Bis(2-chloroethyl) ether

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 01-aug-2016 to 16-feb-2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

TEST MATERIAL:
- Name (as cited): 2,2’-Dichlorodiethyl ether
- Putiry: 99.76%

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: batch n°20150706
- Expiration date of the lot/batch: 27 June 2017
- Purity test date: not specified

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Controlled room temperature (15-25 °C, below 70 RH%), protected from light

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: no treatment

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

- pH: 4.0; 7.0; 9.0
- Composition of buffer:
pH 4.0: 1 mL 0.2 M Sodium hydroxide and 125 mL 0.2 M Potassium hydrogen phthalate was diluted to 500 mL with ultra-pure water
pH 7.0: 74 mL 0.2 M Sodium hydroxide and 125 mL 0.2 M Potassium dihydrogen phosphate was diluted to 500 mL with ultra-pure water
pH 9.0: 53.5 mL 0.2 M Sodium hydroxide and 125 mL 0.2 M Boric acid and Potassium chloride was diluted to 500 mL with ultra-pure water

Details on test conditions:

TEST SYSTEM
- Measures taken to avoid photolytic effects: incubated in the dark
- Test system: closed screw cap tubes
TEST MEDIUM
- Kind and purity of water: steriel ultra-pure water
- Concentration of test substance: 0.005 M test item concentration in each buffer
INCUBATION
- Temperature:: 50°C
-Duration: 5 days

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

0.005 mol/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

0.005 mol/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

0.005 mol/L

Number of replicates:

5 replicates for each pH buffer

Positive controls:

no

Negative controls:

no

Statistical methods:

Not applicable

Preliminary study:

Preliminary Test/Tier 1
Sample solutions at pH 4, 7 and 9 were maintained at 50.0 ± 0.5 °C for a period of 5 days. Results from the Preliminary Test/Tier 1 showed it was not necessary to undertake further testing at pH 4, pH 7 and pH 9.

Transformation products:

not measured

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

No data

% Recovery:

97

St. dev.:

1.6

pH:

4

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

97.6

St. dev.:

3.2

pH:

7

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

99

St. dev.:

2.3

pH:

9

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

4

Temp.:

50 °C

DT50:

113.8 d

Key result

pH:

7

Temp.:

50 °C

DT50:

142.7 d

Key result

pH:

9

Temp.:

50 °C

DT50:

344.8 d

Other kinetic parameters:

No data

The samples were analyzed using GC-FID prior or after the 5 days incubation at 50°C and the % recovey was calculated. The results are as follows:

pH	% recovery
4.0	97.0 +/- 1.6
7.0	97.6 +/- 3.2
9.0	99.0 +/- 2.3

Validity criteria fulfilled:

yes

Conclusions:

Following a 5 days incubation period, Bis(2-chloroethyl) ether recovery was 97.0, 97.6 and 99.0% at pH 4.0, 7.0 and 9.0 at 50°C, respectively.

Executive summary:

An hydrolysis study was conducted to evaluate the stability of Bis(2-chloroethyl) ether based on OECD Guideline No. 111 under GLP. The test item was incubated at a concentration of 0.005M for 5 days in the dark at 50°C, and at pH 4.0, 7.0 and 9.0. The samples were analyzed using GC-FID prior or after the 5 days incubation at 50°C and the % recovey was calculated. The percentage recovery was 97.0, 97.6 and 99% at pH 4.0, 7.0 and 9.0, respectively. Accordingly, Bis(2-chloroethyl) ether is considered to be stable at pH 4.0, 7.0 and 9.0.

The data from this study are considered reliable without restriction (Reliability 1).

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Specific details on test material used for the study:

TEST MATERIAL
Test material (as cited): Bis(2-chloroethyl) ether
Purity: not specified

Radiolabelling:

not specified

Analytical monitoring:

not specified

Temp.:

100 °C

Hydrolysis rate constant:

0 min-1

DT50:

ca. 32 d

Type:

not specified

Remarks on result:

other: in aqueous dioxane

Conclusions:

Bis(2-chlorethyl) ether showed a half-life of 32 days following hydrolysis testing at 100°C. Allowing for a factor of two decrease in rate constant for each 10°C decrement, the half-life is calculated as 22 years (or 256 times slower) at 20°C.

Executive summary:

The data on hydrolysis of Bis(2-chloroethyl) ether originate from a collection of data published by US EPA (Mabey et al., 1982). U.S. EPA reports are subjected to a formal review process. It is thus assumed that a variety of data sources have been consulted, that the test methodology and identity of the test substance has been evaluated, and that a reliable and representative value for the endpoint has been selected. Accordingly, this data was assigned a reliability score of 2.

A hydrolysis rate constant of 1.5 x 10^-5 min^-1 has been reported for Bis(2-chloroethyl) ether in aqueous dioxane at 100°C (Bohme & Sell, 1948). This rate constant corresponds to a half-life of 32 days. Allowing for a factor of two decrease in rate constant for each 10°C decrement, the half-life is calculated as 22 years (or 256 times slower) at 20°C. This rate constant is much slower than expected based on a simple analogy to ethyl chloride where a half-life of 38 days is predicted at pH 7 and 25°C (Mabey & Mill, 1978).

The relatively slow hydrolysis rate of Bis(2-chloroethyl) ether compared with ethyl chloride is suggested to be due to the effect on the adjacent carbon of the -OCH2CH2Cl group. Data have been obtained which show that aqueous solvolysis of 2-methoxyethyl iodide at 60°C is 6.4 x 10^-3 times the rate of ethyl iodide under the same reaction conditions (Streitwieser, 1962). Assuming that this 6.4 x 10^-3 factor holds for the chloroaliphatic compounds as well as for the iodo compounds, the 38 day half-life of ethyl chloride can be used to obtain a half-life of 16 years for Bis(2-chloroethyl) ether. This estimate of the half-life is in fair agreement with the 22 year half-life calculated from the aqueous dioxane solvent data.

Accordingly, Bis(2 -chloroethyl) ether is considered to show a slow hydrolysis rate under environmentally relevant conditions.

Reference 3

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

2mL pyrex bulbs were filled Bis(2-chloroethyl) ether diluted in MilliQ water (resistivity: 16 MΩ/cm) at pH 6.9. The bulbs were sealed and placed in a thermostatic oil bath at various temperature ranging from 80-95°C. The bulbs were protected from light to prevent photolysis. At regular intervals (duration of incubation not stated), Bis(2-chloroethyl) ether and its degradation products were analysed using GC.

GLP compliance:

not specified

Specific details on test material used for the study:

Purity: not specified

Radiolabelling:

no

Analytical monitoring:

yes

Remarks:

GC method

Details on sampling:

- Sampling intervals for the parent/transformation products: not specified
- Sample storage conditions before analysis: not specified

Buffers:

No data- pH:
- Type and final molarity of buffer: no data
- Composition of buffer: no data

Details on test conditions:

No data

Number of replicates:

No specified

Positive controls:

not specified

Negative controls:

not specified

Transformation products:

yes

No.:

#1

No.:

#2

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

No data

pH:

6.9

Temp.:

80 °C

DT50:

189 h

Type:

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

pH:

6.9

Temp.:

85 °C

DT50:

109 h

Type:

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

pH:

6.9

Temp.:

90 °C

DT50:

64 h

Type:

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

pH:

6.9

Temp.:

95

DT50:

44 h

Type:

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

Other kinetic parameters:

From Arrhenius' law, the activation energy was estimated at 108.3 KJ/mole.

Validity criteria fulfilled:

yes

Conclusions:

The half-life of Bis(2-chloroethyl) ether in distilled water at pH 6.9 was determined to be 44, 64, 109 and 189 hours at 95, 90, 85 and 80°C, respectively.

Executive summary:

In this published study, the hydrolysis of Bis(2-chloroethyl) ether in distilled water (pH 6.9) was studied at various temperatures. Samples were added to pyrex bulbs and incubated in a thermostatic oil bath protected from light (to avoid photolysis). Quantification of Bis(2-chloroethyl) ether and its degradation product was obtained using a GC-FID system. The half-life of Bis(2-chloroethyl) ether in distilled water at pH 6.9 was determined to be 44, 64, 109 and 189 hours at 95, 90, 85 and 80°C, respectively. These data were used to extrapolate the half-life of Bis(2-chloroethyl) ether at lower temperatures. This approach suggests that the half-life of the test substance is 202 years at 10°C and 22 years at 25°C. The main degradation products following hydrolysis are 1,4-Dioxane and HCl.

The methdological details of this study are provided in sufficient details. In addition, the data have been subject to peer-review. Accordingly, a relibaility score of 2 has been assigned.

Description of key information

In a study based on OECD Guideline No. 111, Bis(2-chloroethyl) ether was found to be stable at pH 4.0, 7.0 and 9.0. The test item was incubated at a concentration of 0.005M for 5 days in the dark at 50°C. The samples were analyzed using GC-FID prior or after the 5 days incubation and the % recovey was calculated. Whatever the pH considered (4-9), the percentage recovery was at least 97%. Accordingly, hydrolysis at environmental pH is considered to be very limited. The mean estimated half-life was 200.4 days at pH ranfing from 4 to 9.

Key value for chemical safety assessment

Half-life for hydrolysis:

200.4 d

at the temperature of:

50 °C

Additional information

Three studies on the hydrolysis of Bis(2-chloroethyl ether) are available.

An hydrolysis study was conducted to evaluate the stability of Bis(2-chloroethyl) ether based on OECD Guideline No. 111 under GLP. The test item was incubated at a concentration of 0.005M for 5 days in the dark at 50°C, and at pH 4.0, 7.0 and 9.0. The samples were analyzed using GC-FID prior or after the 5 days incubation at 50°C and the % recovey was calculated. The percentage recovery was 97.0, 97.6 and 99% at pH 4.0, 7.0 and 9.0, respectively. Accordingly, Bis(2-chloroethyl) ether is considered to be stable at pH 4.0, 7.0 and 9.0. The data from this study are considered reliable without restriction (Reliability 1).

In the databook entitled "Aquatic Fate Porcess Data for Organic Priority Pollutants" published by U.S. EPA (Mabey et al., 1982), a hydrolysis rate constant of 1.5 x 10^-5min^-1has been reported for Bis(2-chloroethyl) ether in aqueous dioxane at 100°C (Bohme & Sell, 1948). This rate constant corresponds to a half-life of 32 days. Allowing for a factor of two decrease in rate constant for each 10°C decrement, the half-life is calculated as 22 years (or 256 times slower) at 20°C. This rate constant is much slower than expected based on a simple analogy to ethyl chloride where a half-life of 38 days is predicted at pH 7 and 25°C (Mabey & Mill, 1978). The relatively slow hydrolysis rate of Bis(2-chloroethyl) ether compared with ethyl chloride is suggested to be due to the effect on the adjacent carbon of the -OCH2CH2Cl group. Data have been obtained which show that aqueous solvolysis of 2-methoxyethyl iodide at 60°C is 6.4 x 10^-3times the rate of ethyl iodide under the same reaction conditions (Streitwieser, 1962). Assuming that this 6.4 x 10^-3factor holds for the chloroaliphatic compounds as well as for the iodo compounds, the 38 day half-life of ethyl chloride can be used to obtain a half-life of 16 years for Bis(2-chloroethyl) ether. This estimate of the half-life is in fair agreement with the 22 year half-life calculated from the aqueous dioxane solvent data. U.S. EPA reports are subjected to a formal review process. It is thus assumed that a variety of data sources have been consulted, that the test methodology and identity of the test substance has been evaluated, and that a reliable and representative value for the endpoint has been selected. Accordingly, this data was assigned a reliability score of 2.

In a published study by Milano et al. (Environ. Technol. Lett., 1989, 10:291-300), the hydrolysis of Bis(2-chloroethyl) ether in distilled water (pH 6.9) was studied at various temperatures. Samples were added to pyrex bulbs and incubated in a thermostatic oil bath protected from light (to avoid photolysis). Quantification of Bis(2-chloroethyl) ether and its degradation product was obtained using a GC-FID system. The half-life of Bis(2-chloroethyl) ether in distilled water at pH 6.9 was determined to be 44, 64, 109 and 189 hours at 95, 90, 85 and 80°C, respectively. These data were used to extrapolate the half-life of Bis(2-chloroethyl) ether at lower temperatures. This approach suggests that the half-life of the test substance is 202 years at 10°C and 22 years at 25°C. The main degradation products following hydrolysis are 1,4-Dioxane and HCl. The methdological details of this study are provided in sufficient details. In addition, the data have been subject to peer-review. Accordingly, a relibaility score of 2 has been assigned.

Based on an overall assessment of available data, Bis(2-chloroethyl) ether is assumed to exhibit a slow hydrolysis rate under environmentally relevant conditions.