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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
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
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. proportion of immature erythrocyte among total erythrocytes not evaluated, dose level: only a dose of 300 mg/ml was evaluated (no limit test))

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984

Materials and methods

Principles of method if other than guideline:
Method: other: in vivo micronucleus test
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzothiazole-2-thiol
EC Number:
205-736-8
EC Name:
Benzothiazole-2-thiol
Cas Number:
149-30-4
Molecular formula:
C7H5NS2
IUPAC Name:
1,3-benzothiazole-2-thiol
Details on test material:
Rotax (mercaptobenzothiazole lot #39-14B), purity: 98.1 %

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Duration of treatment / exposure:
single dose or 2 times 300 mg/kg
Frequency of treatment:
once or twice
Post exposure period:
up to 72 h
Doses / concentrations
Remarks:
Doses / Concentrations:
300 mg/kg bw
Basis:

No. of animals per sex per dose:
8 per dose (4 males and 4 females)
Control animals:
yes, concurrent vehicle

Examinations

Tissues and cell types examined:
polychromatic erythrocytes prepared from the femur of treated mice

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

Pre-experiment (toxicity)

Immediate mortality was observed in four of four animals at the 1,666.6 mg/kg dose level. At 500 mg/kg, two females died within four hours of the first dose. The remaining two males had decreased muscle tone and activity and ptosis. Total death occurring at this level was two of four animals. At 166.6 and 50 mg/kg, the majority of the animals showed no signs, but an occasional animal had decreased tone. No signs were observed at the 16.6 mg/kg level. No mortality occurred at the 166.6, 50 and 16.6 mg/kg levels.

Main experiment:

Pharmacological Effects of Treatment

The following signs were observed at the first dose: prostration, hypoactivity, hypernea, ptosis, tremors upon stimulation and an occasional animal exhibited a loss of righting. Observations at 4 and 24 hours following the first dose included ptosis with no other visible signs in all treated animals. No mortality occurred in the study.

Genotoxicity:

The results for test article mercaptobenzothiazole were negative in the micronucleus test at a dose level of 300 mg/kg in the single dose groups and with a second dose of 300 mg/kg in the multiple dose group administered in a split dose regimen. The test material did not produce a statistically significant increase in the number of micronuclei per 1000 polychromatic erythrocytes in the treated versus the control group. In addition to these criteria, all animals administered mercaptobenzothiazole were within the normal historical range of spontaneous micronuclei incidence.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative