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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:
From January 18 to 28, 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted in compliance with OECD Guideline 404 without any deviation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
inspected on September 22, 1999 / signed on January 18, 2000

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Physical state: White solid (but some samples were received as liquid, due to stability in supercooled state)
- Storage condition of test material: At room temperature, protected from light and under nitrogen atmosphere


Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France
- Age at study initiation: No data available
- Weight at study initiation: 2.5 ± 0.2 kg
- Housing: Animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet: 112 C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France), ad libitum
- Water: Drinking water filtered by a FG Millipore membrane (0.22 micron), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3 °C
- Humidity: 30–70%
- Air changes: Approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: January 18, 2000 To: January 28, 2000

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: moistened with water
Controls:
other: untreated skin served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 500 mg (ground to a fine powder using a mortar and pestle)
- Purified water was used to moisten the test substance and ensure good contact with the skin
Duration of treatment / exposure:
4 hours
Observation period:
Observations at 1, 24, 48 and 72 hours and daily as needed up to 14 days after removal of the dressing.
Number of animals:
3 male animals
Details on study design:
TEST SITE
- Area of exposure: Right flank
- % coverage: no data available
- Type of wrap if used: The test substance and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: After removal of the dressing, any residual test substance was wiped off by means of a dry gauze pad.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scale, as described in OECD Guideline 404

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
probability of weak irritation
Remarks:
A well-defined erythema (score 2) was noted on Day 1, then a very slight erythema (score 1) persisted up to Day 5. Dryness of the skin was recorded between Day 6 and Day 10
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
probability of weak irritation
Remarks:
A very slight erythema was observed on Day 1 and 2 only
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
In one animal, a well-defined erythema (grade 2) was noted on day 1, then a very slight erythema (grade 1) persisted up to day 5. Dryness of the skin was recorded between day 6 and day 10.
In a second animal, a very slight erythema (grade 1) was observed on days 1 and 2 only.
No cutaneous reactions were observed in the third animal.
Other effects:
None

Any other information on results incl. tables

Table 7.3.1/1: Mean irritant/corrosive response data for each animal at each observation time

 

Score at time point

Erythema (Animal no 1 / 2 / 3)

Max. score 4

Oedema (Animal no 1 / 2 / 3)

Max. score 4

1 h (D1)

2 / 1 / 0

0 / 0 / 0

24 h (D2)

1 / 1 / 0

0 / 0 / 0

48 h (D3)

1 / 0 / 0

0 / 0 / 0

72 h (D4)

1 / 0 / 0

0 / 0 / 0

D5

1 / - / -

0 / - / -

D6

0 / - / -

0 / - / -

D7

0 / - / -

0 / - / -

D8

0 / - / -

0 / - / -

D9

0 / - / -

0 / - / -

D10

0 / - / -

0 / - / -

D11

0 / - / -

0 / - / -

Average 24, 48 and 72 h

1.0 / 0.3 / 0.0

0.0 / 0.0 / 0.0

 

-:Cutaneous examination not performed

Applicant's summary and conclusion

Interpretation of results:
not irritating
Conclusions:
Under the test conditions, test material is not classified as irritating to skin according to the annex I of the Regulation EC No. 1272/2008 (CLP) and of the GHS.
Executive summary:

In a primary dermal irritation study performed according to the OECD Guideline No. 404/EU Method B.4, and in compliance with GLP, 500 mg of test material moistened with purified water was applied on the clipped skin of the right flank area of 3 male New Zealand White rabbits. Test sites were covered with a semi-occlusive dressing for 4 h. The untreated skin served as control. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48, 72 hours after removal of the dressing and then daily until reversibility of cutaneous reactions.

 

In one animal, a well-defined erythema was noted on day 1, then a very slight erythema persisted up to day 5. Dryness of the skin was recorded between day 6 and day 10. In a second animal, a very slight erythema was observed on days 1 and 2 only. No cutaneous reactions were observed in the third animal. Mean scores over 24, 48 and 72 hours for each animal were 1.0, 0.3 and 0.0 for erythema and 0.0, 0.0 and 0.0 for oedema.

 

Therefore, test material is not classified as irritating to skin according to the annex I of the Regulation EC No. 1272/2008 (CLP) and of the GHS.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.