Registration Dossier

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:
key study
Study period:
1987-09-22 till 1987-12-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-study according to OECD guideline without deviations (OECD 474)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
Remarks:
(bone marrow)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: solid
- Batch 1410

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Chalres River, Cléon, France
- Age at study initiation: 7 weeks
- Weight at study initiation: 29g (males) 22g (females)
- Housing: wire mesh bottom stainless steel cages
- Diet / Water (e.g. ad libitum): ad lib.
- Acclimation period:2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 60+/-10
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
10% gum arabic, freshly prepared
Details on exposure:
no
Duration of treatment / exposure:
single
Frequency of treatment:
single treatment on day 1
Post exposure period:
24, 48 and 72 h
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
1000 mg/kg BW
Basis:
actual ingested
Remarks:
Doses / Concentrations:
2000 mg/kg BW
Basis:
actual ingested
Remarks:
Doses / Concentrations:
4000 mg/kg BW
Basis:
actual ingested
No. of animals per sex per dose:
15
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide ip (15 males and 15 females)

Examinations

Tissues and cell types examined:
bone marrow smears
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION:
both femurs severed, bone marrow flushed out with calf`s serum, cells opbtained by mild centrifugation and spread over slides after mild homogenization; fixed with methanol and stained automatically

Evaluation criteria:
An increase in micronucleated polychromatic cells shows a possible genotoxic effect.
When the ratio PCE / NCE decreases, this represents marrow cytotoxicity.
Statistics:
no

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Remarks:
for all doses similar to that of control animals
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RESULTS OF DEFINITIVE STUDY
- Ratio of PCE/NCE (for Micronucleus assay): similar for control and 24/48h-groups; 72 h not evaluated
- Appropriateness of dose levels and route: 3 cases of mortality (high dose, only males, 24/48h)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
According to GHS criteria, no classification of undecylenic acid is required
Executive summary:

The in vivo genotoxic potential of undecylenic acid was assessed in the mouse by micronucleus test according to OECD guideline 474 and EU method B.12. Undecylenic acid was administered once by oral gavage at dose levels of 1,2 and 4 g/kg bw to CD-1 mice. Each group consisted of 15 male and 15 female animals. Cyclophosphamide served as positive control.

No clinical signs were reported throughout the study, but three maled of the highest dose group were found dead 24 or 72 h after treatment. The PCE/NCE ratio obtained in all treated animals (24 and 48h after treatment) was similar to that of the control animals, and evaluation of the samples obtained 72 h after treatment was not considered necessary.

Under the experimental conditions, undecylenic acid did not reveal any in vivo genotoxic activity in the micronucleaus test in mice.