Cyclohexyldimethoxymethylsilane

Endpoint summary

Description of key information

In the key study performed in accordance with OECD Test Guideline 406 (guinea pig maximisation test) and in compliance with GLP, with no deviations, cyclohexyl(dimethoxy)methylsilane is not considered to be a skin sensitiser (Huntingdon Research Centre Ltd, 1989b)

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:

14.03.1989 to 08.04.1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method. 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: D. Hall, Newchurch, England
- Age at study initiation: No data
- Weight at study initiation: 330-387 g
- Housing: Suspended cages with wire mesh floors.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Approximately 21
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14.03.1989 To: 08.04.1989

Route:

intradermal and epicutaneous

Vehicle:

other: Alembicol D

Concentration / amount:

Intradermal induction: 0.1 ml 50:50 FCA/water, 0.1 ml of 20% v/v test substance in Alembicol D and in 50:50 mixture of FCA and Alembicol D
Topical induction: 100%

Day(s)/duration:

Day 1 for intradermal induction, Day 8 for epidermal induction/48h of application for the dressing

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: Alembicol D

Concentration / amount:

Topical challenge: 0.2 ml of the test item in 80 and 40% v/v in Alembicol D

Day(s)/duration:

Day 22/24h of application

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

20 test females
10 control females

Details on study design:

RANGE FINDING TESTS: The intradermal and topical irritancy of a range of dilutions of Silan PSX 854 was investigated to identify (a) irritant test substance concentrations suitable for the induction phase of the main study and (b) non-irritant concentration by the topical route of administration for the challenge phase. Based on the results the following concentrations were selected: Induction intradermal injection: 20% v/v in Alembicol D, and induction topical application: as supplied (undiluted); for the challenge phase 80% and 40% v/v in Alembicol D.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: One intradermal injection and one topical application
- Exposure period: Topical application for 48 hours
- Test groups: Intradermal injection: (1) Freund's complete adjuvant (FCA) diluted with an equal volume of water for irrigation; (2) Silan PSX 854, 20%; (3) Silan PSX 854, 20% in 50:50 mixture of FCA and Alembicol. Topical application: Patch saturated with occlusive dressing applied for 48 hours.
- Control group: Treated similarly to test animals with the exception that the test substance was omitted from the intradermal injections and topical application.
- Site: Dorsal skin on scapular region
- Frequency of applications: One week apart

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: Two weeks after induction period
- Exposure period: 24 hours
- Test groups: Patch saturated with approximately 0.2 ml test substance applied to all animals
- Control group: Treated the same as the test group
- Site: Left flank
- Concentrations: 80 and 40 % v/v in Alembicol D
- Evaluation (hr after challenge): 24, 48 and 72 hours after patch removal

Challenge controls:

A positive control was not included in this study, but historical controls for the laboratory were presented for formalin.

Positive control substance(s):

yes

Positive control results:

Historical controls confirmed sensitivity of the laboratory that conducted the test.

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

40 or 80% tested

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

One animal died, three animals gave an inconclusive result. Even if these three animals are assumed to be positive there were fewer than 30% of animals affected, which means that the criteria for a positive result were not met.

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

72

Group:

negative control

Dose level:

80 or 40%

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

localised dermal reaction (restricted to a small area of the challenge site)

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Group:

positive control

Remarks on result:

other: positive control was not included in this study but sensitivity of the strain is checked periodically with formalin, a known sensitiser

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In a guinea pig maximisation study conducted according to OECD Test Guideline 406 and in compliance with GLP (reliability score 1), cyclohexyldimethoxymethylsilane did not induce skin sensitisation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There are two reliable skin sensitisation studies for cyclohexyl(dimethoxy)methylsilane. The key study gave a clear negative result. In the second study an apparent positive result was concluded. However, re-evaluation of the results revealed that the positive results were based on Grade 1 erythema after 24 hours when the undiluted substance was tested. Although this erythema appeared to be more pronounced than in the control group, the preliminary study showed Grade 2 reactions (after 1 hour, resolved by 24 hours) for the neat test substance. Therefore the low irritancy observed in this study is not consistent with the known irritating properties of this substance, which is a Category 2 skin irritant. Therefore expert evaluation of the available data concluded that the substance should not be considered a skin sensitiser

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the key in vivo skin sensitisation study, cyclohexyl(dimethoxy)methylsilane does not meet the criteria for classification as a skin sensitiser according to Regulation (EC) No 1272/2008. There are no data to suggest that classification as a respiratory sensitiser is required.