4-(hydroxymethyl)-4-methyl-1-phenylpyrazolidin-3-one

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 June 2017 to 04 September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-(hydroxymethyl)-4-methyl-1-phenylpyrazolidin-3-one

EC Number:

235-920-3

EC Name:

4-(hydroxymethyl)-4-methyl-1-phenylpyrazolidin-3-one

Cas Number:

13047-13-7

Molecular formula:

C11H14N2O2

IUPAC Name:

4-(hydroxymethyl)-4-methyl-1-phenylpyrazolidin-3-one

Test material form:

solid: particulate/powder

Study design

Analytical monitoring:

yes

Details on sampling:

Samples were taken at t=0 hours, 24 hours and at 5 days (at pH 4 only). Blank buffer solutions containing a similar content of blank spiking solution were treated similarly as the test samples and analysed at t=0 hours.

Buffers:

Acetate buffer pH 4, 0.01 M:
solution of 16.7% 0.01 M sodium acetate and 83.3% 0.01 M acetic acid. The buffer contains 0.0009% (w/v) sodium azide.
Phosphate buffer pH 7, 0.01 M:
solution of 0.01 M potassium di-hydrogenphosphate 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 and 0.01 M potassium chloride adjusted to pH 9 using 1 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.

Duration of test

Duration of test 1

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

14.2 mg/L

Duration of test 2

Duration:

24 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

14.5 mg/L

Duration of test 3

Duration:

24 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

14.2 mg/L

Number of replicates:

2/sampling time

Results and discussion

Preliminary study:

At pH 4, a degree of hydrolysis of ≥ 10% was observed after 5 days.
At pH 7 and pH 9, a degree of hydrolysis of ≥ 10% was already observed after 24 hours.
No test item was detected in the blank buffer solutions.

The mean recoveries 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

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

Key result

pH:

4

Temp.:

20 °C

DT50:

>= 41 - <= 138 d

Type:

not specified

Remarks on result:

other: based on extrapolation of the results at 50 °C

Dissipation DT50 of parent compound 2

Key result

pH:

7

Temp.:

20 °C

DT50:

>= 1 - <= 5 d

Type:

not specified

Remarks on result:

other: based on extrapolation of the results at 50 °C

Dissipation DT50 of parent compound 3

Key result

pH:

9

Temp.:

20 °C

DT50:

>= 0.2 - <= 0.7 d

Type:

not specified

Remarks on result:

other: based on extrapolation of the results at 50 °C

Any other information on results incl. tables

Preliminary Test: Hydrolysis of the Test Item at pH 4, pH 7 and pH 9

pH code	Sampling time	Analyzed concentration [mg/L]	Degree of hydrolysis [%]		pH
			Individual	Mean
pH 4	0 hours	14.2			4.0
		14.1			4.0
	24 hours	11.1	22	21	4.0
		11.4	20		4.0
	5 days	1.79	87	87	4.0
		1.97	86		4.0
pH 7	0 hours	14.4			7.1
		14.5			7.1
	24 hours	n.d.	100	100	7.1
		n.d.	100		7.1
	5 days	n.a.	n.a.	n.a.	n.a.^1
		n.a.	n.a.		n.a.^1
pH 9	0 hours	14.3			9.0
		14.1			9.0
	24 hours	n.d.	100	100	9.1
		n.d.	100		9.1
	5 days	n.a.	n.a.	n.a.	n.a.^1
		n.a.	n.a.		n.a.^1

n.a.                                 Not applicable. n.d.                                Not detected.              ¹ Determination over 5 days was not performed since the test item was 100% hydrolyzed after 24 hours.                   

 

Applicant's summary and conclusion

Conclusions:

At pH 4, a degree of hydrolysis of ≥ 10% was observed after 5 days.
At pH 7 and pH 9, a degree of hydrolysis of ≥ 10% was already observed after 24 hours.
The half-life time of the substance at 20°C was:
t½ pH 4: > 41 d
pH 7 1-5 d
pH 9 0.2-0.7 d

Executive summary:

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

The buffer solutions were 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. The test substance was spiked to the solutions at a target concentration of 15 mg/L using a spiking solution in acetonitrile.  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 50.1°C ± 0.1°C. Since at pH 7 and pH 9 the test item was completely hydrolysed after 24 hours, only pH 4 was sampled after 5 days.  The samples taken at t=24 hours and t=5 days were cooled to room temperature using running tap water.  

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.

At pH 4, a degree of hydrolysis of ≥ 10% was observed after 5 days. At pH 7 and pH 9, a degree of hydrolysis of ≥ 10% was already observed after 24 hours.  No test item was detected in the blank buffer solutions.

Predicted t_1/2and 90% hydrolysis based on pre-test results

pH	Estimated t1/2 [days]		Estimated 90% hydrolysis [days]
	Minimum	Maximum	Minimum	Maximum
pH 4	41	138	135	458
pH 7	1	5	4	14
pH 9	0.2	0.7	0.7	2