N-[2-[(2-chloro-4,6-dinitrophenyl)azo]-5-(diallylamino)-4-methoxyphenyl]acetamide

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

February 16, 2017 - March 02, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

no

GLP compliance:

no

Type of method:

column elution method

Key result

Water solubility:

< 52.2 µg/L

Conc. based on:

test mat.

Temp.:

20 °C

pH:

5.8

 Individual results

Preliminary visual estimation of the water solubility

Three preliminary tests were carried out with specified amounts of the test item and 100 mL and 500 mL demineralized water, respectively. After each addition of an amount of water, the mixture was stirred for at least 24 hours, and visually checked for any undissolved particles.

Table4: Results of the preliminary visual estimation of the water solubility

Amount of test item / mg	Total volume of dist. water / mL	Appearance of mixture
13.9	100	not dissolved
7.8	500	not dissolved
3.7	500	not dissolved

The preliminary visual experiments showed that the water solubility of the test item is < 10 mg/L. According to the preliminary visual estimation in the main test the water solubility was determined by the column elution method. 

 Column elution method

118.9 mg of the test item were dissolved in 100 mL acetone. For charging the columns in each case 25 mL of the test item solution was added to about 3 g of sea sand and the mixtures were shaken. The solvent was then removed under reduced pressure using a rotary evaporator (40 °C, approx. 20 mbar). The dry residues were placed into the columns of the test apparatus, which have afterwards been filled with water (test temperature: 20 °C; water pH at 23 °C: 5.8). After a swelling time of 2 h pumps were started to rinse the test item coated sand with demineralized water. At the end of the study it was confirmed that residual test item remained on the columns. The residual test item was eluted with 50 mL acetone.

As blank value the used demineralized water was tested. No signal was detected in the range of the retention time of the test item.

The concentration of the test item was quantified by HPLC. Refer to Table 5 to Table 7 for results.

Column 12.5 mL/h:

Rotation period of the fraction collector:                 90 min per fraction

Duration of sampling:                                             about 72 h (32 fractions)

Table5: Column elution method, column 12.5 mL/h

Fraction no.	V / mL	pH	water solubility /µg/L
23	18.5	5.9	< 52.2
24	18.5	5.8	< 52.2
25	18.5	6.0	< 52.2
26	18.5	5.9	< 52.2
27	18.5	5.8	< 52.2

The water solubility was found to be below the quantification limit of 52.2 µg/L.

Column 25.0 mL/h:

Rotation period of the fraction collector:       45 min per fraction

Duration of sampling:                                    about 71 h (62 fractions)

Table6: Column elution method, column 25.0 mL/h

Fraction no.	V / mL	pH	water solubility /µg/L
50	17.5	6.8	< 52.2
51	17.5	6.7	< 52.2
52	17.5	6.8	< 52.2
53	17.5	6.9	< 52.2
54	17.5	6.7	< 52.2

The water solubility was found to be below the quantification limit of 52.2 µg/L.

In both columns the concentration of five consecutive fractions was constant within ± 30 %. No increasing or decreasing tendency was observed.

 

Coating check:

Table7: Coating check

	Amount of test item used for coating / mg	Measured concentration of test item in eluate / µg/L	Amount of test item eluted / mg
Column 12.5 mL/h	29.7	701 / 693	27.88
Column 25.0 mL/h	29.7	725 / 725	29.01

The coating check was successful. Enough test item remained on the columns.

The water solubility c_S of the test item Disperse Blue 291.1 Br was below the quantification limit of 52.2 µg/L (mean value of the columns).

Executive summary:

The water solubility c_S of the test item Disperse Blue 291.1 Br at a temperature of 20 °C was determined according to the column elution method. It was found to be below the quantification limit:

c_S< 52.2 µg/L

 

Reference 2

Endpoint:

water solubility

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Study period:

2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE
EpiSuite 4.1

2. MODEL (incl. version number)
EpiSuite 4.1
WSKOW v1.42
WaterNT v1.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See attachment

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attachment

5. APPLICABILITY DOMAIN
See attachment

6. ADEQUACY OF THE RESULT
See attachment

Principles of method if other than guideline:

WSKOW v1.42 in EpiSuite 4.1: The estimation methodology used by WSKOWWIN (Meylan and Howard, 1994a,b) is described in the document prepared for the U.S. Environmental Protection Agency (OPPT): Upgrade of PCGEMS Water Solubility Estimation Method (May 1994).  A companion document (Validation of Water Solubility Estimation Methods Using Log Kow for Application in PCGEMS & EPI) also discusses the methodology.  WSKOWWIN uses equations 19 and 20 from these documents because they are the best available equations for estimating Wsol.

Equation 19 is:  log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Corrections
Equation 20 is:  log S (mol/L) = 0.693 - 0.96 log Kow - 0.0092(Tm-25) - 0.00314 MW + Corrections

(where MW is molecular weight, Tm is melting point (MP) in deg C [used only for solids])
Corrections are applied to 15 structure types (eg. alcohols, acids, selected phenols, nitros, amines, alkyl pyridines, amino acids, PAHS, multi-nitrogen types, etc); application and magnitude depends on available MP.  

Equation 20 is used when a measured MP is available; otherwise, equation 19 is used. These equations were derived from a dataset consisting of 1450 compounds with measured log Kow, water sol, and MP. Eq 20 has the following statistical accuracy: correlation coefficient (r2) = 0.97, standard deviation = 0.409 log units, and absolute mean error = 0.313 log units.  Application to a validation dataset of 817 compounds gave the following statistical accuracy: correlation coefficient (r2) = 0.902, standard deviation = 0.615 log units, and absolute mean error = 0.480 log units.

GLP compliance:

no

Type of method:

other: calculation

Key result

Water solubility:

0 mg/L

Conc. based on:

act. ingr.

Remarks on result:

other: calculated

Remarks:

WSKOW v1.42

Water solubility:

0.003 mg/L

Conc. based on:

act. ingr.

Remarks on result:

other: calculated

Remarks:

Water Sol (v1.01 est)

Conclusions:

The water solubility of Disperse Blue 291:1 Br is calculated to be 0.0004083 mg/L and 0.0025385 mg/L by WSKOW v1.42 and WATERNT v1.01, respectively

Executive summary:

The water solubility of Disperse Blue 291:1 Br was calculated with WSKOW v1.42 and WATERNT v1.01 included in EpiSuite 4.1. to be 0.0004083 mg/L and 0.0025385 mg/L, respectively.

Hence, the test substance is nearly insoluble in water.

Reference 3

Endpoint:

water solubility

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Study period:

2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE
EpiSuite 4.1

2. MODEL (incl. version number)
EpiSuite 4.1
WSKOW v1.42
WaterNT v1.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See attachment

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attachment

5. APPLICABILITY DOMAIN
See attachment

6. ADEQUACY OF THE RESULT
See attachment

Principles of method if other than guideline:

WSKOW v1.42 in EpiSuite 4.1: The estimation methodology used by WSKOWWIN (Meylan and Howard, 1994a,b) is described in the document prepared for the U.S. Environmental Protection Agency (OPPT): Upgrade of PCGEMS Water Solubility Estimation Method (May 1994).  A companion document (Validation of Water Solubility Estimation Methods Using Log Kow for Application in PCGEMS & EPI) also discusses the methodology.  WSKOWWIN uses equations 19 and 20 from these documents because they are the best available equations for estimating Wsol.

Equation 19 is:  log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Corrections
Equation 20 is:  log S (mol/L) = 0.693 - 0.96 log Kow - 0.0092(Tm-25) - 0.00314 MW + Corrections

(where MW is molecular weight, Tm is melting point (MP) in deg C [used only for solids])
Corrections are applied to 15 structure types (eg. alcohols, acids, selected phenols, nitros, amines, alkyl pyridines, amino acids, PAHS, multi-nitrogen types, etc); application and magnitude depends on available MP.  

Equation 20 is used when a measured MP is available; otherwise, equation 19 is used. These equations were derived from a dataset consisting of 1450 compounds with measured log Kow, water sol, and MP. Eq 20 has the following statistical accuracy: correlation coefficient (r2) = 0.97, standard deviation = 0.409 log units, and absolute mean error = 0.313 log units.  Application to a validation dataset of 817 compounds gave the following statistical accuracy: correlation coefficient (r2) = 0.902, standard deviation = 0.615 log units, and absolute mean error = 0.480 log units.


WATERNT uses a "fragment constant" methodology to predict water solubility.  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 solubility estimate.   We call WATERNT’s methodology the Atom/Fragment Contribution (AFC) method.  Coefficients for individual fragments and groups in WATERNT were derived by multiple regression of 1000 reliably measured water solubility values.
The exact same methodology is used in the KOWWIN Program (estimation of octanol water partition coefficient.
To estimate water solubility, WATERNT initially separates a molecule into distinct atom/fragments.  In general, each non-hydrogen atom (e.g. carbon, nitrogen, oxygen, sulfur, etc.) in a structure is a "core" for a fragment; the exact fragment is determined by what is connected to the atom.  Several functional groups are treated as core "atoms"; these include carbonyl (C=O), thiocarbonyl (C=S), nitro (-NO2), nitrate (ONO2), cyano (-C/N), and isothiocyanate (-N=C=S).  Connections to each core "atom" are either general or specific; specific connections take precedence over general connections.  For example, aromatic carbon, aromatic oxygen and aromatic sulfur atoms have nothing but general connections; i.e., the fragment is the same no matter what is connected to the atom.  In contrast, there are 5 aromatic nitrogen fragments: (a) in a five-member ring, (b) in a six-member ring, (c) if the nitrogen is an oxide-type {i.e. pyridine oxide}, (d) if the nitrogen has a fused ring location {i.e. indolizine}, and (e) if the nitrogen has a +5 valence {i.e. N-methyl pyridinium iodide}; since the oxide-type is most specific, it takes precedence over the other four.  The aliphatic carbon atom is another example; it does not matter what is connected to -CH3, -CH2-, or -CH< , the  fragment is the same; however, an aliphatic carbon with no hydrogens has two possible fragments: (a) if there are four single bonds with 3 or more carbon connections and (b) any other not meeting the first criteria.
It became apparent, for various types of structures, that water solubility estimates made from atom/fragment values alone could or needed to be improved by inclusion of  substructures larger or more complex than "atoms"; hence, correction factors were added to the AFC method.  The term "correction factor" is appropriate because their values are derived from the differences between the water solubility estimates from atoms alone and the measured water solubility values.  The correction factors have two main groupings: first, factors involving aromatic ring substituent positions and second,  miscellaneous factors.  In general, the correction factors are values for various steric interactions, hydrogen-bondings, and effects from polar functional substructures.  Individual correction factors were selected through a tedious process of correlating the differences (between solubility estimates from atom/fragments alone and measured solubility values) with common substructures.
Results of two successive multiple regressions (first for atom/fragments and second for correction factors) yield the following general equation for estimating water solubility of any organic compound:

log WatSol (moles/L)  = Σ(fi * ni)  + Σ(cj * nj)  +  0.24922
(n = 1128,  correlation coef (r2) = 0.940,  standard deviation = 0.537, avg deviation = 0.355)

where   Σ(fi * ni)   is the summation of  fi  (the coefficient for each atom/fragment)   times  ni  (the number of times the atom/fragment occurs in the structure) and Σ(cj * nj)  is the summation of  cj  (the coefficient for each correction factor) times  nj  (the number of times the correction factor is applied in the molecule).

GLP compliance:

no

Type of method:

other: calculation

Water solubility:

0.001 mg/L

Conc. based on:

act. ingr.

Remarks on result:

other: calculated

Remarks:

WSKOW v1.42

Key result

Water solubility:

0.003 mg/L

Conc. based on:

act. ingr.

Remarks on result:

other: calculated

Remarks:

WATERNT (v1.01 est)

Conclusions:

The water solubility of Disperse Blue 291:1 Cl is calculated to be 0.001246 mg/L by WSKOW and 0.0027869 mg/L by WATERNT

Executive summary:

The water solubility of Disperse Blue 291:1 Cl was calculated with WSKOW v1.42 and WATERNT v1.01 included in EpiSuite 4.1. to be 0.001246 mg/L and 0.0027869 mg/L, respectively. Hence, the test substance is nearly insoluble in water.

Reference 4

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

March 31, 2015

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

unsuitable test system

Remarks:

for water insoluble substances the column elution method has to be used

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

not specified

GLP compliance:

no

Type of method:

flask method

Water solubility:

< 20 mg/L

Temp.:

20 °C

pH:

ca. 6.15

Remarks on result:

other: pH satured solution = 6.28

Considering that the product was not completely soluble in reference solution, and that the absorbance of the test solutions were below the sensibility limit of the instrument in visible region, just an approximate solubility value was determined.

Conclusions:

Considering that the product was not completely soluble in reference solution, and that the absorbance of the test solutions were below the sensibility limit of the instrument in visible region, just an approximate solubility value was determined ( << 20 mg/l ).

Executive summary:

Method:

The substance has been tested for water solubility according to the flask method as reported in the OECD 105 Guideline.

 

Results:

Considering that the product was not completely soluble in reference solution, and that the absorbance of the test solutions were below the sensibility limit of the instrument in visible region, just an approximate solubility value was determined ( << 20 mg/l ).

The substance is slightly insoluble in water.

Description of key information

The water solubility of the test item Disperse Blue 291.1 Br at a temperature of 20 °C was determined according to the column elution method. It was found to be below the quantification limit of 52.2 µg/L. Due to the close structural similarity of the source and target substances Disperse Blue 291.1 Br and Disperse Blue 291.1 Cl, respectively, a similar poor water solubility is expected for the target substance.

Using EpiWin calculation models, the water solubility estimated from the calculated partition coefficient of 6.67 for the bromo variant and 6.43 for the chloro variant was 0.41 µg/L and 1.2 µg/L, respectively. The estimation of the WATERNT Program (estimation of water solubility by fragments), led to values for water solubility of 2.5 and 2.8 µg/L for the bromo and chloro variant, respectively.

A test for water solubility with Disperse Blue 291.1 Cl using the shake flask method (not a suitable method for poorly water soluble substances) showed a water solubility of < 20 mg/L.

Based on these data, the estimated value of the WATERNT Program of 2.8 µg/L was chosen as the most valid one.

Key value for chemical safety assessment

Water solubility:

2.8 µg/L

at the temperature of:

25 °C