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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:
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
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): EDGA (ethylendiglycolacrylate)
- CAS 7328-17-8
- Physical state: Liquid
- Lot/batch No. EDGA (lot 1010, Fut No: 3282 stabilized in 500 ppm EMHQ
- Storage condition of test material: 4°C

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
Test substance: 1% in vehicle (Induction)
Test substance: 5% in vehicle (Challenge)
Challengeopen allclose all
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

Results and discussion

Positive control results:
NA

In vivo (non-LLNA)

Resultsopen allclose all
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 .

Applicant's summary and conclusion

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.