2-methyl-2H-isothiazol-3-one

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-11-30 to 2002-01-18

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP study with deviation from guideline: One replicate per sampling interval and per pH level (due to a suggestion by SETAC Europe (1995): Assessing environmental fate and ecotoxicity of pesticides. Samples were taken at the start (0 h) and at the end of the test (120 h) for the preliminary study. This deviation is considered to have no influence on the outcome of the study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

One replicate per sampling interval and per pH level (due to a suggestion by SETAC Europe (1995): Assessing environmental fate and ecotoxicity of pesticides. Samples were taken at the start (0 h) and at the end of the test (120 h) for the prelim. study.

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

7.87 mg/L

Duration:

120 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

9.09 mg/L

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

8.9 mg/L

Transformation products:

no

pH:

4

Temp.:

50 °C

Remarks on result:

other: no hydrolytic degradation

pH:

7

Temp.:

50 °C

Remarks on result:

other: no hydrolytic degradation

pH:

9

Temp.:

50 °C

Remarks on result:

other: no hydrolytic degradation

The test substance MIT was hydroytically stable in sterile aqueous media at pH 4, pH 7 and pH 9 over a period of 5 days at 50ºC in the dark. Since less than 10% decline in the MIT concentration at any pH was observed after 5 days (10% hydrolysis at 50ºC would correspond to a degradation half-life at 25ºC of > 1 year ), the chemical is considered to be hydrolytically stable.

Validity criteria fulfilled:

yes

Remarks:

Validity criteria fulfilled except OECD 111 requires duplicates for each temperature and pH level. Test with single replicate, however this deviation is not expected to affect the conclusion that MIT is hydrolytically stable at the measured pH levels.

Conclusions:

Marginal degradation, if at all (< 2% of initial amount), in buffered aqueous media at pH 4, 7 and 9 occurred in the hydrolysis preliminary test of MIT at 50ºC in the dark over 120 hours. Therefore, MIT can be categorized as a hydrolytically stable compound under environmentally relevant conditions.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not stated in report

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP/Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

An acidic pH of 5 was used instead of 4 and the study was performed only at 1 temperature (24C). Given that RH-573 was stable for more than 30 days in the conditions of the study, these deviations are not expected to modify the conclusion significantly

GLP compliance:

yes

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
Not applicable

Radiolabelling:

yes

Analytical monitoring:

yes

Details on sampling:

Duplicate samples (A and B) were removed from the incubator at the following times:
pH 5: 0, 48, 168, 333, 425 and 720 hours
pH 7: 0, 72, 237, 425, 552 and 720 hours
pH 9: 0, 70, 191.5, 315, 408.5 and 720 hours

Buffers:

Aqueous buffered solutions were prepared at pH 5, 7 and 9 as follows:
pH 5: 146 ml of 0.1 M acetic acid was added to 100 ml of 0.1M NaOH, and distilled water was added to a final volume of one liter.
pH 7: 22.4 ml of 0.1M KH2PO4 was added to 25 ml of 0.1M Na2HPO4, and distilled water was added to a final volume of one liter.
pH 9: 46 ml of 0.04M HCl was added to 500 ml of 0.01M Na2B4O7.10H2O, and distilled water was added to a final volume of one liter.

After preparation, all buffered solutions were sterilized by passing them through a filter (0.25u nylon, Fisher) for sterile use in the definitive hydrolysis study.

Details on test conditions:

Test solutions (approximately 10.0 ppm, consisting of a mixture of approximately 5.0 ppm of non-radioactive material, and approximately 5.0 ppm of radiolabeled material) were prepared in duplicate in sterile 250 ml Erlenmeyer flasks, and aliquots (5.0 ml) of this solution were applied to sterilized 8 ml pyrex sample tubes with teflon caps. During the course of the study these samples were maintained in the dark at 25+/-1C in an incubator. Zero-time concentrations were used for determining the actual applied radiocarbon for each sample.

A solution stability (sorption test) of RH-573 was conducted at a nominal concentration of 10.0 ppm in the three buffer solutions prior to the start of the hydrolysis study. This preliminary examination confirmed that the test compound remains in solution in the test systems over a 48 hour period.

An Orion pH meter was used to measure the pH of all buffers and samples.

Experimental Design
5.0 ml aliquots of the solutions described above were applied to each of twelve pyrex (8 ml) sample tubes. This allowed sampling of duplicates at time zero, and five subsequent intervals over 30 days.

The pH of each sample was measured at each sampling time and aliquots (3 x 50 ul) were analyzed by LSC and 100 ul aliquots by HPLC. Selected samples were also analyzed by TLC for confirmation of product identities.

Duration:

720 h

Temp.:

25 °C

Number of replicates:

2 for each time point and pH

Positive controls:

not specified

Negative controls:

not specified

Statistical methods:

No data.

Preliminary study:

The overall recoveries of radiocarbon at pH 5, 7, and 9 were 100.8%, 106.7%, and 99.3%, respectively. RH-573 did not degrade in any of the buffer solutions during the 30 days of the study.

Transformation products:

no

Remarks on result:

hydrolytically stable based on preliminary test

Other kinetic parameters:

RH-573 is stable to hydrolysis at pH 5,7 and 9. Due to the lack of degradation of RH-573 during the course of this study it was not possible to calculate a half-life from the pH 5, pH 7 or pH 9 data. No degradation products were observed.

Details on results:

Radiochemical Purity of 14C RH-573
The radiochemical purity of 14C RH573 used in this study was determined by HPLC to be 96.8%.

Stability and Solubility Determination
A preliminary examination of solution stability, performed at a concentration of 10.0 ppm in the absence of co-solvent, over 48 hours indicated no loss of 14C RH-573 solubility during that time. The standard deviation for radiolabel recoveries of six sampling times over the 48 hours were <2.9% for pH 5, 1.9% for pH 7 and 1.1% for pH 9 buffers.

Material Balance of 14C RH-573 throughout the Study Period
The material balance of 14C RH-573 hydrolysates was determined by aliquoting the hydrolysis solution at each sampling time and is expressed as percentages of applied radiocarbon. Recoveries averaged 99.3 +/- 4.6%, 100.3 +/-3.6 and 99.3 +/-1.5 for pH 5, 7 and 9, respectively.

Sample pH Measurements
The pH of the buffer solutions did not change significantly during the study period. A slight upward function in pH was detected in pH 5 and 7 solutions.

Solution Sterility
Sterility was preserved throughout the study.

Degradation of 14C RH-573 in Aqueous Solution
14C RH-573 does not appear to degrade appreciably in buffer systems at pH 5, 7 and 9 as evidenced in the kinetic expressions and lack of product formation.

Half-Life of Hydrolysis
Due to the lack of degradation during the 30-day study period, it was not possible to calculate a half-life from the pH 5, pH 7 and pH 9 data. The poor correlation co-efficients (R(2) < 0.1) reflected the length of the half-lives compared to the study duration.

No additional information available.

Validity criteria fulfilled:

yes

Conclusions:

RH-573 is hydrolitically stable in water.

Executive summary:

The hydrolysis of RH-573 was examined at pH 5, 7 and 9 at 24C over a 30 day interval. RH-573 was hydrolitically stable in water.

Description of key information

The test substance MIT was hydroytically stable in sterile aqueous media at pH 4, pH 7 and pH 9 over a period of 5 days at 50ºC in the dark. Since less than 10% decline in the MIT concentration at any pH was observed after 5 days (10% hydrolysis at 50ºC would correspond to a degradation half-life at 25ºC of > 1 year ), the chemical is considered to be hydrolytically stable

Key value for chemical safety assessment

Half-life for hydrolysis:

365 d

at the temperature of:

25 °C