2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane

Endpoint summary

Description of key information

The key information for sensitisation is read across from [2-(3,4-epoxycyclohexyl)ethyl]triethoxysilane (CAS 10217-34-2). The key study for sensitisation in guinea pig finds the test substance sensitising to skin (WIL 2001). 14/20 animals showed positive reactions in a test conducted according to OECD 406 and in compliance with GLP.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The key study was carried out in accordance with OECD 406 and in compliance with GLP (WIL, 2001). There were no deaths or clinical findings or remarkable body weight changes observed during the study. The sensitization incidence index for the test group was 70% (14/20) following challenge dosing. A supporting study (Notox, 1997) confirms the sensitising result of the key study. No data are available for the registered substance itself.

READ-ACROSS JUSTIFICATION

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 sensitisation, the relevant properties are structural similarity and the physical-chemical parameters in the same range. In the following paragraphs the proposed read-across from [2-(3,4-epoxycyclohexyl)ethyl]triethoxysilane (CAS 10217-34-2) to 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane is evaluated point by point.

Read-across hypothesis

The hypothesis is that the target (registration) substance and the source (read-across) substance have similar toxicological properties because they are structurally similar and , hydrolyse to the common silanol hydrolysis product[2-(3,4-epoxycyclohexyl)ethyl]silanetriol and methanol and ethanol, respectively.Based on publically available information, methanol and ethanol are not known to contribute to irritation (OECD, 2004a and 2004b).

Read-across justification

The predicted hydrolysis half-lives of the registered substance,2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane (CAS 3388-04-3), are 0.2 hours at pH 4, 0.3 hours at pH 5, 4 hours at pH 7 and 0.1 hours at pH 9 at 20-25°C. At pH 4 (close to the pH of skin, 5), the hydrolysis rate is less than 1 hour. The products of hydrolysis are[2-(3,4-epoxycyclohexyl)ethyl]silanetrioland methanol.

The read-across substance[2-(3,4-epoxycyclohexyl)ethyl]triethoxysilane (CAS 010217-34-2)has measured hydrolysis half-lives of 0.7 hours at pH 4, 31 hours at pH 7 and 0.4 hours at pH 9 and 25°C.At pH 4 (close to the pH of skin, 5), the hydrolysis rate is less than 1 hour. The products of hydrolysis are[2-(3,4-epoxycyclohexyl)ethyl]silanetrioland ethanol.

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.

Analogue approach justification

(a)   Structural similarity

The registration and read-across substances are structurally similar and are members of an analogue group of epoxyalkyl alkoxysilanes. Both substances are trialkoxysilanes that have a 2-(3,4-epoxycyclohexyl)ethyl side group attached to the silicon atom. In the structure of the registration substance, the three alkoxy groups are methoxy, whereas in the structure of the read-across substance, the three alkoxy groups are ethoxy. The silanol hydrolysis product in both cases is 2-(3,4-epoxycyclohexyl)ethylsilanetriol. The non-silicon-containing hydrolysis products are ethanol and methanol respectively.

 

(b) Similar physicochemical characteristics

Structural similarity and physicochemical properties are relevant to the sensitisation potential of a substance. The parent substances hydrolyse at different rates but both hydrolyse to the same silanol hydrolysis product. The key physicochemical parameters are summarised below.

Table 5.2.3: Key physicochemical parameters

	Target (registration substance)	Source (read-across substance)
CAS number	3388-04-3	10217-34-2
EC number	222-217-1	425-050-4
Chemical Name	2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane	[2-(3,4-epoxycyclohexyl)ethyl]triethoxysilane
Molecular weight  (gmol^-1)	246.38	288.46
log Kow(parent)	2.5 at 20°C	3.9 (predicted)
log Kow(silicon-containing hydrolysis product)	-0.6 at 20°C	-0.6 at 20°C
Water solubility (parent)	1400 mg/l at 20-25°C	830/860 mg/l (two isomers)
Water solubility (silicon-containing hydrolysis product)	1.0E+06 mg/l at 20-25°C	1.0E+06 mg/l at 20-25°C
Hydrolysis at pH 4, and 20-25°C	0.2 hours	0.7 hours
Hydrolysis at pH 7, and 37.5°C	1.5 h	11 hours
Vapour pressure (parent)	0.46 Pa at 25°C	0.3 Pa at 25°C
Vapour pressure (silicon-containing hydrolysis product)	7.5E-06 Pa at 25°C	7.5E-06 Pa at 25°C

(c) Acute toxicity

The acute toxicity of the registered substance and the read-across substance is similar, supporting the notion that the toxicological profiles of the two substances are similar. The acute oral LD₅₀ values are reported to be 13161 mg/kg (Mellon, 1962) and >5000 mg/kg (WIL, 1996) for the registered substance and read-across substance, respectively.

(d) Discussion of the toxicity of the hydrolysis products

The predicted half-lives differ for the registration substance2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane (CAS 3388-04-3) (1.5 h)and the read-across substance[2-(3,4-epoxycyclohexyl)ethyl]triethoxysilane (CAS 010217-34-2)(ca. 11 hours) at neutral pH and body temperature (pH 7, 37.5°C). However at pH 4, which is close to the known pH of the skin (pH 5), the hydrolysis half-livesare comparable (< 1 hour), and both substances will be hydrolysed to their common hydrolysis product[2-(3,4-epoxycyclohexyl)ethyl]silanetriol.herefore the sensitisation studies would reflect the properties of the common silanol hydrolysis product.

Methanol and ethanol are not considered to contribute to potential sensitisation in rats.

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Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data for the related substance [2-(3,4-epoxycyclohexyl)ethyl]triethoxysilane, 2(3,4 -epoxycyclohexyl)ethyltrimethoxy silane is classified as a Category 1B Skin Sensitiser (H317 - May cause an allergic skin reaction) in accordance with Regulation (EC) No 1272/2008.