Reaction mass of 1H-Benzotriazole-1-methanamine, N,N-bis(2-ethylhexyl)-6-methyl- and 2H-Benzotriazole-2-methanamine, N,N-bis(2-ethylhexyl)-5-methyl- and N,N-bis(2-ethylhexyl)-4-methyl-1H-benzotriazole-1-methylamine and 2H-Benzotriazole-2-methanamine, N,N-bis(2-ethylhexyl)-4-methyl- and N,N-bis(2-ethylhexyl)-5-methyl-1H-benzotriazole-1-methylamine

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06-09-2012 to 27-02-2013

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: 0005408236
- Expiration date of the lot/batch: July 2014

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: samples were directly from the different buffer solutions.

Buffers:

- pH: 4,7,9

Composition Buffer:
pH 4:
21.01 g citric acid monohydrate was dissolved in 200 mL sodium hydroxide solution (c = 1 mol/L). This solution was filled up to a volume of 1000 mL with distilled water. 44 mL of hydrochloric acid (c = 1 mol/L) was added to 560 mL of this solution and filled up to a volume of 1000 mL with distilled water. The pH value was adjusted to pH 4 for each hydrolysis temperature.
pH 7:
13.61 g potassium dihydrogen phosphate was dissolved in 1000 mL distilled water. 30 mL of sodium hydroxide solution (c = 1 mol/L) was added to 500 mL of this solution and filled up to a volume of 1000 mL with distilled water. The pH value was adjusted to pH 7 for each hydrolysis temperature.
pH 9:
7.46 g potassium chloride and 6.18 g boric acid was dissolved in 1000 mL distilled water. 21 mL of sodium hydroxide solution (c = 1 mol/L) was added to 500 mL of this solution and filled up to a volume of 1000 mL with distilled water. The pH value was adjusted to pH 9 for each hydrolysis temperature.

Details on test conditions:

The used volumetric flasks were heated at 110 °C and flooded with nitrogen. Solutions of the test item were prepared by first dissolving 40.8 mg of the test item in 50 mL acetonitrile by treating the mixture with ultrasound. Aliquots of the stock solution were diluted 0.5 to 50 mL with the relevant buffers (filled up to the mark). Aliquots were prepared in duplicate.

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

> 8.38 - < 8.39 mg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

> 8.18 - < 8.24 mg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

> 8.17 - < 8.32 mg/L

Number of replicates:

2

Preliminary study:

Corresponding to the results of the preliminary test the decomposition at pH 4, 7 and 9 seems to be below 10 % after 5 days at 50°C. As the test item is not stable in solution it can be assumed that the concentration of hydrolysis product was detected and the results of preliminary test are misleading. In order to clarify this assumption additional tests have been performed.

Test performance:

The preliminary test at pH 4, 7 and 9 seemed to show no degradation. These results are misleading. In the chromatograms of the test item dissolved in buffer solutions and of the standard solutions only one peak was detected. The comparison of the test item and the reference item by means of HPLC and UV/Vis showed that this peak can be dedicated to the reference item. Therefore it can be assumed that test item hydrolysis directly and quantitatively when it is solved in the buffer solutions and thus the test item is not considered to be hydrolytically stable. The determination of the hydrolysis rate is not possible because of the high hydrolysis rate.

Transformation products:

yes

No.:

#1

% Recovery:

0

pH:

4

Temp.:

50 °C

Duration:

5 d

% Recovery:

0

pH:

7

Temp.:

50 °C

Duration:

5 d

% Recovery:

0

pH:

9

Temp.:

50 °C

Duration:

5 d

Key result

Remarks on result:

other: No quantitative result was determined. The determination of the hydrolysis rate is not possible because of the high hydrolysis rate.

Details on results:

The test item hydrolysis directly and quantitatively when it is solved in the buffer solutions. Thus the test item is not considered to be hydrolytically stable at pH 4, 7 and 9. The determination of the hydrolysis rate is not possible because of the very fast hydrolysis. The hydrolysis product was identified as Methyl-1 H-benzotriazole.

Validity criteria fulfilled:

yes

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25-11-2020 to xx-xx-2022
only DRAFT report available, the final report is expected later.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

The buffers described in the guideline were not applicable for NMR analysis. D2O was used instead of H2O to avoid strong signal overlap in the 1H-NMR spectra. Additionally, due to the sample preparation, it was not possible to measure pH during the test.

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Lot/batch No.of test material: 0021500104
- liquid at room temperature

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: Higher Tier tests were conducted until 90 % hydrolysis of the test item was observed or for 30 days whichever came first (time points depend on the pH and temperature conditions; according to the guideline, a minimum of six spaced data points between 10 % and 90 % hydrolysis of the test item were collected for each sample).
- Duplicate samples for each time point contained in separate reaction vessels (NMR tubes)

Buffers:

pH: 4, 7, 9

The buffers described in the OECD Guideline for the Testing of Chemicals 111 were not applicable for NMR analysis. D2O was used instead of H2O for the investigations by NMR to avoid strong signal overlap in the 1H-NMR spectra by an intense and broad water peak. Thus, the pH value which is mentioned related to the NMR investigations is in fact a pD value (negative decadic logarithm of the deuterium concentration).

Aqueous solutions (pH 4 (DCl in D2O) & pH 9 (NaOD in D2O)) were prepared by adding as much DCl or NaOD respectively to D2O until the desired pH value was reached. The pH value was checked with pH idicator paper. Pure D2O was taken for investigations at pH 7.

Due to the sample preparation (flamed sealed NMR tubes), it was not possible to determine the pH values at the beginning or during the experiments. The pH values of the prepared buffers were measured before mixing with acetone/test item. Moreover, it’s not sensible to measure the pH value in a 60 % acetone solution.

Details on test conditions:

Photolysis was excluded by conducting the experiment in amber coloured glass vials in a dark warming cupboard. Oxidation reactions were minimised by removing dissolved oxygen from the buffer (degassing with nitrogen) before addition of the test item.

Number of replicates:

To test the hydrolytic stability a total of 18 samples were prepared (duplicate samples at pH 4, pH 7 and pH 9 according to the OECD Guideline for the Testing of Chemicals 111 each stored at 20 °C, 40 °C or 60 °C).

Preliminary study:

Preliminary tests showed that Irgamet 39 is only fairly poor soluble in water. Therefore, [D6]-acetone had to be used as solubilizer.


Tier 1 testing was not performed because the test item is known to be hydrolytically unstable at environmentally relevant temperatures. The instability and multi-level hydrolysis of the test item in water is known from literature (Wiklund, Per; Chemical Stability of Benzotriazole Copper Surface Passivators in Insulating Oils. Ind. Eng. Chem. Res. 2007, 46, 3312-3316.) and the experimental hydrolysis study (tier 1), see chapter 5.1.2 Siemens AG, 2013, so the hydrolysis test had to be done.

Transformation products:

yes

No.:

#1

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

The final hydrolysis product could be identified as Irgamet TTZ. Its generation in the hydrolysis reaction mixture was proven by adding Irgamet TTZ to a mixture mimicing full hydrolysis of Irgamet 39 (500 μL of a stock solution of 47.24 mg Irgamet 39 in 5 mL acetone-[D6] were treated with 150 μL trifluoroacetic anhydride) which led to a signal increase of the NMR signals belonging to Irgamet TTZ (see Figure 28 on page 31). Therefore, a stock solution of Irgamet TTZ (31.87 mg) in 5 mL acetone-[D6] was prepared and 50 μL were added to a solution of Irgamet 39 in acetone-[D6] (500 μL; 0.47 mg/mL). Furthermore, Irgamet TTZ was identified as the final hydrolysis product through i) detecting Irgamet TTZ using HPLC-UV and HRMS (see GLP-study no 20L00222 water solubility; Competence Center Analytics, BASF SE, D-67056 Ludwigshafen); ii) stirring Irgamet 39 (26.89 mg) in D2O (5 mL) for 4 h led to the NMR detection of mainly Irgamet TTZ signals in the aromatic region and Irgamet 39 could not be detected.

The following mechanism can be proposed: In an equilibrium, the bond between the linking CH2-group and the aliphatic moiety of Irgamet 39 gets hydrolyzed generating TTZ-CH2-OH and Bis(2-ethylhexyl) amine as the corresponding amine. Further hydrolysis of the bond between the CH2-group and the aromatic moiety of TTZ-CH2-OH yields Irgamet TTZ and formaldehyde monohydrate. Formaldehyde monohydrate is then further converted to POM, probably by reaction with formaldehyde provided by an equilibrium of formaldehyde monohydrate with small amounts of formaldehyde (below the NMR detection limit).

Considering the proposed mechanism, another hydrolysis path, in particular the hydrolysis of the bond between the linking CH2-group and the aliphatic nitrogen, might be conceivable. However, we did not detect any CH2-OH signals that showed a coupling to the aliphatic region as is the case for Irgamet 39.
In addition, the 1H-1H-NOESY spectrum did not show any signal of a linking CH2-group that has through-space interactions with an aliphatic moiety except for the signals of Irgamet 39.

pH:

4

Temp.:

20 °C

Hydrolysis rate constant:

0.006 h-1

DT50:

116.6 h

Type:

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

Remarks on result:

other: calculated using Arrhenius equation

pH:

7

Temp.:

20 °C

Hydrolysis rate constant:

0.006 h-1

DT50:

117.3 h

Type:

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

Remarks on result:

other: calculated using Arrhenius equation

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

0.006 h-1

DT50:

115.4 h

Type:

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

Remarks on result:

other: calculated using Arrhenius equation

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

0.009 h-1

DT50:

81.4 h

Type:

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

Remarks on result:

other: calculated using Arrhenius equation

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.009 h-1

DT50:

81.4 h

Type:

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

Remarks on result:

other: calculated using Arrhenius equation

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0.009 h-1

DT50:

80.8 h

Type:

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

Remarks on result:

other: calculated using Arrhenius equation

pH:

4

Temp.:

60 °C

Hydrolysis rate constant:

0.07 h-1

DT50:

10 h

Type:

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

pH:

4

Temp.:

40 °C

Hydrolysis rate constant:

0.029 h-1

DT50:

24 h

Type:

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

pH:

4

Temp.:

20 °C

Hydrolysis rate constant:

0.005 h-1

DT50:

129 h

Type:

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

pH:

7

Temp.:

60 °C

Hydrolysis rate constant:

0.075 h-1

DT50:

9.2 h

Type:

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

pH:

7

Temp.:

40 °C

Hydrolysis rate constant:

0.028 h-1

DT50:

25.1 h

Type:

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

Key result

pH:

7

Temp.:

20 °C

Hydrolysis rate constant:

0.006 h-1

DT50:

126 h

Type:

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

pH:

9

Temp.:

60 °C

Hydrolysis rate constant:

0.071 h-1

DT50:

9.7 h

Type:

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

pH:

9

Temp.:

40 °C

Hydrolysis rate constant:

0.027 h-1

DT50:

25.7 h

Type:

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

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

0.006 h-1

DT50:

123.5 h

Type:

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

Other kinetic parameters:

Assuming first order reactions, hydrolysis rates and half-lives for other temperatures can be calculated at pH 4, pH 7 and pH 9 according to the Arrhenius equation.
By plotting the natural logarithm of the rate constants against the reciprocal of the temperature (in K), the rate constants and half-lives at 20 °C and 25 °C were obtained by extrapolation. The other results were determined experimentally.

Details on results:

Over the many experiments conducted associated with the hydrolysis of Irgamet 39 an instant increase in signal intensity of 1H-NMR signals at ~ 6.1 ppm and the appearance of a very intense signal at ~ 4.8 ppm could be ubiquitously observed directly upon addition of any of the aqueous solutions to the Irgamet 39/[D6]-acetone stock solution.
The signals at ~ 6.1 ppm could be assigned to the TTZ-CH2-OH isomers that are suggested to be generated through hydrolysis of the bond between the linking CH2-group and the aliphatic amine. The assignment was especially accomplished through acquisition of an edited 1H-13C HSQC spec-trum, 1H-13C HMBC spectrum and shift comparison of the thereby obtained 13C chemical shifts with calculated 13C shifts (by the ISEE program).

The HMBC spectrum showed that the CH2-group only shows coupling to the aromatic region but not to the aliphatic region in contrast to Irgamet 39 which exhibits both mentioned couplings. Furthermore, a 1H-1H-NOESY spectrum (see Figure 31 on page 34) further showed, that Irgamet 39 and TTZ-CH2-OH are in a chemical exchange.

The signal at ~ 4.8 ppm did not show any through-space interactions to both aromatic and aliphatic moieties. Its 13C chemical shift derived from the edited 1H-13C HSQC spectrum fits well to that of formaldehyde monohydrate H2C(OH)2 found in literature. It is known that formaldehyde monohydrate is in equilibrium with formaldehyde under aqueous conditions and that under these condi-tions the equilibrium is on the side of the monohydrate.

As the hydrolysis reaction progressed over time, several small signals increasing in signal intensity were detected next to the signal of formaldehyde monohydrate H2C(OH)2. These fit well with the shifts found in the literature for polyformaldehyde.9 For this reason, we postulate a further reaction of the formaldehyde monohydrate to polyformaldehyde, also known as polyoxymethylene (POM). However, the composition of the different chain lengths of POM could not be determined by NMR.

In some of the 1H-NMR spectra of Irgamet 39 dissolved in [D6]-acetone, a small signal at 9.68 ppm was observed which would fit to the 1H-NMR chemical shift of formaldehyde. Upon addition of any of the aqueous solutions or D2O, this signal vanished which would be in line with the formation of formaldehyde monohydrate H2C(OH)2, the more stable derivative in aqueous me-dium.12 To verify whether formaldehyde was already present in the test item or if it was formed in [D6]-acetone due to residual amounts of water, the test item was dissolved in dry CD2Cl2. The characteristic signal of formaldehyde at 9.68 ppm could not be observed which demonstrates that formaldehyde was not present in the test item.

Conclusions:

The hydrolysis of Irgamet 39 as a function of pH was determined at three different pH-values by the method OECD 111. At each pH hydrolytical decomposition can be observed, e.g. at 20 °C and a pH of 7 with the rate konstant k of 0.0055238 1/h and a DT50 of 126 h. The final hydrolysis product could be identified as Irgamet TTZ.

Executive summary:

The hydrolysis of Irgamet 39 as a function of pH was determined at three different pH-values by the method OECD 111. At each pH hydrolytical decomposition can be observed, e.g. at 20 °C and a pH of 7 with the rate konstant k of 0.0055238 1/h and a DT50 of 126 h.

 

The final hydrolysis product could be identified as Irgamet TTZ.

The following mechanism can be proposed: In an equilibrium, the bond between the linking CH2-group and the aliphatic moiety of Irgamet 39 gets hydrolyzed generating TTZ-CH2-OH and Bis(2-ethylhexyl) amine as the corresponding amine. Further hydrolysis of the bond between the CH2-group and the aromatic moiety of TTZ-CH2-OH yields Irgamet TTZ and formaldehyde monohydrate. Formaldehyde monohydrate is then further converted to POM, probably by reaction with formaldehyde provided by an equilibrium of formaldehyde monohydrate with small amounts of formaldehyde (below the NMR detection limit).

Description of key information

The hydrolysis of Irgamet 39 as a function of pH was determined at three different pH-values by the method OECD 111 (BASF, draft report, 2022). At each pH hydrolytical decomposition can be observed, e.g. at 20 °C and a pH of 7 with the rate konstant k of 0.0055238 1/h and a DT50 of 126 h. The final hydrolysis product could be identified as TTZ (CAS no. 29385-43-1). Additionally the following transformation products were proposed: Formaldehyde (CAS no. 50-00-0), Bis(2-ethylhexyl)amine (CAS no. 106-20-7).

Key value for chemical safety assessment

Half-life for hydrolysis:

126 h

at the temperature of:

20 °C

Additional information

A previous hydrolysis study (tier 1) was performed at 50°C and at three different pH values (4, 7, 9) according to OECD Guideline 111 (Siemens, 2013). The major constituents of test item (1H-Benzotriazole-1-methanamine, N,N-bis(2-ethylhexyl)-5-methyl-, 1H-Benzotriazole-1-methanamine, N,N-bis(2-ethylhexyl)-4-methyl- and 1H-Benzotriazole-1-methanamine, N,N-bis(2-ethylhexyl)-6-methyl- hydrolyse directly and quantitatively when it is solved in the buffer solutions. The determination of the hydrolysis rate was not possible because of the very fast hydrolysis. Thus the test item was not considered to be hydrolytically stable at pH 4, 7 and 9. Methyl-1H-benzotriazole (TTZ) was detected as hydrolysis product. Additionally the following transformation products were proposed: Formaldehyde (CAS no. 50-00-0), Bis(2-ethylhexyl) amine (CAS no. 106-20-7).

 

The tier 2 and 3 study (BASF 2022) was performed to provide relevant information on hydrolysis at environmentaly relevant conditions. The final hydrolysis product could be identified as TTZ.

The following mechanism can be proposed: In an equilibrium, the bond between the linking CH2-group and the aliphatic moiety of Irgamet 39 gets hydrolyzed generating TTZ-CH2-OH and Bis(2-ethylhexyl) amine as the corresponding amine. Further hydrolysis of the bond between the CH2-group and the aromatic moiety of TTZ-CH2-OH yields Irgamet TTZ and formaldehyde monohydrate. Formaldehyde monohydrate is then further converted to POM, probably by reaction with formaldehyde provided by an equilibrium of formaldehyde monohydrate with small amounts of formaldehyde (below the NMR detection limit).