Titanium 2,2',2''-nitrilotrisethanolate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 21, 2020 - August 17, 2020

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:

not applicable

Remarks:

alternative method was needed as the test substance is highly water reactive

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

not applicable

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

not applicable

GLP compliance:

yes

Specific details on test material used for the study:

Date of Receipt December 26, 2019
Identification Tyzor TE
Appearance Light Yellow Liquid
Chemical (CAS) Name Titanium 2,2’,2”-nitrilotrisethanolate (with approx 20% propanol)
CAS Number 15879-01-3
Formulation type Chemical
Manufacturer’s Address Dorf Ketal Chemicals (I) Private Limited,
Dorf Ketal Tower - 2, Kanchpada,
Malad (W) Mumbai - 400 064.
India
Batch Number 3340015437
Molecular Weight Not Provided
Molecular Formula C6H15NO3.xTi
Manufacture date October, 2019
Expiry date September, 2021
Storage Conditions Room temperature (20°C to 30°C)
Safety Precautions Aprons, masks, caps, gloves and goggles will be used to ensure the health and safety of the personnel

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: The tier-1 will be performed at 50±0.5°C and pH 4,7 and 9.0 for 5 days duration with sampling interval of 0hr, 2hr, 5hr, day1, and day 5.
- Sampling method: The test was performed at 25 deg. C. An amount of test substance (above the water solubility) was added to the buffer solution. The amount of hydrolysis products formed was determined as function of time. The test was performed in duplicate. At each sampling time, samples were taken from each test and analyzed in duplicate. The hydrolysis of the test substance was determined by the quantitative analysis of the hydrolysis product propanol.


- Sample storage conditions before analysis: Stored Room temperature (20°C to 30°C)
- Other observation, if any (e.g.: precipitation, color change etc.): white precipitate was observed during the hydrolysis. this is most likely due to the formation of the insoluble titanium oxides.

Buffers:

- pH: 4, 7 & 9
- Type and final molarity of buffer: acetate buffer pH 4, 0.01 M, phosphate buffer pH 7, 0.01 M, borate buffer pH 9, 0.01 M was used.

Details on test conditions:

TEST SYSTEM
The Buffer solutions were pre-equilibrated at 35°C , 45°C , 55°C, prior to fortification of test item. Accurately dispensed 0.1mL of “spike stock” in to 10mL of two replicate test matrices representing pH 4.0, 7.0 and 9.0 buffer medium for 0th minute occasion taken in 15mL capacity amber colored vial. Likewise, the same procedure of dispensing 0.1mL of “spike stock” was carried out for 10th and 30th minute occasion at appropriate intervals followed by incubation for specific period 10 and 30 minutes..
After fortification of test item, immediately the 0th minute occasion test solution was shaken well, cooled to around ~20°C with freezing mixture (ice and sodium chloride), dispensed 1.0mL from the test solutions in to GC head space sampler vials, crimped air tight and injected in to gas chromatograph equilibrated with the set conditions. The Reference standard was used as bracketing standard during the assay. The same procedure was followed for the test solutions incubated at 55°C for assay.
Additional occasions of test item in pH 4.0, 7.0 and 9.0, representing 60th , 120th and 180th minute was carried out by preparing fresh solutions of test item “Spike stock” and “reference standard” next day following the above set of procedures detailed above in the same section.The assay has been carried out with reference standard as bracketing solution.The details on the reference standard and test solution concentration representing 60th, 120th and 180th minute were provided in Table-19.
pH check was carried out for buffer solution preparation and further during the experimentation.
Temperature was recorded during the experimentation phase.

Sterility check was determined for all the pH Buffer medium initially and finally Agar plates were used to determine sterility. During sampling, 0.2 ml of the three buffer solutions was aseptically added to agar plate. The agar plates were incubated in incubator at 35°C for 7 days. After incubation, the Agar plates were examined for microbial growth..

Number of replicates:

Two

Positive controls:

no

Negative controls:

yes

Remarks:

Blank buffer solutions

Preliminary study:

The test substance is known to be hydrolytically unstable. Therefore, the preliminary test was not performed.

Transformation products:

yes

No.:

#1

No.:

#2

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

The predicted hydrolysis product, Ethanol, was detected by GC-MS. Additionally, the formation of a white precipitation was observed during the hydrolysis study. This is most likely due to the formation of the insoluble titanium oxides.

The response of the hydrolysis product Ethanol was > 98% (area). In the chromatograms, small additional peaks were observed at 3.27 minutes, 7.02 minutes, 8.87 minutes, 8.90 minutes and 9.44 minutes (only at pH 4)., all ≤ 1% at the specific mass fragments monitored. The additional peaks might derive from impurities in the test substance and/or hydrolysis products.

To achieve sufficient sensitivity for the analysis of the identified hydrolysis product, selected ion monitoring was used as detection method. Therefore it was not possible to obtain accurate information on the mass fraction of the unknown peaks nor to record their entire mass spectrum, and hence it was not possible to identify these additional peaks.

pH:

4

Temp.:

35 °C

DT50:

<= 10 min

Type:

not specified

pH:

7

Temp.:

35 °C

DT50:

<= 10 min

Type:

not specified

pH:

9

Temp.:

25 °C

DT50:

<= 10 min

Type:

not specified

Validity criteria fulfilled:

yes

Conclusions:

Half-life time of titanium 2,2',2''-nitrilotrisethanolate at 35°C, 45°C, 55°C and at pH values normally found in the environment (pH 4-9) were determined in this study. Since the test substance is highly hydrolytically unstable and quantitative analysis of the test substance is not possible, half-life time was determined based on the analysis of the hydrolysis product triethanolamine. Based on the results, it was safely concluded that the hydrolysis half-life time irrespective of the temperature and pH is less than 10 minutes.

Executive summary:

The hydrolysis behavior of Tyzor TE was studied following the hydrolysis product Viz.,2-Propanol, since the identity of the test item, was kinetically could not be followed because of its faster hydrolysis behaviour.

The method validation has been carried out with the parametersViz.,Specificity, Linearity, Assay accuracy and precision. The dynamic linear range comprises the concentration range of 33.39µg/mL to 430.42µg/mL. The instrument response was found to be linear with the six different concentrations, of 2-Propanol substantiated by correlation coefficient and regression coefficient values 0.9993 and 0.9986 respectively.

The assay accuracy and precision parameter was studied by fortification technique at two levels (T1 = 50.08µg/mL and T2 = 400.64µg/mL). The mean recovery in µg/mL for T1 level (50.08µg/mL) was found to be 47.37 ±0.80, 46.62±0.40 and 50.33±0.56 with respect to pH buffer medium 4.0, 7.0 and 9.0. The mean recovery in µg/mL for T2 level (400.64µg/mL) was found to be 385.59 ±3.49, 403.21±7.62 and 397.16±7.28 with respect to pH buffer medium 4.0, 7.0 and 9.0. The limit of detection was 33.39µg/mL, established based on lowest concentration of dynamic linear range, while limit of quantification was established as 50.08µg/mL based on recovery study.

The Hydrolysis Tier-1, study was carried out at 144.75µg/mL, of Tyzor TE in three different buffers incubated at 50°C for a period of 5 days. The hydrolysis yield of test item as 2-Propanol calculated with respect to 0 hour concentration was found to 0.2g per g of test item, incubated at 50°C in pH 4.0 pH 7.0 and pH 9.0 buffer medium. The concentration of 2-Propanol was found to be 0.4g 2-Propanol / g of test item throughout different occasions of sampling up to 5 days of incubation at 50°C in pH 4.0 7.0 and 9.0 buffer medium.

The hydrolysis Tier–2, study was carried at around 100µg/mL of Tyzor TE in pH 4.0, 7.0 9.0 buffer medium at three different temperaturesViz.,35°C, 45°C and 55°C, to evaluate rate constant followed by half life period (T_1/2). The rate constant (K) could not be derived since the test item hydrolysis product was monitored throughout the experiment. However due to the steady formation of 2-Propanol of 0.4g per g of test item from 0^thminute to 180^thminute, the half life of the test item was concluded as <10 minutes.

The assay has been carried out using GC equipped with head space sampler where sample equilibration was maintained at respective incubation temperature. The partial pressure exerted by the 2-propanol dictates the instrument response, hence separate linear equation was derived for each temperature of incubation in the respective matrices of pH 4.0, 7.0 and 9.0 buffer medium. This linear equation was used to assay the 2-propanol concentration in the test solution.

A striking feature was observed, that, irrespective of the temperature of incubation / equilibration / occasions of sampling / buffer medium, the 2-Propanol formation as hydrolyzed product of test item was 0.4g per g of test item. This clearly augments that the formation of 2-Propanol was complete within a time lag of around 10minutes, when the test item was introduced to and pH buffered aqueous medium.

Description of key information

Hydrolytically unstable with the half-life time of < 5 minutes at 25 deg. C at pH 4, 7 and 9.

Key value for chemical safety assessment

Additional information

Study was performed by using OECD 111 in accordance with GLP. However, as the substance is highly hydrolytically unstable it was not possible to perform the test as outlined in the guidelines. In order to obtain as much information on hydrolysis as possible, an alternative test was designed. The hydrolytic stability was tested in buffered aqueous solutions at pH 4.0, 7.0, and 9.0 at 25°C for 40 minutes. The progress of the hydrolysis was followed by monitoring ethanol, the main degradation product. Additionally, the formation of a white precipitation was observed during the hydrolysis study. This is most likely due to the formation of the insoluble titanium oxides. No other degradation product could be identified.

The response of the hydrolysis product ethanol was > 98% (area). In the chromatograms, small additional peaks were observed at 3.27 minutes, 7.02 minutes, 8.87 minutes, 8.90 minutes and 9.44 minutes (only at pH 4), all ≤ 1% at the specific mass fragments monitored. The additional peaks might derive from impurities in the test substance and/or hydrolysis products. To achieve sufficient sensitivity for the analysis of the identified hydrolysis product, selected ion monitoring was used as detection method. Therefore it was not possible to obtain accurate information on the mass fraction of the unknown peaks or to record their entire mass spectrum, and hence it was not possible to identify these additional peaks.

Based on the results, it was concluded that the substance is hydrolytically unstable with hydrolysis half-life time of <5 minutes.

The results of this study are considered reliable to be used for C&L purposes to conclude this substance to be hydrolytically unstable releasing only ethanol and hydrated titanium dioxide when in contact with water. Based on the results this substance can be considered as rapidly degradable.