Ethoxytrimethylsilane

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Principles of method if other than guideline:

The result was obtained using an appropriate QSAR method (see attached QMRF and QPRF for details).

GLP compliance:

no

Transformation products:

yes

No.:

#1

No.:

#2

Key result

pH:

7

DT50:

6.1 h

Type:

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

Remarks on result:

other: 20-25 °C

pH:

4

DT50:

0.3 h

Type:

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

Remarks on result:

other: 20-25 °C

pH:

5

DT50:

0.4 h

Type:

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

Remarks on result:

other: 20-25 °C

pH:

9

DT50:

0.1 h

Type:

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

Remarks on result:

other: 20-25 °C

Conclusions:

A hydrolysis half life of approximately 6.1 h at 20-25°C and pH 7 was obtained using an accepted calculation method. The result is considered to be reliable.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

GLP compliance:

no

Remarks:

ISO 9001: 2008 certificate (01/04/2012 - 31/03/2015)

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

Buffer Solutions:
pH 4.0: CertiPur, Citric acid + hydrochloric acid + sodium hydroxide,
company Merck

pH 7.0: Baker Analyzed, Potassium dihydrogen phosphate +
disodiumhydrogen phosphate, company J. T. Baker

pH 9.0: CertiPur, Boronic acid + potassium chloride + sodium
hydroxide, company Merck

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Bruker Avance DPX400, 5 mm ATM BBI probehead with z-gradients

TEST MEDIUM
- Kind and purity of water: Water-d2 / Na-TSP-d4 (5006.46 mg D2O + 21.53 mg Na- TSP-d4)

Duration:

1 h

pH:

4

Temp.:

25 °C

Duration:

1 h

pH:

7

Temp.:

25 °C

Duration:

1 h

pH:

9

Temp.:

25 °C

Transformation products:

not measured

pH:

4

Temp.:

25 °C

DT50:

< 2 min

Type:

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

pH:

7

Temp.:

25 °C

DT50:

2.2 min

Type:

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

pH:

9

Temp.:

25 °C

DT50:

6.1 min

Type:

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

Summary of Results:

Parameter	Result	Method
Degradation -Abiotic Degradation -Hydrolysis as a Function of pH	t1/2 (pH 4) = << 2 min	EC test guideline C.7 (in analogy to OECD testing method 111)
	t1/2 (pH 7) = 2.2 min
	t1/2 (pH 9) = 6.1 min

 

 

 At pH = 4 only signals of trimethylsilanol and ethanol could be observed after the first measurement. There was no signal of ethoxysilane detectable. Therefore it was concluded that hydrolysis was already completed when the first spectrum of this pH series was measured. Because hydrolysis was finished after the first 1H NMR measurement (about 2 minutes after mixing the test sample) no exact half-life time or reaction rate could be calculated.

At pH = 7 and pH = 9 decreasing signals of ethoxysilyl groups and increasing signals of EtOH could be observed. Half-life time and reaction rate could be calculated from a (ln c[EtOSi] vs. t) plot assuming first-order kinetics and using the Na-TSP-d4 as internal standard. This evaluation is based on the sum of the two ethoxysilyl signals.

Validity criteria fulfilled:

yes

Conclusions:

The hydrolysis half-life is < 2 min at pH4, 2.2 min at pH7 and 6.1 min at pH9 (25 °C). Thus, the substance is hydrolytically unstable under environmental conditions.

Description of key information

DT50 = 2.2 min at 25 °C and pH 7 (EU Method C.7)

Key value for chemical safety assessment

Half-life for hydrolysis:

2.2 min

at the temperature of:

25 °C

Additional information

One experimental study according to EU Method C.7 (GLP) is available for ethoxytrimethylsilane (CAS 1825-62-3). The measured half-lives at pH 4, pH 7 and pH 9 were < 2 min, 2.2 min and 6.1 min at 25 °C, respectively.

Furthermore, a QSAR that was developed by Peter Fisk Associates (2014) predicts half-lives of 0.3 h at pH 4, 0.4 h at pH 5, 6.1 h at pH 7 and 0.1 h at pH 9 (20-25 °C). As the hydrolysis reaction may be acid or base catalysed, the rate of reaction is expected to be slowest at pH 7 and increase with increasing or decreasing pH. 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. This is supported by studies for various organosilicon compounds in which calculation of kH3O+ and kOH- from the experimental results at pH 4 and 9, respectively, resulted in reasonable estimates of the half-life at pH 7. Therefore, at low pH:

k_obs≈k_H3O+[H₃O⁺]

At pH 4 [H₃O⁺]=10^-4mol dm^-3and at pH2 [H₃O⁺]=10^-2mol dm^-3; therefore, k_obsat pH 2 should be approximately 100 times greater than k_obsat 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 ethoxytrimethylsilane at pH 2 is therefore 0.003 h when considering the predicted value of 0.3 h at pH4. However, it is likely that factors such as diffusion become rate-determining when the half-life is less than 5-10 seconds. Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions and the half-lives at 37.5 °C (relevant for in vivo studies) are expected to be faster than those at 20-25 °C. 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 ethoxytrimethylsilane the hydrolysis half-life at 37.5 °C and pH 2 is very fast (relevant for conditions in the stomach following oral exposure) and it is not appropriate to apply any further correction for temperature to the limit value and the hydrolysis half-life is therefore less than 5 seconds.

The initial hydrolysis products are trimethylsilanol and ethanol. It can be concluded that the submission substance will hydrolyse rapidly under environmentally relevant conditions.