Trimethylsilane

Endpoint summary

Description of key information

No sensitisation data are available for the registered substance. Data are available for the structural analogue, tetramethylsilane (CAS 75-76-3), from a skin sensitisation study, conducted in accordance with OECD 406 (Buehler method) and in compliance with GLP. Tetramethylsilane was not sensitising in the guinea pig (Hüls, 1998). No skin reactions were observed at challenge.

Information on tetramethylsilane is included for completeness only.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18.11.1997 to 25.06.1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

See endpoint summary for justification of read across

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

Buehler test

Justification for non-LLNA method:

An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Buehler method for a relevant read-across substance. Furthermore, the LLNA test method is not considered to be suitable for substances that contain silicon. Please refer to the attached document for further details.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmnH
- Age at study initiation: 'young'
- Weight at study initiation: <500 g
- Housing: Maximum five animals in conventional Type IV Makrolon cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: Preliminary study: from: 18.11.1997 to 21.11.1997. Main study: from: 26.05.1998 to 25.06.1998

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Concentration / amount:

Induction and challenge phases: undiluted test substance.

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Concentration / amount:

Induction and challenge phases: undiluted test substance.

No. of animals per dose:

20 test animals, 10 control.

Details on study design:

RANGE FINDING TESTS: 0.3cm3 of each of the test substance concentrations 5, 25, 50% (in corn oil) and undiluted test substance were applied to patches of surgical gauze. These were placed on the clipped flanks of each of three animals. The patches were covered with occlusive plaster and left in place for six hours. Each animal recieved two patches on each flank. After removal of the patch, residual test substance was cleared away using corn oil The dermal reactions were assessed 30 and 54 hours after the start of treatment. In the 4th week of the test, three guinea-pigs,kept under the same conditions, but without treatment, were used to re-determine the maximum non-irritant concentration for the challenge treatment. This additional determination was conducted because it was suspected that the sensitivity of the skin changed as the weight of the animals increased. In this test, the concentration administered and the experimental conditions were the same as those of the preliminary test.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three
- Exposure period: Six hours
- Test groups: Undiluted test substance
- Control group: Corn oil only
- Site: Left flank
- Frequency of applications: Weekly
- Duration: 28 days from first induction to challenge exposure
- Concentrations: Undiluted test substance


B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: Day 28
- Exposure period: Six hours
- Test groups: Undiluted test substance
- Control group: Corn oil only
- Site: Right flank
- Concentrations: Undiluted test substance
- Evaluation (hr after challenge): 24 and 48 hours after removal of patches.

Challenge controls:

Corn oil

Positive control substance(s):

yes

Remarks:

α-cinnamaldehyde. The most recent reliability check was performed in November/December 1997

Positive control results:

No positive control.

Key result

Reading:

1st reading

Hours after challenge:

30

Group:

test chemical

Dose level:

undiluted test substance

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No significant treatment-related observations.

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

54

Group:

test chemical

Dose level:

undiluted test substance

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No significant treatment-related observations.

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

undiluted corn oil

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No significant treatment-related observations.

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

54

Group:

negative control

Dose level:

undiluted corn oil

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No significant treatment-related observations.

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

In a well conducted skin sensitisation study conducted to OECD 406 (Buehler method) and GLP (reliability score 1) tetramethylsilane was not sensitising to the skin of guinea-pigs.

Executive summary:

In a well conducted skin sensitisation study conducted to OECD 406 (Buehler method) and GLP (reliability score 1) tetramethylsilane was not sensitising to the skin of guinea-pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There are no measured data available to assess the skin sensitisation potential of trimethylsilane, and testing is not technically feasible because the substance is a gas. Therefore data for the structural analogue substance tetramethylsilane (CAS 75-76-3) has been used to assess its skin sensitisation potential. Tetramethylsilane was not sensitising (Hüls, 1998) when tested in the guinea-pig Buehler assay (OECD 406).

Information on tetramethylsilane is included for completeness only.

Read-across justification

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 the relevant properties are structural similarity as well as physical-chemical properties in the same range. In the following paragraphs the proposed read-across from triethylsilane to trimethylsilane is discussed. A report considering read across for all endpoints is attached in Section 13.

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. Trimethylsilane has a half-life in water of days and tetramethylsilane is hydrolytically stable, so reaction products do not need to be considered for the human health hazard assessment of these substances.

(a) Structural similarity

The registration and read-across substances are structurally similar and are members of an analogue group of alkylsilanes. The substances contain a silicon atom to which is attached three or four alkyl (methyl/ethyl) groups. For the registered substance there are three methyl groups, for tetramethylsilane there are four methyl group. The registered substance also has an Si-H group. There is no evidence that the Si-H group is sensitising.

(b) Similar physicochemical characteristics

The key physicochemical parameters are summarised below.

-	Target (registration substance)	Source (read-across substance )
CAS number	993-07-7	75-76-3
EC number	213-603-0	200-899-1
Chemical Name	Trimethylsilane	Tetramethylsilane
Molecular weight  (gmol^-1)	74.20	88.23
log Kow	2.2 at 20°C	2.7 at 20°C
Water solubility at 20°C	Estimated to be 1400 mg/l at 20°C, in practice the concentration is not expected to be achieved due to very high volatility of the substance	19.6 mg/l at 25°C
Vapour pressure	Not applicable (substance is a gas), expected to be greater than 1.0E+05 Pa	79 000 Pa at 20°C

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on a reliable in vivo study on tetramethylsilane, trimethylsilane is not classified as a skin sensitiser according to Regulation (EC) No 1272/2008.

There are no data to suggest that trimethylsilane is a respiratory sensitiser.

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 sensitisation, the relevant properties are physicochemical properties and structural similarity. In the following paragraphs the proposed read-across from tetramethylsilane to trimethylsilane is discussed. A report considering read across for all endpoints is attached in Section 13.

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 in the context of toxicological testing (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.

Read-across justification

(a)  The registration and read-across substances are structurally similar and are members of an analogue group of alkylsilanes. Both contain a silicon atom to which is attached three or four methyl groups. For the registered substance there are three methyl groups, for the read-across substance there are four. The registered substance also has an Si-H group. There is no evidence that the Si-H group is sensitising. It is therefore not considered likely that replacing Si-H with Si-CH₃would be likely to confer additional skin sensitising properties on the registration substance; however, this cannot be demonstrated experimentally due to the physical state of trimethylsilane at ambient temperature and pressure.

(b)  The key physicochemical parameters are summarised below.

Table: Key physicochemical parameters

	Target (registration substance)	Source substance (read-across)
CAS number	000993-07-7	000075-76-3
EC number	213-603-0	200-899-1
Chemical Name	Trimethylsilane	Tetramethylsilane
Molecular weight (gmol-1)	74.20	88.23
log Kow (parent)	2.2	2.7
Water solubility (parent)	Estimated to be 1400 mg/l (QSAR), limited by condensation reactions following abiotic reaction to silanol	19.6 mg/l
Vapour pressure (parent)	Not applicable (substance is a gas)	79000 Pa at 20°C