StudyTitle Study Director
Test Facility

Sponsor

Internal distribution Study No. FINAL REPORT Partition coefficient n-octanol/water of according to OECD Guideline No. 117.

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 Quality Assurance Unit Summary 1 . General information 2. Information on the test substance 2.1. Identity 

### 3.

4. 5. 2.2. Physical-chemical and analytical data Test method and conditions 3.1 . Principle 3.2. Equipment and conditions 3.3. Reference substances 3.4. HPLC procedure Results Conclusion Appendix 1 : Partition coefficient calculations Appendix 2: Graph log Pow= f(log k) Appendix 3 : Chromatogram ofthe reference substances Appendix 4 : Chromatogram of the test substance Total number of pages : 15 Page 2/15 Page


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The Swiss GLP Monitoring Authorities Swiss Federal Office of Public Health Swiss Agencyforthe Environment, Forests and Landscape lntercantonal Office for the Control of Medldnes 

# Statement of GLP Compliance
It is hereby confirmed that during the period of the following Test Facility of March 31 - April 1, 2005

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 Environmental Toxicity Studies Physical-chemical Testing 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.

Bem, June 2005 Swiss Agency for the Environment, Forests and LandscapeStudy No. - Final report Page 4/15
STATEMENT OFCOMPLIANCE WITH GOOD LABORATORY PRACTICE: Study No. Testsubstance Title Partition coefficient n-octanol/water of according to OECD Guideline No. 117. This study has been performed in compliance with the Swiss Ordinance relating to Good Laboratory Practice, adopted May 18th, 2005 [AS 813.112.1]. This ordinance is based on the OECD Principles of Good Laboratory Practice, as revised in 1997 and adopted November 26th.1997 by decision of the OECD Council [C(97)186/Final]. The undersigned declare that this studywas carried out according to the procedures herein described and this report represents a true and accurate record of the results obtained. Study director

Test Facility Management: Date: 

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### (Study No. - Final report Page 5/15
QUALITY ASSURANCE UNIT STATEMENT Study No. Testsubstance Studytitle Partition coefficient n-octanol/water of according to OECD Guideline No. 117. Testfacilities are periodically inspected and the results are reported to the responsible persons and the management. Experimental procedures (process-based) were periodically inspected. The study plan andthis final report were audited bythe QualityAssurance Unit. The dates are given below: Dates of Reports to Dates and Types of QAU inspections the Study Director and to the Management September 11, 2006 Study plan September 11 , 2006 September 13, 2006 Preparation and stabilization of the September 13, 2006 system

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# ~ 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 6/15
SUMMARY

The Partition Coefficient n-octanol/water of was determined by the Reverse Phase High Performance Liquid Chromatographic Method according to the OECD Guidelines for Testing of Chemicals, Method No. 117. The result is: Partition coefficient n-octanol/water of log 

### Pow= 3.6.

### Study No. - Final report Page 7/15


### 1. GENERAL INFORMATION Study No. Purpose
Guidelines
Study Director Laboratory Technician Schedule: Partition coefficient n-octanol/water of by the Reverse Phase High Performance Liquid Chromatographic Method. OECD Guidelines forTesting of Chemicals, Method No. 117 (1989). 92/69/EEC, Method A.a. Partition coefficient (HPLC method)

Study initiation date: August 30, 2006 Start of experiments: September 13, 2006 End of experiments : September 14, 2006 Studycompletion date: 

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



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

### CAS No. 

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

- Sample tested Lot No. Purity Expiration date (GC) May 14, 2007. Page 8/15

### Study No. - Final report Page 9/15



### 3. TEST METHOD AND CONDITIONS 3. 1. 

### Principle of the method Reverse phase High Performance Liquid Chromatography on octadecyl-modified silica stationary phase is used. Partitioning on the column occurs in order of hydrophobicity when a suitable mobile phase is used. From relationships between the measured retention times and the known octanol/water partition coefficients of reference substances, the partition coefficient of the test substance is calculated. 3.2. Equipment and conditions HPLC 

### equipment :

The operating conditions were: -Column -Mobile phase -Flow rate

- Column temperature

- Detector temperature

- Injected volumeStudy No. 

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3.

### 3. Reference substances Seven substances were chosen having log Pow ranging from 

### 0.9 to 

### 5.7. Thiourea is used as an unretained compound for the determination of the "dead time" to. Individual solutions of these eight substances in acetonitrile were prepared at the concentrations given in Table 1. Table 1 Substance log Pow Concentration Art. No. Purity [gil] [%] Thiourea 

# --- 1.6 88810 100.0 Aniline 

### 0.9 2.0 10400 100.0 Methyl benzoate 

### 2.1 1.8 12460 99.9 Benzophenone 

### 3.2 2.0 12750 99.9 Naphthalene 

### 3.6 2.0 70211 99.8 1,2,4-Trichloro- 

### 4.2 4.0 91170 99.1 benzene n-Butylbenzene 

### 4.6 4.0 19610 98.7 Triphenylamine 

### 5.7 4.0 92930 99.9 Supplier : Fluka, Buchs (AG), Switzerland. On the day of the determination, a calibration mixture of these eight substances was prepared by mixing 2 ml of each of the individual solutions and adding enough doubledistilled water to obtain a solvent composition similarto the mobile-phase (1

### 0.6 ml).

### Study No. - Final report Page 11/15



### 3.4. HPLC procedure A solution of the test substance was prepared in the mobile phase (22.4 mg in 

### 50 ml). After equilibration of the HPLC system, the calibration mixture was injected first, followed by the test chemical solution twice and the calibration mixture again. See Appendixes 3 and 

### 4 for examples of the chromatograms obtained. Retention times tR were measured and averaged and the decimal logarithms of the capacityfactors kwere calculated. The linear regression parameters of the relationship log Pow = 

### f(log k) were also calculated from the data obtained with the calibration mixture and, therewith, log Pow of the test substance was determined from its measured capacity factor. 

### 4. RESULTS Detailed results are given in Appendix 1 

### and illustrated by the graph in Appendix 2. 

### 5. CONCLUSION The chromatogram shows one peak at retention time 6.995 minutes, corresponding to a partition coefficient (log value) of 3.6. Therefore: Partition coefficient n-octanol/water of 

### log 

### Pow= 3.6. N.B.: The determination was performed at 35 

## oc (temperature of the column), but the value obtained above can be considered to represent the value at an unspecified, probably ambient temperature since no mention is made in the guidelines of the temperature at which the tabulated reference substances log Pow values were determined. Partition coefficients of the test and reference substances are assumed to vary with temperature in the same way.Study No. - Final report Appendix 1

PARTITION COEFFICIENT DETERMINATION BY REVERSE-PHASE HPLC

REFERENCE SUBSTANCES log Pow tR1 tR2 tAm thiourea 1.75 1.75 1.75 Aniline 0.9 2.57 2.58 2.58 Methyl benzoate 2.1 3.72 3.74 3.73 Benzophenone 3.2 5.38 5.41 5.40 Naphthalene 3.6 6.33 6.36 6.35 1,2,4-trichlorobenzene 4.2 9.99 10.04 10.02 n-butylbenzene 4.6 12.58 12.65 12.62 triphenylamine 5.7 21.02 21.14 21.08 Page 12/15

k log k 0.471 -0.327 1.131 0.054 2.083 0.319 2.626 0.419 4.723 0.674 6.209 0.793 11.046 1.043 tR1, tR2, tAm: retention times (1 rst measurement, 2nd measurement, average) k = (tR/t0)-1 : capacity factor, tO : "dead time", i.e. retention time ofthiourea Linear regression parameters : log Pow = a * log k

### + b Correlation coefficient r = 0.9972 a= 3.4353 b = 2.0113 TEST SUBSTANCE : tR1 tR2 tAm k log k log Pow 2.9969 0.4767 

### 3.6Study No. - Final report

log Pow 6.0

5.0

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Hi- 2Q Chromatogram of the reference substances Page 14/15

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### Study No. - Final report Appendix 4

Chromatogram of Page 15/15