main component 1 (isomer 1): 2-{6-fluoro-4-[3-(2,5-disulfo-phenylazo)-4-hydroxy-2-sulfonapht-7-ylamino]-1,3,5-triazin-2-ylamino}-3-{6-fluoro-4-[3-(1,5-disulfonaphth-2-ylazo)-4-hydroxy-2-sulfonaphth-7-ylamino]-1,3,5-triazin-2-ylamino}-propane sodium salt;main component 1 (isomer 2): 2-{6-fluoro-4-[3-(2,5-disulfo-phenylazo)-4-hydroxy-2-sulfonaphth-7-ylamino]-1,3,5-triazin-2-ylamino}-3-{6-fluoro-4-[3-(2,5-disulfo-phenylazo)-4-hydroxy-2-sulfonaphth-7-ylamino]-1,3,5-triazin-2-ylamino}-propane sodium salt;main component 2: 2,3-bis-{6-fluoro-4-[3-(2,5-disulfo-phenylazo)-4-hydroxy-2-sulfonaphth-7-ylamino]-1,3,5-triazin-2-ylamino}-propane sodium salt;main component 3: 2,3-bis-{6-fluoro-4-[3-(1,5-disulfonaphth-2-ylazo)-4-hydroxy-2-sulfonaphth-7-ylamino]-1,3,5-triazin-2-ylamino}-propane sodium salt

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 October 1996 to 14 November 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

No randomization of the animals was performed. They were distributed according to the sex into groups of five.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

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:

422-610-1

EC Name:

-

Molecular formula:

multi constituent

IUPAC Name:

tetracosasodium 2-[(1E)-2-[6-({4-[(1-{[4-({6-[(1E)-2-(2,5-disulfonatophenyl)diazen-1-yl]-5-hydroxy-7-sulfonatonaphthalen-2-yl}amino)-6-fluoro-1,3,5-triazin-2-yl]amino}propan-2-yl)amino]-6-fluoro-1,3,5-triazin-2-yl}amino)-1-hydroxy-3-sulfonatonaphthalen-2-yl]diazen-1-yl]benzene-1,4-disulfonate 2-[(1E)-2-[6-({4-[(2-{[4-({6-[(1E)-2-(2,5-disulfonatophenyl)diazen-1-yl]-5-hydroxy-7-sulfonatonaphthalen-2-yl}amino)-6-fluoro-1,3,5-triazin-2-yl]amino}propyl)amino]-6-fluoro-1,3,5-triazin-2-yl}amino)-1-hydroxy-3-sulfonatonaphthalen-2-yl]diazen-1-yl]naphthalene-1,5-disulfonate 3-[(1E)-2-[6-({4-[(1-{[4-({6-[(1E)-2-(4,8-disulfonatonaphthalen-2-yl)diazen-1-yl]-5-hydroxy-7-sulfonatonaphthalen-2-yl}amino)-6-fluoro-1,3,5-triazin-2-yl]amino}propan-2-yl)amino]-6-fluoro-1,3,5-triazin-2-yl}amino)-1-hydroxy-3-sulfonatonaphthalen-2-yl]diazen-1-yl]naphthalene-1,5-disulfonate 5-[(1E)-2-[6-({4-[(2-{[4-({6-[(1E)-2-(2,5-disulfonatophenyl)diazen-1-yl]-5-hydroxy-7-sulfonatonaphthalen-2-yl}amino)-6-fluoro-1,3,5-triazin-2-yl]amino}propyl)amino]-6-fluoro-1,3,5-triazin-2-yl}amino)-1-hydroxy-3-sulfonatonaphthalen-2-yl]diazen-1-yl]naphthalene-1,6-disulfonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): FAT 40'557/A
- Lot/batch No.: PV 1
- Purity: Approx. 65%
- Expiry date: 30 September 1996
- Stability of Test Article: Stable under storage condition
- Stability of Test Article Dilution: Stable in polyethylene glycol for at least 48 hours
- Storage: In the original container at room temperature away from direct sunlight.

Specific details on test material used for the study:

Identity: FAT 40557/A
Batch-no.: PV1
Purity: 65 %
Appearance: Solid powder, red-brown
Stability in test article: Stable under storage condition; expiration date: 30-SEP-1996
Stability of Test Article Dilution: Stable in polyethylene glycol for at least 48 hours
Expiration date: 30 September, 2002
Storage conditions: In the original container at room temperature away from direct sunlight.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, 4414 Füllinsdorf / Switzerland
- Age at start of treatment: males: 8 weeks, females: 10 weeks
- Weight at start of treatment: males: 191.1 - 202.0 g, females 177-198.8 g
- Fasting period before study: 19.5 hours
- Housing: Groups of five in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet: Pelleted standard Kliba 343, Batch no. 78/96 rat maintenance diet (Kliba Mühlen AG, CH-4303 Kaiseraugst) available ad libitum
- Water: Community tap water from Itingen, available ad libitum.
- Acclimation period: One week under laboratory conditions, after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70 (values above 70 % during cleaning process possible)
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Treatment: 09-OCT-1996 to 23-OCT-1996

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg bw

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
- Frequency of observations and weighing: Mortality / Viability: Four times during test day 1, and once daily during days 2-15, Body Weights: Test days 1 (pre-administration), 8 and 15, Symptoms: Each animal was examined for changes in appearance and behaviour four times during day 1, and daily during days 2-15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (general behaviour, respiration, eye, nose, motility, body posture, motor susceptibility, skin), gross pathology

Statistics:

The LOGIT-Model could not be used as no deaths occurred.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

other: Diarrhea was noted in one male animal on test day 1, 5 hours after the test article administration.

Gross pathology:

No macroscopic findings were observed at necropsy.

Any other information on results incl. tables

The animals received a single dose of the test article on a mg/kg body weight basis by oral gavage following fasting for approximately 19.5 hours, but with free access to water. Food was provided again approximately 3 hours after dosing.

Rationale:

Oral administration was used as this is one possible route of human exposure during manufacture, handling and use of the test article.

Necropsy:

Necropsies were performed by experienced prosectors. At the end of the observation period all animals were sacrificed by intraperitoneal injection of NARCOREN (Rhone Merieux 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.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral median lethal dose (LD50) of FAT 40557/A was estimated to be greater than 2000 mg/kg bw.

Executive summary:

In a GLP-compliant oral toxicity study, performed according to OECD guideline 401, Wistar rats (5/sex) were administered the test substance (2000 mg/kg bw in polyethylene glycol) by oral gavage followed by a 14-day observation period. Mortality did not occur, body weights were within the range of physiological variability known for rats of this strain and age, and no macroscopic findings were observed at necropsy. Diarrhoea was noted in one male animal on test day 1. Based on these observations, the oral median lethal dose (LD50) of FAT 40557/A in an acute oral toxicity of the test substance in rats of both sexes observed for a period of 14 days was greater than 2000 mg/kg bw.