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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: comparable to guideline study with acceptable restrictions (e.g. only 50 cells analysed for each animal, limit test with 1000 mg/kg bw)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
yes
Remarks:
number of cells analysed per dose group (50)
GLP compliance:
yes
Type of assay:
chromosome aberration assay

Test material

Constituent 1
Chemical structure
Reference substance name:
N,N-dicyclohexylbenzothiazole-2-sulphenamide
EC Number:
225-625-8
EC Name:
N,N-dicyclohexylbenzothiazole-2-sulphenamide
Cas Number:
4979-32-2
Molecular formula:
C19H26N2S2
IUPAC Name:
N-(1,3-benzothiazol-2-ylsulfanyl)-N-cyclohexylcyclohexanamine
Details on test material:
IUCLID4 Test substance: other TS: Santocure DCBS

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
single administration
Frequency of treatment:
once
Post exposure period:
6 h, 24 h, 48 h
Doses / concentrations
Remarks:
Doses / Concentrations:
1000 mg/kg bw
Basis:

No. of animals per sex per dose:
15/sex and dose DCBS treatment group and vehicle control (5 males and 5 females each at 6 h, 24 h and 48 h),
positive control: 5 males and 5 females
Control animals:
yes, concurrent vehicle

Examinations

Tissues and cell types examined:
bone marrow cells

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Clinical observations:


Clinical signs were observed for all 1000 mg/kg treated animals at 24 and 48 hours after application. The clinical signs observed were depression, red stains on nose/eyes, soft faeces, slight depression, urine stains, and rough coat. No animal died during the study


 


Body weight: A significant changes in body weight was seen for the 48 hours (1000 mg/kg bw) treatment group.


 


Mitotic index: No statistically significant differences between the mean mitotic indices of the test groups and the vehicle control were seen.


 


Chromosome aberrations: positive control group (cyclophosphamide)signifcant increase in aberrant cells


 


1000 mg/kg treatment (6 h and 24 h groups): no statistically significant increase in the frequency of chromosome aberrations compared to control values.


 


1000 mg/kg treatment (48 h): No statistically significant increase in aberrant cells was noted for the 48 hour treatment group (1 % aberrant cells) compared to historical control data (0.27% aberrant cells), whereas comparison to the current negative control (0% aberrant cells) revealed a statistically relevant difference using the non-parametric analysis. Further statistical analysis was performed on the 48-hours results and comparisons were made with historical control data and data from the current solvent control. The author concluded that the statistical significant increase in aberrations seen at 48 hours is based upon comparison with control value of zero. Based on these findings, the authors concluded that the test substance DCBS is not clastogenic.


 


Average chromosome number(normal diploid chromosome number rat: 42 chromosome: No statistically significant differences between the mean chromosome numbers of the test group and the vehicle control were noted


 


 


Santocure DCBS did not produce chromosome damage as measured by significant  increases in chromosome aberrations or chromosome number as compared to concurrent controls in the rat bone marrow assay.

Applicant's summary and conclusion

Conclusions:
Interpretation of results: negative
Executive summary:

The genotoxic potential of DCBS was evaluated in an in vivo bone marrow chromosome aberration assay. Male and female Sprague-Dawley CD® rats were administered with 1000 mg/kg bw test substance once via gavage. Groups of 5 males and 5 females (treatment group and vehicle control each) were sacrificed at 6, 24 and 48 hours following test substance administration. The body weight and clinical observations were recorded during the study. The bone marrow cells were prepared and at least 50 mitotic cells per animal were analysed for cytogenetic aberrations. Clinical signs were observed for all 1000 mg/kg treated animals at 24 and 48 hours after application. The clinical signs observed were depression, red stains on nose/eyes, soft faeces, slight depression, urine stains, and rough coat. No animal died during the study. A significant change in body weight was seen for the 48 hours (1000 mg/kg bw) treatment group. No statistically significant differences between the mean mitotic indices of the test groups and the vehicle control were seen. A statistically significant increase in percent aberrant cells and the mean number of aberrations per cell was seen in the positive control group (cyclophosphamide). Results from the 6- and 24 hours sacrifice data show that no statistically significant increase in the frequency of chromosome aberrations compared to control values was seen in the groups treated with DCBS. No statistically significant increase in aberrant cells was noted for the 48 hour treatment group (1 % aberrant cells) compared to historical control data (0.27% aberrant cells), whereas comparison to the current negative control (0% aberrant cells) revealed a statistically relevant difference using the non-parametric analysis. Further statistical analysis was performed on the 48-hours results and comparisons were made with historical control data and data from the current solvent control. The author concluded that the statistical significant increase in aberrations seen at 48 hours is based upon comparison with control value of zero. Based on these findings, the authors concluded that the test substance DCBS is not clastogenic. Moreover, the average number of chromosomes in the examined metaphases was determined for each animal and all treatment groups were statistically compared to the control group. Rats have a normal diploid chromosome number of 42. No statistically significant differences between the mean chromosome numbers of the test group and the vehicle control were noted (Monsanto Co 1985).