2-cyano-N-methylacetamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981-05-12 - 1981-08-27

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study conducted without GLP compliance

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

more doses, higher number of animals

GLP compliance:

no

Test type:

acute toxic class method

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:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wihelm Gassner, Sulzfeld
- Age at study initiation: about 12 weeks
- Fasting period before study: No feed 16 h before application, water ad libitum
- Housing: V-II-A-Steel wire-mesh cage Typ DK-III (Becker & Co., Castrop - Rauxel)
- Diet (ad libitum): HERILAN, MRH-Haltung, H. Eggersmann KG, Rinteln / Dosages of 2150 mg/kg & 215 mg/kg: SSNIFF R, SSNIFF, Versuchstierdiäten, Soest
- Water (ad libitum): VE-water on working days, tap water on holidays
- Acclimation period: min. 1 week

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

aqua dest.

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2150 mg/kg: 21.50 g/V, 1470 mg/kg: 14.70 g/V, 1000 mg/kg: 10.00 g/V, 681 mg/kg: 6.81 g/V, 316 mg/kg: 3.16 mg/kg, 215 mg/kg: 2.15 g/V
- Justification for choice of vehicle: aqueous preparation according to the physiological medium

Doses:

2150, 1470, 1000, 681, 316 and 215 mg/kg bw

No. of animals per sex per dose:

5 per sex per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 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, body weight, histopathology

Statistics:

No details available.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 681 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 387 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 1 778 mg/kg bw

Based on:

test mat.

Mortality:

No animals died in the 215 mg/kg bw dose group.
In the 316 mg/kg bw dose group one animal died within the first day.
All male animals in the 681 mg/kg bw dose group died within 24 hours, additionally, one female died within this group.
In the 1000 mg/kg bw dose group two animals died within 5 days.
In the 1470 mg/kg bw dose group one animal died after 2 days, two further animals died within 5 days.
In the 2150 mg/kg bw dose group two animals died within 24 h and another one within the following 5 days.

Clinical signs:

other: The results of intoxication were poisoning, characterized by dyspnea, apathy, abnormal positions, stagger, tonic cramps, ruffled haircoat, skin redness, hypohydration, general bad condition starting at a dose level of 215 mg/kg bw, partially 15 min after

Gross pathology:

Animals died during the study were examined as soon as possible. In general, accumulative hyperemia is recorded in these animals. In the stomach bloody ulcerations in the regions of glands and in the intestine multiple hämatinised contents were found.
Sacrified animals after the test duration showed no findings.

Other findings:

No further findings are reported.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The study was performed similar to the standard OECD testing guideline without certificated GLP compliance. The LD50 was identified to be 681 mg/kg bw for both female and male together, resulting in a classification and labeling as "oral toxicity category 4", "H302: Harmful if swallowed" according to EU GHS (1272/2008 EG).

Executive summary:

The acute oral toxicity of 2 -cyano-N-methylacetamide was investigated in male and female rats. Doses of 215 mg/kg bw, 316 mg/kg bw, 681 mg/kg bw, 1000 mg/kg bw, 1470 mg/kg bw and 2150 mg/kw bw were applied to 5 animals per sex per dose. The substance was administered by oral gavage. The main symptoms of intoxication were dyspnea, apathy, abnormal body positions, staggering, tonic cramps, ruffled haircoat, skin redness, hypohydration and a general bad condition of the animals, starting at the lowest dose level partially already 15 min after application. All male animals (as well as one female rat) died in the dose group of 681 mg/kg bw. Two femals died within 5 days at a dose of 1000 mg/kg bw. In the 1470 mg/kg bw dose group one female died after 2 days, two further animals died within 5 days. Two animals died within 24 h after a dose of 2150 mg/kg bw, followed by one more animal within the following 5 days. No animal died in the lowest dose group. Dead animals were examined as soon as possible, finding included accumulative hyperemia, bloody ulcerations in the stomach glands region and multiple hämatinised contents in the intestine. No oberservations like this were made in the sacrified animals after 14 days. Due to this results, the oral toxicity is characterised by a LD50 value of 681 mg/kg bw for both male and female rats together.