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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
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study design follow OECD Guideline 474 (1999), but uses slightly different terminology. Sufficient reporting details given. Non GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
more parameters than micronuclei in erythroblasts recorded. 1000 Bone marrow cells evaluated without giving the actual number of erythroblasts. Lower number of animals acceptable as no gender-specific effects known
GLP compliance:
no
Remarks:
Study pre-dates GLP.
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
- Name of test material (as cited in study report): TK 10047 (Tinuvin P)
- Lot/batch No.: EN 2790

Test animals

Species:
hamster, Chinese
Strain:
other: Chinese
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Tierzuchtinstitut of the University of Zurich
- Weight at study initiation: Females = 27-31 g and males = 20-34 g.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 24°C.
- Humidity (%): 50 to 60%.
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: CMC (carboxymethyl cellulose)
- Concentration of test material in vehicle: 0.5%
- Amount of vehicle (if gavage or dermal): 20 mL/kg bw
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: not reported.
Duration of treatment / exposure:
One application on 2 consecutive days.
Frequency of treatment:
Single application/day.
Post exposure period:
24 h after the second application the animals were sacrificed.
Doses / concentrationsopen allclose all
Dose / conc.:
500 mg/kg bw/day (actual dose received)
Dose / conc.:
1 000 mg/kg bw/day (actual dose received)
Dose / conc.:
2 000 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
3/sex/dose
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide
- Route of administration: oral gavage.
- Doses / concentrations: 128 mg/kg bw.

Examinations

Tissues and cell types examined:
Bone marrow was harvested from the shafts of both femurs.
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION: Small drops of the mixture were transferred on the end of a slide, spread out by pulling it behind a polished cover glass and the preparations were air-dried. At the next day the slides were stained in undiluted May-Grünwald solution for 2 minutes and subsequently with Giemsa solution (5%) for 9 minutes. After rinsing with distilled water and air-drying the slides were cleared in Xylol and mounted in Evikitt.
Evaluation criteria:
1,000 Bone marrow cells were scored from each animals and the following anomalies were registered:

a) Single Jolly bodies,
b) fragments of nuclei in erythrocytes,
c) micronuclei in erythroblasts,
d) micronuclei in leucopoietic cells,
e) bizarre forms of nuclei,
f) polyploid cells and
g) necrobiotic cells
Statistics:
Chi-square test

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
No genotoxicity was observed in the micronucleus assay in Chinese hamsters upon oral dosing with 500, 1000 and 2000 mg/kg bw.