1,1'-(4-methyl-1,3-phenylene)bis-1H-pyrrole-2,5-dione

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-02-29 to 2017-07-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

(2004)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May, 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1,1'-(4-methyl-1,3-phenylene)bis-1H-pyrrole-2,5-dione

EC Number:

229-175-3

EC Name:

1,1'-(4-methyl-1,3-phenylene)bis-1H-pyrrole-2,5-dione

Cas Number:

6422-83-9

Molecular formula:

C15H10N2O4

IUPAC Name:

1,1'-(4-methyl-1,3-phenylene)bis-1H-pyrrole-2,5-dione

Test material form:

solid: particulate/powder

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products:
For the preliminary test, samples were taken at test start (0 h) and test end (120 h)
For the advanced test, samples were taken at test start (0 h) and at a minimum of 8 spaced points for pH 4 and 7 (actual 10 for pH 4 and 9 for pH 7), normally between 10 and 90% of hydrolysis. Due to the rapid hydrolysis at pH 9, only 1 to 5 additional samples could be obtained.
- Sampling intervals/times for sterility check:
As the test duration was 120 h for each test condition, no determination of CFU was deemed necessary.

Buffers:

- pH: 4, 7, 9
- Type and final molarity of buffer:
Buffer solution pH 4:
0.18 g of NaOH and 5.7555 g of mono potassium citrate were dissolved in 500 mL double distilled water.
Buffer pH 7 (preliminary test):
0.7358 g of NaOH and 4.3012 g of KH2PO4 were dissolved in 500 mL double distilled water.
Buffer solution pH 7 (advanced test):
3.854 g of ammonium acetate were dissolved in 500 mL double distilled water.
Buffer pH 9:
0.426 g NaOH, 1.8638 g KCI and 1.5458 g H3BO3 were dissolved in 500 mL double distilled water.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: HPLC vials, volume: 4 mL
- Measures taken to avoid photolytic effects: Photolytic effects were avoided by using opaque water baths.
- If no traps were used, is the test system closed/open: closed

TEST MATERIAL
- Volume used/treatment: 2 mL
- Kind and purity of water: Double distilled water, ROTH; batches: 335233316, 415234632, 086239961; conductivity: ≤ 2.0 µS/cm, for Transformation products: HPLC grade water, VWR
- Preparation of test medium: 30 mg/L buffer pH 4, 7 and 9 with 1% acetonitrile, respectively. The test concentration was fixed at 30 mg/L, due to the sensitivity of the analytical method.
- Identity and concentration of co-solvent: Acetonitrile, ≤ 1 % (v/v)

OTHER TEST CONDITIONS
- Adjustment of pH: No

Duration of test

Duration of test 1

Duration:

54.8 h

pH:

4

Temp.:

20 °C

Initial conc. measured:

31.4 mg/L

Duration of test 2

Duration:

34.8 h

pH:

4

Temp.:

30 °C

Initial conc. measured:

30.5 mg/L

Duration of test 3

Duration:

8.83 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

30.9 mg/L

Duration of test 4

Duration:

24.3 h

pH:

7

Temp.:

20 °C

Initial conc. measured:

30.7 mg/L

Duration of test 5

Duration:

8.33

pH:

7

Temp.:

30 °C

Initial conc. measured:

30.7 mg/L

Duration of test 6

Duration:

1.78 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

32 mg/L

Duration of test 7

Duration:

1.22 h

pH:

9

Temp.:

5 °C

Initial conc. measured:

18.9 mg/L

Duration of test 8

Duration:

0.717 h

pH:

9

Temp.:

10 °C

Initial conc. measured:

17.4 mg/L

Duration of test 9

Duration:

0.18 h

pH:

9

Temp.:

20 °C

Initial conc. measured:

11.5 mg/L

Number of replicates:

Duplicates per pH value and sampling date, single injected

Positive controls:

no

Remarks:

according to guideline not necessary

Negative controls:

yes

Remarks:

Buffer solutions (pH value 4, 7 and 9 with 1% acetonitrile)

Results and discussion

Preliminary study:

In the preliminary test, no significant signal could be obtained for any pH condition after incubation at 50 °C for 120 h, corresponding to a degradation of 100%.

Transformation products:

yes

Identity of transformation products

Identity of transformation products 1

No.:

#1

Reference

Reference substance name:

Unnamed

Identity of transformation products 2

No.:

#2

Reference

Reference substance name:

Unnamed

Identity of transformation products 3

No.:

#3

Reference

Reference substance name:

Unnamed

Identity of transformation products 4

No.:

#4

Reference

Reference substance name:

Unnamed

Identity of transformation products 5

No.:

#5

Reference

Reference substance name:

Unnamed

Identity of transformation products 6

No.:

#6

Reference

Reference substance name:

Unnamed

Identity of transformation products 7

No.:

#8

Reference

Reference substance name:

Unnamed

Identity of transformation products 8

No.:

#9

Reference

Reference substance name:

Unnamed

Identity of transformation products 9

No.:

#10

Reference

Reference substance name:

Unnamed

Identity of transformation products 10

No.:

#11

Reference

Reference substance name:

Unnamed

Details on hydrolysis and appearance of transformation product(s):

- Formation and decline of each transformation product during test:
For all test conditions the In concentration vs. time plots have regression graphs with slopes significantly non zero (perfect line for pH 9 at 20 “C). Therefore first order reaction kinetics was applied for data computation. A confirmation of pseudo first order reaction kinetics with coefficients of determination > 0.8 could be obtained for all test conditions.

Total recovery of test substance (in %)

Total recovery of test substance (in %) 1

% Recovery:

11

pH:

4

Temp.:

20 °C

Duration:

54.8 h

Total recovery of test substance (in %) 2

% Recovery:

5

pH:

4

Temp.:

30 °C

Duration:

34.8 h

Total recovery of test substance (in %) 3

% Recovery:

7

pH:

4

Temp.:

50 °C

Duration:

8.83 h

Total recovery of test substance (in %) 4

% Recovery:

1

pH:

7

Temp.:

20 °C

Duration:

24.3 h

Total recovery of test substance (in %) 5

% Recovery:

2

pH:

7

Temp.:

30 °C

Duration:

8.33 h

Total recovery of test substance (in %) 6

% Recovery:

1

pH:

7

Temp.:

50 °C

Duration:

1.78 h

Total recovery of test substance (in %) 7

% Recovery:

2

pH:

9

Temp.:

5 °C

Duration:

1.22 h

Total recovery of test substance (in %) 8

% Recovery:

1

pH:

9

Temp.:

10 °C

Duration:

0.717 h

Total recovery of test substance (in %) 9

% Recovery:

4

pH:

9

Temp.:

20 °C

Duration:

0.183 h

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

Key result

pH:

4

Temp.:

20 °C

Hydrolysis rate constant:

0 s-1

DT50:

16.7 h

Type:

(pseudo-)first order (= half-life)

Dissipation DT50 of parent compound 2

Key result

pH:

4

Temp.:

30 °C

Hydrolysis rate constant:

0 s-1

DT50:

8.08 h

Type:

(pseudo-)first order (= half-life)

Dissipation DT50 of parent compound 3

Key result

pH:

4

Temp.:

50 °C

Hydrolysis rate constant:

0 s-1

DT50:

2.28 h

Type:

(pseudo-)first order (= half-life)

Dissipation DT50 of parent compound 4

Key result

pH:

7

Temp.:

20 °C

Hydrolysis rate constant:

0 s-1

DT50:

3.58 h

Type:

(pseudo-)first order (= half-life)

Dissipation DT50 of parent compound 5

Key result

pH:

7

Temp.:

30 °C

Hydrolysis rate constant:

0 s-1

DT50:

1.39 h

Type:

(pseudo-)first order (= half-life)

Dissipation DT50 of parent compound 6

Key result

pH:

7

Temp.:

50 °C

Hydrolysis rate constant:

0.001 s-1

DT50:

0.262 h

Type:

(pseudo-)first order (= half-life)

Dissipation DT50 of parent compound 7

Key result

pH:

9

Temp.:

5 °C

Hydrolysis rate constant:

0.001 s-1

DT50:

0.238 h

Type:

(pseudo-)first order (= half-life)

Dissipation DT50 of parent compound 8

Key result

pH:

9

Temp.:

10 °C

Hydrolysis rate constant:

0.002 s-1

DT50:

0.11 h

Type:

(pseudo-)first order (= half-life)

Dissipation DT50 of parent compound 9

Key result

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

0.005 s-1

DT50:

0.041 h

Type:

(pseudo-)first order (= half-life)

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes
- Anomalies or problems encountered (if yes): no

MAJOR TRANSFORMATION PRODUCTS
Major transformation products were observed at all pH values and temperatures.
At pH 4 and 20 “C Trans 10 and at 30 and 50 °C Trans 10 and 11 were identified as major transformation products.
At pH 7 and 20 °C Trans 2, 6 and 8, at 30 °C Trans 2 and 8 and at 50 °C Trans 2, 8 and 11 were identified.
At pH 9 and 5 and 10 °C Trans 8 and at 20 °C Trans 2 and 8 was identified.

PATHWAYS OF HYDROLYSIS
- Figures of chemical structures attached: No

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

In the present study conducted according to OECD guideline 111 (2004), 30 mg/L of the test substance were dissolved in three buffers, pH 4, 7 and 9 and incubated at different temperatures (5, 10, 20, 30, and 50°C). The test item showed a moderate hydrolysis rate (2.4 h ≤ t1/2 ≤ 30 d) for pH 4 at 20 and 30 °C as well as for pH 7 at 20 °C and a fast hydrolysis rate (t1/2 ≤ 2.4 h) for the remaining test conditions (pH 4 at 50 °C, pH 7 at 30 and 50 °C as well as for pH 9 at 5, 10 and 20°C), with the higher half-lives at acidic conditions. Major transformation products were observed at all pH values and temperatures.