2-Butenoic acid, 3-amino-, 1-methylethyl ester

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1994

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

isopropyl (E)-3-aminobut-2-enoate

EC Number:

604-269-0

Cas Number:

14205-46-0

Molecular formula:

C7 H13 N O2

IUPAC Name:

isopropyl (E)-3-aminobut-2-enoate

Details on test material:

- Name of test material (as cited in study report): 3-Aminocrotonic acid isopropylester
- Appearance: clear liquid
- Purity: 97.0 %
- Batch No. 7/89

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- none for the test item
- deionized water for the positive substance cyclophosphamide

Duration of treatment / exposure:

animals were sacrificed 24, 48 and 72 hours after treatment; the negative and positive control animals were sacrificed after 24 h

Frequency of treatment:

single treatment

Post exposure period:

24h to 72h

Doses / concentrations

Remarks:

Doses / Concentrations:
3 ml/kg bw
Basis:
actual ingested
dose was selected based on a pilot study with 3, 5, 7, and 10 ml/kg bw

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide 20 mg/kg bw

Examinations

Tissues and cell types examined:

bone marrow (taken from at least one femur of from each sacrificed animal) smears, 1000 polychromatic erythrocytes were counted per animal, ratio of normochromatic to polychromatic cells was established

Evaluation criteria:

1000 polychromatic erythrocytes were counted per animal for micronuclei, ratio of normochromatic to polychromatic cells was established
positive criteria: relevant and significantly increased in the micronucleus bearing polychromatic erythrocytes

Statistics:

yes

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

altered ratio between polychromatic and normochromatic erythrocytes; clinical signs, 2 of 40 treated animals died

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Any other information on results incl. tables

clinical signs: apathy, roughened fur, staggering gait, prone position, spasm, shivering and difficulty in breathing; 2 of the 40 test substance treated animals died

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative

Executive summary:

In a bone marrow micronucleus test performed according to OECD TG 474, 3 ml/kg bw test substance was given per gavage to 5 males and 5 female mice per group. The animals were sacrificed 24, 48, and 72 hours after treatment. General toxicity and bone marrow toxicity became obvious. No indication of a clastogenic effect of the test item was found under the conditions of this test.