Black HM 2482

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From February 5th to February 26th, 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted May 12, 1981

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

EWG Directive 84/449/ EWG, Amtsblatt der Europaeischen Gemein-schaften L 251, Jahrgang 27, 19. 9. 84. B.1. Akute Toxizitaet -oral / 96.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

400-920-6

EC Name:

-

Cas Number:

89857-06-7

Molecular formula:

C50 H53 N11 O14 S

IUPAC Name:

5'-[2-(7-{2-[4-(2-{1'-[3-(dimethylazaniumyl)propyl]-6'-hydroxy-4'-methyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium-5'-yl}diazen-1-yl)phenyl]diazen-1-yl}-8-hydroxy-6-sulfonatonaphthalen-2-yl)diazen-1-yl]-6'-hydroxy-3,4'-dimethyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium bis(2-hydroxypropanoate)

Test animals

Species:

rat

Strain:

Wistar

Remarks:

KFM-Han

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintier farm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: males: 186 - 197 g; females: 168 - 182 g
- Housing: groups of 5 in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, Switzerland).
- Diet: pelleted standard Kliba 343, Batch 15/84 rat maintenance diet ("Kliba", Klingentalmuehle AG, Switzerland), ad libitum
- Water: community tap water from Itingen, ad libitum
- Acclimation period: one week under laboratory conditions, after veterinary examination
- Method of randomisation in assigning animals to test and control groups: computer-generated random algorithm

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Air changes: 10 -15 per hr
- Photoperiod: 12 hours artificial fluorescent light / 12 hours dark, at least 8 hours music/light period

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2% solution of CMC, carboxymethyl cellulose natrium salt purum, visc. 100 CPS

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2% solution of CMC in distilled water

MAXIMUM DOSE VOLUME APPLIED: Group 1: 20 ml at 5000 mg/kg

DOSAGE PREPARATION: The test article was placed into a glass beaker pn a tared Mettler PK 4800 balance and the vehicle (2% solution of CMC, carboxymethylcellulose natriumsalt purum, visc. 100 CPS, Fluka AG, CH 9470 Buchs / Switzerland in distilled water) was added. A weight by volume dilution was prepared using a homogenizer (Ultra-Turrax, Janke and Kunkel, Staufen, FRG). Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer (Auer-Bittmann, Switzerland). The preparation was made immediately prior to dosing.

Doses:

5000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

The animals received the test article on a mg/kg body weight base by oral gavage after being fasted for 12 to 18 hours (access to water was not interrupted). Food was again presented approximately one hour after dosing.
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: 4 times during test day 1 and daily during days 2 - 15 for mortality/viability. Test days 1 (pre-administration), 8 and 15 for body weights. Each animal was examined for changes in appearance and behaviour 4 times during day 1, and daily during days 2 - 15.
- Necropsy of survivors performed: yes. Necropsies were performed by experienced prosectors. AII animals were necropsied. AII animals were anesthetized by intraperitoneal injection of sodium pentobarbital and killed by exsanguination.
- Examinations performed: clinical signs, body weight, pathology,: Observations included general behavior, nose, respiration, eye, motility, body position, motor susceptibility, skin...

Statistics:

The LOGIT-Model could not be applied to the observed rates of death. The LD50 was estimated without use of a statistical model.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

No changes were observed.

Gross pathology:

No gross pathological changes were observed in any of the animals.

Applicant's summary and conclusion

Interpretation of results:

other: not classified as harmful/toxic according to the CLP Regulation (EC) No.1272/2008

Conclusions:

LD50 (male/female rats) > 5000 mg/kg bw

Executive summary:

The test item was evaluated for acute oral toxicity when administered in Wistar rats by single oral gavage, followed by an observation period of 15 days. The study was performed according to the OECD Guideline No. 401. 
The test item was administered to rats of both sexes by oral gavage at a dose of 5000 mg/kg. The following death rate was was observed: 0% at 5000 mg/kg. Dyspnea was observed in treated animals and all rats had recovered within 3 hours after treatment. No macroscopic organ changes were observed.

The acute oral LD50 of the test item in rats of both sexes, observed over a period of 15 days, was estimated to be greater than 5000 mg/kg.