D-Glucitol, 1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-, 2,3,4,6-tetraacetate, (1S)-

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 27 July 2016 to 01 August 2016

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Cross-reference

Reason / purpose for cross-reference:

other: Reference to the validated analytical method used for the quantification of the hydrolysis samples.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

2004

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 835.2120 (Hydrolysis of Parent and Degradates as a Function of pH at 25°C)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

[(2R,3R,4R,5S,6S)-3,4,5-tris(acetyloxy)-6-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}oxan-2-yl]methyl acetate

EC Number:

930-010-9

Cas Number:

461432-25-7

Molecular formula:

C29H33ClO10

IUPAC Name:

[(2R,3R,4R,5S,6S)-3,4,5-tris(acetyloxy)-6-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}oxan-2-yl]methyl acetate

Test material form:

solid: particulate/powder

Details on test material:

Appearance: White crystalline solid
Storage conditions: At room temperature protected from light

Specific details on test material used for the study:

water solubility: 11.2 µg/L

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Details on sampling:

- The buffer solutions were filter-sterilised through a 0.2 µm FP 30/0.2 CA-S filter (Whatman) and transferred into sterile vessels.
- To exclude oxygen, nitrogen gas was purged through the solutions for 5 minutes.
- The substance was spiked to the buffer solutions at a target concentration of 5.61 μg/L using a spiking solution in acetonitrile.
- The spiking volume was < 1% of the sample volume; nominal concentrations were not corrected for the spiking volume.

- For each sampling time, duplicate sterile vessels under vacuum were filled with 6 mL test solution and placed in the dark in a temperature controlled environment.

- Samples for analysis were taken immediately after preparation (t=0) and after 5 days.
- The samples taken after 5 days were cooled to room temperature using running tap water.

- Blank buffer solutions containing a similar content of blank spiking solution (acetonitrile) were treated similarly as the test samples and analysed at t=0.

- The pH of the test solutions (except for the blanks) was determined at each sampling time.

Buffers:

- Acetate buffer pH 4: aqueous solution of 16.7% 0.01 M sodium acetate and 83.3% 0.01 M acetic acid.
- Phosphate buffer pH 7: aqueous solution of 0.01 M potassium di-hydrogenphosphate adjusted to pH 7 using 1 N sodium hydroxide.
- Borate buffer pH 9: aqueous solution of 0.01 M boric acid and 0.01 M potassium chloride adjusted to pH 9 using 1 N sodium hydroxide.

- Type of water: tap water purified by a purification system

Details on test conditions:

- Tier 1 preliminary test at pH 4, 7 and 9 and at 49.9 ± 0.1°C; 5 days.
- All solutions containing the substance were protected from light.

Number of replicates:

Two

Positive controls:

no

Negative controls:

no

Results and discussion

Preliminary study:

At pH 7 and pH 9 a decrease in concentration of > 10% was observed after 5 days. No hydrolysis was observed at pH 4; at pH 4 an increase in concentration was measured after 5 days.
The responses of all test samples were below the calibration range and therefore calculated by extrapolation of the calibration curve. The concentrations analysed are therefore regarded as estimated values.

Test performance:

RECOVERIES
- Recovery is the concentration analysed at t=0 relative to the nominal concentration.
- Recoveries for the duplicate pH 4 samples: 58% and 51%
- Recoveries for the duplicate pH 7 samples: 108% and 94%
- Recoveries for the duplicate pH 9 samples: 93% and 67%

Transformation products:

not specified

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

4

Temp.:

50 °C

Remarks on result:

other: No hydrolysis after 5 days (estimated result due to methodological limitations).

Dissipation DT50 of parent compound 2

pH:

7

Temp.:

50 °C

Remarks on result:

other: Hydrolysis of > 10% after 5 days (estimated result due to methodological limitations).

Dissipation DT50 of parent compound 3

pH:

9

Temp.:

50 °C

Remarks on result:

other: Hydrolysis of > 10% after 5 days (estimated result due to methodological limitations).

Details on results:

No substance was detected in the blank buffer solutions.

Any other information on results incl. tables

Table: Preliminary test (Tier 1) results

pH code	Sampling time	Analysed concentration [mg/L]	Degree of hydrolysis [%]		Actual pH
			Individual	Mean
pH 4	0 hours	0.0033			4.1
		0.0029			4.1
	5 days	0.0039	-27	-41	4.2
		0.0047	-55		4.2
pH 7	0 hours	0.0060			7.1
		0.0053			7.1
	5 days	0.0029	48	45	7.0
		0.0033	42		7.0
pH 9	0 hours	0.0052			9.0
		0.0038			9.0
	5 days	not detected	not applicable	not applicable	9.0
		not detected	not applicable		9.0

Applicant's summary and conclusion

Conclusions:

Hydrolysis as a function of pH of the substance can not be determined due to the low water solubility of the substance. There is no analytical method available that is sensitive enough for quantification of the hydrolysis samples.

Executive summary:

The rate of hydrolysis of the substance at pH values normally found in the environment (pH 4-9) was determined in a GLP-compliant study according to EC C.7, OECD 111 and EPA OPPTS 835.2120.

The study was performed at a concentration half the water solubility. The concentrations were determined using an analytical method that was not sensitive enough to determine the concentations of the hydrolysis samples accurately. The following indicative results were obtained from the preliminary test: a decrease in concentration of > 10% at pH 7 and pH 9 after 5 days and an increase in concentration after 5 days at pH 4. A Tier 2 study was not conducted. It was concluded that hydrolysis as a function of pH can not be determined due to the low water solubility of the substance. There is no analytical method available that is sensitive enough for quantification of the hydrolysis samples.