Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Start of study: September 16 - End of study: October 17, 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 1a : GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Remarks:
Principles of Good Laboratory Practice, annex of paragraph 19a, section 1 of the chemical law of July 25, 1994
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
α,α-Dimethyl-ethyl ester benzeneacetic acid
EC Number:
608-307-7
Cas Number:
2901-13-5
Molecular formula:
C12 H16 O2
IUPAC Name:
α,α-Dimethyl-ethyl ester benzeneacetic acid
Details on test material:
Name: Dimethylphenylessigsäureethylester
Synonyms: EDMPA
Chemical name: Benzeneacetic acid, α,α-dimethyl-, ethyl ester
Certificate of analysis: March 18, 1997
Purity: 99.8%
Appearance: clear, colorless liquid
Solubility: 0.3 g/L in water, miscible with alcohol, acetone and toluene
Batch number: B 0006
Date of production: March 12, 1997
Date of expiry: March 13, 1998
Storage conditions: darkness at approximately 5°C in a refrigerator
Stability and homogeneity in the vehicle: is guaranteed for 4 hours

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HARLAN WINKELMANN Gartenstr. 27 D-33178 Borchen SPF breeding colony
- Weight at study initiation: mean: 371 g
- Housing: in fully air-conditioned rooms in in macrolon cages (type 4) on soft wood granulate in groups of 5 animals
- Diet (e.g. ad libitum): ssniff Ms-H (V2233)
- Water (e.g. ad libitum): tap water in plastic bottles
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 50 ± 20%
- Photoperiod (hrs dark / hrs light): 12h/12h

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: sesame oil (Oleum sesami DAB 10)
Concentration / amount:
Induction phase: 5%
Challenge phase: 100%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: sesame oil (Oleum sesami DAB 10)
Concentration / amount:
Induction phase: 5%
Challenge phase: 100%
No. of animals per dose:
Determination of the primary non-irritant concentration: 3
Determination of the tolerance of the intradermal injections: 2
Control group: 5
Treatment group: 10
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 intradermal injections/animal
- Exposure period: 48h under an occlusive bandage with an impermeable film and an elastic bandage for the dermal induction.
- Test groups:
Intradermal induction (Day 1)
Site 1: 50% Freund's Adjuvant
Site 2: substance in Oleum sesami DAB 10
Site 3: substance in 50% Freund's Adjuvant
- Control group:
Intradermal induction (Day 1)
Site 1: 50% Freund's Adjuvant
Site 2: Oleum sesami DAB 10
Site 3: equal volume of Oleum sesami DAB 10 and 50% Freund's Adjuvant
Dermal induction (Day 8) : Oleum sesami DAB 10
- Site: dorsal area of 2 x 4 cm
- Concentrations: intradermal induction: 5%, dermal induction: 100%

B. CHALLENGE EXPOSURE (Day 22)
- No. of exposures: 1
- Exposure period: 24 hours under an occlusive bandage with an impermeable film and an elastic bandage.
- Site: 5x 5 cm on the left flank
- Concentrations: 100%
- Evaluation (hr after challenge): 24h

Positive control substance(s):
yes
Remarks:
The validity of the test system is confirmed by the periodically conducted positive control test using benzocain for the maximization test (report number 97.0326, dated June 02, 1997; Hoechst Marion Roussel, Preclinical Development Germany, Drug Safety).

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Hours after challenge:
24
Group:
test chemical
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No
Remarks on result:
other: . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No.
Hours after challenge:
48
Group:
test chemical
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No
Remarks on result:
other: . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No.

Any other information on results incl. tables

The body weight gains of the animals were not impaired. The treated animals showed no clinical signs of intoxication throughout the study.

Intradermal induction treatment:

- with Freund's adjuvant (with and without substance): severe erythema and oedema as well as indurations and encrustations.

- test substance in sesame oil: slight erythema and oedema.

Due to these strong irritations reactions of the skin, 10 % SDS was not administered at day 7.

Dermal induction treatment:

- site previously treated with Freund's adujvant: well defined erythema and oedema, indurated and encrusted skin as well as necrosis.

- test substance in sesame oil: no signs of irritation.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study, the substance showed no evidence for sensitizing properties.