Reaction products of diazotised 2-aminophenol-4-sulfonamide coupled with 7-amino-4-hydroxynaphthalene-2-sulfonic acid, subsequently diazotised and coupled with 3-oxo-N-phenylbutanamide and 3 aminophenol, chelated with chromium (3+), potassium salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

other: read across from analogue substance

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

A 2:1:1 mixture of: trisodium N(1')-N(2):N(1''')-N(2'')-η-6-[2-amino-4-(or 6)-hydroxy-(or 4-amino-2-hydroxy)phenylazo]-6''-(1-carbaniloyl-2-hydroxyprop-1-enylazo)-5',5'''-disulfamoyl-3,3''-disulfonatobis(naphthalene-2,1'-azobenzene-1,2'-diolato-O(1),O(2'))-chromate; trisodium N(1')-N(2):N(1''')-N(2'')-η-6,6''-bis(1-carbaniloyl-2-hydroxyprop-1-enylazo)-5',5'''-disulfamoyl-3,3''-disulfonatobis(naphthalene-2,1'azobenzene-1,2'-diolato-O(1),O(2'))-chromate; trisodium N(1')-N(2):N(1''')-N(2'')-η-6,6''-bis[2-amino-4-(or 6)-hydroxy-(or 4-amino-2-hydroxy)phenylazo]5',5'''-disulfamoyl-3,3''-disulfonatobis(naphthalene-2,1'azobenzene-1,2'-diolato-O(1),O(2'))-chromate

EC Number:

402-850-1

EC Name:

A 2:1:1 mixture of: trisodium N(1')-N(2):N(1''')-N(2'')-η-6-[2-amino-4-(or 6)-hydroxy-(or 4-amino-2-hydroxy)phenylazo]-6''-(1-carbaniloyl-2-hydroxyprop-1-enylazo)-5',5'''-disulfamoyl-3,3''-disulfonatobis(naphthalene-2,1'-azobenzene-1,2'-diolato-O(1),O(2'))-chromate; trisodium N(1')-N(2):N(1''')-N(2'')-η-6,6''-bis(1-carbaniloyl-2-hydroxyprop-1-enylazo)-5',5'''-disulfamoyl-3,3''-disulfonatobis(naphthalene-2,1'azobenzene-1,2'-diolato-O(1),O(2'))-chromate; trisodium N(1')-N(2):N(1''')-N(2'')-η-6,6''-bis[2-amino-4-(or 6)-hydroxy-(or 4-amino-2-hydroxy)phenylazo]5',5'''-disulfamoyl-3,3''-disulfonatobis(naphthalene-2,1'azobenzene-1,2'-diolato-O(1),O(2'))-chromate

Molecular formula:

not applicable being an UVCB

IUPAC Name:

reaction mass of: trisodium N(1')-N(2):N(1''')-N(2'')-η-6-[2-amino-4-(or 6)-hydroxy-(or 4-amino-2-hydroxy)phenylazo]-6''-(1-carbaniloyl-2-hydroxyprop-1-enylazo)-5',5'''-disulfamoyl-3,3''-disulfonatobis(naphthalene-2,1'-azobenzene-1,2'-diolato-O(1),O(2'))-chromate;trisodium N(1')-N(2):N(1''')-N(2'')-η-6,6''-bis(1-carbaniloyl-2-hydroxyprop-1-enylazo)-5',5'''-disulfamoyl-3,3''-disulfonatobis(naphthalene-2,1'azobenzene-1,2'-diolato-O(1),O(2'))-chromate;trisodium N(1')-N(2):N(1''')-N(2'')-η-6,6''-bis[2-amino-4-(or 6)-hydroxy-(or 4-amino-2-hydroxy)phenylazo]5',5'''-disulfamoyl-3,3''-disulfonatobis(naphthalene-2,1'azobenzene-1,2'-diolato-O(1),O(2'))-chromate (2:1:1)

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madörin AG, 4414 Füllinsdorf, CH
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: males: 193 to 250 g; females: 156 to 211 g
- Fasting period before study: 12 to 18 hours
- Housing: standard laboratory conditions. Groups of five in Makrolon type-3 cages with standard softwood bedding ("lignocel", Schill AG, 4132 Muttenz, CH)
- Diet: ad libitum; palleted standard Kliba 343, Batch 77/87 and 79/87 rat maintenance diet ("Kliba", Klingentalmühle AG,.4303 Kaiseraugst, CH) (analytical test report demonstrates suitability)
- Water: ad libitum; community tap water from Itingen (bacteriological assay and chemical water analysis demonstrated suitability)
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C ± 3 degrees
- Humidity: 40 to 70 %
- Air changes: 10 to 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

TEST ITEM PREPARATION
- The test item was placed into a glass beaker on a tared Mettler PK 300 balance, and the vehicle polyethylene glycol (PEG 400) was added. A weight by volume dilution was prepared using a homogeniser.
- Homogeneity of the test item in the vehicle was maintained during treatment using a magnetic stirrer.
- The preparation was made immediately prior to dosing.

TREATMENT
The animals received the test item on a mg/kg bw base by oral gavage after fasting for 12 to 18 hours (access to water was not interrupted). Food was again presented approximately one hour after dosing.
Application Volume/kg b.w.:
Group 1: 10 mL at 2000 mg/kg bw
Group 2: 20 mL at 5000 mg/kg bw

Doses:

2000 mg/kg bw
5000 mg/kg bw

No. of animals per sex per dose:

5 females and 5 males per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations: four times during test day 1, then daily during days 2-15
- Frequency of weighing: test days 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: all animals were killed by intraperitoneal injection of sodium pentobarbitone
- Observations recorded: signs and symptoms, mortality, body weights, macroscopic findings
- Specific signs and symptoms observed:
General behaviour: aggressiveness, vocalisation, restlessness / excitation, nervousness, fear, sedation, somnolence, sleep, coma
Respiration: apnoea, dyspnea, rales
Eye: chromodacryorrhea, exophthalmos, miosis, mydriasis, whitish discharge, lid adhesion, lacrimation
Nose: rhinorrhoea, epistaxis
Motility: akinesia, ataxia, dropped head, hyperkInesia, hypokinesia, paralysis (flaccid), paralysis (spastic), paddling movements, stiff movements, rolling movements
Body posture: ventral body position, latero-abdominal position, hunched posture
Motor susceptibility: spasms, tonic muscle spasms, clonic muscle spasms, opisthotonus, saltatory spasms, trismus, retching, "Straub" phenomenon, tremor, muscle-twitching, muscle-twitching (generalised)
Skin: erythema, oedema, necrosis
Various: loss of weight, emaciation, negative corneal reflex, diarrhoea, ruffled fur, salivation, pallor, cyanosis

Statistics:

no statistical method applied

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

Male, 2000 mg/kg bw, number of animals: 5, numebr of death: 0
Male, 5000 mg/kg bw, number of animals: 5, number of death:0
Female, 2000 mg/kg bw, number of animals: 5, number of death:0
Female, 5000 mg/kg bw, number of animals: 5, number of death:0

Clinical signs:

other: 2000 mg/kg : sedation, dispnea, piloerection, hunched posture 5000 mg/kg : sedation, dispnea, piloerection, hunched posture, movement disorder, diarrhoea the surviving rats recovered within 4 to 6 observation days

Gross pathology:

No pathological changes were revealed for the animals sacrificed at the end of the test
Lung: several dark-red foci, in part, black
Liver, stomach, intestine, kidneys, adrenalas, spleen: black

Applicant's summary and conclusion

Interpretation of results:

other: not classified under Regulation 1272/2008

Conclusions:

The substance was tested following OECD401. Under the experimental conditions the LD50 > 5000 mg/kg bw