Reaction products of diazotized mixture of aniline, toluidines and xylidines coupled with mixture of aniline, toluidines and xylidines, subsequently diazotized then coupled with 2-naphthol

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

supporting 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:

1. SOFTWARE: ACD Labs/Percepta (2017 Release).

2. MODEL (incl. version number): ACD/LogS0 GALAS

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL:
Structural formula: C17H14N2O
Structural codes:
a. SMILES: Cc3ccccc3/N=N/c1c2ccccc2ccc1O
b. InChI: InChI=1S/C17H14N2O/c1-12-6-2-5-9-15(12)18-19-17-14-8-4-3-7-13(14)10-11-16(17)20/h2-11,20H,1H3/b19-18+
c. Other structural representation: mol file

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: water solubility
- Unambiguous algorithm: GALAS algorithm, where GALAS (Global, Adjusted Locally According to Similarity) models consist of two parts: (1) a global linear model, and (2) local corrections based on the analysis of global model performance for the most similar compounds from the training set. The global QSAR was developed using PLS in combination with bootstrapping technique. Further details are available on the attached QMRF.
- Defined domain of applicability: Applicability domain of the model is defined based on the training set compounds. This procedure takes into account the following two aspects: 1) Similarity of the tested compound to the training set. No reliable predictions can be made if there are no similar compounds in the training set; 2) Consistence of the experimental values with regard to the baseline model for similar compounds.
- Appropriate measures of goodness-of-fit and robustness and predictivity: Please see attached QMRF.
- Mechanistic interpretation: The only mechanistic consideration utilized in model building is the use of a linear regression method (PLS) and the fragmental descriptors. In other words it is assumed that the final predicted value is composed of a linear combination of all the contributions of structural moieties making up the test molecule.

5. APPLICABILITY DOMAIN
- Descriptor domain: Detailed structural and/or response limits of the applicability domain are not defined. The applicability domain of predictions is assessed using the Reliability Index (RI). This index provides values in a range from 0 to 1 and gives an evaluation of whether a target compound falls within the model applicability domain. Estimation of the RI takes into account the following two aspects: similarity of the tested compound to the training set and consistency of experimental values for similar compounds. For RI values lower than 0.3 the target compound is considered outside the model AD and the prediction is assessed as not reliable.
The target compound Solvent Orange 2 (CAS No. 2646-17-5) is included in the model applicability domain since the RI is greater than 0.3.
Descriptor domain: not applicable.
- Structural and mechanistic domains: Not applicable.
- Similarity with analogues in the training set: ACD/Percepta displays up to 5 most structurally similar structures from the training set along with their experimental test results. The similarity of the target compound with respect to the training set compounds is analysed in terms of “property-specific” similarity.
The five identified analogues of Solvent Orange 2 (CAS No. 2646-17-5) exhibit moderate similarity with respect to the target (similarity index ranging from 0.70 to 0.86), meaning that the target compound is moderately represented in the training set of the model, and experimental LogS0 values ranging from -3.90 (Benzenamine, 4-methyl-2-[(4-methylphenyl)azo]-) to -5.92 (Yellow AB).

6. ADEQUACY OF THE RESULT
An intrinsic solubility (LogS0) equal to -5.27, corresponding to a water solubility of 1.41 mg/L (slightly soluble), was estimated for the target Solvent Orange 2 (CAS No. 2646-17-5). The prediction was assessed as moderately reliable (reliability index equal to 0.63).
The water solubility (LogS0) QSAR prediction was assessed as adequate for regulatory purposes.

Qualifier:

according to guideline

Guideline:

other:

Version / remarks:

REACH Guidance on QSARs R.6 (2008)

Principles of method if other than guideline:

- Software tool(s) used including version: ACD Labs/Percepta (2017 release)
- Model(s) used: ACD/LogS0 GALAS
- Model description: see field 'Justification for type of information' and 'Attached justification'
- Justification of QSAR prediction: see field 'Justification for type of information' and 'Attached justification'

Specific details on test material used for the study:

SMILES: Cc3ccccc3/N=N/c1c2ccccc2ccc1O

Key result

Water solubility:

1.41 mg/L

Temp.:

25 °C

Remarks on result:

other: Based on QSAR prediction

The QSAR prediction was assessed as moderately reliable, based on the reliability index equal to 0.63, and the following considerations: 1) moderately similar training set analogues; 2) experimental LogS0 water solubility values of training set analogues in the range of -3.90 to -5.92 (i.e., slightly soluble experimental values as for the predicted value of the target).

Conclusions:

An intrinsic solubility (LogS0) equal to -5.27, corresponding to a water solubility of 1.41 mg/L (slightly soluble), was estimated for the target Solvent Orange 2 (CAS No. 2646-17-5). The prediction was assessed as moderately reliable.

Executive summary:

This study was designed to generate estimated in silico (non-testing) data for Solvent Orange 2 (CAS No. 2646 -17-5) to be used for its hazard assessment. QSAR prediction was provided for the water solubility endpoint. A reliability score of 2 was assigned, since results derived from a valid QSAR model and falling into its applicability domain, with adequate and reliable documentation/justification. The ACD/LogS0 model implemented in ACD/Percepta (2017 release) was employed. ACD/LogS0 GALAS provides a quantitative estimate of the compound’s solubility in water at 25°C (in terms of intrinsic solubility Log S0, mmol/mL) derived on the basis of GALAS methodology. An intrinsic solubility (LogS0) equal to -5.27, corresponding to a water solubility of 1.41 mg/L (slightly soluble), was estimated by the model. The prediction was assessed as moderately reliable, based on the reliability index equal to 0.63 and the following considerations:

- moderately similar training set analogues;

- experimental LogS0 water solubility values of training set analogues in the range of -3.90 to -5.92 (i.e., slightly soluble experimental values as for the predicted value of the target).

The water solubility (LogS0) QSAR prediction was assessed as adequate for regulatory purposes.

Reference 2

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

supporting 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:

1. SOFTWARE: ACD Labs/Percepta (2017 Release).

2. MODEL (incl. version number): ACD/LogS0 GALAS

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL:
Structural formula: C24H20N4O
Structural codes:
a. SMILES: Cc4ccccc4/N=N/c3ccc(/N=N/c1c2ccccc2ccc1O)c(C)c3
b. InChI: InChI=1S/C24H20N4O/c1-16-7-3-6-10-21(16)26-25-19-12-13-22(17(2)15-19)27-28-24-20-9-5-4-8-18(20)11-14-23(24)29/h3-15,29H,1-2H3/b26-25+,28-27+
c. Other structural representation: mol file

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: water solubility
- Unambiguous algorithm: GALAS algorithm, where GALAS (Global, Adjusted Locally According to Similarity) models consist of two parts: (1) a global linear model, and (2) local corrections based on the analysis of global model performance for the most similar compounds from the training set. The global QSAR was developed using PLS in combination with bootstrapping technique. Further details are available on the attached QMRF.
- Defined domain of applicability: Applicability domain of the model is defined based on the training set compounds. This procedure takes into account the following two aspects: 1) Similarity of the tested compound to the training set. No reliable predictions can be made if there are no similar compounds in the training set; 2) Consistence of the experimental values with regard to the baseline model for similar compounds.
- Appropriate measures of goodness-of-fit and robustness and predictivity: Please see attached QMRF.
- Mechanistic interpretation: The only mechanistic consideration utilized in model building is the use of a linear regression method (PLS) and the fragmental descriptors. In other words it is assumed that the final predicted value is composed of a linear combination of all the contributions of structural moieties making up the test molecule.

5. APPLICABILITY DOMAIN
- Descriptor domain: Detailed structural and/or response limits of the applicability domain are not defined. The applicability domain of predictions is assessed using the Reliability Index (RI). This index provides values in a range from 0 to 1 and gives an evaluation of whether a target compound falls within the model applicability domain. Estimation of the RI takes into account the following two aspects: similarity of the tested compound to the training set and consistency of experimental values for similar compounds. For RI values lower than 0.3 the target compound is considered outside the model AD and the prediction is assessed as not reliable.
The target compound Solvent Red 24 (CAS No. 85-83-6) is included in the model applicability domain since the RI is greater than 0.3.
Descriptor domain: not applicable.
- Structural and mechanistic domains: Not applicable.
- Similarity with analogues in the training set: ACD/Percepta displays up to 5 most structurally similar structures from the training set along with their experimental test results. The similarity of the target compound with respect to the training set compounds is analysed in terms of “property-specific” similarity.
The five identified analogues of Solvent Red 24 (CAS No. 85-83-6) exhibit moderate similarity with respect to the target (similarity index ranging from 0.61 to 0.82), meaning that the target compound is moderately represented in the training set of the model, and experimental LogS0 values ranging from -3.90 (Benzenamine, 4-methyl-2-[(4-methylphenyl)azo]-) to -9.72 (p-Hydroxy-p-bis azobenzene).

6. ADEQUACY OF THE RESULT
An intrinsic solubility (LogS0) equal to -8.16, corresponding to a water solubility of 0.0026 mg/L (insoluble), was estimated for the target Solvent Red 24 (CAS No. 85-83-6). The prediction was assessed as borderline reliable (reliability index equal to 0.42).
The water solubility (LogS0) QSAR prediction was assessed as adequate for regulatory purposes.

Qualifier:

according to guideline

Guideline:

other:

Version / remarks:

REACH Guidance on QSARs R.6 (2008)

Principles of method if other than guideline:

- Software tool(s) used including version: ACD Labs/Percepta (2017 release)
- Model(s) used: ACD/LogS0 GALAS
- Model description: see field 'Justification for type of information' and 'Attached justification'
- Justification of QSAR prediction: see field 'Justification for type of information' and 'Attached justification'

Specific details on test material used for the study:

SMILES: Cc4ccccc4/N=N/c3ccc(/N=N/c1c2ccccc2ccc1O)c(C)c3

Key result

Water solubility:

0.003 mg/L

Temp.:

25 °C

Remarks on result:

other: Based on QSAR prediction

In the case of the target Solvent Red 24 (CAS No. 85-83-6), the prediction was assessed as borderline reliable, based on the reliability index equal to 0.42, and the following consideration:

- experimental data of structural analogues: wide range of experimental LogS0 water solubility values (LogS0 -3.90 to -9.72, i.e. from slightly soluble to insoluble).

Conclusions:

An intrinsic solubility (LogS0) equal to -8.16, corresponding to a water solubility of 0.0026 mg/L (insoluble), was estimated for the target Solvent Red 24 (CAS No. 85-83-6). The prediction was assessed as borderline reliable.

Executive summary:

This study was designed to generate estimated in silico (non-testing) data for Solvent Red 24 (CAS No. 85-83-6) to be used for its hazard assessment. QSAR prediction was provided for the water solubility endpoint. A reliability score of 2 was assigned, since results derived from a valid QSAR model and falling into its applicability domain, with adequate and reliable documentation/justification. The ACD/LogS0 model implemented in ACD/Percepta (2017 release) was employed. ACD/LogS0 GALAS provides a quantitative estimate of the compound’s solubility in water at 25°C (in terms of intrinsic solubility Log S0, mmol/mL) derived on the basis of GALAS methodology. An intrinsic solubility (LogS0) equal to -8.16, corresponding to a water solubility of 0.0026 mg/L (insoluble), was estimated by the model. The prediction was assessed as borderline reliable, based on the reliability index equal to 0.42 and the following consideration:

•       experimental data of structural analogues: wide range of experimental LogS0 water solubility values (LogS0 -3.90 to -9.72, i.e. from slightly soluble to insoluble).

The water solubility (LogS0) QSAR prediction was assessed as adequate for regulatory purposes.

Reference 3

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

supporting 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:

1. SOFTWARE: ACD Labs/Percepta (2017 Release).

2. MODEL (incl. version number): ACD/LogS0 GALAS

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL:
Structural formula: C16H12N2O
Structural codes:
a. SMILES: Oc3ccc1ccccc1c3/N=N/c2ccccc2
b. InChI: InChI=1S/C16H12N2O/c19-15-11-10-12-6-4-5-9-14(12)16(15)18-17-13-7-2-1-3-8-13/h1-11,19H/b18-17+
c. Other structural representation: mol file

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: water solubility
- Unambiguous algorithm: GALAS algorithm, where GALAS (Global, Adjusted Locally According to Similarity) models consist of two parts: (1) a global linear model, and (2) local corrections based on the analysis of global model performance for the most similar compounds from the training set. The global QSAR was developed using PLS in combination with bootstrapping technique. Further details are available on the attached QMRF.
- Defined domain of applicability: Applicability domain of the model is defined based on the training set compounds. This procedure takes into account the following two aspects: 1) Similarity of the tested compound to the training set. No reliable predictions can be made if there are no similar compounds in the training set; 2) Consistence of the experimental values with regard to the baseline model for similar compounds.
- Appropriate measures of goodness-of-fit and robustness and predictivity: Please see attached QMRF.
- Mechanistic interpretation: The only mechanistic consideration utilized in model building is the use of a linear regression method (PLS) and the fragmental descriptors. In other words it is assumed that the final predicted value is composed of a linear combination of all the contributions of structural moieties making up the test molecule.

5. APPLICABILITY DOMAIN
- Descriptor domain: Detailed structural and/or response limits of the applicability domain are not defined. The applicability domain of predictions is assessed using the Reliability Index (RI). This index provides values in a range from 0 to 1 and gives an evaluation of whether a target compound falls within the model applicability domain. Estimation of the RI takes into account the following two aspects: similarity of the tested compound to the training set and consistency of experimental values for similar compounds. For RI values lower than 0.3 the target compound is considered outside the model AD and the prediction is assessed as not reliable.
The target compound Solvent Yellow 14 (CAS No. 842-07-9) is included in the model applicability domain since the RI is greater than 0.3.
Descriptor domain: not applicable.
- Structural and mechanistic domains: Not applicable.
- Similarity with analogues in the training set: ACD/Percepta displays up to 5 most structurally similar structures from the training set along with their experimental test results. The similarity of the target compound with respect to the training set compounds is analysed in terms of “property-specific” similarity.
Four structural analogues were identified for the target Solvent Yellow 14. The four identified analogues of Solvent Yellow 14 (CAS No. 842-07-9) were moderately similar to the target (similarity index ranging from 0.71 to 0.86), meaning that the target compound is moderately represented in the training set of the model, and were characterised by experimental LogS0 values ranging from -4.45 (Azobenzene) to -5.92 (Yellow AB).

6. ADEQUACY OF THE RESULT
An intrinsic solubility (LogS0) equal to -5.22, corresponding to a water solubility of 1.5 mg/L (slightly soluble), was estimated for the target Solvent Yellow 14 (CAS No. 842-07-9). The prediction was assessed as moderately reliable (reliability index equal to 0.56).
The water solubility (LogS0) QSAR prediction was assessed as adequate for regulatory purposes.

Qualifier:

according to guideline

Guideline:

other:

Version / remarks:

REACH Guidance on QSARs R.6 (2008)

Principles of method if other than guideline:

- Software tool(s) used including version: ACD Labs/Percepta (2017 release)
- Model(s) used: ACD/LogS0 GALAS
- Model description: see field 'Justification for type of information' and 'Attached justification'
- Justification of QSAR prediction: see field 'Justification for type of information' and 'Attached justification'

Specific details on test material used for the study:

SMILES: Oc3ccc1ccccc1c3/N=N/c2ccccc2

Key result

Water solubility:

1.5 mg/L

Temp.:

25 °C

Remarks on result:

other: Based on QSAR prediction

The QSAR prediction was assessed as moderately reliable, based on the reliability index equal to 0.56, and the following considerations:

- moderately similar training set analogues;

- experimental LogS0 water solubility values of training set analogues in the range of -4.45 to -5.92 (i.e., slightly soluble experimental values as for the predicted value of the target).

Conclusions:

An intrinsic solubility (LogS0) equal to -5.22, corresponding to a water solubility of 1.5 mg/L (slightly soluble), was estimated for the target Solvent Yellow 14 (CAS No. 842-07-9). The prediction was assessed as moderately reliable.

Executive summary:

This study was designed to generate estimated in silico (non-testing) data for Solvent Yellow 14 (CAS No. 842-07-9) to be used for its hazard assessment. QSAR prediction was provided for the water solubility endpoint. A reliability score of 2 was assigned, since results derived from a valid QSAR model and falling into its applicability domain, with adequate and reliable documentation/justification. The ACD/LogS0 model implemented in ACD/Percepta (2017 release) was employed. ACD/LogS0 GALAS provides a quantitative estimate of the compound’s solubility in water at 25°C (in terms of intrinsic solubility Log S0, mmol/mL) derived on the basis of GALAS methodology. An intrinsic solubility (LogS0) equal to -5.22, corresponding to a water solubility of 1.5 mg/L (slightly soluble), was estimated by the model. The prediction was assessed as moderately reliable, based on the reliability index equal to 0.56 and the following considerations:

- moderately similar training set analogues;

- experimental LogS0 water solubility values of training set analogues in the range of -4.45 to -5.92 (i.e., slightly soluble experimental values as for the predicted value of the target).

The water solubility (LogS0) QSAR prediction was assessed as adequate for regulatory purposes.

Reference 4

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

GLP compliance:

yes

Type of method:

column elution method

Key result

Water solubility:

ca. 13.82 µg/L

Conc. based on:

other: sum of the water solubility of the three main constituents, i.e. SY14, SO2, SR24

Loading of aqueous phase:

1 000 mg/L

Incubation duration:

>= 16 - <= 20 h

Temp.:

20 °C

pH:

ca. 6

Details on results:

The quantification results of the Solvent Red 24 Mix were obtained by sum of SR24, SY14 and SO2 (see attached file for details).

Validation of the analytical method:

The performances of the method were within NF T90-210 acceptance criteria.

An analytical method using HPLC-MS/MS has been developed to determine the content of SR24, SY14 and SO2, three specific moiety of the test item Solvent red 24 mix in UP water. This analytical method is considered fully validated in this matrix with respective LOQ of 0.054 μg/L, 0.101 μg/L and 0.114 μg/L for SR24, SY14 and SO2.

Conclusions:

The water solubility of solvent red 24 mix was calculated after quantification of SR24, SY14 and SO2 (the three constituents chemically defined in the UVCB substance).
The water solubility of SR24, SY14 and SO2 were measured with column elution method. The analytical methods were validated.
The water solubility of solvent red 24 mix has been calculated to be 13.82 ug/L, at 20°C, pH 6. The test substance is therefore considered highly insoluble in water.

Description of key information

Solvent Red 24 mix is a UVCB substance composed of three chemically defined constituents: Solvent Red 24 (CAS No. 85-83-6), Solvent Orange 2 (CAS No. 2646-17-5), and Solvent Yellow 14 (CAS No. 842-07-9).

Solvent Red 24 mix was tested for water solubility through two kind of tests: one experimental test and one in silico (QSAR) test.

Both tests focused on the three constituents chemically well defined of the UVCB substance, i.e. SR24, SY14 and SO2. Based on the water solubility results/predictions of these three constituents as well as the concentration of each constituent in the UVCB substance, the water solubility of solvent red 24 mix was calculated.

The experimental study is the key study and gave a result of 13.82 ug/L, at 20°C, pH 6.

The QSAR study is a supporting study and gave a result of 0.218 mg/L. Further details are specified below.

Details regarding the QSAR conclusion for water solubility:

Solvent Red 24 Mix is a UVCB substance, composed of three chemically defined constituents: Solvent Red 24 (CAS No. 85-83-6, composition percentage >85%), Solvent Orange 2 (CAS No. 2646-17-5, composition percentage <10%), and Solvent Yellow 14 (CAS No. 842-07-9, composition percentage <5%). More specifically, the constituent Solvent Red 24 was considered as the representative substance of the substance family 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivatives (CAS No. 70879-65-1), the latter of which represents the overall major constituent (>85%) of the UVCB Solvent Red 24 Mix. The substance Solvent Red 24 is a mono-constituent substance with an expected concentration greater than 40% in 2-naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs., and with a concentration between 35 and 55% in the UVCB Solvent Red 24 Mix.

QSAR predictions for the water solubility property were provided for the three main constituents of the UVCB. Overall, the three main constituents of the UVCB substance Solvent Red 24 Mix were predicted to be insoluble (Solvent Red 24) and slightly soluble (Solvent Orange 2 and Solvent Yellow 14).

Based on the obtained QSAR predictions, conclusions for the UVCB target substance Solvent Red 24 Mix were derived following a weighted mean approach, where the percentage of composition of the three main constituents in the UVCB Solvent Red 24 Mix were taken into account.

Hence, following a weighted mean approach, an overall slightly water soluble value of 0.218 mg/L was calculated for the UVCB target compound Solvent Red 24 Mix. A summary table is reported below.

Summary of the in silico predictions for water solubility.

Name (CAS No.)	Concentration %	Endpoint	Prediction (mg/L)	Reliability assessment	Adequacy
		PHYSICO-CHEMICAL PROPERTIES
Solvent Red 24 (85-83-6)	85%*	Water solubility	0.0026^a	Borderline Reliable	Adequate (Klimisch 2)
Solvent Orange 2 (2646-17-5)	10%		1.41^a	Moderate Reliable	Adequate (Klimisch 2)
Solvent Yellow 14 (842-07-9)	5%		1.5^a	Moderate Reliable	Adequate (Klimisch 2)
Solvent Red 24 Mix (UVCB)	--	Weighted mean approach	0.218	--	--

*Concentration percentage of the main constituent Solvent Red 24 was adjusted from > 80% to 85% in order to reach a total composition percentage of 100% in the UVCB substance for the weighted mean calculation.

^aPrediction generated with ACD/Percepta.

Key value for chemical safety assessment

Water solubility:

13.82 µg/L

at the temperature of:

20 °C