Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The key study for the sensitisation of triethoxy(3-thiocyanatopropyl)silane (CAS No. 34708-08-2, EC No. 252-161-3) found the test material to be not sensitising in a study conducted according OECD Test Guideline 406 (non-LLNA, Buehler test) and in compliance with GLP (Harlan Laboratories Ltd., 2012, reliability score 1). An LLNA study was not performed because the test method is not considered to be suitable for substances that contain silicon.

 

As per the ECHA Endpoint Specific guidance (Chapter R.7a, version 6, July 2017) existing data of good quality that were generated before 10 May 2017, or for which the study was initiated before 10 May 2017, can be used to address the skin sensitisation endpoint. The OECD 406 Test Guideline study for triethoxy(3-thiocyanatopropyl)silane was conducted in 2012 and therefore additional testing for this endpoint is not required.

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:
2012
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 the 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 to 6 weeks
- Weight at study initiation: 302.4 - 411.7g
- Housing: in groups of up to ten in stainless steel cages with standard softwood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 or 7 days

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
Concentration / amount:
Undiluted test substance (induction).
15% and 5% in diglyme (first challenge).
Route:
epicutaneous, occlusive
Vehicle:
other: diglyme
Concentration / amount:
Undiluted test substance (induction).
15% and 5% in diglyme (first challenge).
No. of animals per dose:
20 for test group, 10 for control group
Details on study design:
Twenty Albino Dunkin Hartley guinea pigs (males) of the test group were treated topically with the undiluted test item once a week for a 3-week induction phase. Two weeks after the last induction, the animals were challenged with 15% and 5% (weight/weight) test item in diglyme.

The ten animals of the control group 1 were not treated during the induction. The animals were challenged with 15% (the highest non-irritating concentration) and 5% (weight/weight) test item in diglyme.

Due to ambiguous results in the first challenge, a second challenge was conducted using the same test animals and ten additional naive control animals (control groups 2 and 3). The same concentrations of 15% and 5% of the test item in diglyme were used.
Challenge controls:
Refer to table.
Positive control substance(s):
yes
Remarks:
2-mercapto-benzothiazole or alpha-hexylcinnamaldehyde
Positive control results:
Positive controls were assessed at the laboratory at least twice a year. During 2011 (prior to this experiment), the result from the positive control study had resulted in allergic contact dermatitis in >15% of the test animals when testing alpha-hexylcinnamaldehyde as a skin sensitiser. Alpha-hexylcinnamaldehyde is recommended to use by the Commission Regulation (EC) No 440/2008, B.6 and OECD 406 since it causes moderate skin sensitisation in guinea pigs. No further details are provided.
Key result
Reading:
other: first challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
15%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: first challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
15%
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: first challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: first challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: first challenge
Hours after challenge:
24
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: first challenge
Hours after challenge:
48
Group:
negative control
Dose level:
5%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: second challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
15%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: second challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
15%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: second challenege
Hours after challenge:
24
Group:
negative control
Dose level:
15%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: second challenge
Hours after challenge:
48
Group:
negative control
Dose level:
15%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: second challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: second challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: second challenge
Hours after challenge:
24
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: second challenge
Hours after challenge:
48
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Group:
positive control
Dose level:
alpha-hexylcinnamaldehyde
Remarks on result:
other: The results from the positive control study (report not available) confirm alpha-hexylcinnamaldehyde as skin sensitizer, as it produced allergic contact dermatitis in >15% of the test animals.

Positive controls:

Positive controls were assessed at the laboratory at least twice a year. During 2011 (prior to this experiment), the result from the positive control study had resulted in allergic contact dermatitis in >15% of the test animals when testing alpha-hexylcinnamaldehyde as a skin sensitiser. Alpha-hexylcinnamaldehyde is recommended to use by the Commission Regulation (EC) No 440/2008, B.6 and OECD 406 since it causes moderate skin sensitisation in guinea pigs. No further details are provided.

 

Results of First Challenge:

All animals of control group 1 and 18 of 20 animals of the test group did not show any skin reactions after the first challenge with 15% (weight/weight) test item in diglyme. Two animals of the test group (animals no.16 and no. 19) showed discrete or patchy erythema at the 48-hour reading after the first challenge with 15% test item in diglyme. One animal of control group 1 (animal no.12) and one animal of the test group (animal no. 19) showed discrete or patchy erythema at the 48-hour reading after the first challenge with 5% test item in diglyme and another animal of the test group (animal no. 32) showed discrete or patchy erythema at the 24-hour as well as at 48-hour reading after the first challenge with 5% test item in diglyme.

 

Results of Second Challenge:

One animal (animal no. 19) of the test group showed discrete or patchy erythema at the 48-hour reading after the challenge with 15% (weight/weight) test item in diglyme and one animal of the test group (animal no. 14) showed discrete or patchy erythema at the 24-hour reading after the challenge with 5% (weight/weight) test item in diglyme. No skin reactions occurred in the control groups.

Interpretation of results:
GHS criteria not met
Conclusions:
Based on study conducted according to OECD Test Guideline 406 (non-LLNA, Buehler test) and in compliance with GLP (Harlan Laboratories Ltd., 2012, reliability score 1), triethoxy(3-thiocyanatopropyl)silane is concluded to be not sensitising in the male guinea pig when tested at 5 and 15% in diglyme under occlusive conditions for 6 hours. Induction was conducted once a week for 3 weeks, with the first challenge two weeks after the last induction dose. A separate second challenge was performed to further assess overall incidence. After the confirmatory second challenge, the overall incidence of test-item skin reactions was 10%.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In the key non-adjuvant sensitisation test, conducted according to OECD Test Guideline 406 and in compliance with GLP (Harlan Laboratories Ltd., 2012, reliability score 1), male guinea pigs (20 test item and 10 controls) were exposed to 5 of 15% of the test item and to diglyme, respectively, under occlusive conditions for 6 hours. Induction was conducted once a week for 3 weeks, with the first challenge two weeks after the last induction dose. An incidence of 10% was observed for each of the triethoxy(3-thiocyanatopropyl)silane concentrations of 5% and 15% in diglyme in the first challenge. However, as different animals responded, the overall incidence in this first challenge was 15%, which is the threshold for sensitisers as defined by the OECD and EC guidelines. Therefore, a second challenge was performed, again testing the same concentrations of 5% and 15%. In this second challenge, an incidence of 5% was observed for each of the tested concentrations of 5% and 15% of test item in diglyme in the second challenge and the overall incidence in this second challenge was 10%, which is below the 15% threshold. Taking into account that one control animal also responded in the first challenge and the incidence of the skin reactions decreased in the second challenge, the observed skin reactions are attributed to a slight irritation of the skin and not to a true sensitisation. Therefore, the test item is considered not sensitising.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the findings in a non-adjuvant sensitisation test in guinea pigs, triethoxy(3-thiocyanatopropyl)silane does not require classification as a skin sensitiser in accordance with Regulation (EC) No 1272/2008.