Registration Dossier

Administrative data

Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 September 2017 - 03 October 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 105 (Water Solubility)
Version / remarks:
1995
Deviations:
no
Qualifier:
according to
Guideline:
EU Method A.6 (Water Solubility)
Version / remarks:
2014
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 830.7840 (Water Solubility)
Version / remarks:
1998
Deviations:
no
GLP compliance:
yes
Type of method:
column elution method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Physical appearance: white powder with lumps
- Test item storage: at room temperature protected from light

Results and discussion

Water solubility
Key result
Water solubility:
< 0.002 mg/L
Conc. based on:
test mat. (dissolved fraction)
Temp.:
20 °C
Remarks on result:
other: Despite several flow rate switches from 24 mL/h to 12 mL/h and elution over a total period of 6 days, this is considered the best possible value to achieve for water solubility of the substance.
Details on results:
Mean concentration in the water samples (n=10) obtained at the flowrate of 24 mL/h was 0.000761 mg/L. CV= 44%.
Mean concentration in the water samples (n=10) obtained at the flowrate of 12 mL/h was 0.00165 mg/L. CV= 30%.
Overall mean concnetration: 0.00121 mg/L. Maximum difference = 74%.

The mean concentrations of the samples taken at a flow rate of 24 and 12 mL/h were 0.04 and 0.01 mg/L, respectively. Since the concentrations decreased at 12 mL/h, the flow rate was increased to 24 mL/h and sampling was repeated. The mean concentration of the repeated series was 0.002 mg/L. The turbidity of the eluates was >0.2 NTU which indicated the presence of undissolved material.

After 4 days of further elution at a flow rate of 3 mL/min, the flow rate was increased to 24 mL/h and ten samples were taken. Thereafter the flow rate was halved and ten samples were taken. The results for the samples of this test are summarized above. The coefficients of variation (CV) of the test samples (n=10) at a flow rate of 24 and 12 mL/h were 44 and 30%, respectively. The turbidity of the eluates was 0.6 NTU at both flow rates, which indicated the presence of undissolved material.
Since 0.5 µm frits were used and since elution was performed over a total period of 6 days, it is not considered possible to obtain a more accurate value for water solubility. Based on the mean concentrations at 24 mL/h and 12 mL/h, it was decided to report water solubility to be <0.002 mg/L.

The pH of the aqueous samples was 6.3 and 6.4.

Any other information on results incl. tables

Small responses were observed in chromatograms of the blank column at the retention time of the test item. The maximum contribution to the samples was 5.1% based on peak area. This is considered negligible.

Applicant's summary and conclusion

Conclusions:
The water solubility of the substance at 20°C was determined to be < 0.002 mg/L.
The pH of the aqueous samples was between 6.3 and 6.4.
Executive summary:

The water solubility of the substance was determined using the column elution method in a GLP study according to EC A.6, OECD 105 and OPPTS 830.7840.

Quantification was performed by UPLC-MS/MS. Despite applying several flow rate switches from 24 to 12 mL/h and elution over a total period of 6 days, coefficients of variations of the tests were not <30%, and undissolved material was detected in the eluates (though 0.5 µm column end frits were used). Therefore, based on the mean measured concentrations at 24 mL/h and 12 mL/h, the water solubility at 20°C was concluded to be <0.002 mg/L.The pH of the aqueous samples was between 6.3 and 6.4.