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Partition coefficient

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Reference
Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
2009
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
Remarks:
Documented QSAR from a well established program.
Justification for type of information:
The result obtained by the calculation method is further endorsed by the closeness of the results for the free acid phenoxy acetic acid by using either the experimental method or the same calculation method as used here. See the records "Hansch 1995.Partition coefficient PhAA" and "QSAR.Partition coefficient PhAA".

1. SOFTWARE
The logKow is estimated using the QSAR model KOWWIN v1.67. The programme is part of the Estimation Programs Interface (EPI) SuiteTM that was developed by the US Environmental Protection Agency's Office of Pollution Prevention and Toxics and Syracuse Research Corporation (SRC).

2. MODEL (incl. version number)
KOWWIN v1.67.

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Structures are entered by SMILES notations. For the SMILES see under Test Material Information.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Important information on the performance, development and application of EPI SuiteTM, and the individual programs within it, can be found under the Help tab of the programme. Copyright United States Environmental Protection Agency for EPI SuiteTM. See also https://www.epa.gov/tsca-screening-tools/epi-suitetm-estimation-program-interface
- Defined endpoint: Yes, partition coefficient n-octanol/water..
- Unambiguous algorithm: A description and equations are provided in the User Guide included in the Help to the programme.
- Defined domain of applicability: The minimum and maximum values for molecular weight are ca. 27 and 990. For details see under the Help tab of the programme.
- Appropriate measures of goodness-of-fit and robustness and predictivity:
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 validation set estimation error is within 0.2 for 39.6 % and 1.5 for 99.1 % of the substances.
- Mechanistic interpretation: The article by Meylan, W.M. and P.H. Howard of 1995 Atom/fragment contribution method for estimating octanol-water partition coefficients. J. Pharm. Sci. 84: 83-92, describes the program methodology, i.e. the "fragment constant" methodology of KOWWIN.

5. APPLICABILITY DOMAIN
- Descriptor domain: The intended application domain is organic chemicals. Inorganic and organometallic chemicals generally are outside the domain.
- Structural and mechanistic domains: See the description included in the Help of the programme.
- Similarity with analogues in the training set: 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.
- Other considerations (as appropriate): /

6. ADEQUACY OF THE RESULT
The estimated logPow is adequate if not too close to the threshold criteria set in adaptations of endpoints in column 2 or in CLP.
The result obtained by the calculation method is further endorsed by the closeness of the results for the free acid phenoxy acetic acid by using either the experimental method or the same calculation method as used here. See the records "Hansch 1995.Partition coefficient PhAA" and "QSAR.Partition coefficient PhAA".
Reason / purpose:
other: QSAR model supporting information
Reason / purpose:
other: QSAR model supporting information
Qualifier:
no guideline followed
Principles of method if other than guideline:
The logKow was estimated using the QSAR model KOWWIN v1.67 within EpiSuite v4.0.
GLP compliance:
no
Type of method:
calculation method (fragments)
Partition coefficient type:
octanol-water
Key result
Type:
log Pow
Partition coefficient:
-2.48
Remarks on result:
other: Temperature and pH are not available for QSAR-methods.

KOWWIN Program (v1.67) Results:

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

                  Log Kow(version 1.67 estimate): -2.48

SMILES : c1(OCC(=O)O([Na]))ccccc1

CHEM  : Na Phenoxy acetic acid

MOL FOR: C8 H7 O3 Na1

MOL WT : 174.13

 TYPE  NUM   LOGKOW FRAGMENT DESCRIPTION  COEFF   VALUE  
 Frag  1  -CH2-  [aliphatic carbon]  0.4911  0.4911  
 Frag  6  Aromatic Carbon  0.2940  1.7640  
 Frag  1 -O-  [oxygen, one aromatic attach]   -0.4664  -0.4664  
 Frag  1  -C(=O)O [ester, aliphatic attach]  -0.9505  -0.9505  
 Factor  1 C(=O)-O-{Na,K,Li}  [coef*(1+0.5*(NUM-1))]   -3.5500  -3.5500  
 Const    Equation Constant    0.2290  
         Log Kow  =   -2.4828
Executive summary:

The logKow was estimated using the model KOWWIN v1.67 within EpiSuite v4.0.

The log Kow of Na phenoxyacetate is calculated to -2.48.

Description of key information

Using the QSAR KOWWIN model for the salt and the free acid and comparing

the obtained data of the free acid with experimental data, it was concluded that the calculated value of the log Pow of sodium phenoxyacetate of -2.48 is reliable.

Key value for chemical safety assessment

Log Kow (Log Pow):
-2.48

Additional information

The results for the free acid phenoxy acetic acid (PhAA) were not used here to obtain a result for the target substance sodium phenoxyacetate (NaPhAA) by read-across. But it was the purpose of this exercise to check the reliability of the QSAR-method that was applied to estimate the partition coefficient of NaPhAA. The reliability was checked by comparing the experimentally determined partition coefficient for PhAA with the calculated result for PhAA, using the same estimation method as for NaPhAA.

Data from phenoxyacetic acid PhAA were obtained in addition to data on sodium phenoxyacetate NaPhAA. Both substances are well soluble in water. It can be assumed that the salt NaPhAA is dissociated to Na+ and the anion phenoxyacetate in dilute aqueous solution. PhAA is ionized in the neutral pH range, see section 4.21, according to the reported dissociation constant of 3.17. PhAA can therefore be expected also to be present as the anion phenoxyacetate in dilute and neutral aqueous solutions.

The logPow for PhAA was calculated to 1.33 respectively was experimentally determined to 1.34 for the non-ionized molecule at low pH. The closeness of both data, 1.33 and 1.34, is a good indicator that the used QSAR model is reliable for this substance.

The calculated log Pow of the salt NaPhAA is lower than that of the free acid, which is not unexpected as the salt is dissociated at the about neutral pH in dilute aqueous solution, impeding the dissolution in the unpolar octanol.