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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
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
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:
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

Constituent 1
Chemical structure
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.