Trihexadecyl citrate

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 October 2017 to 4 May 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

27 July 1995

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Other quality assurance:

ISO/IEC 17025 (General requirements for the competence of testing and calibration laboratories)

Type of method:

flask method

Test material

Test material information

Constituent 1

Reference substance name:

Trihexadecyl citrate

EC Number:

224-931-9

EC Name:

Trihexadecyl citrate

Cas Number:

4560-68-3

Molecular formula:

C55H106O6

IUPAC Name:

trihexadecyl citrate

Test material form:

liquid

Specific details on test material used for the study:

The test substance, Triisocetyl Citrate was allocated the Smithers Viscient code ESTS 262/17 for reference throughout the study.
Name: Triisocetyl Citrate
Physical state: Clear liquid
Arrival date: 4 September 2017
Re-test date: 4 September 2019
Storage conditions: Room temperature (15 to 30°C)

Results and discussion

Water solubility

Key result

Water solubility:

ca. 0.069 µg/L

Conc. based on:

test mat.

Incubation duration:

ca. 9 d

Temp.:

20 °C

pH:

> 5.22 - < 6.79

Details on results:

Analytical Procedure for Water Solubility Testing
The method was assessed against the criteria detailed in the following sections:
Specificity
Diluent and water control samples were free of any components that interfered with the analysis of Triisocetyl Citrate. The method was therefore considered specific for Triisocetyl Citrate. Example chromatograms of diluent and a water control sample are shown in Figure 2 and Figure 3 (attached).
Sensitivity
The lowest calibration standard used was 0.0005 µg/mL and this demonstrated sufficient sensitivity. The LOQ was 0.01 µg/mL. Example chromatograms of the lowest standard and the LOQ are shown in Figure 4 and Figure 7 (attached), respectively.
Linearity
Response of the LC/MS-ToF system to Triisocetyl Citrate was quadratic with a 1/x weighting, over the range 0.0005 to 0.05 μg/mL, with a correlation coefficient >0.99. The linearity of detector response was therefore established. Example chromatograms of the lowest and highest calibration standards are shown in Figure 4 and Figure 5 (attached)and a representative calibration plot is shown in Figure 6 (attached).
Accuracy (Recovery)
The accuracy of the spiked double-distilled water was within 70 to 110% mean recovery for 0.01 and 0.1 µg/mL recovery levels; the 0.001 µg/mL failed the acceptance criteria. However as the actual measured water solubility values were between 0.01 and 0.1 µg/mL these acceptable validation levels were sufficient. The full results are shown in Table 2 (attached). Example chromatograms of validation samples are shown in Figure 7 and Figure 8 (attached).

Precision (Repeatability)
The precision of the spiked double-distilled water had a percent standard deviation (%RSD) of < 20% for 0.01 and 0.1 µg/mL. The full results are shown in Table 2 (attached). Example chromatograms of validation samples are shown in Figure 7 and Figure 8 (attached).



The water solubility test was initiated on 13 March 2018 at 08:25 and finished on 23 March 2018 at 07:55. The test temperature was set at 20 ± 0.5°C. The actual temperature measured during the test ranged from 19.6°C to 20.7°C with a mean temperature of 19.9°C. The higher 20.7°C was caused by the incubator door being opened in order to place the test vessel inside; the temperature was out of specification for 15 minutes which is not considered significant.

The sampling times and pH measurements are shown in Table 7 (attached) and the water solubility results shown in Table 8 (attached).

For the analysis, 8 mL of water was taken from the vessels and 2 mL THF added to the samples. The control was treated in like manner. During the test, it was found that the solubility was higher than expected, so the samples were further diluted fivefold, to be within the calibration range.

The samples were found to be within the validation range and a mean water solubility concentration of 0.069 µg/mL was found with a %RSD of 15.7 % between the two test vessels. Example chromatograms are shown in Figure 26 to Figure 28 (attached).

Applicant's summary and conclusion

Conclusions:

The water solubility of the test substance was found to be 0.069 µg/l at 20 °C, under the conditions of the test.

Executive summary:

In this guideline (OECD 105) study, [conducted with GLP certification], the water solubility of the test substance was found to be 0.069 µg/l at 20 °C.