# REPORT
StudyTitle: DETERMINATION OFTHE FREEZING POINT

### I FREEZING RANGE AND OFTHE BOILING POINT

### I BOILING RANGE OF DEA/Acid anhydride reaction product

Data RequirementITest Guidelines: OECD No. 102, 103 EEC Directive 92/69, A.1 and A.2 Study Director: Mrs. AlessandraTognucci StudyCompletion Date: December 17, 2003 Test Facility: RCC Ltd Environmental Chemistry& Pharmanalytics CH-4452 ltingen/Switzerland Sponsor: RockwoollnternationalA/S Hovedgaden 584 DK-2640 Hedehusene Denmark
RCC Study Number: 848616 Page 1 of 15RCC Study Number848616 DEA/Acid anhydride reaction product 

# GLP CERTIFICATE REPORT

The Swiss GLP Monitoring Authorities
Swiss Federal Offioeof PublicHealth SwissAgencyforthe Environment. Forests and Landscape **~** Swissmedic 

### r . SwissAgencyfor 

## SW1ssmed1c TherapeutlcProducts 

# Statement of GLP Compliance

Itis herebyconfirmed that during the period of thefollowingTest Facilities of November 18- 22, 2002 

### RCC Ltd 4452 ltingen Switzerland

were inspected by the Federal Office of Public Health, the Swiss Agency for Therapeutic Products and the Swiss Agencyfo'rthe Environment, Forests and Landscape with respectto the compliancewith the Swiss legislation onGood Laboratory Practice. TestFacilities -Toxicology -Environmental Chemistryand

Pharmanalytics Areas ofexpertise* TOX, ACC, MUT, OTH (Safety Pharmacology) ACC, ECT, ENF, EMN, PCT, RES, OTH (Animal metabolism)

The inspections were performed in agreement with the OECD Guidelines for National GLP Inspections and Audits. Itwas found that the aforementioned testfacilities were operating in compliancewith the Swiss Ordinance relating to Good Laboratory Practice [RS 813.016.5] at thetimetheywere inspected.

Bern, March2003 Federal Officeof Public Health The Director

Prof. Th. Zeltner

•TOX::Toxicology :ACC =Analyticaland Clinical Chemlstty : ECT= Environmental toxicityon aquaticand terrestrial organisms : ENF =BehaviourInwater. soliand air. Bioaccumulation ; EMN =Studieson effects onmesocosmsand natural ecosystems: MUT• Mutagenicity; PCT =Physical-chemicaltesting: RES= Residue studies:OTH::Other, tobespecified. Page2RCC Study Number848616 DEA/Acid anhydride reaction product 

### GOOD LABORATORY PRACTICE REPORT Page 3



# STATEMENT OF COMPLIANCE

RCC Study Number: Test Item: Study Director: Title: 848616 DEA/Acid anhydride reaction product Mrs. Alessandra Tognucci Determination of the Freezing Point 

### I Freezing Range and of the Boiling Point 

### I Boiling Range of DEAl Acid anhydride reaction product

This study was conducted in compliance with the Swiss Ordinance relating to Good Laboratory Practice, adopted February2nd, 2000 [RS 813.016.5]. This Ordinance is based on the OECD Principles of Good Laboratory Practice, as revised in 1997 and adopted November 26th, 1997 bydecision ofthe OECD Council [C(97)1861Final]
.

.Study Director:RCC Study Number848616 REPORT Page4 DEAl Acid anhydride reaction product 

# SIGNATURES

Study Director:

Management: Dr. Jorn Schreitmuller



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# ckJo3RCC Study Number848616 DENAcidanhydride reaction product REPORT 

# QUALITYASSURANCE UNIT
RCC Ltd, Environmental Chemistry & Pharmanalytics, CH-4452 ltingen 

### I Switzerland STATEMENT RCC Study Number: 848616 Test Item: DEA/Acid anhydride reaction product Study Director: Mrs. Alessandra Tognucci Page 5

Title: Determination of the Freezing Point 

### I Freezing Range and of the Boiling Point 

### I Boiling Range of DEA/Acid anhydride reaction product The general facilities and activities are inspected periodically and the results are reported to the responsible person and the management. Study procedures were periodically inspected. The study plan and this report were audited by the QualityAssurance Unit. The dates are given below: Dates and Types of QAU Inspections Dates of Reports tothe Study Directorand tothe Management June 06, 2003 Study Plan June06, 2003 September23, 2003 Process based September23, 2003 December02 

### I 03, 2003 Final report December03, 2003 This statement also confirmsthatthis final report reflects the raw data. QualityAssurance: 

# J Margot Richter-AuerRCC Study Number848616 DEA/Acid anhydride reaction product 

# CONTENTS REPORT Page 6

GLP CERTIFICATE........................................................................................................2 STATEMENT OF COMPLIANCE....................................................................................3 SIGNATURES ................................................................................................................4 QUALITYASSURANCE UNIT........................................................................................5 CONTENTS....................................................................................................................6 PREFACE.......................................................................................................................7 DATA REQUIREMENT 

### ITEST GUIDELINES ................................................................8 SUMMARY OF STUDY PLAN AMENDMENTS ..............................................................8 1 PURPOSE.............................................................................................................9 2 MATERIALAND METHODS..................................................................................9 2.1 TEST ITEM...................................................................................................9 3 FREEZING POINT 

### I FREEZING RANGE ............................................................ 10 3.1 PRINCIPLE OFTHE TEST ........................................................................ 10 3.2 PERFORMANCE OFTHE TEST................................................................ 10 3.2.1 PreliminaryTest............................................................................ 10 3.2.2 Main Test...................................................................................... 10

.4 BOILING POINT 

### I BOILING RANGE ................................................................... 11 4.1 PRINCIPLE OF THE TEST ........................................................................ 11 4.2 PERFORMANCE OF THE TEST................................................................ 11 4.2.1 Test System.................................................................................. 11 4.2.2 PreliminaryTest............................................................................ 11 4.2.3 Main Study.................................................................................... 11 5 DATA HANDLING................................................................................................ 12 5.1 FREEZING POINT 

### I FREEZING RANGE ................................................... 12 5.2 BOILING POINT 

### I BOILING RANGE .......................................................... 12 6 RESULTS............................................................................................................ 13 6.1 FREEZING POINT 

### I FREEZING RANGE ................................................... 13 6.2 BOILING POINT 

### I BOILING RANGE .......................................................... 13 6.3 CONCLUSION............................................................................................ 14 Figure 1: DSC-curve for the determination of the boiling of DEA/Acid anhydride reaction product (preliminarytest) .............................................................. 15RCC Study Number848616 DEA/Acid anhydride reaction product 

# PREFACE
GENERAL Title:
Sponsor:

Study Monitor:

Test Facility:

RESPONSIBILITIES Study Director: Deputy Study Director: Technical Coordinator: Reporting: Head of RCC QualityAssurance:

SCHEDULE Experimental starting date: Experimental completion date: Studycompletion date:

ARCHIVING REPORT Page 7

Determination of the Freezing Point 

### I Freezing Range and of the Boiling Point 

### I Boiling Range of DEAl Acid anhydride reaction product Rockwool International A/S Hovedgaden 584 DK-2640 Hedehusene Denmark Mr. Flemming A. Simonsen Danish Toxicology Centre Kogle Aile 2 Dk-2970 H0RSHOLM Denmark RCC Ltd Environmental Chemistry& Pharmanalytics Zelgliweg 1 CH-4452 ltingeniSwitzerland

Mrs. AlessandraTognucci Mr. Michael Lindemann Mrs. Barbara FIOkiger and Mr. Christoph Wild Dr. HansjOrg Widmer Mrs. IrisWuthrich

October 16, 2003 October30, 2003 December 17, 2003

### Iwih

RCC Ltd, CH-4452 ltingeniSwitzerland will retain the study plan, raw data, a sample of test item and thefinal report ofthe presentstudyfor at leastten years. No datawill be

**disca~ded** withoutthe sponsor's consent.RCC Study Number848616 REPORT PageS DEAl Acid anhydride reaction product 

# DATA REQUIREMENT

# ITEST GUIDELINES

This study followed the procedures indicated by the following internationally accepted guidelines and recommendations: EEC Directive 92/69, Part A, Methods for the determination of physico-chemical properties, A.1 "Melting/Freezing temperature", EEC Publication No. L383, December 1992. EEC Directive 92/69, Part A, Methods for the determination of physico-chemical properties, A.2 "Boiling temperature", EEC Publication No. L383, December 1992. OECD Guideline for Testing of Chemicals No. 102, "Melting Point 

### I Melting Range", adopted July27, 1995. OECD Guidelinefor Testing of Chemicals No. 103, "Boiling Point", adopted July27, 1995.


# SUMMARY OF STUDY PLAN AMENDMENTS

FirstAmendmentto Study Plan: 1) Concerning: StudyTitle Alteration: Melting Point 

### I Melting Range replaced by Freezing Point 

### I Freezing Range Reason for Alteration: Physical state of test item at room temperature is liquid 2) Concerning: Schedule Alteration: Anticipated experimental starting date Anticipated experimental completion date Anticipated date of draft report Reason forAlteration: Test item batch delivered later 3) Concerning: Test Item Alteration: New batch used for study New expiration date Reason for Alteration: New batch to be used by request of sponsorRCC Study Number848616 REPORT Page 10 DEAl Acid anhydride reaction product 

# 3 FREEZING POINT

# I FREEZING RANGE 3.1 PRINCIPLE OFTHE TEST The above mentioned guidelines contain several different methods for the determination of the freezing point 

### I freezing range. These are, between others, thermal analysis using a calorimeter and visual test (e.g. capillary method), where the melting orfreezing temperature, respectively, is measured. In the present study a combination of both methods was applied. The test item was cooled down slowly in a glass tube immersed into a cooling bath, while the consistency of the sample wasjudgedvisually. Thermocouples were inserted into the sample with the aim to utilise the heat effect of a phase transformation for the detection of the freezing point.


## 3.2 PERFORMANCE OF THE TEST 3.2.1 PreliminaryTest 1 ml of the test item was filled into avial and stored in afreezer for 27 hours at about- 21

# oc. After storage, the sample was assessed visually. 

### 3.2.2 Main Test In a first test, about 15 ml of the test item were filled in a test tube and cooled down using acetone and dry ice. The probe of a thermocouple was placed in the centre of the sample. ·The temperature was measured with an appropriate thermocouple. A second and third test

was carried out with about 20 ml of test item. The temperature/time curves were recorded during the cooling of the test item. Additionally, the physical state was observed visually.RCC Study Number848616 REPORT Page 11 DEAl Acid anhydride reaction product 

# 4 BOILING POINT./BOILING RANGE 4.1 PRINCIPLE OFTHE TEST The above mentioned guidelines contain several different methods for the determination of the boiling point 

### I boiling range. These methods include thermal analysis using a calorimeter and visual tests (e.g. capillary tester), where the boiling temperature is measured. In the present studythe thermal analysis was used forthe preliminaryand main test
. A phasetransformation, e.g. melting or evaporation, ora reaction, e.g. dissociation, usually is associated with a heat effect. In the calorimeter, two identical aluminium sample containers, one filled with the test then and the other empty (used as a reference), are heated at a constant rate. During the experiment, the heat effect, i.e. the difference in heatflow, between the sample container and the reference container is registered.


## 4.2 PERFORMANCE OFTHE TEST 4.2.1 Test System Thermal Analysis (Preliminaryand Main Test) Instrument: Sample cups: Test conditions: Reference cup:


### 4.2.2 PreliminaryTest Differential Scanning Calorimeter DSC 821, MettlerToledo Aluminium cups with a normed pinhole. Thetestwas performed in an air atmosphere. Emptyaluminium cup.

A test item amount of 8.24 mg was heated up from 25°C to 400°C at a rate of 20 K/min. The quantities of heat absorbed or released were measured and recorded. Before and after the test, the weight and the appearance ofthe sample were determined. 

### 4.2.3 Main Study A test item amount of 8.31 mg was heated up from 25°C to 400°C at a rate of 10 K/min. The quantities of heat absorbed or released were measured and recorded. Before and after the test, the weight and the appearance ofthe sample were determined.RCC Study Number848616 REPORT Page 12 DEN Acid anhydride reaction product 

# 5 DATA HANDLING 5.1 FREEZING POINT

## I FREEZING RANGE The freezing point is defined as the temperature at which phase transition from liquid to solid state at normal atmospheric pressure takes place. This temperature ideally corresponds to the temperature at the melting point. As the phase transition of many substances takes place over a large temperature range, it is often described as . the freezing respectively melting range. Results will be given in degrees Centigrade and in Kelvin.


## 5.2 BOILING POINT

## I BOILING RANGE The standard boiling point is defined as the temperature at which the vapour pressure of a liquid is the same as the standard pressure (101.325 KPa). The measured boiling point depends on the atmospheric pressure. Thermal Analysis As the phase transition from liquid to vapour of many substances takes place over a large temperature range, it is often described as the boiling range. If the difference between the temperature at the beginning and at the final stage of boiling is within 1 K, the temperature at the beginning of boiling is taken as the boiling point, otherwise the two temperatures will be reported. A correction to normalized pressure can be made. Because the correction factor for the ·boiling point is a specific parameter for each test item, the correction factor had to be

determined. The determination of this correction factor by the used method is not applicable, therefore no correction will be applied to the boiling point observed. Conversion of units (Kto °C): t = T- 273.2 with t = Celsius temperature, degrees Centigrade [°C] T 

## = Thermodynamictemperature, Kelvin [K]RCC Study Number848616 DENAcidanhydride reaction product 

# 6 RESULTS REPORT



## 6.1 FREEZING POINT

## I FREEZING RANGE Page 13

The determination of the freezing point 

### I freezing range of. the test item was performed according to the EEC Directive 92/69, A.1 "Melting/Freezing temperature
.., December 1992 and to the OECD Guideline No. 102:
.. Melting point 

### I melting range..,adopted July27, 1995. A preliminarytest was performed to check if the test item becomes solid if stored in afreezer at about - 21

# oc. About 1 ml ofthe test item was placed in a small vial and stored for 27 hours at about - 21

# oc. After storage the sample was judged visually and was found tobe at the physical change from highly viscous to solid. Based on this observation the freezing point 

### I range was around - 21

# oc. During the main tests, 15 ml and twice 20 ml of the test item DEAl Acid anhydride reaction product were placed in a test tube and cooled down from room temperature to about - 53°C (firsttest), - 32°C (second test) and - 25°C (third test) using a dry ice and acetone mixture. From the recorded temperature curves, no freezing point or range could be deduced. By visual observation during the first test, the test item began to solidify at - 16.7°C and was solid at- 29.6°C. During the second test, the test item was very viscous at- 19.8°C and was completely solid at - 20.9°C. During the third test, the test item turned very viscous in the temperature range from - 21.1 to - 22.6°C and was completely solid at - 22.9°C. The first test was not used for the result evaluation, as something inhibited the freezing of DEA/Acid anhydride reaction product. In conclusion, thefreezing range for DEA/Acid anhydride reaction productwas determined to be at which is equal to - 20.9°Cto- 22.9°C 250.3 Kto252.3 K.


## 6.2 BOILING POINT

## I BOILING RANGE The determination of the boiling point 

### I boiling range of the test item was performed according to the EEC Directive 92/69, A.2 "Boiling temperature
.., December 1992 and to the OECD Guideline No. 103:
.. Boiling point
..,adopted July27, 1995. The DSC-curve of the preliminary test (heating rate of 20 Klmin from 25°C to 400°C) is shown in Figure 1 . Endothermic heat effects were observed between about 1 

# oooc and about 260°C. After the experiment, the sample had lost 55.7 °/o of its mass and black foam had formed around the pinhole of the aluminium cup. The colour of the sample residue in the cup had changed to black. The DSC-curve of the main test (heating rate of 1 0 Kimin from 25°C to 400°C) showed endothermic heat effects in the temperature range from about 1 

# oooc to about 260°C. After the experiment the sample had lost 62.3 o/o of its mass and black foam had formed around the pinhole ofthe aluminium cup. The colour ofthe sample residue in the cup had changed to black.RCC Study Number848616 DEA/Acid anhydride reaction product REPORT Page 14
The test item DEA/Acid anhydride reaction product is a complex mixture of monomers, dimers, trimers and polymers that also contains water. Therefore, the endothermic effects observed cannot be deduced to boiling only but are combined effects of boiling and polymerisation. In conclusion boiling and polymerisation of DEA/Acid anhydride reaction product was observed between
which is equal to



## 6.3 CONCLUSION 1

# oooc and 260°C 373 Kand 533 K.

Thefreezing range of DEAl Acid anhydride reaction product was observed between
Boiling and polymerisation of DEAl Acid anhydride reaction productwas observed between 1

# oooc and 260°C.Aexo mw 0 -30 -40 Experiment: 848616/DEA/boil_pt1/16.10.2003/wic, 16.10.2003 10:18:48 Methodenname: PreTest 25-400/20°C/min/Air Methode: PreTest 25-400/20°C/min/Air 25.0-400.0°C 20.00°C/min

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