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Physical & Chemical properties

Partition coefficient

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Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06 Nov 2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
log Pow estimated based on solubility in 1-octanol and in water. A limit of solubility in 1-octanol was determined (< 20 mg/L), therefore a clear log Pow cannot be estimated.
Cross-referenceopen allclose all
Reason / purpose:
reference to other study
Reference
Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 Sep - 31 Oct 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 105 (Water Solubility)
GLP compliance:
no
Type of method:
flask method
Water solubility:
820 g/L
Incubation duration:
>= 24 - <= 72 h
Temp.:
20 °C
pH:
4.53
Remarks on result:
other: pH reported for a 40% sample solution

Calibration

The calibration of the analytical method resulted in the following calibration curve:

R-Square: 99.8813%

Offset: -0.1313

Slope: 0.1038

Curve: 0.0006

 

 

Study results

The concentrations of the different test solutions were calculated automatically using the equation of the calibration curve. The results are summarised in the table below:

 

Incubation time

[hours]

Water solubility

[g/L]

Average

[g/L]

24

810

820±10.0

48

830

72

820

 

The water solubility of the test item at 20 °C is 820 ± 10.0 g/L (standard deviation).

The pH value of a sample solution (40%) was 4.53.

Reason / purpose:
reference to other study
Reference
Endpoint:
solubility in organic solvents / fat solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 Sep - 31 Oct 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guideline 105
Version / remarks:
According to ECHA “Guidance on Information Requirements and Chemical Safety Assessment - Chapter R.7a: Endpoint specific guidance” (version 6.0, 2017), table “Table R.7.1-6 Methods for determination of partition coefficient n-octanol/water”, there is no current guideline to measure the solubility in octanol. A test method can be based on the principled of OECD Guideline 105.
GLP compliance:
no
Medium:
n-octanol
Solubility:
< 20 mg/L
Temp.:
20 °C
Test substance stable:
not determined

Calibration

The calibration of the analytical method resulted in the following calibration curve:

R-Square: 99.8813%

Offset: -0.1313

Slope: 0.1038

Curve: 0.0006

 

 

Study results

The concentrations of the different test solutions were calculated automatically using the equation of the calibration curve. The results are summarised in the table below:

 

Test muxture

Time [h]

Average of test item [mg/L]

Total average of test item [mg/L]

1

24

< 20

< 20

2

48

< 20

3

72

< 20

 

n-Octanol solubility of the test item Sodium Hydroxymethanesulphonate is < 20 mg/L.

The n-octanol solubility was determined at 20 °C.

Reason / purpose:
reference to other study
Reference
Endpoint:
partition coefficient
Remarks:
Octanol/Water partition coefficient as a function of pH (LogD)
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
ARChem SPARC. version 4.6

2. MODEL
LogD

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables".

5. APPLICABILITY DOMAIN
See information provided in "Any other information of materials and methods incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Qualifier:
according to
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
Calculation based on SPARC version v4.6, "LogD" model

- Software tool(s) used including version: SPARC v4.6
- Model(s) used: LogD
SPARC calculates the liquid-liquid distribution coefficient as a function of pH. The calculation method conbines the output of two other models: the octanol / water partition coefficient (LogPow) model included in the "Properties" section, and the pKa (dissociation constant) model.
The LogPow is obtained by combining the calculated activities at infinite dilution of the molecular species of interest in each of the liquid phases, as described by Hilal et al. 2004.
For the pKa calculation, SPARC breaks the molecule into two type of functional units: the reaction center (with known chemical properties) and the perturber. pKa of the reaction center is adjusted for the molecule in question using the mechanistic perturbation models.
For the complete method's description see field 'Any other information on materials and methods incl. tables'.
The datasets used for the LogPow and pKa models development and for the external validation are described in the field 'Any other information on materials and methods incl. tables'.
- Model description: see field 'Any other information on materials and methods incl. tables'.
- Justification of QSAR prediction: see field 'Justification for type of information' and 'overall remarks'.
GLP compliance:
no
Type of method:
other: QSAR
Partition coefficient type:
octanol-water
Type:
log Pow
Partition coefficient:
-7.419
Temp.:
20 °C
pH:
5
Remarks on result:
other: LogD calculated at pH 5
Type:
log Pow
Partition coefficient:
-7.558
Temp.:
20 °C
pH:
7
Remarks on result:
other: LogD calculated at pH 7
Type:
log Pow
Partition coefficient:
-7.56
Temp.:
20 °C
pH:
9
Remarks on result:
other: LogD calculated at pH 9

QSAR result. For detailed description of the model and its applicability, see "Any other information of materials and methods incl. tables".

LogD results

pH

LogD

 

pH

LogD

0

-3.386

7.5

-7.559

0.5

-3.651

8

-7.56

1

-4.038

8.5

-7.56

1.5

-4.496

9

-7.56

2

-4.981

9.5

-7.561

2.5

-5.473

10

-7.562

3

-5.964

10.5

-7.566

3.5

-6.441

11

-7.58

4

-6.875

11.5

-7.621

4.5

-7.214

12

-7.729

5

-7.419

12.5

-7.958

5.5

-7.51

13

-8.32

6

-7.543

13.5

-8.765

6.5

-7.555

14

-9.246

7

-7.558

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: EU Method A.8 - Appendix 1 (Partition Coefficient - Estimation method)
Version / remarks:
May 2008
Qualifier:
according to
Guideline:
other: Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specific guidance
Version / remarks:
Version 4.1, October 2015
GLP compliance:
no
Type of method:
estimation method (solubility ratio)
Partition coefficient type:
octanol-water

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Partition coefficient
Type:
log Pow
Partition coefficient:
< -4.6
Temp.:
20 °C
Remarks on result:
other: Estimation method, no pH measured.

Any other information on results incl. tables

The partition coefficient of the test item is calculated from the individual solubilities of the test item in water and 1-octanol, respectively.

 

Water solubility of the test item is 820 ± 10.0 g/L (standard deviation), report 18-13688/1-4.

 

n-Octanol solubility of the test item is < 20 mg/L, report 18-13688/1-5.

 

Pow = solubility of test item in 1-octanol / solubility of test item in water

Pow = (< 20 mg/L / 820 g/L)

Pow < (0.02 g/L / 820 g/L)

Pow < 2.4E-5

log Pow < -4.6

The partition coefficient of the test item was calculated from the individual solubilities in 1-octanol and water at 20 °C, respectively. The log Pow value can be reported as: log Pow < -4.6

Applicant's summary and conclusion

Conclusions:
The partition coefficient of the substance is estimated to be < -4.6 (EU Method 1.8 - Estimation method, supported by LogD calculation).
Executive summary:

Earlier investigations showed that neither the shake flask nor the HPLC methods were applicable for the determination of the log Pow of the substance. The estimation method (as described within EU Method A.8) based on indivisual solubilities in water and in octanol was selected. As the solubility in octanol resulted as a limit value (< 20 mg/L), no precise log Pow could be calculated. Furthermore, the substance is ionisable, hence the evaluation of the influence of pH on the log Pow was considered as relevant. For these two reasons, the LogD calculation by means of the QSAR model implemented in the ARChem SPARC software was performed and is used as supporting information.

 

A log Pow < -4.6 (at 20 °C) was estimated by the solubility ratio.

The results of the QSAR LogD calculation support the estimated log Pow: LogD at 20 °C = -7.419 (pH 5), -7.558 (pH 7), -7.56 (pH 9)