2-{4-[4-[4-fluoro-6-(2-(2-vinylsulfonylethoxy)ethylamino)-1,3,5-triazin-2-ylamino]phenylazo]phenylazo}naphthalene-4,6,8-trisulfonate, trisodium salt

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 May 2001 to 23 May 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

442-230-8

EC Name:

-

Cas Number:

321679-52-1

Molecular formula:

Hill formula: C31 H25 F N9 Na3 O12 S4 CAS formula: C31 H28 F N9 O12 S4 · 3 Na

IUPAC Name:

trisodium 7-(2-{4-[2-(4-{[4-({2-[2-(ethenesulfonyl)ethoxy]ethyl}amino)-6-fluoro-1,3,5-triazin-2-yl]amino}phenyl)diazen-1-yl]phenyl}diazen-1-yl)naphthalene-1,3,5-trisulfonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): FAT 40'800/A
- Lot/batch No.: WP 2/01
- Purity: approx. 70%
- Stability: Stable under storage conditions
- Stability of test item in vehicle: 24 hours
- Expiry date: 14 February 2007
- Storage: room temperature (range of 20 ±3 °C), away from direct sunlight

Specific details on test material used for the study:

Identity: FAT 40800/A
Batch number: WP 2/01
Active ingredient: ca. 70 %
Aggregate state at room temperature: Solid / powder
Color: Dark orange
Stability of test item: Stable under storage conditions
Stability of test item in vehicle: 24 hours at room temperature
Storage conditions: At room temperature at about 20 °C, away form direct sunlight
Expiration Date: February 14, 2007

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd., Biotechnology & Animal Breeding Division, CH-4414 Füllinsdorf
- Age at study initiation: Males: 9 weeks, Females: 12 weeks
- Weight at study initiation: Males: 230.6 - 246 g, Females: 187.7 - 210.4 g
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz) during treatment and observation.
- Diet: Pelleted standard Kliba 3433, batch no. 07/00 rat maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst) available ad libitum.
- Water: Community tap water from Itingen, available ad libitum.
- Acclimation period: Under laboratory conditions, after health examination.

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

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 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.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Observations: Mortality/Viability: Daily during acclimatization and at least one, two, three and approximately five hours after the test item administration, depending on the occurrence of clinical signs of toxicity. At least once daily during days 2-15, depending on the occurrence of clinical signs of toxicity.
Body weights: On test days 1 (pre-administration), 8 and 15.
Clinical signs: Daily during acclimatization and at least one, two, three and approximately five hours or more on test day 1 after the test item administration, depending on the occurrence of clinical signs of toxicity. At least once daily during days 2-15, depending on the occurrence of clinical signs of toxicity. All abnormalities were recorded.
- Necropsy: At the end of the observation period all animals were sacrificed by intraperitoneal injection of NARCOREN (Rhône Mérieux GmbH, D-88471 Laupheim) at a dose of at least 2.0 mL/kg body weight (equivalent to at least 320 mg sodium pentobarbitone/kg body weight). The animals were examined macroscopically and all abnormalities recorded. Thereafter, they were discarded.

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: In all animals slight discoloration and test item residuals were noted from the second to the sixth/seventh observation day. Those findings were considered to be test item-related non toxic effects.

Gross pathology:

No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose (LD50) of FAT 40800/A after single dermal exposure to Wistar rats of both sexes, observed over a period of 14 days is >2000 mg/kg bw.

Executive summary:

In a GLP-compliant dermal toxicity study, performed according to OECD guideline 402, a group of Wistar rats (5/sex/dose) were exposed to the test substance (2000 mg/kg bw). The test substance was dissolved in water and applied on the skin with a syringe and covered with an dressing for 24 hours. The treated skin was washed after 24 hours and a 14-day observation period followed. No deaths occurred during the study. In all animals, slight discoloration and test substance residuals were noted from the second to the sixth/seventh observation day. Those findings were considered to be test substance-related non toxic effects. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. Based on the study results, the median lethal dose (LD50) of FAT 40800/A after single dermal administration to Wistar rats of both sexes, observed over a period of 14 days is >2000 mg/kg bw.