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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:
july 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study (OECD 404)

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Tangled Multi-Walled Carbon Nanotubes
EC Number:
701-160-0
Cas Number:
7782-42-5
Molecular formula:
Hollow tubular carbon, 1-dimensional nano structures with hexagonal arrangement of carbon atoms
IUPAC Name:
Tangled Multi-Walled Carbon Nanotubes
Constituent 2
Reference substance name:
GRAPHISTRENGTH C100
IUPAC Name:
GRAPHISTRENGTH C100
Test material form:
solid: nanoform

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:Grimaud frères selection S.A.S., La Corbière, Roussay, France
- Age at study initiation:2 to 4 months old
- Weight at study initiation:2.5 +/- 0.1 Kg
- Housing:individually in Techniplast (64 cm x 63 cm x 30 cm) or Pajon (50 cm x 57 cm x 75 cm) cages.
- Diet :110C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France), ad libitum.
Food is analyzed regularly by the supplier for composition and contaminant levels.
- Water :filtered by a FG Millipore membrane (0.22 micron), ad libitum.
Bacteriological and chemical analyses of water are performed regularly by external laboratories. These analyses include the detection of possible contaminants (pesticides, heavy metals and
nitrosamines).
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):18 +/- 3
- Humidity (%):30 to 70
- Air changes (per hr):approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light):12h/12h

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped using electric clippers
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated skin served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):Doses of 500 mg of the test item in its original form
Duration of treatment / exposure:
The durations of exposure were 3 minutes, 1 hour and 4 hours, for the first single animal.
Since the test item was neither severely irritant nor corrosive on this first animal, it was then applied simultaneously for 4 hours to two other animals.
Observation period:
The skin was examined approximately 1 hour, 24, 48 and 72 hours after removal of the dressing. Since there were persistent irritation reactions at 72 hours, the observation period was extended up to their complete reversibility (day 8).
Number of animals:
The test item was first evaluated on a single animal; since the test item was neither severely irritant nor corrosive on this first animal, it was then applied simultaneously to two other animals.
Details on study design:
TEST SITE
- Area of exposure: 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.
- coverage:approximately 6 cm2
- Type of wrap if used:The test item in its original form were placed on a gauze pad moistened with purified water.The gauze pad was 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 (if done):After removal of the dressing, any residual test item was wiped off by means of a dry cotton pad or a cotton pad moistened with acetone then with water.
- Time after start of exposure:3 minutes, 1 hour, 4 hours

SCORING SYSTEM:Draize scale:
-Erythema and eschar formation
-Edema formation

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
edema score
Basis:
animal: #1, 2 and 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 4 hours exposure
Irritation parameter:
erythema score
Basis:
animal: # 1, 2 and 3
Time point:
24/48/72 h
Remarks on result:
other: Not calculated due to the coloration of the skin
Irritant / corrosive response data:
After a 3-minute exposure (one animal): No cutaneous reactions were observed.
A grey coloration of the skin was noted from day 1 until day 4.

After a 1-hour exposure (one animal):
A grey coloration of the skin was noted from day 1 until day 4. This coloration could have masked a possible very slight erythema (grade 1) on day 1. No cutaneous reactions were observed from day 2 until day 4.

After a 4-hour exposure (three animals):
A grey coloration of the skin was noted in all the animals all over the observation period. This coloration could have masked a possible very slight or well-defined erythema (grade 1 or 2) from day 1 until day 2, 3 or 4.
A very slight erythema (grade 1) was noted in 1/3 animals on days 4 and 5. A dryness of the skin was noted in 2/3 animals between day 4 and day 7.

Due to the coloration of the skin, the mean scores over 24, 48 and 72 hours for each animal were not calculable for erythema. For edema, the mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 0.0.
However, taking into account the possible erythema masked by the coloration, the maximal mean values over 24, 48 and 72 hours for erythema could be: 0.3, 1.0 and 1.3.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
When applied topically to rabbits, GRAPHISTRENGTH C100 micronised, induced a skin coloration preventing conclusions about its skin irritation potential. However, taking into account the possible maximal mean values for erythema, the test item GRAPHISTRENGTH C100 micronised could be slightly irritant.
However, taking into account the possible maximal mean values for erythema, the test item GRAPHISTRENGTH C100 micronised could be slightly irritant.
Executive summary:

The potential of the test item GRAPHISTRENGTH C100 micronised to induce skin irritation was evaluated in rabbits according to OECD No. 404 and Good Laboratory Practice Regulations. The test item was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. Since the test item was neither severely irritant nor corrosive on this first animal, it was then applied simultaneously for 4 hours to two other animals. A single dose of 500 mg of the test item in its original form was applied to the closely-clipped skin of one flank. The test item 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 reversibility of cutaneous reactions (day 8). The mean values of the scores for edema were calculated for each animal.

After a 3-minute exposure (one animal):

No cutaneous reactions were observed. A grey coloration of the skin was noted from day 1 until day 4.

After a 1-hour exposure (one animal):

A grey coloration of the skin was noted from day 1 until day 4. This coloration could have masked a possible very slight erythema on day 1. No cutaneous reactions were observed from day 2 until day 4.

After a 4-hour exposure (three animals)

A grey coloration of the skin was noted in all the animals all over the observation period. This coloration could have masked a possible very slight or well-defined erythema from day 1 until day 2, 3 or 4.

A very slight erythema was noted in 1/3 animals on days 4 and 5. A dryness of the skin was noted in 2/3 animals between day 4 and day 7.

Due to the coloration of the skin, the mean scores over 24, 48 and 72 hours for each animal were not calculable for erythema. For edema, the mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 0.0. However, taking into account the possible erythema masked by the coloration, the maximal mean values over 24, 48 and 72 hours for erythema could be: 0.3, 1.0 and 1.3.

The test item GRAPHISTRENGTH C100 micronised, induced a skin coloration preventing conclusions about its skin irritation potential. However, taking into account the possible maximal mean values for erythema, the test item GRAPHISTRENGTH C100 micronised could be slightly irritant.