Triethoxy(2,4,4-trimethylpentyl)silane

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

key 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

Justification for type of information:

See attached QMRFs/QPRFs

Principles of method if other than guideline:

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

The model for hydrolysis at pH 7 has been developed for, and applies specifically to di- and tri-alkoxysilanes. It is a multiple linear regression based model with descriptors representing (i) steric effects of the alkoxy group, (ii) steric effects of the side-chain(s), and (iii) electronic effects of the side-chain(s).

The models for hydrolysis at pH 4, 5 and 9 have been developed for, and apply specifically to organosilicon compounds. They are linear regression based models where the descriptor is the half-life at pH 7.

Transformation products:

yes

No.:

#1

No.:

#2

Key result

pH:

4

DT50:

0.9 h

Remarks on result:

other: 20 - 25°C

Key result

pH:

7

DT50:

43 h

Remarks on result:

other: 20 - 25°C

Key result

pH:

9

DT50:

0.5 h

Remarks on result:

other: 20 - 25°C

Conclusions:

Hydrolysis half-lives of 0.9 h at pH 4, 43 h at pH 7 and 0.5 h at pH 9 and 20-25°C were obtained for the substance using a validated calculation method. The result is considered to be reliable.

Description of key information

Hydrolysis: half-life 0.9 h at pH 4, 43 h at pH 7 and 0.5 h at pH 9 and 20-25°C (QSAR)

Additional information

There are no reliable measured hydrolysis data for the submission substance. The hydrolysis half-lives of the substance have been predicted using validated QSAR estimation methods.

Hydrolysis half-lives of 0.9 h at pH 4, 43 h at pH 7 and 0.5 h at pH 9 and 20-25°C were predicted for the substance using validated QSAR estimation methods. The results are considered to be reliable and are selected as key study.

As the hydrolysis reaction may be acid or base catalysed, the rate of reaction is expected to be slowest at pH 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. This is supported by studies for various organosilicon compounds in which calculation of k_H3O+ and k_OH- 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^-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 triethoxy(2,4,4-trimethylpentyl)silane at pH 2 and 20-25°C is therefore 0.009 hours (approximately 32 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 triethoxy(2,4,4-trimethylpentyl)silane the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 16 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half-life is 0.003 h (approximately 11 seconds). At 37.5°C and pH 5.5 (relevant for dermal exposure), the hydrolysis half-life will be between half-lives at pH 4 and pH 7 (0.2 - 16 hours).

The hydrolysis products for the submission substance are (2,4,4-trimethylpentyl)silanetriol (1 mole) and ethanol (3 moles).

A supporting study for the read-across substance trimethoxy(methyl)silane (CAS 1185-55-3) is presented. In this study, the hydrolysis of trimethoxy(methyl)silane was investigated under conditions designed to mimic the rat stomach after dosing the substance in corn oil. The half-life for disappearance of trimethoxy(methyl)silane applied in corn oil to gastric simulation buffer was 33 minutes at pH 3 and 37°C and appears to be determined by phase transfer. The data suggest that, in the investigated system, hydrolysis occurs rapidly once trimethoxy(methyl)silane comes into contact with the aqueous layer and the rate determining step is the transfer of the trimethoxy(methyl)silane from the corn oil to the water. Combined recoveries of trimethoxy(methyl)silane and methanol (in mole equivalents of trimethoxy(methyl)silane; 3 moles methanol to 1 mole trimethoxy(methyl)silane assumed) were 87.5 to 104% and methanol content increased proportionally to the decrease in trimethoxy(methyl)silane. The study was conducted according to an appropriate test protocol and is considered reliable.

Trimethoxy(methyl)silane and triethoxy(2,4,4-timethylpentyl)silane are both trialkoxysilanes with an alkyl side-chain; the differences between the two substances are that the alkyl chain is C1 for trimethoxy(methyl)silane and C8 for triethoxy(2,4,4-trimethylpentl)silane and that the alkoxy group is methoxy for trimethoxy(methyl)silane and ethoxy for triethoxy(2,4,4-trimethylpentyl)silane. Therefore, it is not intended to read-across the half-life for trimethoxy(methyl)silane to triethoxy(2,4,4-trimethylpentyl)silane but to indicate the type of behaviour that might be observed for triethoxy(2,4,4-trimethylpentyl)silane. Thus, in animal studies using corn oil as vehicle, triethoxy(2,4,4-trimethylpentyl)silane could potentially hydrolyse more slowly than its predicted half-life at pH 2 and 37°C would suggest. This effect might be more pronounced for a substance with lower water solubility and higher log K_ow.  It is uncertain to what extent the in vitro test results are relevant for conditions present in the rat stomach (for example composition of the applied gastric simulant was highly simplified, type/speed of mixing is expected to strongly influence phase partitioning).

The hydrolysis rates of the read-across substances used in other areas are discussed below:

Hydrolysis of the supporting substance, trimethoxy(2,4,4-trimethylpentyl)silane (CAS 34396-03-7)

Data for the substance, trimethoxy(2,4,4-trimethylpentyl)silane (CAS 34396-03-7) are used as supporting information for the submission substance, triethoxy(2,4,4-trimethylpentyl)silane for the repeated dose toxicity inhalation endpoint.

 

For trimethoxy(2,4,4-trimethylpentyl)silane, hydrolysis half-lives at 20-25°C of 0.3 h at pH 4, 5.7 h at pH 7 and 0.1 h at pH 9 were determined using validated QSAR estimation methods.

 

The half-lives at pH 2 and 25°C, at pH 7 and 37.5°C and pH 2 and 37.5°C may be calculated in the same way as for the registration substance above. This gives half-life of 0.003 h (approximately 11 seconds) at pH 2 and 25°C. at pH 2 and 37.5°C, the half-life (relevant for conditions in the stomach), the half-life is 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 submission substance at pH 2 and 37.5°C is approximately 5 seconds.

 

At pH 7 and 37.5°C (relevant for lungs and blood), the half-life is approximately 2 hours.

 

The products of hydrolysis are (2,4,4-trimethylpentyl)silanetriol (1 mole) and methanol (3 moles).

 

Hydrolysis of the read-across substance, trichloro(2,4,4-trimethylpentyl)silane (CAS 18379-25-4)

Data for the substance, trichloro(2,4,4-trimethylpentyl)silane(CAS 18379-25-4) are read-across to the submission substance triethoxy(2,4,4-trimethylpentyl)silane for the long-term toxicity to aquatic invertebrates endpoint. The formation of the same silanol hydrolysis product by both substances is relevant to this read-across, as discussed in the appropriate section for the endpoint.

 

For trichloro(2,4,4-trimethylpentyl)silane, hydrolysis half-lives has been read-across from trichloro(methyl)silane (CAS 75-79-6 ). Hydrolysis half-lives of <1 minute at pH 4, <1 minute at pH 7 and <1 minute at pH 9 and 1.5°C were determined in accordance with OECD 111 (Dow Corning Corporation 2001). 

The hydrolysis products are (2,4,4-trimethylpentyl)silanetriol (1 mole) and hydrochloric acid (3 moles).

 

Hydrolysis of the read-across substance, triethoxy(octyl)silane (CAS 2943-75-1)

Data for the substance, triethoxy(octyl)silane (CAS 2943-75-1) are read-across to the submission substance triethoxy(2,4,4-trimethylpentyl)silane for the mammalian mutagenicity and bioaccumulation endpoints. For the short-term toxicity to fish, short-term toxicity to aquatic invertebrates and toxicity to aqautic algae endpoints, data for triethoxy(octyl)silane have been used as supporting studies. The hydrolysis half-lives and the silanol hydrolysis products of the two substances are relevant to this read-across, as discussed in the appropriate sections for each endpoint.

 

For triethoxy(octyl)silane, hydrolysis half-lives at 20-25°C of 0.7 h at pH 4, 30 h at pH 7 and 0.4 h at pH 9 were determined using validated QSAR estimation methods.

 

The half-lives at pH 2 and 25°C, at pH 7 and 37.5°C and at pH 2 and 37.5°C may be calculated in the same way as for the registration substance above. This gives a half-life of 0.007 h (25 seconds) at pH 2 and 25°C and 11 h at pH 7 and 37.5°C. At pH 2 and 37.5°C, the half-life is approximately 5 seconds.

 

The hydrolysis products are octylsilanetriol (1 mole) and ethanol (3 moles).