lithium hydrogen 7-{(E)-[2-amino-4-(2-naphthyl)-1,3-thiazol-5-yl]diazenyl}naphthalene-1,3,5-trisulfonate (2:1:1)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-04-14 to 2010-04-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Meets the criteria for classification as reliable without restriction according to Klimisch et al (1997).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

lithium hydrogen 7-{(E)-[2-amino-4-(2-naphthyl)-1,3-thiazol-5-yl]diazenyl}naphthalene-1,3,5-trisulfonate (2:1:1)

EC Number:

940-433-0

Molecular formula:

C23H14Li2N4O9S4

IUPAC Name:

lithium hydrogen 7-{(E)-[2-amino-4-(2-naphthyl)-1,3-thiazol-5-yl]diazenyl}naphthalene-1,3,5-trisulfonate (2:1:1)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Hillcrest, Belton, Loughborough, UK
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.22 - 2.47 kg
- Housing: animals housed individually in suspended cages
- Diet : free access to food was allowed throughout the study (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK)
- Water : free access to water was allowed throughout the study
- Acclimation period: at least 5 days

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

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

test material moistened with water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied : 0.5g of test material moistened sufficiently with 0.5ml of distilled water to acheive a dry paste

Duration of treatment / exposure:

4h

Observation period:

Immediately following removal of the patches and approx. 1, 24, 48 and 72h (performed approx. 68h) later the test sites were examined for evidence of primary irritation and scored according to a 4 point scale.

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: dorsal/flank area
- Type of wrap if used: The moistened test material was introduced under a 2.5cm x 2.5cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. The trunk of each rabbit was wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing : Any Residual test material was removed by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4h

SCORING SYSTEM:
Immediately following removal of the patches and approximately 1, 24, 48 and 72 (performed approximately 68) hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale:

Erythema and Eschar Formation Value
No erythema .................................................................................................... 0
Very slight erythema (barely perceptible) ........................................................ 1
Well-defined erythema ..................................................................................... 2
Moderate to severe erythema .......................................................................... 3
Severe erythema (beef redness) to eschar formation preventing grading of
erythema ......................................................................................................... 4

Oedema Formation Value
No oedema ....................................................................................................... 0
Very slight oedema (barely perceptible) ........................................................... 1
Slight oedema (edges of area well-defined by definite raising) ........................ 2
Moderate oedema (raised approximately 1 millimetre) .................................... 3
Severe oedema (raised more than I millimetre and extending beyond the area
of exposure) ..................................................................................................... 4

Any other skin reactions and clinical signs of toxicity, if present, were also recorded.

Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period

The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the two test rabbits (8 values) and this total was divided by four to give the primary irritation index of the test material. The test material was classified according to the following scheme devised by 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, p.46-59:
Primary Irritation Index/ Classification of lrritancy
0/ Non-irritant
>O to 2/ Mild irritant
>2 to 5/ Moderate irritant
>5 to 8/ Severe irritant
If irreversible alteration of the dermal tissue is noted in any rabbit, as judged by the Study Director, which include ulceration and clear necrosis or signs of scar tissue, the test material is classified as corrosive to rabbit skin. Classification according to Draize may, therefore, not be applicable.

The results were evaluated according to EU labelling regulations Commission Directive 2001/59/EC for classification and labelling of dangerous substances.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 69095 male

Time point:

other: highest score at 24, 48 & 72h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48h

Results 2

Irritation parameter:

erythema score

Basis:

animal: 69096 male

Time point:

other: highest score at 24, 48 & 72h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48h

Results 3

Irritation parameter:

edema score

Basis:

animal: 69095 male

Time point:

other: highest score at 24, 48 & 72h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

edema score

Basis:

animal: 69096

Time point:

other: highest score at 24, 48 & 72h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Very slight erythema was noted at both treated skin sites at the 24-Hour observation. No other evidence of skin irritation was noted during the study.

Other effects:

Both animals showed expected gain in bodyweight during the study.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material produced a primary irritation index of 0.5 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. The test material did not meet the criteria for classification as irritant or corrosive according to the EU labelling regulations Commission Directive 2001/59/EC.

Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following: OECD Guidelines for the Testing of Chemicals No. 404 "Acute Dermal IrritationlCorrosion" (adopted 24 April 2002) Method B4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC) No. 440/2008

Results & Conclusions

The test material produced a primary irritation index of 0.5 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. The test material did not meet the criteria for classification as irritant or corrosive according to the EU labelling regulations Commission Directive 2001/59/EC.