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Administrative data

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
Study period:
1998
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: US EPA (1997) Toxic Substances Control Act Test Guidelines ; Title 40 CFR Part 799
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
See attachment
Type of assay:
micronucleus assay

Test material

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals or test system and environmental conditions:
Male weight: 28 - 30 g
Female weight: 22-24 g

Humidity: 48-60 %
Temperature: 20-24°C

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
1% methylcellulose
Duration of treatment / exposure:
24 hours with positive control
48 hours with negative control
Doses / concentrations
Remarks:
Doses / Concentrations:
Intraperitoneal injection
Basis:
nominal conc.
60, 120, 240 mg/kg BW
No. of animals per sex per dose:
Male: 0 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
Male: 60 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
Male: 120 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
Male: 240 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
Male: 0 mg/kg; No. of animals: 5; Sacrifice time: 48 hours
Male: 240 mg/kg; No. of animals: 5; Sacrifice time: 48 hours
Female: 0 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
Female: 60 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
Female: 120 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
Female: 240 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
Female: 0 mg/kg; No. of animals: 5; Sacrifice times: 48 hours
Female: 240 mg/kg; No. of animals: 5; Sacrifice times: 48 hours
Positive control(s):
mitomycin C
- Route of administration: Orally by intragastric gavage
- Doses / concentrations: 12mg/kg bw

Examinations

Tissues and cell types examined:
Femur bone marrow: proximal epiphysis
Evaluation criteria:
Micronuclei are identified by the following criteria:
- Large enough to discern morphological characteristics
- Should possess a generally rounded shape with a clearly defined outline
- Should be deeply stained and similar in colour to the nuclei of other cells - not black
- Should lie in the same focal plane as the cell
- Lack internal structure, ie they are pyktonic
- There should be no micronucleous-like debris in the area surrounding the cell
Statistics:
Clinical signs and mortalities
Micronucleated immature erythocyte counts (mie)
Micronucleated mature erythocytes (mme)
Proportion of immature erythocytes (%ie/ie+me)

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Doses producing toxicity: The results of a preliminary test indicated that the maximum dose level tolerated was 240 mg/kg. In preliminary tests, dose levels of 320 mg/kg or more produced mortality. There were no mortalities in the main test. Clinical signs were confined to the intermediate and high dose group (both sexes) and consisted of lethargy, loss of righting reflex, splayed limbs and waddling (intermediate group only). Recovery was complete in all animals by 3 hours after dosing. No adverse clinical signs were obtained for the vehicle control or positive control treated animals over the duration of the test. Observations: The test substance did not cause any statistically significant increases in the number of micronucleated immature or mature erythrocytes at either sampling time. The test substance did not cause any significant decreases in the proportion of immature erythrocytes. The positive control caused large, highly significant increases (p<0.001) in the frequency of micronucleated immature erythrocytes.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Since the test substance did not cause any significant increase in the incidence of micronucleated immature erythocytes or any substantial decrease in the proportion of immature erythocytes, it is conclued that Cl-TTA Solid did not show any evidence of causing chromosome damage or bone marrow cell toxicity when administered by intraperitoneal injection in this in vivo test procedure.

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