Isobutyldimethoxymethylsilane

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There are no sensitisation data for the registered substance so data has been read-across from the structurally similar read-across substance isobutyl(trimethoxy)silane.

In a traditional Buehler skin sensitisation study to GLP (Hüls, 1993d) twenty Dunkin-Hartley guinea-pigs were exposed to three separate induction phases on their shaved left flanks. On Day 0 undiluted test substance was applied under an occlusive patch for six hours. On Days and 14 this process was repeated with a 50% solution in corn oil and after each application the skin was monitored for reactions. Ten negative controls had patches with corn oil only applied to their left flanks. On Day 28 both negative controls and test animals had an occlusive patch of 50% test substance (in corn oil) applied to their right flanks for 6 hours. The skin was then assessed at 6, 24, 48 and 72 hours after administration. There were no skin reactions in any of the test or negative control animals during the challenge phase and it was concluded that isobutyl(trimethoxy)silane is not a skin sensitiser.

To reduce animal testing REACH recommends to make use of a read-across approach where appropriate based on the high accordance in properties relevant for the specific endpoint. In the case of acutetoxicity the relevant properties are structural similarity, physical-chemical parameters in the same range and they hydrolyse to similar silicon-containing hydrolysis products. In the following paragraphs the proposed read-across from isobutyl(trimethoxy)silane to isobutyl(dimethoxy)methylsilane is evaluated point by point.

Read-across hypothesis

The hypothesis is that the source and target substances have similar toxicological properties because they are structurally similar and have similar physicochemical properties. This is discussed further below and additional information is given in supporting reports (PFA, 2013aa and PFA, 2015t).

Isobutyl(dimethoxy)methylsilane hydrolyses rapidly, with calculated hydrolysis half-lives of 0.2 hours at pH 4, 1.7 hours at pH 7 and 0.04 hours at pH 9 and 25°C. At 37.5ºC and pH 7 the calculated hydrolysis half-life is approximately 0.6 hours. At 37.5ºC and pH 2 the hydrolysis half -life is approximately 5 seconds. At 37.5ºC and pH 4 the calculated hydrolysis half-life is 0.07 hours. At 37.5ºC and pH 5.5 (relevant for dermal exposure), the hydrolysis half -life will be in between the half-lives at pH 4 and pH 7 at 37.5ºC. The products of hydrolysis are isobutyl(methyl)silanediol and methanol.

Isobutyl(trimethoxy)silane (CAS 18395-30-7) hydrolyses rapidly, with calculated hydrolysis half-lives of 0.2 hours at pH 4, 4.1 hours at pH 7 and 0.1 hours at pH 9 and 25°C. At 37.5ºC and pH 7 the calculated hydrolysis half-life is approximately 1.5 hours. At 37.5ºC and pH 2 the hydrolysis half -life is approximately 5 seconds. At 37.5ºC and pH 4 the calculated hydrolysis half-life is 0.07 hours. At 37.5ºC and pH 5.5 (relevant for dermal exposure), the hydrolysis half -life will be in between the half-lives at pH 4 and pH 7 at 37.5ºC. The products of hydrolysis are (2-methylpropyl)silanetriol and methanol.

The non-silanol hydrolysis product, methanol, does not contribute to any adverse effects for acute toxicity at the relevant dose levels based on publicly available information (OECD 2004a).

Read-across justification

(a) Structural similarity

The registration and read-across substance are structurally similar and are members of a structural class of alkoxysilane substances. The registered substance, isobutyl(dimethoxy)methylsilane, has two methoxy groups bound to silicon, the read-across substance, isobutyl(trimethoxy)silane, has three methoxy groups. The registration and read-across substance both have an identical hydrocarbon side-chain (isobutyl) bound to the silicon, and the registration substance also has a methyl group attached. Both substances hydrolyse rapidly to produce the similar silicon-containing hydrolysis products, isobutyl(methyl)silanediol or (2-methylpropyl)silanetriol, and methanol.

(b) Similar physicochemical characteristics

The key physicochemical parameters are summarised below.

Table: Key physicochemical parameters

-	Target (registration substance)	Source (read-across substance
CAS number	18293-82-8	18395-30-7
EC number	242-171-6	242-272-5
Chemical Name	Isobutyl(dimethoxy)methylsilane	Isobutyl(trimethoxy)silane
Molecular weight  (gmol^-1)	162.31	178.31
log Kow	Waived because the substance hydrolyses rapidly in water to form isobutyl(methyl)silanediol and methanol.. Isobutyl(dimethoxy)methylsilane has a calculated log Kowof 3.4. A log Kowof 1.0 has been calculated for the silanol hydrolysis product. Methanol has a measured log Kowof -0.82 to -0.64	Waived because the substance hydrolyses rapidly in water to form (2 -methylpropyl)silanetriol and methanol. Isobutyl(trimethoxy)silane has a calculated log Kowof 2.1. A log Kowof -1.0 has been calculated for the silanol hydrolysis product. Methanol has a measured log Kowof -0.82 to -0.64
Water solubility at 20°C	Waived because the substance hydrolyses rapidly in water to form isobutyl(methyl)silanediol and methanol. Isobutyl(methyl)silanediol has a calculated water solubility of 8.1E+04 mg/l. However, the saturation concentration is limited by condensation reactions above approximately 100mg/l. Methanol is miscible in water.	Waived because the substance hydrolyses rapidly in water to form (2 -methylpropyl)silanetriol and methanol. (2 -methylpropyl)silanetriol is predicted to be very soluble, however solubility is expected to be limited by condensation reactions. Methanol is miscible in water.
Vapour pressure at 20°C	Isobutyl(dimethoxy)methylsilane has a calculated vapour pressure of 310 Pa at 25°C. Isobutyl(methyl)silanediol has a calculated vapour pressure of 0.33Pa at 25°C. Methanol has a measured vapour pressure of 12790Pa.	Isobutyl(trimethoxy)silane has a calculated vapour pressure of 190 Pa at 25°C. ((2-methylpropyl)silanetriol) has a calculated vapour pressure of 0.00294 Pa at 25°C. Methanol has a measured vapour pressure of 12790Pa.

PFA (2013a). Peter Fisk Associates, Application of Category - Analogue - QSAR for Reconsile, PFA.300.006.014

PFA, (2015t). Peter Fisk Associates, Analogue report – mammalian toxicity of alkyl alkoxysilanes, PFA.404.002.002.

Migrated from Short description of key information:
In a sensitisation study conducted according to an appropriate guideline and in compliance with GLP the read-across substance isobutyl(trimethoxy)silane was found to be non-sensitising. These data are read across to isobutyl(dimethoxy)methylsilane.

Justification for selection of skin sensitisation endpoint:
Study was conducted according to an appropriate OECD test guideline and in compliance with GLP.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available read-across data from isobutyl(trimethoxy)silane, the registered substance isobutyl(dimethoxy)methylsilane does not require classification for sensitisation according to Regulation (EC) No. 1272/2008.