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Water solubility

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Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 105 (Water Solubility)
Deviations:
yes
Remarks:
Please refer to principle of method.
Qualifier:
equivalent or similar to
Guideline:
EU Method A.6 (Water Solubility)
Deviations:
yes
Remarks:
Please refer to principle of method.
Principles of method if other than guideline:
During the method validation study the test item could not be recovered from ultrapure water due to its behaviour and volatile properties, therefore solubility pre-test was performed. The water solubility test based on the OECD 105, EC A.6 and OPPTS 830.7840 guidelines is technically not feasible. For the determination of water solubility with visual detection was performed according to the Study Plan. This process deviates from the guideline but is considered scientifically valid.
GLP compliance:
yes (incl. certificate)
Type of method:
flask method
Key result
Water solubility:
< 100 mg/L
Conc. based on:
test mat.
Temp.:
20 °C
pH:
7.12

Analytical results

Whether the sample was directly measured into aquatic media or spiked with organic solvent, the test substance immediately begun to move towards the surface of the water. That samples prepared in aqueous matrices were not homogeneous the phase separation. Thus, the entire sample volume was extracted with n-hexan but no improvement regarding the recovery was achieved. Thus, further trials according to the above mentioned protocol were performed.

 

The results were as follows:

 

Recovery of fortified samples

at 0.4 mg/L concentration level 32% (standard deviation 44%),

at 5 mg/L concentration level  63% (standard deviation 8%),

at 25 mg/L concentration level 65% (standard deviation 8%).

 

Recovery samples

Recovery samples from ultrapure water were prepared at 0.5 mg/L and 1.5 mg/L concentration levels. At 0.5 mg/L level the recovery was determined to be 57% (SD 76%) and at 1.5 mg/L the recovery was determined to be 28% (SD 34%).

 

Due to the high standard variation and the low recovery from aqueous media it was concluded that it was technically not possible to validate a suitable analytical method.

Water solubility test restuls

 

Water solubility test

Test Item, (mL)

Total volume of the volumetric flask (mL)

Observation

pH value

0.129

10

cloudy liquid, stains floating on the surface and the test item forms bubbles

-

50

cloudy liquid, stains floating on the surface and the test item forms bubbles

100

slightly cloudy liquid, stains floating on the surface and the test item forms bubbles

200

slightly cloudy liquid, stains floating on the surface and the test item forms bubbles

500

barely cloudy liquid, ring-shaped phase, small stains floating on the surface, droplets on the wall of the flask

1000

barely cloudy liquid, ring-shaped phase, small stains floating on the surface, droplets on the wall of the flask

7.12

Conclusions:
The water solubiltiy was determined to be below 100 mg/L.
Executive summary:

A study was conducted equivalent to OECD 105. During the method validation study the test item could not be recovered from ultrapure water due to its behaviour and volatile properties. Therefore determination of the water solubility and execution of the main test according to the OECD TG 105 neither using the shake flask nor the column elution method were technically feasible. Thus, based on this observation the preliminary test with visual detection was performed for the determination of the water solubility. A known amount of test item was added to an increased volume of water and the solutions were observed visually after 10 minutes of shaking. The test item was weighed by volume calculated by the know density of test item. After each addition of an amount of test item, the mixture was vigorously shaken by hand for 10 minutes, and then was checked visually at which step the test item has completely dissolved. If the test item does not dissolve, a new measurement was made in a larger volumetric flask. At the lowest concentration 100 mg (0.129 mL) of the test item was dissolved in 1 L of ultrapure water. A phase separation between water and test item was observed. It was technically not possible to test lower concentration as visual observation of a phase separation of lower volumes was not possible. Therefore, it was concluded that the water solubility is below 100 mg/L.

Endpoint:
water solubility
Data waiving:
study technically not feasible
Justification for data waiving:
other:
Justification for type of information:
In accordance with Annex XI section 2 of regulation (EC) No 1907/2006 the test was waived as testing is technically not possible. During the method validation study the test item could not be recovered from ultrapure water due to its behaviour and volatile properties. Furthermore, the substance cannot be detected using UV/VIS and the eluent is not compatible with LC/MS detection. Please refer to the study record for more details about the analytical trials. Thus, the determination of the water solubility using the flask method or the column elution method was not possible as the test item concentration in the water could not be determined. Please refer to the study records in IUCLID section 4.7, 4.8 and section 8 for more details about the analytical trials.
Endpoint:
water solubility
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
2019-05-08
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:
Please refer to the QMRF and QPRF files provided under the section attached justification.
Qualifier:
according to
Guideline:
other: ECHA Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals
Deviations:
no
Principles of method if other than guideline:
Calculation using WATERNT v1.01 as part of EPISUITE
GLP compliance:
no
Type of method:
other: Calculation
Specific details on test material used for the study:
SMILES: C(=CCCC(C=C)C)(C)C
Key result
Water solubility:
17.817 mg/L
Conc. based on:
test mat.
Temp.:
25 °C
Remarks on result:
other: The substance is within the applicability domain of the model. The calculation based on the uncharged molecule.
Conclusions:
Using WATERNT v1.01 the water solubility of the test item was calculated to be 17.817 mg/L at 25 °C. The substance is within the applicability domain of the model.
Executive summary:

The water solubility was calculated using WATERNT v1.01 as part of EPISuite v4.11 from US Environmental Protection Agency.

Using WATERNT v1.01 the water solubility of the test item was calculated to be 17.817 at 25 °C (EPI Suite, 2014).

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model is applicable to the query chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model is relevant for the regulatory purpose.

 

For assessment and jsutification of these 4 requirements the QMRF and QPRF files were developed and attached to this study record.

 

Description of the prediction Model

The prediction model was descripted using the harmonised template for summarising and reporting key information on (Q)SAR models. For more details please refer to the attached QSAR Model Reporting Format (QMRF) file. 

 

Assessment of estimation domain

The assessment of the estimation domain was documented in the QSAR Prediction Reporting Format file (QPRF). Please refer to the attached document for the details of the prediction and the assessment of the estimation domain.

Description of key information

The water solubility was calculated to be 17.817 mg/L at 25 °C.

Key value for chemical safety assessment

Water solubility:
17.817 mg/L
at the temperature of:
25 °C

Additional information

It was technically not possible to validate a suitable analytical method to determine the water solubility according to OECD TG 105. Thus, the available data were evaluated in an weight of evidence approach.

Testing technically not possible

In accordance with Annex XI section 2 of regulation (EC) No 1907/2006 the test was waived as testing is technically not possible. During the method validation study the test item could not be recovered from ultrapure water due to its behaviour and volatile properties. Furthermore, the substance cannot be detected using UV/VIS and the eluent is not compatible with LC/MS detection. Please refer to the study record for more details about the analytical trials. Thus, the determination of the water solubility using the flask method or the column elution method was not possible as the test item concentration in the water could not be determined. Please refer to the study records in IUCLID section 4.7, 4.8 and section 8 for more details about the analytical trials.

Experimental results

The study was conducted equivalent to OECD 105. During the method validation study the test item could not be recovered from ultrapure water due to its behaviour and volatile properties. Therefore determination of the water solubility and execution of the main test according to the OECD TG 105 neither using the shake flask nor the column elution method were technically feasible. Thus, based on this observation the preliminary test with visual detection was performed for the determination of the water solubility. A known amount of test item was added to an increased volume of water and the solutions were observed visually after 10 minutes of shaking. The test item was weighed by volume calculated by the know density of test item. After each addition of an amount of test item, the mixture was vigorously shaken by hand for 10 minutes, and then was checked visually at which step the test item has completely dissolved. If the test item does not dissolve, a new measurement was made in a larger volumetric flask. At the lowest concentration 100 mg (0.129 mL) of the test item was dissolved in 1 L of ultrapure water. A phase separation between water and test item was observed. It was technically not possible to test lower concentration as visual observation of a phase separation of lower volumes was not possible. Therefore, it was concluded that the water solubility is below 100 mg/L.

QSAR estimation

In this weight of evidence approache the water solubility was calculated using WATERNT v1.01 as part of EPISuite v4.11 from US Environmental Protection Agency.

Using WATERNT v1.01 the water solubility of the test item was calculated to be 17.817 at 25 °C (EPI Suite, 2014).

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model is applicable to the query chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model is relevant for the regulatory purpose.

 

For assessment and jsutification of these 4 requirements the QMRF and QPRF files were developed and attached to the study record.

Conclusion

It was technically not possible to validate a suitable analytical method to determine the water solubility according to OECD TG 105. Thus, the available data were evaluated in a weight of evidence approach. In a study according to the preliminary test as described in OECD TG 105, the water solubility was determined to be below 100 mg/L. The water solubility was estimated using WATERNT program. The substance is in the applicability domain of the model. Thus, the calculated water solubility of 17.817 mg/L was regarded as reliable and chosen as key value for chemical risk assessment.