(Z)-pent-2-enenitrile

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:

No data

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Relevant methodological deficiencies: male mice only tested, administrated volume was higher than recommended, animals were sacrificed 6 hours after the last administration instead of 18-24 hours.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

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 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

only males were used, administrated volume was higher than recommended, animals were sacrificed 6 hours after the last administration instead of 18-24 hours.

Principles of method if other than guideline:

Method: described in Boller and Schmid (1970) and Schmid (1975)

GLP compliance:

no

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

(Z)-pent-2-enenitrile

EC Number:

247-323-5

EC Name:

(Z)-pent-2-enenitrile

Cas Number:

25899-50-7

Molecular formula:

C5H7N

IUPAC Name:

(2Z)-pent-2-enenitrile

Constituent 2

Reference substance name:

pent-2-enenitrile (Z)

IUPAC Name:

pent-2-enenitrile (Z)

Details on test material:

- Name of test material (as cited in study report): cis-pentene-2 nitrile commercial
- Physical state: pale yellow liquid

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Carworth Farm Lane-Petter
- Age at study initiation: no data
- Weight at study initiation: 25-30 g
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study: no
- Housing: no data
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
No data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: arachis oil
- Justification for choice of solvent/vehicle: no data
- Concentration of test material in vehicle: 0.8 and 4 µL/mL
- Amount of vehicle (if gavage or dermal): 2 x 25 mL/kg

Details on exposure:

No details

Duration of treatment / exposure:

30 hours

Frequency of treatment:

2 administration (at 0 and 24 hour)

Post exposure period:

6 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
2 x 0.02 mL/kg and 2 x 0.1 mL/kg
Basis:
nominal conc.

No. of animals per sex per dose:

10 males per dose

Control animals:

yes, concurrent vehicle

Positive control(s):

Benzene (Prolabo, lot n° 79.018)
- Justification for choice of positive control(s): benzene is a recognised clastogenic substance
- Route of administration: oral (gavage)
- Doses / concentrations: 2 x 1.25 mL/kg

Examinations

Tissues and cell types examined:

bone marrow (2000 polychromatic erythrocytes per animal)

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION:
Based on a preliminary study.

DETAILS OF SLIDE PREPARATION:
Bone marrow was collected in calf embryo serum. After centrigation, the pellet was homogenized, applied to a slide and coloured with May Grünwald-Giemsa.

METHOD OF ANALYSIS:
1000 polychromatic erythrocytes were counted by 2 persons and a mean  value was calculated.

Evaluation criteria:

% of polychromatic erythrocytes with micronuclei

Statistics:

The % of polychromatic erythrocytes with micronuclei in the control and treated groups were compared with the Student t-test.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Dose range:  2 x 0.25 and 2 x 0.1 mL/kg
- Clinical signs of toxicity in test animals: At 2 x 0.25 mL/kg, 4/5 animals died. At 2 x 0.1 mL/kg, no mortality was observed, but animals were 
prostrated during the hour following the administration.

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): see Table 7.6.2/
- Ratio of PCE/NCE (for Micronucleus assay): no data
- Appropriateness of dose levels and route: no data
- Statistical evaluation: no statistically significant increase in the  number of micronuclei was observed in the treated animals.

Any other information on results incl. tables

Table 7.6.2/1: Results of in vivo micronucleus test with cis-pentene-2-nitrile

Group	Dose	No. of mice	% polychromatic erythrocytes with micronuclei
Control (arachis oil)	0	10	0.22 ± 0.08
Cis-pentene-2 nitrile com.	2 x 0.02 mL/kg	10	0.14 ± 0.04
Cis-pentene-2 nitrile com.	2 x 0.1 mL/kg	10	0.13 ± 0.07
Benzene	2 x 1.25 mL/kg	10	3.25 ± 0.72

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
In this study with Cis-pentene-2-nitrile commercial, there was not a significant increase in the frequency of micronucleated polychromatic
erythrocytes in bone marrow after treatment.

Executive summary:

In a Swiss CFLP mouse bone marrow micronucleus assay, 10 males/dose were treated by oral gavage with cis-pentene-2-nitrile commercial (purity unknown) at doses of 0, 2 x 0.02 and 2 x 0.1 mL/kg bw. Bone marrow cells were harvested at 6 hours post-treatment. The vehicle was arachis oil.

 

Cis-pentene-2-nitrile commercial was tested at an adequate dose (based on a preliminary study results). The positive control induced the appropriate response.There was not a significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after treatment.