N-(2-hydroxyethyl)stearamide

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From June 19, 2012 to August 27, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7550 (Partition Coefficient, n-octanol / H2O, Shake Flask Method)

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Principles of method if other than guideline:

Since the test substance is a surface active material, the partition coefficient was determined by the estimation method using the n-octanol solubility of the test substance and the critical micelle concentration.

GLP compliance:

yes

Type of method:

other: Estimation method

Partition coefficient type:

octanol-water

Type:

Pow

Partition coefficient:

28 500

Temp.:

20 °C

Remarks on result:

other: no information on pH

Type:

log Pow

Partition coefficient:

4.46

Temp.:

20 °C

Remarks on result:

other: no information on pH

Details on results:

Results
1. Preliminary test
After the stirring period, undissolved test substance was observed in the test samples. From this, it was concluded that the n-octanol solubility of the test substance at 20°C was < 11.5 g/L based on visual observation of 6 hours.

2. Main study
The results for the samples taken at 24, 48 and 72 hours are given in Table 1. The 48-hour measurement was significantly lower than the 24- and 72- hour measurements (maximum difference > 15%). Therefore it was decided to take samples after an extended stirring time. The results for the samples taken at 96, 120 and 144 hours are given in Table 2.
The octanol phases were two-times centrifuged at 16421 g and 20°C for 10 minutes. Accurate weighed volumes of 50 μL of the phases were diluted with 50/50 (v/v) acetonitrile/water in volumetric flasks of 10 mL. The solutions were further diluted with 50/50 (v/v) acetonitrile/water to obtain concentrations within the calibration range.

The 96-hour measurement was significantly higher than the 120- and 144- hour measurements (maximum difference > 15%). According to the guidelines, the octanol solubility of the test substance was given as the mean value of the 120- and 144-hour measurements.

The Pow, calculated as the quotient of the n-octanol- and critical micelle concentration, is > 2.85x10(4). It corresponds with a log Pow value of > 4.46.

A small response was detected in the pre-treated samples from the blank octanol mixture. This was smaller than the lowest standard.

Table 1: Main study – n-octanol solubility of the test substance

Stirring time	Analysed concentration	Mean	MD
[hours]	[g/L]	[g/L]	[%]
24	42	30.9	118
48	10.8
72	39.9

Table 2: Main study – n-octanol solubility of the test substance

Stirring time	Analysed concentration	Mean	MD
[hours]	[g/L]	[g/L]	[%]
96	34.5	28.5	1.6
120	28.3
144	27.2

Conclusions:

Under the study conditions, the partition coefficient (log Pow) was determined to be 4.46 at 20°C.

Executive summary:

A study was conducted to determine the partition coefficient of the test substance, C16-18 MEA (purity not specified) according to OECD Guideline 207, EPA OPPTS Guideline 830.7550 and EU Method A.8, in compliance with GLP. In this method, the solubility of the test substance in n-octanol and in water was determined. For this surface active substance, the critical micelle concentration (CMC) was used as an alternative to the water solubility. Under the study conditions, the partition coefficient (log Pow) was determined to be 4.46 at 20°C (Baltussen, 2012).

Reference 2

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

QSAR prediction from a well-known and acknowledged tool. See below under ''attached background material section' for QPRF containing methodology and domain evaluation details.

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSARs: Chapter R.6. QSARs and grouping of chemicals

Principles of method if other than guideline:

The partition coefficient (log Kow) value for the test substance were estimated using the group contributions methodology of Molinspiration (miLogP2.2 - November 2005). Since the test substance is a UVCB, the log Kow values were predicted for the individual constituents using SMILES codes as the input parameter.

Type of method:

other: Group contributions

Partition coefficient type:

other: QSAR prediction

Key result

Type:

log Pow

Partition coefficient:

ca. 2.25 - ca. 8.84

Remarks on result:

other: predicted for the main constituents

Remarks:

Molinspiration (miLogP2.2)

Key result

Type:

log Pow

Partition coefficient:

ca. 6.67

Remarks on result:

other: weighted average Log Kow

Remarks:

Molinspiration (miLogP2.2)

Predicted value:

Using the group contribution method of molinspiration model, the partition coefficient (Log Kow) values for the different constituents were predicted as follows:

Table 1: Log Kow predictions: Group contribution-based method

Constituents/Carbon chain length*	Mean/adjusted conc.	Mole fraction Xi = (mi/Mi)/∑ (mi/Mi)	Log Kow	Log Kow * xi
C8	1.5	0.02413	2.25	5.43E-02
C14	4	0.04440	5.28	2.34E-01
C16	42.5	0.42755	6.29	2.69E+00
C18	51.5	0.47371	7.3	3.46E+00
C18'	1.5	0.01388	6.81	9.45E-02
C20	1	0.00847	8.27	7.01E-02
C22	1	0.00785	8.84	6.94E-02
			Log Kow =	6.67

*Glycerol or MEA residues have not been considered for the QSAR prediction

Conclusions:

Using the group contribution method, of molinspiration (miLogP 2.2), the weighted average partition coefficient (log Kow) value for test substance was predicted to be 6.67.

Executive summary:

The partition coefficient (log Kow) value for the test substance, C16-18 MEA was predicted using the group contribution method, of Molinspiration (miLogP 2.2) program. Since the test substance is a UVCB, the log Kow values were predicted for the individual constituents using SMILES codes as the input parameter. Using the group contribution method, the log Kow values for the individual constituents of the test substance ranged from 2.25 to 8.84. All constituents meet the molecular weight and log Kow descriptor domain criteria. Given that the constituents are structurally very similar and vary only in the carbon chain length, a weighted average value, which considers the percentage of the constituent in the substance, was considered to dampen the errors in predictions (if any). Therefore, the weighted average log Kow value was calculated as 6.67. Overall, considering either the individual log Kow predictions for the constituents or the weighted average values, the test substance is expected to be less hydrophobic with a good absorption and low accumulation potential. Therefore, the log Kow predictions for the test substance using Molinspiration (miLogP 2.2), can be considered to be reliable with moderate confidence.

Reference 3

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

QSAR prediction from a well-known and acknowledged tool. See below under ''attached background material section' for QPRF containing methodology and domain evaluation details.

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSARs: Chapter R.6. QSARs and grouping of chemicals

Principles of method if other than guideline:

The partition coefficient (log Kow) value for the test substance were estimated using the KOWWIN v.1.68. program in EPI SuiteTM v4.11. Since the test substance is a UVCB, the log Kow values were predicted for the individual constituents using SMILES codes as the input parameter.

Type of method:

other: Fragment constant method

Partition coefficient type:

other: QSAR prediction

Key result

Type:

log Pow

Partition coefficient:

ca. 1.28 - ca. 8.15

Remarks on result:

other: predicted for the main constituents

Remarks:

KOWWIN v.1.68. EPI SuiteTM v4.11

Key result

Type:

log Pow

Partition coefficient:

ca. 5.58

Remarks on result:

other: weighted average Log Kow

Remarks:

KOWWIN v.1.68. EPI SuiteTM v4.11

Predicted value (model result):

The predicted log Kow values for the different constituents using the fragment constant-based method were as follows:

Table 2: Log Kow predictions: Fragment constant-based method

Constituents/Carbon chain length*	Mean/ adjusted conc	Mole fraction Xi = (mi/Mi)/∑ (mi/Mi)	Log Kow	Log Kow * xi	Domain evaluation
C8	1.5	0.02413	1.28	0.030809494	MW, Structural fragment (ID)
C14	4	0.04440	4.22	0.187360679	MW, Structural fragment (ID)
C16	42.5	0.42755	5.21	2.227540874	MW, Structural fragment (ID)
C18	51.5	0.47371	6.19	2.932262665	MW, Structural fragment (ID)
C18'	1.5	0.01388	5.97	0.082881401	MW, Structural fragment (ID)
C20	1	0.00847	7.17	0.060749267	MW (ID), Structural fragment (OD) - 1 out of 5 fragments (aliphatic carbon (-CH2-), exceeds by 2 instances)
C22	1	0.00785	8.15	0.064003974	MW (ID), Structural fragment (OD) - 1 out of 5 fragments (aliphatic carbon (-CH2-), exceeds by 4 instances)
			Log Kow=	5.586

*Glycerol or MEA residues have not been considered for the QSAR prediction

Log Kow prediction results:

                 Log Kow(version 1.69 estimate): 1.28

 

SMILES : CCCCCCCC(=O)NCCO

CHEM  :

MOL FOR: C10 H21 N1 O2

MOL WT : 187.28

-------+-----+--------------------------------------------+---------+--------

 TYPE | NUM |       LOGKOW FRAGMENT DESCRIPTION        | COEFF | VALUE

-------+-----+--------------------------------------------+---------+--------

 Frag | 1 | -CH3   [aliphatic carbon]               | 0.5473 | 0.5473

 Frag | 8 | -CH2-  [aliphatic carbon]               | 0.4911 | 3.9288

 Frag | 1 | -OH    [hydroxy, aliphatic attach]      |-1.4086 | -1.4086

 Frag | 1 | -NH-   [aliphatic attach]               |-1.4962 | -1.4962

 Frag | 1 | -C(=O)N [aliphatic attach]              |-0.5236 | -0.5236

 Const |    | Equation Constant                        |        | 0.2290

-------+-----+--------------------------------------------+---------+--------

                                                        Log Kow  =  1.2767

 

 

                 Log Kow(version 1.69 estimate): 4.22

 

SMILES : CCCCCCCCCCCCCC(=O)NCCO

CHEM  :

MOL FOR: C16 H33 N1 O2

MOL WT : 271.45

-------+-----+--------------------------------------------+---------+--------

 TYPE | NUM |       LOGKOW FRAGMENT DESCRIPTION        | COEFF | VALUE

-------+-----+--------------------------------------------+---------+--------

 Frag | 1 | -CH3   [aliphatic carbon]               | 0.5473 | 0.5473

 Frag | 14 | -CH2-  [aliphatic carbon]               | 0.4911 | 6.8754

 Frag | 1 | -OH    [hydroxy, aliphatic attach]      |-1.4086 | -1.4086

 Frag | 1 | -NH-   [aliphatic attach]               |-1.4962 | -1.4962

 Frag | 1 | -C(=O)N [aliphatic attach]              |-0.5236 | -0.5236

 Const |    | Equation Constant                        |        | 0.2290

-------+-----+--------------------------------------------+---------+--------

                                                        Log Kow  =  4.2233

 

 

 

                 Log Kow(version 1.69 estimate): 5.21

 

SMILES : CCCCCCCCCCCCCCCC(=O)NCCO

CHEM  :

MOL FOR: C18 H37 N1 O2

MOL WT : 299.50

-------+-----+--------------------------------------------+---------+--------

 TYPE | NUM |       LOGKOW FRAGMENT DESCRIPTION        | COEFF | VALUE

-------+-----+--------------------------------------------+---------+--------

 Frag | 1 | -CH3   [aliphatic carbon]               | 0.5473 | 0.5473

 Frag | 16 | -CH2-  [aliphatic carbon]               | 0.4911 | 7.8576

 Frag | 1 | -OH    [hydroxy, aliphatic attach]      |-1.4086 | -1.4086

 Frag | 1 | -NH-   [aliphatic attach]               |-1.4962 | -1.4962

 Frag | 1 | -C(=O)N [aliphatic attach]              |-0.5236 | -0.5236

 Const |    | Equation Constant                        |        | 0.2290

-------+-----+--------------------------------------------+---------+--------

                                                        Log Kow  =  5.2055

 

 

                 Log Kow(version 1.69 estimate): 6.19

 

SMILES : CCCCCCCCCCCCCCCCCC(=O)NCCO

CHEM  :

MOL FOR: C20 H41 N1 O2

MOL WT : 327.56

-------+-----+--------------------------------------------+---------+--------

 TYPE | NUM |       LOGKOW FRAGMENT DESCRIPTION        | COEFF | VALUE

-------+-----+--------------------------------------------+---------+--------

 Frag | 1 | -CH3   [aliphatic carbon]               | 0.5473 | 0.5473

 Frag | 18 | -CH2-  [aliphatic carbon]               | 0.4911 | 8.8398

 Frag | 1 | -OH    [hydroxy, aliphatic attach]      |-1.4086 | -1.4086

 Frag | 1 | -NH-   [aliphatic attach]               |-1.4962 | -1.4962

 Frag | 1 | -C(=O)N [aliphatic attach]              |-0.5236 | -0.5236

 Const |    | Equation Constant                        |        | 0.2290

-------+-----+--------------------------------------------+---------+--------

                                                        Log Kow  =  6.1877

 

 

                 Log Kow(version 1.69 estimate): 5.97

 

SMILES : CCCCCCCCC=CCCCCCCCC(=O)NCCO

CHEM  :

MOL FOR: C20 H39 N1 O2

MOL WT : 325.54

-------+-----+--------------------------------------------+---------+--------

 TYPE | NUM |       LOGKOW FRAGMENT DESCRIPTION        | COEFF | VALUE

-------+-----+--------------------------------------------+---------+--------

 Frag | 1 | -CH3   [aliphatic carbon]               | 0.5473 | 0.5473

 Frag | 16 | -CH2-  [aliphatic carbon]               | 0.4911 | 7.8576

 Frag | 2 | =CH- or =C< [olefinc carbon]            | 0.3836 | 0.7672

 Frag | 1 | -OH    [hydroxy, aliphatic attach]      |-1.4086 | -1.4086

 Frag | 1 | -NH-   [aliphatic attach]               |-1.4962 | -1.4962

 Frag | 1 | -C(=O)N [aliphatic attach]              |-0.5236 | -0.5236

 Const |    | Equation Constant                        |        | 0.2290

-------+-----+--------------------------------------------+---------+--------

                                                        Log Kow  =  5.9727

 

 

                 Log Kow(version 1.69 estimate): 7.17

 

SMILES : CCCCCCCCCCCCCCCCCCCC(=O)NCCO

CHEM  :

MOL FOR: C22 H45 N1 O2

MOL WT : 355.61

-------+-----+--------------------------------------------+---------+--------

 TYPE | NUM |       LOGKOW FRAGMENT DESCRIPTION        | COEFF | VALUE

-------+-----+--------------------------------------------+---------+--------

 Frag | 1 | -CH3   [aliphatic carbon]               | 0.5473 | 0.5473

 Frag | 20 | -CH2-  [aliphatic carbon]               | 0.4911 | 9.8220

 Frag | 1 | -OH    [hydroxy, aliphatic attach]      |-1.4086 | -1.4086

 Frag | 1 | -NH-   [aliphatic attach]               |-1.4962 | -1.4962

 Frag | 1 | -C(=O)N [aliphatic attach]              |-0.5236 | -0.5236

 Const |    | Equation Constant                        |        | 0.2290

-------+-----+--------------------------------------------+---------+--------

                                                        Log Kow  =  7.1699

 

 

                 Log Kow(version 1.69 estimate): 8.15

 

SMILES : CCCCCCCCCCCCCCCCCCCCCC(=O)NCCO

CHEM  :

MOL FOR: C24 H49 N1 O2

MOL WT : 383.66

-------+-----+--------------------------------------------+---------+--------

 TYPE | NUM |       LOGKOW FRAGMENT DESCRIPTION        | COEFF | VALUE

-------+-----+--------------------------------------------+---------+--------

 Frag | 1 | -CH3   [aliphatic carbon]               | 0.5473 | 0.5473

 Frag | 22 | -CH2-  [aliphatic carbon]               | 0.4911 | 10.8042

 Frag | 1 | -OH    [hydroxy, aliphatic attach]      |-1.4086 | -1.4086

 Frag | 1 | -NH-   [aliphatic attach]               |-1.4962 | -1.4962

 Frag | 1 | -C(=O)N [aliphatic attach]              |-0.5236 | -0.5236

 Const |    | Equation Constant                        |        | 0.2290

-------+-----+--------------------------------------------+---------+--------

                                                        Log Kow  =  8.1521

Conclusions:

Using the fragment constant method, of KOWWIN V.1.68 program of EPI SuiteTM, the weighted average partition coefficient (log Kow) value for test substance was predicted to be 5.58.

Executive summary:

The partition coefficient (log Kow) value for the test substance, C16-18 MEA was predicted using the fragment constant method, of KOWWIN V.1.68 program. Since the test substance is a UVCB, the log Kow values were predicted for the individual constituents using SMILES codes as the input parameter. Using the fragment constant method, the log Kow values for the individual constituents of the test substance ranged from 1.28 to 8.15. All constituents meet the molecular weight and structural fragment descriptor domain criteria, except for one fragment of two constituents that exceeded the maximum number of instances. Given that the constituents are structurally very similar and vary only in the carbon chain length, a weighted average value, which considers the percentage of the constituent in the substance, was considered to dampen the errors in predictions (if any). Therefore, the weighted average log Kow value was calculated as 5.58. Overall, considering either the individual log Kow predictions for the constituents or the weighted average values, the test substance is expected to be less hydrophobic with a good absorption and low accumulation potential. Therefore, the log Kow predictions for the test substance using KOWWIN v1.69 can be considered to be reliable with moderate confidence.

Reference 4

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

QSAR prediction from a well-known and acknowledged tool. See below under ''attached background material section" for QPRF containing methodology and domain evaluation details.

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSARs: Chapter R.6. QSARs and grouping of chemicals

Principles of method if other than guideline:

The partition coefficient (log Kow) value for the test substance were estimated using the efficient partition algorithm (EPA) and associative neural network (ASNN) method of the ALOGPS v.2.1 program from the virtual computational chemistry laboratory. Since the test substance is a UVCB, the log Kow values were predicted for the individual constituents using SMILES codes as the input parameter.

Type of method:

other: Efficient Partition Algorithm (EPA) and Associative Neural Network (ASNN)

Partition coefficient type:

other: QSAR

Key result

Type:

log Pow

Partition coefficient:

ca. 1.43 - ca. 8.59

Remarks on result:

other: predicted for the main constituents

Remarks:

(ALOGPS v.2.1)

Key result

Type:

log Pow

Partition coefficient:

ca. 6.09

Remarks on result:

other: weighted average Log Kow

Remarks:

(ALOGPS v.2.1)

Predicted value (model result):

The predicted Partition coefficient (Log Kow) values for the different constituents using the Efficient Partition Algorithm (EPA) Associative Neural Network (ASNN) method were as follows:

Table 1: Log Kow predictions: EPA and ASNN based method

Constituents/Carbon chain length*	Mean/adjusted conc	Mole fraction Xi = (mi/Mi)/∑ (mi/Mi)	Log Kow	Log Kow * xi
C8	1.5	0.02413	1.43	0.03450895
C14	4	0.04440	4.93	0.218883447
C16	42.5	0.42755	5.74	2.45414292
C18	51.5	0.47371	6.67	3.159643291
C18'	1.5	0.01388	6.74	0.093571297
C20	1	0.00847	7.86	0.066595431
C22	1	0.00785	8.59	0.067459403
			Log Kow=	6.09

*Glycerol or MEA residues have not been considered for the QSAR prediction

Conclusions:

Using the efficient partition algorithm and associative neural networks based regression equations from ALOGPS V.2.1, the weighted average Partition coefficient (log Kow) value for test substance was predicted to be 6.09.

Executive summary:

The partition coefficient (log Kow) value for the test substance, C16-18 DEA was predicted using the EPA and ASNN based regression equations from ALOGPS V.2.1. Since the test substance is a UVCB, the log Kow values were predicted for the individual constituents using SMILES codes as the input parameter. Using the EPA and ASNN-based regression equations, the log Kow values for the individual constituents of the test substance ranged from 1.43 to 8.59. All constituents meet the E-indices, molecular weight and number of non-hydrogen atoms descriptor domain criteria. Further, given that the constituents are structurally very similar and vary only in the carbon chain length, a weighted average value, which considers the percentage of the constituent in the substance, was considered to dampen the errors in predictions (if any). Therefore, the weighted average log Kow value was calculated as 6.09. Overall, considering either the individual log Kow predictions for the constituents or the weighted average values, the test substance is expected to be less hydrophobic with a good absorption and low accumulation potential. Therefore, the log Kow predictions for the test substance using ALOGPS v.2.1 can be considered to be reliable with moderate confidence.

Description of key information

The partition coefficient was determined according to OECD Guidelines 107 and 117 and EU Method A.8 (HPLC method). Weighted average partition coefficient values for the substance were also modelled using the fragment constant method of the KOWWIN V.1.68 program of EPI Suite, the group contribution method of Molinspiration (miLogP 2.2) and the efficient partition algorithm and associative neural network-based regression equations from ALOGPS V.2.1.

Key value for chemical safety assessment

Log Kow (Log Pow):

4.46

at the temperature of:

20 °C

Additional information

The partition coefficient measured according to OECD Guideline 107 was 4.46. 

Using the fragment constant method of the KOWWIN V.1.68 program of EPI Suite, the weighted average partition coefficient (log Kow) value for test substance was predicted to be 5.58. According to the group contribution method of Molinspiration (miLogP 2.2), the weighted average log Kow was 6.67. According to the efficient partition algorithm and associative neural network-based regression equations from ALOGPS V.2.1, the weighted average log Kow was 6.09. 

The measured log Kow was retained as key value for risk assessment purposes.