2,2'-methylenebis[6-(1-methylcyclohexyl)-p-cresol]

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 June 2015 to 10 September 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - HPLC Method)

Version / remarks:

European Community (EC), EC no. 440/2008, Part A: Methods for the Determination of Physico-Chemical Properties, Guideline A.8: “Partition Coefficient”, Official Journal of the European Union no. L142, May 31, 2008.

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

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.

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

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.

Deviations:

no

GLP compliance:

yes

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

Identification: 2,2'-methylenebis[6-(1-methylcyclohexyl)-p-cresol]
Appearance: White to cream powder
Batch: WWP4J0001
Purity/Composition: 92.2%
Test substance storage: At room temperature
Stable under storage conditions until: 03 September 2018 (retest date)
Purity/composition correction factor: Yes, correction factor is according to purity
Test substance handling: No specific handling conditions required

Analytical method:

high-performance liquid chromatography

Type:

log Pow

Partition coefficient:

9.9

Temp.:

35 °C

pH:

7

Remarks on result:

other:

Remarks:

Temp is the column temperature (HPLC method)

Type:

Pow

Partition coefficient:

8 300 000 000

Temp.:

35 °C

pH:

7

Remarks on result:

other:

Remarks:

Temp is the column temperature (HPLC method)

Details on results:

Calculation of the Pow
The log Pow of the test item was calculated to be 10.7 using the Rekker calculation method.

HPLC Method
In the chromatogram of the test solution, one major peak was observed at a retention time of 91 minutes and one small peak at a retention time of 97 minutes.
The equation of the regression line was: logk’ = 0.284 x log Pow – 0.610 (r = 0.997, n = 12).

P_owof the test substance

Substance	tr,1 [min]	tr,2 [min]	Mean tr (n=2)	Log Pow	Pow	Area %
Formamide (t0)   Biphenyl 1,2,4-Trichlorobenzene Dibenzyl Triphenylamine 4,4’-DDT Benzo[ghi]perylene   TI206533-Peak1 TI206533-Peak2	0.567   2.365 2.730 3.848 6.906 9.827 15.644   91.483 97.083	0.565   2.364 2.729 3.847 6.905 9.829 15.652   91.489 97.156	0.566                 91.486 97.120	4.0 4.2 4.8 5.7 6.5 7.2   9.9 10.0	8.3 x 10^9 1.0 x 10^10	98 2.4

 

Conclusions:

The HPLC method was applied for the determination of the partition coefficient (Pow) of 2,2'- methylenebis[6-(1-methylcyclohexyl)-p-cresol].
The Pow and log Pow value of the main component at neutral pH was:
8.3e9 Pow; 9.9 log Pow

Executive summary:

The aim of the study was to determine the physico-chemical properties for 2,2'-methylenebis[6-(1-methylcyclohexyl)-p-cresol].

 

The study was based on the following guidelines:

European Community (EC), EC no. 440/2008, Part A: Methods for the Determination of Physico-Chemical Properties, Guideline A.8: “Partition Coefficient”, Official Journal of the European Union no. 142, May 31, 2008.

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.

 

The calculation method was used for a preliminary estimation of the P_owof the test substance.

Calculation was performed using the Rekker calculation method (PrologP 6.0, module in Pallas 3.0, CompuDrug International, San Francisco, CA, USA). The calculation showed a log P_owoutside the range of the methods. Testing according to OECD 123 Slow-Stirring Method however is not possible since concentration in the aqueous phase cannot be measured accurately. As an alternative, it was decided to use the HPLC method for determination of the P_ow.

According to the guidelines, the determination of the P_owof the test substance should be performed in its non-ionised form. Therefore, the pKa values of the test substance were calculated using the Perrin calculation method (pKalc 5.0, module in Pallas 3.0, CompuDrug International). Based on the calculations, it was decided to perform the HPLC method at neutral pH.

Solutions of reference substances and the test substance were analysed. The capacity factor (k') of each compound was calculated from its retention time. The log k’ values of the references substances were plotted against the known log P_owvalues. 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 for the test substance was calculated by substituting its mean log k’ and extrapolating the calibration curve. The value of log P_owobtained from duplicate measurements was within ± 0.1 log units.

 

Calculation of the P_ow

The log P_owof the test item was calculated to be 10.7 using the Rekker calculation method.

 

HPLC Method

In the chromatogram of the test solution, one major peak was observed at a retention time of 91 minutes and one small peak at a retention time of 97 minutes.

 

The HPLC method was applied for the determination of the partition coefficient (Pow) of 2,2'- methylenebis[6-(1-methylcyclohexyl)-p-cresol].

The P_owand log P_owvalue of the main component at neutral pH was:

	Pow	Log Pow	Area %
Main component	8.3 x 10^9	9.9	98

 

Description of key information

Key value determined in a GLP accredited laboratory study using the HPLC method, performed in accordance with EU Method A.8, OECD Guideline 117 and US EPA Procedure OPPTS 830.7570.

Key value for chemical safety assessment

Log Kow (Log Pow):

9.9

at the temperature of:

35 °C

Additional information

The calculation method was used for a preliminary estimation of the P_owof the test substance.

Calculation was performed using the Rekker calculation method (PrologP 6.0, module in Pallas 3.0, CompuDrug International, San Francisco, CA, USA). The calculation showed a log P_owoutside the range of the methods. Testing according to OECD 123 Slow-Stirring Method however is not possible since concentration in the aqueous phase cannot be measured accurately. As an alternative, it was decided to use the HPLC method for determination of the P_ow.

According to the guidelines, the determination of the P_owof the test substance should be performed in its non-ionised form. Therefore, the pKa values of the test substance were calculated using the Perrin calculation method (pKalc 5.0, module in Pallas 3.0, CompuDrug International). Based on the calculations, it was decided to perform the HPLC method at neutral pH.

Solutions of reference substances and the test substance were analysed. The capacity factor (k') of each compound was calculated from its retention time. The log k’ values of the references substances were plotted against the known log P_owvalues. 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 for the test substance was calculated by substituting its mean log k’ and extrapolating the calibration curve. The value of log P_owobtained from duplicate measurements was within ± 0.1 log units.

 

Calculation of the P_ow

The log P_owof the test item was calculated to be 10.7 using the Rekker calculation method.

 

HPLC Method

In the chromatogram of the test solution, one major peak was observed at a retention time of 91 minutes and one small peak at a retention time of 97 minutes.

 

The HPLC method was applied for the determination of the partition coefficient (Pow) of 2,2'- methylenebis[6-(1-methylcyclohexyl)-p-cresol].

The P_owand log P_owvalue of the main component at neutral pH was:

	Pow	Log Pow	Area %
Main component	8.3 x 10^9	9.9	98