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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study design appears to follow OECD Guideline 475 (1997). Contains sufficient detail to suggest GLP-like characteristics, but no statement of certification (reasonably thorough description of authors, dates, design, results and interpretation).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
yes
Remarks:
Lower number of males in groups administered test article (acceptable, as no gender-difference in toxicity).
GLP compliance:
no
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
No details provided.
- Name of test material (as cited in study report): TK 10047 (Tinuvin P)
- Lot/batch No.: EN 2790
- Expiration date of the lot/batch: Not reported
- Storage condition of test material: Not reported

Test animals

Species:
hamster, Chinese
Strain:
other: Chinese
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: females = 21-29 g and males = 18-24 g.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 C ± 1 °C
- Humidity (%): 55 ± 5%
- 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:
Once/day for 2 days.
Frequency of treatment:
Once/day for 2 days.
Post exposure period:
Animals were sacrificed 4h after the second dose.
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:
6 Females and 4 males/treatment group.
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide
- Route of administration: IP
- Doses / concentrations: 64 mg/kg bw

Examinations

Tissues and cell types examined:
Bone marrow from the shafts of both femors.
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION: Bone marrow was suspended in balanced salt solution and diluted to hypotonicity with distilled water, kept in a waterbath at 4 to 6 ºC for 23 minutes and then centrifuged for 10 min at 200 x g. The pellets were then fixed in methanol acetic acid 3:1 for a period of 30 min at room temperature. After resuspension of the pellet and centrifugation for 5 min at 150 x g, the fixative was changed and the specimen stored overnight at 4 C. Finally the pellets again were resuspended, centrifuged for 5 min at 150 x g and resuspended in some 0.5 ml fixative in order to obtain a more concentrated cell suspension. These specimens were pipetted onto wet slides and stained with acetic-orcein.
Evaluation criteria:
Four animals (two females and two males) from each group treated with the various doses of TK 10 047 and from the negative and from the positive control group each were analysed by reference to the following criteria:

a) Chromatid-type aberrations. These changes include "breaks" and "exchanges". All discontinuations exceeding the diameter of a chromatid were designated as breaks.
b) Chromosome-type aberrations. This category comprises "acentric fragments", "minutes" (very small chromosome fragments), "ring chromosomes" and "dicentrics".
c) Chromatid gaps. All interruptions of the chromatid continuity which were smaller than the diameter were designated as gaps.
d) Chromosome pulverizations. Completely pulverized metaphase chromosomes were distinguished from incomplete pulverizations with recognizable chromosome fragments.

100 metaphases were analysed per animal.
Statistics:
Statistics not required.

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 genotoxic effects were oberved in Chinese hamsters upon gavage dosing of 500, 1000 or 2000 mg/kg bw.