3-(dimethoxymethylsilyl)propyl methacrylate

Endpoint summary

Description of key information

The key studies for skin and eye irritation were read across from the analogous substances 3-(trimethoxysilylpropyl) methacrylate (CAS 2530-85-0) and [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3). The available studies were conducted according to current guideline and in compliance with GLP. The test materials were concluded to not be an irritant to the skin or eyes of rabbits (WIL 2001, WIL 2000, Bioservice 2003b, Bioservice 2003c).

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

3 -Trimethoxysilylpropyl methacrylate was determined to be not irritating to rabbit skin (WIL, 2001) and 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.

[Dimethoxy(methyl)silyl]methyl methacrylate  was concluded to be not irritating to skin (Bioservice, 2003b) and eyes (Bioservice, 2003c).

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.

Read-across justification

There are no available measured data for 3-[dimethoxy(methyl)silyl]propyl methacrylate (CAS 14513-34-9) for skin and eye irritation. Therefore, the Annex requirements are fulfilled by data on structurally analogous substances. This document describes the analogue approach for fulfilling this endpoint by read-across from two source substances, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) and [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3), 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 5.6.4) 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 rate is expected to be between 0.018h and 1.87 h. At pH 7 (the pH of eye), the hydrolysis rate is 1.87 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).

The second source substance [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3), has a silicon atom bound to two methoxy groups, one methyl group and one methyl methacrylate group. Its predicted hydrolysis half-lives are 1.8 h at pH 7, 0.2 h at pH 4, 0.04 h at pH 9 and 25°C.

At pH of skin, 5.5, the hydrolysis rate is expected to be between 0.2 h and 1.8 h. At pH 7 (the pH of eye), the hydrolysis rate is 1.8 h.

The hydrolysis products in this case are [dihydroxy(methyl)silyl]methyl methacrylate (1 mole) and methanol (2 moles). The source substance has a log Kow of 2.4 at 20°C, vapour pressure of 37 Pa at 25°C and water solubility of 2500 mg/l.

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

The registration and the first read-across substance, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0), are structurally similar and are members of an analogue group of alkoxysilanes and silanols containing a methacrylate group. Both substances have a propyl methacrylate side-chain attached to the silicon atom.

In addition to the propylmethacrylate side-chain, the target substance has two methoxy groups and one methyl group bound to silicon. The source substance has three methoxy groups bound to silicon. Therefore, the difference between the two structures is that one of the three methoxy groups in the source substance is replaced by a methyl group in the target substance. The silanol hydrolysis products are 3-[dihydroxy(methyl)silyl]propyl methacrylate and 3-(trihydroxysilyl)propyl methacrylate for the registered substance and read-across substance, respectively. The common non silanol hydrolysis product is methanol.

These two substances both hydrolyse at a similar rate to a disilanol (1 mole) or a trisilanol (1 mole) and methanol (2 or 3 moles). The hydrolysis products of these two substances are structurally similar in the same way as the parent substances. They both have a propyl methacrylate side-chain. The difference is that the registered substance has a methyl group attached to the silicon atom instead of one of the methoxy groups in the source substance.

The source substance, [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3), and the target substance, 3-[dimethoxy(methyl)silyl]propyl methacrylate (CAS 14513-34-9), are structurally similar. They are both dimethoxy silanes with one methyl group bound to silicon. The difference is that the source substance has a methyl methacrylate side-chain attached to the silicon atom, while the target substance has a propyl methacrylate side-chain instead.

These two substances both hydrolyse at a similar rate to a disilanol (1 mole) and methanol (2 moles). The hydrolysis products of these two substances are structurally similar in the same way as the parent substances. They are both disilanols with one methyl side-chain. The difference is that the source substance has a methyl methacrylate side-chain, whereas the target substance has propyl methacrylate side-chain (see Table 1).

Table 2: Physico-chemical properties

Property		Target substance		Source substance		Source substance
Substance name		3-[Dimethoxy(methyl)silyl]propyl methacrylate		3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0)		[dimethoxy(methyl)silyl]methyl methacrylate
CAS number		14513-34-9		2530-85-0		121177-93-3
Hydrolysis half-life at pH 5and 25ºC		0.2 hours (QSAR)		0.3 hours (QSAR)		0.2 (QSAR)
Hydrolysis half-life at pH 7and 25ºC		1.5 hours		1.7 hours		1.8 hours
Silanol hydrolysis product		3-[dihydroxy(methyl)silyl]propyl methacrylate		3-(trihydroxysilyl)propyl methacrylate		[dihydroxy(methyl)silyl]methyl methacrylate
Non-Si hydrolysis product		methanol		methanol		methanol
LogKow value		3.4 at 20°C (QSAR)		2.1 at 20°C (QSAR)		2.4 at 20°C (QSAR)
Vapour pressure		1.3 Pa at 25°C (QSAR)		2.3 Pa at 25°C (QSAR)		37 Pa at 25°C (QSAR)
Water solubility		240 mg/L at 20°C (QSAR)		2200 mg/l at 20°C (QSAR)		2500 mg/l

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.

[Dimethoxy(methyl)silyl]methyl methacrylate  was concluded to be not irritating to skin (Bioservice, 2003b) and eyes (Bioservice, 2003c).

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.

4. AE A.4 Bias that influences the prediction

Data on the source substances 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) and [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3) were read-across to the registered (target) substance 3-[dimethoxy(methyl)silyl]propyl methacrylate (CAS 14513-34-9). The source substances and the target substance have similar chemical structure and physico-chemical properties. All three substances hydrolyse at similar rate, and produce 3-[dihydroxy(methyl)silyl]propyl methacrylate, 3-(trihydroxysilyl)propyl methacrylate or [dihydroxy(methyl)silyl]methyl methacrylate, as the silicon-containing hydrolysis products. They share a common non-silanol hydrolysis product, methanol. Therefore, their toxicological properties are expected to be similar, with similar irritation effects. These substances are the closest structural analogues to the target substance; other alkoxysilanes with methacrylate side-chains show consistent results.       

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

The source substances as well as 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-[dihydroxy(methyl)silyl]propyl methacrylate, 3-(trihydroxysilyl)propyl methacrylate or [dihydroxy(methyl)silyl]methyl methacrylate and methanol.  The source and target substances have been profiled using the OECD QSAR Toolbox v. 4.1. The three 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. Opthalmologic 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-[dimethoxy(methyl)silyl]propyl methacrylate, therefore, data are read-across from the structurally analogous substances 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) and [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3). These three substances hydrolyse at similar rate to a disilanol (1 mole) or a trisilanol (1 mole) and methanol (2 or 3 moles). The non-silanol hydrolysis product, methanol, is not expected to be relevant for this endpoint. Moreover, they have similar physico-chemical properties. Thus, all three substances are expected to have similar toxicity profiles.

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

Neither the target substance, 3-[dimethoxy(methyl)silyl]propyl methacrylate, nor the source substances, 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0)  and [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3), 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 test substance in the study with the second source substance, [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-3), has a purity of 98.6%.

The target substance, 3-[dimethoxy(methyl)silyl]propyl methacrylate (CAS 14513-34-9), 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.

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 on the analogous substance 3-(trimethoxysilylpropyl) methacrylate (CAS 2530 -85 -0)

no classification is required for irritation according to Regulation (EC) No. 1272/2008.