Registration Dossier

Administrative data

Description of key information

In an OECD 406 study in guinea pigs dermal application of EOEOEA initiated a high frequency of occurrence/ positive reactions (90% of the animals) and therefore EOEOEA should according to the CLP criteria be classified as Skin Sens 1A.

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:
1989-03-30 to 1989-04-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance to GLP and comparable to the OECD 406 guideline, the Guinea pig mazimization test
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not applicable
Principles of method if other than guideline:
NA
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Data from the in vivo non-LLNA study was already available prior start of present registration
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dunkin Hartley guinea pigs from Shamrock Bio Service breeding centre (France)
- Age at study initiation: no data
- Weight at study initiation: 347 +/- 19 g (males); 348 +/- 18 g (males)
- Housing: individually housed in sterilized polycarbonate cages
- Diet (e.g. ad libitum): certified pellet diet ad libitum
- Water (e.g. ad libitum): filtered water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes (per hr): non-recycled and filtered by absolute filters
- Photoperiod (hrs dark / hrs light): 12 hours cycle

IN-LIFE DATES: 23.3.89 - 27.4.89
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
Test substance: 1% in vehicle (Induction)
Test substance: 5% in vehicle (Challenge)
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
Test substance: 1% in vehicle (Induction)
Test substance: 5% in vehicle (Challenge)
No. of animals per dose:
Control group: 5 male/female
Treated group: 10 male/female
Details on study design:
RANGE FINDING TESTS:
A preliminary test was performed to define dose levels for the main study. Sensitization was performed by intradermal route with 1% test substance in vehicle showing no irritation. Sensitization by cutaneous route was performed with testsubstance in its original form. Challenge application was performed at 5% test substance (maximum non-irritant dose) covered with an occlusive dressing for 24 hours.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 injections. 1: 50% Freund´s adjuvant, 2: Test substance and/or vehicle, 3: Adjuvant mixture + test substance and/or vehicle
- Exposure period: day 1-9
- Test groups: 1: 50% Freund´s adjuvant, 2: Test substance and/or vehicle, 3: Adjuvant mixture + test substance and/or vehicle
- Control group: 1: 50% Freund´s adjuvant, 2: Test substance and/or vehicle, 3: Adjuvant mixture + test substance and/or vehicle
- Site: clipped just before treatment on day 1 and 8 on the scapular area (4 x 2 cm)
- Frequency of applications: 2
- Duration: 10 days
- Concentrations: Injection: 01 ml (1%); Cutaneous: 0.5 ml (100%)

B. CHALLENGE EXPOSURE
- No. of exposures: occlusive dressing for 24 hr on day 26
- Day(s) of challenge: 24 hr
- Exposure period: 24 hr
- Test groups: 0.5 ml of 5% in vehicle (paraffin oil) and 0.5ml of vehicle on each flank
- Control group: 0.5 ml of 5% in vehicle (paraffin oil) and 0.5ml of vehicle on each flank
- Site: site clipped again and shaved on day 25 on each flank (2 x 2 cm)
- Concentrations: 5%
- Evaluation (hr after challenge): 24 and 48hr

OTHER: challenge application made with test substance at 5% = maximum non-irritant dose
Challenge controls:
yes
Positive control substance(s):
no
Positive control results:
NA
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5% in paraffin oil
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
-
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5% in paraffin oil . No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: -.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5% in paraffin oil
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
-
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5% in paraffin oil. No with. + reactions: 20.0. Total no. in groups: 20.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5% in paraffin oil
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
-
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5% in paraffin oil. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5% in paraffin oil
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
-
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5% in paraffin oil. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
other: Histopahthological examinations
Hours after challenge:
48
Group:
test group
Dose level:
5% in paraffin oil
No. with + reactions:
18
Total no. in group:
20
Clinical observations:
2 females were considered not to have reacted after histopahtological examination
Remarks on result:
other: see Remark
Remarks:
Reading: other: Histopahthological examinations. . Hours after challenge: 48.0. Group: test group. Dose level: 5% in paraffin oil. No with. + reactions: 18.0. Total no. in groups: 20.0. Clinical observations: 2 females were considered not to have reacted after histopahtological examination .
Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In the Guinea pig mazimization test, the test substance EDGA (EOEOEA) after an intradermal induction dose of 1% in paraffin oil and a challange dose of 5% in paraffin oil induced weak to moderate cutaneous reactions considered a result of a weak to moderate sensitisation reaction in 90% of the guinea pigs. EOEOEA should according to the CLP criteria be classified as Skin Sens 1A.
Executive summary:

In the Guinea pig mazimization test, the test substance EDGA (EOEOEA) after an intradermal induction dose of 1% in paraffin oil and a challange dose of 5% in paraffin oil induced weak to moderate cutaneous reactions (considered a result of a weak to moderate sensitisation reaction) in 90% of the guinea pigs. Due to the high rate of positive reactions (90% of the animals) EOEOEA should according to the CLP criteria be classified as Skin Sens 1A.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Migrated from Short description of key information:
In the Guinea pig mazimization test, the test substance EDGA (EOEOEA) after an intradermal induction dose of 1% in paraffin oil and a challange dose of 5% in paraffin oil induced weak to moderate cutaneous reactions (considered a result of a weak to moderate sensitisation reaction) in 90% of the guinea pigs. Due to the high rate of positive reactions (90% of the animals) EOEOEA should according to the CLP criteria be classified as Skin Sens 1A.

Justification for selection of skin sensitisation endpoint:
Guinea pig mazimization test of high validity.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Due to the high rate of positive reactions (90% of the animals) EOEOEA should according to the CLP criteria be classified as Skin Sens 1A.