[3-(Hydroxy-kO)-4-{[2-(hydroxy-kO) carbopolycyl-1-yl]diazenyl-kN1}-6-substituted-carbopolycyle-1-sulfonato(3-)]chromium, reaction products with hydrogen amino-4-hydroxy carbopolycyle-2-sulfonate, sodium 2-[(aminophenyl)sulfonyl]ethyl sulfate, amino-5-substituted-phenol and 2,4,6-trichloro-1,3,5-triazine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Remarks:

RCC Ltd, CH-4452 Itingen, Switzerland

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): FAT 40821/A
- Purity: Approx. 81%
- Lot/batch No.: TVR1
- Expiration date: 1 February 2010
- Stability of test item: Stable under storage conditions
- Storage condition: At room temperature (range of 20 ± 5°C), light and moisture (desiccator) protected.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories France, BP 0109, F-69592 L'Arbresle
- Age at treatment: 13 weeks (male), 11 weeks (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 38/04, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 93/04) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

0.5 g test substance moistened with approximately 0.5 mL purified water.

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

1 male, 2 females

Details on study design:

TREATMENT
Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was clipped again. Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test. On the day of treatment, 0.5 g of FAT 40821/A was placed on a surgical gauze patch (ca. 4 cm x 4 cm). This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape. The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.

OBSERVATIONS
Viability/Mortality: Daily from acclimatization of the animals to the termination of test.
Clinical signs: Daily from acclimatization of the animals to the termination of test.
Body weights: At start of acclimatization, on the day of application and at termination of observation.

SCORING SYSTEM:
The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004 approximately 1, 24, 48 and 72 hours, as well as 7 days after the removal of the dressing, gauze patch and test item. To allow further examination of the test sites all animals were re-clipped on completion of the 48- and 72-hour examination. If evident, corrosive or staining properties of the test item were described and recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1 hour

Score:

1.67

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 hours

Score:

0.67

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48 and 72 hours

Score:

0.33

Max. score:

4

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 7 days

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48, 72 hours and 7 days

Score:

0

Max. score:

4

Irritant / corrosive response data:

- Very slight to well-defined erythema were observed in all animals one hour after treatment and very slight erythema persisted up to 24- or 72-hour examinations in two animals, respectively. Very slight swelling (oedema) was noted in all animals one hour after treatment. No abnormal findings were observed on the treated skin of any animal 7 days after treatment, the end of the observation period.
- Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Other effects:

- Slight black staining produced by the test item of the treated skin was observed in all animals at the observations performed 1 and 24 hours after treatment and persisted up to the 48-hour examination in two of these animals.
- No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
- The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Test substance is considered to be not irritating or corrosive to the rabbit skin.

Executive summary:

In a GLP compliant skin irritation study, performed according to OECD guideline 404, the test substance (moistened, 0.5 g) was applied, semi-occlusive, to the skin of three New Zealand White rabbits for 4 hours. After 4 hours, the dressing was removed and the skin was flushed with lukewarm tap water and observations were made for an additional 7 days. The test substance showed an edema score of 0 during the whole observation period. An erythema score of 1.67 and 0.67 was observed after 1 and 24 hours, respectively. An erythema score of 0.33 was observed after 48 and 72 hours. Erythema was fully reverisble within 7 days. Slight black staining was observed in all animals up to 48 hours. No corrosive effects were noted. Also no other clinical signs of test item related effects were observed. Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.

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