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Physical & Chemical properties

Water solubility

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Reference
Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
only DRAFT report available, the final report is expected later.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 105 (Water Solubility)
Principles of method if other than guideline:
Determination of the water solubility of test was only possible using NMR which leads to rather high LOQ. Other techniques as HPLC and mass spectrometry were technically not possible.
Different HPLC methods were tried as quantitation methods. The rapid degradation of the test item when applying chromatograph-ic conditions prevented the quantitation using HPLC.
Additionally, detection with high resolution mass spectrometry (HRMS) was performed. By direct injection, test item detected, but a quantitative statement cannot be concluded from this.
Overall, the determination was complicated further by the hydrolytic instability of the test item and the low water solubility.
For further details of the instability of the test item and the behaviour in water see GLP-study 20L00223 (hydrolysis as a function of the pH), from Competence Center Analytics, BASF SE, D-67056 Ludwigshafen.
Type of method:
other: NMR method
Key result
Water solubility:
< 0.2 mg/L
Conc. based on:
test mat. (total fraction)
Incubation duration:
4 h
Temp.:
23 °C
Remarks on result:
other: below the LOD
Details on results:
Determination of the water solubility using NMR
Method: The determination of the test item in water phases was performed using NMR.
Limit of detection (LOD): 29.97 mg of the test item were weighed into a 5 mL volumetric flask, filled with [D6]-acetone and diluted.
With a signal-to-noise-ratio of 3, the LOD was determined to be 0.2 mg/L.

The results of the flask method with stirring times of 24 h-72 h (see additional information) show a broad range of values without clear tendencies. This led to the assumption that the test item is unstable.
Hydrolysis experiments which confirm the instability in water were performed using NMR (see results under GLP-study no. 20L00223 (hydrolysis as a function of the pH), which refers to the endpoint 5.1.2.)
The hydrolysis mechanism described in literature4 could be con-firmed and TTZ was found as a hydrolysis product of the test item.
The corresponding masses were detected with HRMS as well.

The flask method with shortened stirring times was performed. The test item and TTZ were used for calibration.
Due to the same retention time of the test item and of TTZ (see Figure 4 on page 10 and Figure 5 on page 10) and the comparable UV-spectra of the peaks (see Figure 6 on page 11 and Figure 7 on page 11), it is most likely, that the chromato-graphic conditions already led to a degradation of the test item to TTZ. The test item and TTZ were analysed using normal phase chromatography (see next chapter). In hope that exclusion of water from the eluent might allow the chromatographic analysis of test item without hydrolysis caused by water from the eluent.

Conclusions:
The water solubility was determined to be below the LOD which is 0.2 mg/L

Description of key information

The solubility is below the LOD  which is 0.2 mg/L.

Key value for chemical safety assessment

Additional information

Determination of the water solubility of test item was only possible using NMR which leads to rather high LOQ. Other tech-niques as HPLC and mass spectrometry were technically not possible.
Different HPLC methods were tried as quantitation methods. The rapid degradation of the test item when applying chromatograph-ic conditions prevented the quantitation using HPLC.
Additionally, detection with high resolution mass spectrometry (HRMS) was performed. By direct injection, test item was detected, but a quantitative statement cannot be concluded from this.
Overall, the determination was complicated further by the hydrolytic instability of the test item and the low water solubility.
For further details of the instability of the test item and the behaviour in water see GLP-study 20L00223 (hydrolysis as a function of the pH), corresponding to endpoint 5.1.2.