2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar-heptyl ar',ar''-Me derivs.

Adsorption / desorption

Link to relevant study record(s)

Reference

Endpoint:

adsorption / desorption: screening

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE: EPI Suite (U.S. Environmental Protection Agency, 2012)

2. MODEL (incl. version number): KOCWIN (a module of EPI Suite (U.S. Environmental Protection Agency, 2012)) for soil adsorption coefficient v2.00, U.S. EPA, 2010

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL:
i. 2-Naphthalenol,1-((4-(phenylazo)phenyl)azo)-,ar-heptyl ar',ar' Methyl derivatives (Automate Red B Component 1): Cc2cc(ccc2/N=N/c1ccccc1)/N=N/c3c4ccccc4c(CCCCCCC)cc3O
ii. 2-Naphthalenol,1-((4-(phenylazo)phenyl)azo)-,ar-heptyl ar',ar' Methyl derivatives (Automate Red B Component 2): Cc1cc(ccc1)/N=N/c2ccc(cc2C)/N=N/c3c4ccccc4c(CCCCCCC)cc3O
iii. 2-Naphthalenol,1-((4-(phenylazo)phenyl)azo)-,ar-heptyl ar',ar' Methyl derivatives (Automate Red B Component 3): Cc1cc(ccc1)/N=N/c2ccc(cc2C)/N=N/c3c4ccc(C)cc4c(CCCCCCC)cc3O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL

- Defined endpoint: Soil adsorption coefficient (KOC). The KOC describes the partitioning equilibrium for a substance between water and the organic carbon contained in soil or sediment.

- Unambiguous algorithm:
MCI Method: The molecular connectivity index (MCI) derived for the molecular structure and a series of correction factor for structural fragments. If no fragment is defined ('non-polar' molecules), no correction is applied. Log KOC = 0.5213 MCI + 0.60 + ΣPfN where ΣPfN is the summation of the products of all applicable correction factor coefficients multiplied by the number of times (N) that factor is counted for the structure.

KOW Method: Log KOW and a series of correction factor for structural fragments. If no fragment is defined ('non-polar' molecules), no correction is applied. Log KOC = 0.55313 Log KOW + 0.9251 + ΣPfN where ΣPfN is the summation of the products of all applicable correction factor coefficients multiplied by the number of times (N) that factor is counted for the structure.

- Defined domain of applicability: KOCWIN does not provide explicit information about applicability domain of the model. The applicability domain can be derived from the training data set and the fragments with correction. If a given target consist of fragments that are not aliphatic or aromatic and do not have a correction factor listed they have to be considered out of domain.

- Appropriate measures of goodness-of-fit and robustness and predictivity: The predications are considered reliable because the estimated KOC values for the analogues are consistent with the experimental data. In addition, KOCWIN is
considered reliable based on the correlation between the experimental and KOCWIN estimated log KOC values presented by the developers. Based on data presented by the developers, approx. 95% of all predictions of Log
KOC for the training set falls within the range of ±0.7 of the experimental value. This can be used to define the 95% confidence interval for the KOC of the target. The major contribution of the uncertainty is likely to come from the variability in
the soil and sediment matrixes that were used for determining experimental data of the training set. This level of uncertainty of the KOCWIN estimation indicates that the uncertainty of the QSAR method is similar to the uncertainty often associated with experimental measurements.

- Mechanistic interpretation: The dominant driving force for partitioning into soil organic carbon of the molecules in the training set is hydrophobicity. Likewise, partitioning of the target is driven by hydrophobicity.

5. APPLICABILITY DOMAIN

i. Descriptor Domain: In domain. Not specified by developer. For both MCI and KOW methods, the minimum to maximum of molecular mass in the training data: 32 < MW < 665 [g/mol]. The MWs of the targets are 464.6 g/mol, 478.6 g/mol and 492.7 g/mol for Automate Red B Component 1, Automate Red B Component 2 and Automate Red B Component 3, respectively.

ii. Structural fragment domain: In domain. The model does not specify structural fragment domain. Assessed as all molecules with either aliphatic structural fragment or with a fragment with a correction factor. Fragments of the target: azo and aromatic hydroxy are represented by structural fragments in the model training set.

iii. Mechanism domain: In domain. The model does not define a mechanism of partitioning. However, the dominant driving force for partitioning into soil organic carbon of the molecules in the training set is hydrophobicity. Likewise, partitioning of the target is driven by hydrophobicity.

iv. Metabolic domain: Not Relevant.

Structural analogues: Analogues were identified using a sub-structural search for relevant fragments present in the target. The substructures that were searched were azo, alkyl, and aromatic hydroxy. Examples of structural analogues are evaluated for the model performance. KOCWIN estimated Log KOC values for the analogues are consistent with the experimental data. As the prediction is based on the contribution of the structural fragments, the prediction for the target is considered reliable. For these analogues, the predictions by both methods are very close to the experimental value. The Log KOC values estimated by MCI method are slightly closer to the experimental values than those by Log KOW method. Based on this finding, preference is given to the MCI method for estimating the target.

6. ADEQUACY OF THE RESULT
The predications are considered reliable because the estimated KOC values for the analogues are consistent with the experimental data. In addition, KOCWIN is considered reliable based on the correlation between the experimental and KOCWIN estimated log KOC values presented by the developers.

Principles of method if other than guideline:

The soil adsorption coefficients (KOC) of 2-Naphthalenol,1-((4-(phenylazo)phenyl)azo)-,ar-heptyl ar',ar' Methyl derivatives (Automate Red B, nonvolatile) were estimated using quantitative structure-activity relationship (QSAR) algorithm implemented in KOCWIN v2.00 which is a module of the Estimation Program Interface Suite program (EPI Suite, v4.1, U.S. Environmental Protection Agency, 2012). Automate Red B, nonvolatile is a mixture of three main analogous components: Automate Red B Component 1, Automate Red B Component 2 and Automate Red B Component 3. The molecular weights of Automate Red B Component 1, Automate Red B Component 2 and Automate Red B Component 3 were 464.6 g/mol, 478.6 g/mol and 492.7 g/mol respectively. KOCWIN was chosen due to its estimation accuracy and the transparency of the model and training set.

GLP compliance:

no

Type of method:

other: QSAR estimation

Media:

other: QSAR estimation

Specific details on test material used for the study:

Chemical Name: 2-NAPHTHALENOL,1-((4-(PHENYLAZO)PHENYL)AZO)-,AR-HEPTYL AR',AR' METHYL DERIVATIVES (AUTOMATE RED B, NONVOLATILE)
Molecular Weight:
2-Naphthalenol,1-((4-(phenylazo)phenyl)azo)- ,ar-heptyl ar',ar' Methyl derivatives, Automate Red B Component 1 MW = 464.6
2-Naphthalenol,1-((4-(phenylazo)phenyl)azo)- ,ar-heptyl ar',ar' Methyl derivatives, Automate Red B Component 2 MW = 478.6
2-Naphthalenol,1-((4-(phenylazo)phenyl)azo)- ,ar-heptyl ar',ar' Methyl derivatives, Automate Red B Component 3 MW = 492.7

SMILES code:
i. 2-Naphthalenol,1-((4-(phenylazo)phenyl)azo)-,ar-heptyl ar',ar' Methyl derivatives (Automate Red B Component 1): Cc2cc(ccc2/N=N/c1ccccc1)/N=N/c3c4ccccc4c(CCCCCCC)cc3O
ii. 2-Naphthalenol,1-((4-(phenylazo)phenyl)azo)-,ar-heptyl ar',ar' Methyl derivatives (Automate Red B Component 2): Cc1cc(ccc1)/N=N/c2ccc(cc2C)/N=N/c3c4ccccc4c(CCCCCCC)cc3O
iii. 2-Naphthalenol,1-((4-(phenylazo)phenyl)azo)-,ar-heptyl ar',ar' Methyl derivatives (Automate Red B Component 3): Cc1cc(ccc1)/N=N/c2ccc(cc2C)/N=N/c3c4ccc(C)cc4c(CCCCCCC)cc3O

Radiolabelling:

no

Key result

Type:

log Koc

Value:

8.15

Remarks on result:

other: Automate Red B Component 1

Key result

Type:

log Koc

Value:

8.35

Remarks on result:

other: Automate Red B Component 2

Key result

Type:

log Koc

Value:

8.56

Remarks on result:

other: Automate Red B Component 3

KOC Estimate from MCI	Automate Red B Component 1	Automate Red B Component 2	Automate Red B Component 3
First Order Molecular Connectivity Index	17.152	17.546	17.940
Non-Corrected Log KOC (0.5213 MCI + 0.60)	9.5412	9.7466	9.9519
Fragment Correction(s):
Azo (-N=N-)	-1.2951	-1.2951	-1.2951
Aromatic Hydroxy (aromatic-OH)	-0.0966	-0.0966	-0.0966
Corrected Log KOC	8.1496	8.3549	8.5602
Estimated KOC	1.411e+008 L/kg	2.264e+008 L/kg	3.633e+008 L/kg

KOC Estimate from Log KOW	Automate Red B Component 1	Automate Red B Component 2	Automate Red B Component 3
Log KOW (Kowwin estimate)	11.67	12.21	12.76
Non-Corrected Log KOC (0.55313 logKow + 0.9251)	7.3801	7.6788	7.9830
Fragment Correction(s):
Azo (-N=N-)	0.8621	0.8621	0.8621
Aromatic Hydroxy (aromatic-OH)	0.1668	0.1668	0.1668
Corrected LogKOC	8.4090	8.7077	9.0119
Estimated KOC	2.565e+008 L/kg	5.102e+008 L/kg	1.028e+009 L/kg

Structural analogues: Analogues were identified using a sub-structural search for relevant fragments present in the target. The substructures that were searched were azo, alkyl, and aromatic hydroxy. Examples of structural analogues are evaluated for the model performance. A comparison of the experimental and predicted values is shown in the table below.

CAS	Name	Log KOC Exp	Log KOC Est (MCI)	Log KOC Est (KOW)
103-33-3	azobenzene	3.3	3.58	3.47
90-15-3	1-naphthol	3.1	3.31	2.67
63-25-2	Carbaril	2.4	2.55	2.13
132-66-1	Naptalam	3.34	2.93	1.81
143-08-8	1-nonanol	1.89	1.84	2.60

Validity criteria fulfilled:

yes

Conclusions:

It is with high confidence to conclude that the Log KOC of Automate Red B Components 1, 2 and 3 are estimated to be 8.15, 8.35, and 8.56, respectively.

Executive summary:

The soil adsorption coefficients (KOC) of 2-Naphthalenol,1-((4-(phenylazo)phenyl)azo)-,ar-heptyl ar',ar' Methyl derivatives (Automate Red B, nonvolatile) were estimated using quantitative structure-activity relationship (QSAR) algorithm implemented in KOCWIN v2.00 which is a module of the Estimation Program Interface Suite program (EPI Suite, v4.1, U.S. Environmental Protection Agency, 2012). Automate Red B, nonvolatile is a mixture of three main analogous components: Automate Red B Component 1, Automate Red B Component 2 and Automate Red B Component 3. The molecular weights of Automate Red B Component 1, Automate Red B Component 2 and Automate Red B Component 3 were 464.6 g/mol, 478.6 g/mol and 492.7 g/mol respectively. KOCWIN was chosen due to its estimation accuracy and the transparency of the model and training set.

The KOCWIN model estimates KOC either from the octanol-water coefficient (KOW) or from a first-order molecular connectivity index (MCI). Structural analogues as identified in the training set have been processed parallel to the target. The model does not define parametric or structural domain. However, the analogues identified from within the training set suggest coverage of relevant substructures present in the target (azo, alkyl, and aromatic hydroxy). A comparison of experimental and predicted values for structural analogues was performed to decide on the preferred model for the prediction. Confidence intervals of the estimation are derived based on the error histogram provided by the model developer indicating that 95% of the substances in the training dataset are predicted within ± 0.7 log units of the experimental value.

Simplified molecular input line entry system (SMILES) codes for the molecules were used as the input for the KOCWIN model. The estimated KOC value for Automate Red B Component 1, 2 & 3 are presented in the table below. Preference is given to the MCI method because the Log KOC values for structural analogues estimated by MCI method are slightly closer to the experimental values than those by Log KOW method. The estimation by KOCWIN MCI method is deemed reliable because the estimated KOC values of structural analogues agree well with existing experimental data. It is with high confidence to conclude that the Log KOC of Automate Red B Components 1, 2 and 3 are estimated to be 8.15, 8.35, and 8.56, respectively.

Predicted KOC for Automate Red B, non-volatile based upon MCI and KOW Methods

Compound	KOW Method, L/kg	MCI Method, L/kg	Log KOC Value*
Automate Red B Component 1	2.565e+008	1.411e+008	8.15
Automate Red B Component 2	5.102e+008	2.264e+008	8.35
Automate Red B Component 3	1.028e+009	3.633e+008	8.56

*Final Log KOC determination based on the MCI method

Description of key information

The log Koc values for the three main components of 2-Naphthalenol,1-((4-(phenylazo)phenyl)azo)-,ar-heptyl ar',ar' Methyl deriviatives, were estimated to be 8.15, 8.35, and 8.56 based on the KOCWIN outputs (KOCWIN, v 2.00). The estimation by KOCWIN is deemed reliable because the estimated KOC values of structural analogues agree well with existing experimental data. The Log Koc of 8.56 was reported as the representative value for the test material in order to be conservative in environmental fate and risk predictions.

Key value for chemical safety assessment

Koc at 20 °C:

363 000 000

Additional information

[LogKoc: 8.56]