N-ethyl-4-[[4-(ethylamino)-m-tolylphenyl][4-(ethylimino)-3-methylcyclohexa-2,5-dien-1-ylidene]methyl]-m-toluidine monoacetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-05-18 to 2000-07-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant study report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(1996)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(1996)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

(1998)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-ethyl-4-[[4-(ethylamino)-m-tolylphenyl][4-(ethylimino)-3-methylcyclohexa-2,5-dien-1-ylidene]methyl]-m-toluidine monoacetate

EC Number:

305-170-2

EC Name:

N-ethyl-4-[[4-(ethylamino)-m-tolylphenyl][4-(ethylimino)-3-methylcyclohexa-2,5-dien-1-ylidene]methyl]-m-toluidine monoacetate

Cas Number:

94349-52-7

Molecular formula:

C28H38N3.C2H3O2

IUPAC Name:

[4-[bis[4-(ethylamino)-3-methyl-phenyl]methylene]-2-methyl-cyclohexa-2,5-dien-1-ylidene]-ethyl-ammonium;acetate

Details on test material:

- Physical state: liquid
- Storage condition of test material: at room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Deutschland, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: male animals approx. 8 - 12 weeks, female animals approx. 13 - 18 weeks
- Weight at study initiation: males: 178 - 183 g; females: 171 g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Single housing
- Diet: ad libitum (Kliba-Labordiaet, Provimi Kliba SA, Kaiseraugst, Switzerland)
- Water: ad libitum (tap water)
- Acclimation period: for at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5 and 20 g/100 mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Aqueous formulation corresponds to the physiological medium.

CLASS METHOD
- Rationale for the selection of the starting dose: Based on the physical and chemical characteristics of the test substance and its composition, some acute oral toxicity was expected. Therefore, a starting dose of 500 mg/kg body weight has been chosen in the first step with 3 male animals. As none of those animals died, 2000 mg/kg body weight were administered to 3 male animals in a second step. Because all animals died at the second step, 500 mg/kg body weight have been tested in a third step with 3 female animals. Because 2 animals survived the third step the study was terminated.

Doses:

200, 500 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 17 days
- Frequency of observations and weighing: observations were done at least once each workday; weighing was performed at the start of the study, weekly thereafter and at the end of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 500 - < 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 350 - < 1 400 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: recalculated based on dye content of registered substance (74% w/w) versus tested material (52% w/w)

Mortality:

All animals of. the 2000 mg/kg dose group died until study day 8. One female animal of the 500 mg/kg dose group died on study day 2.

Clinical signs:

other: Male animals: Signs of toxicity noted in the 2000 mg/kg dose group comprised impaired and poor general state, dyspnoea, gasping, apathy, abdominal position, staggering, paresis, tremor, piloerection, smeared fur, diarrhea, reduced feces, exsiccosis, viole

Gross pathology:

Necropsy findings of the animal that died at 500 mg/kg comprised moderate dilation of stomach, small intestine and large intestine as well as blue and/or red discoloration of the stomach content. In the animals that died at 2000 mg/kg blue and or red discoloration of intestinal tract content and same organs and tissues was observed. No macroscopic pathologic abnormalities were noted in the surviving animals examined at the end of the observation period.