Ethyl cyanoacetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl cyanoacetate

EC Number:

203-309-0

EC Name:

Ethyl cyanoacetate

Cas Number:

105-56-6

Molecular formula:

C5H7NO2

IUPAC Name:

ethyl 2-cyanoacetate

Details on test material:

Batch No. Tank 434
ID No. 3633/81 410

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 6 to 8 weeks
- Fasting period before study: ca 16 hours
- Housing: conventionel, by gender separated, max. 5 animals
- Diet: 3 hours p.a. ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 30 - 70 %
- Air changes: 15 times/ h
- Photoperiod: 12 h dark/ 12 h light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

application volume: 1.89 cm³/kg body weight


- Rationale for the selection of the starting dose:

Doses:

2000 mg ethyl cyanoacetate pro kg body weight

No. of animals per sex per dose:

5 female animals per dose
5 male animals per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 1/2, 1, 2, 3, 4, 5, 6 hours p.a., after this daily
- Frequency of weighing: day 0, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ changes

Results and discussion

Preliminary study:

2000 mg ethyl cyanoacetate pro kg body weight were administered to 2 male and 2 female rats as a preliminary study. The results were recognized in the test outcome.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: Observations were performed 0.5, 1, 2, 3, 4, 5, 6, hours after administration (p.a.) of the test substance and then at least once a day for a total of 2 weeks. 2 - 6 hours p.a. all animals indicated symptoms of poisoning. All animals showed changes in the

Gross pathology:

All animals were killed by CO2 14 days p.a. and subjected to a necropsy including a gross pathological examination.
The pathological examination showed no signs for macroscopic changes of the organs conditional on the test substance.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of ethyl cyanoacetate is estimated to be higher than 2000 mg/kg body weight in rats for a single dose.
The pathological examination showed no signs for macroscopic changes of the organs conditional on the test substance.
Therefore the test substance ethyl cyanoacetate is practically nontoxic according to the EC-guideline 93/21.

Executive summary:

Aim of the study

It was the aim of the study to investigate acute toxic effects of the test substance after a single oral administration.

Methods

The OECD-Guideline 401, "Acute Oral Toxicity" OECD 1981, updated Guideline was adopted in Feb. 1987, was applied.

Administration

Ethyl cyanoacetate was administered once oral by stomach intubation to Bor: WISW (SPF Cpb) rats. The dosing was performed sequentially to 5 male and 5 female animals, each using a dose of 2000 mg per kg body weight.

The dose volume was 1.89 cm³ per kg body weight for all animals.

Investigations

Body weight: before administration, 7 and 14 days p.a.

Clinical observations were performed 0.5, 1, 2, 3, 4, 5, 6, hours p.a. of the test substance and then at least once a day for a total of 2 weeks.

Necropsy: all animals were sacrificed and necropsied 14 days p.a.

Results

Mortality

No mortality was observed.

Body weights

Males and females: Body weight and body weight gain of all animals were inconspicuous.

Clinical observations

2 - 6 hours p.a. all animals indicated symptoms of poisoning. All animals showed changes in the fur. Some animals showed changes in gait, ventral and lateral position, sedation or ataxia, decreased motility, tremor, vocalization, stagger, increased respiratory frequency, Straub phenomenon and disturbance of equilibrium.

Necropsy findings

The pathological examination showed no signs for macroscopic changes of the organs conditional on the test substance.

Sex differences

The response to the test substance at 2000 mg/kg body weight did not indicate a sex difference.