Registration Dossier

Administrative data

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method

Data source

Referenceopen allclose all

Reference Type:
other:
Title:
Unnamed
Year:
2017
Report Date:
2017
Reference Type:
other: EPIWIN calculation
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Principles of method if other than guideline:
Estimation of log Kow using KOWWIN v1.68
GLP compliance:
no
Type of method:
other: estimation method
Partition coefficient type:
octanol-water

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Results and discussion

Partition coefficient
Key result
Type:
log Pow
Partition coefficient:
-1.31
Temp.:
25 °C
Remarks on result:
other: The substance is within the applicability domain of the model.

Any other information on results incl. tables

 KOWWIN Program (v1.68) Results:

===============================

Log Kow(version 1.68 estimate): -1.31

SMILES : CC1(CO)C(O)CCC2(C)C1CC(O)C3(C)OC4=C(C(O)C23)C(=O)OC(=C4)c5cccnc5

CHEM :

MOL FOR: C25 H31 N1 O7

MOL WT : 457.53

 

TYPE

NUM

LOGKOW FRAGMENT DESCRIPTION

COEFF

VALUE

Frag

3

-CH3 [aliphatic carbon]

0.5473

1.6419

Frag

4

-CH2- [aliphatic carbon]

0.4911

1.9644

Frag

5

-CH [aliphatic carbon]

0.3614

1.8070

Frag

4

=CH- or =C< [olefinc carbon]

0.3836

1.5344

Frag

4

-OH [hydroxy, aliphatic attach]

-1.4086

-5.6344

Frag

1

-O- [oxygen, aliphatic attach]

-1.2566

-1.2566

Frag

5

Aromatic Carbon

0.2940

1.4700

Frag

1

Aromatic Nitrogen

-0.7324

-0.7324

Frag

1

-C(=O)O [ester, aliphatic attach]

-0.9505

-0.9505

Frag

3

-tert Carbon [3 or more carbon attach]

0.2676

0.8028

Factor

1

Cyclic ester correction

-1.0577

-1.0577

Factor

1

Multi-alcohol correction

0.4064

0.4064

Factor

4

Fused aliphatic ring unit correction

-0.3421

-1.3684

Factor

1

Pyridine ring (non-fused) correction

-0.1621

-0.1621

Const

 

Equation Constant

 

0.2290

 

Log Kow = -1.3062

Applicant's summary and conclusion

Executive summary:

QPRF: KOWWIN v1.68 (01 Nov. 2013)

 

1.

Substance

See “Test material identity”

2.

General information

 

2.1

Date of QPRF

See “Data Source (Reference)”

2.2

QPRF author and contact details

See “Data Source (Reference)”

3.

Prediction

3.1

Endpoint
(OECD Principle 1)

Endpoint

Octanol-water partition coefficient (log Kow)

Dependent variable

Octanol-water partition coefficient (log Kow)

3.2

Algorithm
(OECD Principle 2)

Model or submodel name

KOWWIN

Model version

v. 1.68

Reference to QMRF

QMRF: Estimation of Octanol-Water Partition Coefficient using KOWWIN v1.68 (EPI Suite v4.11)

Predicted value (model result)

See “Results and discussion”

Input for prediction

Chemical structure via CAS number or SMILES

Descriptor values

- Chemical structure

- Fragments

- Correction factors

3.3

Applicability domain
(OECD principle 3)

Domains:

1) Molecular weight
(range of test data set: 18.02 to 719.92 g/mol; On-Line KOWWIN User’s Guide, Ch. 6.2.3 Estimation Domain)

Substance (not) within range (457.53 g/mol)

2) Fragments: Number of instances of the identified fragments does not exceed the maximum number as listed in Appendix D (On-Line KOWWIN User’s Guide)

Fulfilled.

3) Fragments: Substance has a functional group(s) or other structural features not represented in the training set, and for which no fragment coefficient was developed (Appendix D, On-Line KOWWIN User’s Guide)

Not applicable.

4) Correction factors: Number of instances of the identified correction factor does not exceed the maximum number as listed in Appendix D (On-Line KOWWIN User’s Guide)

Fulfilled.

 

3.4

The uncertainty of the prediction
(OECD principle 4)

According to REACH Guidance Document R.7a, (Nov. 2012), solubility in water is difficult to model accurately. For this reason, as well as the fact that the experimental error on solubility measurements can be quite high (generally reckoned to be about 0.5 log unit), the prediction of aqueous solubility is not as accurate as is the prediction of octanol/water partitioning.

3.5

The chemical mechanisms according to the model underpinning the predicted result
(OECD principle 5)

The water solubility of a substance depends on its affinity for water as well as its affinity for its own crystal structure. In general, substances with high melting points have poor solubility in any solvent.

 

References

- US EPA (2012). On-Line KOWWIN User’s Guide.

 

 

Assessment of estimation domain (molecular weight, fragments, correction factors):

Applicability Domain of KOWWIN v1.68

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Model:

KOWWIN v1.68

Substance:

 

CAS:

155850-27-4

SMILES:

CC1(CO)C(O)CCC2(C)C1CC(O)C3(C)OC4=C(C(O)C23)C(=O)OC(=C4)c5cccnc5

Molecular Weight:

457.53

 

 

 

 

 

 

 

 

Molecular weight

Minimum

Maximum

Average

 

 

 

 

Training set

18.02

719.92

199.98

 

 

 

 

Validation set

27.03

991.15

258.98

 

 

 

 

Assessment of molecular weight

Molecular weight within range of training and validation set.

 

 

 

 

 

 

 

Appendix D: KOWWIN Fragments. Correction Factors. Coefficients and Frequency

 

 

 

 

 

The Tables below lists KOWWIN Fragment and Correction Factor descriptors with their coefficient values (Coef).

 

 

 

Max = maximum number of the fragment or correction factor that occurs in any individual compound

 

 

 

 

Number = the number of individual compounds having the fragment or correction factor in the dataset

 

 

 

 

The training dataset includes a total of 2447 compounds.

 

 

 

 

 

 

The validation dataset includes a total of 10946 compounds.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Part 1: Fragments

 

 

 

 

 

 

 

Fragment

Descriptor

Coef

Training Set

Validation Set

No. of instances of each fragment for the current substance

 

 

 

Max

Number

Max

Number

.

-CH3

[aliphatic carbon]

0.5473

13

1401

20

7413

3

-CH2-

[aliphatic carbon]

0.4911

18

1083

28

7051

4

-CH

[aliphatic carbon]

0.3614

16

460

23

3864

5

=CH- or =C<  

[olefinc carbon]

0.3836

10

239

10

1847

4

-OH

[hydroxy. aliphatic attach]

-1.4086

6

187

9

1525

4

-O-

[oxygen. aliphatic attach]

-1.2566

5

108

12

1235

1

Aromatic Carbon

 

0.294

24

1790

30

8792

5

Aromatic Nitrogen

 

-0.7324

4

251

4

1349

1

-C(=O)O  

[ester. aliphatic attach]

-0.9505

3

113

6

1178

1

-tert Carbon  

[3 or more carbon attach]

0.2676

4

130

8

1381

3

Part 2: Correction Factors

 

 

 

 

 

 

.

Correction Factor Descriptor

Coef

Training Set

Validation Set

No. of instances of each correction factor for the current substance

Max

Number

Max

Number

.

Cyclic ester  correction

 

-1.0577

1

14

2

144

1

Multi-alcohol correction

 

0.4064

1

97

1

499

1

Fused aliphatic ring unit correction

 

-0.3421

8

41

8

684

4

Pyridine ring (non-fused)  correction

 

-0.1621

1

128

3

476

1