DL-α-(aminomethyl)-p-hydroxybenzylic alcohol hydrochloride

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

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:

Batch (Lot) Number: D151-1710037
Expiry date: 26 October 2019
Physical Description: White to off white powder (determined by Charles River Den Bosch)
Purity/Composition: 99.8% w/w
Storage Conditions: At room temperature protected from light

Radiolabelling:

no

Analytical monitoring:

yes

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. Buffer contained 0.0009% (w/v) sodium azide.
Phosphate buffer pH 7, 0.01 M Solution of 0.01 M potassium di-hydrogen-phosphate in water adjusted to pH 7 using 1N sodium hydroxide. Buffer contained 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 1N sodium hydroxide. Buffer contained 0.0009% (w/v) sodium azide.
Acetate buffer pH 9, 0.1 M Solution of 0.1 M ammonium acetate in water adjusted to pH 9 using ammonia solution, 25%. Buffer contained 0.0009% (w/v) sodium azide.

Details on test conditions:

The rate of hydrolysis of the test item as a function of pH was determined at pH values normally found in the environment (pH 4-9).

Preliminary Test - Tier 1
Test item solutions were prepared in the buffer solutions at a target concentration of 300 mg/L. 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 49.4°C  0.8°C.
The concentration of the test item in the test samples was determined immediately after preparation (t=0) and after 2.4 hours and 5 days. The samples taken at t=2.4 hours and t=5 days were cooled to room temperature using running tap water.
Analysis was performed on subsamples of 300 µL. The samples and the blank buffer solutions were diluted in a 3:7 (v:v) ratio with acetonitrile and analyzed.
The pH of each of the test solutions (except for the blanks) was determined at each sampling time.

Main Study - Tier 2
Test samples were prepared and treated similarly as during the preliminary test. The concentrations of the test item were determined immediately after preparation (t=0) and at several sampling points after t=0.
Blank buffer solutions were treated similarly as the test samples and analyzed at t=0.
The pH of each of the test solutions (except for the blanks) was determined at least at the beginning and at the end of the test.

Duration:

0 h

pH:

4

Temp.:

49.4 °C

Initial conc. measured:

ca. 280 mg/L

Duration:

2.4 h

pH:

4

Temp.:

49.4 °C

Initial conc. measured:

ca. 280 mg/L

Duration:

5 d

pH:

4

Temp.:

49.4 °C

Initial conc. measured:

ca. 292 mg/L

Duration:

0 h

pH:

7

Temp.:

49.4 °C

Initial conc. measured:

ca. 341 mg/L

Remarks:

estimated concentration from calibration curve

Duration:

2.4 h

pH:

7

Temp.:

49.4 °C

Initial conc. measured:

>= 343 - <= 346 mg/L

Remarks:

estimated concentration from calibration curve

Duration:

5 d

pH:

7

Temp.:

49.4

Initial conc. measured:

>= 351 - <= 358 mg/L

Remarks:

estimated concentration from calibration curve

Duration:

0 h

pH:

9

Temp.:

49.4

Initial conc. measured:

>= 289 - <= 292 mg/L

Duration:

2.4 h

pH:

9

Temp.:

49.4 °C

Initial conc. measured:

>= 290 - <= 298 mg/L

Duration:

5 d

pH:

9

Initial conc. measured:

ca. 221 mg/L

Number of replicates:

duplicate

Positive controls:

no

Negative controls:

yes

Statistical methods:

Not Applicable

Preliminary study:

At pH 4 and pH 7, a degree of hydrolysis of < 10% was observed after 5 days. It demonstrated that the half-life time of the test item at 25°C is > 1 year. According to the guideline, no further tests were required.
At pH 9, a degree of hydrolysis of ≥ 10% was observed after 5 days. According to the guideline, the higher Tier test was required to determine the half-life time of the test item.
No test item was detected in the blank buffer solutions.
The mean recoveries of the of the test item containing buffer solutions at t=0 fell within the criterion range of 90-110%. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test item.

Transformation products:

not measured

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Remarks on result:

hydrolytically stable based on preliminary test

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Remarks on result:

hydrolytically stable based on preliminary test

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

ca. 0 h-1

DT50:

ca. 305 d

Type:

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

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0 h-1

DT50:

149 d

Type:

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

pH:

9

Temp.:

50 °C

Hydrolysis rate constant:

ca. 0.005 h-1

DT50:

ca. 5.8 d

Type:

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

pH:

9

Temp.:

60 °C

Hydrolysis rate constant:

0.011 h-1

DT50:

ca. 2.6 d

Type:

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

Validity criteria fulfilled:

yes

Description of key information

The rate constant (kobs) and half-life time of the test item at each temperature (20, 50 and 60°C) was

obtained and the Arrhenius equation was used to determine the rate constant and half-life time at 25°C , which were calculated to be 1.93 x10E-4 hours and 149 days respectively.

Key value for chemical safety assessment

Half-life for hydrolysis:

149 d

at the temperature of:

25 °C