Reaction mass of pentasodium 2-{[4-chloro-6-(ethyl{3-[(2-sulfonatoethyl)sulfonyl]phenyl}amino)-1,3,5-triazin-2-yl]amino}-5-hydroxy-6-({2-sulfonato-4-[(4-sulfonatophenyl)diazenyl]phenyl}diazenyl)naphthalene-1,7-disulfonate and tetrasodium 2-[(4-chloro-6-{ethyl[3-(vinylsulfonyl)phenyl]amino}-1,3,5-triazin-2-yl)amino]-5-hydroxy-6-({2-sulfonato-4-[(4-sulfonatophenyl)diazenyl]phenyl}diazenyl)naphthalene-1,7-disulfonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 December 2005 to 03 Febuary 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)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Details on test material:

-Batch No.: ROE 805 BOP 04/05
-Colour: Dark red
-Solubility in water: >100g/L at 20 °C
-Solubility in vehicle: Miscible
-Stability in solvent: 7 days in Water, Saline, Polyethylene Glycol, Carboxymethylcellulose, and 1 day in Vaseline and FCA at room temperature.
-Storage: At room temperature, in the desicator
-Expiration Date: October 01, 2010
-Purity: Approx. 82 % organic part (Na-salt),
all coloured components = 80.3 %;
Main component 1: 36.2 %,
Main component 2: 27.5 %, Oligomers: 10 %

Specific details on test material used for the study:

Identity: FAT 40824/A
Batch: Red ROE 805 BOP 04/05
Appearance: dark red powder
Purity: Organic part (Na-salt): approx. 82 %; Main component 1 : approx. 36.2 %; Main component 2: approx. 27.5 %; Oligomers: 10%
Expiration date: 01 October 2010
Stability in water: Max. 7 days at room temperature
Storage: At room temperature at about 20 °C, in a desiccator because test substance is hygroscopic, away from direct sunlight

Test animals

Species:

rat

Strain:

other: Rat, HanRcc:WIST (SPF)

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 at study initiation: 12-13 weeks
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet: Pelleted standard Provimi Kliba 3433 rat/moitse maintenance diet, batch no. 63/05 ad libitum.
- Water: Community tap water from Fiillinsdorf ad libitum.
- Fasting period before study: 18-19 hours

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): Air-conditioned with 10-15 air changes per hour.
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The dose formulations were made shortly before each dosing occasion using a magnetic stirrer and a spatula as homogenizers.The test item was weighed into a tared glass beaker on a surtable precision balance and the vehicle added (weight/volume). Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3 females per group and two groups per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights.

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.

Remarks on result:

other: no mortality observed at highest dose group tested (2000 mg/kg bw)

Mortality:

No deaths occurred during the study.

Clinical signs:

other: Slightly ruffled fur was observed in two of 6 animals from the 2- to 3- hour reading. Dark red feces were noted in both cages on test 2 and 3.

Gross pathology:

No macroscopic findlings were recorded at necropsy.

Other findings:

No data

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose ( LD50) of FAT 40824/A to female rat was greater than 2000 mg/kg bw.

Executive summary:

In a GLP compliant acute toxicity study conducted according to OECD TG 423, two groups, each of three female Wistar rats, were treated with FAT 40824/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. Slightly ruffled fur was observed in two out 6 animals from the 2- to the 3-hour reading. Dark red feces were noted in both cages on test day 2 and 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 of FAT 40824/A after single oral administration to female rats, observed over a period of 14 days (LD50) is greater than 2000 mg/kg body weight