3,3'-dimethylbiphenyl-4,4'-diyl diisocyanate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

EEC No. L383 A, dated December 1992

Deviations:

yes

Remarks:

Measurement of the hydrolysis product instead of the parent material due to the physicochemical instability of TODI. A method for analysis of the hydrolysis product was provided by the Sponsor. This was implemented and validated.

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

see above

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

The buffered test solutions were thermostated (25 ± 2°C, and 50°± 0.5 °C) for the duration of the hydrolysis test periods. The reaction solutions were analysed at the start of the test, and after suitable time periods (typically 10 or 20 minutes up to 2 hours, then every 100 to 200 minutes) until the peak area of the degradation product reached a plateau.

Buffers:

pH 4.0: 2 mL 0.2 M Sodium hydroxide and 250 mL 0.2 M Potassium hydrogen phthalate was diluted 1000 mL with ultra-pure water
pH 7.0: 147.8 mL 0.2 M Sodium hydroxide and 250 mL 0.2 M Potassium dihydrogen phosphate was diluted 1000 mL with ultra-pure water
pH 9.0: 107 mL 0.2 M Sodium hydroxide and 250 mL 0.2 M Boric acid and Potassium chloride was diluted 1000 mL with ultra-pure water

Details on test conditions:

pH: The hydrolysis was examined at three different pH values 4, 7 and 9 in the dark.
Temperature: 50 °C ± 0.5 °C and 25 ± 2 °C
Light and oxygen: The hydrolysis reaction was carried out using a dark thermostat to avoid photolytic effects. Nitrogen was bubbled into the water for five minutes before the preparation of the solutions in order to exclude oxygen. All glassware, water and buffer solution were sterilised.
Apparatus
HPLC system: Merck-Hitachi LaChrom HPLC system: D-7000 Interface, No.: 1231-056 L-7100 HPLC pump, No.: 1272-0309 L-7200
Autosampler, No.: 1273-016 L-7400
UV Detector, No.: 1260-088 Jetstream II Plus, No.: 160706
Mass Spectrometer LCQ Duo, Finnigan, No.: 00360
Balances: BP 221S Sartorius, No.: 11809117 L 2200P Sartorius, No.: 38100037
Ultrasonic bath: Elmasonic S 300 H, No.: 010890105 pH meter: OP – 211/1, Radelkis No.: 6431
Thermostat: LP 132, No.: 870595
Hot Air Steriliser: ATP line FED, WTB Binder, No.: 9110-0035
Water purification system: MILLIPORE, DIRECT Q3, FOMNO 7334I

Duration:

1 130 min

pH:

4

Temp.:

25 °C

Initial conc. measured:

> 4.5 - < 5.5 other: µg/mL

Duration:

940 min

pH:

4

Temp.:

50 °C

Initial conc. measured:

> 4.5 - < 5.5 other: µg/mL

Duration:

1 747 min

pH:

7

Temp.:

25 °C

Initial conc. measured:

> 4.5 - < 5.5 other: µg/mL

Duration:

230 min

pH:

7

Temp.:

50 °C

Initial conc. measured:

> 4.5 - < 5.5 other: µg/mL

Duration:

990 min

pH:

9

Temp.:

25 °C

Initial conc. measured:

> 4.5 - < 5.5 other: µg/mL

Duration:

810 min

pH:

9

Temp.:

50 °C

Initial conc. measured:

> 4.5 - < 5.5 other: %

Number of replicates:

10

Positive controls:

no

Negative controls:

yes

Remarks:

Acetonitrile

Statistical methods:

The chromatograms were evaluated with the help of “LaChrom” chromatogram processor software. Calculations were carried out using EXCEL for Windows.
Due to physico-chemical properties of the test item (low water solubility and abiotic degradation) the Sponsor provided an analytical method for the determination of the degradation product. The hydrolysis reaction was evaluated based on the formation of the degradation product because the decrease in TODI concentration could not be followed analytically. Hence measurement of the hydrolysis product was considered to be a valid method to assess the rate of hydrolysis.
The rate constant (kobs) for pH 7 was determined from the plot of the logarithms of the peak areas versus time using the expression:
kobs = (1/t)*ln(c0/ct) (eq. 1)
kobs = slope (eq. 2)
Calculation of the half-life: t1/2 = ln2/kobs (eq. 3)
where t = time
c0 = concentration at time 0
ct = concentration at time t

Preliminary study:

The hydrolysis test was performed at 50 ± 0.5 °C and 25 ± 2 °C, at pH 4, 7 and 9. One sample was analysed at each time point.

For each assay, the first ‘start’ time point for hydrolysis was made as quickly as the sample could be loaded into the HPLC system and analysed (typically 3 to 5 minutes). At the first time point and all subsequent time points at pH 4 and 9 at 50 ± 0.5 °C, the maximal amount of hydrolysis product was measured, hence the t1/2 was less that the first measurement time point. At 25°C, pH 9 full hydrolysis was within 30 minutes with 50% at the ‘start’ time point; at 25°C, pH 4 full hydrolysis was found at the first time point. It is concluded that TODI hydrolysed rapidly (in less than 30 minutes) at 25 and 50 °C at pH 4 and 9. At pH 7 hydrolysis of 100% was reached within 29 hours (25°C) and 2.5 hours (50°C). For the tests carried out at pH 7 the log-transformed data of peak areas against time were plotted. A line was fitted on the measured data and the rate constant and the half-life were obtained from its slope according to equations 2 and 3. The t1/2 at pH 4 and 9, at 25 and 50 °C was lower than or equal to 2 minutes; at pH7 the t1/2 was 16 hours and 1.2 hours at 25 and 50 °C respectively.

Transformation products:

yes

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

Due to the very rapid degradation of TODI, it was not possible to measure its concentrations, but the hydrolysis products could be measured. In agreement with the Sponsor, the formation of the hydrolysis product as the measure of hydrolysis rate was performed in this study.

% Recovery:

ca. 0

pH:

4

Temp.:

25 °C

Duration:

1 130 min

% Recovery:

ca. 0

pH:

4

Temp.:

50 °C

Duration:

940 min

% Recovery:

ca. 0

pH:

9

Temp.:

25 °C

Duration:

990 min

% Recovery:

ca. 0

pH:

9

Temp.:

50 °C

Duration:

810 min

% Recovery:

ca. 0

pH:

7

Temp.:

25 °C

Duration:

1 147 min

% Recovery:

ca. 0

pH:

7

Temp.:

50 °C

Duration:

230 min

pH:

4

Temp.:

25 °C

DT50:

<= 2 min

pH:

4

Temp.:

50 °C

DT50:

<= 2 min

pH:

9

Temp.:

25 °C

DT50:

<= 2 min

pH:

9

Temp.:

50 °C

DT50:

<= 2 min

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0 d-1

DT50:

16 h

Type:

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

Key result

pH:

7

Temp.:

50 °C

Hydrolysis rate constant:

0.01 d-1

DT50:

1.2 h

Type:

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

Details on results:

TEST CONDITIONS
- pH, temperature, and other experimental conditions maintained throughout the study: Yes

TRANSFORMATION PRODUCTS
At pH4:
- Range of maximum concentrations in % of the applied amount and day(s) of incubation when observed: 100 % immediately after start (25°C and 50°C)

At pH7:
- Range of maximum concentrations in % of the applied amount and day(s) of incubation when observed:
- Range of maximum concentrations in % of the applied amount at end of study period: 100 % after 29 hours (25°C) and after 2,9 hours (50°C)

At pH9:
- Range of maximum concentrations in % of the applied amount and day(s) of incubation when observed: 100 % after 30 minutes (25°C) and immediatley after start (50°C)


MINERALISATION (distinguish between dark and irradiated samples)
- % of applied radioactivity present as CO2 at end of study:



SUPPLEMENTARY EXPERIMENT (if any): RESULTS: Pre-study prior to preliminary test
Pre-study: TODI was dissolved in acetonitrile. 100µL of water was added to 1 ml of the organic stock solution. The sample was allowed to stand for 5, 30 and 60 minutes. During this time a white precipitate was formed. The precipitate was dissolved with the addition of 1 mL acetonitrile, and 5 µL acetic acid was added to the sample and it was analysed by Mass Spectrometry.
Hydrolysis was found to be very fast, based on the mass spectra, TODI (m/z 265) disappeared and the hydrolysed products (m/z 240 and 214) appeared when in contact with water for 60 minutes.

Based on the mass sectra, TODA (substance name: 4,4'-bi-o-toluidine; alternative name: 3,3' -Dimethyl -4,4'-diamino-biphenyl, CAS no. 119 -93 -7, EC no. 204 -358 -0) was supposed to be the product of hydrolysis (m/z = 213.8) after 30 min and 60 min after contact with water.

Validity criteria fulfilled:

yes

Conclusions:

Hydrolysis of TODI was found to be very fast and the half-life time at pH 4 and 9 was less than the minimum time taken to make the initial sample analysis.
At pH7 only, the hydrolysis reaction could be followed and a half-life calculated. By the analysis of the degradation product, the calculated half-life was 1.2 hours at 50°C and 16 hours at 25°C

Executive summary:

This study followed the procedures indicated by the following internationally accepted guidelines: Organisation for Economic Co-operation and Development (OECD), OECD Guidelines for Testing of Chemicals, Guideline No. 111, "Hydrolysis as a Function of pH", adopted 13 April 2004 European Economic Community (EEC), Directive 92/69, Part C, C.7 "Degradation: Abiotic Degradation: Hydrolysis as a Function of pH", Official Journal of the European Communities No. L 383 A, dated December 29, 1992. The purpose of this study was to evaluate the rate of hydrolysis of TODI in solutions of different pH values.

The t1/2 at pH 4 and 9, at 25 and 50 °C was lower than or equal as 2 minutes; at pH7 the t1/2 was 16 hours and 1.2 hours at 25 and 50 °C respectively.

Thus, hydrolysis of TODI was found to be very fast. At pH 4 and 9 decomposition product had reached a plateau at the earliest measurement time, the half-life was less than the minimum time taken to make the initial sample analysis. At pH 7 only, the hydrolysis reaction could be followed and a half-life calculated.

The calculated half-life was 1.2 hours at 50°C at pH 7 for TODI (analysed by the degradation product).

Description of key information

TODI hydrolyses very fast. The calculated half-life was 1.2 hours at 50°C.

Key value for chemical safety assessment

Half-life for hydrolysis:

0.01 d

at the temperature of:

323.2 K

Additional information

The hydrolysis of TODI was found to be very fast, therefore no further testing was necessary. At pH 4 and 9 decomposition product had reached a plateau at the earliest measurement time, the half-life was less than the minimum time taken to make the initial sample analysis (the t1/2 at pH 4 and 9, at 25 and 50 °C was lower than or equal as 2 minutes). At pH 7 only, the hydrolysis reaction could be followed and a half-life calculated. The calculated half-life was 1.2 hours at 50°C at pH 7 for TODI (analysed by the degradation product TODA).