Dibutyl [[bis[(2-ethylhexyl)oxy]phosphinothioyl]thio]succinate

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

7 November 2017 to 12 October 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

no

GLP compliance:

no

Type of method:

column elution method

Specific details on test material used for the study:

CAS No.: 68413-48-9
Purity: 84%
Description: Pale yellow, clear liquid

Water solubility:

0 mg/L

Conc. based on:

act. ingr. (total fraction)

Temp.:

25 °C

Remarks on result:

other: Preliminary results using EPI Suite

Key result

Water solubility:

1.2 µg/L

Conc. based on:

test mat.

Temp.:

20 °C

pH:

5

Remarks on result:

other:

Remarks:

The standard deviation is 0.11 micro g/L.

Prior to the definitive test, three failed definitive tests were conducted. In addition, the initial analytical method used in support of these tests was modified and revalidated.

The first water solubility column elution test system was set up on 9 March 2018 and was allowed to equilibrate until 16 March 2018, at which time it was sampled. Difficulties with variable sample results and results above the standard curve prevented the production of reliable results until 18 April 2018. These results confirmed that the set of results from 16 March 2018 (25 mL/hr column flow) did not meet guideline acceptance criteria when compared with the second day’s, 17 March 2018, results (12.5 mL/hr column flow). The percent difference between the two interval’s results was >30% (guideline criteria). Therefore, a second definitive sampling was performed on this column. Results of these two analyses indicated the column had failed with extremely variable results. A second water solubility column elution test system (new column) was set up on 1 June 2018, and the column was sampled on 7 June 2018. This represented the third attempt at a definitive experiment. The analysis of the day 1 and 2 intervals failed due to variable sample results and results that exceeded the standard curve. A second sampling of the second column was performed on 18 June 2018, which represented the fourth definitive test. The first analysis of the two sample sets failed for similar reasons. It was decided at this time that the original validated method was not suitable for the analysis of these samples and a modified analytical method was developed and validated.

Due to the highly variable results and consistent failure of standard curves, the original validated analytical method was re-valuated. The QC failure rate highlights the difficulty with quantitation of the test material at very low concentrations. Analysis of butanedioic acid, 2-[[bis[(2- ethylhexyl)oxy]phosphinothioyl]thio]-, 1,4-dibutyl ester presented many challenges due to its chemical properties. Butanedioic acid, 2-[[bis[(2-ethylhexyl)oxy]phosphinothioyl]thio]-, 1,4-dibutyl ester is highly non-polar with a very low water solubility (low ppb range) and a high partition coefficient (Log Kow >6.5. These properties cause the test substance to be strongly retained on typical reversed-phase columns, and require low concentration calibration curves. During the re-validation, the concentration of the LOQ fortification samples (0.010 µg/L) needed to be prepared at a concentration close to the lowest standard, 0.0050 ug/L, but within the calibration curve. This was done to achieve the lowest reasonably quantifiable concentration for the test substance in the water solubility samples. This increased the possibility of the LOQ QC sample recovery failure if the instrument peak area should fall below the low point on the curve. Additionally, strongly retained compounds can potentially experience matrix-related quantitation effects which can vary depending on the quantity and type of matrix present.

A direct dilution method validation with LC-MS/MS detection was initially performed. This met acceptance criteria for the validation. This methodology was successful in support of this testing, but was ultimately determined to be insufficiently robust to support the water solubility testing due to the analytical variability discussed above. A series of changes to the method were implemented to address this variability, which were primarily associated with the use of a different type of analytical column and which reduced the retention of the test substance during the analysis. These changes reduced the analytical variability and improved the robustness of the analytical method. This updated methodology was validated as part of the water solubility study and used in support of that testing.

Prior to the full validation of the modified method, all refrigerated system samples from fourth definitive test were reanalyzed with calibration standards using the new method. These results indicated the new method was suitable for the analysis. On 12 July 2018, the modified method was validated and samples from the fourth definitive test were re-diluted and reanalyzed. The reanalysis generated an acceptable standard curve; however, some sample responses were above the standard curve and required re-dilution. Analysis of the rediluted samples provided results that met all criteria for acceptance.

Conclusions:

The overall mean water solubility of the test substance is 1.2 ± 0.11 µg/L.

Executive summary:

In a study performed to the guideline OECD 105, the aqueous solubility of the test item has been determined to be 1.2 µg/mL at 20 °C, Smithers Viscient (ESG) Ltd. (2018).

Description of key information

In a study performed to the guideline OECD 105, the aqueous solubility of the test item has been determined to be 1.2 µg/L at 20 °C, Smithers Viscient (ESG) Ltd. (2018).

Key value for chemical safety assessment

Water solubility:

1.2 µg/L

at the temperature of:

20 °C