Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 1999-04-09 To 1999-08-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 1a: The study was performed according to OECD guideline 406 and GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Esterol C
- Physical state: light yellow liquid
- Analytical purity: 78.09 % (amount of C18 esters)
- Composition of test material, percentage of components: Misture of methylesters of saturated and unsaturated C16 to C20 fatty acids, no data
- Lot/batch No.: 9906501
- Acid number: 9.30 mgKOH/g
- Expiration date of the lot/batch: December 1999
- Storage condition of test material: in dark and at room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Hartley / Crl: (HA) Br
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France, 76410 Saint-Aubin-lès-Elbeuf, France.
- Age at study initiation: approximately 3 months old
- Weight at study initiation: 378 +/- 14 g (males), 368 +/- 16 g (females)
- Housing: individually in polycarbonate cages (48 cm x 27 cm x20 cm)
- Diet : free access to "106 pelleted diet" (UAR, 91360 Villemoisson-sur-Orge, France)
- Water : drinking water filtered by a FG Millipore membrane (0.22 µm), ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/-2°C
- Humidity (%): 30 to 70 %
- Air changes (per hr): approximately 12 cycles/hours of filtered, non-recylcled air
- Photoperiod : 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 1999-04-01 To: 1999-05-03

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
Induction (treated group)
- Intradermal injections: Esterol C at the concentration of 75% (W/W) in corn oil
- Topical aplication: Esterol C undiluted

Challenge (all group)
- topical application: Esterol C undiluted
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
Induction (treated group)
- Intradermal injections: Esterol C at the concentration of 75% (W/W) in corn oil
- Topical aplication: Esterol C undiluted

Challenge (all group)
- topical application: Esterol C undiluted
No. of animals per dose:
control group (5 males and 5 females)
Treated group (10 males and 10 females)
Details on study design:
RANGE FINDING TESTS: In a preliminary study, the following concentrations were tested: 75 %, 50 % and 25 %. In order to respect the criteria for the
selection of concentrations (the concentration should be well-tolerated systematically and locally, intradermal injections should cause moderate
irritant effect but no necrosis or ulceration of the skin), concentration chosen for the main study was 75 % (W/W).


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and cutaneous)
- Test groups: Esterol C in Freund's complete adjuvant (FCA) or in corn oil
- Control group: FCA and corn oil
- Site: dorsal skin of the scapular region
- Frequency of applications: on day 1 and day 8
- Duration: 0-8 days
- Concentrations: 75 % (intradermal), undiluted (cutaneous)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 22
- Exposure period: 24h
- Test groups: Esterol C
- Control group: Esterol C
- Site: posterior right flank (test substance), posterior left flank (vehicle)
- Concentrations: O.5 ml (undiluted test substance or vehicle)
- Evaluation (hr after challenge) : 24 and 48


OTHER:
Positive control substance(s):
yes
Remarks:
DNCB (CIT study No. 17335 TSG)-september 1998

Results and discussion

Positive control results:
The species and strain which were used showed previously a satifactory sensitization response in 90 % animals treated with a positive sensitizer,
2,4 -Dinitro chlorobenzene. (CIT study No. 17335 TSG-September 1998)

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5 ml (undiluted test substance)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No clinical signs were observed during the study
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 ml (undiluted test substance). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No clinical signs were observed during the study.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5 ml (undiluted test substance)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No clinical signs were observed during the study
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 ml (undiluted test substance). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No clinical signs were observed during the study.
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No clinical signs were observed during the study
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control group
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No clinical signs were observed during the study
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:

Any other information on results incl. tables

The LLNA test has not been performed because a valid Guinea Pig maximisation test is existing

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The test substance Esterol C does not induce delayed contact hypersensitivity in guinea-pigs.
Executive summary:

In a dermal sensitization study (Manciaux, 1999) with Esterol C (batch No. 99.06.501) in corn oil, Hartley guinea-pigs were tested using the method of Guinea pig maximisation test. No clinical signs and no deaths were noted during the study. No cutaneous reactions were observed after the challenge application. Under the experimental conditions of the study, Esterol C does not induce delayed contact hypersensitivity in guinea pig.