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Water solubility

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Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
unsuitable test system
Remarks:
A standard OECD 105 study is inappropriate for the accurate measurement of water solubility of such a large hydrophobic molecule.
Qualifier:
according to guideline
Guideline:
OECD Guideline 105 (Water Solubility)
GLP compliance:
no
Type of method:
flask method
Water solubility:
ca. 0.006 g/L
Temp.:
20 °C
pH:
ca. 7.35
Water solubility:
ca. 0.001 g/L
Temp.:
20 °C
pH:
ca. 8.25
Water solubility:
ca. 0.003 g/L
Temp.:
20 °C
pH:
ca. 8.46
Details on results:
The water solubility of Phytosqualan® at 20 °C is 0.002 +/- 0.001 g/L
Conclusions:
Interpretation of results (migrated information): slightly soluble (0.1-100 mg/L)
Endpoint:
water solubility
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
21/04/2017
Reliability:
1 (reliable without restriction)
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:
See enclosed study report, QRPF and QMRF documents.
Principles of method if other than guideline:
The purpose of the in silico study was to determine the water solubility of test item in pure water at 25°C. The determination was performed using a regression method in which validated log KOW values are plotted against
the log of sub-cooled liquid water solubility from studies of high quality. These have been carried out using one of the methods recommended in the OECD guideline 105 or an adaptation of these.
Type of method:
other: QSPR model adapted specifically to OECD test guideline 105
Remarks:
The result below is the anticipated water solubility value following a study conducted according to OECD guideline 105 or acceptable modifications thereof (e.g. using a slow-stir method instead of shake flask).
Specific details on test material used for the study:
QSAR based on 2,6,10,15,19,23-hexamethyltetracosane chemical structure only
Key result
Water solubility:
>= 0 - <= 0 mg/L
Conc. based on:
other: Substance chemical structure
Remarks:
95% confidence limits
Temp.:
25 °C
Remarks on result:
other: pH not applicable
Remarks:
from structure, no pH dependency anticipated
Details on results:
anticipated water solubility value following a study conducted according to OECD guideline 105 or acceptable modifications thereof (e.g. using a slow-stir method instead of shake flask): 5.39.10-13 mg test item.L-1 at 25°C
Conclusions:
The water solubility is calculated as follows:
- water solubility at 25°C = 5.39.10-13 mg test item.L-1
- 95% confidence limits = 4.92.10-13 to 5.90.10-13 mg test item.L-1
Executive summary:

Introduction.

A Quantitative Structure-Property Relationship (QSPR) model was used to calculate the water solubility of the test item 2,6,10,15,19,23-hexamethyltetracosane. This QSPR model has been validated as a QSAR model to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004) and predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 105, "Water Solubility". The criterion predicted was the solubility in water in mg.L-1.

Methods.

The purpose of the in silico study was to determine the water solubility of test item in pure water at 25°C.

The determination was performed using a regression method in which validated log KOW values are plotted against the log of sub-cooled liquid water solubility from studies of high quality. These have been carried out using one of the methods recommended in the OECD guideline 105 or an adaptation of these.

Results.

The result below is the anticipated water solubility value following a study conducted according to OECD guideline 105 or acceptable modifications thereof (e.g. using a slow-stir method instead of shake flask). The water solubility is calculated as follows:

- water solubility at 25°C = 5.39.10-13  mg test item.L-1

- 95% confidence limits = 4.92.10-13 to 5.90.10-13  mg test item.L-1

Description of key information

The water solubility of the test substance has been first determined by performing a shake flask assay according to the OECD guideline n°105: “Water solubility”, adopted July, 27, 1995.

In fact, as initial considerations, the OCDE guideline mentioned that shake flask method covers solubilities above 10-2g/L. Therefore a preliminary test must be performed in order to ensure the method is applicable to the test substance. As a result of the preliminary test, the author concluded that 100 mL is still not enough to completely dissolve the test substance in water after 24h. Therefore the final test was carried out over 72 hours while the guideline recommends to allow more time (up to 96 hours) to ascertain that the flask method is a relevant test method for the substance. The water solubility of the substance at 20 °C was determined as 0.002 +/- 0.001 g/L as the mean of the three values obtained at 24, 48 and 72 hours. Nevertheless, there are significant differences between the individual daily results (for example reduction from 7, 5 and 6 mg/L in three replicates to 1, 2 and 1 mg/L of substance between 24 and 48 h suggesting that the substance formed emulsions in the test solution which led to inconsistencies). No indication is provided of the Limit of detection or quantification so it is not clear if the results are above or below the LOQ. Since the test substance is poorly soluble, the test should have been performed up to 96 hours. A final result of 3 mg/L was found at 72 hours. The study was repeated and a value of 1 mg/L was determined. A statement was made that the accuracy of the study is questionable due to the low solubility of the substance. This study cannot be considered an accurate determination of the water solubility and a qualitative value of <2 mg/L should be considered.

The result of the final test should not be considered as valid since the equilibrium time might not been reached, results between days are inconsistent and many details are not included in the report. Moreover the flask method is not adapted for such low water solubility and the likely emulsification of the substance during high energy mixing appears to have led to misleadingly high results.

A standard OECD 105 study is inappropriate for the accurate measurement of water solubility of such a large hydrophobic molecule. Therefore is it assessed as a "disregarded study", and such determination by calculation (QSAR) is currently the most appropriate method available.

To conclude, the only valid results are the ones from the study intitled "Determination of the water solubility of 2,6,10,15,19,23-hexamethyltetracosane - QSPR model adapted specifically to OECD test guideline 105" performed by Kreatis, 2017.

The result below is the anticipated water solubility by QSAR value following a study conducted according to OECD guideline 105 or acceptable modifications thereof (e.g. using a slow-stir method instead of shake flask). The water solubility is calculated as follows:

- water solubility at 25°C = 5.39.10-13  mg test item.L-1

- 95% confidence limits = 4.92.10-13 to 5.90.10-13  mg test item.L-1

Key value for chemical safety assessment

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

Additional information