1-cyanoallyl acetate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)

Version / remarks:

1992

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

1-cyanoallyl acetate

EC Number:

239-743-2

EC Name:

1-cyanoallyl acetate

Cas Number:

15667-63-7

Molecular formula:

C6H7NO2

IUPAC Name:

1-cyanoprop-2-en-1-yl acetate

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, Borchen, Germany
- Fasting period before study: 16 hours
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 days

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: water (aqua ad niectabilia)
- Amount of vehicle (if gavage or dermal): 10 ml/kg bw

Duration of treatment / exposure:

single dose

Frequency of treatment:

single dose

Post exposure period:

sampling time 24 and 48 h post application

Doses / concentrations

Remarks:

Doses / Concentrations:
males: 31.6 mg/kg bw., females 21.5 mg/kg bw.
Basis: maximum tolerated dose as determined in a prexperiment
nominal conc.

No. of animals per sex per dose:

negative control: 12
positive control: 6
test material: 14
Evaluation: 7 test material group, 6 negative control, 5 positive control

Control animals:

other: physiological saline solution (0.9 %)

Positive control(s):

- cyclophosphamide
- Route of administration: oral (gavage)
- Doses / concentrations: 31.6 mg/kg bw

Examinations

Tissues and cell types examined:

bone marrow smear of the femurs
From each animal 1000 PCEs were scored.

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION:
highest tolerable dose (higher concentrations caused severe toxic symptoms)

METHOD OF ANALYSIS:
scoring under microscope

Evaluation criteria:

test substance is considered mutagenic if it produces a statistically significant (p< 0.05) and reproducible positive response at any of the test points compared to the negative control group

Statistics:

Poisson test

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

hypokinesiahypokinesia, tremor, clonic convulsions (females only), decreased muscle tone, loss of righting reflexes. One female animal died.

RESULTS OF RANGE-FINDING STUDY
- Dose range: 31.6 - 38.3 mg/kg bw (males), 21.5-31.6 mg/kg bw (females)
- Solubility: yes
- Clinical signs of toxicity in test animals: severe toxicity symptoms, one female of the high dose died.
- Evidence of cytotoxicity in tissue analyzed: no
- Rationale for exposure: methodical reasons


RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): no
- Ratio of PCE/NCE (for Micronucleus assay): slightly lower in the test group, no clear myelotoxic effect can be deduced from the findings
control: 2.8/1.6 (24 h), 1.6/3.0 (48 h) ACA: 2.0/1.4 (24 h), 2.0/0 (48 h), values are presented as males/females

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative
No significant test material related increase in micronucleated PCEs was observed. Therefore the substance is considered non mutagenic in the mouse micronucleus assay. In the positive control animals, a significant increase in the number of PCEs was observed and thus validated the test.