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Genetic toxicity in vivo

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
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 run to a method comparable with current guidelines and to GLP
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
micronucleus assay
Specific details on test material used for the study:
Supplied by Ordnance Systems, Inc., Kingsport, Tennessee
Lot no.:BAE 07B 305001
Purity:99.6%
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
None stated
Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: neat polyethylene glycol (PEG 200)

No additional data
Details on exposure:
None stated
Duration of treatment / exposure:
14 day
Frequency of treatment:
Daily
Post exposure period:
None stated
Remarks:
Doses / Concentrations:
0, 1000, 1500, and 2000 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
6 rats/sex/dose
Control animals:
yes, concurrent vehicle
Positive control(s):
The positive control group received a single dose of 200 mg/kg of EMS two days prior to study termination.
Tissues and cell types examined:
The samples for micronucleus assay evaluations were prepared using the MicroFlow Plus Kit® (Litron Laboratories) following the manufacturer’s instructions. Briefly, peripheral blood (approximately 120 μL) was collected from the saphenous vein by puncturing the vein with an 18 gauge needle and collecting the blood using a pipette with a tip that was pre-coated in anti-coagulant.
Peripheral blood samples were processed for flow cytometric evaluation of micronucleated reticulocytes (MN-RET).
Details of tissue and slide preparation:
None stated
Evaluation criteria:
None stated
Statistics:
A one-way analysis of variance (ANOVA) was used to test for significant differences in %MN-RET for female and male rats separately. The Tukey multiple comparison test was used to evaluate the differences between dose groups. The results were considered to be statistically significant at p < 0.05. SPSS® version 16.0 was used for all analyses.
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
The frequency of micronucleated reticulocytes (%MN-RET) ranged from 0.20 to 0.23% in female rats and 0.21 to 0.27% in male rats treated with 1, 1.5, and 2 g/kg per day of the test substance in neat PEG 200. Treatment with the test substance did not statistically significantly (p = 0.096 and p = 0.616, respectively) increase the frequency of micronucleated reticulocytes (%MN-RET) in the peripheral blood of female or male rats. The positive control significantly increased, relative to the untreated control, the frequency of micronucleated reticulocytes in the peripheral blood of female and male rats (p = 0.005 and p = 0.047, respectively). These results indicate that the test substance is not genotoxic in rat peripheral blood under the test conditions.
Conclusions:
Interpretation of results (migrated information): negative
The test substance is not genotoxic in rat peripheral blood under the test conditions.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vivo:

Justification for selection of genetic toxicity endpoint

In vivo genotoxicity study performed to internationally accepted guideline and GLP

Justification for classification or non-classification

 In vitro and in vivo tests with NTO were all negative. Based on these findings, the notified substance NTO is not expected to be a genotoxic substance and therefore is not classified in accordance with Regulation (EC) No 1272/2008.