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Endpoint:
hydrolysis
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
- QMRF: see 'Overall remarks, attachments'.
- QPRF: see 'Executive summary'.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Calculation of aqueous hydrolysis rate constant. Software used: SRC HYDROWIN v2.00
GLP compliance:
no
Specific details on test material used for the study:
- SMILES Code: O=C(OCCO)C=C
Estimation method (if used):
HYDROWIN v2.00 (chemical class: ESTER)
pH:
7
Temp.:
25 °C
DT50:
9.001 yr
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Kb half-life; The substance is not within the applicability domain of the model.
pH:
8
Temp.:
25 °C
DT50:
328.762 d
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Kb half-life; The substance is not within the applicability domain of the model.
Other kinetic parameters:
Kb at atom#2: 2.440E-002 L/mol*sec
Total Kb for pH > 8 at 25 °C : 2.440E-002 L/mol*sec
Executive summary:

QPRF: HYDROWIN v2.00

 

1.

Substance

See “Test material identity”

2.

General information

 

2.1

Date of QPRF

24 Oct. 2013

2.2

QPRF author and contact details

BASF SE, Dept. for Product Safety, Ludwigshafen, Germany

3.

Prediction

3.1

Endpoint
(OECD Principle 1)

Endpoint

Aqueous hydrolysis rate

Dependent variable

Hydrolytic half-life

3.2

Algorithm
(OECD Principle 2)

Model or submodel name

WSKOWWIN

Model version

v. 2.00

Reference to QMRF

Estimation of Aqueous Hydrolysis Rate Constants using HYDROWIN v2.00 (EPI Suite v4.11) (QMRF)

Predicted value (model result)

See “Results and discussion”

Input for prediction

Chemical structure via CAS number or SMILES

Descriptor values

- SMILES: structure of the compound as SMILES notation

Fragment values:

- Taft constant (sigma*)

- Steric factor (Es)

- Hammett constants (sigma-meta and sigma-para)

3.3

Applicability domain
(OECD principle 3)

Domains:

1) Chemical class

An equation for the estimation of the aqueous hydrolytic rate constant is available for the chemical class of the substance.

2) Fragments (On-Line HYDROWIN User’s Guide, Appendix E)

Not all fragments were identified.

3.4

The uncertainty of the prediction
(OECD principle 4)

According to REACH Guidance Document R.7a, (Nov. 2012), hydrolysis kinetics are usually determined experimentally. The guidance document also lists HYDROWIN as a means to estimate the hydrolytic half-life. The estimation is limited to only a few chemical classes. The model marks uncertainties of the estimate due to substitute values for missing fragments. As yet, the QSAR equations in HYDROWIN have not been rigorously tested with an external validation dataset. Currently, the number of chemicals with evaluated hydrolysis rates is relatively small in number, and the available data have been used to train the QSAR regressions. The training data set for esters has an acceptable size (n = 124). Equations for the other chemical classes were developed on very small databases (n = 7 to 20); therefore the reliability of estimations for members of other chemical classes than esters is low.

3.5

The chemical mechanisms according to the model underpinning the predicted result
(OECD principle 5)

Hydrolysis is a common degradation route in the environment, where reaction of a substance with water with a net exchange of the X group with an OH at the reaction centre such that RX + H2O →ROH + HX. Hydrolysis is often dependent upon pH as the reaction is commonly catalysed by hydrogen or hydroxide ions.

The model uses the principle of linear free energy relationships (LFER) to estimate the aqueous hydrolysis rate.

References

- US EPA (2012). On-Line HYDROWIN User’s Guide, Appendix E: Fragment Substituent Values Used by HYDROWIN.

- ECHA (2012). REACH Guidance Document R.7a, (Nov. 2012). 381 pp.

Identified fragments for the current substance:

If the substance is an ester:

Applicable

R2 substituent is an alkyl carbon or an aromatic carbon.

yes

R1 substituent is either an alkyl carbon, an aromatic carbon or a hydrogen.

yes

 

Appendix E. Fragment Substituent Values Used by HYDROWIN

Fragment

Es

sigma*

sigma-meta

sigma-para

Fragment identified by HYDROWIN

Substitute fragment (warning by HYDROWIN)

Name of R group according to HYDROWIN

-CH3

-1.12

-0.49

-0.06

-0.14

yes

no

 

-CH2-CH2-CH2-CH3

-1.43

-0.49

-0.07

-0.16

no

yes

n-butyl

-CH=CH2

-3.19

0.07

0.08

-0.09

yes

no

 

-Phenyl

-3.43

0.26

0.05

-0.01

yes

yes

 

-Naphthyl

-3.43

0.26

0.05

-0.01

no

yes

 

 

Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
the test material was not characterized in accordance with GLPs.
Qualifier:
according to
Guideline:
other: TSCA guidelines, section 796.3500 Hydrolysis as a Function of pH at 25 °C.
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): hydroxyethyl acrylate
- Analytical purity: 98.52 %
Radiolabelling:
no
Analytical monitoring:
yes
Buffers:
Buffers : Buffered solutions were prepared at pH 3 with formic acid (0.05 M), pH 7 with potassium dihydrogen phosphate (0.05 M) and at pH 11 using Sodium bicarbonate (0.025 M).
Details on test conditions:
TEST METHOD
Test material was added to the buffered solutions at a concentration less than 1 mm (15 µL test material /150 mL solution). Approximate nominal concentration of HEA was 110 mg/L. The concentration of HEA was at least several orders of magnitude below the water solubility. Portions (10 mL) of the test solutions were transferred to the uniquely labeled 10 ml serum bottles and sealed with Teflon coated rubber septa and aluminum crimp seals. The test solutions were incubated in the dark at 25 ± 1°C. Periodically test solutions were removed for measurement of pH and the analysis of the test material remaining in the solution. Single test samples were removed at each time and analyzed in triplicate by reverse phase HPLC using UV detection.
For test samples at pH 11, 20 µL portions of formic acid were added prior to analysis to adjust the sample to the pH range of 5 to 6 to minimize further hydrolysis. The following sampling schedule is described in the TSCA guidelines:
- Procedure1: If 60-70% conversion occurs within 28 days, then a minimum of 6 measurements will be made at a regular intervals between 20- 70% hydrolysis
- Procedure 2: If the reaction is too slow to conveniently follow the hydrolysis to a high conversion in 28 days, but is still rapid enough to attain at least 20% conversion, the test solution should be analyzed at 15 to 20 time points at regular intervals after 10% conversion is attained.
- Procedure 3: If less than 20% conversion occurs after 28 days, then the concentration of test chemical after 28 days will be determined and a half life of > x days reported.

Methyl ether of hydroquinone (MEHQ) is routinely added to HEA during manufacture to inhibit polymerization; therefore the effect of MEHQ on the hydrolysis of HEA was evaluated. The hydrolysis rate at pH 11for 2 different samples of HEA containing different concentrations of MEHQ were determined. The first sample of HEA contained 398 ppm MEHQ and while the second sample contained 275 ppm MEHQ.

For each hydrolysis experiment, the natural logarithm of the test substance concentration was plotted as a function of time. At a constant pH, straight line was obtained indicating pseudo-first order kinetics. The slope of the regression line was equal to -Kh, where Kh was the pseudo- first order kinetics. Using the relationship, T 1/2 = ln 2/ Kh , the half life of the hydrolysis reaction was determined. The following relationship holds for hydrolysis reactions in buffered systems:

- Kh = KA [ H+] + KB [ OH- ] + KN

Where KA, KB and KN are the second order rate constants for the acid and base catalyzed and neutral water hydrolysis reaction respectively. At a given pH, this equation contains 3 unknowns, KA, KB and KN Thus three equations are required to determine three unknown values. This was accomplished by measuring the hydrolysis rate at pH 3, 7 and 11.
Duration:
28 d
pH:
3
Temp.:
25 °C
Initial conc. measured:
110 mg/L
Duration:
28 d
pH:
7
Temp.:
25 °C
Initial conc. measured:
110 mg/L
Duration:
5 d
pH:
11
Temp.:
25 °C
Initial conc. measured:
110 mg/L
Transformation products:
not measured
Key result
pH:
3
Temp.:
25 °C
DT50:
> 270 d
Type:
(pseudo-)first order (= half-life)
Key result
pH:
7
Temp.:
25 °C
Hydrolysis rate constant:
0 d-1
DT50:
> 270 d
Type:
(pseudo-)first order (= half-life)
Key result
pH:
11
Temp.:
25 °C
Hydrolysis rate constant:
13.72 d-1
DT50:
0.05 d
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r2 = 0.9994
Details on results:
HEA hydrolyzed rapidly at pH 11, with a half life of 0.051 days. In contrast slow hydrolysis was observed at pH 3 and pH 7, with the half lives greater than 230 days. These results were explained by the presence of ester functional groups in HEA which are more susceptible to hydrolysis at higher pH. Based on the hydrolysis rate constant determined for HEA, half lives of 35 to 40 days would be expected at pH 8.

- Effect of MEHQ inhibitor on hydrolysis: Samples of HEA containing 398 and 275 ppm MEHQ had half lives of 1.34 and 1.30 hours respectively. Thus a 45% higher concentration of MEHQ resulted in only a 3% longer half life. These results indicate that varying the MEHQ levels from 275 to 398 ppm in HEA had minimal effect on the rate of hydrolysis at pH 11. This observation was consistent with the fact that the MEHQ was diluted 10,000 fold in the test solutions, thereby minimizing any possible effect on the hydrolysis reaction.

Tables: Hydrolysis of HEA in buffered solutions at 25 °C

 

Time (days)

              pH 3

                   pH 7

Ave mg/L

Std deviation

Ave mg/L

Std deviation

0

111.3

0.3

108.0

0.1

5

109.1

0.3

105.1

0.1

7

121.6

0.5

116.2

0.4

15

117.5

0.1

111.2

0.3

21

115.2

0.4

106.1

0.3

28

114.1

0.4

100.5

0.2

 

 

   Time (days)

                             pH 11

Ave mg/L

Std deviation

0

108.1

1.4

0.5

85.3

0.3

1

61.8

0.0

2

36.3

0.0

3.5

14.5

0.2

4

11.0

0.0

5

6.5

0.1

 

Results for hydrolysis studies for HEA:

pH

Kha(days-1)

Half- life (days)

Correlation coefficient ( r2)

2.84

Nil

-

-

7.03

0.0025

> 270

-

10.87

13.72

0.051

0.9994

aPseudo- first order rate constant determined at indicated pH

 

Calculated KA,KBand KN, second order rate constants:

 

Compound

KA(M-1day-1)

KB(M-1day-1)

KN (day-1)

HEA

Nil

18,500

5.18 × 10-4

 

Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1996 -1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
test material characterization was not audited for compliance with GLP
Principles of method if other than guideline:
In an initial experiment (Experiment A, 28 day duration), the hydrolysis rate for HEA was determined in synthetic seawater at 25 °C. Based on the results of this experiment, a second study was set (Experiment B, 70 to 91 day duration) to determine the hydrolysis rates for HEA at 5, 12, and 25°C in synthetic seawater buffered to pH 8.1.
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): hydroxyethyl acrylate (HEA)
- Analytical purity: 98.52 %
Analytical monitoring:
yes
Buffers:
- pH for experiment A: 8.15
- pH for experiment B: 8.1
- Composition of buffer: For Experiment B buffered seawater was prepared by dissolving 40 g instant ocean and 3.1 g boric acid in 1 L water. The pHof the solution was adjusted from 6.8 to 8.1 with 1M NaOH and sterilized.
Details on test conditions:
TEST MEDIUM
- Test medium: Synthetic sea water

METHOD
In an initial experiment (Experiment A, 28 days duration), the hydrolysis rate for HEA was determined in synthetic sea water at 25 °C. Based on the results of this experiment , a second study was set (Experiment B, 70 to 91 days duration) to determine hydrolysis rate at 5, 12 and 25°C in synthetic sea water buffered to pH 8.1
- Experiment A: Synthetic sea water was prepared by dissolving 40 gm of instant ocean in water and diluting to 1L. The solution was then sterilized. A 15 µL portion of HEA was added to 150 ml of synthetic sea water to obtain a final approximate nominal concentration of 110 mg/L. The pH of the test solution was 8.15. Portions (10 mL) of the test solutions were transferred to uniquely labeled 10 mL serum bottles and sealed with unique Teflon coated rubber septa and aluminum crimp seals. The test solutions were incubated in thedark for 28 days at 25 ± 1 °C. Duplicate samples were removed for the measurement of pH and analyses of HEA remaining in the solution after 0, 5, 14, 21 and 28 days. Each test solution was analyzed in triplicate by reverse phase HPLC using UV detection.
- Experiment B: Test solutions were prepared in the same manner as described above, except that the sea water was buffered to pH 8.1 with boric acid to minimize changes in pH. Buffered sea water was prepared by dissolving 40 gm instant ocean and 3.1 gm boric acid in water and diluting to 1 L. The pH of the solution was adjusted from 6.8 to 8.1 with 1 N NaOH and sterilized. HEA was added to obtain a final approximate nominal concentration of 110 mg/L. Test solutions were incubated in the dark for up to 91 days at 21 ± 1°C, 12 ± 1°C and 5 ± 1°C. Duplicate test solutions were removed for the measurement of ph and the analysis of HEA remaining in the solution after 0, 7, 28, 42, 56, 70 and 91 days. The experiment at 12 °C was terminated after day 70 because of a faulty water bath. Each test solution was analyzed in triplicate by reverse phase HPLC.

For each hydrolysis experiment the natural logarithm of the test substance concentration was plotted as a function of time. At a constant pH, a straight line was obtained indicating pseudo-first order kinetics. The slope of the linear regression line was equal to –Kh where Kh was the pseudo- first order hydrolysis rate constant. Using the relationship, T 1/2 = ln 2/ Kh , the half life of the hydrolysis reaction was determined.
The temperature dependence of hydrolysis reactions were determined by using Arrhenius equation: y = Ae –E/ RK
Duration:
28 d
pH:
8.15
Temp.:
25 °C
Initial conc. measured:
110 mg/L
Duration:
91 d
pH:
8.1
Temp.:
25 °C
Initial conc. measured:
110 mg/L
Duration:
70 d
pH:
8.1
Temp.:
12 °C
Initial conc. measured:
110 mg/L
Duration:
91 d
pH:
8.1
Temp.:
5 °C
Initial conc. measured:
110 mg/L
Number of replicates:
Each test solution was analyzed in triplicate.
Preliminary study:
After 28 days, the concentration of HEA was reduced by 40%. However, the kinetics of hydrolysis were not pseudo-first order as indicated by a decrease in the slope of the line over time (non-linear plot). This was likely due to a decrease in pH of the test solutions from pH 8.15 to 7.85 over the 28-day experiment.
Transformation products:
not measured
pH:
8.1
Temp.:
5 °C
Hydrolysis rate constant:
0 d-1
DT50:
290 d
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r² = 0.8255
pH:
8.1
Temp.:
12 °C
Hydrolysis rate constant:
0.01 d-1
DT50:
100 d
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r² = 0.9527
pH:
8.1
Temp.:
25 °C
Hydrolysis rate constant:
0.04 d-1
DT50:
17 d
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r² = 0.9982
Details on results:
For an overview of the test results, see 'Any other information on results incl. tables'. The 17-day half-life at 25 °C determined in Exp. B suggests that the hydrolysis rate of HEA was accelerated by the synthetic seawater. Investigations into whether borate buffer accelerated the reaction showed that borate buffer did not affect the rate of reaction. Pseudo-first order kinetics were observed, with measured half-lives of 290 days at 5 °C, 100 days at 12 °C, and 17 days at 25 °C. Based on rate constants determined in a previous study which did use seawater, a hydrolysis half-life of 29 days in "regular" water would have been expected at 25 °C (pH 8.1). Thus, seawater appeared to accelerate the rate of HEA hydrolysis.

The results for the hydrolysis of HEA in buffered synthetic sea water at 5, 12 and 25°C are:

Temperature

( °C )

Rate constant

(days-1)a

Half life

(days)

r2 b

5

0.0024

290

0.8255

12

0.0068

100

0.9527

25

0.0399

17

0.9982

apseudo first order rate constant;bcorrelation coefficient

  The results for the hydrolysis of HEA in non buffered synthetic sea water at 25°C (Experiment A) were:

 

Day

 pH

HEA (mg/L)

Std deviation

 RSD

ln (mg/L)

0

8.15

108.6

0.20

0.19 %

4.688

5

8.05

91.0

0.17

0.18 %

4.511

5

8.04

90.7

0.16

0.18 %

4.508

14

7.86

77.6

0.12

0.15 %

4.352

14

7.85

79.4

4.08

5.14 %

4.374

21

7.86

68.6

0.11

0.16 %

4.228

21

7.88

67.8

0.13

0.19 %

4.217

28

7.84

65.6

0.06

0.10 %

4.184

28

7.86

65.5

0.49

0.75 %

4.183

 

After 28 days, the concentration of HEA was reduced by 40% and the kinetics of hydrolysis was not pseudo- first order as indicated by a decrease in the slope of the line over time. This was likely due to a decrease in pH of the test solutions from pH .15 to 7.85 over the 28 day experiment.

 

The results for the hydrolysis of HEA in buffered synthetic sea water at 5°C (Experiment B) were:

 

Day

HEA (mg/L)

Std deviation

 RSD

ln (mg/L)

0

0

106.7

106.3

0.08

0.49

0.07 %

0.46 %

4.670

4.667

7

7

109.8

107.8

3.38

0.08

3.08 %

0.07 %

4.699

4.680

28

28

102.3

102.3

0.13

0.06

0.13 %

0.06 %

4.628

4.628

42

42

100.7

100.6

0.20

0.09

0.20 %

0.09 %

4.613

4.611

56

56

97.9

98.7

0.25

0.23

0.26 %

0.23 %

4.584

4.592

70

70

85.7

85.6

0.11

0.03

0.13 %

0.04 %

4.451

4.449

91

91

90.0

89.1

0.23

0.19

0.26 %

0.21 %

4.500

4.490

 

The results for the hydrolysis of HEA in buffered synthetic sea water at 12 °C (Experiment B) were:

 

Day

HEA (mg/L)

Std deviation

 RSD

ln (mg/L)

0

0

106.7

106.3

0.08

0.49

0.07 %

0.46 %

4.670

4.667

7

7

109.5

104.1

8.85

0.14

8.08 %

0.13 %

4.696

4.645

28

28

92.4

91.3

1.10

0.06

1.19 %

0.07 %

4.526

4.514

42

42

85.3

85.2

0.03

0.08

0.04 %

0.10 %

4.446

4.445

56

56

79.4

79.3

0.05

0.05

0.06 %

0.06 %

4.375

4.473

70

70

64.9

64.9

0.13

0.13

0.20 %

0.20 %

4.173

4.172

 

The results for the hydrolysis of HEA in buffered synthetic sea water at 25°C (Experiment B) were:

 

Day

HEA (mg/L)

Std deviation

 RSD

ln (mg/L)

0

0

106.7

106.3

0.08

0.49

0.07 %

0.46 %

4.670

4.667

7

7

82.1

82.5

0.11

0.05

0.13 %

0.06 %

4.408

4.413

28

28

37.8

36.9

0.06

0.04

0.16 %

0.12 %

3.631

3.608

42

42

20.5

21.6

0.03

0.05

0.17 %

0.24 %

3.023

3.070

56

56

12.6

12.5

0.03

0.01

0.20 %

0.04 %

2.536

2.528

70

70

6.0

6.2

0.25

0.01

4.15 %

0.20 %

1.789

1.818

91

91

3.0

2.9

0.06

0.06

1.95 %

2.01 %

1.094

1.071

 

Description of key information

In contact with water at neutral pH no hydrolysis of 2-hydroxyethyl acrylate will be observed. In alkaline water, the substance will hydrolyse rapidly.

Key value for chemical safety assessment

Additional information

QSAR-disclaimer

In Article 13 of Regulation (EC) No 1907/2006, it is laid down that information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI (of the same Regulation) are met. Furthermore according to Article 25 of the same Regulation testing on vertebrate animals shall be undertaken only as a last resort.

 

According to Annex XI of Regulation (EC) No 1907/2006 (Q)SAR results can be used if (1) the scientific validity of the (Q)SAR model has been established, (2) the substance falls within the applicability domain of the (Q)SAR model, (3) the results are adequate for the purpose of classification and labeling and/or risk assessment and (4) adequate and reliable documentation of the applied method is provided.

 

For the assessment of 2-hydroxyethyl acrylate (Q)SAR results were used for hydrolysis.The criteria listed in Annex XI of Regulation (EC) No 1907/2006 are considered to be not entirely adequately fulfilled, as unidentified fragments were identified. Nevertheless, the QSAR data provides an indication of the hydrolysis rate.