trisodium 3-[(E)-2-(4-{[4-chloro-6-({2-[(4-{[4-(ethenesulfonyl)phenyl]amino}-6-fluoro-1,3,5-triazin-2-yl)amino]propyl}amino)-1,3,5-triazin-2-yl]amino}-5-sulfonaphthalen-1-yl)diazen-1-yl]naphthalene-1,5-disulfonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 June 2006 to 09 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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class 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 40826/A
- Lot/batch No.: TZ 5604 BOP 01/06
- Expiration date: 1 February 2011
- Purity: Content of organic part (Na-salt): approx. 78%. Oligomers: 13%. Main component: approx. 48%.
- Stability of test item: Stable under storage conditions
- Stability of test item dilution: Stable in water for at least 7 days at room temperature.
- Storage conditions: At room temperature (range of 20 ± 5 °C) in a exsiccator, light protected.

Specific details on test material used for the study:

Identity: FAT 40826/A
Batch no.: TZ 5604 BOP 01/06
Expiration date: February 01, 2011
Purity: Content of organic part (Na-salt): approx. 78 %; Oligomers: 13 %; Main component: approx. 48 %
Solubility in water: Approx. >50 g/L at room temperature
Stability in water: Max. 7 days at room temperature
pH: 7.6 (1 g/L)
Aggregate state/physical form at room temperature: Solid (orange powder)
Storage conditions: At room temperature at about 20 °C, away from direct sunlight
Specific instructions: Store in desiccator

Test animals

Species:

rat

Strain:

Wistar

Sex:

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: 12-13 weeks
- Fasting period before study: approximately 18 hours
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding ('Lignocel' Schill AG, CH-4132 Muttenz/Switzerland).
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 001/06 (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.

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

APPLICATION VOLUME: Test item dilution of 0.2 g/mL administered at a volume dosage of 10 mL/kg body weight.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females/group

Control animals:

no

Details on study design:

The animals received a single dose of the test item by oral gavage administration at 2000 mg/kg body weight after being fasted for approximately 18 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing. The application volume was 10 mL/kg body weight.
Rationale: Oral administration was considered to be an appropriate application method as it is a possible route of human exposure during manufacture, handling and use of the test item.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

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: Hunched posture was noted in all animals from the 30-minute to the 3- or 5-hour reading. Additionally, slight to moderate ruffled fur was noted in two animals from the 1-hour to the 5-hour reading, in three animals from the 3- to the 5-hour reading and in

Gross pathology:

No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose (LD50) of FAT 40826/A is greater than 2000 mg/kg body weight.

Executive summary:

In a GLP-compliant oral toxicity study, performed according to OECD guideline 423, two groups, each of three female Wistar rats were treated with FAT 40826/A by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (purified water) at a concentration of 0.2 g/mL and administered at a volume dosage of 10 mL/kg. 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. 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. All animals survived until the end of the study period. Hunched posture was noted in all animals from the 30-minute to the 3- or 5-hour reading. Additionally, slight to moderate ruffled fur was noted in two animals from the 1-hour to the 5-hour reading, in three animals from the 3- to the 5-hour reading and in one animal from the 30-minute to the 5-hour reading. Slight sedation was observed in three animals at the 5-hour reading. Reddish colored feces appeared in the cages at the 5-hour or 2-day examination and were still noted on test day 3. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. The median lethal dose (LD₅₀) of FAT 40826/A after single oral administration to female rats, observed over a period of 14 days is greater than 2000 mg/kg body weight.