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Hydrolysis

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Description of key information

The test item showed a fast hydrolysis (T1/2=< 2.4 h) at pH 9 at 20 and 30 °C as well as a moderate hydrolysis (2.4 h >= T1/2=< 30 d) for the test conditions: pH 4 at 50 °C; pH 7 at 20, 30, 50 °C; pH 9 at 10 °C. At pH 4 at 20 and 30 °C, only a slow hydrolysis (T1/2 > 30 d) of the test item was observed.

Key value for chemical safety assessment

Half-life for hydrolysis:
86.4 h
at the temperature of:
20 °C

Additional information

Hydrolysis as a function of pH was determined according to OECD Guideline No. 111 and Council Regulation (EC) No. 440/2008, Method C.7 for the test item 1 ,6-Bis-(maleinimido)-2,2,4 -trimethylhexan (batch number: 0493122001) from 2014-10-16 to 2015-01-15. Analyses of the test item 1 ,6-Bis-(maleinimido)-2,2,4-trimethylhexan was performed via LC-DAD on a reversed phase column using an external standard. Two chromatographic methods were employed, as the analytical system had to be changed for the advanced testing. The analytical methods were validated with satisfactory results with regard to linearity, accuracy, precision and specificity.

The preliminary test was conducted with a test item concentration of 35 mg/L in buffer solutions at pH 4, 7 and 9 and 50 °C. For all pH values the advanced test was performed, as a significant reduction (> 10 %) of the test item concentration was observed in the preliminary test. The advanced test was conducted with a test item concentration of 35 mg/L in buffer solutions of pH 4 and 7 at temperatures of 20, 30 and 50 °C and at temperatures of 10, 20 and 30 °C for pH 9. Samples were taken at test start (0 h) and at at least 10 spaced points until test end. Buffer solutions were analysed at test start and test end and there was no analytical interference with the test item. Reaction rate constants and half-lives were calculated from the analysed samples based on a first respectively pseudo first order reaction kinetic model. The test item showed a fast hydrolysis (T1/2=< 2.4 h) at pH 9 at 20 and 30 °C as well as a moderate hydrolysis (2.4 h >= T1/2=< 30 d) for the test conditions: pH 4 at 50 °C; pH 7 at 20, 30, 50 °C; pH 9 at 10 °C. At pH 4 at 20 and 30 °C, only a slow hydrolysis (T1/2 > 30 d) of the test item was observed.

Transformation product signals were evaluated from the LC-DAD chromatograms of the definitive study. Major transformation products (≥ 10 % of the initial peak area of the parent molecule) were observed at retention time (RT; given in minutes) 0.48 (#1 and 2) for the pH 4 test medium and at RT 1.11 (#5 and 6) and 1.49 (#7 and 8) for the pH 7 and 9 test media. One further transformation product was postulated based on chemical deliberations and could be qualitatively verified at RT 0.28 (#3 and 4) (co-elution with buffer components) in the pH 4 test medium. Identification was performed via LC-MS/MS by postulation of possible transformation products based on molecule and molecule adduct signals and verification of the postulates by MS/MS experiments.

Identity and transformation pathways of the hydrolysis products were identified as follows:

RT0.48 was identified to be a mixture of 1-(6-amino-2,4,4-trimethylhexyl)-1H-pyrrole-2,5-dione and 1-(6-amino-2,2,4-trimethylhexyl)-1H-pyrrole-2,5-dione (#1 and #2, direct transformation products of the test item), which transformed into 2,2,4-trimethylhexane-1,6-diamine and 2,4,4-trimethylhexane-1,6-diamine (RT0.28, #4 and #3).

RT1.49 was identified to be a mixture of (2Z)-4-{[6-(2,5-dioxo-2,5-dihydro-1H-pyrrole-1-yl)-3,3,5-trimethylhexyl]amino}-4-oxobut-2-enoic acid and (2Z)-4-{[6-(2,5-dioxo-2,5-dihydro-1H-pyrrole-1-yl)-3,5,5-trimethylhexyl]amino}-4-oxobut-2-enoic acid (#7 and #8, direct transformation products of the test item), which transformed into (2Z)-3-({6-[(2E)-3-carboxyprop-2-enamido]-3,3,5-trimethylhexyl}carbamoyl)prop-2-enoic acid and (2Z)-3-({6-[(2E)-3-carboxyprop-2-enamido]-3,5,5-trimethylhexyl}carbamoyl)prop-2-enoic acid (RT 1.11, #5 and #6).

Mass balance was calculated for the test item and transformation product signals by evaluation of the LC-DAD chromatograms. Transformation products were quantified against the test item as standard. For RT 0.48 in the pH 4 test medium a response factor of two was applied due to the total elimination of one of two chromophoric group. The mass balance was calculated to be 58.5 – 95.3 % at pH4, 57.6 – 67.6 % at pH 7 and 56.7 – 72.3 % at pH 9

Reaction Rate Constants and Half-Lives of 1,6-Bis-(maleinimido)-2,2,4-trimethylhexan

 

 

pH4

pH7

pH9

20°C

30°C

50°C

20°C

30°C

50°C

10°C

20°C

30°C

Reaction rate constant kobs[1/s]

 

4.19x 10-8

 

9.13x 10-8

 

5.35x 10-7

 

2.23x 10-6

 

7.17x 10-6

 

5.69x 10-5

 

6.64x 10-5

 

2.20x 10-4

 

6.67x 10-4

Half-life T½

[min]

 

-

 

174

 

52.5

 

17.3

Half-life T½

[h]

 

45931

 

21091

 

360

 

86.4

 

26.8

 

3.38

 

2.90

 

0.875

 

0.289

Half-life T½

[d]

 

1911

 

87.91

 

15.0

 

3.60

 

1.12

 

0.141

 

-

Number of data points

 

11

 

11

 

11

 

11

 

11

 

10

 

11

 

11

 

10

Slope of regression

graph

 

 

Significantlynonzero

1)  = T½ extrapolated