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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian cell study: DNA damage and/or repair
Remarks:
Type of genotoxicity: DNA damage and/or repair
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and appropriate guidelines
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)
Principles of method if other than guideline:
not relevant
GLP compliance:
yes
Type of assay:
unscheduled DNA synthesis

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
identification: FR-513
Description: Off-white flakes
Batch #: 201059107
Storage conditions: Room temperature, in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
Sprague-Dawley CD (Ctr;CD (SD) IGS BR) strain rats were obtained from Charles River UK Ltd, Margate, Kent, UK.
Weight: male 200 gr-243 gr (start of experiment); Age: 6-9 weeks old
Acclimatisation period: at least 5 days
Housing: The animals were housed in groups of up to five in solid floor polypropylene cages with woodflake bedding. Free access to drinking water and food was allowed throughout the study. The diet, drinking water and bedding were routinely analysed for contaminants.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30-70% respectively.
Air change was at least 15 changes per hour and the lightning was controlled by a time switch to give 12 hr continuous light (06:00 to 18:00) and 12 hr darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Archis oil
Description: Pale straw coloured slightly viscous liquid
Storage: Room temperature
Details on exposure:
All animals were dosed once only at room temperature at the appropriate dose level by gavage usin a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its body weight at the time of dosing.
Duration of treatment / exposure:
Treatment: 16 hr (experiment 1); 2 hr (experiment 2)

Frequency of treatment:
once
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2000 mg/kg
Basis:
nominal in diet
range finder test
Remarks:
Doses / Concentrations:
670 mg/kg; 2000 mg/kg
Basis:
nominal in diet
main test 1
Remarks:
Doses / Concentrations:
670 mg/kg; 2000 mg/kg
Basis:
nominal in diet
main test 2
No. of animals per sex per dose:
range finder: 2 (1 male; 1 female) (2 males 0 females)
main test 1: 4 per dose (males); main test 2: 4 per dose (males)
Control animals:
yes
Positive control(s):
2- Acetamididofluorene (2AAF)
Off-white solid
Storage: room temperature
Dose: 50 mg/kg

Sym-Dimethylhydrazine dihydrochloride (NDHC)
White crystalline solid
storage conditions: room temperature, over silica gel
Dose: 40 mg/kg

Examinations

Tissues and cell types examined:
Liver Hepatocytes
Details of tissue and slide preparation:
See attached document on tissue and slide preparation
Evaluation criteria:
The coded slides were scored using an automated image analysis system linked to a computer programe (Grain) which followed the UKEMS guidelines for statistical analysis. For further details see attached document on evaluation criteria
Statistics:
no

Results and discussion

Test resultsopen allclose all
Sex:
male/female
Genotoxicity:
not determined
Remarks:
range finder test
Toxicity:
yes
Remarks:
2000 mg/kg: ataxia, lethargy, red colored urine (no deaths)
Vehicle controls validity:
not examined
Negative controls validity:
not examined
Positive controls validity:
not examined
Sex:
male
Genotoxicity:
negative
Remarks:
no increase in the incidence of cells in repair at any dose level
Toxicity:
yes
Remarks:
main test 1+2: lethargy and ataxia
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
there were no marked increases in the incidence of unscheduled DNA synthesis in animals dosed with the test material at either time point. Both positive and negative controls produced marked increases in the incidence of cells in repair and the vehicle control groups gave acceptable values for net nuclear grain counts.
Further see attached document on results

Any other information on results incl. tables

See attached document on tables

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative The test material did not induce any marked or toxcologiacally significant increases in the incidence of cells undergoing DNA synthesis
The test material did not induce any marked or toxicologically significant increases in the incidence of cells undergoing unscheduled DNA synthesis in isolated rat hepatocytes following in vivo exposure for 2 or 16 hr. Therefore the test material was considered to be non-genotoxic under the conditions of the study.
Executive summary:

A study was performed to assess the potential of the test material to induce DNA repair in isolated rat hepatocytes following in vivo administration. The method used has been designed to comply with the relevant guidelines such as OECD 486.

The study resulted in no marked increases in the incidence of unscheduled DNA synthesis in animals dosed with the test material at either time point. Both positive and negative controls produced marked increases in the incidence of cells in repair and the vehicle control groups gave acceptable values for net nuclear grain counts. Therefore the test material was considered to be non-genotoxic under the conditions of the study.