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Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 27th, 2012 - April 7th, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Version / remarks:
(2004)
Deviations:
no
Qualifier:
according to
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
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
Samples for analysis were taken immediately after preparation (t=0) and after 5 days. The samples taken at t=5 days were cooled to room temperature using running tap water.

Buffers:
Acetate buffer pH 4, 0.01 M: solution of 16.7% 0.01 M sodium acetate in water and 83.3% 0.01 M acetic acid in water. The buffer contains 0.0009% (w/v) sodium azide.

Phosphate buffer pH 7, 0.01 M: solution of 0.01 M potassium di-hydrogenphosphate in water adjusted to pH 7 using 1 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.

Borate buffer pH 9, 0.01 M: solution of 0.01 M boric acid in water and 0.01 M potassium chloride in water adjusted to pH 9 using 1 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.
Details on test conditions:
Performance of the study:
The rate of hydrolysis of the test substance as a function of pH was determined at pH values normally found in the environment (pH 4-9).

Preliminary test - Tier 1:
The test substance was spiked to the buffer solutions at a target concentration of 20 mg/L using a spiking solution in water. Each solution was filter-sterilised through a 0.2 µm FP 30/0.2 CA-S filter (Whatman, Dassel, Germany) and transferred into a sterile vessel. To exclude oxygen, nitrogen gas was purged through the solution for 5 minutes. 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 at 49.9°C +/- 0.1°C.

The concentration of the test substance in the test samples was determined immediately after preparation (t=0) and after 5 days. The samples taken at t=5 days were cooled to room temperature using running tap water. The samples were diluted with buffer solution to obtain a concentration within the calibration range.

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

The pH of each of the test solutions (except for the blanks) was determined at each sampling time.
Number of replicates:
Two
Positive controls:
no
Negative controls:
no
Preliminary study:
At pH 4, 7 and pH 9, < 10% of hydrolysis was observed after 5 day (half-life time at 25°C is > 1 year). According to the guideline, no further tests were required.
Test performance:
RECOVERIES
- Recovery is the concentration analysed at t=0 relative to the nominal concentration.
- Mean recovery in the table below is the mean of duplicate test samples.
- The mean recoveries of all the buffer solutions fell within he acceptable range of 90-110%; the analytical method was adequate to support the hydrolysis study on the test substance.
Transformation products:
not measured
% Recovery:
100
pH:
4
Temp.:
50 °C
Duration:
5 d
Remarks on result:
other: actual recovery: 107%
% Recovery:
100
pH:
7
Temp.:
50 °C
Duration:
5 d
Remarks on result:
other: actual recovery: 102%
% Recovery:
100
pH:
9
Temp.:
50 °C
Duration:
5 d
Remarks on result:
other: actual recovery: 101%
Key result
Remarks on result:
other: hydrolytically stable based on preliminary test (at pH 4, 7 and 9)
Details on results:
The analytical results of the preliminary test are given in the table hereunder.

At pH 4, pH 7 and pH 9 a degree of hydrolysis of < 10% was observed after 5 days. It demonstrated that the half-life time of the test substance at 25°C is > 1 year. According to the guideline, no further tests were required.

No test substance was detected in the blank buffer solutions.

The mean recoveries of the buffer solutions fell within the criterion range of 90-110%. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test substance.

Table. Preliminary test - hydrolysis of the substance at pH 4, pH 7 and pH 9 at 50.0 ±1 °C:

pH code

Sampling time

Analysed concentration
[mg/l]

Degree of hydrolysis
[%]

Actual pH

Individual

Mean

 

 

 

 

 

 

pH 4

0 hours

21.6

 

 

4.1

 

 

21.4

 

 

4.1

 

 

 

 

 

 

 

5 days

20.9

2.8

3.3

4.1

 

 

20.7

3.8

 

4.1

 

 

 

 

 

 

pH 7

0 hours

20.5

 

 

7.0

 

 

20.5

 

 

7.1

 

 

 

 

 

 

 

5 days

19.4

5.1

4.7

7.0

 

 

19.6

4.3

 

7.0

 

 

 

 

 

 

pH 9

0 hours

20.1

 

 

9.0

 

 

20.1

 

 

9.0

 

 

 

 

 

 

 

5 days

19.5

3.0

2.9

9.0

 

 

19.6

2.8

 

9.0

 

 

 

 

 

 

Validity criteria fulfilled:
yes
Conclusions:
A hydrolysis study was carried out according to EC C.7, OECD 111, EPA OPPTS 830.2120 and GLP. At pH 4, 7 and 9 and 50 °C, a degree of < 10% of hydrolysis was observed after 5 days. This corresponds with a half-life time at 25°C of > 1 year; the substance can be considered hydrolytically stable at pH 4, 7 and 9.
Endpoint:
hydrolysis
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: read-across from a structural analogue
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The substance Accelerator (Reaction mass of 2,2'-[(4-methylphenyl)imino]bisethanol and 2-[[2-(2-hydroxyethoxy)ethyl](4-methylphenyl)amino]-ethanol)) is a structural analogue of 2,2'-[(3-methylphenyl)imino]bisethanol. Accelerator contains ca. 50-60% of 2,2'-[(4-methylphenyl)imino]bisethanol as the main constituent. The only difference between 2,2'-[(4-methylphenyl)imino]bisethanol and the target chemical 2,2'-[(3-methylphenyl)imino]bisethanol is the position of the methyl group in the phenyl ring (para vs meta with regard to the imino group). This is not expected to have any significant influnce on either physico-chemical properties or toxicological behavior of the substances. Next to 2,2'-[(4-methylphenyl)imino]bisethanol Accelerator contains ca. 35-45% of 2-{[2-(2-hydroxyethoxy)ethyl](4-methylphenyl)amino}ethanol, which contains the same structural moiety of 2,2'-[(4-methylphenyl)imino]bisethanol, but with one alcohol moiety transformed into the ester bond with ethylene glycol. As Accelerator contains over 50% of the structural analogue of 2,2'-[(3-methylphenyl)imino]bisethanol, with the only difference being the position of the methyl group in the phenyl ring, it is considered acceptable to read across the results of the hydrolysis study from Accelerator to 2,2'-[(3-methylphenyl)imino]bisethanol. Furthermore, a structural analogue of 2-{[2-(2-hydroxyethoxy)ethyl](4-methylphenyl)amino}ethanol, 2-{[2-(2-hydroxyethoxy)ethyl](3-methylphenyl)amino}ethanol, differing only by the position of the methyl group in the phenyl ring (meta vs. para) is also present as an impurity up to 7% concentration in the target chemical 2,2'-[(3-methylphenyl)imino]bisethanol.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source chemical is the Reaction mass of 2,2'-[(4-methylphenyl)imino]bisethanol and 2-[[2-(2-hydroxyethoxy)ethyl](4-methylphenyl)amino]-ethanol)), containing ca. 50-60% of 2,2'-[(4-methylphenyl)imino]bisethanol, ca. 35-45% of 2-{[2-(2-hydroxyethoxy)ethyl](4-methylphenyl)amino}ethanol and ca. 2-4% of 2-[{2-[2-(2-hydroxyethoxy)ethoxy]ethyl}(4-methylphenyl)amino]ethanol. The purity of the substance is ca. 90-100%.

The target chemical is 2,2'-[(3-methylphenyl)imino]bisethanol with the purity of 90-100%. The substance contains up to 7% 2-{[2-(2-hydroxyethoxy)ethyl](3-methylphenyl)amino}ethanol as an impurity.

3. ANALOGUE APPROACH JUSTIFICATION
The substance Accelerator (Reaction mass of 2,2'-[(4-methylphenyl)imino]bisethanol and 2-[[2-(2-hydroxyethoxy)ethyl](4-methylphenyl)amino]-ethanol)) is a structural analogue of 2,2'-[(3-methylphenyl)imino]bisethanol. Accelerator contains ca. 50-60% of 2,2'-[(4-methylphenyl)imino]bisethanol as the main constituent. The only difference between 2,2'-[(4-methylphenyl)imino]bisethanol and the target chemical 2,2'-[(3-methylphenyl)imino]bisethanol is the position of the methyl group in the phenyl ring (para vs meta with regard to the imino group). This is not expected to have influnce on hydrolytical behavior of the substances. Next to 2,2'-[(4-methylphenyl)imino]bisethanol Accelerator contains ca. 35-45% of 2-{[2-(2-hydroxyethoxy)ethyl](4-methylphenyl)amino}ethanol, which contains the same structural moiety of 2,2'-[(4-methylphenyl)imino]bisethanol, but with one alcohol moiety transformed into the ester bond with ethylene glycol. The presence of the ester moiety is not expected to influence the hydrolytical stability of the substances. As Accelerator contains over 50% of the structural analogue of 2,2'-[(3-methylphenyl)imino]bisethanol, with the only difference being the position of the methyl group in the phenyl ring, it is considered acceptable to read across the results of the hydrolysis study from Accelerator to 2,2'-[(3-methylphenyl)imino]bisethanol. Furthermore, a structural analogue of 2-{[2-(2-hydroxyethoxy)ethyl](4-methylphenyl)amino}ethanol, 2-{[2-(2-hydroxyethoxy)ethyl](3-methylphenyl)amino}ethanol, differing only by the position of the methyl group in the phenyl ring (meta vs. para) is also present as an impurity up to 7% concentration in the target chemical 2,2'-[(3-methylphenyl)imino]bisethanol.

Furthermore, the data matrix constructed based on the available physico-chemical and (eco)toxicological properties of both substances indicates that the substances have comparable properties across the complete range of endpoints.

Based on this, read-across from Accelerator to 2,2'-[(3-methylphenyl)imino]bisethanol is considered to be justified.

4. DATA MATRIX
Accelerator 2,2'-[(3-methylphenyl)imino]bisethanol

Molecular weight ~217 195.26
State of the substance at ambient conditions Clear slightly yellowish to brown viscous liquid Colourless solidified melt
Melting/freezing point [ºC] Not determined (glass transition temp. of -28ºC) 66.9
Boiling point [ºC] - (decomposition of test item at >275ºC) - (reaction and/or decomposition of the test item at > 225°C)
Relative density at 20 ºC 1.11 1.115
Vapour pressure at 25 ºC [Pa] 0.0025 0.000223 (calculated)
Surface tension [mN/m] 65.2, not surface active 65.4 at 1 g/L, not surface active
Water solubility at 20 ºC [mg/L] 21800 9330
Partition coefficient n-octanol/water [log Pow] 2.17 1.9
Flash point [ºC] 176 193
Flammability Not flammable, not pyrophoric Not flammable, not pyrophoric
Explosive properties Not explosive Not explosive
Auto-ignition temperature 395ºC 395ºC
Oxidising properties Not oxidizing Not oxidizing
Viscosity (dynamic, mPas) 2797 5474
Ready biodegradability Not readily biodegradable Not readily biodegradable
Hydrolysis as function of pH Half life for hydrolysis >1 y at 25 ºC, hydrolytically stable Read-across
Adsorption/desorption [log Koc] 2.33 (weight-averaged of 4 main components) Read-across
Acute toxicity to daphnia, EC50 [mg/L] 48 107 mg/L
Growth inhibition algae, EC50, NOEC [mg/L] >100; 100 >100; 100
Acute toxicity to fish, LC50 [mg/L] >100 >102
Acute oral, LD50 [mg/kg bw] 619 300-2000
Skin irritation/corrosion Skin irritant cat 2. Read-across
Eye irritation/corrosion Corrosive, cat 1. Read-across
Skin sensitisation Sensitiser Read-across
In vitro gene mutation in bacteria (Ames test) Mutagenic Non-mutagenic
In vitro cytogenicity in mammalian cells Not clastogenic, does not disturb mitotic processes Not clastogenic, does not disturb mitotic processes
In vivo genotox (Comet) Not mutagenic No data
28-day repeated dose toxicity NOAEL 100 mg/kg bw LOAEL 50 mg/kg bw/day



Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Version / remarks:
(2004)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 835.2120 (Hydrolysis of Parent and Degradates as a Function of pH at 25°C)
Version / remarks:
(2008)
Deviations:
no
Preliminary study:
At pH 4, 7 and pH 9, < 10% of hydrolysis was observed after 5 day (half-life time at 25°C is > 1 year). According to the guideline, no further tests were required.
Test performance:
RECOVERIES
- Recovery is the concentration analysed at t=0 relative to the nominal concentration.
- Mean recovery in the table below is the mean of duplicate test samples.
- The mean recoveries of all the buffer solutions fell within he acceptable range of 90-110%; the analytical method was adequate to support the hydrolysis study on the test substance.
Transformation products:
not measured
% Recovery:
100
pH:
4
Temp.:
50 °C
Duration:
5 d
Remarks on result:
other: actual recovery: 107%
% Recovery:
100
pH:
7
Temp.:
50 °C
Duration:
5 d
Remarks on result:
other: actual recovery: 102%
% Recovery:
100
pH:
9
Temp.:
50 °C
Duration:
5 d
Remarks on result:
other: actual recovery: 101%
Key result
Remarks on result:
other: hydrolytically stable based on preliminary test (at pH 4, 7 and 9)
Details on results:
The analytical results of the preliminary test are given in the table hereunder.

At pH 4, pH 7 and pH 9 a degree of hydrolysis of < 10% was observed after 5 days. It demonstrated that the half-life time of the test substance at 25°C is > 1 year. According to the guideline, no further tests were required.

No test substance was detected in the blank buffer solutions.

The mean recoveries of the buffer solutions fell within the criterion range of 90-110%. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test substance.

Table. Preliminary test - hydrolysis of the substance at pH 4, pH 7 and pH 9 at 50.0 ±1 °C:

pH code

Sampling time

Analysed concentration
[mg/l]

Degree of hydrolysis
[%]

Actual pH

Individual

Mean

 

 

 

 

 

 

pH 4

0 hours

21.6

 

 

4.1

 

 

21.4

 

 

4.1

 

 

 

 

 

 

 

5 days

20.9

2.8

3.3

4.1

 

 

20.7

3.8

 

4.1

 

 

 

 

 

 

pH 7

0 hours

20.5

 

 

7.0

 

 

20.5

 

 

7.1

 

 

 

 

 

 

 

5 days

19.4

5.1

4.7

7.0

 

 

19.6

4.3

 

7.0

 

 

 

 

 

 

pH 9

0 hours

20.1

 

 

9.0

 

 

20.1

 

 

9.0

 

 

 

 

 

 

 

5 days

19.5

3.0

2.9

9.0

 

 

19.6

2.8

 

9.0

 

 

 

 

 

 

Validity criteria fulfilled:
yes
Conclusions:
A hydrolysis study with a structural analogue of 2,2'-[(3-methylphenyl)imino]bisethanol, Accelerator, was carried out according to EC C.7, OECD 111, EPA OPPTS 830.2120 and GLP. At pH 4, 7 and 9 and 50 °C, a degree of < 10% of hydrolysis was observed after 5 days. This corresponds with a half-life time at 25°C of > 1 year; thus the substance can be considered hydrolytically stable at pH 4, 7 and 9. This result can be read across to 2,2'-[(3-methylphenyl)imino]bisethanol.
Executive summary:

A hydrolysis study with a structural analogue of 2,2'-[(3-methylphenyl)imino]bisethanol, Accelerator, was carried out according to EC C.7, OECD 111, EPA OPPTS 830.2120 and GLP.  At pH 4, 7 and 9 and 50 °C, a degree of < 10% of hydrolysis was observed after 5 days. This corresponds with a half-life time at 25°C of > 1 year; thus the substance can be considered hydrolytically stable at pH 4, 7 and 9. According to the guideline, no further tests were required. The mean recoveries of the buffer solutions fell within the criterion range of 90-110%. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test substance.

This result can be read across to 2,2'-[(3-methylphenyl)imino]bisethanol.  

Description of key information

In a Tier 1 study (in accordance with EC C.7, OECD 111, EPA OPPTS 830.2120), performed with a structural analogue of 2,2’-[(3-methylphenyl)imino]bisethanol, Accelerator, < 10% of hydrolysis was observed at pH 4, 7 and 9 after 5 days at 50 °C. Therefore the half-life time at 25°C is > 1 year and the substance can be considered hydrolytically stable at pH 4, 7 and 9. This result can be read across to 2,2’-[(3-methylphenyl)imino]bisethanol.

Key value for chemical safety assessment

Additional information

No hydrolysis study with 2,2’-[(3 -methylphenyl)imino]bisethanol is available; however, adequate data are available on its structural analogue Accelerator (Reaction mass of 2,2’-[(4-methylphenyl)imino]bisethanol and 2-[[2-(2-hydroxyethoxy)ethyl](4-methylphenyl)amino]-ethanol). Based on structural similarities of the substances and their similar physico-chemical and (eco)toxicological properties, read-across from Accelerator to 2,2’-[(3-methylphenyl)imino]bisethanol is considered to be justified.

The hydrolysis study with the structural analogue of 2,2’-[(3-methylphenyl)imino]bisethanol, Accelerator, was carried out according to EC C.7, OECD 111, EPA OPPTS 830.2120 and GLP. At pH 4, 7 and 9 and 50 °C, a degree of < 10% of hydrolysis was observed after 5 days. This corresponds with a half-life time at 25°C of > 1 year; thus the substance can be considered hydrolytically stable at pH 4, 7 and 9. According to the guideline, no further tests were required. The mean recoveries of the buffer solutions fell within the criterion range of 90-110%. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test substance.

This result can be read across to 2,2’-[(3-methylphenyl)imino]bisethanol.