2,2,4-trimethyl-1-oxa-4-aza-2-silacyclohexane

Endpoint summary

Description of key information

- Skin sensitisation: No alerts for protein binding are found by 9 (out of nine) QSAR Toolbox 4.1 profilers.

- Skin sensitisation test, in 15 male guinea pigs, Induction: intradermal 1 x 0.05 mL and 9 x 0.1 mL of a 0.1 % solution, Challenge: one intradermal with 0.05 mL of a 0.1% solution, no signs for sensitisation, guideline study, non-GLP.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE: QSAR Toolbox 4.1

2. MODEL (incl. version number): Skin sensitisation / protein binding profiler of QSAR Toolbox 4.1

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL: CN1CCO[Si](C)(C)C1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
- Defined endpoint:
- Unambiguous algorithm:
- Defined domain of applicability:
- Appropriate measures of goodness-of-fit and robustness and predictivity:
- Mechanistic interpretation:

5. APPLICABILITY DOMAIN
see attached report

6. ADEQUACY OF THE RESULT
The model provides prediction of chemically-induced skin sensitization. The QSAR Toolbox 4.1 has nine profilers to predict skin sensitisation.
Skin sensitization is initiated by covalent binding of the target substance to skin proteins. The profilers of the QSAR Toolbox 4.1 consider if a
covalent binding of the target molecule and skin proteins is in principle possible, based on mechanistic or empiric reasons. If a covalent binding
is possible based on the structure of the target molecule and a known reaction mechanism an alert for protein binding (skin sensitization) is
reported.
No alerts for protein binding are found by 9 (out of nine) QSAR Toolbox 4.1 profilers.

Principles of method if other than guideline:

QSAR Toolbox 4.1 model.

Key result

Parameter:

other: QSAR

Remarks on result:

no indication of skin sensitisation

Other effects / acceptance of results:

No indication of skin sensitisation.

Interpretation of results:

GHS criteria not met

Conclusions:

No indication of skin sensitisation.

Executive summary:

No alerts for protein binding are found by 9 (out of nine) QSAR Toolbox 4.1 profilers.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

according to guideline

Guideline:

other: Intracutaneous injection with retest according to "APPRAISAL OF THE SAFETY OF CHEMICALS IN FOODS, DRUGS AND COSMETICS, Assoc. of Food and Drug Officials of the United States 1959"

GLP compliance:

no

Remarks:

study conducted prior to implementation of GLP

Type of study:

intracutaneous test

Justification for non-LLNA method:

A test conducted comparable to generally accepted scientific methods with an insufficient documentation is available, which provides data that indicate no sensitizing potential for the test substance. According to REACH Regulation the performance of new animal studies for the purpose of article 17/18 registrations is not mandatory when existing data are available, which were conducted before REACH Regulation entered into force. For this reason and for reasons of animal welfare no additional LLNA was conducted.

Species:

guinea pig

Strain:

Pirbright-Hartley

Remarks:

white

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Kirchborchen, Paderborn
- Weight at study initiation: 300-500 gr
- Diet (e.g. ad libitum): commercial rabbit pellet ration supplemented with greens (kale or lettuce)

Route:

intradermal

Vehicle:

physiological saline

Concentration / amount:

1x 0.05 mL and 9x 0.1 mL of 0.1 % solution

Day(s)/duration:

1 injection per day or 3 per week

Adequacy of induction:

not specified

No.:

#1

Route:

intradermal

Vehicle:

physiological saline

Concentration / amount:

0.05 mL from a 0.1 % solution applied 2 weeks after the last injection from induction

Day(s)/duration:

24h

Adequacy of challenge:

not specified

No. of animals per dose:

15 males

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9
- Exposure period: 10-22 days
- Frequency of applications: 1 per day or 3 per week
- Concentrations: 0.1% (1 x 0.05 ml, 8 x 0.1 ml)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 weeks after 10th injection
- Concentrations: 0.1% (0.1 ml)
- Evaluation (hr after challenge): 24 hours

Positive control substance(s):

not specified

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

No. with + reactions:

0

Total no. in group:

15

Remarks on result:

no indication of skin sensitisation

Table 1: Results of the skin sensitisation test

Animal No.	Pre-injection		Retest
	redness score	swelling Ø cm	redness score	swelling Ø cm
927	1	1.5	1	1
929	1	1.1	1	0.5
930	1	0.7	1	0.5
931	1	0.8	1	0.6
932	1	1.0	1	0.4
933	1	0.9	1	0.4
934	1	1.0	1	0.7
935	1	1.1	1	0.5
936	1	1.1	1	0.5
937	1	1.0	1	0.5
938	1	1.0	1	0.5
939	1-2	1.0	1	0.5
940	1	1.0	1	0.5
941	1	1.0	1	0.5
942	1	1.0	1	0.6
Average	1.0	1.0	1.0	0.6

Interpretation of results:

study cannot be used for classification

Conclusions:

In this study the test substance is not a dermal sensitiser.
In a dermal sensitization study according to “APPRAISAL OF THE SAFETY OF CHEMICALS IN FOODS, DRUGS AND COSMETICS, Assoc. of Food and Drug Officials of the United States 1959” with the test substance diluted in isotonic saline, 15 white male guinea pigs were tested.

Executive summary:

In a dermal sensitization study according to “APPRAISAL OF THE SAFETY OF CHEMICALS IN FOODS, DRUGS AND COSMETICS, Assoc. of Food and Drug Officials of the United States 1959” with the test substance diluted in isotonic saline, 15 white male guinea pigs were tested.

 

After dermal induction with 0.1 % solution of test substance, very slight to slight redness was observed in only one animal (#939). All other animals showed only very slight redness during induction. The average swelling was 1.0 Ø cm.

Challenge treatment was performed with the same concentration of 0.1 %. Here, all animals showed only very slight redness. The average swelling was 0.6 Ø cm

 

The test substance is not a dermal sensitiser in this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data, the test substance does not need to be classified for skin sensitisation according to regulation (EC) 1272/2008 (CLP). Data on respiratory sensitisation are not available.