Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: Magnusson B, Kligman AM (1970) Allergic contact dermatitis in the guinea pig: Identification of contact allergens. CC Thomas, Springfield, IL
Principles of method if other than guideline:
Guinea pig maximisation test; induction via intradermal and occluded patch; 4 challenge exposures at different concentrations on different days.
GLP compliance:
no
Remarks:
Not fully compliant with GLP because the test substance was not subjected to characterisation, homogeneity and stability studies.
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethyl 2,3-epoxy-3-phenylbutyrate
EC Number:
201-061-8
EC Name:
Ethyl 2,3-epoxy-3-phenylbutyrate
Cas Number:
77-83-8
Molecular formula:
C₁₂H₁₄O₃
IUPAC Name:
ethyl 3-methyl-3-phenyloxirane-2-carboxylate
Details on test material:
- Name of test material (as cited in study report): Ethyl methyl phenyl glycidate
- Substance type: Clear colourless liquid
- Physical state: Liquid
- Analytical purity: No data
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Purity test date: No data
- Lot/batch No.: No data
- Expiration date of the lot/batch: No data
- Stability under test conditions: No data
- Storage condition of test material: No data
- Other: Sample reference: S14417T1

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: Intradermal injections - 0.1 % dodecylbenzene sulphonate (DOBS) in 0.9 % physiological saline; occluded patch applications - none
Concentration / amount:
Intradermal injection induction - 2.0 %; occluded patch induction application - 100 %; occluded patch first challenge application - 100 %
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Intradermal injections - 0.1 % dodecylbenzene sulphonate (DOBS) in 0.9 % physiological saline; occluded patch applications - none
Concentration / amount:
Intradermal injection induction - 2.0 %; occluded patch induction application - 100 %; occluded patch first challenge application - 100 %
No. of animals per dose:
Test group - 10; treated control group - 4; untreated control group - 4
Details on study design:
PRELIMINARY INTRADERMAL INJECTION TEST
- No. of animals: 4 female
- Exposure period: 24 hr
- Observations: skin reactions examined, reactions measured in size.
- 2 % test substance in 0.01 % DOBS/saline was selected for intradermal injection induction as it was suitably irritant.

PRELIMINARY OCCLUDED PATCH TEST
- No. of animals: 8 male in 2 groups of 4.
- Exposure period: 24 hr
- Observation period: 48 hr, observations at 24 hr and 48 hr.
- Concentrations: Group 1 - 5.0 %, 10.0 %, 25.0 %. Group 2 - 50.0 %, 100.0 %
- 100 % test substance was selected for both the induction and challenge applications.

MAIN STUDY
- No. of animals: 10 (6 male, 4 female).
- Weight at study initiation: 284 g to 370 g.

A. INTRADERMAL INJECTION INDUCTION
- No. of exposures: 1
- Site: Hair clipped from 2 cm × 4 cm region of dorsal shoulder.
- Injections into the prepared site as follows:
-- 2 × 0.1 mL injections of 50 % Freund's Complete Adjuvant (FCA) in 0.9 % saline
-- 2 × 0.1 mL injections of 2 % test substance in 0.01 % DOBS/saline
-- 2 × 0.1 mL injections of 4 % test substance in 0.01 % DOBS/saline mixed 50:50 with FCA so that concentration of test substance was 2 %.

B. OCCLUDED PATCH INDUCTION
- Period: 1 week after Intradermal Injection Induction
- Site: same site clipped and shaved
- 2 cm × 4 cm filter paper patch, attached to a 4 cm × 6 cm piece of polythene, was saturated with neat test substance and patch applied to site.
- Exposure period: 48 hr

C. CHALLENGE EXPOSURES
- No. of challenge exposures: 4
- Days of challenges:
-- 1: day 0 (14 days after the occluded patch induction)
-- 2: day 7
-- 3: day 15
-- 4: day 22
- Concentrations:
-- 1: 100 % test substance
-- 2: 10.0 % and 1.0 % test substance in acetone/PEG 400
-- 3: 0.1 % and 0.001 % test substance in acetone/PEG 400
-- 4: 1.0 % and 0.1 % test substance in acetone/PEG 400
- Site: same site clipped and shaved
- 8 mm diameter filter paper patch in an 11 mm aluminium patch test cup was saturated with challenge material and patch applied to site.
- Exposure period: 24 hr
- Evaluations: 24 hrs and 48 hrs after challenge.
- Scoring system:
-- 0: No reaction
-- 0.5: Very feint erythema (usually non-confluent)
-- 1: Faint erythema (usually confluent)
-- 2: Moderate erythema
-- 3: Marked erythema (with or without oedema)
-- sp: Small spots of erythema
-- n: Necrosis
-- w: White centre or spots
Challenge controls:
- No. of animals: 16
-- 4 treated controls for 1st challenge
-- 4 treated controls for 2nd challenge.
-- 4 untreated controls for 3rd challenge.
-- 4 untreated controls for 4th challenge.
- Treated animals received four intradermal injections of 50 % Freunds Complete Adjuvant in 0.01 % DOBS/saline followed 7 days later by a 48 hour occluded patch of the test solvent over the injection sites.
- Each group of 4 animals was treated to 1st, 2nd, 3rd and 4th challenge exposures as per the test animals.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: 1st challenge (day 0)
Hours after challenge:
24
Group:
test chemical
Dose level:
100.0 %
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Reading: other: 1st challenge (day 0). . Hours after challenge: 24.0. Group: test group. Dose level: 100.0 %. No with. + reactions: 8.0. Total no. in groups: 10.0.
Reading:
other: 1st challenge (day 0)
Hours after challenge:
48
Group:
test chemical
Dose level:
100.0 %
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: other: 1st challenge (day 0). . Hours after challenge: 48.0. Group: test group. Dose level: 100.0 %. No with. + reactions: 9.0. Total no. in groups: 10.0.
Reading:
other: 2nd challenge (day 7)
Hours after challenge:
24
Group:
test chemical
Dose level:
10.0 %
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Reading: other: 2nd challenge (day 7). . Hours after challenge: 24.0. Group: test group. Dose level: 10.0 %. No with. + reactions: 8.0. Total no. in groups: 10.0.
Reading:
other: 2nd challenge (day 7)
Hours after challenge:
48
Group:
test chemical
Dose level:
10.0 %
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: other: 2nd challenge (day 7). . Hours after challenge: 48.0. Group: test group. Dose level: 10.0 %. No with. + reactions: 7.0. Total no. in groups: 10.0.
Reading:
other: 2nd challenge (day 7)
Hours after challenge:
24
Group:
test chemical
Dose level:
1.0 %
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: other: 2nd challenge (day 7). . Hours after challenge: 24.0. Group: test group. Dose level: 1.0 %. No with. + reactions: 9.0. Total no. in groups: 10.0.
Reading:
other: 2nd challenge (day 7)
Hours after challenge:
48
Group:
test chemical
Dose level:
1.0 %
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Reading: other: 2nd challenge (day 7). . Hours after challenge: 48.0. Group: test group. Dose level: 1.0 %. No with. + reactions: 8.0. Total no. in groups: 10.0.
Reading:
other: 3rd challenge (day 15)
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: 3rd challenge (day 15). . Hours after challenge: 24.0. Group: test group. Dose level: 0.1 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd challenge (day 15)
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: 3rd challenge (day 15). . Hours after challenge: 48.0. Group: test group. Dose level: 0.1 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd challenge (day 15)
Hours after challenge:
24
Group:
test chemical
Dose level:
0.001 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: 3rd challenge (day 15). . Hours after challenge: 24.0. Group: test group. Dose level: 0.001 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd challenge (day 15)
Hours after challenge:
48
Group:
test chemical
Dose level:
0.001 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: 3rd challenge (day 15). . Hours after challenge: 48.0. Group: test group. Dose level: 0.001 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 4th challenge (day 22)
Hours after challenge:
24
Group:
test chemical
Dose level:
1.0 %
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: other: 4th challenge (day 22). . Hours after challenge: 24.0. Group: test group. Dose level: 1.0 %. No with. + reactions: 7.0. Total no. in groups: 10.0.
Reading:
other: 4th challenge (day 22)
Hours after challenge:
48
Group:
test chemical
Dose level:
1.0 %
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
1 additional questionable reaction
Remarks on result:
other: Reading: other: 4th challenge (day 22). . Hours after challenge: 48.0. Group: test group. Dose level: 1.0 %. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: 1 additional questionable reaction.
Reading:
other: 4th challenge (day 22)
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 %
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
other: Reading: other: 4th challenge (day 22). . Hours after challenge: 24.0. Group: test group. Dose level: 0.1 %. No with. + reactions: 4.0. Total no. in groups: 10.0.
Reading:
other: 4th challenge (day 22)
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1 %
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
1 additional questionable reaction
Remarks on result:
other: Reading: other: 4th challenge (day 22). . Hours after challenge: 48.0. Group: test group. Dose level: 0.1 %. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: 1 additional questionable reaction.

Any other information on results incl. tables

Strong skin sensitisation was seen with challenges of 100.0 %, 10.0 % and 1.0 % test material solution, a weak response was seen at 0.1 %, and no response was seen at 0.001 %.

There were no reactions observed in the treated control groups for challenges 1 and 2. One animal in the group for challenge 2 was killed and not scored as it suffered a broken leg. There were also no reactions observed in the untreated control group for challenges 3 and 4.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Conclusions:
The test material was shown to be strongly sensitising in a guinea pig maximisation test.