Tetraethyl orthosilicate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

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)

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

The rates of hydrolysis were followed by an extraction method. Individual kinetic experiments were executed by staggered starts of multiple reaction aliquots, one for each unique reaction time to be sampled. At a predetermined time, the hydrolysis reaction was effectively stopped by addition of the extraction solution. This approach was used to minimize the time required to complete an experiment and achieve convenient sampling intervals to collect hydrolysis data spanning 2-3 half-lifes.
- Sampling intervals for the parent/transformation products: Time intervals between samples were: 0.3 - 5 min at pH4 and 25°C; 0.3 - 15 min at pH9 and 25°C; 0.3-1 min at pH 7 and 25°C; 2-15 min at pH 4 and 10°C; 2-25 minutes at pH 9 and 10°C; 0.3 - 4 min at pH 7 and 35°C; 0.3-30 min at pH 9 and 35°C. On average data was collected 12 discrete times for each kinetic endpoint.
- Sampling method: At the appropriate time, each sample was removed from the water bath and the extraction solution added using a volumetric syringe. The time was recorded. The sample was vortexed for ca. 1 min to separate the aqueous and organic phases. An aliquot of the organic phase was transferred to a GC vial for analysis.
- Sampling intervals/times for pH measurements: pH was not monitored during or after the kinetic experiments as the reaction products were not expected to affect the pH of the solutions.
- Sample storage conditions before analysis: Not applicable

Buffers:

- pH: 4.00
- Type and final molarity of buffer: Formic acid; ionic strength 0.25M
- Composition of buffer: Formic acid; sodium hydroxide; sodium chloride

- pH: 7.00
- Type and final molarity of buffer: Sodium phosphate monobasic; ionic strength 0.25M
- Composition of buffer: Sodium phosphate monobasic; sodium hydroxide; sodium chloride

- pH: 9.00
- Type and final molarity of buffer: Boric acid; ionic strength 0.25M
- Composition of buffer: Boric acid; sodium hydroxide; sodium chloride

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Vessels used for individual hydrolysis kinetic experiments were 15-mL sterile polypropylene centrifuge tubes.
- If no traps were used, is the test system closed/open: Open
- Is there any indication of the test material adsorbing to the walls of the test apparatus? No

TEST MEDIUM
- Preparation of test medium: Nominally 0.10 M stock solutions of the test substance in acetonitrile were prepared in a nitrogen purged glove bag and stored in 20 mL HDPE vials having septum lined open-top caps. The solution of the test substance in acetonitrile was added to the appropriate buffer solution at the start of the experiment.
- Identity and concentration of co-solvent: Acetonitrile; 40 - 45µL of the solution of TEOS in ACN was added to 5 mL of the buffer.

Duration:

25 min

pH:

4

Temp.:

25

Initial conc. measured:

289.85 other: µg/g

Duration:

10 min

pH:

7

Temp.:

25

Initial conc. measured:

288.61 other: µg/g

Duration:

60 min

pH:

9

Temp.:

25

Initial conc. measured:

308.07 other: µg/g

Duration:

60 min

pH:

4

Temp.:

10

Initial conc. measured:

310.84 other: µg/g

Duration:

150 min

pH:

9

Temp.:

10

Initial conc. measured:

322.4 other: µg/g

Duration:

14 min

pH:

4

Temp.:

35

Initial conc. measured:

282.4 other: µg/g

Duration:

30 min

pH:

9

Temp.:

35

Initial conc. measured:

292.3 other: µg/g

Number of replicates:

1; except pH 4 25°C where 2 replicates were used.

Positive controls:

no

Negative controls:

yes

Remarks:

The integrity of the test solution in acetonitrile was checked after each kinetic experiment to check that TEOS had not hydrolysed.

Statistical methods:

The hydrolysis of TEOS in dilute aqueous solution was observed to follow first-order kinetics. The natural logarithm of the concentration was plotted as a function of time. The observed rate constant, k, for the hydrolysis reaction is equal to the slope of a first-order regression line fitted to the data. The half-life of the hydrolysis reaction was calculated from the estimated rate constant according to the following equation: t1/2 = ln 2/k, where k is the reaction rate constant and t1/2 is teh half-life of the test substance.

The observed rate constants as a function of temperature at the two extremes of pH were used to construct an Arrhenius diagram for each catalytic condition by plotting ln k against 1/T for constant pH (4 or 9), where T is the temperature in K. According to the logarithmic form of the Arrhenius equation, ln k = -(Ea/RT) + ln A, the activation energy, Ea, is readily obtained from the slope of the aforementioned plot. Using the values of the Arrhenius parameters, the rate constant can be calculated at any temperature. Descriptive statistics such as average, standard deviation, relative standard deviation (RSD) and linear regression analysis were also performed.

Preliminary study:

The preliminary study was not carried out as TEOS was expected to be hydrolytically unstable.

Transformation products:

not measured

Key result

pH:

4

Temp.:

10 °C

Hydrolysis rate constant:

3.55 h-1

DT50:

0.2 h

Type:

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

Key result

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

6.16 h-1

DT50:

0.11 h

Type:

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

Remarks on result:

other: Rep I

Key result

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

6.69 h-1

DT50:

0.1 h

Type:

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

Remarks on result:

other: Rep II

Key result

pH:

4

Temp.:

35 °C

Hydrolysis rate constant:

9.55 h-1

DT50:

0.07 h

Type:

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

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.16 h-1

DT50:

4.4 h

Type:

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

Key result

pH:

9

Temp.:

10 °C

Hydrolysis rate constant:

0.91 h-1

DT50:

0.76 h

Type:

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

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

3.17 h-1

DT50:

0.22 h

Type:

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

Key result

pH:

9

Temp.:

35 °C

Hydrolysis rate constant:

5.88 h-1

DT50:

0.12 h

Type:

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

Other kinetic parameters:

k(H3O+): A = 0.0000614 h-1; Ea = 28.4 kJ/mol; R2 = 0.9948

k(OH-): A = 0.000000000105 h-1; Ea = 54.5 kJ/mol; R2 = 0.9971

Average solvent extraction efficiencies ranged from 87.9% for pH 4 at 35°C to 98.3% for pH 7 at 25°C.

The hydrolysis of TEOS was observed to follow pseudo first-order kinetics, was pH dependent and increased as a function of temperature.  The half-life of TEOS at 25°C was observed to be 0.11, 4.4, and 0.22 hrs at pH 4, 7, and 9, respectively.  At 10°C, the half-life of TEOS was observed to be 0.20 and 0.76 hrs at pH 4 and 9, respectively.  At 35°C, the half-life of TEOS was observed to be 0.073 and 0.12 hrs at pH 4 and 9, respectively.  The catalytic constants
for the hydronium and hydroxide ion catalyzed hydrolysis reactions were determined from the observed rate constants at pH 4 and 9 at 25°C.  The values of the catalytic constants, k(H3O+) = 61,560 M(-1)hr(-1) and k(OH) = 317,400
M(-1)hr(-1) demonstrate that base catalysis is faster than acid catalysis.  Based on these values, the predicted rate constant at pH 7 and 25 °C of 0.0379 hr(-1), was within a factor of 5 of the observed rate constant, 0.1575 hr(-1). 
This indicated that there was minimal buffer catalysis, though no further hydrolysis experiments were conducted to confirm this finding.  Using the catalytic constants, the minimum hydrolysis rate is predicted to occur at pH of 6.64.
Additional experiments were conducted at 10 and 35 °C. These experiments were conducted at both pH 4 and 9, using 0.05 M buffer concentration employed for the 25°C experiments.  The information of each pH value was used to
construct a linear Arrhenius plot from which the Arrhenius constant (A) and activation energy (Ea) were determined for the specific acid and base catalyzed reactions.  The results show that the activation energy is 2 fold greater for the
hydroxide ion catalyzed hydrolysis reaction than the hydronium ion catalyzed hydrolysis reaction, although a much greater preexponential factor, A, is associated with the former.

Validity criteria fulfilled:

yes

Conclusions:

A hydrolysis half life of 4.4 h was determined at pH 7 and at 25°C in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

Description of key information

Hydrolysis: t1/2 = 0.11 h at pH 4, 4.4 h at pH 7 and 0.22 h at pH 9 and 25°C (OECD 111)

Key value for chemical safety assessment

Half-life for hydrolysis:

4.4 h

at the temperature of:

25 °C

Additional information

The hydrolysis of tetraethyl orthosilicate (CAS 78-10-4; EC No. 201-083-8) was determined at relevant environmental conditions of varying pH (pH 4, pH 7 and pH 9) and temperature (10°C, 25°C and 35°C) according to OECD Test Guideline 111 and in compliance with GLP (Dow Corning Corporation 2003). The test substance was followed by measuring the disappearance as a function of time by an extraction method using gas chromatography with flame ionisation detection (GC-FID). The hydrolysis reaction was followed kinetically by measuring the concentration of the test substance in the extract at various times through 2 -3 half-lives. The measured hydrolysis half-lives are considered reliable and are selected as key study. Hydrolysis half-lives obtained for the submission substance are as follows:

pH 4: 0.2 hours at 10°C, 0.11 hours at 25°C and 0.07 hours at 35°C

pH 7: 4.4 h at 25°C

pH 9: 0.76 hours at 10°C, 0.22 hours at 25°C and 0.12 hours at 35°C

 

A hydrolysis half-life of 48.1 minutes at pH 3 and 25°C was reported in a secondary literature (Yang 1989). The original reference was not available for review and no further information is available. The reliability of this result is not assignable.

As the hydrolysis reaction may be acid or base catalysed, the rate of reaction is expected to be slowest at pH near 7 and increase as the pH is raised or lowered. For an acid-base catalysed reaction in buffered solution, the measured rate constant is a linear combination of terms describing contributions from the uncatalyzed reaction as well as catalysis by hydronium, hydroxide, and general acids or bases.

 

k_obs= k₀+ k_H3O+[H₃O⁺] + k_OH-[OH^-] + k_a[acid] + k_b[base]

 

At extremes of pH and under standard hydrolysis test conditions, it is reasonable to suggest that the rate of hydrolysis is dominated by either the hydronium or hydroxide catalysed mechanism.

 

Therefore, at low pH:

k_obs≈k_H3O+[H₃O⁺]

 

At pH 4 [H₃O⁺] = 10^-4 mol dm^-3 and at pH 2 [H₃O⁺] = 10^-2 mol dm^-3; therefore, k_obs at pH 2 should be approximately 100 times greater than k_obs at pH 4.

 

The half-life of a substance at pH 2 is calculated based on:

t_1/2(pH 2) = t_1/2(pH 4) /100

The calculated half-life of tetraethyl orthosilicate at pH 2 is therefore 0.001 h (3.6 seconds). However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10 seconds. As a worst-case it can therefore be considered that the half-life of the substance at pH 2 and room temperature is approximately 5 seconds.

Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions. Under ideal conditions, hydrolysis rate can be recalculated according to the equation:

DT₅₀(XºC) = DT₅₀(T) x e^(0.08.(T-X))

Where T = temperature for which data are available and X = target temperature.

Thus, for tetraethyl orthosilicate the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is 1.6 h. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), it is not appropriate to apply any further correction for temperature to the limit value and the hydrolysis half -life is therefore approximately 5 seconds.

At concentrations above about 100-150 mg/L (measured as SiO₂ equivalents), condensation products of monosilicic acid can also form. At concentrations >100-150 mg/L of SiO₂, monomeric monosilicic acid condenses into colloidal particles of polysilicic acid (silica sol) or a highly cross-linked network (silica gel).

The condensation rate is dependent on temperature, concentration, and pH of the system. A dynamic equilibrium is established between monomer, oligomers and insoluble amorphous polysilicic acid. The composition of the solution is dependent upon conditions such as pH, temperature and the presence of ions.

Monosilicic acid and its condensation products are naturally occurring substances that are ubiquitous in the environment. Reaction mechanisms of this substance, and related substances, are discussed in the document attached in Section 13 (PFA, 2015ao, Peter Fisk Associates, The aquatic chemistry of inorganic silicic acid generators, PFA.404.001.001).

Hydrolysis of the read-across substance synthetic amorphous silica (CAS 112926-00-8)

Data for the substance synthetic amorphous silica (CAS 112926-00-8) are read-across to the submission substance tetraethyl orthosilicate for the repeated dose toxicity oral, toxicity to reproduction and developmental toxicity endpoints. The formation of the same silanol hydrolysis product is relevant to this read-across, as discussed in the appropriate section for each endpoint.

Tetraethyl orthosilicate undergoes rapid hydrolysis in contact with water to form monosilicic acid and ethanol. Monosilicic acid condenses to insoluble polysilicic acid [equivalent to synthetic amorphous silica (SAS)] at concentrations higher than 100-150 mg/L ‘SiO₂ equivalent’ in water. At very high concentration, polysilicic acid can condense to silicon dioxide (SiO₂).

Reference:

OECD SIDS (2004a). Soluble Silicates. CAS No. 1344-09-8, 6834-92-0, 10213-79-3, 13517-24-3 and 1312-76-1. SIDS Initial Assessment Report for SIAM 18 Paris, France 20-23 April, 2004.

http://www.inchem.org/documents/sids/sids/SolubleSilicates.pdf