Registration Dossier

Administrative data

Description of key information

The key studies for skin and eye irritation were read-across from 3-trimethoxysilylpropyl methacrylate. The selected studies were the only available guideline studies for those endpoints and determined 3-trimethoxysilylpropyl methacrylate to be not irritating. Both tests were conducted in compliance with GLP and were assigned Reliability 1.

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 read-across substance, 3-trimethoxysilylpropyl methacrylate, was determined to be not irritating to rabbit skin (WIL, 2001) or eyes (WIL, 2000) according to EU criteria (EC directive 67/548/EEC and subsequent amendments). Minor reversible erythema was observed in the skin irritation test, and minor reversible conjunctival redness was observed in the eye irritation test.

Read-across justification

There are no available measured data for 3-[tris(trimethylsiloxy)silyl]propylmethacrylate (CAS 17096-07-0) for skin and eye irritation. Annex requirements are therefore fulfilled by use of read-across of reliable measured data for a structural analogue. This document describes the analogue approach for fulfilling this endpoint by read-across from a source substance, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) as well as from one of the silicon-containing hydrolysis products of the target substance, trimethylsilanol (CAS 1066-40-6), according to the Read-across Assessment Framework (RAAF) .

Read-across is proposed in accordance with RAAF Scenario 2: “This scenario covers the analogue approach for which the read-across hypothesis is based on different compounds which have the same type of effect(s). For the REACH information requirement under consideration, the effects obtained in a study conducted with one source substance are used to predict the effects that would be observed in a study with the target substance if it were to be conducted. The same type of effect(s) or absence of effect is predicted. The predicted strength of the effects may be similar or based on a worst case.”

The read-across justification is presented (Table 1) according to RAAF scenario 2 assessment elements (AE) as outlined in Table B1 of the RAAF1:

Table 1: RAAF scenario 2 assessment elements (AE) as given in Appendix B (Table B1) of the RAAF1

AE A.1

Characterisation of source substance

AE A.2

Link of structural similarity and differences with the proposed Prediction

AE A.3

Reliability and adequacy of the source study

AE 2.1

Compounds the test organism is exposed to

AE 2.2

Common underlying mechanism, qualitative aspects

AE 2.3

Common underlying mechanism, quantitative aspects

AE 2.4

Exposure to other compounds than to those linked to the prediction

AE 2.5

Occurrence of other effects than covered by the hypothesis and Justification

AE A.4

Bias that influences the prediction

1. AE A.1 Identity and characterisation of the source substance

The first source substance, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0), has a silicon atom bound to three methoxy groups, and one propyl methacrylate group. Its measured hydrolysis half-lives are 0.018 h at pH 4, 1.87 h at pH 7 and 0.068 h at pH 9 and 20°C.

At pH of skin, 5.5, the hydrolysis half-life is expected to be between 0.018 h and 1.87 h. At pH 7 (the pH of eye), the hydrolysis half-life is 1.87 h. The products of hydrolysis are 3-(trihydroxysilyl)propyl methacrylate (1 mole) and methanol (3 moles).

The second source substance, trimethylsilanol (CAS 1066-40-6), is the silanol hydrolysis product of the target substance. It has a silicon atom bound to three methyl groups and one hydroxyl group. The first source substance has log Kowof 2.1 at 20°C (QSAR), water solubility of 2200 mg/L at 20°C (QSAR) and vapour pressure of 2.3 Pa at 25°C (QSAR).

2. AE A.2 Link of structural similarities and differences with the proposed prediction

The registration substance, 3-[3,3,3 -trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate (CAS 17096-07-0), and the first read-across substance, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0), are members of an analogue group of organosilicon compounds containing a methacrylate group. Both substances have a propyl methacrylate side-chain attached to the silicon atom.

The hypothesis is that the methacrylate functional group has greater biological reactivity than the siloxane part of the target substance and any irritation will be associated with this group. Therefore, organosilicon compounds containing this group were considered for read-across.

In addition to the propylmethacrylate side-chain, the target substance has three (trimethylsilyl)oxy groups bound to the central silicon atom. In addition to the propylmethacrylate side-chain, the source substance has three methoxy groups bound to silicon. Therefore, the difference between the two structures is that the three methoxy groups in the source substance are replaced by three (trimethylsilyl)oxy groups groups in the target substance.

These two substances both hydrolyse to give the same trisilanol (1 mole), 3-(trihydroxysilyl)propyl methacrylate. In addition, the target substance gives trimethylsilanol (3 moles) and the source substance gives methanol (3 moles).

The second source substance, trimethylsilanol (CAS 1066-40-6), is the second hydrolysis product for the target substance. It has a silicon atom bound to three methyl groups and one hydroxyl group. It is an organosilicon compound, (CH3)3SiOH, with no hydrolysable groups. Organosilanol compounds, RnSi(OH)4-n, are the endpoint for hydrolysis of all organosilicon substances, with Si-X (where X can be OR, Cl, etc) hydrolysing to give Si-OH and XH.

Table 2: Physico-chemical properties of the source and target substances

Property

Target substance

Source substance

Source substance

Substance name

3-[3,3,3-Trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate

3-Trimethoxysilylpropyl methacrylate (CAS 2530-85-0)

Trimethylsilanol

CAS number

17096-07-0

2530-85-0

1066-40-6

Hydrolysis half-life at pH 5and 25ºC

2.3 h (QSAR)

0.3 hours (QSAR)

Not applicable

Hydrolysis half-life at pH 7and 25ºC

631 h (QSAR)

1.7 hours

Not applicable

Silanol hydrolysis product

3-(Trihydroxysilyl)propyl methacrylate and trimethylsilanol

3-(Trihydroxysilyl)propyl methacrylate

Not applicable

Non-Si hydrolysis product

Not applicable

Methanol

Not applicable

LogKow value

9.0 at 20°C (QSAR)

2.1 at 20°C (QSAR)

1.19 at 25 ± 0.5°C and pH 7.1 (OECD 107)

Vapour pressure

0.11 Pa at 20°C (OECD 104)

2.3 Pa at 25°C (QSAR)

9 hPa at 25°C (OECD 104)

Water solubility

5.8E-05 mg/L at 20°C (QSAR)

2200 mg/L at 20°C (QSAR)

995 mg/L at 20°C (OECD 105)

3. AE A.3 Reliability and adequacy of the source study

3-Trimethoxysilylpropyl methacrylate was determined to be not irritating to rabbit skin (WIL, 2001; rel. 1) or eyes (WIL, 2000; rel. 1). The studies were conducted according to appropriate OECD Test Guidelines and in compliance with GLP.

In the skin irritation study the test item was applied to one site of closely clipped dorsal area of three female rabbits at a dose of 0.5 ml per application site. The untreated side served as a control group. The application site was covered with a semi - occlusive bandage for 4 hours. No clinical signs of toxicity were found. The test item showed no irritant effects on the intact skin after a contact time of 4 hours.

In the eye irritation study, 0.1 mL of test substance was applied to the eyes of 3 female rabbits. One eye of each animals was untreated as served as a control group. The animals were observed for 72 hours. No clinical signs were observed in any of the test animals as well as no changes in body weight gain. The test item showed no irritant effects on the eyes.

Trimethylsilanol was determined to be not irritating to rabbit skin (Bayer AG, 1986a) and eyes (Bayer AG, 1985b). The studies were conducted according to appropriate OECD Test Guidelines and in compliance with GLP.

In a skin irritation study conducted to OECD 404, but not to GLP (Bayer AG, 1986a), three female New Zealand white rabbits were dermally (shaved, intact) exposed to 0.5 ml of undiluted trimethylsilanol for four hours. After four hours the test substance was washed off the skin with water, and skin reactions were recorded for up to 72 hours. None of the animals had any erythema or oedema at any time point, and therefore the test substance was concluded not to be a skin irritant.

In an eye irritation study conducted to OECD 405, but not to GLP (Bayer AG, 1985b), trimethylsilanol was slightly irritating to the eyes of three male rabbits following a 24-hour exposure. All animals had grade 1 corneal opacity at 60 minutes, which increased in severity (to grade 2) in one animal at 24 and 48 hours. All animals had conjunctival redness (grade 1-3) and conjunctival oedema (chemosis: grade 1-2). All opacity and conjunctival effects were reversed by seven days after treatment. There were no effects on the iris. The irritation did not meet the EU criteria for classification.

4. AE A.4 Bias that influences the prediction

Data on the source substances, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) and trimethylsilanol (CAS 1066-40-6) were read-across to the registered (target) substance 3-[3,3,3-trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate (CAS 17096-07-0).

The first source substance, 3-trimethoxysilylpropyl methacrylate and the target substance are structural analogues because they are both organosilicon compounds with a propylmethacrylate side-chain. These two substances hydrolyse to produce a common hydrolysis product, 3-(trihydroxysilyl)propyl methacrylate. The source substance is the closest structural analogue to the target substance that has measured skin and eye irritation data; other organosilicon compounds with methacrylate side-chains show consistent results.

The second source substance, trimethylsilanol (CAS 1066-40-6), is the silanol hydrolysis product for the target substance.

5. AE A.2.1 Compounds the test organism is exposed to

The source substance, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0), as well as the target substance hydrolyse in contact with water. Therefore, the test organism is exposed to both the parent substances and their hydrolysis products, 3-(trihydroxysilyl)propyl methacrylate, trimethylsilanol and methanol.  The source and target substance have been profiled using the OECD QSAR Toolbox v. 4.1. The two substances and their silanol hydrolysis products show similar profiles for all toxicological endpoints. No alert for skin or eye irritation was detected by OECD QSAR Toolbox v.4.1.

The second source substance, trimethylsilanol (CAS 1066-40-6), is the silanol hydrolysis product for the target substance. In vivo skin and eye irritation studies were available and the substance was concluded to be not irritating to skin or eyes.

The toxic effects of methanol are well established. Ophthalmologic changes and acidosis are described as typical primary effects in humans. Methanol is known to be a mild to moderate eye and skin irritant. At the doses of parent substance, the methanol toxicity is not expected to be relevant.

6. AE A.2.2 and A.2.3 Common underlying mechanism, qualitative and quantitative aspects

No toxicity data are available for the target substance 3-[3,3,3-trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate (CAS 17096-07-0), therefore, data are read-across from the structurally analogous substance 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) and the target substance hydrolysis product trimethylsilanol (CAS 1066-40-6).

The target substance and the first source substance, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0), hydrolyse to form the same trisilanol (1 mole) and methanol (3 moles). The non-silanol hydrolysis product of the source substance, methanol, is not expected to be relevant for this endpoint. Data are also read-across from the second hydrolysis product of the target substance, trimethylsilanol (CAS 1066-40-6).

7. AE 2.4 Exposure to other compounds than to those linked to the prediction

Neither the target substance, 3-[3,3,3-trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate (CAS 17096-07-0), nor the source substances, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0)  and trimethylsilanol (CAS 1066-40-6), have impurities of toxicological concern.

The test substance in the study with the first source substance, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0), has a purity of 98.8%.

The purity of the second source substance (hydrolysis product), trimethylsilanol (CAS 1066-40-6), was not stated in the study report. However, based on substance’s boundary composition there is a known impurity which may be present at a concentration of less than 15%. This impurity is not irritating to eyes or skin.

The target substance, 3-[3,3,3-Trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate (CAS 17096-07-0), has a purity of >98% and no impurities are present at >1%.

8. AE 2.5 Occurrence of Other Effects than Covered by the Hypothesis and Justification

Not relevant.


Justification for classification or non-classification

Based on the available data for 3-[3,3,3-trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate no classification for skin and eye irritation is required according to Regulation (EC) No 1272/2008.