Cyclohexane, 1,3-bis(isocyanatomethyl)-

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 19 February 2016 to 23 June 2016

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

yes

Remarks:

Tier 2 study was performed at 1 instead of 3 temperatures in the preferred range of 10-70°C. Reason: very fast hydrolysis. Hydrolysis at temperatures above room temperature could not be analytically monitored due to methodological limitations.

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

2004

Deviations:

yes

Remarks:

see above

Qualifier:

according to guideline

Guideline:

EPA OPPTS 835.2120 (Hydrolysis of Parent and Degradates as a Function of pH at 25°C)

Version / remarks:

2008

Deviations:

yes

Remarks:

see above

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Remarks:

UPLC-MS

Details on sampling:

PREPARATION OF THE SAMPLES
- Test item was spiked to the buffers using a solution of the test item in acetonitrile (2000 mg/L).
- Target concentration: 10 mg/L
- For each sampling time, duplicate sterile HPLC glass vials were filled with test solution.
- The vessels were placed in a temperature controlled environment in the dark.
- Blank buffers containing a similar content of co-solvent were treated similarly as the test samples (at t=0).

SAMPLING DETAILS
Samples for analysis were taken immediately after preparation (t=0) and at several sampling points after t=0.

pH MEASUREMENTS
The pH of the test solutions (except for the blanks) was determined at least at the beginning and at the end of the test (if appropriate).

Buffers:

Buffer pH 4: 16.7% 0.01 M sodium acetate and 83.3% 0.01 M acetic acid in water.

Buffer pH 7: 0.01 M potassium di-hydrogenphosphate in water adjusted to pH 7 using 1 N sodium hydroxide.

Buffer pH 9: 0.01 M boric acid and 0.01 M potassium chloride in water adjusted to pH 9 using 1 N sodium hydroxide.

Details:
- Sodium azide content in each buffer: 0.0009% (w/v)
- Kind of water: tap water purified by a purification system (Milli-Q, Millipore)

Details on test conditions:

TYPE OF TEST
The test item is known to be highly reactive with water. Therefore no preliminary test was conducted.
The Tier 2 study was performed.

TEST SYSTEM
- Sterilisation method: Each buffer was filter-sterilised through a 0.2 µm FP 30/0.2 CA-S filter (Whatman) and transferred into a sterile vessel.
- Measures to exclude oxygen: nitrogen gas was purged through the sterile buffers for 5 minutes prior to preparation of the blank and test solutions.
- Measures taken to avoid photolytic effects: the test vessels were kept in the dark.

TEST MEDIUM
Identity and concentration of co-solvent: acetonitrile. The volume of the co-solvent was < 1% of the sample volume. Nominal concentrations were not corrected for the spiking volume.

ACTUAL TEMPERATURES
pH 4: 20.4°C ± 0.9°C
pH 7: 21.5°C ± 0.2°C
pH 9: 21.3°C ± 0.2°C

Duration:

0.7 h

pH:

4

Temp.:

20.4 °C

Remarks:

The concentration at t=0 was measured to be below the limit of detection.

Duration:

19.77 h

pH:

7

Temp.:

21.5 °C

Initial conc. measured:

9.2 mg/L

Remarks:

mean (n=2) conc.

Duration:

2.33 h

pH:

9

Temp.:

21.3 °C

Initial conc. measured:

7.3 mg/L

Remarks:

mean (n=2) conc.

Number of replicates:

Two

Positive controls:

no

Negative controls:

no

Preliminary study:

not conducted

Test performance:

pH 4
9 sampling times from 0 h to 0.7 h. Test item (max. 0.45 mg/L) was detected in one of the samples taken at 0.13 h, at 0.20 h and at 0.28 h. No test item was detected in all other samples. This indicated fast hydrolysis that could technically not be monitored.

pH 7
16 sampling times from 0 h to 19.77 h. The concentration decreased from 9.23 mg/L (at t=0) to 2.4 mg/L (at 3.13 h) and to a concentration below the limit of detection (at t=19.77 h).
Lineair regression curve (log. rel. conc. vs time ) over the time period from 0 to 3.13 h: Y = -0.167X + 1.87 (r=0.949).
Plot of the data points and the curve: see attachment

pH 9
13 sampling times from 0 h to 2.33 h. The concentration decreased from 7.48 mg/L (at t=0) to 0.55 mg/L (at t=2.33 h).
Lineair regression curve (log. rel. conc. vs time): Y = -0.271X + 1.52 (r=0.592)
Plot of the data points and the curve: see attachment

RECOVERIES
- Recovery is the concentration analysed at t=0 relative to the nominal concentration.
- The mean (n=2) recovery at pH 7 and pH 9 was calculated (see table below).
- The mean recovery for pH 7 fell within the criterion range of 90-110%.
- The mean recovery for pH 9 fell within the acceptable range for non-labelled chemicals of 70-110%.
- The concentrations analysed in the test samples were not corrected for recovery.

Transformation products:

not specified

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

no data

pH:

4

Temp.:

20.4 °C

Duration:

0 h

Remarks on result:

not determinable because of methodological limitations

Remarks:

The conc. at t=0 was below the limit of detection.

% Recovery:

92

pH:

7.1

Temp.:

21.5 °C

Duration:

0 h

% Recovery:

73

pH:

9

Temp.:

21.3 °C

Duration:

0 h

Key result

pH:

4

Temp.:

20.4 °C

Remarks on result:

not determinable because of methodological limitations

Key result

pH:

7

Temp.:

21.5 °C

Hydrolysis rate constant:

0.384 h-1

DT50:

2 h

Type:

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

Key result

pH:

9

Temp.:

21.3 °C

Hydrolysis rate constant:

0.624 h-1

DT50:

1 h

Type:

other: see "overall remarks"

Pseudo-first behaviour at pH 9 was not demonstrated. Taken the low coefficient of correlation of 0.592 (obtained for all logarithms of the relative concentrations against time) and the obvious high variety in data points (see attachment), it was concluded that there is no linear relationship at pH 9 between the logarithms of the relative concentrations and time. Since the model for pseudo-first order was used for calculation of the half-life time, the result should be interpreted as an estimated value.

Conclusions:

The substance is hydrolytically unstable at pH 4, pH 7 and pH 9.
The half-life time of the substance at ca. 20°C at pH 7 and pH 9 was determined to be 2 hours and 1 hour, resp.
The half-life time of the substance at 20°C at pH 4 could not be determined due to fast hydrolysis.

Executive summary:

The hydrolysis test at pH values normally found in the environment (pH 4, 7 and 9) was performed in a GLP-compliant study according to EC C.7, OECD 111 and EPA OPPTS 835.2120.

Tier 2 study was performed at room temperature (i.e 20°C). Very fast hydrolysis at pH 4 which could not be monitored. The half-life time of the substance at 20°C at pH 4 could therefore not be determined.

The half-life time of the substance at ca. 20°C at pH 7 and pH 9 was determined to be 2 hours and 1 hour, respectively.

Reference 2

Endpoint:

hydrolysis

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The rationale to read across the data is attached in section 13.

Reason / purpose for cross-reference:

read-across source

Preliminary study:

not conducted

Test performance:

pH 4
9 sampling times from 0 h to 0.7 h. Test item (max. 0.45 mg/L) was detected in one of the samples taken at 0.13 h, at 0.20 h and at 0.28 h. No test item was detected in all other samples. This indicated fast hydrolysis that could technically not be monitored.

pH 7
16 sampling times from 0 h to 19.77 h. The concentration decreased from 9.23 mg/L (at t=0) to 2.4 mg/L (at 3.13 h) and to a concentration below the limit of detection (at t=19.77 h).
Lineair regression curve (log. rel. conc. vs time ) over the time period from 0 to 3.13 h: Y = -0.167X + 1.87 (r=0.949).
Plot of the data points and the curve: see attachment

pH 9
13 sampling times from 0 h to 2.33 h. The concentration decreased from 7.48 mg/L (at t=0) to 0.55 mg/L (at t=2.33 h).
Lineair regression curve (log. rel. conc. vs time): Y = -0.271X + 1.52 (r=0.592)
Plot of the data points and the curve: see attachment

RECOVERIES
- Recovery is the concentration analysed at t=0 relative to the nominal concentration.
- The mean (n=2) recovery at pH 7 and pH 9 was calculated (see table below).
- The mean recovery for pH 7 fell within the criterion range of 90-110%.
- The mean recovery for pH 9 fell within the acceptable range for non-labelled chemicals of 70-110%.
- The concentrations analysed in the test samples were not corrected for recovery.

Transformation products:

not specified

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

no data

pH:

4

Temp.:

20.4 °C

Duration:

0 h

Remarks on result:

not determinable because of methodological limitations

Remarks:

The conc. at t=0 was below the limit of detection.

% Recovery:

92

pH:

7.1

Temp.:

21.5 °C

Duration:

0 h

% Recovery:

73

pH:

9

Temp.:

21.3 °C

Duration:

0 h

Key result

pH:

4

Temp.:

20.4 °C

Remarks on result:

not determinable because of methodological limitations

Key result

pH:

7

Temp.:

21.5 °C

Hydrolysis rate constant:

0.384 h-1

DT50:

2 h

Type:

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

Key result

pH:

9

Temp.:

21.3 °C

Hydrolysis rate constant:

0.624 h-1

DT50:

1 h

Type:

other: see "overall remarks"

Pseudo-first behaviour at pH 9 was not demonstrated. Taken the low coefficient of correlation of 0.592 (obtained for all logarithms of the relative concentrations against time) and the obvious high variety in data points (see attachment), it was concluded that there is no linear relationship at pH 9 between the logarithms of the relative concentrations and time. Since the model for pseudo-first order was used for calculation of the half-life time, the result should be interpreted as an estimated value.

Conclusions:

The substance is hydrolytically unstable at pH 4, pH 7 and pH 9. The half-life time of the substance at ca. 20°C at pH 7 and pH 9 was determined to be 2 hours and 1 hour, resp. The half-life time of the substance at 20°C at pH 4 could not be determined due to fast hydrolysis. This result is read across to 1,3-H6XDI.

Executive summary:

The hydrolysis test at pH values normally found in the environment (pH 4, 7 and 9) was performed in a GLP-compliant study according to EC C.7, OECD 111 and EPA OPPTS 835.2120. Tier 2 study was performed at room temperature (i.e 20°C). Very fast hydrolysis at pH 4 which could not be monitored. The half-life time of the substance at 20°C at pH 4 could therefore not be determined. The half-life time of the substance at ca. 20°C at pH 7 and pH 9 was determined to be 2 hours and 1 hour, respectively. This result is read across to 1,3-H6XDI.

Description of key information

The substance is hydrolytically unstable at pH values normally found in the environment (pH 4, 7 and 9).

Additional information

The hydrolysis test at pH values normally found in the environment (pH 4, 7 and 9) was performed with 1,4-H6XDI in a GLP-compliant study according to EC C.7, OECD 111 and EPA OPPTS 835.2120. The half-life time of the substance at ca. 20°C at pH 7 and pH 9 was determined to be 2 hours and 1 hour, resp. The half-life time of the substance at 20°C at pH 4 could not be determined due to fast hydrolysis. This result is read across to 1,3-H6XDI.