Registration Dossier

Administrative data

Endpoint:
water solubility
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
March 30th, 2018
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

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: REACH Guidance on QSARs R.6 (QSPR model adapted specifically from OECD test guideline 105)
Principles of method if other than guideline:
Principle:
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 Guideline for Testing of Chemicals No. 105, "Water Solubility".
In the majority of cases data were obtained from shake flask experiments in which approximately 5 times the quantity of test substance expected to saturate the desired water volume is added to ultra-pure water solubility in three appropriate vessels, closed and agitated using fairly high energy (head-over-heels shaker, or other forms of vigorous mixing) at 30 °C for 24, 48 and 72 hours. Each flask is allowed 24 hours of further equilibration at 20 or 25°C and the contents generally centrifuged and the concentration of test substance measured.
An adaptation from the standard shake-flask method (slow-stir method) is recommended for liquids with an expected solubility <10 mg.L-1 (slow-stir method). Instead of high energy agitation, flasks containing a tap close to the bottom are nearly filled by ultra-pure water, covered by a thin layer of the test item and slow stirred (approximately 100 RPM or less). The aim of this method is to prevent the formation of emulsions that can occur with the shake flask method and lead to a solubility overestimation. The water solubility is given by the mass concentration in water when this has reached a plateau as a function of time.
In rare cases data has been taken from studies performed using a second method described in OECD guideline 105 (2), the column elution method (recommended for solids with water solubility below 10 mg.L-1) in which the substance is coated onto beads in a column generator and water circulated in an attempt to saturate the circulating water. The solution is passed through the column at different flow rates such that the degree of saturation can be ascertained.
GLP compliance:
no
Type of method:
other: QSPR model adapted specifically from OECD test guideline 105

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Smiles: CCCCCCCCCCCCCCCCCCOCC(O)CO
data used as the input: log KOW = 7.8

Results and discussion

Water solubility
Key result
Water solubility:
ca. 0.004 mg/L
Conc. based on:
test mat.
Temp.:
20 °C
Remarks on result:
other: No pH measured because result calculated by QSAR.

Applicant's summary and conclusion

Executive summary:

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.

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 (mg test item.L-1) at 25°C: 4.26E-03

-95% confidence limits (mg test item.L-1): 3.49E-03 – 5.22E-03