Registration Dossier

Administrative data

Description of key information

Skin sensitisation (weight of evidence based on read-across):
CAS 23432-64-6 (OECD 406, GPMT): not sensitising
CAS 23432-65-7 (OECD 406, GPMT): not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
weight of evidence
Justification for type of information:
refer to analogue justification document provided in IUCLID section 13
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Positive control results:
The positive control substance (15% mercaptobenzothiazole in Vaseline) induced positive reactions in 8/10 animals (80%), thus meeting the reliability criteria for the GPMT test (≥ 15% positive response). Positive control substances are used periodically as a reliability check (last check before study May 2013) and not during the study itself.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; challenge: 100%
No. with + reactions:
0
Total no. in group:
5
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%; challenge: 100%
No. with + reactions:
0
Total no. in group:
5
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 5% or 10%; challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 5% or 10%; challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Induction: 2%; challenge: 15%
No. with + reactions:
8
Total no. in group:
10
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In a GPMT according to OECD guideline 406 and in compliance with GLP, two source substances methyl-N-[(trimethoxysilyl)methyl]carbamate (CAS 23432-64-6) and methyl-N-{[dimethoxy(methyl)silyl]methyl}carbamate (CAS 23432-65-7) were not sensitising. Induction (intradermal: 10 and 5%, respectively; topical: 100%) and challenge (100%) with the source substances revealed no skin reactions in any of the 10 animals. Furthermore no skin reactions were observed in the negative controls (induction with corn oil, topical challenge with 100% test item). In conclusion, the source substances are not considered to have skin sensitising potential. As explained in the analogue justification, the differences between the target and the source substances are unlikely to lead to differences in the skin sensitising potential.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

For assessment of skin sensitizing properties of methyl-N-[3-(trimethoxysilyl)propyl]carbamate (CAS 23432-62-4) a weight of evidence approach was applied using the structural analogues, methyl-N-[(trimethoxysilyl)methyl]carbamate (CAS 23432-64-6) and methyl-N-{[dimethoxy(methyl)silyl]methyl}carbamate (CAS 23432-65-7). For more detail, refer to analogue justification document provided in IUCLID section 13.

 

One guinea pig maximisation study with methyl-N-[(trimethoxysilyl)methyl]carbamate (CAS 23432-64-6), conducted in compliance with GLP and according to OECD 406 is available (BSL Bioservice, 2003c). Groups of 5 (control) and 10 female guinea pigs were dosed with multiple intradermal injections (10% test item in corn oil/FCA, while the control group received only the vehicle) on day 0 followed by a topical application on day 7 (100% test item; control group: vehicle). The topical induction consisted of a 48 hour occluded dermal exposure to 0.5 ml of the undiluted test substance. At day 20 a challenge dosing for detection of sensitisation was performed. For challenge dosing, an essentially non-irritating concentration (100%) of the test material was applied under occlusion for 24 hours. Seven animals showed erythema grade 1 at 24 h (Induction first stage). No signs of irritation were observed after the topical application (Induction second stage). No signs of irritation and no signs of general toxicity were observed after challenge. Body weights were comparable within the test and control groups and the historical controls. The number of positive sensitization reactions was 0/5 and 0/10 in the control and test group, respectively. The positive control (15% mercaptobenzothiazole in Vaseline), performed periodically in the laboratory, induced positive reactions in 8/10 animals (80%), thus meeting the reliability criteria for the GPMT test (≥ 15% positive response). In conclusion, methyl-N-[(trimethoxysilyl)methyl]carbamate (CAS 23432-64-6) was not sensitising to skin under the test conditions applied.

 

One further guinea pig maximisation study with methyl-N-{[dimethoxy(methyl)silyl]methyl}carbamate (CAS 23432-65-7), conducted in compliance with GLP and according to OECD 406 is available (BSL Bioservice, 2004a). Groups of 5 (control) and 10 female guinea pigs were dosed with multiple intradermal injections (5% test item in corn oil/FCA, while the control group received only the vehicle) on day 0 followed by a topical application on day 7 (100% test item; control group: vehicle). The topical induction consisted of a 48 hour occluded dermal exposure to 0.5 ml of the undiluted test substance. At day 20 a challenge dosing for detection of sensitisation was performed. For challenge dosing, an essentially non-irritating concentration (100%) of the test material was applied under occlusion for 24 hours.Three animals showed erythema grade 1 at 24 h at the injection position 1. 48 h post-dose erythema grade 1 were observed in 4 animals and necrosis (0.1-0.2 cm diameter; injection position 2) was observed in 6 animals. Erythema grade 1 were observed in 8/10 animals after injection in position 3. No other signs of irritation were observed after the intradermal application (induction first stage). No signs of irritation were observed after the topical application (induction second stage). No signs of irritation and no signs of general toxicity were observed after challenge. Body weights were comparable within the test and control groups and the historical controls. The number of positive sensitization reactions was 0/5 and 0/10 in the control and test group, respectively. The positive control (15% mercaptobenzothiazole in Vaseline), performed periodically in the laboratory, induced positive reactions in 8/10 animals (80%), thus meeting the reliability criteria for the GPMT test (≥ 15% positive response). In conclusion, methyl-N-{[dimethoxy(methyl)silyl]methyl}carbamate (CAS 23432-65-7) was not sensitising to skin under the test conditions applied.

 

In conclusion, based on the available data from 2 structural analogues it was concluded that methyl-N-[3-(trimethoxysilyl)propyl]carbamate (CAS 23432-62-4) is not sensitizing to skin.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Reliable data from structural analogues on skin sensitisation indicates that methyl-N-[3 (trimethoxysilyl)propyl]carbamate do not meet the criteria for classification according to Regulation (EC) 1272/2008, and the available data are therefore conclusive but not sufficient for classification.