Registration Dossier

Diss Factsheets

Environmental fate & pathways

Hydrolysis

Currently viewing:

Administrative data

Link to relevant study record(s)

Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Non-GLP study conducted to OECD 111. However, a number of deviations from the guideline were recorded.
Qualifier:
according to guideline
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Deviations:
yes
Remarks:
Guideline regarding temperature variation (50 ± 0.5°C) not fulfilled
Principles of method if other than guideline:
The demands of the guideline regarding sterility and temperature variation (50 ± 0.5°C) were not fulfilled (the heating cabinet instruction manual stated that the temperature should not vary more than ± 0.4°C, this was however not controlled), but considered to be of little significance to the result.
GLP compliance:
not specified
Remarks:
The demands of the guideline regarding sterility and temperature variation (50 ± 0.5°C) were not fulfilled, but considered to be of little significance to the result. See notes in the field above.
Radiolabelling:
no
Analytical monitoring:
no
Details on sampling:
Tier 1: Sampling interval for the parent/transformation products: 5 days
Tier 2 (pH 9 only): 0, 3, 7, 24, 31, 48, 55, 76,, 150 and 172 hours.
Buffers:
pH 4 buffer: pH 4 ± 0.01 (20°C) (citric acid/sodium hydroxide/hydrogen chloride)
pH 7 buffer: pH 7 ± 0.01 (20°C) (di-sodium hydrogen phosphate/potassium di-hydrogen phosphate)
pH 9 buffer: pH 9 ± 0.01 (20°C) (boric acid/potassium chloride/sodium hydroxide)

All water used were of grade 1 according to EN-ISO 3696-1995.
Details on test conditions:
Tier 1, Preliminary test

Test conditions

The test was started at 2011-11-02. Duplicate samples were made for each pH. About 500 mg of the substance was dissolved in 50 ml of water. The solubility in water, of especially the higher molecular components is very low, and the insoluble material is filtered off by passing the solution through a 0.45 μm syringe filter. 10 ml of the filtered solution is diluted in 20 ml of pH buffer. The mixture was then divided in half and stored for five days, the reference part in a freezer (-20 °C) and the other in a heating cabinet (50 °C).

GC-analysis, composition of dissolved product:

Since the insoluble higher molecular components are filtered off prior to dilution in pH buffers, high temperature GC with on-column injection was run, in order to find out the composition of the product components that actually were dissolved:

Sample preparation: As above, 500 mg/50 ml water (2 replicates), filtered. About 20-25 ml (20-25 g) of the filtered solutions were evaporated to dryness at 80 °C over night in a heating cabinet. The residue, corresponding to the dissolved material was weighed out, results were about 55 mg, which means that only about 20-25 % (22.5% for Rep.1 and 22.5% for Rep. 2) of the 500 mg of substance dissolves in 50 ml of water, the rest is insoluble and is filtered away. The residues were analysed according to the GC-method, see under methods. Results are summarised in Table 2 (presented in section 'Any other information on materials and methods incl. tables').

To compensate for the difference in response due to the silylation a normalisation was done by dividing the area with the ratio between the molecular weight of the derivative and that of the underivatised molecule.

As expected, the water soluble part only consists of the low molecular part of the substance.

pH measurements

pH in the solutions was checked at the start and after five days. Results are summarised in Tables 3 and 4 (presented in section 'Any other information on materials and methods incl. tables').




Duration:
5 d
pH:
4
Temp.:
50 °C
Initial conc. measured:
10 g/L
Duration:
5 d
pH:
7
Temp.:
50 °C
Initial conc. measured:
10 g/L
Duration:
5 d
pH:
9
Temp.:
50 °C
Initial conc. measured:
10 g/L
Number of replicates:
Tier 1: Two replicates
Tier 2: Two replicates
Statistical methods:
The log-transformed data vs. time for CAPA 2047A indicates a linear function equated with a first order reaction rate, which means that the rate constant (kobs) for the hydrolysis of CAPA 2047A at pH 9, 50 °C is given by the expression:

kobs = (1/t) In (A0/At) (2)
Preliminary study:
HPLC- and GC-analysis

After five days the mixtures were analysed using HPLC and GC. The amount of free 6-hydroxyhexanoic acid (hydrolysis product) was quantified using external standard calibration (HPLC).

6-hydroxyhexanoic acid reference was prepared by treating ε-caprolactone with 1 M NaOH at 80 °C for 1 h.

Also the decrease in concentration of the dissolved product CAPA 2047A (oligomers) was estimated by calculating the decrease in area of a group of three peaks representing the different oligomers.
All samples were allowed to reach room temperature and were then injected on the HPLC-system without dilution.

Refer to tables 5 to 7 presented in section 'Any other information on results incl. tables'.
Transformation products:
not measured
pH:
4
Temp.:
50 °C
Remarks on result:
hydrolytically stable based on preliminary test
pH:
7
Temp.:
50 °C
Remarks on result:
hydrolytically stable based on preliminary test
pH:
9
Temp.:
50 °C
DT50:
ca. 35 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: The higher molecular oligomers of CAPA 2043 is not soluble in water, meaning that only the lower molecular oligomers are submitted to the hydrolysis conditions.
Details on results:
Tier 2, Hydrolysis of unstable substances

The preliminary test, Tier 1, indicated hydrolysis of less than 10 % for pH 4 and pH 7. At pH 9 the product seems to be over 90 % hydrolysed after 5 days in 50 °C . Therefore, Tier 2, Hydrolysis of unstable substances, was also performed for pH 9, 50 °C.

Duplicate samples were analysed.

Preparation of solutions was done in the same way as in Tier 1, except no part of the solution was kept in a freezer (-20 °C) for reference. Samples were taken out between 0-172 h after preparation, and analysed by HPLC according to the same methods as in Tier 1. pH was measured at the start and again at the end of the trial.

Refer to tables 8 to 11 presented in section 'Any other information on results incl. tables'.

Table 5. Results for pH 4

pH 4

1,6 HDO (mg/L)

6-hydroxyhexanoic acid (mg/L)

oligomers

(area)

% hydrolysed*

Replicate 1 -20 °C

81

<10

5.621

-

Replicate 1 50 °C

91

22

5.534

2

Replicate 2 -20 °C

71

<10

5.685

-

Replicate 2 50 °C

90

22

5.593

2

* The areas of 3 peaks representing oligomers (product) are summed up. Results from reference samples (-20 °C) are set to 0 = 0 % hydrolysed = no hydrolysis. The amount of hydrolysis taking place is then calculated by:

 

%hydrolysed = (1 -(Area0/Areat)) x 100 (1)

 

Area0 = area of oligomers in reference sample (-20 °C) for Tier 1, and oligomer-area for sample at t = 0 h, for Tier 2. Areat = area of oligomers in sample kept at 50 °C for Tier 1, and oligomer-area for sample at t = n h, for Tier 2.

Table 6. Results for pH 7.

pH 7

1,6 HDO (mg/L)

6-hydroxyhexanoic acid (mg/L)

oligomers

(area)

% hydrolysed

Replicate 1 -20°C

89

<10

5.287

-

Replicate 1 50°C

100

32

5.072

4

Replicate 2 -20°C

87

<10

5.662

-

Replicate 2 50°C

94

34

5.459

4

Table 7. Results for pH 9.

pH 9

1,6 HDO (mg/L)

6-hydroxyhexanoic acid (mg/L)

ε-caprolactone

(mg/L)

oligomers

(area)

%hydrolysed

Replicate 1 -20°C

85

<10

10

5.364

-

Replicate 1 50°C

380

430

<10

0.472

91

Replicate 2 -20°C

90

<10

12

5.665

-

Replicate 2 50°C

400

460

<10

0.545

90

Table 8. Results for 1,6-HDO, Tier 2

Time (h)

1,4-BDO (mg/L)

pH

Replicate 1

Replicate 2

0

100

98

9.1

3

120

110

-

7

160

150

-

24

240

230

-

31

270

250

-

48

280

300

-

55

330

350

-

76

340

350

-

150

410

410

-

172

400

400

8.8

Table 9. Results for 6-hydroxyhexanoic acid, Tier 2

Time (h)

6-hydroxyhexanoic acid (mg/L)

pH

Replicate 1

Replicate 2

0

<10

<10

9.1

3

37

40

-

7

77

76

-

24

200

210

-

31

240

240

-

48

310

310

-

55

330

330

-

76

380

390

-

150

470

470

-

172

480

480

8.8

Table 10. Results for product CAPA 2047A (oligomers), Tier 2

 

Time (h)

Capa 2047A

 

pH

Replicate 1

Replicate 2

area

%hydrolysis

area

%hydrolysis

0

5.686

-

5.722

-

9.1

3

5.364

6

5.400

6

-

7

4.921

14

4.931

14

-

24

3.430

40

3.383

41

-

31

3.016

47

2.965

48

-

48

2.176

62

2.102

63

-

55

1.965

65

1.890

67

-

76

1.390

76

1.308

77

-

150

0.339

94

0.360

94

-

172

0.210

96

0.242

96

8.8

Table 11. Calculation of kobs (pH 9, 50 °C)

t (s)

t (h)

Replicate 1

Replicate 2

At

kobs(s-1)

At

kobs(s-1)

10800

3

5.364

5.4 x 10-6

5.400

5.36 x 10-6

25200

7

4.921

5.73 x 10-6

4.931

5.90 x 10-6

86400

24

3.430

5.85 x 10-6

3.383

6.08 x 10-6

111600

31

3.016

5.68 x 10-6

2.965

5.89 x 10-6

172800

48

2.176

5.56 x 10-6

2.101

5.80 x 10-6

198000

55

1.965

5.37 x 10-6

1.890

5.59 x 10-6

273600

76

1.390

5.15 x 10-6

1.308

5.39 x 10-6

540000

150

0.339

5.22 x 10-6

0.360

5.12 x 10-6

619200

172

0.210

5.33 x 10-6

0.242

5.11 x 10-6

Mean value

5.5 x 10-6

 

5.6 x 10-6

sd

0.2 x 10-6

0.4 x 10-6

Half-life (t0.5) of the reaction at pH 9, 50 °C is then given by:

 

t0.5 = In2/ kobs (3)

 

Which gives t0.5≈35 ± 2 h.

Validity criteria fulfilled:
yes
Conclusions:
Preliminary test (Tier 1) showed that the product CAPA 2047A can be considered stable at pH 4 and 7 (50 °C).
At pH 9 (50 °C), CAPA 2047A seemed to be hydrolysed to a high degree within 5 days. Kinetic studies gave a half-life of about 35 h at the given conditions.
It is also worth mentioning the fact that the higher molecular oligomers of CAPA 2043 is not soluble in water, see Table 2, which means that only the lower molecular oligomers are submitted to the hydrolysis conditions.
Executive summary:

A study was conducted to guideline 111 using the substance CAPA 2047A. The product CAPA 2047A can be considered stable at pH 4 and 7 (50 °C). At pH 9 (50 °C), CAPA 2047A seemed to be hydrolysed to a high degree within 5 days. Kinetic studies gave a half-life of about 35 h at the given conditions for pH 9.

Description of key information

A reliable experimental study (with acceptable restrictions) conducted according to OECD Guideline 111 is available which shows that 2-Oxepanone, polymer with 1,6-hexanediol is hydrolytically stable.

Key value for chemical safety assessment

Additional information

A study was conducted to OECD guideline 111 using the substance 2-Oxepanone, polymer with 1,6-hexanediol. The substance can be considered stable at pH 4 and 7 (50 °C). At pH 9 (50 °C), 2-Oxepanone, polymer with 1,6-hexanediol seemed to be hydrolysed to a high degree within 5 days. Kinetic studies gave a half-life of about 35 h at the given conditions for pH 9.