Cyclopropanemethanol, 1-methyl-2-[(1,2,2-trimethylbicyclo[3.1.0]hex-3-yl)methyl]-

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 October, 1997 - 01 December, 1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

JAVANOL (synonymous with GIV 84-4605) :
Batch No. : 008825
Purity : 88.4% (GC, sum of two peaks)

Radiolabelling:

no

Analytical monitoring:

yes

Remarks:

GC-FID

Details on sampling:

A preliminary screening test was performed at pH4, 7 and 9 at 50°C at a starting JAVANOL concentration of 1 mg/L.

Further tests were performed following the screening study at pH4, at 50°C and 35°C.

Buffers:

Ready-made concentrates (Titrisol®, MERCK, Darmstadt, Germany) were used to prepare buffer solutions by dilution with fresh double-distilled, sterile water:

pH 4.00 ± 0.02 at 20°C (art. No. 9884): after dilution:

citric acid : 0.056 mol/l
NaOH : 0.11 mol/l
HCl : 0.044 mol/l

pH 7.00 ± 0.02 at 20°C (art. No. 9887): after dilution:

KH2PO4 : 0.026 mol/l
Na2HPO4 : 0.041 mol/l

pH 9.00 ± 0.02 at 20°C (art. No. 9889): after dilution:

H3BO3 : 0.05 mol/l
KCl : 0.05 mol/l
NaOH : 0.022 mol/l

In order to avoid any unnecessary excess of inorganic salts that could reduce the solubility of the test substance, these buffer solutions were diluted 10 times with double-distilled water before being used as test media.

Details on test conditions:

Equipment :
Hydrolysis reactions are performed in amber-glass bottles, 250 and 100 ml, with ground-glass or PTFE-lined stoppers.

A constant temperature water bath with a six-position magnetic stirrer (Variomag Electronicrührer, H+P Labortechnik GmbH, Munich, Germany) is used to maintain to ±0.1 °C the bottles temperature.

For temperatures higher than 60 °C, a laboratory oven (SALVIS, Luzern, Switzerland, type TSK 0D, temperature regulation: ± 0.5 °C) is used instead of the water-bath.


Since the test substance is not readily biodegradable, no special sterilising treatment was applied to the glassware which was anyhow routinely hot washed in a laboratory washing machine before use.

According to its chemical structure, the test substance is not easily oxidizable by air and no drastic precaution against air was taken during this test.


Test substance solution :

The water solubility of JAVANOL at 20 °C is 3.8 mg/l. According to the guidelines, the initial concentration to be used for the hydrolysis reaction should not exceed the half of the saturation concentration. Since solubility is expected to be lower in buffer solutions, a rather lower concentration, i.e. 1 mg/l was chosen. Therefore, a stock solution containing 100 mg/l of test substance in acetone was prepared. By a 1:100 dilution of this solution with buffer solution, the test concentration, 1 mg/l, is obtained. The amount of carrier solvent (acetone) does not exceed 1% as required by the guideline.

Preliminary test at 50 °C :

Four 250-ml amber glass bottles were pre-treated with a 1 mg/l aqueous test substance solution overnight. They were rinsed with double-distilled water and filled with 250 ml of diluted buffer solutions.

- 1 bottles with pH 4 buffer
- 2 bottles with pH 7 buffer (marked a and b, to check repeatability)
- 1 bottles with pH 9 buffer.

To each bottle, 2.5 ml of the test substance solution prepared in acetone were precisely added under vigorous stirring. The bottles were closed with a ground-glass stopper and placed in the water bath at 50 °C.

After about two hours of temperature equilibration, 50-ml samples were withdrawn from the middle of each bottle for immediate analysis (time 0) as exposed above. Other 50-ml samples were taken after 2.4, 23 and 120 hours and analysed immediately.


Test 1 at 50 °C for pH 4 :

The purpose of this second test ( named Test 1 according to method C.7 of Directive 92/69/EEC) is to determine whether or not the kinetics of hydrolysis of JAVANOL are pseudo-first order. If the plot of the logarithm of the concentration (or percentage of initial concentration) versus time is a straight line, it can be concluded that the kinetics is pseudo-first-order. A sufficient number of points (at least 4) should be obtained. Linear regression can be performed on these data. The slope is related to the rate constant kobs by:
kobs = -2.303 x slope

The procedure was the same as that of the preliminary test, except that only two bottles at pH 4 were prepared (to check repeatability) and 40-ml samples (instead of 50 ml) were taken, allowing a total of six samples to be analysed. The bottles were allowed to stay overnight before sampling at time 0. Other samples were taken and analysed immediately after 120, 313, 433, 772 and 1105 hours.


Test 2 at 35 °C for pH 4 :

The purpose of this third test ( which corresponds to Test 3 according to method C.7 of Directive 92/69/EEC) is to determine the rate constants and half-life times at another temperature than 50 °C for pH 4 in order to calculate the same parameters at 25 °C with Arrhenius's law.

This test was performed simultaneously with Test 1. The procedure was the same as for Test 1, except the temperature (35 °C).

Duration:

120 h

pH:

3.78

Temp.:

50 °C

Initial conc. measured:

1.043 mg/L

Remarks:

Samples taken at 0, 2.4, 23 and 120 hours of incubation. Detected Concentrations : 0 hrs 1.043 mg/L 2.4 hrs 0.998 mg/L 23 hrs 1.025 mg/L 120 hrs 0.881 mg/L

Duration:

120 h

pH:

6.92

Temp.:

50 °C

Initial conc. measured:

1.01 mg/L

Remarks:

Samples taken at 0, 2.4, 23 and 120 hours of incubation. Detected Concentrations : 0 hrs 1.010 mg/L 2.4 hrs 1.002 mg/L 23 hrs 0.995 mg/L 120 hrs 0.955 mg/L

Duration:

120 h

pH:

6.88

Temp.:

50 °C

Initial conc. measured:

0.995 mg/L

Remarks:

Samples taken at 0, 2.4, 23 and 120 hours of incubation. Detected Concentrations : 0 hrs 0.995 mg/L 2.4 hrs 1.003 mg/L 23 hrs 1.013 mg/L 120 hrs 0.973 mg/L

Duration:

120 h

pH:

8.88

Temp.:

50 °C

Initial conc. measured:

1.027 mg/L

Remarks:

Samples taken at 0, 2.4, 23 and 120 hours of incubation. Detected Concentrations : 0 hrs 1.027 mg/L 2.4 hrs 1.011 mg/L 23 hrs 1.035 mg/L 120 hrs 0.963 mg/L

Duration:

1 105 h

pH:

4.11

Temp.:

50 °C

Initial conc. measured:

1.062 mg/L

Remarks:

Replicate A. Samples taken at 0, 120, 313, 433, 772 and 1105 hours of incubation and analysed.

Duration:

1 105 h

pH:

4.11

Temp.:

50 °C

Initial conc. measured:

1.071 mg/L

Remarks:

Replicate B. Samples taken at 0, 120, 313, 433, 772 and 1105 hours of incubation and analysed.

Duration:

1 105 h

pH:

4.11

Temp.:

35 °C

Initial conc. measured:

1.091 mg/L

Remarks:

Replicate A. Samples taken at 0, 120, 313, 433, 772 and 1105 hours of incubation and analysed.

Duration:

1 105 h

pH:

4.11

Temp.:

35 °C

Initial conc. measured:

1.071 mg/L

Remarks:

Replicate B. Samples taken at 0, 120, 313, 433, 772 and 1105 hours of incubation and analysed.

Positive controls:

no

Negative controls:

no

Preliminary study:

In the preliminary study performed at 50°C with pH4, 7 and 9 buffers, the following results were obtained :

pH4 84.4% of starting concentration remaining
pH7 94.6% and 97.7% of starting concentration remaining in Replicates A and B, respectively
pH9 93.8% of starting concentration remaining.

According to Directive 92/69/EEC, the results were evaluated in relation with the following end-points:

- more than 50 % degradation after 2.4 hours (equivalent to a half-life time smaller than 1 day at 25 °C)

- less than 10 % degradation after 5 days (equivalent to a half-life time higher than 1 year at 25 °C)

The latter of the above-mentioned conditions was met for pH 7 and 9. Consequently, at pH 7 an pH 9, the half-life time at 25 °C is higher than one year and no more testing is required for these pH values.

For pH 4, none of the conditions is met and further testing is necessary.

Transformation products:

no

% Recovery:

84.4

pH:

3.78

Temp.:

50 °C

Duration:

120 h

Remarks on result:

other: pH4 buffer in preliminary test : > than 10% disappearance, therefore need to go to follow-up test.

% Recovery:

94.6

pH:

6.92

Temp.:

50 °C

Duration:

120 h

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

pH7 buffer in preliminary test : < than 10% disappearance, therefore no need to go to follow-up test.

% Recovery:

97.7

pH:

6.88

Temp.:

50 °C

Duration:

120 h

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

pH7 buffer in preliminary test : < than 10% disappearance, therefore no need to go to follow-up test.

% Recovery:

93.8

pH:

8.88

Temp.:

50 °C

Duration:

120 h

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

pH9 buffer in preliminary test : < than 10% disappearance, therefore no need to go to follow-up test.

% Recovery:

55.4

pH:

4.11

Temp.:

50 °C

Duration:

1 105 h

Remarks on result:

other: Average of Replicates A and B at pH4. Rate Constant calculated is 0.0005334 h-1. Average T1/2 at 50°C = 1299 h.

% Recovery:

80.6

pH:

4.11

Temp.:

35 °C

Duration:

1 105 h

Remarks on result:

other: Average of Replicates A and B at pH4. Rate Constant calculated is 0.000182 h-1. Average T1/2 at 35°C = 3798 h.

Key result

pH:

4.11

Temp.:

25 °C

Hydrolysis rate constant:

0 h-1

DT50:

8 204 h

Type:

(pseudo-)first order (= half-life)

Validity criteria fulfilled:

yes

Conclusions:

The abiotic degradation test (hydrolysis as a function of pH) according to OECD method No. 111 was performed on JAVANOL (GIV 84-4605).

In water, JAVANOL is stable at pH 7 and pH 9. The half-life times at 25 °C are higher than one year. At pH 4, there seems to occur a slow hydrolysis with a half-life time slightly lower than on year.

T1/2 at 25°C pH4 : 8204 hours
T1/2 at 25°C pH7 : > 8760 hours (> 1 year)
T1/2 at 25°C pH9 : > 8760 hours (> 1 year)

Description of key information

HYDROLYSIS :

The abiotic degradation test (hydrolysis as a function of pH) according to OECD method No. 111 was performed on JAVANOL (GIV 84-4605).

In water, JAVANOL is stable at pH 7 and pH 9. The half-life times at 25 °C are higher than one year. At pH 4, there seems to occur a slow hydrolysis with a half-life time slightly lower than on year.

T1/2 at 25°C pH4 : 8204 hours

T1/2 at 25°C pH7 : > 8760 hours (> 1 year)

T1/2 at 25°C pH9 : > 8760 hours (> 1 year)

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C

Additional information

HYDROLYSIS :

The abiotic degradation test (hydrolysis as a function of pH) according to OECD method No. 111 was performed on JAVANOL (GIV 84-4605).

In water, JAVANOL is stable at pH 7 and pH 9. The half-life times at 25 °C are higher than one year. At pH 4, there seems to occur a slow hydrolysis with a half-life time slightly lower than on year.

T1/2 at 25°C pH4 : 8204 hours

T1/2 at 25°C pH7 : > 8760 hours (> 1 year)

T1/2 at 25°C pH9 : > 8760 hours (> 1 year)