9,10-Anthracenedione, 1,4,5,8-tetrakis[(4-butylphenyl)amino]-

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2019

Reliability:

1 (reliable without restriction)

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:

The octanol/water partition coefficient of TBPAAQ could not be determined by the shake flask method due to the low solubility of the test substance in both octanol and water. Therefore this endpoint was assessed using QSAR:

SOFTWARE : QSAR model KOWWIN (v1.69, U.S. EPA 2015) which uses a “fragment constant” methodology to predict Log KOW.

MODEL (incl. version number) : QSAR model KOWWIN (v1.69, U.S. EPA 2015) which uses a “fragment constant” methodology to predict Log KOW.

SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL : SMILES code for TBPAAQ:CCCCc1ccc(cc1)Nc2c3c(c(cc2)Nc4ccc(cc4)CCCC)C(=O)c5c(ccc(c5C3(=O))Nc6ccc(cc6)CCCC)Nc7ccc(cc7)CCCC

General Information:
Date of QPRF: September 27, 2019
Purpose: The n-octanol/water partition coefficient of TBPAAQ was estimated in this work using a quantitative structure-activity relationship (QSAR) model
(KOWWIN v1.69, US Environmental Protection Agency, 2015). KOWWIN was chosen due to its estimation accuracy and the transparency of the model and training
set. The compound for which KOW was estimated (i.e., target compound) was TBPAAQ
with a molecular weight of 797 g/mol.

Prediction:
Endpoint (OECD Principle 1):
a. Endpoint: n-octanol/water partition coefficient (POW or KOW)
b. Dependent variable: Log KOW (or Log POW)

Algorithm (OECD Principle 2):
a. Model or submodel name: KOWWIN for n-octanol/water partition
coefficient
b. Model version: v1.69, U.S. EPA, 2015
c. Reference to QMRF: N/A
d. Predicted value (comments): The above predictions are in logarithm units (Log KOW). The corresponding n-octanol/water partition coefficient (Log KOW) for TBPAAQ is 19.9.

Applicability domain (OECD principle 3):
a. Domains:
i. Descriptor domain: N/A
ii. Structural fragment domain: in domain
KOWWIN uses a “fragment constant” methodology to predict Log KOW. 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 KOW estimate. The target compound is within the domain of KOWWIN (v1.69). The functional groups or other structural features of the target compound are all represented in the training set.
iii. Mechanism domain: in domain.
KOWWIN model is developed based on the assumption that the phase transfer enthalpy of a molecule (for hydrophobic molecules this is largely the negative of the solvation enthalpy) is the sum of the phase transfer enthalpies of its fragments. The enthalpy for a list of fragments is estimated from a database of n-octanol/water partitioning coefficient for molecules containing these fragments. Predictions can be made for molecules that contain these fragments. The approach is described in more details by Meylan and Howard (1995) for deriving n-octanol/water partitioning fragment contribution. The target compound is within the domain of KOWWIN (v1.69).
iv. Metabolic domain: not relevant
b. Structural analogues: The training dataset and the validation dataset have been searched for analogues using a sub-structural search for relevant fragments present in the target compound. Examples of structural analogues are evaluated for the model performance. A comparison of the experimental and predicted values is shown in Table 1.
c. Considerations on structural analogues:
Estimated Log KOW values for the analogues using KOWWIN are consistent with the experimental data. As the prediction is based on the contribution of the structural fragments, the prediction for the target compound is considered reliable.

The uncertainty of the prediction (OECD principle 4):
The predictions are considered reliable because the estimated log KOW values for the analogues are consistent with the experimental data. In addition, KOWWIN is considered reliable within the domain based on the correlation between the experimental and KOWWIN estimated Log KOW values presented by the developers. See Table 2.

The chemical and biological mechanisms according to the model underpinning
the predicted result (OECD principle 5):
The KOWWIN model estimates Log KOW based on the assumption that the phase transfer enthalpy of a molecule (for hydrophobic molecules this is largely the
negative of the solvation enthalpy) is the sum of the phase transfer enthalpies of its fragments. The enthalpy for a list of fragments is estimated from a database of noctanol/water partitioning coefficient for molecules containing these fragments. Predictions can be made for molecules that contain these fragments. The approach is described in more details by Meylan and Howard (1995) for deriving noctanol/ water partitioning fragment contribution.

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR assessment

Type:

log Pow

Partition coefficient:

19.9

Remarks on result:

other: QSAR used to predict Log Kow Value.

Conclusions:

The estimated Log KOW value for TBPAAQ was 19.9. The estimation by KOWWIN is deemed reliable with high confidence because TBPAAQ is within the estimation domain of the model, and estimated Log KOW values of structural analogues of TBPAAQ agree well with existing experimental data.

Executive summary:

The n-octanol/water partition coefficient (POW or KOW) of 1,4,5,8-tetrakis[(4-butylphenyl)amino]-9,10-dihydroanthracene-9,10-dione (TBPAAQ, CAS number:108313-21-9) was estimated using quantitative structure-activity relationship (QSAR). The compound for which KOW was estimated was TBPAAQ with a molecular weight of 797 g/mol. The logarithm of KOW (Log KOW or Log POW) was calculated for TBPAAQ using QSAR model KOWWIN (v1.69, U.S. EPA 2015) which uses a “fragment constant” methodology to predict Log KOW. 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 KOW estimate. KOWWIN was chosen due to its estimation accuracy and its transparency of the model and training set. Simplified molecular input line entry system (SMILES) code for TBPAAQ was used as the input for the KOWWIN model.

The estimated Log KOW value for TBPAAQ was 19.9. The estimation by KOWWIN is deemed reliable with high confidence because TBPAAQ is within the estimation domain of the model, and estimated Log KOW values of structural analogues of TBPAAQ agree well with existing experimental data.

Description of key information

The estimated Log Kow value for TBPAAQ was 19.9.  
    
    
    
    
    

The estimated Log KOWvalue for TBPAAQ was 19.9. The estimation by KOWWIN is deemed reliable with high confidence because TBPAAQ is within the estimation domain of the model, and estimated Log KOWvalues of structural analogues of TBPAAQ agree well with existing experimental data.















    
  
  
  
  
  

The n-octanol/water partition coefficient (POW or KOW) of 1,4,5,8-tetrakis[(4-butylphenyl)amino]-9,10-












  





dihydroanthracene-9,10-dione (TBPAAQ, CAS number: 108313-21-9) was estimated using quantitative


















structure-activity relationship (QSAR). The compound for which KOW was estimated was TBPAAQ with


















a molecular weight of 797 g/mol. The logarithm of KOW (Log KOW or Log POW) was calculated for


















TBPAAQ using QSAR model KOWWIN (v1.69, U.S. EPA 2015) which uses a “fragment constant”


















methodology to predict Log KOW.

Key value for chemical safety assessment

Log Kow (Log Pow):

19.9

Additional information

The n-octanol/water partition coefficient (POW or KOW) of 1,4,5,8-tetrakis[(4-butylphenyl)amino]-9,10-

dihydroanthracene-9,10-dione (TBPAAQ, CAS number: 108313-21-9) was estimated using quantitative

structure-activity relationship (QSAR). The compound for which KOW was estimated was TBPAAQ with

a molecular weight of 797 g/mol. The logarithm of KOW (Log KOW or Log POW) was calculated for

TBPAAQ using QSAR model KOWWIN (v1.69, U.S. EPA 2015) which uses a “fragment constant”

methodology to predict Log KOW. 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 KOW estimate. KOWWIN was chosen due to its estimation accuracy and its transparency

of the model and training set. Simplified molecular input line entry system (SMILES) code for TBPAAQ

was used as the input for the KOWWIN model.

The estimated Log KOW value for TBPAAQ was 19.9. The estimation by KOWWIN is deemed reliable

with high confidence because TBPAAQ is within the estimation domain of the model, and estimated Log

KOW values of structural analogues of TBPAAQ agree well with existing experimental data.