Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Version / remarks:
Procedures described previously (King et al. 1981)
Deviations:
not specified
GLP compliance:
not specified
Type of assay:
mammalian erythrocyte micronucleus test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
purity level not specified

Test animals

Species:
mouse
Strain:
NMRI
Sex:
not specified

Administration / exposure

Route of administration:
other: intraperitoneal and per os
Vehicle:
olive oil = negative control
Duration of treatment / exposure:
One administration
Frequency of treatment:
once
Post exposure period:
Expression time 30 to 48 hours
Doses / concentrationsopen allclose all
Dose / conc.:
37.8 mg/kg bw (total dose)
Remarks:
intraperitoneal dose - 3/4 of the reported intraperitoneal LD50 in mice (NIOSH 1980)
Dose / conc.:
18.9 mg/kg bw (total dose)
Remarks:
intraperitoneal dose - half of highest dose
Dose / conc.:
226 mg/kg bw (total dose)
Remarks:
per os dose, equivalent to oral LD50 reported by NIOSH 1980
Dose / conc.:
113 mg/kg bw (total dose)
Remarks:
half of highest dose per os
No. of animals per sex per dose:
5 per dose, except for highest dose per os (3 mice survived among 13 as LD50)
Control animals:
yes, concurrent vehicle
Positive control(s):
procarbazine per os and ip

Examinations

Tissues and cell types examined:
bown marrow erythrocytes
Details of tissue and slide preparation:
point mutation, germinal gene mutations, chromosomal breaks and mitotic chromosome misdistribution
Evaluation criteria:
presence/absence
Statistics:
not specified

Results and discussion

Test results
Key result
Sex:
not specified
Genotoxicity:
negative
Toxicity:
yes
Remarks:
expected as highest dose per os equivalent to LD50
Vehicle controls validity:
not specified
Negative controls validity:
valid
Remarks:
olive oil
Positive controls validity:
valid
Additional information on results:
the failure to observe any of these effects is compatible with the lack of DNA binding of CS and metabolites, in accordance with (von Daniken et al 1981) and (NTP tr377 report, 1990)

Applicant's summary and conclusion

Conclusions:
No genetoxicity (micronucleus) is observed with CS susbtance in mice
Executive summary:

No genetoxicity is observed in micronucleus assay in mice (comparable to OECD 474 methodology) after CS exposure by intraperitoneal and per os routes.