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Description of key information

There are no skin sensitisation data available on the registered substance 1,1,1,3,3,3-hexamethyldisilazane (CAS 999-97-3, EC 213-668-5), therefore read-across from an analogue substance N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine (CAS 7691-02-3) has been used.

The key study for skin sensitisation, conducted according to OECD Test Guideline 406 (Buehler test) and in compliance with GLP, concluded that N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine (CAS 7691-02-3) was not sensitising to skin (Harlan Laboratories 2012).

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:
OECD 406 (Buehler test) commissioned
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
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 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:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan laboratories, The Netherlands
- Age at study initiation: 4-6 weeks
- Weight at study initiation: test group: 373.1-408 g
- Housing: in groups of up to ten in stainless steel cages with standard softwood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
other: diglyme, 75% w/w mixture
Concentration / amount:
INDUCTION: 25% w/w
CHALLENGE: 0.1% w/w and 0.5% w/w
Route:
epicutaneous, occlusive
Vehicle:
other: diglyme, 75% w/w mixture
Concentration / amount:
INDUCTION: 25% w/w
CHALLENGE: 0.1% w/w and 0.5% w/w
No. of animals per dose:
Pretests: 3
Controls: 10
Test group: 20
Details on study design:
RANGE FINDING TESTS: Pretest 1 was performed during the acclimatization of the main study animals. The test item concentrations were selected during the preliminary solubility testing. The test item was formulated in the vehicle. Pretests 2 and 3 were performed during the induction period in order to find the highest non-irritant test item concentration for the challenge.

MAIN STUDY
A. INDUCTION EXPOSURE

The induction of the main test was performed within three weeks. A total of three inductions (one per week) was performed. The test item concentration used for the induction was determined based on the results of pretest 1. A test item concentration of 25% (w/w) in diglyme was well tolerated systemically and caused mild-to-moderate skin irritation.

The application was performed at the same shoulder of the animals in the first and in the second week of the induction period. As crusts were observed after the second induction in the test group, a naive application site on the right shoulder was used for the third induction for both test and control group. After the last induction exposure, the animals were left untreated for approximately 2 weeks before the challenge.


B. CHALLENGE EXPOSURE

The challenge was performed ca. 2 weeks after the last induction. The test item concentration used for the challenge was determined based on the results of the pretests. All concentrations higher than 0.5% (w/w) tested in the pretests produced in signs of skin irritation. Test item concentrations of 0.5% (w/w) and 0.1% (w/w) in diglyme were well tolerated systemically and 0.5% (w/w) in diglyme was the highest non-irritant concentration.
Challenge controls:
No skin reactions were observed.
Positive control substance(s):
yes
Remarks:
alpha-hexylcinnamaldehyde
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Vehicle (diglyme, 75% w/w mixture)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Vehicle (diglyme, 75% w/w mixture)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Vehicle (diglyme, 75% w/w mixture)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Vehicle (diglyme, 75% w/w mixture)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5% test item in diglyme
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5% test item in diglyme
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.5% test item in diglyme
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5% test item in diglyme
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1% test item in diglyme
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1% test item in diglyme
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.1% test item in diglyme
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.1% test item in diglyme
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
alpha-hexylcinnamaldehyde
Remarks on result:
positive indication of skin sensitisation
Remarks:
>15 % of the animals got dermatitis
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
alpha-hexylcinnamaldehyde
Remarks on result:
positive indication of skin sensitisation
Remarks:
>15 % of the animals got dermatitis
Interpretation of results:
GHS criteria not met
Conclusions:
Based on a non-adjuvant sensitisation test in guinea pigs conducted according to OECD Test Guideline 406 and in compliance with GLP, the test item N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylaminen (CAS 7691 -02 -3) was found not sensitising to guinea-pig skin.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There are no skin sensitisation data available on the registered substance 1,1,1,3,3,3-hexamethyldisilazane (CAS 999-97-3, EC 213-668-5), therefore read-across from an analogue substance N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine (CAS 7691 -02 -3) has been used. Please refer to the RAAF report attached in Section 13 for more details about the analogue approach to address skin sensitisation of 1,1,1,3,3,3-hexamethyldisilazane (CAS 999-97-3, EC 213-668-5) by reading across from N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine (CAS 7691-02-3).

In the key skin sensitisation study, conducted according to OECD Test Guideline 406 and in compliance with GLP, twenty males Albino Dunkin Hartley guinea pigs of the test group were treated topically with 25% (weight/weight) test item in diglyme once a week for a 3-week induction phase. Two weeks after the last induction, the animals were challenged with 0.5% and 0.1% (weight/weight) test item in diglyme. The ten animals of the control group were treated with diglyme during the induction. The animals were challenged with 0.5% and 0.1% (weight/weight) test item in diglyme. At induction, skin reactions (discrete or patchy erythema) were observed in all animals of the test group after treatment with 25% test item in diglyme. No skin reactions were observed in the control group after treatment with the vehicle. At challenge, no skin reactions were observed in any of the control and test animals after the challenge with the highest tested non-irritating concentration of 0.5% (weight/weight) test item in diglyme or with 0.1% (weight/weight) test item in diglyme (Harlan Laboratories, 2012).


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data from the analogous substance N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine, 1,1,1,3,3,3-hexamethyldisilazane (CAS 999-97-3, EC 213-668-5) does not require classification for skin sensitisation according to Regulation (EC) No 1272/2008.