2-Hydroxypropyl-β-cyclodextrine ethers

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

.beta.-Cyclodextrin, 2-hydroxypropyl cycloheptaamylose

IUPAC Name:

.beta.-Cyclodextrin, 2-hydroxypropyl cycloheptaamylose

Constituent 2

Reference substance name:

-

EC Number:

420-920-1

EC Name:

-

Cas Number:

128446-35-5

Molecular formula:

Hill formula: (C42H70-nO35)(C3H7O)n; n(mittel)=5,25

IUPAC Name:

5,10,15,25-tetrakis(hydroxymethyl)-40,44,47,49-tetrakis(2-hydroxypropoxy)-20,30,35-tris[(2-hydroxypropoxy)methyl]-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.2³,⁶.2⁸,¹¹.2¹³,¹⁶.2¹⁸,²¹.2²³,²⁶.2²⁸,³¹]nonatetracontane-36,37,38,39,41,42,43,45,46,48-decol

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): hydroxypropylated .beta.-cyclodextrin
- Physical state: white powder
- Analytical purity: 89.16%
- Lot/batch No.: 01 (DRD#: SIETS 96.010)
- Water Solubility: >= 180 g/L (SLI Report #97-10-7113)
- Density: 991 kg/m³ (0.991 g/cm³ ) at 24.9 °C (SLI Report #97-4-6948)

Specific details on test material used for the study:

Test material SS0430.01, batch No. 01

Radiolabelling:

not specified

Study design

Analytical monitoring:

yes

Details on sampling:

The Quality Control samples were prepared at each sampling interval (i.e., days 0 and 5) to be analyzed along with their respective test samples. The results of the QC sample analyses were used to judge the precision and quality control maintained during the analytical process.

Buffers:

- Type and final molarity of buffer:
pH 4: 180 mL of 0.2 M sodium acetate (5.42 g of sodium acetate dissolved in 200 mL of reagent water) was added to 820 mL of 0.2 M glacial acetic acid (12.0 mL of glacial acetic acid diluted to 1000 mL with reagent water) and brought to a final volume of 2000 mL with reagent water.
pH 7: 1000 mL of 0.1 M potassium phosphate monobasic solution (13.6 g potassium phosphate monobasic dissolved in 1000 mL reagent water) was added to 580 mL of 0.1 M sodium hydroxide and diluted to 2000 mL with reagent water.
pH 9: 200 mL of 0.1 M boric acid (1.55 g of boric acid dissolved in 250 mL of reagent water) was added to 236 mL of 0.1 M sodium tetraborate decahydrate (9.52 g sodium tetra hydrate decahydrate dissolved in 250 mL of reagent water) and diluted to 2000 mL reagent water.
- Composition of buffer: Buffers were autoclaved in a Barnstead autoclave at approximately 121°C for 30 minutes. The pH of each buffer solution was confirmed after autoclaving.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: 50-mL volumetric flasks
- Sterilisation method: autoclaved at approximately 121°C for 30 minutes
- Measures taken to avoid photolytic effects: completely covered with aluminum foil
- Measures to exclude oxygen: purged for 5 minutes with sterile nitrogen
TEST MEDIUM
- Volume used/treatment: 50mL
- Preparation of test medium: prepared for each of the three sterile buffer solutions (pH 4, 7 and 9) at a target test concentration of 5 mg/L hydroxypropylated .beta.-cyclodextrin. Each test solution was prepared by diluting a 1.0-mL aliquot of the 250 mg/L hydroxypropylated .beta.-cyclodextrin stock solution with the appropriate sterile buffer solution to a final volume of 50.0 mL.
OTHER TEST CONDITIONS
- Adjustment of pH: yes
- Dissolved oxygen: excluded

Duration of test

Duration of test 1

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

ca. 5.3 mg/L

Duration of test 2

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

ca. 5.1 mg/L

Duration of test 3

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

ca. 4.2 mg/L

Number of replicates:

3 replicates at each pH value

Positive controls:

not specified

Negative controls:

not specified

Results and discussion

Preliminary study:

A preliminary study was performed at 50 °C +-0.5 °C at pH 4.0, 7.0 and 9.0. 2 samples at each pH values were measured 3 times.

Test performance:

The precision and accuracy of the QC sample recoveries demonstrated that the appropriate quality control was maintained during the analysis of the test solutions. Based on the results of the 5-day preliminary study, a test at two additional temperatures was not required to be performed.

Transformation products:

not measured

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

It was determined that hydroxypropylated .beta.-cyclodextrin degraded by 1.1%, -4.2% and 1.9%, respectively, at pH 4, 7, and 9, respectively. The half-life is greater than one year at 20°C.

Total recovery of test substance (in %)

Total recovery of test substance (in %) 1

% Recovery:

104

pH:

4

Temp.:

50 °C

Duration:

5 d

Total recovery of test substance (in %) 2

% Recovery:

100

pH:

7

Temp.:

50 °C

Duration:

5 d

Total recovery of test substance (in %) 3

% Recovery:

82.4

pH:

9

Temp.:

50 °C

Duration:

5 d

Dissipation DT50 of parent compound

Key result

Temp.:

20 °C

DT50:

> 1 yr

Type:

not specified

Remarks on result:

hydrolytically stable based on preliminary test

Details on results:

It was determined that hydroxypropylated .beta.-cyclodextrin degraded by 1.1%, -4.2% and 1.9%, respectively, at pH 4, 7, and 9, respectively. The half-life is greater than one year at 20°C.
The precision and accuracy of the QC sample recoveries demonstrated that the appropriate quality control was maintained during the analysis of the test solutions. Based on the results of this 5-day preliminary study, a definitive test at two additional temperatures was not required to be performed.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

Under the experimental conditions followed in this study, degradation of less than 10% was observed at pH 4, 7 and 9 (i.e., 1.1%, -4.2% and 1.9%, respectively) after being exposed to optimum hydrolysis conditions (i.e., 5 days at 50 +/- 0.1 °C). Based on the results of this study, hydroxypropylated .beta.-cyclodextrin is considered hydrolytically stable at all pHs tested.
Springborn Laboratories,

Executive summary:

The test article, hydroxypropylated .beta.-cyclodextrin , was tested in The Abiotic Degradation by hydrolysis at three different pH values according to OECD Guideline 111.

Hydrolysis is one of the most important naturally occurring reactions in the environment and consequently represents one of the most important degradation pathways. Hydrolysis is defined as the reaction of chemicals with water resulting in the addition of water to the chemical, the substitution of OH- for a group in the chemical, or degradation of the chemical by another hydrolytic pathway. While known to be independent of factors such as sunlight, presence or absence of microbial populations and extent of oxygen supply, the rate of hydrolysis is dependent on pH, temperature and the concentration of the chemical. It has been demonstrated by Mabey and Mill (1978) that for twelve classes of organic chemicals, rates of hydrolysis obtained in the laboratory are comparable to naturally occurring rates. Therefore, hydrolysis studies provide useful information for the evaluation of the persistence of a chemical in the aquatic environment.

The objective of this study was to determine ifhydroxypropylated .beta.-cyclodextrinis stable in water at three different pH values so that the importance of hydrolysis as a transformation route can be better assessed with regard to the overall potential for persistence and/or degradation of the test substance in the environment. This study was initiated on 8 April 1997, the day the Study Director signed the protocol, and was completed on the day the StUdy Director signed the final report. The experimental phase of this study was conducted from 8 to 13 May 1997 at Springborn Laboratories, Inc. (SLJ), located in Wareham, Massachusetts. The analytical chemistry was conducted at Midwest Research Institute, Kansas City, Missouri and the data is archived there. The test system raw data and the final report produced during this study are stored in Springborn's archives at the above location.

 

After 5 days at 50°C +/- 1 °Chydroxypropylated .beta.-cyclodextrindegraded by 1.1%, -4.2%, and 1.9% at pH 4, 7, and 9, respectively. Since the degradation at all pHs tested was less than 10% after being exposed to optimum hydrolysis conditions (i.e., 5 days at 50 +/-0.1 °C),hydroxypropylated .beta.-cyclodextrinis considered hydrolytically stable.