Registration Dossier

Administrative data

Description of key information

The read-across key study for skin irritation was selected as the only available guideline study for this endpoint and determined that the test substance, 3-trimethoxysilylpropyl methacrylate, to be not irritating. The test was conducted according to OECD TG 404 and in compliance with GLP (WIL, 2001).

The read-across key study for eye irritation was selected as the only available guideline study for this endpoint and determined that the test substance, 3-trimethoxysilylpropyl methacrylate, to be not irritating. The test was conducted according to OECD TG 405 and in compliance with GLP (WIL, 2000).

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

There are no measured skin and eye irritation data available for the registration substance therefore reliable data are read across from a structural analogue. The read-across key study for skin irritation was selected as the only available guideline study for this endpoint and determined that the test substance, 3-trimethoxysilylpropyl methacrylate, to be not irritating. The test was conducted according to OECD TG 404 and in compliance with GLP (WIL 2001).

Undiluted test material (0.5 ml) was applied onto the skin of rabbits for 4 hours under semi-occlusive dressing. Clinical signs of toxicity were noted at 1, 24, 48 and 72 hours post-application. No deaths or remarkable body weight changes were observed. Very slight erythema was noted on one animal at 30-60 min observation, which was fully reversible within 1 hours. There were no signs of oedema or any other dermal findings. The test material was concluded to be not irritating to skin under the conditions of the study.

The read-across key study for eye irritation was selected as the only available guideline study for this endpoint and determined that the test substance, 3-trimethoxysilylpropyl methacrylate, to be not irritating. The test was conducted according to OECD TG 405 and in compliance with GLP (WIL, 2000).

Following single instillation of 0.1 ml of undiluted test material into the eyes of 3 female rabbits, minor conjunctival irritation (grade 1) was observed in the treated eye of all animals which completely subsided by 72 hours. There were no corneal or iridial findings. The test substance was concluded to be not irritating under the conditions of the study.

Read-across justification

There are no available measured data for 1,1,3,3-tetramethyldisiloxane-1,3-diyl)dipropane-1,3-diyl dimethacrylate (CAS 18547-93-8) for skin and eye irritation. Therefore, the Annex requirements are fulfilled by data on a structurally analogous substance. This document describes the analogue approach for fulfilling this endpoint by read-across from the source substance, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0), 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 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 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 rate is expected to be between 0.4 minutes and 0.5 hours. At pH 7 (the pH of eye), and 37.5°C the hydrolysis rate is 0.5 h. The products of hydrolysis are 3-(trihydroxysilyl)propyl methacrylate (1 mole) and methanol (3 moles).

The source substance has log Kow of 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

(1,1,3,3-Tetramethyldisiloxane-1,3-diyl)dipropane-1,3-diyl dimethacrylate and 3-trimethoxysilylpropyl methacrylate both are silicon-containing substances that have a methacrylate ester group attached via a propyl group to the silicon atom. The registration substance is a linear siloxane with two silicon atoms connected by one oxygen atom; the Si-O bonds are subject to hydrolysis. Each silicon also has two methyl groups and one propyl methacrylate group. The read-across substance is an alkoxysilyl methacrylate which has three methoxy groups and a propyl methacrylate group attached to the silicon atom.

The silanol hydrolysis products for the registered substance is 3-[hydroxy(dimethyl)silyl]propyl methacrylate. The silanol hydrolysis product of the read-across substance is 3-(trihydroxysilyl)propyl methacrylate. The non-silicon-containing hydrolysis product of the read-across substance is methanol. The registered substance hydrolyses to silanol hydrolysis product only.

Thus, the source and target substances and their silicon-containing hydrolysis products all contain the same propyl methacrylate sidechain. The difference is that the registered substance is a dimer (two silicon atoms instead of one) and has two methyl groups attached to the silicon atom instead of methoxy groups as in the source substance.

Table 2: Physico-chemical properties

 

Target (registration substance)

Source (read-across substance)

CAS number

18547-93-8

2530-85-0

EC number

 242-419-3

219-785-8

Chemical Name

(1,1,3,3-tetramethyldisiloxane-1,3diyl)dipropane-1,3-diyl dimethacrylate

3-trimethoxysilylpropyl methacrylate

Molecular weight (gmol-1)

202.33

248.35

log Kow (parent)

8.1 at 20°C (QSAR)

2.1 at 21±1°C (OECD 107)

log Kow (silicon-containing hydrolysis product)

-2.6 at 20°C (QSAR)

-0.9 at 20°C (QSAR)

Water solubility (parent)

330 mg/l at 20°C (QSAR)

2200 mg/l at 20°C (QSAR)

Water solubility (siliconcontaining hydrolysis product)

The concentration dissolved in water is limited to about 1000 mg/ l by condensation reactions

The concentration dissolved in water is limited to about 1000 mg/ l by condensation reactions.

Vapour pressure (parent)

0.05 Pa at 25°C (QSAR)

2.3 Pa at 25°C (OECD 104)

Vapour      pressure      (silicon-

containing hydrolysis product)

4.8E-02 Pa at 25°C (QSAR)

1.2E-05 Pa at 25°C (QSAR)

 

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) and eyes (WIL, 2000). The studies were conducted according to appropriate OECD Test Guidelines and in compliance with GLP.

Minor reversible erythema was observed in the skin irritation test, and minor reversible conjunctival redness was observed in the eye irritation test.

4. AE A.4 Bias that influences the prediction

Data on the source substance 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) were read-across to the registered (target) substance (1,1,3,3-tetramethyldisiloxane-1,3-diyl)dipropane-1,3-diyl dimethacrylate (CAS 18547-93-8). The predicted half-lives for the registration substance (1,1,3,3-tetramethyldisiloxane-1,3diyl)dipropane-1,3-diyl dimethacrylate (CAS 18547-93-8) (0.9 h) and the read-across substance(3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0)(0.3 h) at pH 5.5 are comparable. Both substances will be hydrolysed to similar siloxane hydrolysis products 3-[hydroxy(dimethyl)silyl]propyl methacrylate and 3-(trihydroxysilyl)propyl methacrylate, respectively. Based on the presence of the methacrylate group in the source and target substances, their irritancy potential is expected to also be similar. No irritation data are available for substances containing the methacrylate group that are closer structural analogues of the target substance.

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

The source substance and the target substance hydrolyse rapidly in contact with water. Therefore, the test organism is exposed to both the parent substances and their hydrolysis products, 3-(trihydroxysilyl)propyl methacrylate (and methanol for the source substance) or 3-[hydroxy(dimethyl)silyl]propyl methacrylate (for the target substance) .  The source and target substances 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 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, (1,1,3,3-tetramethyldisiloxane-1,3-diyl)dipropane-1,3-diyl dimethacrylate (CAS 18547-93-8), therefore, data are read-across from the structurally analogous substance 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0). These two substances hydrolyse at a similar rate to a trisilanol (1 mole) and methanol (3 moles) in the case of the source substance and a monosilanol (2 moles) in the case of the target substance. The non-silanol hydrolysis product, methanol, is not expected to be relevant for this endpoint. Both parent substances and the corresponding silanol hydrolysis products contain the same propyl methacrylate side chain which is expected to be the most significant structural feature for toxicological properties and thus the skin and eye irritation potential are expected to be similar. Since these are local toxicity effects, the approximate 10-fold difference in solubility and different log Kow of the source and target substances is not considered to be significant.

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

Neither the target substance, (1,1,3,3-tetramethyldisiloxane-1,3-diyl)dipropane-1,3-diyl dimethacrylate, nor the source substance, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) have impurities of toxicological concern.

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

The target substance, 1,1,3,3-tetramethyldisiloxane-1,3-diyl)dipropane-1,3-diyl dimethacrylate (CAS 18547-93-8), has a purity of >95%.

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

Not relevant.

OECD (2004): SIDS Initial Assessment Report for SIAM 19, Berlin, Germany, 18-20 October 2004, Methanol, CAS 67-56-1.

 

 

Justification for classification or non-classification

Based on the available data for 3-(trimethoxysilylpropyl) methacrylate, the registered substance, (1,1,3,3-tetramethyldisiloxane-1,3-diyl)dipropane-1,3-diyl dimethacrylate, does not require classification for skin and eye irritation according to Regulation (EC) No. 1272/2008.