Propylene dinonanoate

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 Jun - 19 Oct 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Reason / purpose for cross-reference:

other: Supporting QSAR evaluation

Reason / purpose for cross-reference:

other: Supporting QSAR evaluation

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

GLP compliance:

no

Type of method:

other: Slow-stirring method

Water solubility:

< 0.5 mg/L

Temp.:

20 °C

pH:

6

RESULTS OF THE PRELIMINARY STUDY

Test item quantity (mg)	104.2	104.2	104.2	104.2	104.2	106.31	106.31
Volume of water added (mL)	0.1	0.5	1	2	10	100	100
Time of shake (h)	0.10	0.10	0.10	0.10	0.10	0.10	48
Observation	Not dissolved *	Not dissolved *	Not dissolved *	Not dissolved *	Not dissolved *	Not dissolved *	Not dissolved *
Solubility observed (g/L)	1042.0	208.4	104.2	52.1	10.42	1.063	1.063

* Lot of suspended particles

 

Conclusion of the preliminary test: Due to the presence of lots of suspended particles at the tested solubility 1 g/L, the solubility is probably < 10 mg/L. So column method need to be used.

The behaviour of the test item like an oil permitted to anticipate that the loading of the column was a critical phase.

 

 

 

RESULTS OF THE COLUMN ELUTION METHOD

 

Quantification results and water solubility calculation

Microcolumn no.	Substance internal no.	Instance no.	Time of contact * (h)	Solubility results (mg/L)	Specifications
RRCo-000161_0001_C01	R01	1	17	0.550	-	The column is not at the equilibration plate after 21 h
		2	18	0.553	-
		3	19	0.580	-
		4	20	0.591	-
		5	21	0.600	-
			Average =	0.5748	-
			RSD =	3.9 %	< 30%
RRCo-000161_0001_C02		1	17	< LD**	-	Results very different than the column C01
		2	18	< LD**	-
		3	19	< LD**	-
	R01	4	20	< LD**	-
		5	21	< LD**	-
		6	24	0.824	-
			Average =	< LD**	-
			RSD =	%	< 30%
Average C01 & C02 =				N/A	-
Relative difference (C02 - C01)/C01 =				N/A	< 30%

* after launch of recirculating flow

** LD = Limit Detection = 0.167 mg/L. In the study RRCo-000160_01, the limit of quantification (LOQ) is evaluated at 0.5 mg/L so the limit of detection is estimated at 0.167 mg/L (LOQ/3).

 

Conclusion of the column elution method

The column elution method estimate a solubility between < 0.5 and 0.5 mg/L

As explained in the OECD guideline 105: “The loading of the support material may cause problems, leading to erroneous results, e.g. when the test substance is deposited as an oil. These problems should be examined and the details reported in the final report.”

So the deviation 1 was emitted with the following object:

“The two columns are not in the expected reproducibility due to the propensity of the test substance to behave as an oil (observation of two phases in the column headspace).”

The impact was “the column elution method is not applicable to this test substance.”

Then, the amendment 1 was done to propose an adaptation of the flask method.

 

 

 

RESULTS OF THE FLASK METHOD

 

Quantification results and water solubility calculation

	Sampling no.	Duration at 30 °C [h]	Duration at 20 °C [h]	Quantification result [mg/L]	Sampling difference	Average	Difference between the two last flasks
R01	1	24	24	2.94	31.13%	3,39
R02	1	24	24	3.85
R03	2	48	24	3.24	-12.83%	3.03	-10.67%
R04	2	48	24	2.82
R05	3	72	24	5.85	11.53%	6.18	103.87%
R06	3	72	24	6.52
R07	4	72	144	2.43	-36.57%	1.99	-67.86%
R08	4	72	144	1.54
Average =				3.65
Standard deviation =				1.71
Relative difference =				47%

 

Conclusion of the adaptation of the flask method

Regarding the results of the adaptation of the flask method, the solubility can be estimated about 3.63 mg/L with a RSD of 47 %. The validity criteria are not respected so the deviation 2 was emitted with the conclusion: “the flask method need to be adapted to this test substance” and an amendment was done to propose an adaptation of the flask method using a specific flasks (sampling by the bottom of the flask).

Then, the amendment 2 was done to propose an adaptation of the flask method: the slow stirring method.

 

 

 

RESULTS OF THE SLOW STIRRING METHOD

 

Quantification results and water solubility calculation

Flask no.	Sampling no.	Quantification results [mg/L]	Difference between the flask	Specification
R01	1	< LOQ*	N/A	< 30 %
	2	< LOQ*
	3	< LOQ*
R02	1	2.00	N/A	< 30 %
	2	1.7
	3	1.9
R03	1	< LOQ*	N/A	< 30%
	2	< LOQ*
	3	< LOQ*

* The limit of quantification (LOQ) of the method is validated at 0.5 mg/L

 

Conclusion of the adaptation of the flask method

The results of the slow stirring method demonstrate that the sampling realised in different flasks are not repeatable. This difference may be explained on the flask R02 by the presence of test item in the bottom tap.

The solubility of the test item at 20 ± 0.5 °C was estimated between < 0.5 and 2.0 mg/L with the slow stirring method.

 

 

 

CONCLUSION

The water solubility of the test item at 20.0 ± 0.5 °C was measured using tree different methods. No method demonstrates a sufficient performance to pass the validity criteria.

The column elution method estimate a solubility between < 0.5 and 0.5 mg/L.

The adapted shake flask method estimate a solubility about 3.63 mg/L with a RSD of 47 %.

The slow stirring method estimate a solubility between < 0.5 and 2 mg/L.

To conclude, the solubility of the DPPG was measured between < 0.5 (Limit of quantification of the analytical method) and 3.63 mg/L (maximum value measured with the shake flask method).

Conclusions:

The water solubility of the test substance is estimated to be < 0.5 mg/L at 20 °C and pH ca. 6.

Executive summary:

Three methods were used to determine the water solubility of the test item: column elution, flask and slow stirring. None of them demonstrated sufficient performance to pass the validity criteria.

Considering the results obtained with the slow-stirring method, measurement performed on samples from two flasks resulted consistently as below the limit of quantification of the GC-MS validated analytical method (0.5 mg/L). The results obtained from the samples of the third flask were higher (ca. 2 mg/L). This higher measurement was probably due to the presence of undissolved test item in the bottom tap, from where the sampling was performed. This would lead to including undissolved substance in the results of the GC-MS measurement and therefore to an overestimation of the water solubility. Based on this consideration the higher water solubility (ca. 2 mg/L) is disregarded and it is concluded that the water solubility of the test substance can be estimated to be < 0.5 mg/L (below limit of quantification of the analytical method).

QSAR results obtained with Wskowwin v1.42 (0.001508 mg/L at 25 °C) and Waternt v1.01 (0.0025422 mg/L at 25 °C) support the experimental estimation.

Description of key information

Water solubility <0.5 mg/L (Limit of quantification of the analytical method) at 20 °C, pH ca. 6 (OECD Guideline 105, slow stirring method)

Additional information

QSAR results obtained with Wskowwin v1.42 (0.001508 mg/L at 25 °C) and Waternt v1.01 (0.0025422 mg/L at 25 °C) support the experimental estimation.