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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:
23 October to 08 November 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted in compliance with OECD Guideline No. 404 without any deviations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

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)
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
16 December 2005

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: ONIPPAM / 081007
- Physical state: Green to pale yellow liquid
- Date of receipt: 15 October 2007

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Stored at 4 °C, protected from light and under nitrogen gas
- Stability under test conditions: Test item was considered to be stable during the study period

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Grimaud frères selection S.A.S., La Corbière, Roussay, France.
- Age at study initiation: 2-4 months
- Weight at study initiation: Mean body weight: 3.0 ± 0.3 kg
- Housing: Animals were housed individually in Pajon cages (50 cm x 57 cm x 75 cm).
- Diet: 110C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France), ad libitum
- Water: Drinking water (filtered by a FG Millipore membrane (0.22 µm)), 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 h dark/ 12 h light

IN-LIFE DATES: 23 October to 08 November 2007

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Undiluted
- pH of the test item was not measurable (non-aqueous test item)

CONTROL
- Untreated skin served as control
Duration of treatment / exposure:
4 h
Observation period:
1, 24, 48 and 72 h after removal of the dressing. Since there was a persistent irritation reaction at 72 h, the observation period was extended up to their complete reversibility (Day 15).
Number of animals:
3 males
Details on study design:
PRETREATMENT
Preparation and selection of the animals: The day before treatment, both flanks of each animal were clipped using electric clippers and just before treatment, the skin of each animal was examined in order to check the absence of any signs of skin irritation. Clipping was repeated thereafter on days 4 and 6 for the animal No. 555.

APPLICATION OF THE TEST ITEM
The test item was first evaluated on a single animal (No. 555). The durations of exposure were 3 minutes, 1 hour and 4 hours. Since the test item was not severely irritant nor corrosive on this first animal, it was then applied simultaneously for 4 hours to two other animals (Nos. 560 and 561).

TEST SITE
- Area of exposure: Test substance was applied to an area of approximately 6 cm2 of the anterior left flank (application for 3 minutes), the anterior right flank (application for 1 hour) or the posterior right flank (application for 4 hours) of the animals.
- Type of wrap if used: Test substance was placed on the gauze pad and 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 item was wiped off by means of a dry cotton pad.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
1, 24, 48 and 72 h and Day 5 to 15

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

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
After a 3-minute exposure (one animal)
- A very slight erythema (grade 1) was noted from day 1 until day 6.
- A dryness of the skin was observed from day 4 until day 8.
After a 1-hour exposure (one animal)
- A very slight erythema (grade 1) was noted from day 1 until day 7.
- A dryness of the skin was observed from day 4 until day 8.
After a 4-hour exposure (three animals)
- A very slight or well-defined erythema (grade 1 or 2) was noted in all animals from day 1 until day 6 (1/3 animal) or 7 (2/3 animals).
- A dryness of the skin was recorded in all animals from day 4 until day 8 (1/3 animals) or 15 (end of the observation period; 2/3 animals).
- Mean scores over 24, 48 and 72 hours for each animal were 1.0, 1.0 and 1.3 for erythema and 0.0, 0.0 and 0.0 for edema.
Other effects:
None

Any other information on results incl. tables

Table 7.3.1/1: 4-hour exposure - Individual cutaneous examinations and mean values of the scores recorded for each animal (24, 48 and 72 hours)

 

Score at time point

Erythema (Animal No. 1 / 2 / 3)

Max. score 4

Oedema (Animal No. 1 / 2 / 3)

Max. score 4

Other (Animal No. 1 / 2 / 3)

1 h

2/2/2

0/0/0

*/*/*

24 h

1/1/2

0/0/0

*/*/*

48 h

1/1/1

0/0/0

*/*/*

72 h

1/1/1

0/0/0

S/S/S

Day 5

1/1/1

0/0/0

S/S/S

Day 6

1/1/1

0/0/0

S/S/S

Day 7

1/1/0

0/0/0

S/S/S

Day 8

0/0/0

0/0/0

S/S/S

Day 9

0/0/0

0/0/0

*/S/S

Day 10

-/0/0

-/0/0

-/S/S

Day 11

-/0/0

-/0/0

-/S/S

Day 12

-/0/0

-/0/0

-/S/S

Day 13

-/0/0

-/0/0

-/S/S

Day 14

-/0/0

-/0/0

-/S/S

Day 15

-/0/0

-/0/0

-/S/S

Average 24, 48 and 72 h

1.0/1.0/1.3

0/0/0

-

Reversibility

Completely reversible

-

-

Average time for reversion

8 days

-

-

Animal No. 1 / 2 / 3 = Animal No. 555, 560 and 561, respectively

* = none

S = dryness of the skin

- = cutaneous examination not performed

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the test substance is not classified as irritant according to Regulation (EC) No 1272/2008 (CLP) and to GHS.
Executive summary:

A dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP. The test substance was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. Since the test substance was not severely irritant nor corrosive on this first animal, it was then applied simultaneously for 4 hours to two other animals.

 

A single dose of 0.5 mL of the undiluted test substance was applied to the closely-clipped skin of one flank. The test substance was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily until the end of the observation period. The mean values of the scores for erythema and edema were calculated for each animal.

 

After a 3-minute exposure (one animal): A very slight erythema was noted from day 1 until day 6. A dryness of the skin was observed from day 4 until day 8.

After a 1-hour exposure (one animal): A very slight erythema was noted from day 1 until day 7. A dryness of the skin was observed from day 4 until day 8.

After a 4-hour exposure (three animals): A very slight or well-defined erythema was noted in all animals from day 1 until day 6 (1/3 animal) or 7 (2/3 animals). A dryness of the skin was recorded in all animals from day 4 until day 8 (1/3 animals) or 15 (end of the observation period; 2/3 animals).

 

Mean scores over 24, 48 and 72 hours for each animal were 1.0, 1.0 and 1.3 for erythema and 0.0, 0.0 and 0.0 for edema.

 

Under the test conditions, test substance is not classified as irritant to the skin according to Regulation (EC) No. 1272/2008 (CLP) and GHS.