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Partition coefficient

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Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
2015
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
Model: KOWWIN v.1.68
Submodel: n-octanol/water partition coefficient

2. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
- CGE-PMDA adduct CC(CN)CCCNCC(O)COc1ccccc1C
- Bis CGE-PMDA adduct Cc1ccccc1OCC(O)CNCCCC(C)CNCC(O)COc1ccccc1C
- Tris CGE-PMDA adduct Cc1ccccc1OCC(O)CNCC(C)CCCN(CC(O)COc1ccccc1C)C(O)COc1ccccc1C
- CGE-water (Diol): Cc1ccccc1OCC(O)CO
- CGE-impurity Cc1ccccc1OCC(O)COc1ccccc1C


3. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
KOWWIN uses a “fragment constant” methodology to predict Log Kow. 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 Kow estimate.

4. APPLICABILITY DOMAIN
Descriptor domain:
- Training Set Molecular weights (MW): 18.02 ≤ MW ≤ 719.92 [g·mol-1]
- Validation Molecular weights (MW): 27.03 ≤ MW ≤ 99..15 [g·mol-1]
MWs of the components of CGE-PMDA range from 116 to 595 g·mol-1.

5. ADEQUACY OF THE RESULT
The predications are considered reliable because the estimated Log KOW values for the analogues are consistent with the experimental data. In addition, KOWWIN is considered reliable within the domain based on the correlation between the experimental and KOWWIN estimated Log KOW values presented by the developers.
Qualifier:
no guideline followed
GLP compliance:
no
Type of method:
other: QSAR
Partition coefficient type:
octanol-water
Key result
Type:
log Pow
Partition coefficient:
2.99
Remarks on result:
other: calculated geometric mean
Type:
log Pow
Partition coefficient:
1.97
Remarks on result:
other: Constituent: 1CGE-1MPMD adduct (CAS 1617528-43-4)
Remarks:
name in report: CGE-PMDA adduct
Type:
log Pow
Partition coefficient:
4.08
Remarks on result:
other: Constituent: 2CGE-1MPMD adduct (CAS 1617528-45-6)
Remarks:
name in report: Bis CGE-PMDA adduct
Type:
log Pow
Partition coefficient:
1.41
Remarks on result:
other: Impurity: mephenesin (CAS 59-47-2)
Remarks:
name in report: CGE-water (Diol)
Type:
log Pow
Partition coefficient:
3.85
Remarks on result:
other: Impurity: di-CGE (CAS 17181-49-6)
Remarks:
name in report: CGE-impurity
Type:
log Pow
Partition coefficient:
5.52
Remarks on result:
other: Impurity: 3CGE-1MPMD adduct (no CAS)
Remarks:
name in report: Tris CGE-PMDA adduct
Conclusions:
The calculated geometric mean log Kow of CGE-PMDA adduct is 2.99.
Executive summary:

The n-octanol/water partition coefficients (KOW, also known as POW) of CGE-PMDA adduct, Bis CGE-PMDA adduct, Tris CGE-PMDA adduct, CGE-water (Diol) and CGE-impurity (refer to molecular structures in Section 1.4) were estimated using quantitative structure-activity relationship (QSAR). The molecular weights of these compounds were 280, 445, 609, 182 and 272 g/mol, respectively. The logarithm of KOW(Log KOW, also known as Log POW) was calculated for these molecular structures separately using QSAR model KOWWIN (v1.68, U.S. EPA 2010). KOWWIN uses a “fragment constant” methodology to predict LogKOW. 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 KOW estimate. KOWWIN was chosen due to its estimation accuracy and its transparency of the model and training set.

The simplified molecular input line entry system (SMILES) codes for these compounds wereused as the input for the KOWWIN model. The estimated LogKOWvalues forCGE-PMDA adduct, Bis CGE-PMDA adduct, Tris CGE-PMDA adduct, CGE-water (Diol) and CGE-impuritywere 1.97, 4.08, 5.52, 1.41 and 3.85, respectively. These estimations by KOWWIN are deemed reliable because the unknowns are within the estimation domain of the model, and estimated Log KOW values of structural analogues of these molecules agree well with existing experimental data. It is with high confidence to conclude that the Log KOW of CGE-PMDA adduct, Bis CGE-PMDA adduct, Tris CGE-PMDA adduct, CGE-water (Diol) and CGE-impurity were 1.97, 4.08, 5.52, 1.41 and 3.85, respectively.

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 2017 - August 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
EU Method A.8 (Partition Coefficient - HPLC Method)
Deviations:
not specified
GLP compliance:
yes (incl. certificate)
Type of method:
HPLC method
Partition coefficient type:
octanol-water
Analytical method:
high-performance liquid chromatography
Key result
Type:
log Pow
Partition coefficient:
2.95
Temp.:
20 °C
Remarks on result:
other: geometric mean of six results
Type:
log Pow
Partition coefficient:
1.41
Temp.:
20 °C
pH:
5.99
Remarks on result:
other: Peak 1
Type:
log Pow
Partition coefficient:
2.16
Temp.:
20 °C
pH:
5.99
Remarks on result:
other: Peak 2
Type:
log Pow
Partition coefficient:
3.16
Temp.:
20 °C
pH:
5.99
Remarks on result:
other: Peak 3
Type:
log Pow
Partition coefficient:
3.37
Temp.:
20 °C
pH:
5.99
Remarks on result:
other: Peak 4
Type:
log Pow
Partition coefficient:
3.37
Temp.:
20 °C
pH:
5.99
Remarks on result:
other: Peak 5
Type:
log Pow
Partition coefficient:
4.64
Temp.:
20 °C
pH:
5.99
Remarks on result:
other: Peak 6
Details on results:
The tested substance contains six constituents. The logPow has been determined for all six by the HPLC-method.

The breakdown of log Pow vs HPLC peak area% is as follows:

 

Peak

log Pow

Area%

1

1.41

50.7

2

2.16

1.2

3

3.16

2.4

4

3.37

1.9

5

4.39

2.1

6

4.64

41.7

Conclusions:
The partition coefficient of the test item at pH 6.0 has been determined to be in the range 25.7 to 4.31 x 104, log10 Pow in the range 1.41 to 4.64.
The geometric mean of the partition coefficients of six constituents is 2.95, at 20°C.
Executive summary:

Partition Coefficient (n-Octanol/Water). In the range 25.7 to 4.31 x 104, log10 Pow in the range 1.41 to 4.64, at pH 6.0, using the HPLC method, designed to be compatible with Method A.8 Partition Coefficient of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 117 of the OECD Guidelines for Testing of Chemicals, 13 April 2004.

Description of key information

The reported Log Pow has been determined by the geometric mean of the low Pow of six constituents in the test substance.

Key value for chemical safety assessment

Log Kow (Log Pow):
2.95
at the temperature of:
20 °C

Additional information