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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 (LOGKOW) Programm, Syracus Research Corporation

2. MODEL (incl. version number)
KOWWIN Version 1.65

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
O=C1NC(=O)NC1=CC(C)C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL

- Defined endpoint:
log Kow (log P) – logarithmic octanol/water partition coefficient. The partition coefficient Kow (P) is the ratio of concentrations of a chemical in n-octanol and in water at equilibrium at a specified temperature (typically 25 °C, although partition coefficient is not usually very temperature dependent and training data for KOWWIN are collected at different temperatures).

- Unambiguous algorithm:
The predicted value of the log Kow is calculated through the following equation: log Kow =∑f(j)n(j) + c(j)n(j) + 0.229 where f(j) is the coefficient for each atom/fragment), c(j) is the coefficient for each correction factor, and n(i) is the number of times the atom/fragment (and correction factor) occurs in the test species.

- Defined domain of applicability:
Currently there is no universally accepted definition of model domain. However, it should be considered that log P estimates may be less accurate for compounds outside the molecular weight range of the training set compounds, and/or that have more instances of a given fragment than the maximum for all training set compounds. Although the training set of the model contains a large number of diverse molecules and can be considered abundant, it is also possible that a compound may be characterised by structural features (e.g. functional groups) not represented in the training set, with no respective fragment/correction coefficient developed. These points should be taken into consideration when interpreting model results.

- Appropriate measures of goodness-of-fit and robustness and predictivity:
Training set statistics:
N = 2447 compounds
correlation coefficient R2= 0.982
standard deviation = 0.217
absolute deviation = 0.159
 
Training set estimation error:
within ≤ 0.10 – 45.0%
within ≤ 0.20 – 72.5%
within ≤ 0.40 – 92.4%
within ≤ 0.50 – 96.4%
within ≤ 0.60 – 98.2%
 
External validation set statistics:
N = 10946 compounds
correlation coefficient R2= 0.943
standard deviation = 0.479
absolute deviation = 0.356
 
Validation set estimation error:
within ≤ 0.20 – 39.6%
within ≤ 0.40 – 66.0%
within ≤ 0.50 – 75.6%
within ≤ 0.60 – 82.5%
within ≤ 0.80 – 91.6%
within ≤ 1.00 – 95.6%

- Mechanistic interpretation:
KOWWIN’s "reductionist" fragment constant methodology (i.e. derivation via multiple regression) differs from the "constructionist" fragment constant methodology of Hansch and Leo (Hansch, C. and Leo, A.J., Substituent Constants for Correlation Analysis in Chemistry and Biology, Wiley, New York, 1979). More complete description of KOWWIN methodology is described in: Meylan, W.M., and Howard, P.H., Atom/Fragment Contribution Method for Estimating Octanol-Water Partition Coefficients, J. Pharm. Sci 84: 83-92, 1995.

5. APPLICABILITY DOMAIN

The test substance has a molecular weight and predicted log Kow within the range of the software training set. The number of each type of fragment defined within the test substance structure structure is less than the maximum number of that fragment occurring in a single structure within the software's training set. The test substance is therefore within the applicability domain of this QSAR model. Further, the similar substance 2,4-Imidazolidinedione, 5-(1-MeEt)- (CAS 16935-34-5) is in the validation set of the model. The predicted log Kow value was 0.18 and the experimental value was -0.36 indicating that the model is useful for predicting this endpoint.

6. ADEQUACY OF THE RESULT
The substance fits in the applicability domain of the model. The prediction is valid and can be used for classification and risk assessment.

Data source

Reference
Reference Type:
other: QSAR-method
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Principles of method if other than guideline:
calculated result with KOWWIN (LOGKOW©) Program
GLP compliance:
no
Type of method:
other: QSAR-method
Partition coefficient type:
octanol-water

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Partition coefficient
Type:
log Pow
Partition coefficient:
1.34
Remarks on result:
other: calculated result

Any other information on results incl. tables

the calculated logKowt with KOWWIN (LOGKOW©) Program for the undissociated substance is 1.34

Applicant's summary and conclusion

Conclusions:
result of partition coefficient shows Log Kow 1.34 (calculated result with KOWWIN (LOGKOW©) Program)