4-amino-5-hydroxy-6-(5-{4-chloro-6-[4-(2-sulfonatooxyethanesulfonyl)phenylamino]-1,3,5-triazin-2-ylamino}-2-sulfonatophenylazo)-3-(2-sulfonato-4-(2-sulfonatooxyethanesulfonyl)phenylazo)naphthalene-2,7-disulfonate potassium/sodium;reaction mass of: 4-amino-3-(4-ethenesulfonyl-2-sulfonatophenylazo)-5-hydroxy-6-(5-{4-chloro-6-[4-(2-sulfonatooxyethanesulfonyl)phenylamino]-1,3,5-triazin-2-ylamino}-2-sulfonatophenylazo)naphthalene-2,7-disulfonate potassium/sodium

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 05 to July 18, 2003

Reliability:

1 (reliable without restriction)

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)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

Identification FAT 40'815/A
Description Dark shining solid
Batch number WP 8/03
Expiry date 01-MAY-2010
Purity Approx. 75 %
Stability of test item dilution Stable in water for at least 7 days at room temperature.
Storage conditions In the original container, at room temperature
(range of 20 ± 3 °C), away from direct sunlight.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Test system : Rat, HanBrl: WIST (SPF)
- Rationale : Recognized by the international guidelines as a recommended test system.
- Source : RCC Ltd, Laboratory Animal Services
CH-4414 Füllinsdorf / Switzerland
- Number of animals per group : 5 males and 5 females
- Total number of animals : 5 males and 5 females
- Age when treated : Males: 8 - 9 weeks
Females: 12 weeks
- Acclimatization : Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
Husbandry conditions : Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, and continuously monitored environment with target ranges for room temperature 22 ± 3 °C and for relative humidity between 30-70 % (values above 70 % during cleaning process possible), 12 hours fluorescent light/ 12 hours dark, music during the light period.
- Diet : Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 04/03 (Provimi Kliba AG, CH-4303 Kaiseraugst/ Switzerland) ad libitum. Results of analyses for contaminants are archived at RCC Ltd, Itingen.
- Water : Community tap water from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd, Itingen.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: purified 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: 4 mL
Twenty-four 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.
Rationale : Dermal administration was used as this is one possible route of human exposure during manufacture, handling and use of the test item.

Duration of exposure:

24 h

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 females and 5 males

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: Slight blue discoloration produced by the test item was observed from test day 2 to test day 11 (two males and three females) and 13 (three males and two females), respectively. No systemic or local signs of toxicity were observed during the study period.

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 median lethal dose of FAT40'815/A after single dermal administration to rats of both sexes, observed over a period of 14 days is:
LD50 (rat): greater than 2000 mg/kg body weight

Executive summary:

Under the test conditions, slight discoloration was observed from test day 2 to test day 11 (2 males and 3 females) and 13 (3 males and 2 females) but were reversible. Therefore, no significant adverse effect appeared with a single dose of 2000 mg/kg bw of FAT40'8015/A applied on rat's skin.

The median lethal dose of FAT 40'815/A after single dermal administration to rats of both sexes, observed over a period of 14 days is:

LD50 (rat): greater than 2000 mg/kg body weight