Hyoscine

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-09-04 to 2015-10-14

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)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Details on sampling:

- Solvent for sample stabilization: acidified acetonitrile (1% H3PO4 v/v)- At each sampling time 2.0 mL acetonitrile acidified with 1 % phosphoric acid were added to the sample with a Hamilton syringe (dilution factor = 2) and the sample was homogenized.- Sampling time: Tier 1 Test: at the beginning, after 2.4 hours and after 120 hours; Tier 2 Test: pH 7 at 20°C: 0, 48, 166, 268, 433, 602, 720 hours, pH 9 at 20°C: 0, 48, 95, 166, 268, 337, 433, 602 hours, pH 7 at 35°C: 0, 48, 166, 268, 337, 433, 602, 720 hours, pH 9 at 35°C: 0, 28, 48, 69, 95, 166, 214 hours, pH 7 at 50°C: 0, 44, 69, 95, 166, 214, 337 hours, pH 9 at 50°C: 0, 4, 20, 28, 44, 48, 53, 69 hours

Buffers:

- Type and final molarity of buffer: citrate buffer (pH 4), phosphate buffer (pH 7) and borate buffer (pH 9); concentration of each 0.05 M
- Composition of buffer:
Citrate buffer: 10.519 g citric acid monohydrate were dissolved in 500 mL deionised water. 59 mL of the sodium hydroxide (1M) solution was added and the flask was brought to a total volume of 1 L with deionised water. The pH value of the buffer solution was determined to be 4.00.
Phosphate buffer: 6.810 g Potassium dihydrogenphosphate were dissolved in 500 mL deionised water. 30 mL of the sodium hydroxide (1M) solution was added and the flask was brought to a total volume of 1 L with deionised water.
Borate buffer: 3.747 g potassium chloride and 3.098 g boric acid were dissolved in 500 mL deionised water. 20 mL of the sodium hydroxide (1M) solution was added and the flask was brought to a total volume of 1 L with deionised water.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: normal laboratory glassware and instrumentation; 100 mL (250 mL for Tier 2) volumetric flask; 6 mL glass vials; pH meter (WTW Germany); Water bath; Min.-max.-thermometer and data logger; Climate cabinet, Mass balance; Flat bed shaker
- Measures taken to avoid photolytic effects: photolytic interference was avoided; method not specified
- Measures to exclude oxygen: degassing the buffers with argon for at least five minutes and purging the vessels with argon before preparing the test solution.
- If no traps were used, is the test system closed
- Is there any indication of the test material adsorbing to the walls of the test apparatus? no

Number of replicates:

- Tier 2 Test: Individual replicate test samples (a minimum of duplicate samples contained in separate reaction vessels) were removed and the contents were analysed at each of at least six sampling times (for a minimum of twelve replicate data points).

Positive controls:

no

Negative controls:

no

Transformation products:

not specified

Key result

pH:

7

Temp.:

20 °C

DT50:

163 d

Type:

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

pH:

9

Temp.:

20 °C

DT50:

14 d

Type:

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

pH:

7

Temp.:

35 °C

DT50:

33.3 d

Type:

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

pH:

9

Temp.:

35 °C

DT50:

3.4 d

Type:

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

pH:

7

Temp.:

50 °C

DT50:

7.58 d

Type:

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

pH:

9

Temp.:

50 °C

DT50:

0.96 d

Type:

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

Tier 1 Test:

The hydrolysis of the test item was negligible at pH 4. The degradation of Scopolamine was less than 10% at pH 4 at 50°C over a period of 120 hours. Therefore the corresponding half-life time at pH 4 can be estimated to be longer than one year at 25°C.

The hydrolysis of the test item was more than 10% at pH 7 and pH 9 at 50°C over a period of 120 hours. Based on this results a Tier 2 test at 20°C, 35°C and 50°C was performed at pH 7 and pH 9.

Table 1: Summarized degradation half-life values (Tier 2 Test)

Test-temperature	pH value	Kinetic model	Slope a [h^-1]	Y-axis intercept b	DT50 [h]	DT50 [d]
20°C	pH 7	SFO	-7.85 x 10^-5	6.50 x 10^-3	3918	163
	pH 9	SFO	-9.05 x 10^-4	6.10 x 10^-3	339	14
35°C	pH 7	SFO	-3.83 x 10^-4	4.44 x 10^-3	798	33.3
	pH 9	SFO	-3.73 x 10^-3	3.07 x 10^-4	81	3.4
50°C	pH 7	SFO	-1.67 x 10^-3	2.28 x 10^-3	182	7.58
	pH 9	SFO	-1.32 x 10^-2	2.01 x 10^-3	23	0.96

SFO = Single First Order

Validity criteria fulfilled:

yes

Conclusions:

The half-life time at pH 4 can be estimated to be longer than one year at 25°C. For pH 7 and pH 9 a half-life of 163 and 14 days at 20°C was determined, respectively.

Description of key information

The hydrolysis of the test item was negligible at pH 4. The degradation of Scopolamine was less than 10% at pH 4 at 50°C over a period of 120 hours. Therefore the corresponding half-life time at pH 4 can be estimated to be longer than one year at 25°C.

At 35°C a half-life of 33.3 days for pH 7 and 3.4 days for pH 9 were determined. At 50°C a half-life of 7.58 days for pH 7 and 0.96 days for pH 9 were determined.

At 20 °C, half-lives of 163 days at pH 7 and 14 days at pH 9 were determined.

Key value for chemical safety assessment

Half-life for hydrolysis:

163 d

at the temperature of:

20 °C