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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:
14 July 2008 to 25 July 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material : Tin metal powder (2 – 11 µm)
- Physical state: Solid, grey powder
- Analytical purity: 99.99 %
- Impurities (identity and concentrations): Pb 0.0035 %, Sb 0.0010 %, Cu 0.0003 %, Au 0.0001 %, Al < 0.0001 %, Cd < 0.0001 %, Zn < 0.0002 %, Ag 0.0005 %, Bi 0.0018 %, As 0.0014 %, Fe < 0.0001 %, In 0.0002 %, Ni 0.0002 %, P 0.0016 % and S 0.0028 %
- Purity test date: 05/07/2008
- Lot/batch No.: 061184
- Expiration date of the lot/batch: August 2008
- Storage condition of test material: When not in use the test article was stored in a sealed container, at room temperature in the dark.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Three male rabbits obtained from commercial breeder, acclimated for 7-14 days. Hair removed from dorsum on day prior to treatment and animals confirmed to be healthy with intact, undamaged skin. Bodyweights recorded on day of arrival. Housed in standard laboratory cages - diet, water and environmental conditions complied with animal welfare and UK Home Office guidelines. Measures to enrich the environment using chew blocks and hay were included

TEST ANIMALS
- Source: Harlan UK Ltd., Bicester
- Age at study initiation: 12 to 15 weeks
- Weight at study initiation: 2.29 kg to 2.90 kg
- Housing: On arrival, rabbits were accommodated in cages that conform with the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989).
- Diet: Global Diet TRB 2930C (Harlan Teklad, Bicester, UK), freely available to the animals at all times. Each batch of diet had been analysed for specific constituents and contaminants by the manufacturer.
- Water: Mains water was provided, ad libitum, via cage-mounted water bottles. The water had been periodically analysed for specific contaminants.
- Acclimation period: 7 to 21 days

ENVIRONMENTAL CONDITIONS
- Temperature: 15 to 21 °C
- Humidity: 40 to 70 %
- Air changes: 15 per hour
- Photoperiod: The rooms were illuminated by fluorescent strip-lights for twelve hours daily.

In order to enrich both the environment and the welfare of the animals they were, where practicable, provided with wooden Aspen chew blocks and hay.

Overtly healthy animals were arbitrarily allocated to the study on the day prior to dosing. Electric clippers were used to remove all hair from an area of the dorsum measuring approximately 10 x 8 cm. Only rabbits with dorsal skin showing no pre-existing damage, irritation or multiple areas of active hair growth were accepted onto study.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg of tin metal powder (2-11 µm) per site

The test article was moistened with water before application in order to ensure good contact with the skin.

Duration of treatment / exposure:
4 hours under semi-occlusive dressing
Observation period:
72 hours
Number of animals:
Initially a single rabbit, followed by a further two animals.
Details on study design:
TEST SITE
- Area of exposure: 30 x 20 mm area on the closely clipped dorsum
- Type of wrap if used: The dose was spread uniformly over the designated area and then covered by a dense gauze patch (30 x 20 mm) on Day 1. This in turn was covered by a larger gauze patch (40 x 40 mm) and an open weave, elasticated adhesive compression bandage which was wrapped firmly around the torso to secure the applied dose and patch in the correct position. The dressing was considered to be semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test patch was removed after four hours and the treated skin was lightly brushed clean of any solid residues and swabbed with moist cotton wool. The location of the test site was marked on the dorsum with indelible ink after completion of the cleansing process.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Draize J H (1959) “Dermal Toxicity” in: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p47 ( detailed under section "Any other information on materials and methods incl. tables")

Before the first animal could be dosed, the pH of the test article was checked. A 50 % w/v dispersion in purified water had a pH of 5. Since this was within the acceptable range of pH 2.0 to 11.5, the study continued.
Although no contemporary measurement of pH of the purified water used in the formulation was made, the water comes from one source and is produced on site at Covance, Harrogate from an Elgastat purifier. The typical pH value of the purified water is pH 5.68 (as measured on 03 October 2008)

Each rabbit was weighed on the day before dosing commenced (Day –1).

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 to 72 hour scores
Score:
0
Max. score:
0
Reversibility:
other: No reactions occurred at any time point for any any rabbit, so no possibility for reversibility
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No dermal response to treatment was observed in any animal throughout the observation period.
Other effects:
There were no signs of toxicity or ill health in any rabbit during the observation period.

Any other information on results incl. tables

No dermal reactions were apparent at any site for any of the three rabbits, at any time point from 1 to 72 hours post-exposure.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
The mean scores for erythema and eschar formation and for oedema formation, for each rabbit, were zero. Therefore, the test article did not meet the criteria for classification as irritant or corrosive according to EU criteria.
The test article produced a primary irritation index of 0.0 and was classified as NON-IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted
Executive summary:

500 mg of tin metal powder (2 -11 µm) was applied to moistened sites on the clipped, shaved dorsum of three NZW rabbits and maintained in situ under a semi-occlusive dressing for 4 hours. The sites were assessed at 1, 24, 48 and 72 hours post-exposure and scored for signs of erythema or oedema according to Draize system. No dermal reactions were observed.

Tin metal powder (2 -11 µm) was not irritating and does not require classification as a skin irritant.