Registration Dossier

Administrative data

Endpoint:
in vivo mammalian cell study: DNA damage and/or repair
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
unscheduled DNA synthesis

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Frequency of treatment:
The study was performed in two parts, in Experiment 1 perfusion of the livers commenced approximately 16 hours after dosing and in Experiment 2 perfusion was performed approximately 4 hours after dosing.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 mg/kg bw
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
1000 mg/kg bw
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
2000 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
4

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The test item was considered to be non-genotoxic under the conditions of this study.
Executive summary:

Introduction. A study was performed to assess the potential of the test item to induce DNA repair in isolated rat hepatocytes following in vivo administration. The method used has been designed to be compatible with the OECD Guidelines for Testing of Chemicals No. 486 and follows the recommendations of the UKEMS Sub-Committee on Guidelines for Mutagenicity Testing: Report, Part II revised (Supplementary Mutagenicity Tests: UKEMS recommended procedures, 1993).

Methods. A range-finding test was performed to find suitable dose levels of the test item, route of administration and to determine if the there was any differences in toxicity in male and female rats. As there was no difference in toxicity between sexes the main test was performed using male rats only. The UDS assay was conducted using the oral route of administration using only male animals and with the test item at the maximum dose level of 2000 mg/kg, with 1000 mg/kg as the lower dose level. The study was performed in two parts, in Experiment 1 perfusion of the livers commenced approximately 16 hours after dosing and in Experiment 2 perfusion was performed approximately 4 hours after dosing. Following perfusion the liver hepatocytes were processed to give stained slides which were then scored using a microscope and an automated image analysis system. The method used for scoring the hepatocytes was an area counting method which is compatible with the UKEMS guidelines and OECD test method. Further groups of rats were given a single oral dose of arachis oil, or dosed with 2-acetylaminofluorene (2AAF) at 16 hours or N,N’-dimethylhydrazine dihydrochloride (NDHC) at 4 hours to serve as vehicle and positive controls respectively.

Results. There were no marked increases in the incidence of unscheduled DNA synthesis in animals dosed with the test item at either time point. The positive controls produced marked increases in net nuclear grain counts and in the incidence of cells in repair, and the vehicle control groups gave acceptable values for net nuclear grain counts.