Sodium 5-({4-chloro-6-[ethyl(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)-4-hydroxy-3-[(E)-(1-sulfonato-2-naphthyl)diazenyl]naphthalene-2,7-disulfonate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.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

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes (incl. QA statement)

Remarks:

RCC Ltd., 4452 Itingen, Switzerland

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): FAT 40'817/A
- Description: red powder
- Purity: 93.3%
- Lot/batch No.: WIA 260/2
- Expiration date of the lot/batch: 20 february 2009
- Stability of test item dilution: Stable in purified water for at least 7 days at room temperature.
- Storage condition of test material: At room temperature (range of 20 ± 3 °C), light protected.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: males: 8 weeks, females: 12 weeks
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. lndividually in Makrolon type-3 cages with standard softwood beddlng ('Lignocel', Schill AG, CH-4132 Muttenz) during treatment and observation.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no.78/03 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland), ad libitum,
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

Purified water prepared at RCC Ltd.

Details on dermal exposure:

One day before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10% of the total body surface. Only those animals without injury or irritation on the skin were used in the test. On test day 1, the test item was applied at a dose of 2000 mg/kg body weight evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage. Application volume/kg body weight: 6 mL. 24 Hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels. Thereafter, the reaction sites were assessed. The fur of the animals was shaved on test days 4 (female no. 7), 6 (females nos, 7 and 8) and 11 (all animals) just prior to the assessment of the reaction to facilitate the skin reading.

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

Mortaility/ Viability: Daily during the acclimization period, at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Body weights: On test days 1 (prior to administration), 8 and 15.
Clinical signs: Daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15.

All animalse were killed at the end of the observation period by an intraperitoneal injection of Vetanarcol at a dose of at least 2.0 mL/kg body weight (equivalent to al least 324 mg sodium pentobarbitone/kg body weight) and discarded after macroscopic examinations were peformed. No organs or tissues were retained.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No systemic or local signs of toxicity were observed during the study period. Slight to marked red discoloration produced by the test item of the treated skin area was observed in all animals immediately after removal of the dressing and persisted up to t

Gross pathology:

No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The toxicity of the test substance is greater than 2000 mg/kg bw.

Executive summary:

In a GLP compliant dermal toxicity study, performed according to OECD guideline 402, Wistar rats (5/sex) were treated with the test substance (2000 mg/kg bw) by dermal application. The test substance was diluted in vehicle (purified water), administered on the skin with a syringe and covered with a semi-occlusive dressing for 24 hours. After 24 hours the dressing was removed and the skin was flushed with lukewarm tap water. A 14-day observation period followed. No deaths occurred during the study and the body weight of the animals was within the range commonly recorded for this strain and age. Slight to marked red discoloration produced by the test item of the treated skin area was observed in all animals immediately after removal of the dressing and persisted up to the end of the observation period. No clinical signs or macroscopic findings were observed. Based on the observations, the toxicity of the test substance is greater than 2000 mg/kg bw.