Fatty acids, C18-unsatd., reaction products with acrylic acid and polyethylenepolyamines

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 June 2010 - 31 August 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was conducted in accordance with international guidelines in a GLP testing laboratory.

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:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: after 2.4hrs, 1 day and day 5
- Sampling method: Duplicate aliquots with no further treatment
- Sampling intervals/times for pH measurements: pH was sampled at various times
- Sampling intervals/times for sterility check: no check
- Sample storage conditions before analysis:no storage

Buffers:

- pH:
- Type and final molarity of buffer:
pH4: Potassium hydrogen phthalate 5 mmol dm-3
pH7: Disodium hydrogen orthophospate (anhydrous) 3 mmol dm-3
Potassium dihydorgen orthophospate 2 mmol dm-3
Sodium chloride 2 mmol dm-3
pH9: Disodium tetraborate 1 mmol dm-3
Sodium chloride 2 mmol dm-3

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Glass stoppered flasks
- Sterilisation method: Filtered through a 0.2 micron membrane filter
- Lighting: Shielded from light
- Measures to exclude oxygen: ultrasonication and degassing with nitrogen
- If no traps were used, is the test system closed/open: closed
- Is there any indication of the test material adsorbing to the walls of the test apparatus?: not noted
TEST MEDIUM
- Volume used/treatment: nominal 5g/l in buffer solutions
- Kind and purity of water: reverse osmosis
- Preparation of test medium: pH buffers
- Renewal of test solution: no
- Identity and concentration of co-solvent: n/a
OTHER TEST CONDITIONS
- Adjustment of pH: no

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

5.155 g/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

4.74 g/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

4.89 g/L

Number of replicates:

2 (A and B)

Positive controls:

no

Negative controls:

no

Statistical methods:

See results and discussion for calculations.

Preliminary study:

The mean total peak areas of each standard was corrected to a nominal concentration of 5.00 x 10^3 mg/L and the mean value taken. The concentration of the sample solutions (g/L) was calculated using the following equation:
Cspl=Pspl/Pstd * Cstd * D * 1/1000

where:
Cspl = sample conc. (g/L)
Pspl = mean total peak area of sample solution
Pstd = mean total peak area of standard solution, corrected to nominal standard concentration
Cstd = nominal standard conc. (5.00 x 10^3 mg/L)
D = sample dilution factor (1)

Solution Mean Total Peak Area
Standard 5.00 x 10^3 mg/L 2.884*10^4
Standard 5.15 x 10^3 mg/L 2.984*10^4
Initial Sample A, pH4 2.958*10^4
Initial Sample B, pH4 2.964*10^4
2.4 Hour Sample A, pH4 2.942*10^4
2.4 Hour Sample B, pH4 2.958*10^4
24 Hour Sample A, pH4 2.778*10^4
24 Hour Sample B, pH4 2.774*10^4
Standard 5.10 x 10^3 mg/L 3.051*10^4
Standard 5.17 x 10^3 mg/L 3.273*10^4
Initial Sample A, pH7 2.924*10^4
Initial Sample B, pH7 2.915*10^4
2.4 Hour Sample A, pH7 2.894*10^4
2.4 Hour Sample B, pH7 2.886*10^4
24 Hour Sample A, pH7 2.638*10^4
24 Hour Sample B, pH7 2.636*10^4
Standard 5.06 x 10^3 mg/L 2.939*10^4
Standard 5.09 x 10^3 mg/L 3.120*10^4
Initial Sample A, pH9 2.919*10^4
Initial Sample B, pH9 2.919*10^4
2.4 Hour Sample A, pH9 2.870*10^4
2.4 Hour Sample B, pH9 2.842*10^4
24 Hour Sample A, pH9 2.651*10^4
24 Hour Sample B, pH9 2.622*10^4
Standard 5.02 x 10^3 mg/L 3.166*10^4
Standard 5.04 x 10^3 mg/L 2.852*10^4
120 Hour Sample A, pH4 4.712*10^3
120 Hour Sample B, pH4 4.905*10^3
Standard 5.08 x 10^3 mg/L 2.808*10^4
Standard 5.00 x 10^3 mg/L 3.007*10^4
120 Hour Sample A, pH7 2.066*10^4
120 Hour Sample B, pH7 2.083*10^4
Standard 5.08 x 10^3 mg/L 2.897*10^4
Standard 5.02 x 10^3 mg/L 2.783*10^4
120 Hour Sample A, pH9 2.031*10^4
120 Hour Sample B, pH9 2.107*10^4

Transformation products:

not specified

% Recovery:

>= 99.4 - <= 99.9

pH:

4

Temp.:

50 °C

Duration:

2.4 h

% Recovery:

>= 93.7 - <= 93.8

pH:

4

Temp.:

50 °C

Duration:

24 h

% Recovery:

>= 15.3 - <= 15.9

pH:

4

Temp.:

50 °C

Duration:

120 h

% Recovery:

>= 98.9 - <= 99.1

pH:

7

Temp.:

50 °C

Duration:

2.4 h

% Recovery:

>= 90.3 - <= 90.4

pH:

7

Temp.:

50 °C

Duration:

24 h

% Recovery:

>= 75.5 - <= 76.1

pH:

7

Temp.:

50 °C

Duration:

120 h

% Recovery:

>= 97.3 - <= 98.3

pH:

9

Temp.:

50 °C

Duration:

2.4 h

% Recovery:

>= 89.8 - <= 90.8

pH:

9

Temp.:

50 °C

Duration:

24 h

% Recovery:

>= 73.8 - <= 76.6

pH:

9

Temp.:

50 °C

Duration:

120 h

Key result

Remarks on result:

not determinable because of methodological limitations

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

pH 4 at 50.0 +/- 0.5^oC

	Time (Hours)
	0(A)	0(B)	2.4(A)	2.4(B)	24(A)	24(B)	120(A)	120(B)
Concentration (g/l)	5.15	5.16	5.12	5.15	4.83	4.83	0.788	0.82
% of mean initial concentration	-	-	99.4	99.9	93.8	93.7	15.3	15.9

Result: 15.6% (mean) test item remaining after 5 days at 50°C

pH 7 at 50.0 +/- 0.5°C

	Time (Hours)
	0(A)	0(B)	2.4(A)	2.4(B)	24(A)	24(B)	120(A)	120(B)
Concentration (g/l)	4.75	4.73	4.7	4.69	4.28	4.28	3.58	3.61
% of mean initial concentration	-	-	99.1	98.9	90.4	90.3	75.5	76.1

Result: 75.8% (mean) test item remaining after 5 days at 50C°

pH 9 at 50.0 +/- 0.5°C

	Time (Hours)
	0(A)	0(B)	2.4(A)	2.4(B)	24(A)	24(B)	120(A)	120(B)
Concentration (g/l)	4.89	4.89	4.81	4.76	4.45	4.40	3.61	3.75
% of mean initial concentration	-	-	98.3	97.3	90.8	89.8	73.8	76.6

Result: 75.2% (mean) test item remaining after 5 days at 50°C

Validity criteria fulfilled:

yes

Conclusions:

The percentage of initial concentration of test item remaining in solution after 5 days at 50oC and at pH4 is 15.6%.
The percentage of initial concentration of test item remaining in solution after 5 days at 50oC and at pH7 is 75.8%.
The percentage of initial concentration of test item remaining in solution after 5 days at 50oC and at pH9 is 75.2%.

Executive summary:

The hydrolysis of the test material (PR-4758) was measured in accordance with international guidelines in a GLP testing laboratory, however because of the complex nature of the UVCB substance it was not possible to calculate definitive half-lives of components within the test item, therefore the mean total peak area from the HPLC was calculated and used to determine degradation.

The percentage of initial concentration of test item remaining in solution after 5 days at 50oC and at pH4 was 15.6%, at. pH7 was 75.8% and at pH9 was 75.2%.

Although the test item was determined to be hydrolytically unstable under acidic conditions, no additional testing was performed because no definitive half-life would be expected to be obtained.

Description of key information

Abiotic degradation and hydrolysis: remaining substance = 15.6 %, 75.8 % and 75.2 % at pH 4, pH 7 and pH 9, respectively; No half-life obtained; OECD 111; Butler & White (2010)

Additional information

One key study exists measuring the abiotic degradation and hydrolysis of PR-4758. The study was conducted in accordance with OECD 111 and in accordance with GLP. As half-lifes were unobtainable, despite the substance being hydrolytically unstable at pH 4, further testing at pH 1.2 was not conducted. The reaction mechanism for each hydrolysis process was considered to complex to allow accurate assessment of half-lives as the substance is a complex mixture. Further the substance is stable under environmental pH's. The substance is not stable under some physiological pH's.