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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 - 15 Nov 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Five different test substance concentrations and the vehicle were tested on each animal.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
yes
Remarks:
Five different test substance concentrations and the vehicle were tested on each animal.
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
29 Dec 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Danish Accreditation Fund (DANAK); National Board of Health, Medicines Division, Denmark

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
other: Albino Mol:Russian
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: MØllegaard Breeding and Research Centre, Lille Skensved, Denmark
- Weight at study initiation: 2.1 - 2.2 kg
- Housing: individually in PPO/HIPS (Noryl ®) cages (floor area: 2576 cm²) with perforated floor
- Diet: pelleted complete rabbit diet (Altromin 2123), ad libitum
- Water: domestic quality drinking water acidified with hydrochloric acid to pH 2.5, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ±15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: ethanol 96% and diethyl phthalate (DEP) 1:1
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentrations: 1, 5, 10, 25 and 100%

VEHICLE
- Amount(s) applied: 0.5 mL
- Concentration: 50% ethanol (96%) and 50% diethyl phthalate (DEP)
Duration of treatment / exposure:
4 h
Observation period:
72 h
reading time points: 1, 24, 48 and 72 h
Number of animals:
4 females
Details on study design:
TEST SITE
- Area of exposure: 10 x 10 cm on the dorsal area of the trunk divided into six test sites: two anterior located test sites, two centrally located test sites and two posterior located test sites
- Type of wrap if used: The gauze patches were secured with 2.5 cm wide adhesive tape and fixed with Scanpor tape (5 cm width). Thereafter Nobifix (6 cm width) was loosely wound round the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After removal of the tape and patches, the treated skin was cleaned with lukewarm water.
- Time after start of exposure: 4 hrs

OBSERVATION TIME POINTS
reading time points: 1, 24, 48 and 72 h

SCORING SYSTEM:
- Method of calculation: according to the method described by Draize (Draize et al., 1944)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: #1, #2 and #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: test substance concentrations: 1, 5, 10, 25 and 100%
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: test substance concentration: 100%
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: test substance concentrations: 1 and 5%
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: test substance concentrations: 10 and 25%
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: test substance concentrations: 1, 5, 10, 25 and 100%
Irritant / corrosive response data:
Very slight erythema was observed after 24 h in one rabbit at the test sites exposed to the vehicle and the test substance at concentrations of 1, 5, 10 and 25%, and in the same rabbit after 48 h at the test sites exposed to 10% and 25% test substance concentrations. All effects were fully reversible within 72 h after dosing. No effects occurred the test site exposed to 100%.

Any other information on results incl. tables

Table 1. Results of skin irritation study.

 

 

Erythema Score at hours

Edema Score

Rabbit no.

Test

substance concentration [%]

1

24

48

72

mean (24/48/72 h)

1

24

48

72

mean (24/48/72 h)

1

100

0

0

0

0

0

0

0

0

0

0

25

0

0

0

0

0

0

0

0

0

0

10

0

0

0

0

0

0

0

0

0

0

5

0

0

0

0

0

0

0

0

0

0

1

0

0

0

0

0

0

0

0

0

0

Vehicle

0

0

0

0

0

0

0

0

0

0

2

100

0

0

0

0

0

0

0

0

0

0

25

0

0

0

0

0

0

0

0

0

0

10

0

0

0

0

0

0

0

0

0

0

5

0

0

0

0

0

0

0

0

0

0

1

0

0

0

0

0

0

0

0

0

0

Vehicle

0

0

0

0

0

0

0

0

0

0

3

100

0

0

0

0

0

0

0

0

0

0

25

0

1

1

0

0.67

0

0

0

0

0

10

0

1

1

0

0.67

0

0

0

0

0

5

0

1

1

0

0.33

0

0

0

0

0

1

0

1

0

0

0.33

0

0

0

0

0

Vehicle

0

1

0

0

0.33

0

0

0

0

0

4

100

0

0

0

0

0

0

0

0

0

0

25

0

0

0

0

0

0

0

0

0

0

10

0

0

0

0

0

0

0

0

0

0

5

0

0

0

0

0

0

0

0

0

0

1

0

0

0

0

0

0

0

0

0

0

Vehicle

0

0

0

0

0

0

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the Acute Dermal Irritation/Corrosion Test in rabbits the test substance does not possess any skin irritating potential.
Executive summary:

The primary skin irritant effect was investigated according to OECD Guideline 404, "Acute Dermal Irritation/Corrosion", 1992 and GLP. The study was extended to investigate five different concentrations of the test article and a vehicle control on

each animal. Four rabbits were exposed to different concentrations of the test article at six skin sites. After 4 hours of exposure the test article was removed and the skin was examined 1, 24, 48 and 72 hours after termination of exposure. Under the experimental conditions described in this report, the mean score for erythema and oedema in the four rabbits used were as follows: 0.0, 0.2, 0.2, 0.1, 0.1, 0.1 (100%, 25%, 10%, 5%, 1% and vehicle) and 0.0, 0.0, 0.0, 0.0, 0.0, 0.0 (100%, 25%, 10%, 5%, 1% and vehicle), respectively.