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Administrative data

Description of key information

Skin and eye irritation/corrosivity data are available for constituents of amino functional alkoxysilanes and a related substance, as described in the discussion below.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Amino functional alkoxysilanes is a multiconstituent substance which is the reaction mass of tri-(methoxy/ethoxy)methylsilane and amino-functional (methoxy/ethoxy)-silanes. The identity and abundance of the constituents have been determined by GC analysis. A detailed description of the composition can be found in Section 1.2 of the Chemical Safety Report; in broad terms the composition can be described as shown in the table in Section 7.2.

No guideline skin or eye irritation are available for the registered substance itself.

There is an in vivo skin sensitisation study in guinea pigs for the registered substance, which concludes the test material to be a skin sensitiser. A preliminary dose-range finding study was conducted prior to the main skin sensitisation test, which confirms the irritancy potential of the substance.

A solubility test was performed to define the maximum concentration which was technically applicable to the animals. Solubility was found for the vehicle acetone 99.8%, extra dry, at a concentration of 75%. During the dose-range finding study, two animals were treated topically on one flank with the undiluted test item. Two animals per concentration were treated topically with 75%, 50%, 25% and 12.5% of the test item dissolved in acetone. One animal per concentration was treated topically with 6.25%, 3.125%, 3.1% and 1.5% of the test item dissolved in acetone. Neat test substance was determined to be the highest dose that induced some irritation without systemic effects, and was used in the three topical induction phases. During the preliminary phase, grade 1 erythema (no oedema) was observed up to 48 hours, but not at 72 hours after application. During the induction phases 18/20, 20/20 and 20/20 animals had erythema (no oedema) up to 48 hours in induction phase 1, 2 and 3, respectively. During the third induction phase 3 of the 20 animals had erythema that worsened to grade 2 by 48 hours. The erythema observed in all other animals was grade 1. Grade 1 was described as 'discrete or patchy erythema' and grade 2 as 'moderate and confluent erythema'. None of the animals had grade 3 erythema (intense erythema and swelling). The findings in this test support the conclusion that the test substance is irritating to skin, but cannot be used as a basis of a conclusion for classification.

Skin and eye irritation data are available for a number of the constituents of the registered substance and it is therefore possible to determine the appropriate classification of the substance based on the rules for mixtures specified in Regulation (EC) No 1272/2008.

The available data are summarised in the table below, and then discussed in more detail. Further details of the available data for these substances and other alkoxy and aminofunctional alkoxysilanes are given in supporting reports attached in Section 13 of IUCLID (PFA, 2013t and PFA, 2013v).

Constituent identity

Structure

Skin irritation/corrosion

Eye irritation/corrosion

Trimethoxy(methyl)silane

MeSi(OMe)3

Not irritant

Not irritant

3-aminopropyl(trimethoxy)silane

(MeO)3Si(CH2)3NH2

Irritant (Cat 2)

Corrosive (Cat 1)

Triethoxy(methyl)silane

MeSi(OEt)3

Not irritant

Not irritant

3-aminopropyl(triethoxy)silane

(EtO)3Si(CH2)3NH2

Corrosive (Cat 1B)

Corrosive (Cat 1B)

 N-ethyl-3-trimethoxysilyl-2-methyl-propanamine  (MeO)3SiCH2HC2(CH2)CH2NHCH2CH3  Not irritant  Highly irritating (Eye Dam. Cat. 1)

Trimethoxy(methyl)silane (CAS 1185-55-3)

The key studies for trimethoxy(methyl)silane (CAS 1185-55-3) in skin and eye irritation were in vivo studies conducted in accordance with the appropriate test guidelines and GLP (Hazelton Labs, 1992 and Hoescht, 1991). Trimethoxy(methyl)silane was not irritant to rabbit skin or eyes, although mild effects were observed.

The substance is a major part of Constituents A. It also shares a common silanol hydrolysis product with the trisilane constituents (Constituents B) of the registered substance, methylsilanetriol.

3-aminopropyl(triethoxy)silane (CAS 919-30-2)

The key skin irritation/corrosion study for 3-aminopropyl(triethoxy)silane (CAS 919-30-2), conducted in a manner very similar to OECD 404, found the neat material to be corrosive when in 1-h covered contact with rabbit skin (BRRC, 1990). A 3-min contact resulted in moderate irritation.

The key eye irritation/corrosion study for 3-aminopropyl(triethoxy)silane (CAS 919-30-2) reported that the neat test material (0.1 ml) caused severe irritation with necrosis in rabbit eyes, which had not resolved when the study was terminated at 7 days (BRRC, 1989). The effects of a lower volume (0.005 ml) were not entirely reversed by 21 days.

The substance is a minor constituent of the registered substance (Constituents D) and also shares the same silanol hydrolysis product as the other amino alkoxysilane constituents (Constituents D), 3-aminopropylsilanetriol.

3-(trimethoxysilyl)propylamine (CAS 13822-56-5)

In the key skin irritation study (WIL, 2003), 3-(trimethoxysilyl)propylamine was found to be a skin irritant since effects were not fully reversed at the end of the observation period.

The substance is a constituent of the registered substance (Constituents D) and also shares the same silanol hydrolysis product as the other amino alkoxysilane constituents (Constituents D), 3-aminopropylsilanetriol.

Triethoxy(methyl)silane (CAS 2031-67-6)

A key skin irritation study, conducted in compliance with GLP and according to OECD TG 404, found triethoxy(methyl)silane to be a transient, mild irritant in rabbits. However, the results obtained in this study were not sufficient to require classification of the registered substance as a skin irritant (Hazelton, 1992b).

The key study for eye irritation which was not in compliance with GLP, but was equivalent or similar to OECD TG 405, showed that triethoxy(methyl)silane was not irritating to rabbit eyes. Only minor, transient eye irritation was observed following instillation of the test material into the eyes of six rabbits. The Draize score of 0.06 out of 13 indicates the registered substance would not be considered irritating to the eyes of rabbits (Bushy Run Research Center, 1981).

The substance shares a common silanol hydrolysis product with the trisilane constituents (Constituent B) of the registered substance, methylsilanetriol.

N-ethyl-3-trimethoxysilyl-2-methyl-propanamine (CAS 227085-51-0)

Skin and eye irritation data are also available for N-ethyl-3-trimethoxysilyl-2-methyl-propanamine. In a GLP-compliant skin irritation study, conducted according to OECD 404, the substance was not irritating to rabbit eyes (RCC, 2001c). In a GLP-compliant eye irritation study, conducted according to OECD 405, the substance caused serious eye damage (RCC, 2001d).

The substance shares the same ultimate silanol hydrolysis product as the trisilane and cyclo-trisilane constituents of the registered substance (Constituents B and C).

Conclusions for skin and eye irritation/corrosion

The overwhelming evidence from in vivo eye irritation studies with aminofunctional alkoxysilanes (PFA, 2013v) is that these substances cause serious eye damage, warranting classification in Eye Dam. Category 1. In contrast, none of the (methoxy/ethoxy) methylsilanes requires classification for eye irritation.

Likewise none of the (methoxy/ethoxy) methylsilanes requires classification for skin irritation. There is no clear trend for the aminofunctional alkoxysilanes where results vary from not irritant to corrosive, but the majority of substances in this group are Skin Irritant Category 2. As a worst-case, it can therefore reasonably be assumed that the trisilanes and cyclo-trisilanes containing amine groups are irritating to skin. The available guideline skin sensitisation test on the registered substance supports classification as a skin irritant.

Justification for classification or non-classification

The rules for classification of mixtures specified in Regulation (EC) No 1272/2008 indicate that for skin irritation/corrosion:

  • Constituents present at ≥1% should be taken into account
  • A corrosive ingredient present at <1% can still contribute to classification
  • A weighting factor of 10 should be applied for corrosive substances which are not present at sufficiently high concentrations to lead to classification of the mixture as Cat 1, but may still contribute to classification as Cat 2

According to Table 3.2.3 of the Regulation, the relevant equation for amino functional alkoxysilanes is:

%(10 x Skin Corr 1A, 1B or 1C) + %Skin Irrit. 2 ≥10% → Skin Irrit. 2

The relevant constituents to be taken into account for the overall classification of amino functional alkoxysilanes are Constituents B (concentration range 5-20 %), C (concentration range 5-20 %) and D (concentration range 0-10 %) of which all are known or predicted to be Skin Irrit. Cat 2, with the exception of 3-aminopropyl(triethoxy)silane which is Skin Corr. Cat. 1B. Based on the total concentration range of Constituents B, C and D, the registered substance requires classification as Skin Irrit. Cat. 2.

All of the amine-containing constituents, Constituents B (concentration range 5-20 %), C (concentration range 5-20 %) and D (concentration range 0-10 %), are known or predicted to be Eye Dam. Cat. 1 therefore based on their concentration ranges, the registered substance also requires classification as Eye Dam. Cat. 1 according to Table 3.3.3 of Regulation (EC) No 1272/2008.