Propanamide, 3-amino-2,2-dimethyl-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Remarks:

Research Institute for Organic Syntheses

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Physical state: white powder
- Analytical purity: 99.1 % (HClO4)
- Lot/batch No.: CHAD 0207
- Storage condition of test material: in the dark, at laboratory conditions

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeding farm TOP VELAZ s.r.o., závod Kolec
- Weight at arrival: 130 - 150g
- Fasting period before study: 24 hours before oral administration and 3 hours after application of the test substance
- Housing: conventional animal room - 3 animals of one sex in one plastic breeding cage Velaz T4
- Diet: ST 1 BERGMAN - standard pelleted diet ad libitum, (producer: Mill Kocanda, Jesenice u Prahy)
- Water: drinking tap water ad libitum (quality corresponding to Regulation No. 376/2000 Czech Coll. of Law)
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature 19 - 25°C, permanently monitored
- Humidity (%): relative humidity 30 - 70%, permanently monitored
- Photoperiod (hrs dark / hrs light): light : 12 hour light / 12 hour dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Name: aqua pro injectione
- Quality: sterile, non pyrogen
- Manufacturer: Biotika a.s., Slovenská Lupda, Slovak Republic
- Concentration in vehicle: max. 100 mg/ml

MAXIMUM DOSE VOLUME APPLIED: not exceeding 2 ml/100 g of body weight of animals.

DOSAGE PREPARATION: Immediately before application the test substance was weighed and mixed in vehicle (aqua pro injectione)

Doses:

2000 mg/kg bw.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: immediately before application, the 8th day and before euthanasia of animals
- Necropsy of survivors performed: yes, animals were sacrificed on the 15 th day. Nutritious status, body surface, body foramina, thoracic, abdominal and cranial cavity were evaluated. All gross macroscopic changes of organs and tissues were recorded in special data sheets.
- Time schedule of observations for mortality and clinical signs: daily
- Observations included changes in skin and fur, eyes, visible mucous membranes, behaviour of animals, somatomotor activity, reactions to stimuli, presence of lacrimation, salivation and discharge from nostrils, function of respiratory, digestive and urogenital system.

Statistics:

No data

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality; gross pathology findings in the lung (edema, hemorrhages) in the 2000 mg/kg bw treatment

Mortality:

Male: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: In all males of the dose level 2000 mg/kg no changes in behavior or clinical signs of intoxication were observed between 1 and 30 minutes after application and 3 hours after application. In females of the dose lev

Gross pathology:

Effects on organs:
- Oedema of lung was observed in all males and females.
- Small haemorrhages were observed in 2 males and all females.

Patholoical examination in detail:
- Males - 2000 mg/kg
Animal 1 - Lung - oedema ;
Animal 2 - Lung - oedema, small haemorrhage;
Animal 3 - Lung - oedema, small haemorrhage , Diarrhoea
- Females - 2000 mg/kg
Animal 1, 2 and 3 - Lung - oedema, small haemorrhage