4-mesyl-2-nitrotoluene

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 April 1999 - 20 July 1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Guideline study conducted under GLP. Serious problems with the reproducibility of the analytical method (or the stability of the test system). However, the final conclusion and analytical results, conducted at the end of the study, appear to be valid.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: 0, 2.4h, 5d
- Sampling intervals/times for pH measurements: 0, 2.4h, 5d

Buffers:

- pH: 4, 7, 9
- Composition of buffer:
pH 4: 4.0mL 0.1M NaOH and 10.21g potassium hydrogen phthalate made up to 1000mL with deionised water.
pH 7: 290mL 0.1M NaOH and 6.8g potassium dihydrogen orthophosphate made up to 1000mL with deionised water.
pH 9: 46mL 0.1M HCl and 4.78g borax made up to 1000mL with deionised water.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: glass conical flasks, stoppered, magnetic stirrer bars, 50°C water bath with magnetic stirrer.
- Sterilisation method: autoclave
- Lighting: dark
- Measures taken to avoid photolytic effects: flasks covered with aluminium foil
- Measures to exclude oxygen: buffer solutions ultrasonicated for 15min

TEST MEDIUM
- Volume used/treatment: 900µL aliquot of a 1000 mg/L stock solution of the substance in methanol, was added to 100mL buffer solution.
- Kind and purity of water: deionised

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

4.13 mg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

5.88 mg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

9.6 mg/L

Number of replicates:

Experiments conducted in triplicate

Positive controls:

no

Negative controls:

no

Preliminary study:

Only the preliminary study was conducted. No samples hydrolysed >10% in the 5 day period.

Transformation products:

no

% Recovery:

46

St. dev.:

15

pH:

4.03

Temp.:

49.9 °C

Duration:

0 h

% Recovery:

66

St. dev.:

46

pH:

6.95

Temp.:

49.9 °C

Duration:

0 h

% Recovery:

100

St. dev.:

1.5

pH:

8.97

Temp.:

49.9 °C

Duration:

0 h

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

recovery measured: 107%

% Recovery:

77

St. dev.:

3.5

pH:

4

Temp.:

49.9 °C

Duration:

2.4 h

% Recovery:

> 100

St. dev.:

62

pH:

7

Temp.:

49.9 °C

Duration:

2.4 h

Remarks on result:

other: recovery measured: 179%

% Recovery:

93

St. dev.:

28

pH:

9

Temp.:

49.9 °C

Duration:

2.4 h

% Recovery:

> 100

St. dev.:

2.3

pH:

3.69

Temp.:

50 °C

Duration:

5 d

Remarks on result:

other: recovery measured: 106%

% Recovery:

> 100

St. dev.:

4.6

pH:

6.9

Temp.:

50 °C

Duration:

5 d

Remarks on result:

other: recovery measured: 113%

% Recovery:

> 100

St. dev.:

1

pH:

9.07

Temp.:

50 °C

Duration:

5 d

Remarks on result:

other: recovery measured: 107%

pH:

4

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

None of the samples hydrolysed >10% in the 5 day period.

pH:

7

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

None of the samples hydrolysed >10% in the 5 day period.

pH:

9

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

None of the samples hydrolysed >10% in the 5 day period.

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: pH measurements did not alter markedly over the period of the test. The temperature remained within satisfactory limits during the test. Sterility not reported.
- Anomalies or problems encountered: Measured concentrations of the test substance at pH 4 and 7 at 0h were highly variable; concentrations at 2.4h were variable. All concentrations measured at 5d were approximately the nominal concentration. It was suggested that the variability was due to the test substance not solubilising fully in the short period at the start of the preliminary study, and also due to some chromatographic interferences from the buffers.

Reported values are averages of the three experiments. Estimated half-life >1 year at 25°C. %Recovery reported as compared to initial nominal concentration of 9.0mg/L.

Validity criteria fulfilled:

no

Conclusions:

Serious problems were reported with the analytical method. However, reproducibility in the analytical method (or stability in the test system) seems to have been attained at the end of the 5 day period. The good agreement between the replicate results at the end of the test suggests these may have some credibility, and that the substance does not hydrolyse significantly over the test duration.

Description of key information

<10% hydrolysis in 5 days at pH 4, 7, and 9 and 50 °C; estimated DT50 >1 year at 25 °C, OECD 111, Magor 1999

Additional information

Serious problems were reported with the analytical method, which would normally invalidate the results of the hydrolysis study (Magor, 1999). However, reproducibility in the analytical method (or stability in the test system) seems to have been attained at the end of the 5 day period. The good agreement between the replicate results at the end of the test suggests these final measurements have credibility, and that the substance does not hydrolyse significantly over the duration of the test. Because neither the structure of the molecule, nor other experimental evidence, suggests that the substance may be susceptible to hydrolysis in aqueous solution, the experimental result is in this case considered to be adequate for risk assessment purposes.