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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:
Start of the experimental phase: January 31, 2013; Termination of the in-life phase: May 10, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented GLP guideline study performed on a well identidied test substance..
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: 31 to 32 days
- Weight at study initiation: 303 to 361 g (excluding positive control); positive control: 316 to 370 g
- Housing: in pairs
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): 15 to 20 times
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle


IN-LIFE DATES: From: January 31, 2013 To: May 10, 2013
Route:
intradermal and epicutaneous
Vehicle:
other: aqua ad iniectabilia
Concentration / amount:
Stage 1: intradermal: 0.1% solution of Flocryl ADAM / MC80
Stage 2: epicutaneous: 10% solution of Flocryl ADAM / MC80
Stage 3: epicutaneous: 1% solution of Flocryl ADAM / MC80
Route:
epicutaneous, occlusive
Vehicle:
other: aqua ad iniectabilia
Concentration / amount:
Stage 1: intradermal: 0.1% solution of Flocryl ADAM / MC80
Stage 2: epicutaneous: 10% solution of Flocryl ADAM / MC80
Stage 3: epicutaneous: 1% solution of Flocryl ADAM / MC80
No. of animals per dose:
Vehicle control (aqua ad iniectabilia): 10
Flocryl ADAM / MC80: 20
Positive Control: 20 (historical background of the laboratory)
Details on study design:
RANGE FINDING TESTS:
- Exposure: intradermal or epicutaneous
- No. of animals: 18 (intradermal: 2, epicutaneous: 16)
- Exposure period: 24 hours and 48 hours for the shaved skin, 24 hours for the shaved and depilated skin
- Concentrations: intradermal: 0.01, 0.1, 0.5, 1, 5, 10% of Flocryl ADAM / MC80; epicutaneous: 1, 5, 10, 25, 50, 75, 100% of Flocryl ADAM / MC80

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal, epicutaneous)
- Exposure period: 48 hours (epicutaneous)
- Test groups: 1
- Control group: 1
- Site: shoulder region
- Frequency of applications: day 0: intradermal, day 7: epicutaneous
- Duration: 20 days
- Concentrations: intracutaneous: 0.1% solution of Flocryl ADAM / MC80; epicutaneous: 10% solution of Flocryl ADAM / MC80


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 21
- Exposure period: 24 hours
- Test groups: 1
- Control group: 1
- Site: left flank region (test item), right flank region (vehicle)
- Concentrations: 1% solution of Flocryl ADAM / MC80
- Evaluation (hr after challenge): 48 hours and 72 hours


OTHER: day 6: 0.5 mL sodium laurylsulfate in order to induce a local irritation
Positive control substance(s):
yes
Remarks:
α-hexyl cinnamic aldehyde
Positive control results:
Sensitising reaction in all animals in form of a moderate and confluent erythema (positive control data are obtained from historical background of the laboratory)
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 0.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 0.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: discrete or patchy erythema.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 0%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: discrete or patchy erythema.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
none
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 0.0. Clinical observations: none.
Reading:
rechallenge
Hours after challenge:
72
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
none
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 0.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: discrete or patchy erythema.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.1%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: discrete or patchy erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
moderate and confluent erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: moderate and confluent erythema.
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
10%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
moderate and confluent erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 10%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: moderate and confluent erythema.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
1%
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
none
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 0.0. Clinical observations: none.
Reading:
rechallenge
Hours after challenge:
72
Group:
test chemical
Dose level:
1%
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
none
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 0.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
moderate and confluent erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 10%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: moderate and confluent erythema.
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
10%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 10%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: discrete or patchy erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
100%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
moderate and confluent erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 100%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: moderate and confluent erythema.
Reading:
2nd reading
Hours after challenge:
72
Group:
positive control
Dose level:
100%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: positive control. Dose level: 100%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: discrete or patchy erythema.
Reading:
rechallenge
Hours after challenge:
48
Group:
positive control
Dose level:
0.01%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
moderate and confluent erythema
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.01%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: moderate and confluent erythema.
Reading:
rechallenge
Hours after challenge:
72
Group:
positive control
Dose level:
0.01%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
moderate and confluent erythema
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: positive control. Dose level: 0.01%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: moderate and confluent erythema.
Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The challenge with 2 mL of a 1% solution of Flocryl ADAM / MC80 in aqua ad iniectabilia/animal revealed no skin irritation in any animal and, thus, the test item had no sensitising properties.

The vehicle control revealed no skin reactions.

Animals of the same strain treated with α-hexyl cinnamic aldehyde in sesame oil exhibited a sensitising reaction in all animals in form of a moderate and confluent erythema (grade 2).

Under the present test conditions, Flocryl ADAM / MC80 was found to be not sensitising to guinea pigs in a test model according to MAGNUSSON and KLIGMAN.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A study dating from 1985 by Collier demonstrated sensitization in all animals. However, an in-depth review of the study report revealed several major problems with the study. Furthermore, the test susbstance was not identified and considering the test period, was most probably not a production sample. For these reasons, a new, GLP study has been conducted on a sample with exactly the same substance identity as the registration. This study demonstrated that there was a complete absence of sensitization to the test material. Based on this, the substance is not considered to be sensitizing for classification purposes.


Migrated from Short description of key information:
A guideline study conducted to GLP on a sample with the same substance identity as the registered substance did not show any sensitization in the test animals.

Justification for selection of skin sensitisation endpoint:
Substance has no vapour pressure and aerosols are not produced during manufacture and use. Therefore, the only sensitization end-point which is concerned is dermal.

Justification for classification or non-classification