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Skin sensitisation

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guideline
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.

Test material

Constituent 1
Chemical structure
Reference substance name:
Triethoxy(3-thiocyanatopropyl)silane
EC Number:
252-161-3
EC Name:
Triethoxy(3-thiocyanatopropyl)silane
Cas Number:
34708-08-2
Molecular formula:
C10H21NO3SSi
IUPAC Name:
3-(triethoxysilyl)propyl thiocyanate

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: diglyme
Concentration / amount:
Undiluted test substance (induction).
15% and 5% in diglyme (first challenge).
Challengeopen allclose all
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

Results and discussion

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.

In vivo (non-LLNA)

Resultsopen allclose all
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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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%.