2-cyano-N-methylacetamide

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well reported non guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Principles of method if other than guideline:

Single ip injection with 15 day observation period in mice

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-cyano-N-methylacetamide

EC Number:

228-705-0

EC Name:

2-cyano-N-methylacetamide

Cas Number:

6330-25-2

Molecular formula:

C4H6N2O

IUPAC Name:

2-cyano-N-methylacetamide

Details on test material:

- Name of test material: N-Methylcyanacetamid

- Physical state: powder

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wilhelm Gassner, Sulzfeld
- Age at study initiation: about 4 weeks
- Weight at study initiation: males, 700 mg/kg: 26.0 g; males, 200 mg/kg: 28.0 g; females, 700 mg/kg: 24.0 g; females, 200 mg/kg: 28.0 g
- Fasting period before study: 16 h (water ad libitum)
- Housing: Makrolon cages, Typ I
- Diet (ad libitum): Herilan, MRH-Haltung; H. Eggersmann KG, Rinteln
- Water (ad libitum): VE water on working days, tap water on holidays
- Acclimation period: At least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26
- Humidity (%): 45 - 75
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

water

Doses:

200 and 700 mg/kg

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: less than 15 min, 15 min, 30 min, 1 h, 2 h, 4 h and 5 h after application. Afterwards once per day.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 200 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 279 mg/kg bw

Based on:

test mat.

Mortality:

After a single application of 700 mg/kg all mice (male and female) were dead after 1 day. Three males and one female died 1 day after the application of 200 mg/kg test substance.

Clinical signs:

After 15 min the first clinical signs were observed at both dose levels, including dyspnea, apathy, staggering, convulsions, ruffled haircoat, hypohydration and (a general) bad condition. Additionally, an application of 200 mg/kg resulted in twitching, clonic cramps and spastic gaits of the animals. Petrusions of the eyeballs were observed at the dose level of 700 mg/kg only

Body weight:

200 mg/kg: The males gained body weight during the test, whereas the females has an almost stable weight.
700 mg/kg: Weighting was only performed at the beginning of the experiment, since all animals were dead after 1 day.

Gross pathology:

Neither precipitation of the substance nor adhesions were found in the abdomen of dead and sacrified animals.

Any other information on results incl. tables

Table 1: acute toxicity after intraperitonial application Acute Toxicity Results: Symptoms: Doses (mg/kg) 700 200 Dyspnea 15 min - 2 h 15 min - 1d Apathy 15 min - 2 h 15 min - 1d Abnormal conditions 30 min - 2h 1h - 2 h Staggering 15 min - 30 min 15 min - 5 h Twitching   15 min - 30 min Spastic gait   15 min - 5 h cramps 1h 1h - 2 h Clonic cramps   2 h Ton.-clon cramps 1h - 2 h   Ruffled haircoat 15 min - 2 h 2 h - 1d Hypohydration 15 min - 2 h 15 min - 5 h Petrusion of the eyeball 15 min - 2 h   General bad condition 15 min - 2 h 15 min - 1d Symbols: d = day; h = hour; min = minute Pathology: Dead and scrified animals: neither precipitation of the substance nor adhesions in the abdomen. Table 2: Mortality and body weight Doses (mg/kg) 700 200 Mortality:     Males:     Number of animals: 5 5 Dead animals after:     1 h 3 1 1 d 5 3 2 d 5 3 5 d 5 3 7 d 5 3 15 d 5 3 Females:     Number of animals: 5 5 Dead animals after:     1 h 3 0 1 d 5 1 2 d 5 1 5 d 5 1 7 d 5 1 15 d 5 1 Mean weight (g):     Males:     Beginning of the experiment: 26.0 28.0 After:     4 d   34.5 7 d   35.0 13 d   36.5 Females:     Beginning of the experiment: 24.0 28. 0 After:     4 d   29.7 7 d   29.5 13 d   29.5 Symbols: d = day; h = hour Table 3: Acute toxicity - males Acute toxicity - males LD50 -Determination Duration 15 d     Animal Males     Doses (mg/kg) Number of Animals Dead Animales Mortality Used to determine LD50 value After 15 d (%) 200 5 3 60.0 * 700 5 5 100.0   LD50 value: about 200 Table 4: Acute toxicity - females Acute toxicity - females LD50 -Determination: Duration 15 d     Animal Females     Doses (mg/kg) Number of animals Dead animals Mortality Used to determine LD50 value After 15 d (%) 200 5 1 20 .0 * 700 5 5 100.0 * LD50 value: about 279 Table 5: Acute toxicity - male and female together Acute toxicity - male and female together LD50 -Determination: Duration 15 d   Animal Males and females   Doses (mg/kg) Number of animals Dead Animals Mortality Used to determine LD50 value After 15 d (%) 200 10 4 40.0 * 700 10 10 100.0   LD50 value: about 200

Applicant's summary and conclusion

Executive summary:

The acute toxicity of 2 -cyano-N-methylacetamide via the intraperitonial route was investigated in male and female mice. Doses of 200 mg/kg bw and 700 mg/kw bw were applied to 5 animals per sex per dose. After a single application of the test substance main symptoms of intoxication were dyspnea, apathy, abnormal body positions, staggering, tonic cramps, ruffled haircoat, hypohydration and a general bad condition of the animals, starting at the lowest dose level partially already 15 min after application. After 15 min the first clinical signs were observed at both dose levels, including dyspnea, apathy, staggering, convulsions, ruffled haircoat, hypohydration and (a general) bad condition. Additionally, an application of 200 mg/kg resulted in twitching, clonic cramps and spastic gaits of the animals. Petrusions of the eyeballs were observed at the dose level of 700 mg/kg only. After the application of 700 mg/kg all mice (male and female) were dead after 1 day. Three males and one female died 1 day after the application of 200 mg/kg test substance. Neither precipitation of the substance nor adhesions were found in the abdomen of dead and sacrified animals. The LD50 value for both, male and female together was found at 200 mg/kg bw.