Registration Dossier

Administrative data

Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 May 2011 - 11 July 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method A.6 (Water Solubility)
Deviations:
yes
Remarks:
Shaking at 30°C and equilibration at 20°C periods were reduced. The results showed no indication of an increasing trend in concentration with time; therefore it was considered that using longer times was not required.
Principles of method if other than guideline:
The test was modified from that in the test guidelines, in that the shaking at 30°C and equilibration at 20°C periods were reduced. This was to reduce the amount of hydrolysis of the test item as it was known to contain a hydrolytically unstable functional group. The results showed no indication of an increasing trend in concentration with time; therefore it was considered that using longer times was not required.
GLP compliance:
yes (incl. certificate)
Type of method:
flask method

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Water solubility
Water solubility:
<= 0 g/L
Temp.:
20 °C
Remarks on result:
other: The water solubility of the test item has been determined to be less than or equal to 0.000114 g/L of solution at 20.0 ± 0.5°C.

Any other information on results incl. tables

Preliminary test

The preliminary estimate of water solubility was 1.89 x 10-5g/L.

Definitive test

The mean peak areas relating to the standard and sample solutions are shown in the following table:

 

Solution

Mean Peak Absorbance

Standard 0.20 mg/L

4.967 x 105

Standard 0.20 mg/L

5.178 x 105

Sample blank

3.643 x 104

Sample 1A

3.419 x 105

Sample 1B

4.268 x 105

Sample 2A

2.202 x 106

Sample 2B

2.112 x 106

Sample 3A

2.206 x 105

Sample 3B

1.780 x 105

 

The concentration (g/L) of test item in the sample solutions is shown in the following table:

Sample Number

Time Shaken at 30°C (hours)

Time Equilibrated

at 20°C (hours)

Concentration

(g/L)

Corrected

Concentration

(g/L)

 

Solution pH

 

1

1

0.5

1.10 x 10-5

4.08 x 10-5

6.9

2

2

0.5

6.69 x 10-4

1.14 x 10-4

6.7

3

3

0.5

5.14 x 10-5

1.19 x 10-5

6.9

 

Overall corrected concentration: 1.14 x 10-4g/L at 20.0 ± 0.5°C

Validation

The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 0 to 0.4 mg/L. This was satisfactory with a correlation coefficient of 1.000 being obtained.

Recovery of analysis of the sample procedure was assessed and proved adequate for the test. Recovery data is shown in the following table:

Nominal Concentration

(mg/L)

Recovery Range (%)

Mean Recovery (%)

0.01

23.7 to 32.0

26.9

0.01*

21.3 to 27.7        

24.9

0.1

57.9 to 59.4

58.6

0.5

72.3 to 78.9        

76.0

 

Sample concentrations have been corrected for recovery of analysis (see Discussion).

* glassware used was silanized with dichlorodimethylsilane to assess any adsorption issues.

Discussion

The test was modified from that in the test guidelines, in that the shaking at 30°C and equilibration at 20°C periods were reduced. This was to reduce the amount of hydrolysis of the test item as it was known to contain a hydrolytically unstable functional group. The results showed no indication of an increasing trend in concentration with time; therefore it was considered that using longer times was not required.

As can been seen in the Validation section, the recovery efficiency decreased as the sample concentration reduced. The exact reason(s) for this was not discovered, but may have been due to hydrolysis and/or adsorption. It was still necessary to correct the sample concentrations to reflect the recovery efficiency and as the individual results varied, different recovery percentages were chosen. The preliminary sample, sample 1 and 3 were all considered closest to the 0.01 mg/L recovery level, so 26.9% was used for the correction. Similarly for sample 2, 58.6% was used. Although this approach would not produce an absolute quantitative result, it never the less made allowance for analytical procedures and provided a realistic result for the water solubility.

A calculated value for the water solubility using WSKOW v1.41 @ 2000 U.S. Environmental Protection Agency based on information on the test item provided by the Sponsor was 0.55 mg/L.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): insoluble (< 0.1 mg/L)
The water solubility of the test item has been determined to be less than or equal to 0.000114 g/L of solution at 20.0 ± 0.5°C.
Executive summary:

Less than or equal to 0.000114 g/L of solution at 20.0 ± 0.5°C using the flask method in accordance with Method A6 Water Solubility of Commission Regulation (EC) No 440/2008 of 30 May 2008.