ethyl 3-amino-2-cyanoprop-2-enoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

ethyl 3-amino-2-cyanoprop-2-enoate

Cas Number:

38109-77-2

Molecular formula:

C6H8N2O2

IUPAC Name:

ethyl 3-amino-2-cyanoprop-2-enoate

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): Etoxamide
- Physical state: white powder
- Purity test date: 05. 02. 2002
- Lot/batch No.: 29
- Expiration date of the lot/batch: : 05. 05. 2002
- 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: TOXI/COOP Ltd. Budapest
- Age at study initiation: 7 weeks
- Fasting period before study: overnight (after the test item administration food was withheld for 3 hours)
- Housing: 3 animals / cage in TECHNIPLAST 1291 type cages. (425x266x180 mm)
Cages (without bedding) were steam-sterilized at 121 °C for 20 minutes.
Bedding: Lignocel type (stzream sterilized), and after treatment: for 3 hours cardboard paper (sterilized)
- Diet (e.g. ad libitum): ad libitum, CRLT / N standard diet for rodent (supplied by Charles River Hungary)
- Water (e.g. ad libitum): potable water, ad libitum, offered daily in MAKROLON type drinking bottles sterilized before use
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.0-24.9 °C
- Humidity (%): 28.8-50.8 %
- Air changes (per hr): 10-15 / h
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h artificial light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE CMC 1% aqueous
- Concentration in vehicle: 2000 mg / 20 ml suspension and 200 mg / 20 ml suspension
- Amount of vehicle (if gavage): 20 ml / kg bw.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg / kg bodyweight

Doses:

2000 mg / kg in female rats (n=3)
200 mg / kg in female and male rats (n=3-3)

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations : for 6 hours after treatment and then twice a day
and weighing before treatment, on the 8th and 14th day
- Necropsy of survivors performed: yes (gross, macroscopic)
- Other examinations performed: clinical signs of toxicity, status of skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

> 200 - <= 2 000 mg/kg bw

Mortality:

Incidence of lethality

No. Of lethality / group size
Doses Male Female Total
200 mg/kg 0/3 0/3 0/6
2000 mg/kg - 3/3 3/3

Lethality occured in the 2000 mg/kg dose of test substance. All of the females died (in 2-24 hours) after treatment.

Clinical signs:

After serious CNS depressive symptoms all females died in the 2000 mg/kg dose group in the first day of the study. Clinical symptoms started 10 minutes (incoordinated movement) after treatment, lateral position, and dyspnea occured in 30 minutes and lated till death of animals. Animals in the 200 mg/kg dose groups were symptom-free after treatment and during the study in both sexes.

Body weight:

The mean body weights and body weight gain changed in a similar manner in the 200 mg/kg dose groups that expected from control animals of the same age and strain in both sexes.

Gross pathology:

In the females, died on study gross pathology revealed acute circulatory inefficiency (brain- congestioned and haemorrhages, lung-mottled and haemorrhages) and gastrointestinal injury (white deposit on the wall of stomach intestines filled with bloody, gaseous fluid with mucosal haemorrhages) as the cause of death. No pathologial findings occured at terminal sacrifice.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions the approximate calculated LD50 value of the substance administered to oral route to Wistar rats between 200 and 2000 mg/kg so according to EU regulations the test item is classified to harmful.