4-Hydroxy-3,5-dimethylbenzonitrile

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-01-08 to 2004-03-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to standard test guidelines (OECD 111, EC) and conform GLP requirements. The results of the study can be considered reliable without restriction.

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Qualifier:

according 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:

- Sampling intervals for the parent/transformation products: After incubation, aliquots of each test solution (10 µL) were analysed at the beginning, after 2.4 h and after 120 h.
- Sampling intervals/times for pH measurements: not reported
- Sampling intervals/times for sterility check: not reported
- Sample storage conditions before analysis: not reported

Buffers:

- pH: 4, 7, 9
- Type of buffer:
* pH 4: component: biphthalate
* pH 7: component: phosphate
* pH 9: component: borate
- Buffer solutions were sterilized for 25 min in an autoclave prior to first use.
- Nitrogen was passed through the buffer solutions for 5 minutes except when freshly sterilized.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: 50-mL glass Erlenmeyer flasks stoppered or sealed with inert material (e.g PTFE), fillvolume 50 mL
- Sterilisation method: glassware rinsed with sterile buffer, buffer solutions autoclaved for 25 minutes
- Lighting: not reported
- Measures to exclude oxygen: nitrogen passed through buffer solutions for 5 min to reduce the oxygen in the solution.

TEST MEDIUM
- Volume used/treatment: 50 mL
- Kind and purity of water: water from Milli-Q supply
- Preparation of test medium: an amount of T002251 was dissolved in 2 mL DMF as solubilizer with aid of sonication and filled up to 100 mL with buffer solution (pH 4, 7 or 9). The solution was filtrated (0.45 µm) and diluted in a 1:1 ratio with the respective buffer solution. 2 aliquots of this solution of ~50 mL each were transferred into 50 mL flasks in order to perform a duplicate test.

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

>= 92.589 - <= 93.793 other: µg/mL

Duration:

120 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

>= 91.731 - <= 91.984 other: µg/mL

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

>= 95.952 - <= 96.041 other: µg/mL

Number of replicates:

2

Positive controls:

no

Negative controls:

no

Statistical methods:

not specified

Preliminary study:

A preliminary study was performed at 50°C ± 1 °C at each of pH 4, 7 and 9 in duplicate. Results are as follows:

pH 4*
- 0 hours: initial concentration measured: 93.191 µg/mL
- 2.4 hours: concentration measured: 92.9645 µg/mL
- 5 days: concentration measured: 93.5475 µg/mL

pH 7*
- 0 hours: initial concentration measured: 91.8575 µg/mL
- 2.4 hours: concentration measured: 91.287 µg/mL
- 5 days: concentration measured: 92.451 µg/mL

pH 9*
- 0 hours: initial concentration measured: 95.9965 µg/mL
- 2.4 hours: concentration measured: 96.16 µg/mL
- 5 days: concentration measured: 97.482 µg/mL

* values reported are the mean of 2 concentrations measured.

Test performance:

At pH 4.0, 7.0 and 9.0 the test item was found to be stable at 50°C. Therefore, no further testing was performed.

Transformation products:

not specified

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

no data

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: no data
- Anomalies or problems encountered (if yes): no data

MAJOR TRANSFORMATION PRODUCTS
- no data reported

MINOR TRANSFORMATION PRODUCTS
- no data reported

MINERALISATION (distinguish between dark and irradiated samples)
- no data reported

INDICATION OF UNSTABLE TRANSFORMATION PRODUCTS:
- no data reported

VOLATILIZATION (at end of study)
- no data reported

PATHWAYS OF HYDROLYSIS
- no data reported

UNIDENTIFIED RADIOACTIVITY (at end of study)
- no data reported

Validity criteria fulfilled:

yes

Conclusions:

Hydrolysis was studied for T002251 following guideline OECD 111 during 5 days at pH 4, 7 and 9 and at 50°C. During the preliminary study, T002251 was found to be stable at pH 4.0, pH 7.0 and pH 9.0 (the degradation of T002251 was less than 10% after 5 days). It was concluded that the estimated half-life time at 25°C is longer than 1 year at pH 4.0, 7.0 and 9.0. The results of the test can be considered reliable without restriction.

Description of key information

One study (Tognucci, 2004) was performed according to OECD guideline 111 and regarded as a key study (Klimisch score of 1). A half-life time of > 1 year at 25 °C and pH 7 was determined for T002251.