Pent-3-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:

weight of evidence

Study period:

No data

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Relevant methodological deficiencies: number of mature erythrocytes was not determined; 2 concentrations tested; one sex; sacrifice 6 hours after the last administration instead of 18-24 hours

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:

number of mature erythrocytes was not determined; 2 concentrations tested; one sex; sacrifice 6 hours after the last administration instead of 18-24 hours

Principles of method if other than guideline:

Not applicable.

GLP compliance:

no

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Pent-3-enenitrile

EC Number:

225-060-7

EC Name:

Pent-3-enenitrile

Cas Number:

4635-87-4

Molecular formula:

C5H7N

IUPAC Name:

(3E)-pent-3-enenitrile

Details on test material:

- Name of test material (as cited in study report): trans-pentene-3 nitrile (T3PN)
- 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: complete diet (sterilizable) 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: 0.2 and 1 µL/mL
- Amount of vehicle administered: 0.25 mL per 10 g bw
- Lot/batch no. (if required): no data
- Purity: no data

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
- Preparation of dosing solutions: just before administration

DIET PREPARATION
No data

Duration of treatment / exposure:

24 hours

Frequency of treatment:

twice administration at 24-h interval

Post exposure period:

6 hours after the second administration

Doses / concentrations

Remarks:

Doses / Concentrations:
2 x 0.005 and 2 x 0.025 mL/kg
Basis:
nominal in diet

No. of animals per sex per dose:

10 males/dose

Control animals:

yes, concurrent vehicle

Positive control(s):

Benzene (Prolabo, lot No. 79.018)
- Justification for choice of positive control(s): reference clastogen substance
- Route of administration: oral (gavage)
- Doses / concentrations:2 x 1.875 mL/kg
- Concentration in vehicle: 75 µL/mL

Examinations

Tissues and cell types examined:

Bone marrow erythrocytes

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: based on a preliminary study

TREATMENT AND SAMPLING TIMES:
Treatment twice at 24 h interval,  collected 6 h after the second treatment

DETAILS OF SLIDE PREPARATION:
Sampling performed in the femur, coloured  with Grünwald-Giemsa

METHOD OF ANALYSIS:
Analysis on 2000 cells

Evaluation criteria:

No data

Statistics:

Student t-test

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

1 animal died in the high dose group, prostration in the  other animals

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Dose range:
  at 0.5 mL/kg, 3/3 animals died 0.25 h after the administration
at 0.25 mL/kg, 3/3 animals died some h after the administration
at 0.1 ml/kg, 5/5 animals died in the 0.3 h after the administration
at 0.05 ml/kg, 4/5 animals died ca. 1 h after the administration


RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei: no
- Ratio of PCE/NCE: no data
- Appropriateness of dose levels and route: yes
- Statistical evaluation: no data

Any other information on results incl. tables

Table 7.6.2/1: Results of in vivo micronucleus test with Trans-pentene-3-nitrile

Test Group	Conc. in Diet (mL/kg)	# Male	% PE with micronuclei
Control	0	10	0.14 ± 0.05
Low	2 x 0.005	10	0.13 ± 0.07
High	2 x 0.025	11	0.18 ± 0.05
Positive Control	2 x 1.875	10	6.59 ± 1.59

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Under the test conditions, there was not a significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time.

Executive summary:

In a Swiss mouse bone marrow micronucleus assay, 10 males/group were treated by gavage with trans-3-pentene nitrile (purity unknown) at doses of 2 x 0.005 and 2 x 0.025 mL/kg. The vehicle was arachis oil. Bone marrow cells were harvested at 6 hours after the second administration (on day 1)

 There were signs of toxicity (mortality, prostration) during the study. The positive control induced the appropriate response. There was not a significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time.

Only the percentage of micronuclei in polychromatic erythrocytes is determined. There is no information concerning proportion of immature erythrocytes among total erythrocytes, only two concentrations were tested and the animals were sacrified 6 hours after the last administration instead of 18 -24 hours. Therefore, by weight of evidence with the results observed in in vitro genotoxicity studies, 3 -Pentenetrile is not expected to be genotoxic.