Isobutyldimethoxymethylsilane

Endpoint summary

Description of key information

In key acute oral and inhalation studies conducted according to appropriate guidelines and in compliance with GLP on read-across substance isobutyl(trimethoxy)silane, the LD50 (oral) was found to be > 2000 mg/kg bw and the LC50 (inhalation, 4 hour) was found to be > 11000 mg/m3. These data are read across to isobutyl(dimethoxy)methylsilane. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

11 000 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

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

In the key acute oral toxicity study (Hüls, 1993a) conducted to OECD test guideline 401 (now deleted) and GLP, the oral LD₅₀ was greater than 2000 mg/kg bw in male and female rats. Within the first three hours after administration in males and the first six hours in females, there were signs of toxicity. Within three (males) or six (females) hours there were signs of ruffled fur, crouching posture, mild sedation, ataxia, and swaying motion. By five to six hours there were no signs clinical in 8/10 animals. Six hours after administration, one female was noted with ruffled fur, medium to heavy sedation, ataxia, prone position, hypothermia, laboured breathing, closed eyes and chromodacryorrhea and was also inappetant. After 24 hours there were no remarkable signs in any of the animals.

In the key acute inhalation study (DCC, 1984) that was comparable to OECD 403 and to GLP, the 4 -hour LC₅₀ was greater than 1525 ppm (ca. 11000 mg/m³) (the only concentration tested) in Sprague-Dawley rats. The animals were lethargic and unresponsive during the exposure period. However, on removal from the chamber, the animals quickly recovered and did not show any stress or signs of toxicity during the 14-day observation period.

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 (relevant for lungs and blood) the calculated hydrolysis half-life is approximately 0.6 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half -life is approximately 5 seconds. At 37.5ºC and pH 4 the calculated hydrolysis half-life is 0.07 hours. 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 (relevant for lungs and blood) the calculated hydrolysis half-life is approximately 1.5 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half -life is approximately 5 seconds. At 37.5ºC and pH 4 the calculated hydrolysis half-life is 0.07 hours. 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 (lethality) 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 Kow of 3.4. A log Kow of 1.0 has been calculated for the silanol hydrolysis product. Methanol has a measured log Kow of -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 Kow of 2.1. A log Kow of -1.0 has been calculated for the silanol hydrolysis product. Methanol has a measured log Kow of -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 100 mg/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 0.33 Pa at 25°C. Methanol has a measured vapour pressure of 12790 Pa.	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 12790 Pa.

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 acute toxicity – oral endpoint
The study was carried out in accordance with an appropriate OECD test guideline and in compliance with GLP.

Justification for selection of acute toxicity – inhalation endpoint
The study was carried out in accordance with an appropriate OECD test guideline and in compliance with GLP.

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 acute toxicity according to Regulation (EC) No 1272/2008.