Ammonium sulphamidate

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 May 2011 and 08 November 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

The buffer solutions were filtered through a 0.2 µm membrane filter to ensure they were sterile before commencement of the test. Also these solutions were subjected to ultrasonication and degassing with nitrogen to minimise dissolved oxygen content.

Preparation of samples:
Sample solutions were prepared in stoppered glass flasks at a nominal concentration of 1 g/l in the three buffer solutions. The test solutions were split into individual vessels for each data point. The solutions were shielded from light whilst maintained at the test temperature.

Preliminary test:
Sample solutions at pH 4, 7 and 9 were maintained at 50.0 ± 0.5°C for a period of 120 hours.

Analysis of sample solutions:
The sample solutions were taken from the water bath at various times and the pH of each solution recorded.
The concentration of the sample solution was determined by ion chromatography (IC).

Samples:
Duplicate aliquots (A and B) of sample solution were diluted by a factor of 20 using reverse osmosis water.

Standards:
Duplicate standard solutions of test item were prepared in 5% respective buffer solution in reverse osmosis water at a nominal concentration of 50 mg/l.

Matrix blanks:
5% respective buffer solution in reverse osmosis water.

Buffers:

Buffer Solution (pH 4)
Components: Citric acid, Sodium hydroxide, Sodium chloride
Concentration (mol dm-3): 0.06, 0.07, 0.04

Buffer Solution (pH7)
Components: Disodium hydrogen orthophosphate (anhydrous), Potassium dihydrogen orthophosphate, Sodium chloride
Concentration (mol dm-3): 0.03, 0.02, 0.02

Buffer Solution (pH9)
Components: Disodium tetraborate, Sodium chloride
Concentration (mol dm-3): 0.01, 0.02

The buffer solutions were filtered through a 0.2 µm membrane filter to ensure they were sterile before commencement of the test. Also these solutions were subjected to ultrasonication and degassing with nitrogen to minimise dissolved oxygen content.

Details on test conditions:

Refer to details on sampling and analytical methods.

Duration:

120 h

pH:

4

Initial conc. measured:

0.995 g/L

Duration:

120

pH:

7

Initial conc. measured:

1.01 g/L

Duration:

120

pH:

9

Initial conc. measured:

1.01 g/L

Number of replicates:

Duplicate aliquots (A and B) of sample solution were diluted by a factor of 100 using glass double-distilled water.

Positive controls:

no

Negative controls:

no

Statistical methods:

Not specified.

Preliminary study:

The mean peak areas relating to the standard and sample solutions are shown in the table 1 (please see remarks on results including tables and figures section).

Test performance:

Validation:
The linearity of the detector response with respect to concentration was assessed over the nominal concentration ranges of 5 to 75 mg/l for each buffer matrix. This was satisfactory with correlation coefficients of greater than or equal to 0.997 being obtained for each matrix.

Transformation products:

not specified

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

Less than 10% hydrolysis after 5 days at 50°C.

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Other kinetic parameters:

None.

Details on results:

At pH4, 7 and 9 there was less than 10% hydrolysis after 5 days at 50°C, equivalent to a half-life greater than 1 year at 25°C.

Preliminary test/Tier 1

The mean peak areas relating to the standard and sample solutions are shown in the following table:

Table 1

Solution	Mean Peak Area
Standard 50.7 mg/l	4.976 x 10^7
Standard 51.5 mg/l	5.073 x 10^7
Initial Sample A, pH 4	4.872 x 10^7
Initial Sample B, pH 4	4.929 x 10^7
Standard 50.7 mg/l	5.117 x 10^7
Standard 51.5 mg/l	5.200 x 10^7
Initial Sample A, pH 7	5.088 x 10^7
Initial Sample B, pH 7	5.102 x 10^7
Standard 50.7 mg/l	5.348 x 10^7
Standard 51.5 mg/l	5.495 x 10^7
Initial Sample A, pH 9	5.291 x 10^7
Initial Sample B, pH 9	5.437 x 10^7
Standard 50.4 mg/l	5.446 x 10^7
Standard 50.4 mg/l	5.491 x 10^7
24-Hour Sample A, pH 4	5.396 x 10^7
24-Hour Sample B, pH 4	5.365 x 10^7
Standard 50.4 mg/l	5.334 x 10^7
Standard 50.4 mg/l	5.333 x 10^7
24-Hour Sample A, pH 7	5.240 x 10^7
24-Hour Sample B, pH 7	5.198 x 10^7
Standard 50.4 mg/l	5.268 x 10^7
Standard 50.4 mg/l	5.311 x 10^7
24-Hour Sample A, pH 9	5.179 x 10^7
24-Hour Sample B, pH 9	5.252 x 10^7
Standard 50.0 mg/l	5.220 x 10^7
Standard 50.7 mg/l	5.405 x 10^7
120-Hour Sample A, pH 4	5.314 x 10^7
120-Hour Sample B, pH 4	5.199 x 10^7
Standard 50.0 mg/l	5.210 x 10^7
Standard 50.7 mg/l	5.320 x 10^7
120-Hour Sample A, pH 7	5.241 x 10^7
120-Hour Sample B, pH 7	5.249 x 10^7
Standard 50.0 mg/l	5.264 x 10^7
Standard 50.7 mg/l	5.540 x 10^7
120-Hour Sample A, pH 9	5.211 x 10^7
120-Hour Sample B, pH 9	5.324 x 10^7

Table 2    pH 4 at 50.0 ± 0.5ºC

Time (Hours)	Mean Concentration (g/l)		% of mean initial concentration (g/l)
	A	B	A	B
0	0.990	1.00	-	-
24	0.995	0.989	99.8	99.3
120	1.01	0.986	101	98.9

Result:          Less than 10% hydrolysis after 5 days at 50°C, equivalent to a half-life greater than 1 year at 25°C.

Table 3   pH 7 at 50.0 ± 0.5ºC

Time (Hours)	Mean Concentration (g/l)		% of mean initial concentration (g/l)
	A	B	A	B
0	1.01	1.01	-	-
24	0.990	0.982	98.1	97.4
120	1.00	1.00	99.4	99.5

Result:          Less than 10% hydrolysis after 5 days at 50°C, equivalent to a half-life greater than 1 year at 25°C.

Table 4    pH 9 at 50.0 ± 0.5ºC

Time (Hours)	Mean Concentration (g/l)		% of mean initial concentration (g/l)
	A	B	A	B
0	1.00	1.02	-	-
24	0.987	1.00	97.6	99.0
120	0.972	0.993	96.1	98.2

Result:          Less than 10% hydrolysis after 5 days at 50°C, equivalent to a half-life greater than 1 year at 25°C. 

Validity criteria fulfilled:

yes

Remarks:

The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 5 to 75 mg/l. This was satisfactory with a correlation coefficient of 0.997 being obtained.

Conclusions:

The estimated half-life at 25°C of the test material at pH 4, 7 and 9 is greater than 1 year.

Executive summary:

Hydrolysis as a Function of pH

Assessment of hydrolytic stability was carried out using a procedure designed to be compatible with Method C7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004. 

The results are as follows:

pH	Estimated half-life at 25°C
4	>1 year
7	>1 year
9	>1 year

Reference 2

Endpoint:

hydrolysis

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

sodium sulphamidate

Adequacy of study:

weight of evidence

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
A read across, based on analogue approach, has been performed between ammonium sulphamidate EC 231-871-7 (target chemical) and sodium sulphamidate EC 237-572-8 (source chemical).
The read-across hypothesis, according to Read Across Assessment Framework published by ECHA, is based on the fact that different compounds which have the same type of effect(s). It corresponds to the scenario 2 described as follows:
« This scenario covers the analogue approach for which the read-across hypothesis is based on different compounds which have the same type of effect(s). For the REACH information requirement under consideration, the effects obtained in a study conducted with one source substance are used to predict the effects that would be observed in a study with the target substance if it were to be conducted. The same type of effect(s) or absence of effect is predicted. The predicted strength of the effects may be similar or based on a worst case assumption. »

1) Chemical structure
The target and source substances share the same anionic structure, i.e. a sulphamidate (formula: –OSO2NH2). They only differ by the positive counter ion: an ammonium ion (NH4+) for the target substance and a sodium ion (Na+) for the source substance. It is well known that usually, the counter ion has no impact on the toxicity profile of the substance. For this reason, the QSARs are classically performed on the “core” of the salt and do not consider the counter ion.
See the structures in attached justification.

2) Kinetics
Ammonium sulphamidate
The substance is highly water soluble, meaning its ions dissolve in water. Following oral administration of ammonium sulfamate to dogs for 5 days, 80 to 84% of the dose was excreted as sulfamic acid in the urine, indicating that ammonium sulfamate is readily absorbed into the bloodstream from the gastrointestinal tract. (Pesticide Active Ingredient Information – EXTOXNET)

Sodium sulphamidate
Absorption of sodium sulphamidate from the gastrointestinal tract is supported by the repeated dose reproductive screening study in rats. The high water solubility and small molecular size of sodium sulphamidate allow absorption through passive diffusion. This would suggest that the gastro-intestinal tract provides a route of absorption, following oral administration, before entering the circulatory system via the blood.
Absorption of sodium sulphamidate may also take place via the skin due to small molecular size and water solubility. Although the substance is not a skin sensitizer there is evidence of mild dermal irritation. Therefore damage to the skin surface may allow for increased penetration of the substance through the skin.

Once absorbed, the substance would be distributed in the serum due to the water solubility.

The results of the repeated dose reproductive screening study would suggest that the most likely route of excretion is the kidney due to the likely systemic distribution and water solubility of the test item. Any test item that is not absorbed will be excreted in the faeces. [ECHA’s registration dossier of sodium sulphamidate].

Conclusion
Both substances are absorbed via oral route and are found excreted in urine. Inhalation exposure is not relevant due to the low vapour pressure of each substance.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
1) Physical and chemical information
The physico-chemical properties were compared between the target and the source substance. Synthron data are in blue and Nalco data (found in ECHA’s registration dossier of sodium sulphamidate) are in green. Published data are in purple and other data are in black (please refer to the comparative table in attached justification).

Both substances share some common physico-chemical properties: white solid appearance, decomposition, high partition coefficient, negligible vapour pressure, absence of surface activity, good water solubility, absence of flammability/explosive and oxidizing properties.
Some physico-chemical differences can be highlighted between the two substances: the different molecular weight is attributed to the counter-ion. The boiling and melting points are slightly different as well as the relative density. The dissociation constants vary due to the different counter-ions which cannot be used for the read-across proposal. In this case, the sulphamidic acid is the most appropriate substance. The pKa values around 1.0 (0.9 or 0.997 or 1.05 as found in the "Handbook of Chemistry and Physics", 85th ed.) all refer to the free acid, sulphamidic acid. Ammonium sulphamate contains as cation the ammonium ion with a pKa of 9.25 ("Handbook of Chemistry and Physics", 85th ed.) Any attempt of coming into the region of pH that is near the pKa of the primary amine group (13.6 ± 0.6) would cause the deprotonation of the ammonium ion and the transformation of the target chemical into the respective alkaline metal salt, for instance sodium sulphamidate. Therefore, the pKa of the primary amine group in the sulphamidate anion reported in the sodium sulphamidate dossier is not relevant for ammonium sulphamidate.
Therefore, both substances share many common physico-chemical features, and the observed differences can be attributed to the different counter-ion.

2) Toxicological and ecotoxicological information
The ammonium ion of the target substance may contribute to the toxicity of ammonium sulphamidate, compared to sodium sulphamidate. However, as both substances are highly water soluble, their ions dissolve in water. Therefore, the ammonium ion is no more a concern.
Please refer to the comparative table in attached justification.

Regarding the toxicity endpoints, some common points are shared by the two substances: low acute toxicity by oral route, no mutagenicity in bacteria, mild to no skin or eye irritation. Some differences occurred in the systemic toxicity study: in the repeated dose toxicity study, the NOAEL are not the same between sodium (NOAEL = 1000 mg/kg bw/d) and ammonium sulphamidate (NOEL = 214.3 mg/kg bw/d). In the reproductive study, NOEL for ammonium sulphamidate was found to be 25 mg/kg bw/d in the literature whereas the NOAEL for sodium sulphamidate is 1000 mg/kg bw/d. However, these differences must be considered with caution as the experimental protocols differ.

As for the ecotoxicity endpoints, both substances seem not to be toxic to fish, based on their LC50 > 100 mg/L (LC50 of at least 650 mg/L).

Last, the environmental fate data on both substances indicate that they are likely to be adsorbed into the soil. Their half-life differ as sodium sulphamidate is very stable (half-life > 1 year) and ammonium sulphamidate may be less stable (half-life of 14 days, based on a published data).


3) Classification proposal
The sodium sulphamidate is not classified in ECHA’s registration dossier. Based on the read-across approach, ammonium sulphamidate would not be classified either.

3. ANALOGUE APPROACH JUSTIFICATION
Based on the available elements, it can be assumed that ammonium and sodium sulphamidate may have close kinetic profiles, physico-chemical, toxicological and ecotoxicological properties. The read-across approach is therefore relevant.

Reason / purpose for cross-reference:

read-across source

Transformation products:

not specified

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Details on results:

At pH4, 7 and 9 there was less than 10% hydrolysis after 5 days at 50°C, equivalent to a half-life greater than 1 year at 25°C.

Validity criteria fulfilled:

yes

Conclusions:

Based on the read-across on sodium sulphamidate, ammonium sulphamidate is expected to have a half-life higher than 1 year at 25°C, at pH 4, 7 and 9.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C