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Toxicological information

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:
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

Reference
Name:
Unnamed
Type:
Constituent

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:
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

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.