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Physical & Chemical properties

Partition coefficient

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Administrative data

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 and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE
KOWWIN v 1.68 (EPI Suite v4.1)

2. MODEL (incl. version number)
See Section 1.

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
O=C(O)C=Cc(cccc1)c1
CAS No.: 140-10-3

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint:
Octanol-water partition coefficient (Kow)
- Unambiguous algorithm:
log P = Σ(fini ) + b (Regression 11)
lop P (expl) - log P (eq 1) = Σ(cjnj )
where Σ(fini ) is the summation of fi (the coefficient for each atom/fragment) times ni (the number of times the atom/fragment occurs in the structure) and b is the linear equation constant and Σ(cjnj ) is the summation of cj (the coefficient for each correction factor) times nj (the number of times the correction factor occurs (or is applied) in the molecule).
- Defined domain of applicability:
The molecular weight of trans-cinnamic acid is in the molecular weight range of compounds in the training set
- Appropriate measures of goodness-of-fit and robustness and predictivity:
The KOWWIN training and validation datasets can be downloaded from the Internet at:http://esc.syrres.com/interkow/KowwinData.htm.
Substructure searchable formats of the data can be downloaded at:
http://esc.syrres.com/interkow/EpiSuiteData_ISIS_SDF.htm.
Total Training Set Statistics:
number in dataset = 2447
correlation coef (r2) = 0.982
standard deviation = 0.217
absolute deviation = 0.159
avg Molecular Weight = 199.98
Currently, KOWWIN has been tested on an external validation dataset of 10,946 compounds (compounds not included in the training set). The validation set includes a diverse selection of chemical structures that rigorously test the predictive accuracy of any model. It contains many chemicals that are similar in structure to chemicals in the training set, but also many chemicals that are different from and structurally more complex than chemicals in the training set. The average molecular weight of compounds in the validation set is 258.98 versus 199.98 for the training set.

- Mechanistic interpretation:
The octanol-water partition coefficient is a physical property used extensively to describe a chemical's lipophilic or hydrophobic properties. 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. Coefficients for individual fragments and groups were derived by multiple regression of 2447 reliably measured log P values. KOWWIN’s methodology is known as an Atom/Fragment Contribution (AFC) method.

5. APPLICABILITY DOMAIN
The applicability domain is described by the range of the molecular weight of the training set as well as the identification and number of instances of a given fragment. The number of instances of a given fragment is compared to the maximum for all training set compounds. If this number exceeds the maximum number or a fragment is not identified, the estimate of a substance is regarded to be less accurate.
Limits of applicability:
Range of Molecular Weights in the Training set:
- Minimum = 18.02 g/mol
- Maximum = 719.92 g/mol
- Average = 199.98 g/mol

The target substance is within the validation set and experimental data closely matches the estimated value.

6. ADEQUACY OF THE RESULT
This will be used as part of a weight-of-evidence approach along with the experimental data available as part of the KOWWIN system – together this information is considered adequate to conclude on the octanol-water partition coefficient for the substance.

For more information, see the attached QMRF and QPRF.

Data source

Reference
Reference Type:
other:
Title:
EPI Suite v4.10
Year:
2010
Bibliographic source:
KOWWIN - Meylan and Howard (1995)

Materials and methods

Test guideline
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
Meylan, W.M. and P. H. Howard 1995. Atom/fragment contribution method for estimating octanol-water partition coefficient. J. Pharm. Sci. 84: 83-92.

Test material

Constituent 1
Chemical structure
Reference substance name:
trans-cinnamic acid
EC Number:
205-398-1
EC Name:
trans-cinnamic acid
Cas Number:
140-10-3
Molecular formula:
C9H8O2
IUPAC Name:
3-phenylacrylic acid
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
SMILES: O=C(O)C=Cc(cccc1)c1

Results and discussion

Partition coefficient
Type:
log Pow
Partition coefficient:
2.07
Remarks on result:
other: QSAR predicted value

Any other information on results incl. tables

KOWWIN predicted that cinnamic acid has a log Kow = 2.07

Applicant's summary and conclusion

Conclusions:
KOWWIN predicted that cinnamic acid has a log Kow = 2.07