Methyl cyanoacetate

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:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl cyanoacetate

EC Number:

203-288-8

EC Name:

Methyl cyanoacetate

Cas Number:

105-34-0

Molecular formula:

C4H5NO2

IUPAC Name:

methyl 2-cyanoacetate

Test animals

Species:

rat

Strain:

other: Cpb/Win:WU (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: healthy adult animals
- Weight at study initiation: males 144-167 g, females 114-124 g
- Fasting period before study: 16 hours
- Housing: 5 animals/cage (maximum)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: min 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 03.07.1995 To: 20.07.1995

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.77 ml/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: at 30 minutes, 1, 2, 3, 4, 5 and 6 h after dosing and once daily thereafter for 14 days
- Frequency of weighing: day 0 (prior to dosing), day 7 and day 14
- Necropsy of survivors performed: yes
- Other examinations performed: gross examination of organs at necropsy

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Deaths were noted: on day 0 (3 hours after application) females 1/5, males 0/5

Clinical signs:

other: Male animals: 2/5 animals showed abnormal gait, hunched posture, reduced motility and piloerection at 1h after dosing, during 2-4h after dosing 5/5 males showed these symptoms which subsided in 3/5 animals after 5 h. In the remaining 2/5 animals these cli

Gross pathology:

The female that died 3 h p.a. showed swelling and irritation of the gastric mucosa that was covered with a white removable film. Liver, pancreas, adrenal glands, kidney of this animal showed alterations. Stomach and small intestine had an ensanguined mucus content. The large intestine was empty and the cecum was filled with a hard content.
Two males showed swelling and partly irritation of the gastric mucosa that was covered with a white film. Furthermore adhesion of stomach and pancreas was observed. In the male showing weight spleen and testes were reduced in size.
One surviving female showed swelling and irritation of the gastric mucosa that was covered with a white film. Also adhesion of stomach and pancreas was observed combined with a abscess formation.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

In this acute oral toxicity study in the rat a combined LD50 value of >2000 mg/kg bw was derived.