1-nitroguanidine

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 August 2010 - 27 September 2010

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:

Lot 1288

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: 0, 24, 48, 72, 96 and 168 h
- Sampling method: aliquots were taken from the samples after respective time intervals.

Buffers:

- Buffer solution pH 4.0: Citrate / NaOH / HCl buffer, CertiPUR®, Merck, P/N 1.09435
- Buffer solution pH 7.0: Phosphate buffer, Bernd Kraft GmbH, P/N 03086
- Buffer solution pH 9.0: Boric acid / KCl / NaOH buffer, CertiPUR®, Merck, Art.-Nr. 1.09461

Test solution, pH 4.0:
34.00 mg nitroguanidine test item were weighed into a 100 mL volumetric flask, dissolved in buffer solution pH 4.0 and made up to volume with buffer solution pH 4.0.

Test solution, pH 7.0:
34.22 mg nitroguanidine test item were weighed into a 100 mL volumetric flask, dissolved in buffer solution pH 7.0 and made up to volume with buffer solution pH 7.0.

Test solution 1, pH 9.0:
34.17 mg nitroguanidine test item were weighed into a 100 mL volumetric flask, dissolved in buffer solution pH 9.0 and made up to volume with buffer solution pH 9.0.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: amber glass flasks
- Lighting: none
- Measures taken to avoid photolytic effects: incubationin amber glass flasks
- Is there any indication of the test material adsorbing to the walls of the test apparatus? No

TEST MEDIUM
- Volume used/treatment: 25 ml
- Preparation of test medium: test substance was weighed into a 100 mL volumetric flask, dissolved in buffer solution (pH 4.0, 7.0 or 9.0) and made up to volume with respective buffer solution.
- Renewal of test solution: no

Duration:

7 d

pH:

4

Initial conc. measured:

>= 265.2 - <= 266.1 mg/L

Duration:

7 d

pH:

7

Initial conc. measured:

>= 266.9 - <= 270.5 mg/L

Duration:

42 d

pH:

9

Initial conc. measured:

>= 266.5 - < 270.9 mg/L

Number of replicates:

2

Positive controls:

no

Negative controls:

no

Transformation products:

no

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

At the end of the stability test (1,008 h) the two test solutions and the blank value at pH 9.0 were investigated for the following potential degradation products: Ammelide, ammeline, cyanamide, dicyandiamide, guanidinium, guanylmelamine, melamine.

Test solutions 1 and 2 as well as blank solution (pH 9.0) were injected within further preparation.
Following standard solutions were used:
- 0.518 mg ammelide reference item were weighed into a 50 mL volumetric flask, dissolved in water and made up to volume with water (standard solution I.1, c = 10.15 mg L-1).
- 10 mL of standard solution I.1 were pipetted into a 100 mL volumetric flask and made up to volume with water (standard solution I.2, c = 1.015 mg / L-1).
0.578 mg ammeline reference item were weighed into a 50 mL volumetric flask, dissolved in water and made up to volume with water (standard solution II.1, c = 11.44 mg L-1).
- 10 mL of standard solution II.1 were pipetted into a 100 mL volumetric flask and made up to volume with water (standard solution II.2, c = 1.144 mg / L-1).
0.633 mg dicyandiamide reference item were weighed into a 50 mL volumetric flask, dissolved in water and made up to volume with water (standard solution III.1, c = 12.66 mg L-1).
- 10 mL of standard solution III.1 were pipetted into a 100 mL volumetric flask and made up to volume with water (standard solution III.2, c = 1.266 mg L-1).
0.690 mg guanylmelamine nitrate reference item were weighed into a 50 mL volumetric flask, dissolved in water and made up to volume with water (standard solution IV.1, cguanylmelamine = 10.04 mg L-1).
- 10 mL of standard solution IV.1 were pipetted into a 100 mL volumetric flask and made up to volume with water (standard solution IV.2, c = 1.004 mg L-1).
0.539 mg melamine reference item were weighed into a 50 mL volumetric flask, dissolved in water and made up to volume with water (standard solution V.1, c = 10.78 mg L-1).
- 10 mL of standard solution V.1 were pipetted into a 100 mL volumetric flask and made up to volume with water (standard solution V.2, c = 1.078 mg L-1).
Both standard solutions were injection.

Due to the low concentration of above mentioned substances in the test solutions calculations were performed using the diluted standard solutions x.2.

Above mentioned substances were not found or only in traces (< 0.10 % relating to the initial concentration of nitroguanidine), respectively.

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0 h-1

DT50:

26 156 h

Key result

pH:

9

Temp.:

40

Hydrolysis rate constant:

0 h-1

DT50:

1 643 h

Key result

pH:

9

Temp.:

50

Hydrolysis rate constant:

0.002 h-1

DT50:

351 h

Details on results:

TEST CONDITIONS
- pH, temperature, and other experimental conditions maintained throughout the study: Yes
- Anomalies or problems encountered (if yes):

MAJOR TRANSFORMATION PRODUCTS
The aforementioned substances were not found, or only in traces (< 0.10 % relating to the initial concentration of nitroguanidine), respectively.

PATHWAYS OF HYDROLYSIS
None of the potential degradation products described in the literature (ammelide, ammeline, cyanamide, dicyandiamide, guanidinium, guanylmelamine and melamine) or nitrate, urea, ammonia and nitrite (non-GLP) were detected, or only in traces. Therefore, no pathway of hydrolysis can be proposed.

Hydrolytic stability of nitroguanidine at different pH values –pH 4.0. Storage time in h and concentration of nitroguanidine found after storage time t c_{NQ, t} in % relating to the initial concentration.

	cNQ, found [%]
	25 °C		40 °C		50 °C
Storage time [h]	solution 1	solution 2	solution 1	solution 2	solution 1	solution 2
start	98.8	98.2	98.8	98.2	98.8	98.2
24	98.5	98.1	98.8	98.3	99.1	98.3
48	98.2	97.9	98.2	98.1	98.3	97.9
72	99.3	99.4	99.4	98.6	99.5	98.9
96	99.2	99.1	99.1	98.5	99.2	98.4
168	99.5	99.3	99.3	98.0	98.5	98.2

Hydrolytic stability of nitroguanidine at different pH values –pH 7.0. Storage time in h and concentration of nitroguanidine found after storage time t c_{NQ, t} in % relating to the initial concentration.

	cNQ, t [%]
	25 °C		40 °C		50 °C
Storage time [h]	solution 1	solution 2	solution 1	solution 2	solution 1	solution 2
start	98.2	98.8	98.2	98.8	98.2	98.8
24	98.2	111.8^1	98.4	98.7	99.9	98.8
48	97.7	98.4	97.8	98.6	97.6	98.8
72	98.5	99.4	98.5	99.8	98.5	99.2
96	98.9	99.1	98.9	99.1	99.0	99.1
168	98.7	99.4	98.9	99.3	98.9	99.2

¹outlier (Grubbs,)

Hydrolytic stability of nitroguanidine at different pH values –pH 9.0. Storage time in h and concentration of nitroguanidine found after storage time t c_{NQ, t} in % relating to the initial concentration.

	cNQ, t [%]
	25 °C		40 °C		50 °C
Storage time [h]	solution 1	solution 2	solution 1	solution 2	solution 1	solution 2
start	98.3	98.8	98.3	98.8	98.3	98.8
24	98.2	98.2	98.0	97.4	94.5	93.8
48	99.3	98.1	96.8	96.3	90.2	88.8
72	99.0	98.6	96.9	95.9	86.1	84.6
96	99.3	98.4	96.1	95.4	85.4	83.5
168	97.5	97.0	92.9	92.2	71.4	70.2
240	97.8	96.9	90.4	89.8	60.8	59.7
336	97.5	97.2	88.2	87.3	50.9	49.8
408	n.a.	n.a.	n.a.	n.a.	44.1	43.1
504	n.a.	n.a.	79.9	79.1	36.8	36.0
576	n.a.	n.a.	n.a.	n.a.	32.1	31.7
744	96.8	96.7	72.6	72.0	22.8	22.7
1008	96.0	96.1	65.1	64.3	13.5	13.7

n.a. = not analysed

Validity criteria fulfilled:

yes

Conclusions:

OECD guideline 111 defines a substance as hydrolytically stable, if “less than 10 per cent of the reaction is observed after five days (t1/2 > 1 year)” at 50 °C. Hence, nitroguanidine is proven to be hydrolytically stable according to OECD guideline 111 at pH 4.0 and 7.0.
Nitroguanidine is not hydrolytically stable at pH 9.0 and 50 °C. At 50 °C, the half-life is 351 h (= 14.625 d). However, at 25 °C the half-life is 26,156 h (1,090 days).

Executive summary:

The hydrolytic stability of nitroguanidine was determined in accordance with OECD guideline 111. Aqueous test solutions were prepared with buffer solutions pH 4.0, pH 7.0 and pH 9.0. Concentration of the test solutions was approx. 6.5 mg nitroguanidine per 25 mL, this corresponds to approx. 260 mg/L or 2.5 mmol/L, respectively. Test solutions were incubated at 25, 40 and 50 °C initially for seven days. Nitroguanidine concentration was analysed after 24, 48, 72, 96 and 168 h.

Nitroguanidine concentration did not change significantly at pH 4.0 and 7.0. Recovery rate of nitroguanidine after seven days (168 h) storage at 50 °C was 98.4 % (pH 4.0) and 99.1 % (pH 7.0) (mean of two independent solutions, each). Hence, nitroguanidine is proven to be hydrolytically stable in accordance to OECD guideline 111 [1]. No further measurements were necessary at these pH levels. Hydrolysis tests were finished after 168 h.

Nitroguanidine concentration decreased significantly at pH 9.0 and 50°C. The recovery rate after five days is less than 90 %. Hence, the determination of the hydrolysis rate was necessary. The hydrolysis test was extended up to 1008 h. Hydrolysis of nitroguanidine was found to be a reaction of pseudo first order. Hydrolysis rates as well as half life t_0.5,T, which is equivalent to the time after which the concentration of the test item is reduced by 50 % (DT₅₀), were determined. Furthermore the Arrhenius collision number and the activation energy were ascertained.

Hydrolsis at pH 9.0. Temperature in °C and K as well as hydrolysis rate constant k_Tin h^-1and half time t_{0.5, T}in h.

 

temperature [°C]	temperature [K]	hydrolysis rate constant kT [h^-1]	half time t0.5, T [h]
25	298	0.000026	26,156
40	313	0.000422	1,643
50	323	0.001973	351

Arrhenius collision number was found to be 3.18 × 10¹⁹, Arrhenius acitivation energy is 137.33 kJ mol^‑1.

Test solutions at pH 9.0 were investigated for the potential degradation products ammelide, ammeline, cyanamide, dicyandiamide, guanidinium, guanylmelamine and melamine at the end of the stability test (1,008 h or 42 days). The aforementioned substances were not detected, or detected only in traces (below 0.10 % relating to the initial concentration of nitroguanidine). Hence, no pathway of hydrolysis can be proposed.

At pH 4 and 7 nitroguanidine was hydrolytically stable under screening conditions (50 °C). At pH 9 and the standard reporting temperature of 25 °C the hydrolytic half-life was determined to be 26,156 h (1,090 d).

Description of key information

Nitroguanidine is hydrolytically stable at pH 4 and 7 at 50 °C, respectively. The full test was conducted at pH 9 only, resulting in a hydrolytic half-life of 26,156 h (1,090 d) at 25 °C. Hence nitroguanidine is hydrolytically stable at environmentally relevant conditions. Specification of a half-life for chemical safety assessment is not necessary.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 090 d

at the temperature of:

25 °C

Additional information

The hydrolytic stability of nitroguanidine was determined in accordance with OECD guideline 111 at pH 4.0, pH 7.0 and pH 9.0. Test solutions were incubated at 25, 40 and 50 °C initially for seven days. Nitroguanidine concentration did not change significantly at pH 4.0 and 7.0. Nitroguanidine concentration decreased significantly at pH 9.0 and 50°C. Hydrolysis of nitroguanidine was found to be a reaction of pseudo first order. Half-lives (t_1/2), are 26,660 h, 1,643 h, and 351 h at 25 °C, 40 °C, and 50 °C, respectively. Potential degradation products described in the literature (ammelide, ammeline, cyanamide, dicyandiamide, guanidinium, guanylmelamine and melamine) as well as nitrate, urea, ammonia and nitrite (non-GLP) were not detected or only in traces. Therefore, no pathway of hydrolysis can be proposed.