Registration Dossier

Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 22, 2015 - October 29, 2015
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The calculation method meets general accepted scientific principles, considered to be reliable with acceptable restriction.
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The partition coefficient n-octanol/water of the test substance was determined using individually measured n-octanol solubility and water solubility.
GLP compliance:
no
Remarks:
The testing reported here meets the requirements of ANSI/ISO/IEC 17025-2005 "General Requirements for the Competence of Testing and Calibration Laboratories", in accordance with A2LA Certificate # 2052.01.
Type of method:
other:
Partition coefficient type:
octanol-water

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MTDID 15655 (Z-Acetate)
- Substance type: Single component
- Physical state: Liquid

Study design

Analytical method:
high-performance liquid chromatography

Results and discussion

Partition coefficient
Type:
log Pow
Partition coefficient:
7.16
Remarks on result:
other: pH and temperature not measured
Details on results:
The log Kow of Z-acetate can be calculated based on the equation of Kow = C (n-octanol)/C (water), where C (n-octanol) is the measured solubility in n-octanol and C(water) is the measured solubility in water.

The average n-octanol solubility of Z-Acetate was determined in this study to be 50.1 g/L (RSD= 11%). Taking into account of the RSD% in the measurements, n-octanol solubility of Z-Acetate ranged from 44.99 - 55.611 g/L.

The average water solubility of Z-Acetate was previously determined to be 3.5 µg/L (RSD= 50%) (see section 4.8). Taking into account of the RSD% in the measurements, the water solubility of Z-Acetate ranged from 1.75-5.52 µg/L.

Based on the average measured n-octanol solubility of 50.1 g/L and average measured water solubility of 3.5 µg/L, the calculated average Kow is 1.43E+07, the average log Pow is 7.16.

The Kow range can be calculated using the experimental error limits of the contributing measurements. Given the calculated low n-octanol solubility of 44.99 g/L and calculated high water solubility of 5.25 µg/L, the low Kow is calculated to be 8.57E+06, the low calculated log Kow is 6.93.

Similarly, using the calculated high n-octanol solubility of 55.611 g/L and calculated low measured water solubility of 1.75 µg/L, the high Kow is calculatedto be 3.18E+07, the high calculated log Kow is 7.50.

Therefore, Z-acetate has an average log Kow of 7.16, with a range of 6.93 - 7.50.

Although the water solubility had a high RSD%, the result does not have substantial effect on the log Kow.

Any other information on results incl. tables

 Table 1. n-Octanol solubility results of Z-Acetate

Day

Z-Acetate Conc. in n-Octanol
(g/L)

Average

(g/L)

RPD%

Sample

Dup 1

Dup 2.

 

 

 

4

1

55.5

55.7

55.6

0.36

2

58.0

60.3

59.2

3.9

3

51.4

50.5

51.0

1.8

Day 4 average

55.2

 

% RSD

6.8

 

 

 

 

5

1

54.8

45.5

50.2

19

2

53.7

47.6

50.7

12

3

51.9

52.5

52.2

1.1

Day 5 average

51.0

 

% RSD

7.2

 

6

1

42.9

45.4

44.2

5.7

2

45.0

43.8

44.4

2.7

3

43.0

44.8

43.9

4.1

Day 6 average

44.2

 

% RSD

2.4

 

Overall Avg. (g/L)

50.1

Overall RSD% (n= 18)

11

Table 2. Calculation of partition coefficient of Z-acetate

 

Average

Low

High

Octanol solubility (g/L)

50.1

44.99

55.611

RSD%

11

 

 

 

 

 

 

Water solubility

3.5

1.75

5.25

RSD%

50

 

 

 

 

 

 

 Kow

1.43E+07

8.57E+06

3.18E+07

Average log Kow

7.16

6.93

7.50

Applicant's summary and conclusion

Conclusions:
The n-octanol/water partition coefficient (Log Kow) of Z-Acetate was calculated to be 7.16, based on the ratio of solubility in water and in n-octanol, measured separately.
Executive summary:

The n-octanol/water partition coefficient (Log Kow) of Z-Acetate was determined based on the equation Kow = Solubility (n-octanol)/Solubility (water), where the solubility of Z-acetate in n-octanol and in water were measured separately.

The n-octanol solubility of Z-acetate was determined in this study. Triplicate test vessels containing approximately 1 mL of test substance were prepared. Then, 10 mL n-octanol was added to the test vessels. The samples were allowed to incubate in an orbital shaker at approximately 30°C and at a setting of 100 ± 10 (RPM) for approximately 4, 5 and 6 days. After incubation, the vessels were removed and allowed to equilibrate at room temperature out of direct light for ~24 hours. Duplicate aliquots of the n-octanol phase were removed from each of the test vessels and diluted with acetonitrile appropriately for quantitative LC/MS/MS.

Based on the result of this study, the average n-octanol solubility of Z-acetate was determined to be 50.1 g/L (RSD = 11%), with a calculated range of 44.99 - 55.61 g/L. The water solubility of Z-Acetate was previously determined to be 3.5 µg/L (RSD= 50%), with a calculated range of 1.75 - 5.25 µg/L.

Based on the range of measured n-octanol solubility and the range of measured water solubility, Z-acetate has a calculated log Kow range of 6.93 - 7.50. Based on the average measured n-octanol solubility of 50.1 g/L and average measured water solubility of 3.5 µg/L, the calculated average Kow is 1.43E+07, the average log Kow is 7.16.

No guideline exists for measurement of octanol solubility. Per Chapter R.7a of Guidance on Information Requirements and Chemical Safety Assessment, the general principles of OECD TG105 (water solubility) apply tp octanol solubility measurement. This study was not conducted under GLP. However, the testing laboratory meets the requirements of ANSI/ISO/IEC 17025-2005 "General Requirements for the Competence of Testing and Calibration Laboratories," with solubility measurement being within the scope of the accreditation. The calculation method meets general accepted scientific principles. Although the water solubility had a high RSD%, the result does not have substantial effect on the log Kow. Therefore, it is considered to be reliable with acceptable restriction.