY SPINAL CORD 

 SAL. GLAND MAND SKIN SPLEEN STOMACH 

 THYMUS THYROID GLANDS TRACHEA URINARY BLADDER 

 UTERUS CERVIX VAGINA DIAPHRAGM 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

Study of in Albino RatsAcute Inhalation Toxicity

-53-
 TABLE 9 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 9 SPONSOR INDIVIDUAL MACROSCOPIC FINDINGS SPONSOR NO 

 

 ANIMAL NO. 95113 GROUP 1: 102,878 PPM FEMALE SCHEDULED EUTH 02/06/08 DATE OF DEATH: 02/06/08 STUDY DAY: 14 

 GRADE 

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

 NO SIGNIFICANT 

 CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES 

 HEART INTESTINE KIDNEYS LIVER 

 LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS 

 OVARIES PANCREAS PITUITARY SPINAL CORD 

 SAL. GLAND MAND SKIN SPLEEN STOMACH 

 THYMUS THYROID GLANDS TRACHEA URINARY BLADDER 

 UTERUS CERVIX VAGINA DIAPHRAGM 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

Study of in Albino RatsAcute Inhalation Toxicity

-54-
 TABLE 9 

 PROJECT NO.: ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS PAGE 10 INDIVIDUAL MACROSCOPIC FINDINGS SPONSOR NO 

 

 ANIMAL NO. 95114 GROUP 1: 102,878 PPM FEMALE SCHEDULED EUTH 02/06/08 DATE OF DEATH: 02/06/08 STUDY DAY: 14 

 GRADE 

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

 NO SIGNIFICANT 

 CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES 

 HEART INTESTINE KIDNEYS LIVER 

 LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS 

 OVARIES PANCREAS PITUITARY SPINAL CORD 

 SAL. GLAND MAND SKIN SPLEEN STOMACH 

 THYMUS THYROID GLANDS TRACHEA URINARY BLADDER 

 UTERUS CERVIX VAGINA DIAPHRAGM 

 

 GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT 

 

Study of in Albino RatsAcute Inhalation Toxicity

-55-
APPENDIX A

Certificate Of Analysis (Sponsor-Provided Data)

Acute Inhalation Toxicity

Study of in Albino Rats

-56-

 
 " CERTIFICATE OF ANALYSIS

 This is to advise you that the product listed below

 has been classified BY GC/FID, GC/MSD

 Data are provided below.

 LOT Number: 

 GROSS 

TARE .

NET 

 ANALYSIS: 

Possible Impurities

 

 

Unknowns N.D. m%

1. Analysis done using GC-FID with calculated response factors for

impurities (11/30/07)

2. Compound Id verified by GC-MSD.

3. N.D. = non-detect: detection limit by GC-FID is 1ppm.

 

 

 

 

 

Acute Inhalation Toxicity

Study of in Albino Rats

-57-

 
APPENDIX B

Animal Room Environmental Conditions

Acute Inhalation Toxicity

Study of in Albino Rats

-58-

 
TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY

ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS

SPONSOR:PROJECT NO -

01/16/08 12:0

02/06/08 10:0

STUDY SPECIFICATIONS: DATE IN: TIME IN:

DATE OUT: TIME OUT:

B ROOM 53 SENSOR 2RAT

LOW TEMPERATURE oF: 66.0 HIGH TEMPERATURE oF: 76.0 LOW 

HIGH 

ROOM SPECIFICATIONS:SPECIES:

TEMPERATURE HUMIDITY

DATE MEAN (oF) MEAN (%RH)

LOW TEMPERATURE oC: 18.9 HIGH TEMPERATURE oC: 24.4

MEAN (oC)

16-Jan-08 21.4 70.4 37.3

17-Jan-08 21.3 70.4 39.2

18-Jan-08 21.3 70.4 37.2

19-Jan-08 21.3 70.4 37.2

20-Jan-08 21.4 70.4 35.9

21-Jan-08 21.3 70.4 36.4

22-Jan-08 21.4 70.4 37.7

23-Jan-08 21.3 70.4 37.0

24-Jan-08 21.3 70.4 37.7

25-Jan-08 21.4 70.5 37.4

26-Jan-08 21.4 70.5 38.3

27-Jan-08 21.3 70.4 38.8

28-Jan-08 21.4 70.5 39.4

29-Jan-08 21.4 70.5 41.8

30-Jan-08 21.3 70.4 38.3

31-Jan-08 21.4 70.5 39.9

01-Feb-08 21.4 70.4 42.8

02-Feb-08 21.4 70.5 40.8

03-Feb-08 21.4 70.5 40.7

04-Feb-08 21.4 70.6 44.3

05-Feb-08 21.3 70.4 48.1

06-Feb-08 21.5 70.6 42.6

NOTE: + = VALUE WAS GREATER THAN HIGH RANGE

 - = VALUE WAS LESS THAN LOW RANGENOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES

-59-

 
TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY

ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS

SPONSOR:PROJECT NO

01/16/08 12:0

02/06/08 10:0

STUDY SPECIFICATIONS: DATE IN: TIME IN:

DATE OUT: TIME OUT:

B ROOM 53 SENSOR 2RAT

LOW TEMPERATURE oF: 66.0 HIGH TEMPERATURE oF: 76.0 LOW 

HIGH 

ROOM SPECIFICATIONS:SPECIES:

TEMPERATURE HUMIDITY

DATE MEAN (oF) MEAN (%RH)

LOW TEMPERATURE oC: 18.9 HIGH TEMPERATURE oC: 24.4

MEAN (oC)

TEMPERATURE oF 70.4 70.6 70.5

48.135.939.5

22MEAN MIN MAX

TEMPERATURE oC 21.3 21.5 21.4HUMIDITY (%RH)GRAND STATSN DAYS

4/2/

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

-60-

 
TEMPERATURE/HUMIDITY - END OF STUDY SUMMARY REPORT

ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS

SPONSOR:PROJECT NO.: 10:30 02-Apr-08 

B ROOM 53 SENSOR 2RAT

LOW TEMPERATURE: 66.0HIGH TEMPERATURE: 76.0LOW HUMIDITY: 30.0HIGH HUMIDITY: 70.0ROOM SPECIFICATIONS:SPECIES:

TEMPERATURE HUMIDITY

01/16/0812:0010:0002/06/08

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

ROOM B ROOM 53 SENSOR 2 SUMMARY

MEANMINMAX

70.467.671.3

39.533.656.7

SD 0.22 3.42

N SAMPLES 502 502N DAYSFIRST DAYLAST DAY

01/16/0802/06/08

22

4/2/2

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

-61-

 
TEMPERATURE/HUMIDITY - END OF STUDY SUMMARY REPORT

ACUTE INHALATION TOXICITY STUDY OF IN ALBINO RATS

SPONSOR:PROJECT NO.: 10:30 02-Apr-08 

STUDY SUMMARY

MEANMINMAX

70.467.671.3

39.533.656.7

SD 0.22 3.42

N SAMPLES 502 502FIRST DAYLAST DAY

01/16/0802/06/08

N DAYS 22

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

-62-

 
APPENDIX C

Study Protocol

Acute Inhalation Toxicity

Study of in Albino Rats

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Acute Inhalation Toxicity

Study of in Albino Rats

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Study of in Albino Rats

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Study of in Albino Rats

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Study of in Albino Rats

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Study of in Albino Rats

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Study of in Albino Rats

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Study of in Albino Rats

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Acute Inhalation Toxicity

Study of in Albino Rats

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Study of in Albino Rats

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Study of in Albino Rats

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Acute Inhalation Toxicity

Study of in Albino Rats

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Acute Inhalation Toxicity

Study of in Albino Rats

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Acute Inhalation Toxicity

Study of in Albino Rats

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Acute Inhalation Toxicity

Study of in Albino Rats

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