2-methyl-p-phenylenediamine

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Peer reviewed handbook or data collection can be assessed as data source reliable with restrictions, thus a Klimisch 2 rating was given.

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Principles of method if other than guideline:

- Model(s) used: no model used, just prediction based on the structural functions of the molecule.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From November 24, 2015 to April 05 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

conducted in sterile natural water at 12 and 25°C

Principles of method if other than guideline:

The hydrolytic stability of 2,5-diaminotoluene was investigated in sterile natural water at two different temperatures. The target concentration in the test was 10 mg/L and was below half of the water solubility of the test item.

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: Main Test: Based on the results of the preliminary test, a main test was conducted for 25 °C with the intervals of 0.25, 1, 2, 4, 6 and 12 hours. For 12 °C samples were taken after 0.25, 1, 4, 7, 12 and 24 hours.- Sampling method: Duplicate samples were taken.- Sampling methods for the volatile compounds, if any: Since the test systems were entirely closed, evaporation was not an issue and had not to be corrected for (as had been checked gravimetrically).- Sampling intervals/times for pH measurements and Sample storage conditions before analysis: At the respective sampling intervals, the pH values were measured and the weight of the samples determined (in order to evaluate any loss by evaporation). Thereafter, the samples were stabilised with 1% thioglycerol and analysed, after a dilution step of 1:100, by LC-MS in order to determine if degradation of the test item was higher than 10 % within 5 days.- Sampling intervals/times for sterility check: Aliquots of 0.5 mL of the test solutions from the start and end of the study were uniformly distributed onto the surface of agar plates (Merck, CASO-Agar Caseinpepton-Sojamehlpepton-Agar for Microbiology) and incubated in the dark at room temperature for up to 10 days. In addition, a positive control (1 mL tap water) and a negative control (1 mL sterile purified water) were incubated under the same conditions. The colonies that developed on these plates at the end of the respective exposure period were counted.- Other observation, if any (e.g.: precipitation, color change etc.):

Buffers:

No buffer, sterile natural river water (pH 8.4) was used.

Estimation method (if used):

Degradation rates of the test item were calculated according to the FOCUS Guidance (2006) on estimating persistence and degradation kinetics from Environmental Fate Studies [3] using the software tool CAKE (version 3.1, Release) [4]. According to the Guidance, if degradation rates for use in modelling can be described by Single First-Order (SFO) kinetics, no other models need to be calculated. In this study, SFO met the requirements in all cases. Thus the SFO model output was selected and is presented in this study.

Details on test conditions:

TEST SYSTEM- Type, material and volume of test flasks, other equipment used: Hydrolysis was performed at 25 °C and 12 °C in sterile filtrated natural water. For each temperature, samples of 10 mL, each containing the test item, were incubated under constant shaking in a thermo-regulated water bath at the desired temperature in the dark (to avoid photolytic effects).- Sterilisation method: Natural water was collected in Germersheim (Germany) close to the bank of the river Rhine (49.220034 N / 8.383418 E) and passed through a 0.2 μm filter. Thereafter, it was sterilized by a “NALGENE” Rapid Flow disposable filter with PES membrane (pore size 0.2 μm). To minimise the process of microbial degradation during incubation, all glass equipment (including the incubation vessels) was sterilized by an autoclave (Priorclave Compact 40 Benchtop; 121 °C for 20 min) prior to use.All treatments were performed on the sterile bench under laminar flow conditions.Total plate counts (bacteria) were determined for the test solutions immediately after sterilisation i.e. at the start of incubation and at the end of the incubation period.- Lighting: in the dark - Measures to exclude oxygen: none- Details on test procedure for unstable compounds: /- Details of traps for volatile, if any: not used- If no traps were used, is the test system closed/open: closed- Is there any indication of the test material adsorbing to the walls of the test apparatus? NoTEST MEDIUM- Volume used/treatment: 10 mL- Kind and purity of water: natural river water used.Parameters of Natural Pond Water at Sampling:Source: Rhein bei Germersheim, GermanyCoordinates: 49.220034 N / 08.383418 EBatch No.: Rhein bei Germersheim 06/14Sampling date: June 25, 2014Filtration after sampling: Yes, 0.2 μmStorage conditions until use: About 4 °C in the darkpH: 8.44Total hardness: 200 mg/L CaCO3Conductivity: 363 μS/cmTOC: 1.870 mg/L ± 6.2%DOC: 1.846 mg/L ± 5.8%. TOC and DOC values are very similar since these were measured after sterile filtration- Preparation of test medium: natural river water used- Renewal of test solution: no- Identity and concentration of co-solvent: not usedOTHER TEST CONDITIONS- Adjustment of pH: no- Dissolved oxygen: /

Duration:

24 h

pH:

8.44

Temp.:

12 °C

Initial conc. measured:

10 mg/L

Duration:

12 h

pH:

8.44

Temp.:

25 °C

Initial conc. measured:

10.5 mg/L

Number of replicates:

At each sampling interval, duplicate samples per temperature were taken.

Positive controls:

no

Negative controls:

no

Preliminary study:

Initially, a preliminary test was performed with the test item for up to 2 days at 25 °C and 12 °C in the dark, using sterilized natural river water. The aim of the preliminary test was to estimate the degradation rate of the test item and to determine reasonable sampling intervals for the main test.2,5-diaminotoluene degraded very rapidly at 25 °C and 12 °C, representing 0.8% and 10.7% of the applied amount on day 1 and <0.1% and 1.6% of applied after two days for 25 °C and 12 °C, respectively.

Test performance:

Based on the results of the preliminary test, a main test was conducted. For 25 °C, samples were taken after 0.25, 1, 2, 4, 6 and 12 hours. For 12 °C samples were taken after 0.25, 1, 4, 7, 12 and 24 hours.At 25 °C, 2,5-diaminotoluene degraded rapidly representing mean values of 56.8 % after 4 hours and 4.7% of the applied amount after 12 hours of incubation in the dark. At 12 °C, the test item degraded more slowly showing a lag phase for at least 7 hours. After 12 hours, the test item represented 40.8% and 18.5% of the applied dose after 24 hours. From the structure of the test item, hydrolysis is not to be expected but the disappearance could be related to auto-oxidation processes.

Transformation products:

not measured

% Recovery:

4.7

pH:

7.32

Temp.:

25 °C

Duration:

12 h

% Recovery:

18.5

pH:

7.27

Temp.:

12 °C

Duration:

24 h

pH:

7.2

Temp.:

25 °C

Hydrolysis rate constant:

0.191 d-1

DT50:

3.63 h

St. dev.:

0.019

Type:

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

Remarks on result:

other: Model: SFO Parent, M0: 121.6, k = 0.1911, χ2-error: 8.58, r2: 0.9628

pH:

7.2

Temp.:

12 °C

Hydrolysis rate constant:

0.058 d-1

DT50:

11.9 h

St. dev.:

0.012

Type:

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

Remarks on result:

other: Model: SFO Parent, M0: 117.9, k = 0.05823, χ2-error: 16.6, r2: 0.7941

Other kinetic parameters:

DT90 at 25°C: 12.1 hoursDT90 at 12°C: 39.6 hours

Details on results:

TEST CONDITIONS- pH, sterility, temperature, and other experimental conditions maintained throughout the study: YespH values of the time 0 samples represented the pH value of sterile natural water. Those from day 0 onwards, represented the pH value after the samples had been stabilized with 1% thioglycerol to avoid excessive degradation of the test item.- Anomalies or problems encountered (if yes): Due to the lag phase at 12°C, the kinetic fit of the experimental data was not optimal and was therefore additionally estimated based on the experimental value after 12 hours of incubation. The estimated DT50 value of about 10 to 12 hours confirmed the calculated DT50 quite accurately, demonstrating that the way of calculating the data did not impact very much on the DT50 value.PATHWAYS OF HYDROLYSIS- Description of pathways: From the structure of the test item, hydrolysis is not to be expected but the disappearance could be related to auto-oxidation processes.

Validity criteria fulfilled:

not applicable

Conclusions:

2,5-diaminotoluene degraded rapidly in sterile natural water at 25 °C and 12 °C. At 25 °C, DT50 value was calculated to be 3.63 hours and at 12 °C, estimated to be 10 to 12 hours.

Executive summary:

The hydrolytic stability of 2,5-diaminotoluene was investigated in sterile natural water at two different temperatures in the dark, following OECD 111 guideline and GLP. The target concentration in the test was 10 mg/L and was below half of the water solubility of the test item. At 25 °C, 2,5-diaminotoluene degraded rapidly representing mean values of 56.8 % after 4 hours and 4.7% of the applied amount after 12 hours of incubation in the dark. At 12 °C, the test item degraded more slowly showing a lag phase for at least 7 hours. After 12 hours, the test item represented 40.8% and 18.5% of the applied dose after 24 hours. From the structure of the test item, hydrolysis is not to be expected but the disappearance could be related to auto-oxidation processes. The temperatures remained constant throughout the respective incubation periods and no significant variation of pH values was observed in the natural water. The samples also remained sterile throughout the study. 2,5-diaminotoluene degraded rapidly in sterile natural water at 25 °C and 12 °C. At 25 °C, DT50 value was calculated to be 3.63 hours and at 12 °C, estimated to be 10 to 12 hours.

Reference 3

Endpoint:

hydrolysis

Remarks:

The transformation processes are not related to hydrolysis but to oxydation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline available

Principles of method if other than guideline:

- Principle of test / Short description of test conditions / Parameters analysed : this review pursues the aim to provide a synopsis of the current state of knowledge of (aut)oxidative reactions of PTD. Monomeric and oligomeric reaction products are presented together with the reaction conditions and analytical techniques applied for their generation and identification. Analytical data of these transformation products, e.g., electrochemical potentials, UV/VIS absorbance maxima, and mass spectrometric data, are tabulated. The certainty of the substance identification is rated with respect to the performance of the applied analytical techniques, to the concordance of results achieved by different methods, and to the traceability of the analytical procedure. Reaction pathways are outlined for both compounds.

GLP compliance:

no

Analytical monitoring:

yes

In contact with air or oxidizing agents like peroxides, phenylenediamines are easily transformed into complex mixtures of monomeric, dimeric, oligomeric, and polymeric oxidation products. Furthermore, the amines might undergo photolytic or photooxidative degradation when exposed to sunlight.

A visual sign of the reactivity of phenylenediamines is the development or change of color of their aqueous, oxygen containing, or air-exposed solutions within a few hours. Within a few hours, the solutions turn dark brown and, subsequently, a black-brown precipitate forms. The formation of the reaction products and thus the transformation of PTD is pH-dependent and accelerated under alkaline conditions.

 

Monomeric reaction products:

The oxidation of PTD results in the formation of the semitoluquinone diimine radical cation (STQDIRC), for instance by reaction with bromine in acetate buffer, which is unstable and very reactive. The toluquinone diimine of PTD was UV/VIS spectroscopically determined in aqueous solution at pH 4 and 7 after electrochemical PTD oxidation. PTD also transformed into the corresponding quinones by oxidation with Ce(IV) ions in perchloric acid. Probably, the reaction proceeded via the hydrolysis of the intermediate semiquinone diimine.

 

Dimeric products:

Dimeric compounds are generated either by the reaction (autoxidation) of two molecules of PTD or by the reaction of one of the aryldiamines with one of its oxidation products. The structural elucidation of dimeric oxidation products of PTD is challenging, since a determination of the ring positions of the methyl groups is required. In the last years, only Goux et al. made efforts in this direction. The spectroelectrochemical oxidation of PTD on a platinum electrode at neutral pH resulted in the formation of a dimer proven by UV/VIS and EPR spectra. The compound did not form at pH 2 and 10. The molecular structure could not be precisely defined, since the position of the methyl groups could not be clarified with the applied analytical techniques. Recently, Fischer et al. detected UV-photolysis products of PTD by means of HPLC-ESI-MS. Chromatographic retention times and molecular masses of 241.2 and 242.2, respectively, would be consistent with dimeric structures. A further characterization of these compounds remains outstanding.

 

Trimeric reaction products:

Goux et al. determined a Bandrowski Base (BB) like strusture for PTD by spectroelectrochemical methods (cyclic voltammetry-UV/VIS spectroscopy) in the pH range of 4 to 7. The structural evidence is merely based on the comparison of the obtained UV spectra with that of a BB standard. Fischer et al. tentatively identified a compound with a molecular mass of 343.3 amu as a trimeric PTD derivative formed during UV-photolysis of aqueous PTD solutions.

 

Reaction pathways of PTD:

According to an early investigation, the STQDIRC, is formed by the action of bromine on PTD in an acetate buffer/methanol solution. Recently, the occurrence of this radical was confirmed, and the pH dependence of its generation and reactivity was determined based on combined electrochemical (cyclic voltammetry) and in situ spectroscopic (EPR and UV/VIS absorbance) measurements. The radical has a lifetime of a few hours at neutral pH, but it reacts much faster at low and high pH. Subsequently, the toluquinone diimine (TQDI) is formed which attacks a PTD molecule to yield a dimeric product, not further characterized yet. Trimeric products including a BB-like structure originate from the reaction of dimeric intermediates with STQDIRC or TQDI.

 

Intrinsic difficulties of process and product elucidation:

Investigating reaction pathways and products of aryldiamines, one has to cope with some fundamental difficulties. First of all, the reaction of aqueous aryldiamine solutions with oxygen or oxygen-containing oxidants is able to proceed during several days with increasing yield of oligomeric and polymeric compounds. It is not clear whether a distinct reaction equilibrium can be practically reached and how the corresponding product spectrum will be composed of. Only a few dimeric and trimeric compounds, e.g., DAB and BB, seem to be relatively stable. Consequently, most of the detected products are intermediates whose lifetimes are highly variable and regulated by factors widely unknown. Due to the low selectivity of involved radical reactions, it can be assumed that the number of potential reaction products rises with the increasing degree of oligomerization of the attacked intermediates almost exponentially, forming a reaction cascade. Additionally, the whole reaction system seems to comprise autocatalytic steps including variable induction periods and feedback loops making it extremely sensible against smallest differences in substance composition, e.g., stoichiometric aryldiamine to oxidant ratio, content of impurities, spatial distribution of reactants in the reaction vessel, and against changes of physical reaction conditions, e.g., temperature and eventually radiation.

If autocatalytic reaction steps take place, the time-dependent product composition depends on the homogeneity of the distribution of all reaction factors, e.g., reactants, temperature, and light, in the reaction vessel. The dimension of the latter becomes a critical factor as well as its material composition, surface area, and surface properties. Up to now, no study has addressed these points.

Conclusions:

Despite of more than 100 years of research the understanding of (aut)oxidation processes of PTD is fragmentary. Many reaction products are not or not unambiguously identified. None of the PTD reaction products is satisfactorily characterized. For this, the reasons are manifold. Some belong to the above mentioned intrinsic complexity of the reaction. Others originate from an insufficient control or documentation of the reaction conditions strongly limiting the comparability of independent studies. Older investigations are handicapped by the lower performance of the applied separation and detection techniques. Generally, the evaluation of analytical data is impeded by the lack of required reference chemicals.

Description of key information

Aromatic amines are resistant to hydrolysis (Harris, 1990; Solomons, 1980). Even if from the structure of the test item, hydrolysis is not to be expected, disappearance of 2,5-diaminotoluene was observed in a study conducted following OECD 111 guideline and GLP in sterile natural water at two different temperatures in the dark. The disappearance could be related to auto-oxidation processes. The target concentration in the test was 10 mg/L and was below half of the water solubility of the test item. At 25 °C, 2,5-diaminotoluene degraded rapidly representing mean values of 56.8 % after 4 hours and 4.7% of the applied amount after 12 hours of incubation in the dark. At 12 °C, the test item degraded more slowly showing a lag phase for at least 7 hours. After 12 hours, the test item represented 40.8% and 18.5% of the applied dose after 24 hours. The temperatures remained constant throughout the respective incubation periods and no significant variation of pH values was observed in the natural water. The samples also remained sterile throughout the study. 2,5-diaminotoluene degraded rapidly in sterile natural water at 25 °C and 12 °C. At 25 °C, DT50 value was calculated to be 3.63 hours and at 12 °C, estimated to be comprised between 10 and 12 hours. Rapid abiotic degradation in water is confirmed through aquatic toxicity testing in which it was observed a decrease of the measured test item concentrations. A literature review aimed at providing a synopsis of the current state of knowledge of (aut)oxidative reactions of PTD. A few studies were conducted to elucidate the oxidative transformation of PTD.

Most of the detected products are intermediates whose lifetimes are highly variable and regulated by factors widely unknown. The semitoluquinone diimine radical cation (STQDIRC) is firstly formed. The radical has a lifetime of a few hours at neutral pH, but it reacts much faster at low and high pH. Subsequently, the toluquinone diimine (TQDI) is formed which attacks a PTD molecule to yield a dimeric product, not further characterized yet. Trimeric products including a Bandrowski Base (BB)-like structure originate from the reaction of dimeric intermediates with STQDIRC or TQDI.

At environmentally relevant pH, it can be expected that the toluquinone diimine (TQDI) is formed which attacks a PTD molecule to yield a trimeric product.

Key value for chemical safety assessment

Half-life for hydrolysis:

12 h

at the temperature of:

12 °C

Additional information

An additionnal half-life of 3.36 hours at 25°C was considered for chemical safety assessment.