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Partition coefficient

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Endpoint:
partition coefficient
Data waiving:
study technically not feasible
Justification for data waiving:
other:
Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE
EPI Suite (US EPA) 4.1

2. MODEL (incl. version number)
KOWWIN v1.68

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
C(=O)(C1C(C(=O)NCCNCCNCCN)C(CCCCCC)C=CC1CCCCCCCC(=O)NCCNCCNCCN)NCCNCCNCCN

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Partition coefficient (n-Octanol/Water)
- Unambiguous algorithm:
Results of the two successive multiple regressions (first for atom/fragments and second for correction factors) yield the following general equation for estimating log P of any organic compound: log P = Σ(fini ) + Σ(cjnj ) + 0.229 (num = 2447, r2 = 0.982, std dev = 0.217, mean error = 0.159)

- Defined domain of applicability:
Log P estimates are less accurate for compounds outside the MW range (18.02 – 719.92) of the training set compounds or of the validation set compounds (27.03 – 991.15), and/or that have more instances of a given fragment than the maximum for all training set compounds.

- Appropriate measures of goodness-of-fit and robustness and predictivity: R² = 0.94

- Mechanistic interpretation:
KOWWIN uses a "fragment constant" methodology to predict log P. In a "fragment constant" method, a structure is divided into fragments (atom or larger functional groups) and coefficient values of each fragment or group are summed together to yield the log P estimate. KOWWIN’s methodology is known as an Atom/Fragment Contribution (AFC) method. Coefficients for individual fragments and groups were derived by multiple regression of 2447 reliably measured log P values. KOWWIN’s "reductionist" fragment constant methodology (i.e. derivation via multiple regression) differs from the "constructionist" fragment constant methodology of Hansch and Leo (1979) that is available in the CLOGP Program (Daylight, 1995).
5. APPLICABILITY DOMAIN
- Descriptor domain: Molecular weight 781.19

- Structural and mechanistic domains:
Functional groups are within the domain of the model.
-CH3 (aliphatic carbon) 1 fragment
-CH2- (aliphatic carbon) 30 fragments
-CH (aliphatic carbon) 4 fragments
=CH- or =C< (olefinic carbon) 2 fragments
-NH2 (aliphatic attach) 3 fragments
-NH- (aliphatic attach) 9 fragments
-C(=O)N (aliphatic attach) 3 fragments

- Similarity with analogues in the training set:
There are close structural analogues (e.g., e.g., aliphatic amines, amides, etc.) in the training set.

6. ADEQUACY OF THE RESULT
The prediction is reliable and log Kow is required for risk assessment and classification and labelling purposes.

This endpoint study record is part of a Weight of Evidence approach comprising of several (QSAR) predictions. The data sources agree as to the partition coefficient value and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: EPI Suite (US EPA) 4.1
- Model(s) used: KOWWIN v1.68 (September 2010)
- Model description: see field 'Justification for type of information'
- Justification of QSAR prediction: see field 'Justification for type of information'
GLP compliance:
no
Type of method:
calculation method (fragments)
Partition coefficient type:
octanol-water
Specific details on test material used for the study:
SMILES: C(=O)(C1C(C(=O)NCCNCCNCCN)C(CCCCCC)C=CC1CCCCCCCC(=O)NCCNCCNCCN)NCCNCCNCCN
Molecular formula: C40 H84 N12 O3
Mol Wt.: 781.19
Type:
log Pow
Partition coefficient:
-1.56
Temp.:
20 °C
pH:
7
Remarks on result:
other: temp. and pH are defaults used by KOWWIN
Conclusions:
The EPI Suite (US EPA) Version 4.1 model KOWWIN v1.68 (September 2010) estimated the Log Kow to be -1.56.
Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE
EPI Suite (US EPA) 4.1

2. MODEL (incl. version number)
KOWWIN v1.68

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
C1(=O)C2C(C(=O)N1CCNCCNCCN)C(CCCCCC)C=CC2CCCCCCCC(=O)NCCNCCNCCN

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Partition coefficient (n-Octanol/Water)
- Unambiguous algorithm:
Results of the two successive multiple regressions (first for atom/fragments and second for correction factors) yield the following general equation for estimating log P of any organic compound: log P = Σ(fini ) + Σ(cjnj ) + 0.229 (num = 2447, r2 = 0.982, std dev = 0.217, mean error = 0.159)

- Defined domain of applicability:
Log P estimates are less accurate for compounds outside the MW range (18.02 – 719.92) of the training set compounds or of the validation set compounds (27.03 – 991.15), and/or that have more instances of a given fragment than the maximum for all training set compounds.

- Appropriate measures of goodness-of-fit and robustness and predictivity: R² = 0.94

- Mechanistic interpretation:
KOWWIN uses a "fragment constant" methodology to predict log P. In a "fragment constant" method, a structure is divided into fragments (atom or larger functional groups) and coefficient values of each fragment or group are summed together to yield the log P estimate. KOWWIN’s methodology is known as an Atom/Fragment Contribution (AFC) method. Coefficients for individual fragments and groups were derived by multiple regression of 2447 reliably measured log P values. KOWWIN’s "reductionist" fragment constant methodology (i.e. derivation via multiple regression) differs from the "constructionist" fragment constant methodology of Hansch and Leo (1979) that is available in the CLOGP Program (Daylight, 1995).
5. APPLICABILITY DOMAIN
- Descriptor domain: Molecular weight 781.19

- Structural and mechanistic domains:
Functional groups are within the domain of the model.
-CH3 (aliphatic carbon) 1 fragment
-CH2- (aliphatic carbon) 24 fragments
-CH (aliphatic carbon) 4 fragments
=CH- or =C< (olefinic carbon) 2 fragments
-NH2 (aliphatic attach) 2 fragments
-NH- (aliphatic attach) 5 fragments
-N< (aliphatic attach) 1 fragment
-C(=O)N (aliphatic attach) 3 fragments
-CO-N-CO- 5 member ring (not pyrroledione) 1 fragment
- fuesed aliphatic ring correction applied

- Similarity with analogues in the training set:
There are close structural analogues (e.g., e.g., aliphatic amines, amides, etc.) in the training set.

6. ADEQUACY OF THE RESULT
The prediction is reliable and log Kow is required for risk assessment and classification and labelling purposes.

This endpoint study record is part of a Weight of Evidence approach comprising of several (QSAR) predictions. The data sources agree as to the partition coefficient value and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: EPI Suite (US EPA) 4.1
- Model(s) used: KOWWIN v1.68 (September 2010)
- Model description: see field 'Justification for type of information'
- Justification of QSAR prediction: see field 'Justification for type of information'
GLP compliance:
no
Type of method:
calculation method (fragments)
Partition coefficient type:
octanol-water
Specific details on test material used for the study:
SMILES: C1(=O)C2C(C(=O)N1CCNCCNCCN)C(CCCCCC)C=CC2CCCCCCCC(=O)NCCNCCNCCN
Molecular formula: C34 H66 N8 O3
Mol Wt.: 634.96
Type:
log Pow
Partition coefficient:
1.2
Temp.:
20 °C
pH:
7
Remarks on result:
other: temp. and pH are defaults used by KOWWIN
Conclusions:
The EPI Suite (US EPA) Version 4.1 model KOWWIN v1.68 (September 2010) estimated the Log Kow to be 1.2.
Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE
EPI Suite (US EPA) 4.1

2. MODEL (incl. version number)
KOWWIN v1.68

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
C(=O)(CCCCCCCCC=CCC=CCCCC)NCCNCCNCCN

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Partition coefficient (n-Octanol/Water)
- Unambiguous algorithm:
Results of the two successive multiple regressions (first for atom/fragments and second for correction factors) yield the following general equation for estimating log P of any organic compound: log P = Σ(fini ) + Σ(cjnj ) + 0.229 (num = 2447, r2 = 0.982, std dev = 0.217, mean error = 0.159)

- Defined domain of applicability:
Log P estimates are less accurate for compounds outside the MW range (18.02 – 719.92) of the training set compounds or of the validation set compounds (27.03 – 991.15), and/or that have more instances of a given fragment than the maximum for all training set compounds.

- Appropriate measures of goodness-of-fit and robustness and predictivity: R² = 0.94

- Mechanistic interpretation:
KOWWIN uses a "fragment constant" methodology to predict log P. In a "fragment constant" method, a structure is divided into fragments (atom or larger functional groups) and coefficient values of each fragment or group are summed together to yield the log P estimate. KOWWIN’s methodology is known as an Atom/Fragment Contribution (AFC) method. Coefficients for individual fragments and groups were derived by multiple regression of 2447 reliably measured log P values. KOWWIN’s "reductionist" fragment constant methodology (i.e. derivation via multiple regression) differs from the "constructionist" fragment constant methodology of Hansch and Leo (1979) that is available in the CLOGP Program (Daylight, 1995).
5. APPLICABILITY DOMAIN
- Descriptor domain: Molecular weight 781.19

- Structural and mechanistic domains:
Functional groups are within the domain of the model.
-CH3 (aliphatic carbon) 1 fragment
-CH2- (aliphatic carbon) 18 fragments
=CH- or =C< (olefinic carbon) 4 fragments
-NH2 (aliphatic attach) 1 fragment
-NH- (aliphatic attach) 3 fragments
-C(=O)N (aliphatic attach) 1 fragment

- Similarity with analogues in the training set:
There are close structural analogues (e.g., e.g., aliphatic amines, amides, etc.) in the training set.

6. ADEQUACY OF THE RESULT
The prediction is reliable and log Kow is required for risk assessment and classification and labelling purposes.

This endpoint study record is part of a Weight of Evidence approach comprising of several (QSAR) predictions. The data sources agree as to the partition coefficient value and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: EPI Suite (US EPA) 4.1
- Model(s) used: KOWWIN v1.68 (September 2010)
- Model description: see field 'Justification for type of information'
- Justification of QSAR prediction: see field 'Justification for type of information'
GLP compliance:
no
Type of method:
calculation method (fragments)
Partition coefficient type:
octanol-water
Specific details on test material used for the study:
SMILES: C(=O)(CCCCCCCCC=CCC=CCCCC)NCCNCCNCCN
Molecular formula: C24 H48 N4 O1
Mol Wt.: 408.68
Type:
log Pow
Partition coefficient:
4.72
Temp.:
20 °C
pH:
7
Remarks on result:
other: temp. and pH are defaults used by KOWWIN
Conclusions:
The EPI Suite (US EPA) Version 4.1 model KOWWIN v1.68 (September 2010) estimated the Log Kow to be 4.72.

Description of key information

The substance is an UVCB substance. Due to its complex composition, methods for the experimental measurement of octanol-water partition coefficient (Kow) of fatty acids, tall-oil, reaction products with maleic anhydride and triethylenetetramine are technically not applicable. On the basis of the high solubility in water (fully miscible in the range of 5 - 95% by weight) and the chemical nature, Kow value for the substance is expected to be low. Estimated Log Kow value for the main constituents have been estimated using KOWWIN (v.1.68, September 2010; US EPA) and were for the three main components -1.56, 1.2 and 4.72, respectively. Considering the ratios of components this results in a weighted value for log Pow of 1.74, rounded up conservatively to 2, which is the value uesed for hazard and risk assessment. It should be noted that higher amounts of maleic anhydride as starting material do result in lower log Pow values. The log Pow value conservatively estimated (~2) is in good alignment with the observation of the substance being fully miscible in water.

Key value for chemical safety assessment

Log Kow (Log Pow):
2
at the temperature of:
20 °C

Additional information