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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
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed publication

Data source

Reference
Reference Type:
publication
Title:
Gene mutation in vivo toxicity study if the test chemical
Author:
Wild et al
Year:
1983
Bibliographic source:
Food and chemical toxicology

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Micronucleus assay was performed in NMRI mice to determine the mutagenic nature of the test chemical
GLP compliance:
not specified
Type of assay:
other: Micronucleus assay in mice

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: 2'-acetonaphthone
- Substance type: Organic
- Physical state: Solid

Test animals

Species:
mouse
Strain:
NMRI
Details on species / strain selection:
No data available
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: lvanovas GmbH, Kisslegg
- Age at study initiation: 10 to 14 week old
- Weight at study initiation: No data
- Assigned to test groups randomly: No data
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): standard chow (Altromin) ad libitum
- Water (e.g. ad libitum): Water ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%):No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: To: No data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: Olive oil
- Justification for choice of solvent/vehicle: The chemical was soluble in olive oil
- Concentration of test material in vehicle: 0, 340, 681 or 876 mg/Kg
- Amount of vehicle (if gavage or dermal): No data
- Type and concentration of dispersant aid (if powder): No data
- Lot/batch no. (if required): No data
- Purity: No data
Details on exposure:
No data
Duration of treatment / exposure:
0 and 24 hours
Frequency of treatment:
Once
Post exposure period:
6 hours
Doses / concentrations
Remarks:
0, 340, 681 or 876 mg/Kg
No. of animals per sex per dose:
Total: 16
0 mg/Kg: 4
405 mg/Kg: 4
809 mg/Kg: 4
1213 mg/Kg: 4
Control animals:
yes, concurrent vehicle
Positive control(s):
No data available

Examinations

Tissues and cell types examined:
Bone marrow micronucleus were examined.
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: No data

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): 30 hrs

DETAILS OF SLIDE PREPARATION: The smears were stained according to the method of Schmid (1976)

METHOD OF ANALYSIS: increase in the number of micronucleus

OTHER: No data
Evaluation criteria:
The smears were noted for micronucleated polychromatic erythrocytes.
Statistics:
Statistical significance was determined according to the methods of Kastenbaum & Bowman (1970).

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
Remarks on result:
other: No mutagenic potential
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range: No data
- Solubility: No data
- Clinical signs of toxicity in test animals: No data
- Evidence of cytotoxicity in tissue analyzed: No data
- Rationale for exposure: No data
- Harvest times: No data
- High dose with and without activation: No data
- Other: No data


RESULTS OF DEFINITIVE STUDY
- Types of structural aberrations for significant dose levels (for Cytogenetic or SCE assay): No data
- Induction of micronuclei (for Micronucleus assay):Yes
- Ratio of PCE/NCE (for Micronucleus assay): Refer table below
- Appropriateness of dose levels and route: Intra-peritoneal
- Statistical evaluation:No data

Applicant's summary and conclusion

Conclusions:
The test chemical did not produce genetic effects in a micronucleus assay performed in NMR1 mice and hence is not likely to classify as a gene mutant in vivo.
Executive summary:

Gene mutation toxicity was performed to determine the mutagenic nature of the test chemical in vivo. Micronucleus assay was performed using bone marrow smears of male and female NMRI mice. The test chemical was dissolved in olive oil and used at dose levels of 0, 340, 681 or 876 mg/Kg. The chemical was given intraperitoneally during the 24 hrs study period. The mice were killed and bone-marrow smears were prepared 30 hr after treatment. The smears were stained according to the method of Schmid (1976) and were observed for genetic effects in polychromated erthrocytes. As seen by the results, the test chemical did not produce genetic effects in the micronucleus assay performed in NMR1 mice. Hence, it is not likely to classify as a gene mutant in vivo.