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Description of key information

The key information for irritation/corrosion is read across from [2-(3,4-epoxycyclohexyl)ethyl]triethoxysilane (CAS 10217-34-2). A 4 hour semiocclusive study in rabbit found the test material not irritating to skin (WIL 1996). Very slight erythema was observed on a single male rabbit at 72 hours post dose which subsided by day 4. There was no oedema or other dermal findings.

A single unwashed exposure to undiluted test material was also found not irritating to rabbit eye (WIL 1996). None of the rabbits vocalized upon instillation of the test material. The left (control) eyes were free of evidence of ocular irritation and other findings for the duration of the study. An iridial reaction was noted in the treated eye of 1/6 animals. There were no corneal findings. Minor conjunctival irritation was noted for all rabbits. All irritation was reversible and completely subsided by termination (day 3) or earlier.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key information for irritation/corrosion is read across from [2-(3,4-epoxycyclohexyl)ethyl]triethoxysilane (CAS 10217-34-2). A 4 hour semiocclusive study in rabbit found the test material not irritating to skin (WIL 1996). Very slight erythema was observed on a single male rabbit at 72 hours post dose which subsided by day 4. There was no oedema or other dermal findings.

A single unwashed exposure to undiluted test material was also found not irritating to rabbit eye (WIL 1996). None of the rabbits vocalized upon instillation of the test material. The left (control) eyes were free of evidence of ocular irritation and other findings for the duration of the study. An iridial reaction was noted in the treated eye of 1/6 animals. There were no corneal findings. Minor conjunctival irritation was noted for all rabbits. All irritation was reversible and completely subsided by termination (day 3) or earlier.

The key studies for skin and eye irritation are both guideline studies conducted in compliance with GLP (WIL, 1996 and WIL, 1996 respectively). Reliability 4 summary data are available for the registered substance itself, which support the absence of irritant effects relevant for classification and labelling (Mellon, 1962). Read-across is considered to be Reliability 2.

The following information is taken into account for any hazard / risk assessment:

The key information for irritation/corrosion is read across from [2-(3,4-epoxycyclohexyl)ethyl]triethoxysilane (CAS 10217-34-2). A 4 hour semiocclusive study in rabbit found the test material not irritating to skin (WIL 1996). Very slight erythema was observed on a single male rabbit at 72 hours post dose which subsided by day 4. There was no oedema or other dermal findings.

A single unwashed exposure to undiluted test material was also found not irritating to rabbit eye (WIL 1996). None of the rabbits vocalized upon instillation of the test material. The left (control) eyes were free of evidence of ocular irritation and other findings for the duration of the study. An iridial reaction was noted in the treated eye of 1/6 animals. There were no corneal findings. Minor conjunctival irritation was noted for all rabbits. All irritation was reversible and completely subsided by termination (day 3) or earlier.

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 irritation, 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 they 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). Further information on the analogue approach on epoxysilanes is attached to IUCLID Section 13 (PFA, 2013q).

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 skin pH of 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 skin pH of 5), the hydrolysis half-life 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 irritation 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.

Table5.3.3.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 20-25°C

0.2 hours

0.7 hours

Hydrolysis at pH 7 37.5°C

1.5 hours

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 10217-34-2)(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 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.

(a)   Discussion of irritation properties of the non-silanol hydrolysis products

The non-silanol hydrolysis products, methanol and ethanol, do not contribute to any irritant effects at the relevant concentrations based on publicly available information (OECD, 2004a; OECD, 2004b).

Methanol and ethanol are not considered to contribute to irritant effects in rats, and hence the read-across is valid.

 



Justification for selection of skin irritation / corrosion endpoint:
The study was conducted according to an appropriate guideline and was compliant with GLP. The study is a read across from CAS 10217-34-2.

Justification for selection of eye irritation endpoint:
The study was conducted according to an appropriate guideline and was compliant with GLP. The study is a read across from CAS 10217-34-2.

Justification for classification or non-classification

Based on the available information, no classification and labelling is required for skin or eye irritation for 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane in accordance with Regulation (EC) No 1272/2008.