Estradiol

Partition coefficient

Link to relevant study record(s)

Reference

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:

3. PREDICTION
3.1 Endpoint (OECD Principle 1)
a. Endpoint:
Logarithmic octanol-water partition coefficient
b. Dependent variable:
log Pow or log Kow
3.2 Algorithm (OECD Principle 2)
a. Model or submodel name:
Individual model KOWWIN included in the Estimation Programs Interface (EPI) Suite.
 

b. Model version:
KOWWIN v1.68 included in EPISuite v 4.11, ©2000 – 2012
c. Reference to QMRF:
“QSAR Model Reporting Format (QMRF) for log Kow estimation”, Currenta GmbH & Co. OHG, 2011-05-19.
d. Predicted value (model result):
log Kow = 3.9429
e. Predicted value (comments):
No information available
f. Input for prediction:
The CAS number was entered in the initial data entry screen. In the structure window, the molecular weight, structural formula and the structure of the input SMILES notation is shown.
g. Descriptor values:
The molecule is separated into distinct atom/fragments using an Atom/Fragment Contribution method. Based on structure of the molecule, various steric interactions, hydrogen-bondings, and effects from polar functional substructures were identified and individual correction factors were selected through a tedious process of correlating the differences (between log Kow estimates from atom/fragments alone and measured log Kow values) with common substructures.
For estradiol the following fragment descriptors were applied:

Type NUM Fragment Fragment Description
Frag 1 -CH3 aliphatic carbon
Frag 6 -CH2- aliphatic carbon
Frag 4 -CH aliphatic carbon
Frag 1 -OH hydroxy, aliphatic attach
Frag 6 aromatic Carbon
Frag 1 -OH hydroxy, aromatic attach
Frag 1 -tert Carbon 3 or more carbon attach

3.3 Applicability domain (OECD principle 3)
a. Domains:
i. Molecular weights:
With a molecular weight of 272.39 g/mole the substance is within the range of the training set (18.02 - 719.92) as well as in the range of the validation set (27.03 - 991.15).
ii. Structural fragment domain:
Regarding the structure of estradiol, the fragment descriptors found by the program are complete and listed in Appendix D (KOWWIN Fragment and Correction Factor descriptors). Additionally the substance is not listed in Appendix F (Compounds that exceed the Fragment & Molecular Weight Domains).
iii. Mechanism domain: No information available
iv. Metabolic domain, if relevant: Not relevant.
b. Structural analogues: Optional
c. Considerations on structural analogues: Optional
3.4 The uncertainty of the prediction (OECD principle 4)
Estradiol is not highly complex and the rules applied for the substance appears appropriate. An individual uncertainty for the investigated substance is not available.
3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5).
No information available.
4. Adequacy (Optional)
4.1 Regulatory purpose:
The data may be used under any regulatory purpose.
4.2 Approach for regulatory interpretation of the model result:
If no experimental data are available, the estimated value is used to fill data gaps needed for hazard and risk assessment, classification and labelling and PBT / vPvB assessment. Further the value can be used for other calculations.
4.3 Outcome:
The prediction of the logarithmic octanol-water partition coefficient yields a useful result for further evaluation.
4.4 Conclusion:
The result is considered as useful for regulatory purposes.

Guideline:

other: REACH guidance QSARs R6, May/July 2008

Principles of method if other than guideline:

Estimation Program Interface EPI-Suite version 4.11: KOWWIN for estimating the logarithmic octanol-water partition coefficient (log Kow).
The Estimation Programs Interface was developed by the US Environmental Agency's Office of Pollution Prevention and Toxics and Syracuse Research Corporation (SRC).© 2000 - 2012 U.S. Environmental Protection Agency for EPI SuiteTM (Published online in November 2012).

GLP compliance:

no

Type of method:

calculation method (fragments)

Partition coefficient type:

octanol-water

Key result

Type:

log Pow

Partition coefficient:

3.942

Remarks on result:

other: Calculation with KOWWIN

Validity of model:

1. Defined Endpoint: Octanol-water partition coefficient

2. Unambiguous algorithm: The molecule is separated into distinct atom/fragments using an Atom/Fragment Contribution method. Based on structure of the molecule, the following fragments were applied: aliphatic carbon. hydroxy (aliphatic attach),

aromatic carbon and tert. carbon (3 or more carbon attach) is applied.

The number of times of the fragments that occurs in the structure of the substance applied by the program is verified.

3. Applicability domain: With a molecular weight of 272.39 g/mole the substance is within the range of the training set (18.02 - 719.92) as well as in the range of the validation set (27.03 - 991.15).

4. Statistical characteristics:Correlation coefficient of the total training set r² = 0.982; Correlation coefficient of the total validation set r² = 0.943.

5. Mechanistic interpretation: The structural fragments used as descriptors reflect the lipophilic or hydrophobic properties of the substances, and so the octanol-water partition coefficient.

6. Adequacy of prediction: The result for estra-1,3,5(10)-triene-3,17-diol falls within the applicability domain described above and the estimation rules applied for the substance appears appropriate. Therefore the predicted value can be considered reliable yielding a useful result for further assessment.

Conclusions:

The QSAR determination of the logarithmic octanol-water partition coefficient using the model KOWWIN included in the Estimation Program Interface (EPI) Suite v4.1 revealed a value of 3.94 of the substance. The predicted value can be considered reliable yielding a useful result for further assessment.

Executive summary:

The logarithmic octanol-water partition coefficient (log Kow) for estra-1,3,5(10)-triene-3,17-diol was predicted using the QSAR calculation of the Estimation Program Interface (EPI) Suite v 4.11. The log Kow was estimated to be 3.94. The predicted value can be considered reliable yielding a useful result for further assessment.

Description of key information

The QSAR determination of the logarithmic octanol-water partition coefficient using the model KOWWIN included in the Estimation Program Interface (EPI) Suite v4.1 revealed a value of 3.94 of the substance. The predicted value can be considered reliable yielding a useful result for further assessment.

Key value for chemical safety assessment

Log Kow (Log Pow):

3.942

at the temperature of:

20 °C