Registration Dossier

Administrative data

Description of key information

The key study for sensitisation found the test material to be not sensitising in a reliable study carried out according OECD 406 and in compliance with GLP (Harlan 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:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
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:
Control group 10, test group 20
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
Reading:
other: first challenge
Hours after challenge:
24
Group:
test group
Dose level:
15%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
other: first challenge
Hours after challenge:
48
Group:
test group
Dose level:
15%
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
other:
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
Reading:
other:
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
Reading:
other: first challenge
Hours after challenge:
24
Group:
test group
Dose level:
5%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
other: first challenge
Hours after challenge:
48
Group:
test group
Dose level:
5%
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
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
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
Reading:
other: second challenge
Hours after challenge:
24
Group:
test group
Dose level:
15%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
other: second challenge
Hours after challenge:
48
Group:
test group
Dose level:
15%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
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
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
Reading:
other: second challenge
Hours after challenge:
24
Group:
test group
Dose level:
5%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
other: second challenge
Hours after challenge:
48
Group:
test group
Dose level:
15%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
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
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
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 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.

Interpretation of results:
GHS criteria not met
Conclusions:
The test material is concluded to be not sensitising in a reliable study carried out according to current OECD guideline and in compliance with GLP.
Executive summary:

In this non-adjuvant sensitisation test, conducted according to OECD TG 406 and in compliance with GLP, an incidence of 10% was observed for each of the tested concentrations of 5% and 15% of test item 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 animal of control group 1 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 to not be sensitising.

Based on the above mentioned findings in a non-adjuvant sensitization test in guinea pigs and in accordance with Regulation (EC) No 1272/2008, triethoxy(3-thiocyanatopropyl)silane is not classified as a skin sensitiser.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In the key non-adjuvant sensitization test, conducted according to OECD 406 and in compliance with GLP, an incidence of 10% was observed for each of the tested concentrations of 5% and 15% of test item 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 sensitizers 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 animal of control group 1 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 sensitization. Therefore, the test item is considered to be not sensitizing (Harlan, 2012).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the findings in a non-adjuvant sensitization test in guinea pigs, in accordance with Regulation (EC) No 1272/2008, triethoxy(3-thiocyanatopropyl)silane does not have to be classified as a skin sensitizer.