Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: other: erythrocyte micronuleus test
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: secondary literature: reproduced from SIAR 6-tert-Butyl-m-cresol, 08.08.2002 - well conducted study, carried out by Chemicals Evaluation and Research Institute, Hita Labo., (Japan) (2002), reliability 1 according the preevaluated OECD SIDS IUCLID

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)
Principles of method if other than guideline:
OECD Guide-line 474 "Genetic Toxicology: Micronucleus Test"
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
produced by Sumitomo Chemical, Lot No. 20213, Purity:99.0%

Test animals

Species:
mouse
Strain:
other: Crj: CD-1 (ICR) SPF
Sex:
male
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Duration of treatment / exposure:
twice in the interval in 24 hours
Frequency of treatment:
twice in the interval in 24 hours, no further treatment
Post exposure period:
terminal killing: 24 hours after final application
Doses / concentrations
Remarks:
Doses / Concentrations:
31.3, 62.5, 125 mg/kg (Note1)
Basis:
nominal conc.
No. of animals per sex per dose:
No. of animals per dose: 6 (the analysis object:5)
Control animals:
not specified
Positive control(s):
Positive control: Mitomycin C (MMC) 2mg/kg in inj. water, single application

Examinations

Tissues and cell types examined:
micronucleated polychromatic erythrocytes (MNPCE), Polychromatic erythrocytes(PCE), Total erythrocytes(TE)
Details of tissue and slide preparation:
Preparation of specimens: bone marrow cells from the femur two specimens for each animal
Evaluation criteria:
Analysis:
1) Frequency of micronucleated polychromatic erythrocytes (MNPCE): MNPCE/Polychromatic erythrocytes(PCE) ratio (1000 PCE/specimen)
2) Effects to bone marrow cells PCE/Total erythrocytes(TE) ratio (500 TE/ specimen)
Statistics:
MNPCE/PCE: Binomial test with condition (Kastenbaum & Bowman) PCE/TE: t-test

Results and discussion

Test results
Sex:
male
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

result: negative
Dose level(mg/kg) 0 31.3 62.5 125 MMC
PCE/TE ratio(%) 45.5±5.12 57.4±5.72* 50.4±8.59 51.6±4.92 46.3±11.0
MNPCE/PCE ratio(%) 0.13±0.09 0.07±0.08 0.17±0.06 0.15±0.05 6.47±1.35**
( * P< 0.05 ** P< 0.01)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Micronucleus test in mice is negative.
Executive summary:

method: mammalian erythrocyte micronuleus test in mice according OECD TG 474

result: micronucleus test in mice is negative

reference: chemicals Evaluation and Research Institute, Japan (20029