3-[tris(acetoxy)silyl]propyl methacrylate

Endpoint summary

Description of key information

The key study for skin irritation was read across from triacetoxyethylsilane (CAS 17689-77-9), which has the hydrolysis product acetic acid in common with the registered substance. The key skin irritation/corrosion study (Hazleton, 1989), which was comparable to OECD 405 and conducted to GLP, found triacetoxyethylsilane corrosive to the skin of rabbits following a three minute exposure under semi-occlusive conditions. There are no in vivo eye irritation studies. In accordance with Column 2 of REACH Annex VIII, the in vivo eye irritation study (required in Section 8.2.1) does not need to be conducted as the substance is classified as corrosive to skin.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The key study for skin irritation is read across from the structurally analogous substance, triacetoxyethylsilane (CAS 17689-77-9), which has the hydrolysis product acetic acid in common with the registered substance.

The available key skin irritation/corrosion study on triacetoxyethylsilane (CAS17689-77-9) clearly showed that the substance is corrosive to the skin. In this study the animals were exposed to the test substance for three minutes, rather than the four hours recommended by OECD TG 404. However, in light of the severity of the local reaction to this substance, an exposure period of three minutes is sufficient to clearly distinguish the category for classification. In this study grade 2 erythema and edema were observed in all animals within the first hour after dressing removal. The overall reactions peaked between 24 and 48 hours after dressing removal. By 72 hours the edema began to reverse in all of the animals. However, erythema persisted for longer, such that two of the animals still had Grade 4 erythema on Day 14. Burns of varying sizes were observed in five of the six exposed animals.

Due to the corrosive effects of triacetoxyethylsilane (CAS 17689-77-9) to the skin, both the read-across substance and the registered substance are predicted to be severely irritating to the eye and they are also likely to cause respiratory irritation based on the production of acetic acid following hydrolysis.

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 relevant properties are structural similarity, hydrolysis rate and the physical-chemical parameters in the same range. In the following paragraphs the proposed read-across from triacetoxyethylsilane (CAS 17689 -77 -9) to 3-[tris(acetoxy)silyl]propyl methacrylate is evaluated point by point.

Read-across hypothesis

The hypothesis is that the substances both hydrolyse rapidly in contact with moisture resulting in the production of acetic acid, which is known for its corrosive properties (OECD SIDS, 2004), with the resulting predominant corrosive effect. This is discussed further below.

Read-across justification

The predicted hydrolysis half-life of the registered substance, 3-[tris(acetoxy)silyl]propyl methacrylate, is <1 minute at 25°C and pH 4, 7 and 9. The products of hydrolysis are 3-(trihydroxysilyl)propyl methacrylate and acetic acid .

The read-across substance triacetoxyethylsilane (CAS 17689-77-9) has measured hydrolysis half-lives at 25°C of <13 s (0.2 min) at pH 4, 7 and 9. 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. The hydrolysis products are ethylsilanetriol and acetic acid.

The available half-lives for the read-across substances were all measured at 22 -25ºC. Reaction rate increases with temperature and the half-lives at 37.5ºC (relevant for in vivo studies) are expected to be significantly faster.

Therefore, the predicted half-lives for the registration and read-across substances are short (<1 minute) so both substances will be hydrolysed to a silicon-containing hydrolysis product and acetic acid very rapidly. Therefore, read-across from triacetoxyethylsilane (CAS 17689-77-9) to 3-[tris(acetoxy)silyl]propyl methacrylate (CAS 51772 -85 -1) for skin irritation is valid.

 

Analogue approach justification

(a)               Structural similarity

The registration and read-across substances are structurally similar triacetoxysilanes. The registered and the read-across substance both have three three acetoxy groups attached to the silicon. However, the two differ in that the read-across substance has an ethyl group attached to the silicon atom, whereas the registered substance has a propylmethacrylate side chain. Both hydrolyse rapidly to produce the silicon-containing hydrolysis products, 3-(trihydroxysilyl)propyl methacrylate or ethylsilanetriol and the common non-silicon hydrolysis product acetic acid. Acetic acid is known to have corrosive effects, common to both the registered substance and the read-across aubstance.

 

(b) Similar physicochemical characteristics

The similarity of the physicochemical properties and hydrolysis rates at pH relevant to skin exposure is important. Both parent substances hydrolyse rapidly and the hydrolysis products have comparable low log K_owand vapour pressure. The key physicochemical parameters are summarised below.

 

Table 5.2.3: Key physicochemical parameters

 

	Target (registration substance)	Source (read-across substance
CAS number	051772-85-1	017689-77-9
EC number	257-407-3	241-677-4
Chemical Name	3-[tris(acetoxy)silyl]propyl methacrylate	triacetoxyethylsilane
Molecular weight  (gmol^-1)	332.39	234.28
log Kow(parent)	Not relevant	Not relevant
log Kow(silicon-containing hydrolysis product)	-0.9	-1.9
Water solubility (parent)	Not relevant	Not relevant
Water solubility (silicon-containing hydrolysis product)	limited to about 1000 mg/l by condensation reactions	miscible at 20°C (QSAR)
Vapour pressure (parent)	0.009 Pa at 25°C	5.1 Pa at 20°C
Vapour pressure (silicon-containing hydrolysis product)	1.2E-05 Pa at 25°C	0.015 Pa at 25°C (QSAR)

 

Justification for classification or non-classification

On the basis of the available in vivo skin irritation/corrosion studies on the analogous substance, triacetoxyethylsilane (CAS 17689-77-9) the registered substance, 3-[tris(acetoxy)silyl]propyl methacrylate (CAS 51772 -85 -1), is classified 'Skin Corr. 1B' with the hazard statement 'H314: Causes severe skin burns and eye damage' according to the criteria of Regulation (EC) No 1272/2008/EC. It is assumed that substances that are corrosive to the skin are also damaging to the eyes, so there is no separate labelling for the eyes. There are no specific data for respiratory irritation, however the substance is proposed to be classified as STOT SE 3, ‘H335: May cause respiratory irritation’.