Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
secondary source
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Remarks:
Shin Nippon Biomedical Laboratories, LTD. (Japan)
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2,2,6,6-tetramethylpiperidin-4-ol

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan, Inc
- Age at study initiation: 7 weeks old
- Weight at study initiation: 273-299g
- Acclimation period: 6 days

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: water
Duration of treatment / exposure:
2 days
Frequency of treatment:
2
Post exposure period:
24 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 250, 500, 1000, 1500 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide
- Route of administration: oral: gavage
- Doses / concentrations: 20 mg/kg

Examinations

Tissues and cell types examined:
immature erythrocytes (IE)
micronucleated immature erythrocytes (MNIE)
erythrocytes
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION: The bone marrow cells suspension was smeared onto a clean slide. The slides were stained with acridine orange solution.

METHOD OF ANALYSIS: The coded smear slides were observed under a microscope.
Statistics:
The IE ratio, an indicator of suppression of bone marrow cell growth, was analyzed by Student's t-test. For the incidence of MNIE's, tables of Kastenbaum and Bowman were applied.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
Remarks:
1 of 6 animals died at 1500mg/kg
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

Any other information on results incl. tables

The micronucleated immature erythrocytes (MNIE) % values of this substance treatment groups were within 0.08 to 0.12% and no significant difference was observed in comparison with the negative control group (0.07%).

The immature erythrocytes (IE) % values were 47.30% at 250 mg/kg, 45.47% at 500 mg/kg, 43.90% at 1000 mg/kg and 39.96% at 1500 mg/kg, respectively, and these displayed significant differences in comparison with the negative control group (50.87%).

MNIE % and IE % were 3.50% and 40.20%, respectively in the positive control group, and showed significant differences in comparison with the negative control group. The negative control incidences of MNIE among tests was within the range of the laboratory background data and positive control ones showed remarkable increase.

This chemical dose not induce micronuclei under the test conditions employed.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative