Pentane-2,4-dione

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Adopted according to OECD SIDS (publicly available peer reviewed source). Original document not available.

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Unnamed

Year:

2001

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 483 (Mammalian Spermatogonial Chromosome Aberration Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

other: mouse spermatogonia chromosomal aberration test

Test material

Test material information

Constituent 1

Details on test material:

Purity: 99.59%

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle: Water
- Amount of vehicle: 10 mL/kg bw (negative control)

Duration of treatment / exposure:

single application

Frequency of treatment:

single application

Doses / concentrations

Remarks:

Doses / Concentrations:
800 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

Adriblastin (5 mg/kg bw)

Examinations

Tissues and cell types examined:

Spermatogonial cells

Details of tissue and slide preparation:

CITERIA FOR DOSE SELECTION:
In a preceding study the bioavailability of the test material was confirmed. It was determined that 800 mg/kg bw administered orally were close to the MTD as shown by signs of toxicity in the treated animals such as reduction of spontaneous activity, eyelid closure, apathy and tremor. In this previous test the systemic distribution of the test substance was also checked and it was found that after oral administration the test substance was detectable in blood serum up to four hours post-treatment.

TREATMENT AND SAMPLING TIMES:
For the investigation of chromosomal aberrations in germ cells, spermatogonial cells were prepared 24 and 48 hours after single test substance administration. Five male mice were examined at each time point.

METHOD OF ANALYSIS:
At least 100 metaphases per animal were scored for cytogenetic damage. Gaps, breaks, fragments, deletions, exchanges and chromosomal disintegrations were recognized as structural chromosome aberrations.

Statistics:

Statistical analysis of results observed was included and confirmed by the non-parametric Mann-Whitney test.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

After preparation and examination of spread spermatogonial cells (100 cells of each animal, i.e. 500 per dose and time point were analysed) no reduction in the mitotic index could be observed, indicating that 2,4-pentanedione at the indicated dose and the indicated application route was not cytotoxic for spermatogonial cells. No statistically significant or biologically relevant increase in the number of numerical and structural aberration as compared to vehicle treated controls could be found. Aberration rates were 0.8 % and 1.0 % for the 24 h and the 48 h treatment, respectively, as compared to the vehicle control value of 0.6 % . The mean aberration frequencies observed after treatment with 2,4-pentanedione were consistently below 2% aberrant cells exclusive gaps, given as the upper limit of a tolerable vehicle control value. The positive control showed a statistically significant response (9 % aberration rate excluding gaps). In conclusion, 2,4-pentanedione is being considered non-mutagenic under the conditions of this assay.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative