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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
April - August 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An old and reliable study is available on an analogue substance of the registered substance before the registration data ; so no new study with animal will be performed.

Test material

Constituent 1
Chemical structure
Reference substance name:
Octyl acrylate
EC Number:
219-696-4
EC Name:
Octyl acrylate
Cas Number:
2499-59-4
Molecular formula:
C11H20O2
IUPAC Name:
octyl acrylate
Test material form:
liquid
Details on test material:
Names in the report : Acrylate de n-octyle / Acrylate de n-octyl
Colourless liquid
storage conditions: at room temperature and protected from light
Specific details on test material used for the study:
no

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France, 76410 Saint-Aubin-les-Elbeuf, France
-Females were nulliparous and non-pregnant.
- Age at study initiation: 3 months old
- Weight at study initiation: 341 +/-10 g (males), 344+/-17 (females)
- Housing:individually in polycarbonate cages
- Diet (e.g. ad libitum): free access to "106 pelleted diet"
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-2
- Humidity (%):30-70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: corn oil
Concentration / amount:
10%
Day(s)/duration:
on Day 1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
on Day 8
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
on Day 22
No. of animals per dose:
range-finding study : 2 males and 2 females
Main study : 15 males and 15 females
Details on study design:
RANGE FINDING TESTS:
By intradermal route: 24 hours before treatment, the dorsal region of the animal was clipped; intradermal administrations of the test substance formulation at different concentrations were performed in the intersacpular region; cutaneous reactions were evaluated appox. 24,48 and 6 days after injection.
By cutaneous route: 24 hours before teatment, both flank regions of the animals were clipped; a volume of 0.5 ml of the undiluted test substance of test substance formation at the chosen concentrations was placed on a dry gauze pad (approx. 4 cm²) which was then applied to the skin and held in place by an occlusive dressing for 24 hours; cutaneous reactions were evaluated approx. 24 and 48 hours after removal of the dressings.

MAIN STUDY
For all animals and before each treatment, the application sites were clipped on days 1 and 7 (intersacpular region 4 cm x 2 cm), clipped and shaved on day 21 (each flank 2 cm x 2 cm) and clipped on day 25 (each flank 2 cm x 2 cm).

A. INDUCTION EXPOSURE
- No. of exposures: 2 (day 1 : intradermal route ; day 8 : topical route)
- Control group: corn oil
- Site: intersacpular region
- Concentrations: intradermal route = 10% in corn oil ; topical route = 100 % (undiluted)
-Intradermal route : 3 injections per animal of 0.1 ml were made into each side of the interscapular region:
First injection (anterior site): FCA diluted at 50% (v/v) with 0.9% NaCL fro treated and control groups
Second injection (middle site): test substance at 10% (w/w) in corn oil for treated group ; vehicucle for control group
Third injection (posterior site): test substance at 10% (w/w) in a mixture FCA/0.9% NoCl 50/50 (v/v) for treated group ; vehicle at 50% (w/w) in a mixture FCA/0.9% NoCl 50/50 (v/v) for control group.
-topical roue: on day 8, 0.5 ml of the undiluted substance for treated group, and 0.5mlm of vehicle for control group. The test substance or the vehicule was placed on a dry gauze pad, which was then applied to the interscapular region. The pad was held in place for 48 hours by means of an adhesive hypoallergenic dressing and an adhesive anallergenic waterproof plaster. on removal of the dressing, no residual test substance was observed.

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (cutaneous)
- Day(s) of challenge: day 22
- Test groups: 0.5 ml of the undiluted test substance
- Control group: 0.5 ml of the vehicle
- Site: posterior right flank (treated), left (control group)
- Evaluation (hr after challenge): 24 and 48h after removal of the dressing
The test substance or the vehicule was placed on a dry gauze pad, which was then applied to the posterior region. The pad was held in place for 24 hours by means of an occlusive anallergenic waterproof plaster. On removal of the dressing, no residual test substance was observed.

Challenge controls:
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10% then 100%
No. with + reactions:
18
Total no. in group:
20
Clinical observations:
18 animals showed a grade 2 erythema ; one with grade 1
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
10% then 100%
No. with + reactions:
17
Total no. in group:
20
Clinical observations:
well defined or moderate erythema were observed : 10 animals with grade 2 and 7 animals with a grade 3
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no erythema with grade 2 was observed in control group ; only grade 1
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no erythema with grade 2 was observed in control group

Any other information on results incl. tables

Range findings study reasults :

Intradermal induction: In order to respect the criteria for the selection of concentrations (the concentration should be well-tolerated systemically and locally, interdermal injections shold cause moderate irritant effect but no necrosis or ulceration of the skin), concentration chosen for the main study was 10% (w/w).

Application by cutaneous route: In order to respect the criteria for the selection of concentrations (the concentration should be well-tolerated systemically and locally, cutaneous application for the induction should cause at most weak of moderate skin reactions or be the maximal practicable concentration; cutaneous application for the challenge phase should be the highest concentration which does not cause irritant effect), concentratop, chosen for the topical application of the induction phase and for the challenge application was 100%.

Main study / Clinical examinations :

One animal of the treated group was found dead on day 19. No clinical sign was observed prior to death. As such spontaneous mortality is sometimes observed in this species, it was not attributed to treatment with the test substance. No clinical signs and no other mortality were observed during the study.

The bodyweight gain of the treated animals was similar to that of the control animals.

Cutaneous reactions

On day 10, after the cutaneous application of the induction period, signs of irritation were observed at the interscapular region in the control and treated group.

After challenge application, a very slight erythema (grade 1) was observed in all the animals of the control group.

In the treated group, at the 24 -hours reading, a very slight or well-defined erythema was noted in 1/19 and 18/19 animals, respectively. A slight edema was recorded in 6/19 animals. A the 48 -hour reading, a very sight well-defined or moderate erythema was noted in 1/19, 10/19 and 7/19 animals, respectively. A slight oedema was observed in 12/19 animals. Dryness of the skin was noted in 1/10 animals of the control group and in 12/19 animals of the treated group.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
Under the experimental conditions and according to the maximization method of Magnusson and Kligman, the test substance n-octyl acrylate induces delayed contact hypersensitivity in 100% guinea-pigs.
Executive summary:

The potential of the test substance, n-octyl acrylate to induce delayed contact hypersensitivity was evaluated in guinea-pigs according to the maximalisation method of Magnusson and Kligman and to the OECD 406 test guidelines.

Thirty guinea-pigs were allocated to two groups: a control group 1 (5M/5F) and a treated group 2 (10M/10F). On Day 1, intradermal injections of Freund's complete adjuvant mixed with the test substance (treated group, 10%) or the vehicle (control group) were performed in the intrascapular region. On Day 7, the same region received a topical application of sodium lauryl sulfate in vaseline (10%, w/w) in order to induce local irritation. On Day 8, the test substance (treated group, undiluted) or the vehicle (control group) was applied to the same test site which was then covered by an occlusive dressing for 48 hours. On Day 22, after a rest period of 12 days, all animals of the treated (undiluted) and control groups were challenged by a cutaneous application of the test substance to the right flank. The left flank served as control and received the vehicule only. Test substance and vehicle were maintained under an occlusive dressing for 24 hours. Skin reactions were evaluated approximately 24 and 48 hours after removal of the dressing. At the end of the study, animals were killed without examination of internal organs. Skin samples were taken from the challenge application sites of all the animals. No histological examination was performed.

No clinical signs were noted during the study. One treated male was found dead during the study; this death was not related to treatment.

After the challenge application, a very slight erythema was observed in all the animals of the control group. In the treated group, at the 24 -hours reading, a very slight or well-defined erythema was noted in 1/19 and 18/19 animals, respectively. A slight edema was recorded in 6/19 animals. A the 48 -hour reading, a very sight well-defined or moderate erythema was noted in 1/19, 10/19 and 7/19 animals, respectively. A slight oedema was observed in 12/19 animals. Dryness of the skin was noted in 1/10 animals of the control group and in 12/19 animals of the treated group. As the cutaneous reactions observed in the animals of the treated groups were of higher severity than those recorded in the animals of the control group, they were attributed to the sensitizing potential of the test substance.

The species and strain used showed a satisfactory sensitization response in 90% animals treated with DNCB.

In conclusion, under the experimental conditions and according to the maximization method of Magnusson and Kligman, the test substance n-octyl acrylate induces delayed contact hypersensitivity in 100% guinea-pigs.