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: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 05 to Jully 30, 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Experimental test performed under GLP conditions and according to OECD Guideline and EC method.

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

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:

standard acute method

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
Purity Approx. 75 %
Expiry date 01-MAY-2010
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.
Safety precautions Routine hygienic procedures were used to ensure the health
and safety of the personnel.

Test animals

Species:

rat

Strain:

Wistar

Sex:

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 : 3 females
- Total number of animals : 6 females
- Age when treated : 12 weeks
- Identification : 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 animals without any visible signs of illness were used for the study.
- Husbandry conditions : 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.
- Faste period before treatment : approximately 17 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: purified water

Details on oral exposure:

The test item was diluted in vehicle (purified water) at a concentration of 0.2 g/mL and administered at a volume dosage of 10mL/kg.

Doses:

a single dose of 2000 mg/kg body weight

No. of animals per sex per dose:

6 females

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 17 hours (access to water was permitted). Food was provided again 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.
Observations :
Mortality / Viability Daily during acclimatization and twice daily during days 1 -15.
Body weights On test days 1 (prior to administration), 8 and 15.
Clinical signs Daily during acclimatization and at approximately 1,2,3 and 5 hours after administration on test day 1. Once daily during days 2-15.

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:

Female: 2000 mg/kg bw; Number of animals: 6; Number of deaths: 0

Clinical signs:

other: No clinical signs were observed during the course of the study.

Gross pathology:

No macroscopic findings were recorded 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 oral administration to female rats, observed over a period of 14 days is:
LD50 (female rat): greater than 2000 mg/kg body weight

Executive summary:

All animals survived, no clinical signs were observed during the course of the study. Only one animal showed a loss of body weight (0.5%), another animal did not gain body weight from test day 8 to the end of the observation period and for the remaining animals their body weight was within the range commonly recorded for this strain and age.

No significant adversed effect of FAT40812/A via single oral dose of 2000 mg/kg bw in female rat can be concluded.

LD50 (female rat) >2000 mg/kg body weight