1,2-Propanediamine, N1-(2-aminoethyl)-3-(4-ethoxyphenyl)-, hydrochloride (1:2), (2S)-

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2014

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
Estimation Program Interface EPI-Suite version 4.11
2. MODEL (incl. version number)
KOWWIN v1.68 included in EPISuite v 4.11, ©2000 - 2012
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
A SMILES notation 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.
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
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 1,2-Propanediamine, N1-(2-aminoethyl)-3-(4-ethoxyphenyl)- the following fragment descriptors were applied:

Type Number Fragment Fragment Description
Frag 1 -CH3 [aliphatic carbon]
Frag 5 -CH2- [aliphatic carbon]
Frag 1 -CH [aliphatic carbon]
Frag 2 -NH2 [aliphatic attach]
Frag 1 -NH- [aliphatic attach]
Frag 6 aromatic carbon
Frag 1 -O- [oxygen, one aromatic attach]
Factor 1 benzene to -C-C-N- correction
Const equation constant

5. APPLICABILITY DOMAIN
a. Domains:
i. Molecular weights:
With a molecular weight of 237.35 g/mole the substance is within the range of the training set (18.02 - 719.92 g/mole) as well as in the range of the validation set (27.03 - 991.15 g/mole).
ii. Structural fragment domain:
Regarding the structure of 1,2-Propanediamine, N1-(2-aminoethyl)-3-(4-ethoxyphenyl)-, 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: Not relevant.
c. Considerations on structural analogues: Not relevant.
The uncertainty of the prediction (OECD principle 4)
1,2-Propanediamine, N1-(2-aminoethyl)-3-(4-ethoxyphenyl)- is not highly complex and the rules applied for the substance appear appropriate. An individual uncertainty for the investigated substance is not available.

6. ADEQUACY OF THE RESULT
Regulatory purpose:
The data may be used under any regulatory purpose.
Approach for regulatory interpretation of the model result:
If no experimental data is 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.
Outcome:
The prediction of the logarithmic octanol-water partition coefficient yields a useful result for further evaluation.
Conclusion:
The result is considered as useful for regulatory purposes.

Qualifier:

according to guideline

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:

other: QSAR

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

0.34

Temp.:

25 °C

Remarks on result:

other: pH not reported

Details on results:

The QSAR determination revealed a logarithmic octanol-water partition coefficient of 1,2-Propanediamine, N 1-(2-aminoethyl)-3-(4-ethoxyphenyl)- of the substance.

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:

-CH3, -CH2- and -CH - [aliphatic carbon], -NH2, -NH- [aliphatic attach] and aromatic carbon and a correction factor for benzene to -C-C-N- 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 237.35 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 1,2-Propanediamine, N 1-(2-aminoethyl)-3-(4-ethoxyphenyl)- 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 for 1,2-Propanediamine, N 1-(2-aminoethyl)-3-(4-ethoxyphenyl)- using the model KOWWIN included in the Estimation Program Interface (EPI) Suite v4.11 revealed a value of 0.34. 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 1,2-Propanediamine, N 1-(2-aminoethyl)-3-(4-ethoxyphenyl)- was predicted using the QSAR calculation of the Estimation Program Interface (EPI) Suite v 4.11. The log Kow was estimated to be 0.34. The predicted value can be considered reliable yielding a useful result for further assessment.

The partition coefficient (log Pow) was calculated for the main substance without HCl as this displays a worst case. This calculation can be used as read-across as HCl will increase the water solubility and even lower the log Kow for 1,2-Propanediamine, N1-(2-aminoethyl)-3-(4-ethoxyphenyl)-, dihydrochloride, (2S)-.

Description of key information

The calculated partition coefficient (log Pow) of 1 ,2-Propanediamine, Nl-(2-aminoethyl)-3-(4-ethoxyphenyl)- is 0.34.

Key value for chemical safety assessment

Log Kow (Log Pow):

0.34

at the temperature of:

25 °C

Additional information

The partition coefficient (log Pow) was calculated for the main substance without HCl as this displays a worst case. This calculation can be used as read-across as HCl will increase the water solubility and even lower the log Kow for 1,2-Propanediamine, N1-(2-aminoethyl)-3-(4-ethoxyphenyl)-, dihydrochloride, (2S)-.