(3-chloropropyl)dimethoxymethylsilane

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:

0.1 h

Remarks on result:

other: 20-25°C

Key result

pH:

5

DT50:

0.2 h

Remarks on result:

other: 20-25°C

Key result

pH:

7

DT50:

1.3 h

Remarks on result:

other: 20-25°C

Key result

pH:

9

DT50:

0.03 h

Remarks on result:

other: 20-25°C

Conclusions:

Hydrolysis half-life values of 0.1 h at pH 4, 1.3 h at pH 7 and 0.03 h at pH 9 and at 20-25°C were obtained using an accepted calculation method. The result is considered to be reliable.

Description of key information

Hydrolysis: half-lives of 0.1 h at pH 4, 1.3 h at pH 7, 0.03 h at pH 9 and 20-25°C (QSAR)

Additional information

Hydrolysis half-lives of 0.1 h at pH 4, 0.2 h at pH 5, 1.3 h at pH 7 and 0.03 h at pH 9 and 20-25°C was obtained for the submission substance using validated QSAR estimation methods. The result is considered to be reliable and is selected as key study.

 

The predicted result is supported by a measured hydrolysis study for (3-chloropropyl)trimethoxysilane (CAS 2530-87-2). Hydrolysis half-lives of < 0.083 h (< 5 minutes) at pH 4 and < 0.1 h at pH 9 and 25°C. At pH 7, half-lives of 4.5 h at 20°C, 3.1 h a 25°C, 1 h at 40°C and 0.51 h at 50°C were measured for (3-chloropropyl)trimethoxysilane in accordance with OECD 111 test method and in compliance with GLP. At pH 4 and pH 9, the hydrolysis half-lives were estimated at 25°C because the test substance was hydrolytically unstable (Schaap 2014).

In a non-standard study for (3-chloropropyl)trimethoxysilane (CAS 2530-87-2), the disappearance of the methoxy groups was monitored by the use of ¹H-NMR; hydrolysis half-lives of 0.88 h at pH 7 and 0.37 h at pH 9 and 25°C were determined (Dow Corning Corporation 1995). In this supporting study, (3-chloropropyl)trimethoxysilane was an impurity in another substance and the study was designed primarily to determine the half-life of the major constituent.

 

(3-Chloropropyl)trimethoxysilane is a structural analogue of 3-chloropropyl(dimethoxy)methylsilane in which a Si-OCH₃ group is present rather than the Si-CH₃ group. On the basis of the proposed mechanisms of the hydrolysis reaction, the dialkoxysilane would be expected to hydrolyse more rapidly than the trialkoxysilane at acidic pH and more slowly at alkaline pH. At pH 7, both acid- and alkali-catalysed hydrolysis may occur and it is difficult to predict a precise value of the half-life for 3-chloropropyl(dimethoxy)methylsilane based on the data for (3-chloropropyl)trimethoxysilane. However, based on consideration of the available data for the category of alkoxysilanes, half-lives at pH 7 for the two substances are expected to be of the same order of magnitude.

 

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.

 

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 3-chloropropyl(dimethoxy)methylsilane at pH 2 is therefore 0.001 hours (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 for the substance at pH 2 and 25°C 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) * e^(0.08.(T-X))

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

Thus, for 3-chloropropyl(dimethoxy)methylsilane the hydrolysis half-life at 37.5°C and pH 7 (relevant for lungs and blood) is 0.48 hours. At 37.5°C 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.

 

The products of hydrolysis are 3-chloropropyl(methyl)silanediol and methanol.

 

The hydrolysis half-lives for other substances used for read-across are discussed below:

 

Hydrolysis of the read-across substance dichloro(3-chloropropyl)methylsilane (CAS 7787-93-1)

Data for the substance, dichloro(3-chloropropyl)methylsilane (CAS 7787-93-1) are read-across to the submission substance 3-chloropropyl(dimethoxy)methylsilane for short-term toxicity to fish, toxicity to microorganisms, mammalian cytogenicity and mammalian mutagenicity endpoints. The hydrolysis half-lives and the formation of the same silanol hydrolysis product of the two substances are relevant to this read-across as discussed in relevant section for each endpoint.

 

For dichloro(3-chloropropyl)methylsilane, hydrolysis half-lives at 25°C of << 1 minute at pH 4, pH 7 and pH 9 were reported based on read-across from other dichlorosilanes.

 

The hydrolysis products are 3-chloropropyl(methyl)silanediol and hydrogen chloride.

 

Hydrolysis of the read-across substance 3-chloropropyl(diethoxy)methylsilane (CAS 13501-76-3)

Data for the substance, 3-chloropropyl(diethoxy)methylsilane (CAS 13501-76-3) are read-across to the submission substance 3-chloropropyl(dimethoxy)methylsilane for biodegradation in water, short-term toxicity to fish, short-term toxicity to aquatic algae, acute toxicity: dermal, skin sensitisation and in vivo mammalian cytogenicity endpoints. In addition, for the following endpoints, skin irritation, eye irritation, bacteria mutagenicity and mammalian mutagenicity data, for 3-chloropropyl(diethoxy)methylsilane are used as supporting information. The hydrolysis half-lives and the formation of the same silanol hydrolysis product of the two substances are relevant to this read-across as discussed in relevant section for each endpoint.

 

For 3-chloropropyl(diethoxy)methylsilane, hydrolysis half-lives at 20-25°C of 0.4 h at pH 4, 9.5 h at pH 7 and 0.2 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 0.004 h (14 seconds) at pH 2 and 25°C, and 3.5 h at pH 7 and 37.5°C. 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 for the substance at pH 2 and 37.5°C is approximately 5 seconds.

 

The hydrolysis products are 3-chloropropyl(methyl)silanediol and ethanol.

 

Hydrolysis of the read-across substance (3-chloropropyl)trimethoxysilane (CAS 2530-87-2)

Data for the substance, (3-chloropropyl)trimethoxysilane (CAS 2530-87-2) are read-across to the submission substance 3-chloropropyl(dimethoxy)methylsilane for repeated dose toxicity: inhalation. In addition, for the following endpoints, acute toxicity oral, acute toxicity dermal, skin irritation, eye irritation, skin sensitisation, bacteria mutagenicity, mammalian mutagenicity and in vivo mammalian cytogenicity data for 3-chloropropyl(trimethoxy)silane are used as supporting information. The hydrolysis half-lives and silanol hydrolysis products of the two substances are relevant to this read-across as discussed in relevant section for each endpoint.

 

For (3-chloropropyl)trimethoxysilane, hydrolysis half-lives of <0.083 h (<5 minutes) at pH 4 and <0.1 h at pH 9 and 25°C. At pH 7, half-lives of 4.5 h at 20°C, 3.1 h at 25°C, 1 h at 40°C and 0.51 h at 50°C were measured for (3-chloropropyl)trimethoxysilane in accordance with OECD 111 test method and in compliance with GLP. At pH 4 and pH 9, the hydrolysis half-lives were estimated at 25°C because the test substance was hydrolytically unstable. In a non-standard study (Dow Corning Corporation 1995), the disappearance of the methoxy groups was monitored by the use of ¹H-NMR; hydrolysis half-lives of 0.88 h at pH 7 and 0.37 h at pH 9 and 25°C were determined for (3-chloropropyl)trimethoxysilane. In the supporting study, (3-chloropropyl)trimethoxysilane was an impurity in another substance and the study was designed primarily to determine the half-life of the major constituent.

 

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 approximately 3 seconds at pH 2 and 25°C. 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 for the substance at pH 2 and 25°C is approximately 5 seconds.

 

The hydrolysis half-life at 37.5°C and pH 7 (relevant for lungs and blood) is approximately 1.1 hours. At 37.5°C 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 37.5°C and pH 5.5 (relevant for dermal exposure), the hydrolysis half -life will be in between the half-lives of 0.03 - 1.1 hours at pH 4 and pH 7 at 37.5°C.

 

The hydrolysis products in this case are (3-chloropropyl)silanetriol and methanol.

 

Hydrolysis of the read-across substance chloromethyl(triethoxy)silane (CAS 15267-95-5)

Data for the substance, chloromethyl(triethoxy)silane (CAS 15267-95-5) are read-across to the submission substance 3-chloropropyl(dimethoxy)methylsilane for acute toxicity - oral endpoint. The hydrolysis half-lives and silanol hydrolysis products of the two substances are relevant to this read-across as discussed for the endpoint.

 

For chloromethyl(triethoxy)silane, hydrolysis half-lives at 20-25°C of 0.2 h at pH 4, 2.5 h at pH 7 and 0.1 h at pH 9 were determined using validated QSAR estimation methods. 

 

The hydrolysis products are chloromethylsilanetriol and ethanol.

 

Hydrolysis of the read-across substance (3-chloropropyl)triethoxysilane (CAS 5089-70-3)

Data for the substance, (3-chloropropyl)triethoxysilane (CAS 5089-70-3) are read-across as supporting information to the submission substance 3-chloropropyl(dimethoxy)methylsilane for the following endpoints, acute toxicity oral, acute toxicity dermal, skin irritation, eye irritation, skin sensitisation, bacteria mutagenicity, mammalian mutagenicity and in vitro cytogenicity data. The silanol hydrolysis products of the two substances is relevant to this read-across as discussed in relevant section for each endpoint.

 

For (3-chloropropyl)triethoxysilane, hydrolysis half-lives at 25°C of <24 minutes at pH 4, 35 h at pH 7 and 2 h at pH 9 were determined using relevant test method. 

 

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 0.02 h at pH 2 and 25°C, and 13 h at pH 7 and 37.5°C. At pH 2 and 37.5°C, the half-life is approximately 26.5 seconds.

 

The hydrolysis products are (3-chloropropyl)silanetriol and ethanol