lithium 3-((3,4-dicyanophenyl)sulfonyl)propane-1-sulfonate)

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Start of experimental work : 8th May 2012. End of experimental work 10th August 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Meets the criteria as reliable without restriction according to Klimisch et al (1997).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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:

lithium 3-((3,4-dicyanophenyl)sulfonyl)propane-1-sulfonate)

EC Number:

700-777-2

Cas Number:

667889-11-4

Molecular formula:

C11H9N2O5S2Li

IUPAC Name:

lithium 3-((3,4-dicyanophenyl)sulfonyl)propane-1-sulfonate)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): S193308
- Physical state: Powder
- Analytical purity: 99.4 % w/w
- Lot/batch No.: Batch 422
- Storage condition of test material: Room Temperature

Radiolabelling:

no

Study design

Details on sampling:

Preliminary Hydrolysis Test

For the initial HPLC analysis, the above test solutions were left to reach room temperature and then 0.5 ml of each hydrolysis test was diluted to 10.0 ml with sample diluent.

For the 5 days hydrolysis analysis, one vial of each test was removed from the oven at 50 ºC +/- 0.5ºC after 5 days and allowed to cool to room temperature. 0.5 ml of each test was diluted to 10.0 ml with sample diluent.

Full Hydrolysis Test at pH 9

For the initial analysis at each temperature, each of the remaining aliquots was left to reach room temperature and then 0.5 ml of each hydrolysis test was diluted to 10.0 ml with sample diluent. A blank solution was prepared at the same time by taking 0.5 ml of the pH 9 buffer solution and diluting to 10.0 ml with sample diluent.

For the other time points, one vial of each of the test solutions was removed from each oven at each time point. The test solutions were allowed to reach room temperature before diluting 0.5 ml of each test solution to a separate 10.0 ml volumetric flask and make up to volume with pH sample diluent. A blank solution was prepared at each time point as described above.

Buffers:

Preparation of Buffer Solutions

Three buffer solutions were prepared for preliminary test. The pH 9 buffer solution for the full hydrolysis study was prepared as for the pH 9 buffer in the preliminary test.

pH 4.0 Buffer Solution
164ml of 0.2M acetic acid solution was added to 36ml of 0.2M sodium acetate and diluted to 1 litre with ELGA Ultrapure water. The solution was degassed with helium.

pH 7.0 Buffer Solution
296ml of 0.1N sodium hydroxide solution was added to 500ml of 0.1M monopotassium phosphate solution and diluted to 1 litre with ELGA Ultrapure water. The solution was degassed with helium.

pH 9.0 Buffer Solution
213ml of 0.1N sodium hydroxide solution was added to 500ml of 0.1M boric acid in 0.1M potassium chloride and diluted to 1 litre with ELGA Ultrapure water. The solution was degassed with helium.

All buffers were autocalved at 121ºC for 15 min and then placed in a 50ºC oven to warm overnight.

Buffer blanks were also run to demonstrate specificity.

Details on test conditions:

TEST SYSTEM
- Sterilisation method: All glassware used during the analysis was autoclaved before use.

OTHER TEST CONDITIONS
- Adjustment of pH: The pH of each buffer solution was measured prior to use and no pH adjustment was required. The initial pH's of all test solutions were within 0.1 pH units of required pH, therefore no pH adjustment was necessary.

Duration of test

Duration of test 1

Duration:

5 d

pH:

4

Initial conc. measured:

1.75 g/L

Duration of test 2

Duration:

5 d

pH:

4

Initial conc. measured:

1.568 g/L

Duration of test 3

Duration:

5 d

pH:

7

Initial conc. measured:

1.354 g/L

Duration of test 4

Duration:

5 d

pH:

7

Initial conc. measured:

1.398 g/L

Duration of test 5

Duration:

5 d

pH:

9

Initial conc. measured:

1.318 other: g/ml

Duration of test 6

Duration:

5 d

pH:

9

Initial conc. measured:

1.322 g/L

Number of replicates:

Two replicates per pH.

Positive controls:

no

Negative controls:

no

Results and discussion

Preliminary study:

The pH 4.0 and 7.0 hydrolysis tests showed that there was been less than 10% hydrolysis after 5 days at 50°C ±0.5°C versus the initial time point and therefore no futher testing was required.

The pH 9.0 hydrolysis test showed 99.5% hydrolysis after 5 days at 50°C ±0.5°C versus the initial time point and further testing was required at pH9.0 as stipulated in the test method.

Transformation products:

yes

Identity of transformation products

Identity of transformation products 1

No.:

#1

Reference

Reference substance name:

Unnamed

Molecular weight:

ca. 350

Identity of transformation products 2

No.:

#2

Reference

Reference substance name:

Unnamed

Molecular weight:

ca. 351

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

See attached backgorund material section for details on hydrolysis products.

Dissipation DT50 of parent compound

pH:

9

Temp.:

20 °C

Remarks on result:

not determinable

Remarks:

could not be determined as formation rates were not first order

Any other information on results incl. tables

Results

 

Preliminary Test - Individual Results of Hydrolysis Tests

 

 

Test	Concentration g/L	Initial result g/L	Result after 5 days g/L	% Recovery after 5 days	% Loss
pH4-1	1.758	1.750	1.782	101.8	No loss,1.8% gain
pH4-2	1.578	1.568	1.598	101.9	No loss,1.9% gain
pH7-1	1.348	1.354	1.240	91.6	8.4
pH7-2	1.396	1.398	1.280	91.6	8.4
pH9-1	1.324	1.318	0.00664	0.5	99.5
pH9-2	1.326	1.322	0.00654	0.5	99.5

 

The buffer blanks gave no interferences at or around the retention time of the analyte peaks and specificity in buffer for hydrolysis testing was deemed acceptable.

 

The results of the initial HPLC analysis show that hydrolysis did not occur immediately. At pH 4.0 and 7.0 there has been less than 10% hydrolysis after 5 days at 50°C ± 0.5°C versus the initial time point. As stipulated in the test guideline no further testing is required at these pH's.

 

At pH 9.0 there was almost 100% hydrolysis after 5 days at 50°C ± 0.5°C versus the initial time point and thus further hydrolysis testing is required as stated in the test guideline.

 

Full Hydrolysis Test Results at pH 9

 

For the hydrolysis at pH 9 at 20±0.5ºC, 40±0.5ºC and 50±0.5ºC, the plot of the log transformed data of the test solutions concentrations versus time is a straight line (r>0.99), therefore the reaction is pseudo-first order. See below for the first order rate constant, Kobs, for each temperature and the predicted first order rate constant at 25°C:

 

pH 9 Kobs at 20 ± 0.5°C = 0.0145 days-1 (1254 secs^-1)

pH 9 Kobs at 40 ± 0.5°C = 0.2785 days-1 (24067 secs^-1)

pH 9 Kobs at 50 ± 0.5°C = 0.9826 days-1 (84894 secs^-1)

pH 9 Kobs at 25°C = 0.0316 days^-1

 

Test Item Half-life

pH 9 at 20.0°C±0.5°CTest	Half life, t0.5, is 47.47 days (1139 hours)
pH 9 at 40.0°C±0.5°C Test	Half life, t0.5, is 2.49 days (59.7 hours)
pH 9 at 50.0°C±0.5°C Test	Half life, t0.5, is 0.70 days (16.9 hours)

                                                         

 

Individual Results at pH 9 at20.0 ºC±0.5ºC

Note: there were no significant losses at 4, 23 and 29 hours; therefore these points have not been included for the calculation of the rate constant,K_obs, see the table below for the time points used:

20°C test-1				20°C test-2
Time (days)	C0(mg/L)	Ct(mg/L)	ln(C0/Ct)	Time (days)	C0(mg/L)	Ct(mg/L)	ln(C0/Ct)
0	1549	1549	0.0000	0	1817	1817	0.0000
3	1549	1474	0.0496	3	1817	1748	0.0387
7	1549	1401	0.1004	7	1817	1664	0.0880
14	1549	1269	0.1994	14	1817	1498	0.1931
21	1549	1120	0.3243	21	1817	1318	0.3211
30	1549	1001	0.4366	30	1817	1198	0.4165

 

 

Rates of formation of the major hydrolysis products

The hydrolysis rate constant of the major hydrolysis products could not be determined as the formation rates were not first order.

From the data acquired during the full hydrolysis at pH9, it was noted the formation of two major hydrolysis products (>10%) with retention times of 5.1 and 12.0 minutes.

 

 Identification of Hydrolysis Products by Electrospray LCMS

 

The major hydrolysis products observed during full hydrolysis testing at pH 9.0 were identified by Negative Electrospray LCMS using a Waters ZQ with Waters Alliance 2695 LC with UV and negative ion detection. The peaks were assigned on the basis of their relative retention times. See the attached background material section for the suggested structures.

 

 

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

At pH 4.0 and 7.0 the test item under goes less than 10% hydrolysis after 5 days at 50°C ±0.5°C. In the preliminary test, at pH 9.0 the test item showed 99.5% hydrolysis after 5 days at 50°C ±0.5°C versus the initial time point. In the higher tier tests hydrolysis was found to be pseudo first- order.  Two major (> 10%) hydrolysis products were identified.

Executive summary:

Introduction

Hydrolysis as a function of pH was determined for the test item using a method designed to be compliant with OECD text Method 111 Hydrolysis as a function of pH

Method

Hydrolysis was measured at pH 4.0, pH 7.0 and pH 9.0 using a preliminary test.  The pH 9.0 preliminary hydrolysis tests showed 99.5% hydrolysis after 5 days at 50°C ±0.5°C and as stipulated in the test guideline higher tier hydrolysis testing of the test item at pH 9 was undertaken to determine if hydrolysis followed first-order kinetic behaviour. Major hydrolysis products at pH9 were also identified using electrospray LCMS.

 Results and Conclusion

At pH 4.0 and 7.0 the test item under goes less than 10% hydrolysis after 5 days at 50°C ±0.5°C. In the preliminary test, at pH 9.0 the test item showed 99.5% hydrolysis after 5 days at 50°C ±0.5°C versus the initial time point. In the higher tier tests hydrolysis was found to be pseudo first- order.  Two major hydrolysis products were identified.