Tetra(sodium/potassium)-7-[(E)-{2-acetamido-4-[(E)-(4-{[4-chlor-6-({2-[(4-fluor-6-{[4-(vinylsulfonyl)phenyl]amino}-1,3,5-triazin-2-yl)amino]propyl}amino)-1,3,5-triazin-2-yl]amino}-5-sulfonato-1-naphthyl)diazenyl]-5-methoxyphenyl}diazenyl]-1,3,6-naphthalintrisulfonate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experiment start date - 13 June 2006; Experiment completion date - 04 July 2006; Study competion date - 29 August 2006.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

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

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:

Description: Black sticky powder
Purity: Content of organic part (Na-salt): approx. 80 %;Oligomers: 13 %;Main component: approx. 53 %
Stability: Stable under storage conditions. Stable in water for 7 days.
Storage: At room temperature, desiccated and light protected.

Specific details on test material used for the study:

Identity: FAT 40827/A
Batch: T2 5572 BOP 01/06
Purity: determined in this study
Appearance: black sticky powder
Expiration date: 28.02.2011
Storage: at room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test System: Rat, HanRcc:WIST (SPF)
Number of animals per group: 5 males and 5 females
Total number of animals: 5 males and 5 females
Age at treatment: 8 weeks (male); 12 weeks (females)
Identification: By unique cage number and corresponding color-coded spots on the tail. The animals were marked at acclimatization start.
Randomization: Selected by hand at time of delivery. No computer generated randomization program.
Acclimatization: Under laboratory conditions after health examination. Only healthy animals were used for the study.

Conditions
Standard Laboratory Conditions.
Air-conditioned with ranges for room temperature of 22 ± 3 °C and relative humidity 30-70 % and approximately 10-15 air changes per hour. 12 hours artificial fluorescent light/12 hours dark, music during the light period.
Accommodation: 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 during treatment and observation.
Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet (batch 001/06) ad libitum.
Water: Community tap water, ad libitum.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

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

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

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
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.

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 signs of toxicity were observed during the study period. A purple staining of the treated skin was noted in all animals on days 2 and 3 of the study. The staining persisted still on day 4 in one female.

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 of test item after single dermal administration to rats of both sexes, observed over a period of 14 days is: LD50 (rat, dermal): greater than 2000 mg/kg body weight

Executive summary:

Five male and five female HanRcc:WIST (SPF) rats were treated with test item at 2000 mg/kg by dermal application. The test item was diluted in vehicle (purified water) at a concentration of 0.33 g/mL and administered at a volume dosage of 6 ml/kg. The application period was 24 hours. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded at approximately 30 minutes, 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 were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. No clinical signs were observed during the course of the study. The treated skin area was stained purple in all animals on days 2 and 3 after treatment. The staining persisted still on day 4 in one female. Otherwise, no dermal symptoms were noted. The body weight of the animals was within the range commonly recorded for this strain and age with the exception of one female, which lost 1.4 % of body weight during the first week after treatment. This animal recovered towards the end of the study. No macroscopic findings were observed at necropsy. Therefore, the LD50 of the test article was estimated to be greater than 2000 mg/kg.bw, which indicates that test article shall not be classified in accordance with CLP (Regulation EC No. 1272/2008).