Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 298-130-8 | CAS number: 93777-98-1
The key study for skin irritation is read across from the structurally analogous substance 1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine (CAS 37697-65-7). The study, which was conducted according to OECD TG 404 and in compliance with GLP, reports that the test substance is corrosive to skin (Hazleton, 1990).
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.
The key study for skin irritation is read across from the structurally analogous substance 1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine (CAS 37697-65-7; source substance). The study was conducted according to OECD TG 404 and in compliance with GLP. The source substance, N,N',N''-tributyl-1-methylsilanetriamine (CAS 37697-65-7), is corrosive to skin (Hazleton, 1990).
Following a 3 minute application of the test material onto rabbit skin, erythema was evident in all the animals. Dryness of the treated area could be observed 72 hours post-treatment. The severe lesions at 72-hour observation, were reported to be noticeably reversible within 14 days post-application. Very slight oedema was noted in 4 out of the 6 rabbits, until the end of the 14 day observation period.
Following the 4 hour exposure, erythema was evident in all the animals, with necrosis and dry skin until the end of the observation period. Slight to moderate oedema was reported in 5 out of 6 of the animals at 72 hours post-exposure. There was no evidence for reversibility of the lesions, which remained until day 14 days after the application of the test material. In accordance with Column 2 of REACH Annex VIII, the in vitro eye irritation study (required in Section 8.2.1) does not need to be conducted as the substance is classified as corrosive to skin.
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 1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine (CAS 37697-65-7) to 1,1-dimethyl-N,N'-bis(1-methylpropyl)silanediamine (CAS 93777-98-1; target substance) is evaluated point by point.
The hypothesis is that the predominant corrosive effect is due to the high pH of the substances and to their reactivity with water. The source and target substances produce the amine-functional hydrolysis product, sec-butylamine, which is of high pH and drives their corrosive properties. This is discussed further below.
The measured hydrolysis half-lives of the registered target substance, 1,1-dimethyl-N,N'-bis(1-methylpropyl)silanediamine, at 25°C are <2 minutes at pH 4, 7 and 9. The products of hydrolysis are sec-butylamine (2 moles; CAS 13952-84-6) and dimethylsilanediol (1 mole; CAS 1066-42-8).
The source substance 1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine (CAS 37697-65-7) has measured hydrolysis half-lives at 25°C of < 2 minutes at pH 4 and pH 7 and 5.0 min at pH 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 sec-butylamine (3 moles; CAS 13952-84-6) and methylsilanetriol (1 mole; CAS 2445-53-6).
The available half-lives for the source substance were all measured at 25°C. Reaction rate increases with temperature and the half-lives at 37.5°C (relevant for in vivo studies) are expected to be significantly faster.
No pH or pKa values are available for the parent substances; measurement would not be technically feasible as they hydrolyse extremely rapidly in water. Both substances hydrolyse rapidly to produce an amine, sec-butylamine. This substance (as for other amines) is basic, with a pKaof >9.5 (SIDS INITIAL ASSESSMENT PROFILE for C1 -13 Primary Amines; SIAM 32, 19-21 April 2011). Therefore, solutions of sec-butylamine will be of very high pH (for example a 50% solution of the structurally related substance n-butylamine has a pH of 13 according to the ECHA disseminated dossier for n-butylamine, CAS 109-73-9). Therefore, read-across from 1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine (CAS 37697-65-7) to 1,1-dimethyl-N,N'-bis(1-methylpropyl)silanediamine (CAS 93777-98-1) for skin irritation is valid.
Analogue approach justification
(a) Structural similarity
The target and source substances are structurally similar silylamines. They each have one or two methyl groups and two or three 1-methylpropylamine groups bound to a central silicon atom. The difference between the target and source substance is that the target substance has two methyl groups and two 1-methylpropylamine groups bound to silicon, whereas the source substance has one methyl group and three 1-methylpropylamine groups. Both substances hydrolyse extremely rapidly (half-life for full hydrolysis <2 mins at pH 4 and 7) to produce the silicon-containing hydrolysis products, dimethylsilanediol or methylsilanetriol (1 mole) and the common non-silicon hydrolysis productsec-butylamine (2 moles for the target substance, 3 moles for the source substance).
(b) Similar physicochemical characheristics
The similarity of the physicochemical properties and hydrolysis rates at pH relevant to skin exposure is important. Both parent substances hydrolyse very rapidly to give a common product, sec-butylamine, and silanols that are structurally similar and have similar physicochemical properties. The key physicochemical parameters are summarised below.
Amine leaving group
sec-butylamine (CAS 13952-84-6)
Si hydrolysis product
methylsilanetriol (CAS 2445-53-6)
dimethylsilanediol (CAS 1066-42-8).
t1/2 at pH 7 and 25°C
< 2 min
t1/2 at pH 4 and 25°C
t1/2 at pH 5.5 and 25°C*
< 2 min (estimated)
Vapour pressure amine leaving group
24000 Pa at 25°C
Water solubility amine leaving group
Log Kow amine leaving group
pKa amine leaving group
Vapour pressure silanol hydrolysis product
0.05 Pa at 25°C (QSAR)
7 Pa at 25°C (QSAR)
Water solubility silanol hydrolysis product
1E+06 mg/l (limited to around 1000 mg/l by condensation reactions)
1E+06 mg/l (QSAR) (limited to around 1000 mg/l by condensation reactions)
Log Kow silanol hydrolysis product
*The half-life at pH 5.5 is expected to be between the half-lives at pH 4 and pH 7.
(C) Corrosive effects of the hydrolysis product, sec-butylamine
Both the target and source substances hydrolyse extremely rapidly to generate sec-butylamine. This substance is Classified in Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation) as Skin Corr. 1A. The source substance produces 3 moles of sec-butylamine per mole of parent substance (85% by weight). The target substance produces 2 moles of sec-butylamine per mole of parent substance (72% by weight). Therefore, the read-across from the source to the target substance can be considered conservative.
Based on the available data on the read across substance, 1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine (CAS 37697-65-7), 1,1-dimethyl-N,N'-bis(1-methylpropyl)silanediamine is classified as Corrosive to Skin Category 1B, 'H314; Causes severe skin burns and eye damage' according to Regulation (EC) No 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again