N-isopropylmethacrylamide

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental Starting Date: 17 May 2012, Experimental Completion Date: 03 July 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 835.2110 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Performance of the Test:
Preparation of the Test Solutions:
Stock sample solutions were prepared in glass flasks at a nominal concentration of 1000 mg/L in the three buffer solutions. These were further diluted by a factor of 20 with the relevant buffer to give a nominal concentration of 50 mg/L. The concentration of each test solutions did not exceed the lesser of 0.01 mol/L or half the water solubility.

The test solutions were split into individual vessels for each data point.

The solutions were shielded from light whilst maintained at the test temperature.

Preliminary Test/Tier 1:

pH 4 sample solution: 50.6 mg/L
pH 7 sample solution: 50.3 mg/L
pH 9 sample solution: 50.5 mg/L

Sample solutions at pH 4, 7 and 9 were maintained at 50.0 ± 0.5 °C for a period of 120 hours.


Analysis of Sample Solutions:
The sample solutions were taken from the waterbath at various times and the pH of each solution recorded.

The concentration of the sample solution was determined by high performance liquid chromatography (HPLC).

Samples:
Aliquots were taken for analysis without any further treatment.

Standards:
Duplicate standard solutions of test item were prepared in glass double-distilled water at a nominal concentration of 50 mg/L.

Matrix blanks:
Glass double-distilled water and buffers.

Buffers:

Buffer solution
(pH) Components Concentration
(mmol dm-3)
4 Citric acid 12
Sodium chloride 8.8
Sodium hydroxide 13.6
7 Disodium hydrogen orthophosphate (anhydrous) 6
Potassium dihydrogen orthophosphate 4
Sodium chloride 4
9 Disodium tetraborate 2
Sodium chloride 4


These solutions were subjected to ultrasonication and degassing with nitrogen to minimize dissolved oxygen content.

Estimation method (if used):

Not used.

Details on test conditions:

Refer to details on sampling and analytical methods.

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

0.045 - 0.045 g/L

Duration:

120 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

0.044 - 0.045 g/L

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

0.045 - 0.045 g/L

Number of replicates:

Duplicate.

Positive controls:

no

Negative controls:

no

Statistical methods:

Not specified.

Preliminary study:

The mean peak areas relating to the standard and sample solutions are shown in table 3.23 (please see remarks on results including tables and figures section).

Test performance:

Validation:
The linearity of the detector response with respect to concentration was assessed over the concentration range of 0 to 101 mg/L. This was satisfactory with a correlation coefficient (r2) of 1.000 being obtained.

Transformation products:

not specified

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Other kinetic parameters:

None.

Details on results:

The estimated half-life at 25 °C for the test item at pH 4, 7 and 9 has been determined to be greater than 1 year.

Preliminary test/Tier 1

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

 

Table 3.23

 

Solution	Mean Peak Area
Standard 50.6 mg/L	9.0481 x 10^7
Standard 50.3 mg/L	8.9717 x 10^7
Initial Sample A, pH 4	8.8378 x 10^7
Initial Sample B, pH 4	8.8603 x 10^7
Initial Sample A, pH 7	8.7455 x 10^7
Initial Sample B, pH 7	8.7930 x 10^7
Initial Sample A, pH 9	8.9039 x 10^7
Initial Sample B, pH 9	8.8929 x 10^7
Standard 50.6 mg/L	8.9763 x 10^7
Standard 50.6 mg/L	9.0647 x 10^7
24 Hour Sample A, pH 4	8.8658 x 10^7
24 Hour Sample B, pH 4	8.8642 x 10^7
24 Hour Sample A, pH 7	8.7560 x 10^7
24 Hour Sample B, pH 7	8.7959 x 10^7
24 Hour Sample A, pH 9	8.9073 x 10^7
24 Hour Sample B, pH 9	8.8937 x 10^7
Standard 50.9 mg/L	9.0951 x 10^7
Standard 50.4 mg/L	9.1214 x 10^7
120 Hour Sample A, pH 4	8.8555 x 10^7
120 Hour Sample B, pH 4	8.9047 x 10^7
120 Hour Sample A, pH 7	8.7389 x 10^7
120 Hour Sample B, pH 7	8.6011 x 10^7
120 Hour Sample A, pH 9	8.9166 x 10^7
120 Hour Sample B, pH 9	8.9196 x 10^7

The test item concentrations at the given time points are shown in the following tables:

Table 3.24       pH 4 at 50°C

Time (Hours)	Concentration (g/L)		% of Initial
	A	B	A	B
0	4.48 x 10^-2	4.49 x 10^-2	-	-
24	4.50 x 10^-2	4.50 x 10^-2	100	100
120	4.46 x 10^-2	4.49 x 10^-2	99.4	100

Result:             Less than 10% hydrolysis after 5 days at 50 °C, equivalent to a half-life greater than 1 year at 25 °C.

Table 3.25      pH 7 at 50 ºC

Time (Hours)	Concentration (g/L)		% of Initial
	A	B	A	B
0	4.43 x 10^-2	4.46 x 10^-2	-	-
24	4.45 x 10^-2	4.47 x 10^-2	100	100
120	4.40 x 10^-2	4.33 x 10^-2	99.0	97.5

Result:             Less than 10% hydrolysis after 5 days at 50 °C, equivalent to a half-life greater than 1 year at 25 °C.

Table 3.26     pH 9 at 50 ºC 

Time (Hours)	Concentration (g/L)		% of Initial
	A	B	A	B
0	4.52 x 10^-2	4.51 x 10^-2	-	-
24	4.53 x 10^-2	4.52 x 10^-2	100	100
120	4.49 x 10^-2	4.49 x 10^-2	99.6	99.6

Result:             Less than 10% hydrolysis after 5 days at 50 °C, equivalent to a half-life greater than 1 year at 25 °C.

 

Validity criteria fulfilled:

yes

Conclusions:

The estimated half-life at 25 °C for the test item at pH 4, 7 and 9 has been determined to be greater than 1 year.

Executive summary:

Method

The determination was carried out using a procedure designed to be compatible with Method C7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 440/2008 of 30 May 2008, Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004 and Method 835.2110 of the OPPTS Guidelines.

 

The test system uses sterile buffer solutions at pH’s 4.0, 7.0 and 9.0.

Discussion

The test item was determined to be hydrolytically stable at pH 4, 7 and 9.

Conclusion

The estimated half-life at 25 °C for the test item at pH 4, 7 and 9 has been determined to be greater than 1 year.

Description of key information

The estimated half-life at 25 °C for the test item at pH 4, 7 and 9 has been determined to be greater than 1 year.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C

Additional information

The determination was carried out using a procedure designed to be compatible with Method C7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004.

 

The test system uses sterile buffer solutions at pH’s 4.0, 7.0 and 9.0.

Results at pH 4, pH 7 and pH 9 showed less than 10% hydrolysis after 5 days at 50 °C, equivalent to a half-life greater than 1 year at 25 °C.

As the test item was determined to be hydrolytically stable at pH 4, 7 and 9 (t_½ > 1 year at 25 °C) no additional testing was performed.