2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-8-[2-[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]diazenyl]-, potassium sodium salt (1:?:?), coupled with diazotized 2-[(4-amino-5-methoxy-2-methylphenyl)sulfonyl]ethyl hydrogen sulfate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experiment start date - 15 May 2003; Experiment end date - 05 June 2003; Study completion date - 23 June 2003.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

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 40'812/A
- Purity: Approx. 75%
- Lot/batch No.: WP 3/03
- Expiration date: 23 April 2010
- Stability of test item dilution: Stable in purified water for at least 7 days at room temperature.
- Storage conditions: At room temperature (range of 20 ± 3 °C), away from direct sunlight

Specific details on test material used for the study:

Identity: FAT 40812/A
Batch: WP 8/03
Purity: approx. 75 %
Appearance: Solid, dark red-brownish powder
Expiration date: 23 April 2010
Storage: At room temperature at about 20 °C

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 when treated: 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: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 84/02 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland), ad libitum,
- 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): 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

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.

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:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Daily during the acclimatization and twice during days 1-15.
Body weights: On test days 1 (prior to administration), 8 and 15.
Clinical signs: Daily during the acclimatization period and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15.
- Necropsy of survivors performed: Macroscopic examinations were performed. 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: Light red discoloration of the treated skin area produced by the test item was observed in all male and female animals from test day 2 after removal of the dressing to either test day 11, 12, 13, 14, or 15.

Gross pathology:

No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 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 (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 no macroscopic findings were observed. Light red discoloration of the treated skin area produced by the test item was observed in all male and female animals. Two females showed a loss of body weight (0.5 % and 0.6 %) between test day 1 and 8 and another female showed also a loss of body weight (0.3 %) between test day 8 and the end of the observation period. The body weight of the remaining female and all male animals was within the range commonly recorded for this strain and age. Based on the observations, the LD50 of the test substance was determined to be greater than 2000 mg/kg bw.