Isobutyldimethoxymethylsilane

Endpoint summary

Description of key information

In in vivo skin irritation studies conducted to an appropriate guide and in compliance with GLP read-across substance  isobutyl(trimethoxy)silane was found to be irritating to skin but not irritating to eyes. These data are read across to isobutyl(dimethoxy)methylsilane. 

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

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

In a skin irritation study conducted according to OECD 404 and to GLP (Hüls, 1993b), 30-60 minutes after patch removal, animals had clearly defined erythema and oedema (moderate in one animal, severe in two animals). After 24 and 48 hours skin redness remained unchanged, but oedema had reduced (clearly defined in one animal, moderate in two animals). After 72 hours each animal had clearly defined or moderately severe erythema and oedema. After 6 and 8 days two animals had barely perceptible irritation, and one animal had clearly defined erythema and oedema. After 10 and 14 days all animals had barely perceptible redness and swelling. By day 17 all irritation had reversed. It was concluded that isobutyl(trimethoxy)silane was irritating to the skin. There were no signs of systemic toxicity.

In an eye irritation study conducted according to test guideline OECD 405 and to GLP (Hüls, 1993c), isobutyl(trimethoxy)silane

was not irritating to the eyes of rabbits. There were some minor signs of irritation involving the conjunctivae, which had reversed by 72 hours in two of the animals and by day 6 in one animal. 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 acute toxicity 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 irritation at the relevant concentrations 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.

Justification for selection of skin irritation / corrosion endpoint:
Study was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP.

Justification for selection of eye irritation endpoint:
Study was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Based on the available in vivo data for read-across substance isobutyl(trimethoxy)silane, the registered substance isobutyl(dimethoxy)methylsilane requires classification as 'Category 2: Skin irritant' with the hazard statement 'H315: Causes skin irritation' according to Regulation (EC) No 1272/2008. There is no classification required for eye irritation, based on read-across in vivo data.