ethyl N2-dodecanoyl-.sc.l.sc.-argininate hydrochloride

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 March 13, 2001 to May 15, 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Guideline study with GLP.

Reason / purpose for cross-reference:

other: Preliminary study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

L.A.E.
Appearance: White solid
Batch: 2625
Expiry date: April 2001
Purity: 92-94%

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

- pH: 7
- Type and final molarity of buffer: 0.1M
- Composition of buffer: Potassium dihydrogen orthophosphate solution
- Temperature: 50ºC±0.5ºC

- pH: 9
- Type and final molarity of buffer: 0.1M
- Composition of buffer: Potassium chloride and boric acid
- Temperature: 50ºC±0.5ºC

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Volumetric flask
- Sterilisation method: Ethanol and allowed to drip dry
- Measures to exclude oxygen: Autoclaved or purged with Nitrogen (pH 9) of helium (pH 7)
- Is there any indication of the test material adsorbing to the walls of the test apparatus? No

Duration:

4 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

200.17 mg/L

Duration:

41 h

pH:

7

Temp.:

70 °C

Initial conc. measured:

29.993 mg/L

Duration:

48 h

pH:

9

Temp.:

25 °C

Initial conc. measured:

60.453 mg/L

Duration:

72 h

pH:

7

Temp.:

60 °C

Initial conc. measured:

29.993 mg/L

Duration:

141 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

29.993 mg/L

Number of replicates:

Two replicates.

Positive controls:

no

Negative controls:

yes

Preliminary study:

The preliminary test has been reported as supporting study.

Test performance:

Test 1. was performed to determine the order of the hydrolysis reaction in buffered solutions at pH7 and pH9 at 50ºC. The concentration of the test substance was monitored as a function of time and the plot of log (% remaining) versus time was found to produce a straight line graph indicating pseudo-first order behaviour.

In test 3, hydrolysis at pH7 and 60ºC and 70ºC was monitored over 3 and 2 days respectively. The rate constant was calculated at 60ºC and 70ºC and these were used to extrapolate values for the rate constant at 25ºC using the Arrhenius relationship. At pH 9 and 25ºC, test substance concentrations were monitored over 2 days and the half-life calculated directly from the data.

Transformation products:

not specified

Key result

pH:

7

Temp.:

25 °C

DT50:

57 d

Key result

pH:

9

Temp.:

25 °C

DT50:

34 h

Other kinetic parameters:

The concentration of the test substance was monitored as a function of time and the plot of log(% remaining) versus time was found to produce a straight line graph indicating pseudo-first order behaviour.

Details on results:

The detector response was found to be linear over the concentration ranges employed.

Mean recoveries showed that standard solutions could be prepared and analysed reproducibly.

Peaks observed in the chromatograms of the blank solutions were negligible.

Validity criteria fulfilled:

yes

Conclusions:

The results indicate that at 25ºC, Nα-Lauroyl-L-arginine ethyl ester monohydrochloride (L.A.E.) possess a half-time of 57 days at pH 7, and 34 hours at pH 9.

Executive summary:

The study was performed to obtain estimates of the rate of hydrolisis of N^α-Lauroyl-L-arginine ethyl ester monohydrochloride (L.A.E.) under pH conditions relevant to the environment. The test has been performed in accordance with the EEC methods for the Determination of Ecotoxicity, Directive 92/69/EEC, Part C, Test C.7 and de OECD Method 111.

Test 1. was performed to determine the order of the hydrolysis reaction in buffered solutions at pH7 and pH9 at 50ºC. The concentration of the test substance was monitored as a function of time and the plot of log (% remaining) versus time was found to produce a straight line graph indicating pseudo-first order behaviour.

In test 3, hydrolysis at pH7 and 60ºC and 70ºC was monitored over 3 and 2 days respectively. The rate constant was calculated at 60ºC and 70ºC and these were used to extrapolate values for the rate constant at 25ºC using the Arrhenius relationship. At pH 9 and 25ºC, test substance concentrations were monitored over 2 days and the half-life calculated directly from the data.

The half -time of LAE at pH 7 and 25ºC is 57 days and at pH 9 and 25ºC is 34 hours.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From January 13, 2000 to October 20, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Guideline study with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

L.A.E.
Appearance: White solid
Batch: 2625
Expiry date: April 2001
Purity: 92-94%

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

- pH: 4
- Type and final molarity of buffer: 0.1M
- Composition of buffer: Potassium dihydrate citrate solution.
- Temperature: 50ºC±0.5ºC

- pH: 7
- Type and final molarity of buffer: 0.1M
- Composition of buffer: Potassium dihydrogen orthophosphate solution
- Temperature: 50ºC±0.5ºC

- pH: 9
- Type and final molarity of buffer: 0.1M
- Composition of buffer: Potassium chloride and boric acid
- Temperature: 50ºC±0.5ºC

Details on test conditions:

Duplicate solutions were prepared at each pH value.
Blanks containing buffer solution only (one at each pH) were treated in the same manner as the test solutions.

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

48.423 mg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

21.147 mg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

189.21 mg/L

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

40.096 mg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

21.155 mg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

194.59 mg/L

Number of replicates:

2 for each pH sample: 4, 7 and 9.

Positive controls:

no

Negative controls:

yes

Preliminary study:

Results indicate that at 25ºC, L.A.E will possess half-life times of greater than 1 year at pH4 and between 1 day and 1 year at pH7 and pH9.

Transformation products:

not measured

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

pH=4; % Mean recovery: 104.2
pH=4; % Mean recovery: 103.1
pH=7; % Mean recovery: 70.2
pH=7; % Mean recovery: 56.8
pH=9; % Mean recovery: 108.6
pH=9; % Mean recovery: 104.4

% Recovery:

ca. 100

pH:

4

Duration:

ca. 0 h

% Recovery:

ca. 100

pH:

7

Duration:

ca. 0 h

% Recovery:

ca. 100

pH:

9

Duration:

ca. 0 h

% Recovery:

ca. 93

pH:

4

Duration:

ca. 2.4 h

% Recovery:

ca. 72.9

pH:

7

Duration:

ca. 2.4 h

% Recovery:

ca. 57.3

pH:

9

Duration:

ca. 2.4 h

% Recovery:

ca. 95.9

pH:

4

Duration:

ca. 5 d

% Recovery:

ca. 0

pH:

7

Duration:

ca. 5 d

% Recovery:

ca. 0

pH:

9

Duration:

ca. 5 d

Key result

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Key result

pH:

7

Temp.:

25 °C

DT50:

> 24 h

Key result

pH:

9

Temp.:

25 °C

DT50:

> 24 h

Validity criteria fulfilled:

yes

Conclusions:

Nα-Lauroyl-L-arginine ethyl ester monohydrochloride (L.A.E): the half-life at 25ºC can be estimated as greater than 1 year at pH4 and between 1 day and 1 year at pH7 and pH9.

Executive summary:

According to OECD Guideline 111 and EU method C.7 (Hydrolysis as a Function of pH) and the results of the test method it can be estimated that for N^α-Lauroyl-L-arginine ethyl ester monohydrochloride (L.A.E):

- 10% hydrolisis occurring in 5 days at 50ºC is equivalent to a half-life time of 1 year at 25ºC.

- 50% hydrolisis occurring in 2,4 hours at 50ºC is equivalent to a half-life of 1 day at 25ºC.

Applying these criteria to the results obtained for N^α-Lauroyl-L-arginine ethyl ester monohydrochloride (L.A.E), the half-life at 25ºC can be estimated as greater than 1 year at pH4 and between 1 day and 1 year at pH7 and pH9.

Description of key information

Key study: Test method according to EU method C.7 and OECD 107. GLP study. The half-life time at pH 7 and 25 ºC is 57 days and the half-time of LAE at pH 9 and 25ºC is 34 hours.

Key value for chemical safety assessment

Half-life for hydrolysis:

57 d

at the temperature of:

25 °C

Additional information

- Supporting study 1:

The rate of hydrolisis of N^α-Lauroyl-L-arginine ethyl ester monohydrochloride (LAE) under pH conditions was measured according to OECD 111 and EU method C.7..Applying these criteria to the results obtained for N^α-Lauroyl-L-arginine ethyl ester monohydrochloride (LAE), the half-life at 25ºC can be estimated as greater than 1 year at pH4 and between 1 day and 1 year at pH7 and pH9.