Heptanal, oligomeric reaction products with aniline

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 July 2016 to 03 November 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)

Deviations:

yes

Remarks:

see "Any other information on materials and methods incl. tables" for more details.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)

Deviations:

no

Remarks:

see "Any other information on materials and methods incl. tables" for more details.

Qualifier:

according to guideline

Guideline:

other: see "Versions / remarks"

Version / remarks:

European Community (EC), EC no. 2016/266, Part A: Methods for the Determination of
Physico-Chemical Properties, Guideline A.24: "Partition Coefficient (n-octanol/water),
High Performance Liquid Chromatography (HPLC) Method", Official Journal of the
European Union no. L54, March 1, 2016.

Deviations:

yes

Remarks:

see "Any other information on materials and methods incl. tables" for more details.

GLP compliance:

yes

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

Performance of the study
Four methods are available for the determination of the partition coefficient (Pow) of the test item. The principle of each method is described below:
 
Shake flask method
Test item is partitioned in a two-phase system of n-octanol and water. After phase separation, the concentration of the test item in both phases is determined by a suitable analytical method. The shake flask method can be used for test item with a log Pow value in the range of-2 to 4.
 
HPLC method
A solution of the test item is injected onto a reversed-phase UPLC column. The log Pow value is calculated from the retention time of the test item. The HPLC method covers log Pow values in the range of 0 to at least 6.
 
Estimation method
The solubility of the test item in n-octanol and in water is determined. The quotient of the n-octanol solubility and the water solubility is an estimation of the Pow. The estimation method can be applied if the shake flask method and HPLC method are not applicable.
 
Calculation method
The calculation method is based on the theoretical fragmentation of the molecule into suitable sub-structures for which reliable log Pow increments are known. The log Pow is obtained by summing the fragment values and the correction terms for intramolecular interactions. Lists of fragment constants and correction terms are available.
 
The test item was a reaction mass and was considered a complex substance. Therefore, the partition coefficient was investigated with the HPLC method using buffer at pH 7. Obtained chromatograms, however, were not meaningful and lacked repeatability. Tests were most probably hampered by insufficient solubility of the test item in buffer pH 7. The partition coefficient was, therefore, determined at neutral pH.
Solutions of reference substances and the test item were analysed. The capacity factor (k') ofeach compound was calculated from its retention time. The log k’ values of the referencessubstances were plotted against the known log Pow values. A linear regression program was used to calculate the calibration curve. Linear regression analysis was performed using the least squares method. The coefficient of correlation (r) was calculated. The log Pow value forthe test item was calculated by substituting its mean log k’ in the calibration curve. The valueof log Pow obtained from duplicate measurements was within+/-0.1 log units.
 
Analytical conditions
Instrument: Acquity UPLC system (Waters, Milford, MA, USA)
Detector: Acquity UPLC TUV detector (Waters)
Column: Acquity UPLC HSS T3, 100 mm x2.1 mm i.d., dp = 1.8 μm (Waters)
Column temperature: 35°C+/-1°C
Mobile phase A – methanol / B – water.
Gradient:
Time [minutes]          %A                  %B
0                                75                   25
20                               75                    25
21                               100                 0
31                               100                 0
31.1                            75                   25
45                               75                   25

Flow: 0.4 mL/min
Injection volume: 5 μL
UV detection: 210 nm

Preparation of the solutions
Solution of the unretained compound
A 5.0 g/L stock solution of formamide (99.2%, [75-12-7], Alfa Aesar GmbH & Co Kg, Karlsruhe, Germany) in methanol was used. The stock solution was diluted to obtain an end solution of 75/25 (v/v) methanol/water.
The formamide blank solution was 75/25 (v/v) methanol/water.
 
Reference substance solutions
Stock solutions of the reference substances at concentrations of approximately 1 g/L in methanol were used. The stock solutions were diluted to obtain an end solution of 75/25 (v/v) methanol/water.
The blank solution for the mixture of reference substances was 75/25 (v/v) methanol/water.
 
Test solution
A 1000 mg/L stock solution of the test item was prepared in methanol. The stock solution was diluted to obtain an end solution of 75/25 (v/v) methanol/water. The final concentration of the test item solution was 10.0 mg/L.
The test item blank solution was 75/25 (v/v) methanol/water
 
Reference substance solution with log Pow > 6.5
A stock solution of benzo[ghi]perylene at a concentration of approximately 1 g/L in DMF was used. The stock solution was diluted to obtain an end solution of 75/25 (v/v) DMF/water.
The blank solution for the mixture of reference substances was 75/25 (v/v) DMF/water.
 
Injections
The reference substance and test item solutions were injected in duplicate. Blank solutions
were analysed by single injection.
 

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

> 7.2

Temp.:

35.1 °C

pH:

7

Details on results:

The equation of the regression line was: log k’ = 0.317´log Pow– 0.764 (r = 0.995, n = 14).

P_owof the test item

Substance	tr,1 [min]	tr,2 [min]	mean tr (n=2)	log Pow	Pow	Area %
Formamide (t0)	0.589	0.589	0.589
Benzylalcohol	0.761	0.763		1.1
Toluene	1.482	1.485		2.7
1,4-Dichlorobenzene	1.915	1.919		3.4
Biphenyl	2.570	2.578		4.0
Dibenzyl	4.290	4.303		4.8
4,4’-DDT	11.397	11.445		6.5
Benzo[ghi]perylene	17.985	18.005		7.2
Test item – peak 1	0.728	0.728	0.728	< 1.1	< 1.3´10^1	12
Test item – peak 2	12.332	12.285	12.309	6.5	3.2´10^6	14
Test item – peak 3	22.782	22.782	22.782	> 7.2	> 1.6´10^7	7.0
Test item – peak 4	22.854	22.853	22.854	> 7.2	> 1.6´10^7	10
Test item – peak 5	22.978	22.978	22.978	> 7.2	> 1.6´10^7	19
Test item – peak 6	23.197	23.197	23.197	> 7.2	> 1.6´10^7	9.7
Test item – peak 7	25.456	25.454	25.455	> 7.2	> 1.6´10^7	21
Test item – peak 8	29.963	29.958	29.961	> 7.2	> 1.6´10^7	6.6

 

 

Conclusions:

The HPLC method was applied for the determination of the partition coefficient of Hepteen Base® at neutral pH.
log Pow : > 7.2
Pow: > 1.6 x 10 ^7

Executive summary:

The HPLC method was applied for the determination of the partition coefficient (P_ow) of Hepteen Base®.

 

The P_owand log P_owvalues of the test item at neutral pH were:

	Pow	log Pow	Area %
Test item – peak 1	< 1.3´10^1	< 1.1	12
Test item – peak 2	3.2´10^6	6.5	14
Test item – peak 3	> 1.6´10^7	> 7.2	7.0
Test item – peak 4	> 1.6´10^7	> 7.2	10
Test item – peak 5	> 1.6´10^7	> 7.2	19
Test item – peak 6	> 1.6´10^7	> 7.2	9.7
Test item – peak 7	> 1.6´10^7	> 7.2	21
Test item – peak 8	> 1.6´10^7	> 7.2	6.6

 

Description of key information

Partition coefficient for Hepteen Base ® was determined to be:

log Pow : > 7.2

Pow: > 1.6 x 10^7

Key value for chemical safety assessment

Log Kow (Log Pow):

7.2

at the temperature of:

35.1 °C

Additional information

A study using UPLC was conduced to determine the partition coefficient of Hepteen Base®. The experiment was conducted in accordance with the following guidelines in a GLP accredited laboratory.

European Community (EC), EC no. 2016/266, Part A: Methods for the Determination of Physico-Chemical Properties, Guideline A.24: "Partition Coefficient (n-octanol/water), High Performance Liquid Chromatography (HPLC) Method", Official Journal of the

European Union no. L54, March 1, 2016.

Organization for Economic Co-operation and Development (OECD), OECD Guidelines for the Testing of Chemicals no. 117: "Partition Coefficient (n-octanol/water), High Performance Liquid Chromatography (HPLC) Method", April 13, 2004.

United States Environmental Protection Agency (EPA), Product Properties Test Guidelines no. OPPTS 830.7570: "Partition Coefficient (n-octanol/water), Estimation by Liquid Chromatography", August 1996.