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Administrative data

Description of key information

No measured repeated dose toxicity data are available for the registration substance therefore this endpoint is filled by read-across of data on structural analogues.

In a rat inhalation 28-day repeat dose study (Dow Corning Corporation, 2005) conducted by whole-body exposure of tetramethylsilane (CAS 75 -76 -3), the No-Observed-Adverse-Effect-Concentration (NOAEC) was considered to be at least 24000 mg/m³ (5000 ppm), the highest concentration tested.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
24 000 mg/m³
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No measured repeated dose toxicity data are available for the registration substance therefore this endpoint is filled by read-across of data on structural analogues.

In the key repeated dose inhalation study conducted according to OECD 422 study and in compliance with GLP (Dow Corning Corporation, 2005), whole body exposure of rats to tetramethylsilane for 28 days did not result in any adverse effects attributable to treatment. Therefore the NOAEC for systemic toxicity of the adult rats was considered to be at least 5000 ppm (the highest concentration tested), which is equivalent to approximately 24000 mg/m³.

Supporting information is available from a repeat-dose inhalation administration study (Mitsubishi, 2001). Whole body exposure of trimethylsilane to rats for 28 consecutive days did not result in any findings attributable to treatment. The No-Observed-Adverse-Effect-Concentration (NOAEC) was therefore considered to be 4730 mg/m³ (4.73 mg/L), the highest concentration tested.

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 repeated dose toxicity the relevant properties are structural similarity, hydrolysis stability and the physical-chemical parameters in the same range. In the following paragraphs the proposed read-across from trimethylsilane and tetramethylsilane to triethylsilane is evaluated point by point.

Read-across from trimethylsilane and tetramethylsilane for repeated dose toxicity by the inhalation route

Read-across hypothesis

The hypothesis is that source and target substances have similar toxicological properties because they are structurally similar and have similar physicochemical properties.

The substances are hydrolytically stable (triethylsilane, trimethylsilane and tetramethylsilane have half-lives in water of days) so reaction products do not need to be considered for the human health hazard assessment of these substances.

Triethylsilane reacts slowly in water with measured hydrolysis half-lives of 218 hours at pH 4 and 25°C, 377 hours at pH 7 and 20°C and 56.8 hours at pH 9 and 20°C in accordance with OECD 111. The products of hydrolysis are triethylsilanol and hydrogen.

Trimethylsilane reacts slowly in water, with a measured hydrolysis half-life of about 3 days at 24.7°C. The reaction products are trimethylsilanol and hydrogen.

Tetramethylsilane has no structural groups that make it susceptible to hydrolysis, so it is stable in water.

Read-across justification

(a) Purity and impurities

In the studies with the read-across substance tetramethylsilane, the test substance is >98% pure; impurities are not specified. In the studies with the read-across substance trimethylsilane, the test substance is 99.9% pure.

The Substance Identity Profile for the target substance, triethylsilane, indicates that the substance is >98% and may contain a chloro(alkyl)silane impurity. The data available for this impurity and its hydrolysis products indicate that they are not SVHC and will not impact the classification and labelling of the target substance.

(b) Structural similarity

The target and source substances are structurally similar and are members of an analogue group of alkylsilanes. They are structurally similar because they are all alkylsilanes with three or four short alkyl chains bound to silicon. The general structural formula is R’SiR3, where R’ is -CH3or -H and R is -CH2CH3or CH3.

The source substance is triethylsilane and has three ethyl groups and one hydrogen bound to silicon (R is -CH2CH3and R’ is -H).

The supporting read-across substance, trimethylsilane, is structurally similar because it also has three short-chain alkyl groups and one hydrogen bound to silicon. The difference is that the alkyl groups are methyl instead of ethyl (R is -CH3and R’ is -H).

The key read-across substance, tetramethylsilane, has four methyl groups bound to silicon (R and R’ are -CH3). The differences between this substance and the target substance are that the ethyl groups in the target substance are replaced by methyl groups and the -H group in the target substance is also replaced by a methyl group.

(c) Similar physicochemical characteristics

The key physicochemical parameters are summarised below.

The three substances all have low molecular weight (74-116), moderate log Kow (2.2-3.6) and fairly low water solubility (2-59 mg/l). The vapour pressures are moderately high to high (2700 - >100000 Pa at 20°C).

They do not hydrolyse rapidly under conditions relevant for inhalation exposure. The key read-across substance is the least reactive (no hydrolysable groups) and the supporting read-across substance trimethylsilane is the most reactive (half-life at pH 7 and 37°C h = approximately 1 day). The target substance is in between (half-life at pH 7 and 37°C h = approximately 6 days).

Key physicochemical parameters

 -

Target (registration substance)

Source (read-across substance

Source (read-across substance

CAS number

617-86-7

993-07-7

75-76-3

EC number

210-535-3

213-603-0

200-899-1

Chemical Name

Triethylsilane

Trimethylsilane

Tetramethylsilane

Molecular weight
 (gmol-1)

116.28

74.20

88.23

log Kow

3.6 (QSAR)

2.2 (QSAR)

2.7 (QSAR)

Water solubility at 20°C

2 mg/l (QSAR)

59 mg/l (QSAR)

(but may not be achieved due to the high volatility of the substance

19.6 mg/l (measured)

Vapour pressure at 20°C

2700 Pa (QSAR)

Not applicable (substance is a gas; expected to be >1E+05 Pa at 20°C)

79 000 Pa (measured)

 Hydrolysis half-life at pH 7 and 37°C  150 h  ca. 1 day  No hydrolysable groups

(d) QSAR Toolbox Profiles

The target and source substances have been profiled using the OECD QSAR Toolbox. The profiles of the three substances are consistent. The substances:

·        Are classified 'High (class III)' by the 'Toxic hazard classification by Cramer' profilers.Toxic hazard classification by Cramer profilers (original and extension) are built on basis of the original paper of Cramer. (G.M. Cramer and R.A. Ford Estimation of toxic hazard - a decision tree approach. Food and Cosmetics Toxicology, Volume 16, Issue 6, December 1978, Page 255-276.) Categorization rules classify chemicals into different levels of toxicological concern (when administered orally) are organized in a tree-like scheme. The decision tree comprises 33 structural rules (and 5 additional rules for the extension profiler) and places compounds in one of the three classes: Low (Class I), Intermediate (Class II) and High (Class III). The profiler places all silicon compounds in the High concern category because it does not have enough information about these compounds to place them in another category. The alert therefore tells us only that silicon compounds may be toxic and information is required about their toxicological profile; it is not a specific alert indicating a known problem or mechanism of toxic action.

·        Are 'Not known precedent reproductive and developmental toxic potential' in the DART (Developmental and Reproductive Toxicity) scheme profiler.

·        Are 'Not Categorized' in the Repeated Dose (HESS) profiler.

·        Are ‘No Alert Found’ in rtER Expert System ver.1 - USEPA. This identifies potential estrogen receptor binders and is therefore relevant for reproductive and developmental toxicity.

·        Are ‘Non-binders’ in Estrogen Receptor Binding. This is relevant for reproductive and developmental toxicity.

·        Are ‘Not possible to classify according to these rules’ in Retinoic Acid Receptor Binding. Retinoic acid receptor (RAR) binding is a molecular initiating event associated with developmental toxicity.

·        Have no alerts for DNA binding, protein binding or genetic toxicity.

(e) Toxicokinetics

No data are available for the toxicokinetics of any of the substances, therefore the toxicokinetic behaviour has been predicted. As the substances have similar structures and physicochemical properties, their toxicokinetic behaviour is predicted to be similar.

(f) Similar toxicity

The available toxicity data for the target and two source substances, shows that the three substances have a profile of low acute toxicity, no skin or eye irritation and negative genetic toxicity. Repeated dose inhalation studies gave NOAECs of at least the highest dose tested (no adverse effects) for the two source substances. Tetramethylsilane was negative in a skin sensitisation test.

   Triethylsilane (target substance) Trimethylsilane (source substance)

Tetramethylsilane

(source substance)

 CAS number  617-86-7  993-07-7  75-76-3
 Acute oral LD50  >2000 mg/kg bw -  >2000 mg/kg bw
 Acute inhalation LD50  -  >5400 mg/m3  >21300 mg/m3
 Acute dermal LD50  -  -  >2000 mg/kg bw
 Skin irritation  Not irritating  Not irritating
 Eye irritation  Not irritating  -  Not irritating
 Skin sensitisation  -  -  Not sensitising
 Genetic toxicity  Negative  Negative  Negative
 Repeated dose toxicity (NOAEC)  -  >4730 mg/m3  >24000 mg/m3
 Toxicity to reproduction/development (NOAEC)  -  -  >24000 mg/m3

Justification for classification or non-classification

Based on the available data on tetramethylsilane, triethylsilane does not require classification for repeated dose toxicity according to Regulation (EC) No 1272/2008.