StudyTitle Study Director
Test Facility

Sponsor

Internal distribution Study No. FINAL REPORT
Determination ofthe density of accordingto OECD Guideline No. 109 (pycnometer)

Archives Author.Study No. - Final report


### CONTENTS:

Title page Contents Statement of GLP compliance (Swiss GLP monitoring authorities) Statement of GLP compliance (Study Director) and signatures QualityAssurance Unit Summary 1 . General information 2. Information on the test substance 2. 1 . Identity


### 3. 4. 2.2. Physical-chemical and analytical data General test method Results Total number of pages : 12 Page 2/12 Page

1 2 

### 3 4 5 6 7 

### 8 8 8 9-11 12Study No. - Final report Page 3/12

The Swiss GLP Monitoring Authorities Swiss Federal Officeof Public Health

It is hereby confirmed that during the period of the following Test Facility of Swiss Agency forthe Environment, Forests and Landscape

March 31 - April 1, 2005 

# I lntercantonal Office for the Control of Medicines

was inspected by the Swiss Agency for the Environment, Forests and Landscape with respect to the compliance with the Swiss legislation on Good Laboratory Practice. Test Facility Areas ofexpertise

The inspection was performed in agreement with the OECD Guidelines for National GLP Inspections and Audits. It was found that the aforementioned test facility was operating in compliance with the Swiss Ordinance on Good Laboratory Practice [SR 813.016.5] at the time it was inspected.

Bern, June 2005 Swiss Agencyforthe Environment, Forests and Landscape
Philippe RochStudy No. - Final report Page 4/12
STATEMENT OF COMPLIANCE WITH GOOD LABORATORY PRACTICE: Study No. Test substance Title Determination of the density of according to OECD Guideline No. 109 (pycnometer). This study has been performed in compliance with the Swiss Ordinance relating to Good Laboratory Practice, adopted May 18th, 2005 [RS 813.112.1]. This ordinance is based on the OECD Principles of Good Laboratory Practice, as revised in 1997 and adopted November26th, 1997 by decision of the OECD Council [C(97)186/Final]. The undersigned declare that this study was carried out according to the procedures herein described and this report represents a true and accurate record ofthe results obtained. Study director

Test Facility Management:

Date:Study No. - Final report Page 5/12
QUALITY ASSURANCE UNIT STATEMENT Study No. Test substance Studytitle Determination of the density of according to OECD Guideline No. 109 (pycnometer). Testfacilities are periodically inspected and the results are reported to the responsible persons and the management. Experimental procedures were periodically inspected. The study plan and this final report were audited by the Quality Assurance Unit. The dates are given below:
Dates and Types of QAU inspections Dates of Reports to the Study Director and

to the Management February 1 8\ 2007 February 1st, 2007 Study plan February 1st, 2007 Weighting and filling of the February 1 8\ 2007 pycnometerwith the displacement liquid Final report
The methods and procedures as used in the reference study are accurately described in this document and reported results reflect accurately the raw data of the study. Manager, Quality Assurance Unit

DateStudy No. - Final report Page 6/12
SUMMARY

The density of was determined according to the OECD guideline No. 109 (pycnometer). The result can be expressed as follows:
p = 1.12 g/cm3 (at 25°C)Study No. - Final report Page 7/12

1. GENERAL INFORMATION Study No. Purpose Guidelines
Study Director Laboratory Technician Schedule: Study initiation date Start of experiments : End of experiments : Study completion date:
Archives Determining the density of using a pycnometer OECD Guideline for the Testing of Chemicals No. 109, Paris, 1995 92/69/EEC, method A.3.

January 2nd, 2007 February 1 5\ 2007 April 3rd, 2007

The study plan, all data generated and recorded during the study and the final report will be stored in the Archives ofthe for at least ten years after issue of the final report.Study No. - Final report Page 8/12


### 2. INFORMATION ON THE TEST SUBSTANCE 2.1. Identity Commercial name Givaudan Code No. Chemical nature Empirical formula MolecularWeight 

### CAS No. N/A



### 2.2. Physical-chemical and analytical data -General Aspect

- Sample tested Lot No. Purity (GC) Expiration date May 14,2007Study No. - Final report Page 9/12


### 3. GENERALTEST METHOD 3.1 Introduction Many methods exist which allow to measure the densitywith a greater precision than is required for environmental assessment. The pycnometer method is simple and does not require any special or expensive equipment. The method requires the use of a "displacement liquid" in which the test substance is insoluble, which has good wetting properties for it and has a lowvapour pressure. 3.2 Definitions and units The density of a substance is the quotient of the mass m and its volume V: p= 

### m/V Sl unit is kg/m3, but g/cm3 is most often used.
3.3 Principle The density of the solid substance is determined by measuring the difference of weight between avolume (the pycnometer) filled with the displacement liquid and the same volume filled with a known mass ofthe solid immersed in the displacement liquid. 3.4 Equipment

- a dessiccator whose lid can be equipped with a dropping funnel

- a 25-ml pycnometer

- a thermostated water bath (±0.1°C)

- a laboratory balance (± 0.1 mg)

- a sieve with 500 flm mesh size 3.5 Reference Substance No reference substance is required.Study No. - Final report Page 10/12


### 3.6 Operating procedure 

### 3.6.1. Temperature The temperature of the determination has a marked effect on the density of the displacement liquid but not on that of the test substance. For more convenience, the temperature of the experiment (i.e. the temperature of the water-bath) was chosen about

# soc higherthan room temperature (ca. 20°C). 

### 3.6.2 Displacement liquid is almost insoluble in water (less than 10 mg/1 at room temperature). A first test was made with pure water, but it completely failed since the test substance could not be correctly wetted with pure water. Thus a second test was made with a 1% Tween 80 aqueous solution. This was seen to be a good displacement liquid. 

### 3.6.3 Sample preparation The sample of test substance was thoroughly mixed and a specimen of about 60 g was sieved through a 500 !lm mesh sieve and dried in a dessiccatorfor one night. 

### 3.6.4 Density ofthe displacement liquid The pycnometer, empty, clean and dry, was weighed with its stopper: mass m1. It was then filled with deionised water and weighed: mass ms. Afterthat it was filled with the displacement liquid and weighed: mass m4. The density of the displacement liquid was calculated as follows:

with Pothe density ofwater atthe temperature of determination 3.6.5 Density ofthe test substance The pycnometer, empty, clean and dry, was weighed with its stopper: mass m1 The dry pycnometer was filled about to the half with test substance, stopped and weighed: mass m2 The pycnometer was placed in the dessiccator and the dropping funnel affixed to the lid so that the stem penetrates into the pycnometer. The stopcock of the funnel was closed and vacuum was carefully applied to the dessiccator for 15 minutes after it has reached less than 

### 2 kPa.Study No. - Final report Page 11/12
The funnel was filled with displacement liquid and the stopcock slowly opened to allow the liquid to fill the pycnometer 15 mm above the level of the test substance. The stopcock was closed and vacuum applied again to the dessiccator (pressure less than 2 kPa) until any bubble in the liquid has disappeared. Air was allowed to enter the dessiccator, the pycnometer was removed, filled up with displacement liquid and placed in the water-bath for 30 minutes. The pycnometer was closed with its stopper, any excess of liquid was wiped off, and then the pycnometerwas left 15 minutes on the balance scale and weighed: mass m3. At the end of the experiment, the pycnometer was carefully rinsed and filled with deionised water, allowed to equilibrate in the water-bath for 30 minutes, closed and weighed after equilibration as already described in the previous paragraph: mass m4. The density of the test substance was calculated as follows:



### Ps 

## = density of the test substance (g/cm3) 

### p 1 

## = density of the displacement liquid (g/cm3) m 1 

## = weight (g) of the empty pycnometerwith stopper m2 

## = weight (g) of the pycnometer containing test substance
m3 weight (g) of the pycnometer filled with the test substance and the displacement liquid m4 weight (g) of the pycnometerfilled with the displacement liquid The determination was made in duplicate.Study No. - Final report Page 12/12


### 4. RESULTS Temperature ofthe determination: 25°C. The density of water at 25°C is (Logarithmische Rechnetafeln, Kuster, Thiel and Fischbeck, Walter de Gruyter and Co. ed., Berlin, 1965): 

### p0 

## =0.997071 g/cm3 4. 1 First determination: 

### m1 

## =22.1758g m2 = 28.2578g m3 

## =47.5520g m4 = 46.8906g m5 =46.8616g Densityof the displacement liquid: p 1 =0.998242g/cm3 Densityof the test substance: 

### Ps = 1.120g/cm3 4.2 Second determination m1 =24.165lg m2 =30.1875g m3 =46.9360g m4 =46.2803g m5 =46.2571g Density ofthe displacement liquid: p 1 = 0.998118g/cm3 Density ofthe test substance: 

### Ps 1.120g/cm3 4.3 Final result There is no difference between the two determinations. The average of the two determinations was then calculated and rounded off attwo decimal places to express the desired density of Average: After rounding off: 1.120 g/cm3 1.12 g/cm3