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Description of key information

In a Buehler skin sensitisation study conducted to OECD Test Guideline 406 and in compliance with GLP, N,N',N''-tricyclohexyl-1-methylsilanetriamine gave no evidence of sensitising potential in guinea pigs challenged at 1% in liquid paraffin following induction with 1% in the same vehicle.

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:
1988-08-06 to 1990-04-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Information regarding positive control group not included in the report.
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/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa-Credo, France
- Age at study initiation: young adults
- Weight at study initiation: 314 to 415 g
- Housing: housed by sex and in groups of 5-6 in polystyrene cages.
- Diet (e.g. ad libitum): complete pellet guinea-pig maintenance diet, ad libitum
- Water (e.g. ad libitum): filtered and softened mains drinking water, ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16.5 - 24
- Humidity (%): 24 - 66
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route:
epicutaneous, occlusive
Vehicle:
other: liquid paraffin
Concentration / amount:
Range finder: 5% and 1%

Test group:
Induction - 1 %
Challenge - 1 %
0.5 ml of the test article in 1% (W/W) solution in sterile Codex liquid paraffin.

Negative control group: 0.5 ml per animal of sterile Codex liquid paraffin.

Positive control group: not included in the study
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: liquid paraffin
Concentration / amount:
Range finder: 5% and 1%

Test group:
Induction - 1 %
Challenge - 1 %
0.5 ml of the test article in 1% (W/W) solution in sterile Codex liquid paraffin.

Negative control group: 0.5 ml per animal of sterile Codex liquid paraffin.

Positive control group: not included in the study
No. of animals per dose:
Treated group: 10 (+1) males, 10 (+1) females.
Control group: 10 males, 10 females
Details on study design:
RANGE FINDING TESTS: 5 % and 1 %

PRELIMINARY STUDY:
At the preliminary study 5 % and 1 % solution of the test material in sterile Codex liquid paraffin were tested. When 0.5 ml of 5 % solution was applied to the guinea-pig skin, noticeable erythema was observed in the 4 treated animals. At 1 % concentration, slight erythema was noted in 1 out of 4 animals, which had no pathological aspect. No other clinical changes were observed.

MAIN STUDY
A. INDUCTION EXPOSURE
The left lateral abdominal reagion was clipped and shaved. The test material was applied at days 1, 8 and 15 - 3 hours exposures. 0.5 ml per animal of sterile Codex liquid paraffin was applied to the control group of guinea-pigs and 0.5 ml per animal of the test material in 1.0 % (W/W) sterile Codex liquid paraffin was applied to the test group. The animals were not subject to treatment from days 15 to 29 (14-day period). The observations were at 24 and 48 hours post-application.

B. CHALLENGE EXPOSURE
The site of exposure was the right posterior abdominal region. The application was at day 29 for 6 hours. 0.5 ml per animal of the test article in 1.0 % sterile Codex liquid paraffin (posterior flank) and 0.5 ml per animal of vehicle (anterior flank). The test article was applied to clipped and shaved skin under occlusive patch. The observations were at 24 and 48 hours post-application.
Challenge controls:
0.5 ml per animal of sterile Codex liquid paraffin
Positive control substance(s):
no
Positive control results:
No positive group in the study.
Key result
Reading:
other: challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
One female was found dead on day 28 from the study period. Replaced by a female of the complementary group and treated the same way.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: challenge
Hours after challenge:
24
Group:
negative control
Dose level:
0.5 ml of sterile Codex liquid paraffin
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No clinical changes were evident.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
One female was found death on the day of the application. Grey hepatisation, splenomegalia and perforated ulcer were noted.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: challenge
Hours after challenge:
24
Group:
negative control
Dose level:
0.5 ml sterile Codex liquid paraffin
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
No clinical changes were evident.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
One female was found dead on day 28 from the study period. Replaced by a female of the complementary group and treated the same way.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: challenge
Hours after challenge:
48
Group:
negative control
Dose level:
0.5 ml sterile Codex paraffin
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No clinical changes were observed.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
One female was found death on the day of the application. Grey hepatisation, splenomegalia and perforated ulcer were noted.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: challenge
Hours after challenge:
48
Group:
negative control
Dose level:
0.5 sterile Codex liquid paraffin
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
No clinical changes were observed.
Remarks on result:
no indication of skin sensitisation
Reading:
other: not applicable
Group:
positive control
Dose level:
not applicable
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
other: not applicable

An increase in body weight was observed in all the animals of the control and test group.

Interpretation of results:
GHS criteria not met
Conclusions:
N,N',N''-Tricyclohexyl-1-methylsilanetriamine is found not sensitising to guinea-pig skin, reported in a reliable study conducted according to GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In the key study for skin irritation, semiocclusive application of undiluted test substance for three minutes to six male rabbits was found to result in erythema and edema with mean global scores (24 hours + 48 hours + 72 hours) of 3.44 for erythema and 1.17 for edema. The effects were not fully reversible within 14 days. Therefore, the concentration used in the challenge and induction phases was 1% in liquid paraffin. No evidence of delayed contact hypersensitivity was observed in any of the 20 test animals. Cutaneous abnormality was observed in 1 out of 20 test animals. It was concluded that the test substance was not sensitising under the conditions of the test.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data, N,N',N''-tricyclohexyl-1-methylsilanetriamine does not require classification for sensitisation according to Regulation (EC) No 1272/2008.

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