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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:
22 Jun - 16 Jul 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 2021
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.

Test material

Constituent 1
Chemical structure
Reference substance name:
2,6-dibromo-4-cyanophenyl octanoate
EC Number:
216-885-3
EC Name:
2,6-dibromo-4-cyanophenyl octanoate
Cas Number:
1689-99-2
Molecular formula:
C15H17Br2NO2
IUPAC Name:
2,6-dibromo-4-cyanophenyl octanoate
Test material form:
liquid: viscous

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Remarks:
Crl: (HA) BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France (Saint-Aubin-les-Elbeuf, France)
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately 3 months
- Weight at study initiation: 342 ± 10 g (males), 345 ± 10 g (females)
- Housing: individually in polycarbonate cages equipped with dust-free sawdust (SICSA, Alfortville, France)
- Diet: 106 pelleted diet (UAR, Villemoisson-sur-Orge, France), ad libitum
- Water: filtered drinking water (0.22 µm FG Millipore membrane), ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): approximately 12
- Photoperiod (hrs dark / hrs light): 12 / 12
- IN-LIFE DATES: From: 22 Jun 1999 To: 16 Jul 1999

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
corn oil
Concentration / amount:
0.1 mL at a concentration of 5% (w/w)
Day(s)/duration:
single injection on Day 1
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
0.5 mL at a concentration of 50% (w/w)
Day(s)/duration:
starting on Day 8 for 48 h
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
0.5 mL at a concentration of 50% (w/w)
Day(s)/duration:
starting on Day 22 for 24 h
No. of animals per dose:
10 (control, 5 per sex), 20 (treatment group, 10 per sex)
Details on study design:
RANGE FINDING TESTS
A. INDUCTION EXPOSURE
For intradermal induction: One male and one female guinea pig were each given intradermal injections of the following test item concentrations: 5% with or without FCA. The injection sites were evaluated 24 and 48 h and 6 days after the injections.
For topical induction: Two concentrations (25% and 50%) were tested on two guinea pigs. 0.5 mL of test substance formulation were placed on a dry gauze pad and applied to the skin by means of an occlusive dressing for 24 h. The skin reactions were evaluated 24 and 48 h after removal of the dressing. No skin reactions were recorded for both time points after topical application of the test formulations (25 - 50%).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) Freund's Complete Adjuvant (FCA)/sterile physicological saline solution
Injection 2: 5% test substance in corn oil
Injection 3: 5% test substance in corn oil in a 1:1 mixture of (v/v) FCA/0.9% NaCl
Epicutaneous: 50% test substance in corn oil
- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/sterile physicological saline solution
Injection 2: corn oil
Injection 3: corn oil in a 1:1 mixture (v/v) FCA/0.9% NaCl
Epicutaneous: corn oil
- Site: interscapular region (intradermal + epicutaneous)
- Frequency of applications: once (each)
- Duration: intradermal induction was performed on Day 1, topical induction was performed on Day 8-10
- Concentrations: intradermal 5%, epicutaneous 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (challenge)
- Day(s) of challenge: challenge was performed three weeks after intradermal induction on Day 22
- Exposure period: 24 h
- Test groups: test substance and vehicle only
- Control group: test substance and vehicle only
- Site: posterior flanks (right: test substance; left: vehicle)
- Concentrations: 50%
- Evaluation (hr after challenge): 24 and 48 h after removal of dressing

OTHER:
The animals were observed for clinical signs and mortality at least once daily throughout the entire study period. Individual body weights were recorded on the day of allocation into the groups and on Days 1, 8, 15 and 25 of the study.
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
yes
Remarks:
The GPMT was checked for reliability in a separate study on female guinea pigs using DNCB as a positive control substance.

Results and discussion

Positive control results:
The positive control DNCB at a concentration of 1% (w/w) induced positive skin sensitization reactions in 9/10 (90%) guinea-pigs.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
induction: 5% (intradermal), 50% (epicutaneous); challenge: 50% (epicutaneous)
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
induction: 0% (intradermal), 0% (epicutaneous); challenge: 50% (epicutaneous)
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
induction: 5% (intradermal), 50% (epicutaneous); challenge: 50% (epicutaneous)
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
induction: 0% (intradermal), 0% (epicutaneous); challenge: 50% (epicutaneous)
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
induction: 0.1% (intradermal), 1% (epicutaneous); challenge: 1% (epicutaneous)
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group for positive control
Dose level:
induction: 0% (intradermal), 0% (epicutaneous); challenge: 0% (epicutaneous)
No. with + reactions:
0
Total no. in group:
5
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
induction: 0.1% (intradermal), 1% (epicutaneous); challenge: 1% (epicutaneous)
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control group for positive control
Dose level:
induction: 0% (intradermal), 0% (epicutaneous); challenge: 0% (epicutaneous)
No. with + reactions:
0
Total no. in group:
5

Any other information on results incl. tables

An ocular lesion recorded in one animal of the treated group (male no. 36), from Day 23, was not considered to be a consequence of treatment with the test substance. No other clinical signs and no mortality were observed during the study. The body weight gain of the treated animals was similar to that of the control animals. No cutaneous reactions were observed in the animals of the control group. In the treated group, a well-defined or moderate erythema (grade 2 or 3) was noted in all animals at the 24 and 48-hour readings. A very slight or slight oedema (grade 1 or 2) was recorded in 6/20 animals at the 24-hour reading and in 15/20 animals at the 48-hour reading. Dryness of the skin was observed in all animals at the 48-hour reading.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
The study was conducted according to OECD guideline 406, under GLP and is considered valid and reliable. Under the test conditions, the test substance produced a sensitizing reaction to the skin of guinea pigs.