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Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information
The in vivo micronucleus test in mice at 3 concentration levels showed no evidence for mutagenic potential.
Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: genome mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP and Guideline study. Well documented.
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Qualifier:
according to guideline
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes (incl. QA statement)
Type of assay:
micronucleus assay
Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd. Manston , Kent
- Age at study initiation: 5-8 wks
- Weight at study initiation: 23-30 (male), 20-26 (female)
- Assigned to test groups randomly: yes
- Fasting period before study:
- Housing: groups of five by sex in solid floor polypropylene cage with saw dust bedding.
- Diet (e.g. ad libitum): Rat and mouse expanded diet no. 1, special diet services ltd. Witham, Essex, U.K.
- Water (e.g. ad libitum): drinking water
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 44-46
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: arachis oil supplied by Philip Harris Scientific
- Concentration of test material in vehicle: 100 / 200 mg/ml (Range finding), 50-200 mg/l (Main study)
- Lot/batch no. (if required): Co/730
Remarks:
Doses / Concentrations:
2000 mg/kg
Basis:
nominal conc.
Oral an IP, Range finding study and Main Study
Remarks:
Doses / Concentrations:
1000 mg/kg
Basis:
nominal conc.
Oral an IP, Range finding study and Main Study
Remarks:
Doses / Concentrations:
500 mg/kg
Basis:
nominal conc.
Main Study
No. of animals per sex per dose:
5
Control animals:
other: vehicle and positive controls
Positive control(s):
cyclophosphamide
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not specified
Positive controls validity:
valid
Conclusions:
Interpretation of results (migrated information): negative
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Justification for classification or non-classification

There are 4 in vitro studies on mutagenicity of the target substance. The Ames-tests all showed positive effects only with S9 -activation, whilst the mouse lymphoma study showed positive results with and without activation. Therefore the test results of the in vitro studies are ambiguous. The only in vivo micronucleus study showed negative results at all doses. A classification as mutagenic is not justified with this results.