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Toxicological information

Genetic toxicity: in vivo

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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented publication/ study report which meets basic scientific principles
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2000
Reference Type:
secondary source
Title:
Fragrance material review on methyl ionone (mixture of isomers)
Author:
Lalko J et al.
Year:
2007
Bibliographic source:
Food and Chemical Toxicology 45 (2007) S300–S307
Reference Type:
secondary source
Title:
A toxicologic and dermatologic assessment of ionones when used as fragrance ingredients
Author:
Belsito D et al.
Year:
2007
Bibliographic source:
Food and Chemical Toxicology 45 (2007) S130–S167

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
micronucleua assay
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Ionone, methyl-
EC Number:
215-635-0
EC Name:
Ionone, methyl-
Cas Number:
1335-46-2
Molecular formula:
C14H22O
IUPAC Name:
Ionone, methyl-

Test animals

Species:
mouse
Strain:
ICR
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil
Details on exposure:
Volume injected: 20 ml/kg bw
Duration of treatment / exposure:
Bone marrow was collected 24 and 48 hours after dose administration.
Frequency of treatment:
single application
Post exposure period:
24, 48 h
Doses / concentrations
Remarks:
Doses / Concentrations:
462.5, 925, or 1850 mg/kg body weight
Basis:
nominal conc.
No. of animals per sex per dose:
5
Control animals:
not specified
Positive control(s):
- Cyclophosphamide
- Route of administration: IP injection
- Doses / concentrations: 2.5 mg/ml bw

Examinations

Tissues and cell types examined:
erythrocytes
Details of tissue and slide preparation:
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
24 and 48 h

DETAILS OF SLIDE PREPARATION:
Immediately following sacrifice, the femurs were exposed, cut just above the knee and the bone marrow was aspirated into a syringe containing fetal bovine serum. The cells were centrifuged; the supernatant was drawn off and then resuspended. The bone marrow suspension was spread onto a clean glass slide (two to four slides were prepared for each mouse). The slides were fixed in methanol, stained with May-Gruenwald-Giemsa and permanently mounted.

METHOD OF ANALYSIS:
2000 polychromatic erythrocytes were scored for the presence of micronuclei. The number of micronucleated normochromatic erythrocytes in the field of 2000 polychromatic erythrocytes was enumerated. The proportion of polychromatic erythrocytes to total erythrocytes was also recorded per 1000 erythrocytes.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
not specified
Negative controls validity:
not specified
Positive controls validity:
not specified

Any other information on results incl. tables

No effects, slight to moderate reduction (up to 35%) in the ratio of  
polychromatic erythrocytes to total erythrocytes were observed in some of  the 
test article-treated groups relative to the respective vehicle controls. 
A statistically significant increase in micronucleated  polychromatic 
erythrocytes (8 MNPCE/10000 PCE) was observed in male mice 24 hrs after 
treatment with 925 mg/kg. 
However, this response is not considered biologically relevant (each of the 
five animals had no more  than 3 MPCE, which are within the range of historical 
solvent control:  0-7 MN/2000 PCE/animal). 
No significant increase and no dose responsiveness increase was observed in any 
other test article treated group regardless of dose level, sex, or bone marrow 
collection time.

Applicant's summary and conclusion