Bis-O-(benzylidene)-D-glucitol

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study conducted between July 1988 and August 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Principles of method if other than guideline:

This study was undertaken to provide product chemistry data for registration purposes. The full OECD method "Hydrolysis as a function of pH" was not required however the method used was based on these guidelines.. A 7-day study at a single temperature, with determination at 3 pH's was requested. The abiotic degradation was to be avaluated and as far as possible, sterile conditions were employed.

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Preparation of samples for analysis:
At intervals, portions of the solutions at each pH were removed and allowed to reach room temperature. Owing to the low concentartions of GEL-ALL-MD involved, the solutions were concentrated using C18 Sep-pak cartridges. An aliquot (10ml) from each solution was passed slowly through a fresh sep-pak. (The sep-paks were previously conditioned with methanol (5ml) followed by double distilled water (15 ml)). When the test solution had drained from the cartridge, the adsorbed material was eluted with methanol (1 ml). The methanol solution collected from each Sep-Pak was stored at -20 deg C prior to analysis.

At the end of the 7 day period, the frozen samples were allowed to thaw and a solution of biphenyl in methanol (1 ml, 3.9 mg (1. soln.)-1) added to each, as a marker, prior to analysis by HPLC.

Buffers:

- pH: 4, 7 and 9
- Type and final molarity of buffer: 3.95, 7 and 9.06
- Composition of buffer:

PH 7:
0.02 M potassium dihydrogen phosphate
0.03 M disodium hydrogen phosphate
0.02 M sodium chloride

pH 9:
0.01 M borax
0.02 M sodium chloride

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used:
- Sterilisation method:sterilised by heating in an oven to 150 deg C for 20 minutes.
- Lighting: Daylight was excluded from the cabinet to minimise the possibility of photolytic effects.
- Measures taken to avoid photolytic effects: Daylight was excluded from the cabinet.
- Measures to exclude oxygen: Nitrogen was bubbled through the solution to remove any dissolved oxygen.
- Is there any indication of the test material adsorbing to the walls of the test apparatus? None
TEST MEDIUM
- Volume used/treatment 100 ml
- Kind and purity of water:double distilled water
- Preparation of test medium:
- Renewal of test solution: not stated
- Identity and concentration of co-solvent: acetonitrile (80% acetonitrile/double distilled water (69.8 mg/l solution)
OTHER TEST CONDITIONS
- Adjustment of pH: 3.95, 7.00 and 9.06 after sterilisation.
- Dissolved oxygen: Nitrogen gas was bubbled through to remove dissolved oxygen

Duration:

7 d

pH:

4

Temp.:

25 °C

Initial conc. measured:

0.74 mg/L

Duration:

7 d

pH:

7

Temp.:

25 °C

Initial conc. measured:

ca. 0.73 mg/L

Duration:

7 d

pH:

9

Temp.:

25 °C

Initial conc. measured:

ca. 0.7 mg/L

Positive controls:

no

Negative controls:

no

Statistical methods:

The rate constant and half life of GELL-ALL-MD was calculated by regression analysis.

Preliminary study:

Not conducted

Test performance:

A reduction in concentartion was not observed at a pH of 7 or 9 over the 7-day period

At pH 4 there was a 45% drop in concentartion noted:
Initial concentartion: 0.74 mg
Final Concentartion: 0.41 mg

Transformation products:

no

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

0.004 h-1

DT50:

ca. 200 h

Type:

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

Other kinetic parameters:

pH 4:
Observed rate constant: ko = 3.5 x 10E-3 h-1
half life: ca 200 h

Details on results:

A linear plot was obtained for log10 (concentartion GELL-ALL-MD) against time indicating pseudo-first order kinetics for the hydrolysis. The sampling period corresponded to a drop in GEL-ALL-MD concentration of 45%, and the kinetic parameters evaluated from the data were found to be:

Observed rate constant: ko = 3.5 x 10E-3 h-1
half life: ca 200 h

Validity criteria fulfilled:

yes

Conclusions:

The hydrolysis characteristics of Gel-All-MD were studied at 25°C under abiotic conditions at three pHs. The study was performed over approximately seven days.

pH 7 and pH 9:
A reduction in concentartion of Gel-All-MD was not observed

pH 4:
The concentration of GEL-ALL_MD dropped by 45% during the study. The hydrolysis reaction was found to have pseudo-first order kinetics and the following parameters were calculated:

Observed rate constant: 3.5 x 10E-3
Half life: ca 200 h

At 25°C after seven days GEL-ALL-MD appeared to be stable in both neutral and alkaline solution but unstable under acidic conditions. No prediction is made for the behaviour of the test material over a longer period.

Executive summary:

The hydrolysis characteristics of Gel-All-MD have been studied at 25°C, under abiotic conditions. Solutions at three pHs (approximately pH 4, 7 and 9) were analysed over a seven day period. A significant and consistent drop in concentration was only observed under acidic conditions. This indicates that the test material is subject to acid catalysed hydrolysis.

At pH 3.95 a 45% drop in concentration was observed over a 7 day interval:

Initial concentration: 0.74 mg/l solution

final concentration: 0.41 mg/l solution

The reaction was shown to obey pseudo-first order kinetics and the following parameters were obtained:

observed rate constant: 3.50 x 10^-3/h

half life: ca 200 hours

Gel-All-MD was found to be stable over seven days at pH 7 and at a pH of 9.06

Reference 2

Endpoint:

hydrolysis

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please see Section 13 for "Read-across justification to support the REACH registration of Bis-O-(benzylidene)-D-glucitol (EC 251-136-4) at 10-100 tpa" for full details.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
It is proposed that the structural similarity and properties of the target substance and the structural analogue (source substance) are sufficiently close for there to be a reasonable expectation of similar effects.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source substance:
IUPAC name: 1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol
EC number: 402-950-5
CAS number: 87826-41-3

Target Substance: Bis-O-(benzylidene)-D-glucitol
IUPAC name: 1,3:2,4-bis-O-dibenzylidene-D-glucitol
EC number: 251-136-4
CAS number: 32647-67-9


3. ANALOGUE APPROACH JUSTIFICATION
Based on the structural similarity of the source substances and target substance, similarity of physic-chemical properties and similarity in experimental (eco)toxicological test data (and toxicokinetic behaviour assessment) it is concluded that target substance and the structural analogue (source substance) are sufficiently close for there to be a reasonable expectation of similar effects, for the endpoints where results have been read-across.

4. DATA MATRIX
Please see Section 13 for "Read-across justification to support the REACH registration of Bis-O-(benzylidene)-D-glucitol (EC 251-136-4) at 10-100 tpa" for full details.

Reason / purpose for cross-reference:

read-across source

Test performance:

A reduction in concentartion was not observed at a pH of 7 or 9 over the 7-day period

At pH 4 there was a 45% drop in concentartion noted:
Initial concentartion: 0.74 mg
Final Concentartion: 0.41 mg

Transformation products:

no

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

0.004 h-1

DT50:

ca. 200 h

Type:

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

pH:

7

Temp.:

25 °C

DT50:

> 7 d

Remarks on result:

hydrolytically stable based on preliminary test

pH:

9

Temp.:

25 °C

DT50:

> 7 d

Remarks on result:

hydrolytically stable based on preliminary test

Validity criteria fulfilled:

yes

Conclusions:

The hydrolysis characteristics of Gel-All-MD were studied at 25°C under abiotic conditions at three pHs. The study was performed over approximately seven days.

pH 7 and pH 9:
A reduction in concentartion of Gel-All-MD was not observed

pH 4:
The concentration of GEL-ALL_MD dropped by 45% during the study. The hydrolysis reaction was found to have pseudo-first order kinetics and the following parameters were calculated:

Observed rate constant: 3.5 x 10E-3
Half life: ca 200 h

At 25°C after seven days GEL-ALL-MD appeared to be stable in both neutral and alkaline solution but unstable under acidic conditions. No prediction is made for the behaviour of the test material over a longer period.

Executive summary:

The hydrolysis characteristics of Gel-All-MD (source substance EC 402-950-5) have been studied at 25°C, under abiotic conditions. Solutions at three pHs (approximately pH 4, 7 and 9) were analysed over a seven day period. A significant and consistent drop in concentration was only observed under acidic conditions. This indicates that the test material is subject to acid catalysed hydrolysis.

At pH 3.95 a 45% drop in concentration was observed over a 7 day interval:

Initial concentration: 0.74 mg/l solution

final concentration: 0.41 mg/l solution

The reaction was shown to obey pseudo-first order kinetics and the following parameters were obtained:

observed rate constant: 3.50 x 10^-3/h

half life: ca 200 hours

Gel-All-MD was found to be stable over seven days at pH 7 and at a pH of 9.06

Description of key information

No hydrolysis study has been conducted on the target substance (EC 251-136-4).

The hydrolysis potential of the substance (EC 251-136-4) has been assessed by reading across the results of a hydrolysis study conducted on a structurally similar analogue substance, which is detailed below.

Source Substance; Gel All MD (EC 402-950-5):

The hydrolysis characteristics of Gel-All-MD (EC 402-950-5) have been studied at 25°C, under abiotic conditions. Solutions at three pHs (approximately pH 4, 7 and 9) were analysed over a seven day period. A significant and consistent drop in concentration was only observed under acidic conditions. This indicates that the test material is subject to acid catalysed hydrolysis.

At pH 3.95 a 45% drop in concentration was observed over a 7 day interval:

Initial concentration: 0.74 mg/l solution

final concentration: 0.41 mg/l solution

The reaction was shown to obey pseudo-first order kinetics and the following parameters were obtained:

observed rate constant: 3.50 x 10^-3/h

half life: ca 200 hours

Gel-All-MD was found to be stable over seven days at pH 7 and at a pH of 9.06

Additional information

Based on the result of an abiotic hydrolysis study conducted on a structurally similar substance, it is considered that the target substance (EC 251-136-4) is likely to be hydrolytically stable at pH 7 and 9. The structurally similar substance showed some hydrolysis under acidic conditions (pH 4), but it is not known if the target substance would also show this.

However, in the absence of any relevant dissociating functional groups in the target substance, significant hydrolysis is not anticipated.