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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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:
2004
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes (incl. QA statement)
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Breeder: Charles River Laboratories, l'Arbresle, France.
- Age at study initiation: approximately 6 weeks
- Weight at study initiation: males: 28 - 33 g; females 21 - 27 g
- Assigned to test groups randomly: yes, the animals were randomly allocated to the groups by sex
- Fasting period before study: no.
- Housing: by groups in polycarbonate cages;
bedding: autoclaved sawdust (SICSA, Alfortville, France)
- Diet (ad libitum): Ssniff R/M-H pelleted maintenance diet (SSNIFF Spezialdiäten GmbH, Soest, Germany).
- Water (ad libitum): drinking water filtered by a FG Millipore membrane (0.22 micron)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C,
- Humidity (%): 30 - 70%
- Air changes (per hr): 12 cycles/hour of filtered non-recycled fresh air
- Photoperiod (hrs dark / hrs light): 12 h/12 h (07:00 - 19:00)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Vehicle
Name: 0.5% methylcellulose

Positive controls
The positive control was Cyclophosphamide 50 mg/kg.
Details on exposure:
For the vehicle and the test item:
• Route: oral, since it is a possible route of exposure in Man
• Frequency: two treatments separated by 24 hours
• Volume: 10 mL/kg.

For the positive control (CPA):
• Route: oral
• Frequency: one treatment
• Volume: 10 mL/kg.

Duration of treatment / exposure:
48 hours (test item)
24 hours (cyclophosphamide)
Frequency of treatment:
two treatments separated by 24 hours
Post exposure period:
24 hours
No. of animals per sex per dose:
Doses/concentrations:
Test item
males: 250-500-1000 mg/kg
females: 125-250-500 mg/kg
CPA = 50 mg/kg.

5males and 5 females/doses including controls except 8 males and 8 females at the high dose level.
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide

Examinations

Tissues and cell types examined:
Femoral bone marrow.
Erythrocyte cell line.
Details of tissue and slide preparation:
Bone marrow flushed out with fetal colf serum. Centrifugation and straining cell suspension spread on the slide.
Evaluation criteria:
Straining with Giensa.
- 2000 polychromate erythocytes evaluated/animal for MPE.
- PE/NE ratio: 100 erythrocytes.
Statistics:
Yes.
Statistically significant increase in the MPE frequency versus controls.
-historical date and biological relevance also considered.

Results and discussion

Test resultsopen allclose all
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
Remarks:
One mortality at 1000-L. No effect on PE/NE.
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Sex:
female
Genotoxicity:
negative
Toxicity:
no effects
Remarks:
125, 250 and 500 mg/kg/day
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
No clastogenic potential in the mouse up to 2000 mg/kg.