## REPORT

DETERMINATION OF THE MELTING POINT / MELTING RANGE OF TKA 40278 (CGI 827)
Data Requirement / Test Guidelines: OECD No. 102 EEC Directive 92169, A.I Study Director’ Mrs. Alessandra Tognucci Study Completion Date: April 11, 2003 Test Facility: RCC Ltd , Environmental Chemistry & Pharmanalytics CH-4452 Itingen/Switzerland Sponsor; CIBA SPECIALTY CHEMICALS INC. CH - 4002 Basel/Switzerland RCC Study Number: 845417 Page 1 of 12

522RCC Study Number 845417 REPORT Page 2

TKA 40278 (CGI 827) 

## GLP CERTIFICATE

The Swiss GLP Monitoring Authorities



# ~ Swts~ A~ncy for tt~ Env~menL Forests =rid u~ SWISS’metriC 

# Statement of GLP Compliance

It is hereby confirmed that dudng the pedod of the following Test Facilities of November 18 - 22, 2002 RCC Ltd 4452 Itingen Switzerland
were inspected by the Federal Office of Public Health, the Swiss Agency for Therapeutic Products and the Swiss Agency for the Environment, Forests and Landscape with respect to the compliance with the Swiss legislation on Good Laboratory Practice, Test Facilities Areas of expertise Toxicology Environmental Chemistry and Pharmanalytics 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. It was found that the aforementioned test facilities were operating In compliance with the Swiss Ordinance relating to Good Laboratory Practice [RS 813.016.5] at t~e time they were inspected. Federal Office of Public Health The Director

Bern, March 2003 Prof. Th. Zeltner

523RCC Study Number 845417 REPORT Page 3

TKA 40278 (CGI 827) GOOD LABORATORY PRACTICE 

## STATEMENT. OF COMPLIANCE
Rcc Study Number: Test Item: Study Director: Title: 845417 TKA 40278 (CGI 827) Mrs. Alessandra Tognucci Determination of the Melting Point / Melting Range of TKA 40278 (CGI 827) This study was ~onducted in compliance with the Swiss Ordinance relating to Good Laboratory Practice, adopted February 2nd, 2000 [RS 813.016.5]. This Ordinance is based on the OECD Principles of Good Laboratory Practice, as revised in 1997 and adopted November 26t~, 1997 by decision of the OECD Council [C(97)186/Final]. The purity ofthe test item is excluded from the statement of compliance (purity available in Analytical Certifica~5-’~2~-l:,-Ciba Specialty Chemicals Inc.).

Study Director: Mrs. Alessandra Tognucci

524RCC Study Number 845417 REPORT Page 4

TKA 40278 (CGI827) 

## SIGNATURES

Study Director:

Management: Dr. JOrn SchreitmQller

525RCCStudy Number 845417 REPORT Page 5

TKA 40278 (CGI 827) 

# QUALITY ASSURANCE UNIT RC(~ILtd, Environmental Chemistry & Pharmanalytics, CH-4452 Itingen / Switzerland
STATEMENT Rcc S~udy Number: 845417 Test Item: TKA 40278 (CGI 827) StudY Director: Mrs. Alessandra Tognucci Title: Determination of the Melting Point / Melting Range of TKA 40278 (CGI 827) 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 Quality Assurance Unit. The dates are given below: Dates and Typesof QAU Ih~pections Dates of Reports to the Study Director and to the Management January 03, 2003 Study Plan January 03,2003 February 05, 2003 Process based (sample February 05,2003

preparation + measurement April 08, + 09, 2003 Final report April09,2003 This statement also confirms that this final report reflects the raw data. Quality Assurance:

526RCC Study Number 845417 REPORT Page 6

TKA 40278 (CG1827) 

## CERTIFICATION OF GLP AND VERIFICATION OF THE REPORT

The statement of Compliance with Good Laboratory Practice found in this report, and signed by the Study Director is truthful and accurate, and this report as provided by the testing facility is complete and unaltered.

Signature of the Sponsor:

Date:

527RCC Study Number 845417 REPORT Page 7

TKA 40278 (CGI 827) 

## CONTENTS

GLP CERTIFICATE ........................................................................................................ 2 STATEMENT OF COMPLIANCE .................. ~ ................................................................. 3 SIGNATURES ................................................................................................................ 4 QUALITY ASSURANCE UNIT ........................................................................................ 5 CERTIFICATION OF GLP AND VERIFICATION OF THE REPORT .............................. 6 CONTENTS .................................................................................................................... 7 PREFACE
....................................................................................................................... 8 DATA REQUIREMENT / TEST GUIDELINES ................................................................9 SUMMARY OF STUDY PLAN AMENDMENTS ........................................................... ~.. 9 1 PURPOSE ......................................................................... ~ ................................. 10 2 MATERIAL AND METHODS ................................................................................ 10 2.1 TEST ITEM ................................................................................................. 10 2.2 PRINCIPLE OF THE TEST .................~ ...................................................... 10 2.3 PERFORMANCE OF THE TEST ................................................................ 11 2.3.1 Thermal Analysis .......................................................................... 11 2.3.2 Preliminary Test ............................................................................ 11 2.3.3 Main Study .................................................................................... 11 2.4 DATA HANDLING ...................................................................................... 11 3 RESULTS .................................. : ......................................................................... i2 Table: Determination of the melting point of TKA 40278 (CGI 827) (summary) ..... 12

528RCC Study Number 845417 REPORT Page 8

TKA 40278 (CGI 827) 

## PREFACE
GENERAL Title: Sponsor: Monitoring Scientist: Test Facility: Determination of the Melting Point / Melting Range of TKA 40278 (CGI 827) CIBA SPECIALTY CHEMICALS INC. CH-4002 Basel/Switzerland Dr. Moung Sook Lee RCC Ltd Environmental Chemistry & Pharmanalytics Zelgliweg 1 CH-4452 Itingen/Switzerland

RESPONSIBILITIES Study Director: Deputy Study Director: Technical Coordinator: Head of RCC Quality Assurance: Mrs. Alessandra Tognucci Dr. Ute Schmledel Mr. Christoph Wild Mrs. Iris W0thrich

SCHEDULE Experimental starting date: Experimental completion date: Study completion date: Janua~ 02,2003 January 02,2003 April11,2003

ARCHIVING RCC Ltd, CH-4452 Itingen/Switzerland will retain the study plan, raw data, a sample of test item and the final report of the present study for at least ten years. No data will be discarded without the sponsor’s consent.

529RCC Study Number 845417 REPORT Page 9

TKA 40278 (CG1827) 

## DATA REQUIREMENT / TEST 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. OECD Guideline for Testing of Chemicals No. 102, "Melting Point / Melting Range", adopted July 27, 1995.



## SUMMARY OF STUDY PLAN AMENDMENTS
First Amendment to Study Plan: Concernin_g; Schedule Alteration: New experimental starting and completion date Reason: Delay in study

530RCC Study Number 845417 REPORT Page10

TKA 40278 (CGI 827) 

## 1 PURPOSE The ~l~urpose of the study was to evaluate the melting point / melting range of the test item.



## 2 MATERIAL AND METHODS
2.t TESTITEM Data as provided by the sponsor. Identity: Product Name: Batch: Purity: Appearance: Expiration date: Storage: TKA 40278 CGI 827 KL 01/02 See Analytical Certificate, Study No. 14026512-1 ’Ciba Specialty Chemicals Inc. Solid, slightly yellow August 30, 2004 At room temperature at about 20 ~C. The test item is light sensitive.



### 2.2 PRINCIPLE OF THE TEST The above mentioned guidelines contain several different methods for the determination of the melting point ! melting range. These are, between others, thermal analysis using a calorimeter and the capillary method, where the melting resp. freezing temperature is measured. In the present study the capillary method was applied. The sample in the capillary tube is heated automatically in a heating chamber. A beam of light is directed through the test item to a precisely calibrated photocell. The optical properties of most substances change to transparency during melting. The intensity of light reaching the photocell increases and sends a stop signal to the digital indicator reading out the temperature of the heating chamber. In the present study, a transmission of 40 % was defined as end point of melting. This method is not suitable for some highly coloured substances, where the melting point / melting range should be determined visually.
531RCC Study Number 845417 REPORT Page 11

TKA 40278 (CG1827) 

### 2.3 PERFORMANCE OF THE TEST 2,3.1 Thermal Analysis Test System: Instrument: Detection: Capillary tube: Test conditions: BOCHI Melting Point Tester, B-545 40 % transmission using a photocell Glass; (Fa. Bechi; Art. No.: 017590) The test was performed in an air atmosphere. 2,3.2 Preliminary Test The finely ground test item is placed 4 mm to 6 mm high in a capillary tube and packed tightly. During the experiment three of the filled capillary tubes were measured together. The samples were heated up from 45 °C to about 100 °C at a rate of 5 K/min. 2.3.3 Main Study The finely ground test item is placed 4 mm to 6 mm high in a capillary tube and packed tightly. During the experiment six samples were measured in 2 runs. The samples were heated up from 45 °C to 75 °C with a heating rate of 3 K/min and from 75 °C to 95 °C with a rate of 1 K/min. Any unexpected changes in sample appearance are also described in the raw data. 

### 2.4 DATA HANDLING The melting point is defined as the temperature at which phase transition from solid to liquid state at normal atmospheric pressure takes place. This temperature ideally corresponds to the temperature at the solidification point or the freezing point. As the phase transition of many substances takes place over a large temperature range, it is often described as the melting range. Using the capillary method, the temperature of the final stage of melting usually is taken as the melting temperature*. If this is not suitable or applicable, the temperature at the beginning and at the final stage of melting or the temperature of decomposition will be stated. Results will be given in degrees centigrade and in Kelvin. Conversion of units (K to ° C):
with t = T- 273.2 t = Celsius temperature, degrees Centigrade [°C] T = Thermodynamic temperature, Kelvin [K] * For many substances, this corresponds quite well with a light transmission of 40 %, which is used as end point during automatical detection,532RCO Study Number 845417 REPORT Page 12

TKA 40278 (CGI 827) 

## 3 RESULTS The de!ermination of the melting point / melting range of the test item was performed accctrding to the EEC Directive 92/69, A.1 "Melting/Freezing temperature", December 1992 and~o the OECD Guideline No. 102: " Melting point / melting range", adopted July 27, 1995 using the capillary method. The results of the individual main test measureraents are summarized in the attached table. Three filled capillary tubes were placed in the heating chamber and heated up from 45 °C with a rate of 5 K/min. The melting point of the test item was observed visually at 77 °C. After the experiment, the samples were melted and slightly yellow but not completely transparent. In order to determine the melting point more precisely, further tests were performed using the capillary tester. A total of 6 samples were heated with a heating rate of 3 K/rain (from 45 °C to 75 °C) and with 1 K/min. (from 75 °C to 95 °C). All samples were completely molten between 83.7 °C ahd 84.9 °C. After the measurement the samples were slightly yellow but not completely transparent. In conclusion, the mean melting point of TKA 40278 (CGI 827) was determined to be which is equal to ---84.3~C~J: 0;5 ~ ....... 357.5 K+0.5 K
Table: Determination of the melting point of TKA 40278 (CGI 827) (summary) Test Temperature Heating rate in theTemperature Temperature

range relevant 

### [°C] 

### [K] [°C] temperature range

[K/min] 83.8 357.0 Preliminary Test 45-100 5 83.9 357.1 83.7 356.9 91.4" 364.6 Main Test 45 -95 84.7 357.9 84.9 358.1 83.9 357.1 2n~ Main Test 45-95 1 83.7 356.9 84.5 357.7 Mean melting point: 84.3 357.5 Standard deviation: (+) 0.5 0.5 The mean melting point was calculated from the bold values. * outlier (not used for calculation) 533