Reaction mass of Trisodium 4-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-{[1-ethyl-2-hydroxy-4-methyl-6-oxo-5-(sulfonatomethyl)-1,6-dihydropyridin-3-yl]diazenyl}benzenesulfonate and Trisodium 4-({4-chloro-6-[(3-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-{[1-ethyl-2-hydroxy-4-methyl-6-oxo-5-(sulfonatomethyl)-1,6-dihydropyridin-3-yl]diazenyl}benzenesulfonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study initiation date - 24 June 1992; Experiment start date - 01 July 1992; Experiment completion date - 15 July 1999; Study completion date - 20 August 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Trisodium 4-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)- 2-{[1-ethyl-2-hydroxy-4-methyl-6-oxo-5-(sulfonatomethyl)-1,6-dihydropyridin-3- yl]diazenyl}benzenesulfonate

Cas Number:

106359-90-4

IUPAC Name:

Trisodium 4-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)- 2-{[1-ethyl-2-hydroxy-4-methyl-6-oxo-5-(sulfonatomethyl)-1,6-dihydropyridin-3- yl]diazenyl}benzenesulfonate

Test material form:

solid: particulate/powder

Details on test material:

None

Specific details on test material used for the study:

Code number: FAT 40000/G
Batch number: 67/92
Purity: 79.5%
Appearance: solid
Solubility: miscible
Storage: room temperature
Expiration date: 01 June 1993.

Test animals

Species:

rat

Strain:

Wistar

Remarks:

SPF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wölferstrasse 4, CH-4414 Füllinsdorf
- Age at study initiation: males: 8 weeks females: 10 weeks
- Weight at study initiation: males: 199 - 209 g females: 165 - 179 g
- Fasting: overnight
- Housing: Makrolon type-3 cages (size: 22 x 37.5 x 15 cm) with standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard
- Water (e.g. ad libitum): Community tap water
- Acclimation period: One week under laboratory conditions, after veterinary examination. Only animals without any visual signs of illness were used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+-3 °C
- Humidity (%): 40-70 %,
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light (approx. 100 Lux) / 12 hours dark.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

bidistilled

Details on oral exposure:

Application Volume/kg body weight: 10 ml at 2000 mg/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 animals per dose

Control animals:

yes

Details on study design:

Mortality / Viability: Four times during test day 1 (according to the laboratories SOP's the last check was conducted 5 hours after application), and daily during days 2 - 1 5.
Body Weights: Test days 1 (pre-administration), 8 and 15.

Clinical Signs
Each animal was examined for changes in appearance and behaviour four times during day 1, and daily during days 2-15. All abnormalities were recorded. The animals were checked for the clinical signs listed below.
GENERAL BEHAVIOUR
aggressiveness
vocalization
restlessness / excitation
nervousness, fear
sedation
somnolence
sleep
coma

RESPIRATION
apnea
dyspnea
rales

EYE
chromodacryorrhea
exophthalmos
miosis
mydriasis
whitish discharge
lid adhesion
lacrimation
negative corneal reflex

NOSE
rhinorrhea
epistaxis

MOTILITY
akinesia
ataxia
dropped head
hyperkinesia
hypokinesia
paralysis, flaccid
paralysis, spastic
paddling movements
stiff gait
rolling movements

BODY POSTURE
ventral body position

MOTOR SUSCEPTIBILITY
spasms
tonic muscle spasms
clonic muscle spasms
opisthotonus
saltatory spasms
trismus
tremor
muscle-twitching
muscle-twitching
generalized

SKIN: erythema, edema, necrosis
OTHERS: Loss of weight, emaciation, diarrhea, ruflled fur, salivation, pallor, cyanosis.

Necropsy
Necropsies were performed by experienced prosectors. All animals were necropsied. All animals were euthanized by intraperitoneal injection of sodium pentobarbitone

Statistics:

The LOGIT-Model could not be applied to the observed rates of death. The toxicity was estimated without use of a statistical model.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No death occurred during the study period.

Clinical signs:

other: No clinical signs were noted in the animals.

Gross pathology:

No macroscopical organ findings were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of compound FAT 40000/G in rats is greater than 2000 mg/kg bw.

Executive summary:

The acute oral toxicity of FAT 40000/G was evaluated according to OECD test guideline 401 and Directive 84/449 EEC B.1 in a GLP certified laboratory.

The test article FAT 40000/G was administered to groups of 5 male and 5 female rats by oral gavage, at single dose of 2000 mg/kg. The following death rate was observed: 0 % at 2000 mg/kg. No clinical signs were noted in the animals. The body weight gain of the animals was not affected by the test article treatment throughout the entire study period. No macroscopical organ findings were observed.

The acute oral toxicity of FAT 40000/G in rats of both sexes, observed over a period of 15 days, was estimated to be greater than 2000 mg/kg.