Registration Dossier

Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Adequacy of study:
other information

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: EC Commission Directive 2000/32/EC Method B12 OECD Guideline 474 (1997)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test animals

Species:
other: MOuse NMRI BR (SPF)

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
physiological saline
No. of animals per sex per dose:
Male: 0 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
Male: 19 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
Male: 38 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
Male: 75 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
Male: 75 mg/kg; No. of animals: 5; Sacrifice time: 48 hours
Female: 0 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
Female: 19 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
Female: 38 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
Female: 75 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
Female: 75 mg/kg; No. of animals: 5; Sacrifice times: 48 hours

Results and discussion

Additional information on results:
Doses producing toxicity:
In animals dosed with the test material premature deaths
occurred at or above 100mg/kg.

Clinical signs observed at and above 100mg/kg were as
follows: convulsions leading to death, tremors, hunched
posture and quick breathing. Clinical signs observed at and
above 50 mg/kg were as follows: hunched posture, tremors and
quick breathing up to 3 days post dosing. Incidences of
lethargy and rough coat were also noted.

The test material showed no marked difference in its
toxicity to male or female rats, both sexes were used in the
main test.

Adequate evidence of test material toxicity was demonstrated
by the intraperitoneal route; the maximum tolerated dose of
the test material was 75 mg/kg.

Observations:
Animals treated with 75 mg/kg of the test substance
displayed quick breathing and tremors. This was taken to
confirm that systemic absorption had occurred and exposure
to the bone marrow achieved.

The test material did not cause a significant increase in
the frequency of micronucleated polychromatic erythrocytes
of the mice treated in the study compared to concurrent
controls.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative