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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 22, 1988 to September 28, 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline study performed in compliance with GLP, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Version / remarks:
(1983)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
Version / remarks:
(Directive 84/449/EEC)
Deviations:
no
GLP compliance:
yes
Type of assay:
other: Mammalian Erythrocyte Micronucleus Test

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrakis(phenylmethyl)thioperoxydi(carbothioamide)
EC Number:
404-310-0
EC Name:
Tetrakis(phenylmethyl)thioperoxydi(carbothioamide)
Cas Number:
10591-85-2
Molecular formula:
C30H28N2S4
IUPAC Name:
tetrakis(phenylmethyl)thioperoxydi(carbothioamide)

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Corn oil
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (actual dose received)
Dose / conc.:
2 000 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
Male: 0 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
Male: 0 mg/kg; No. of animals: 5; Sacrifice time: 48 hours
Male: 0 mg/kg; No. of animals: 5; Sacrifice time: 72 hours
Male: 2000 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
Male: 2000 mg/kg; No. of animals: 5; Sacrifice time: 48 hours
Male: 2000 mg/kg; No. of animals: 5; Sacrifice time: 72 hours
Female: 0 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
Female: 0 mg/kg; No. of animals: 5; Sacrifice times: 48 hours
Female: 0 mg/kg; No. of animals: 5; Sacrifice times: 72 hours
Female: 2000 mg/kg; No. of animals: 5; Sacrifice times: 24 hours
Female: 2000 mg/kg; No. of animals: 5; Sacrifice times: 48 hours
Female: 2000 mg/kg; No. of animals: 5; Sacrifice times: 72 hours
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide
- Justification for choice of positive control(s): -
- Route of administration: Oral
- Doses / concentrations: 50 mg/kg body weight

Examinations

Tissues and cell types examined:
Bone marrow
Statistics:
The Wilcoxon rank-sum test was used to assess significant differences between the numbers of micronuclei in the treatment and control groups, in which P

Results and discussion

Test resultsopen allclose all
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Remarks:
Doses producing toxicity: No signs of toxicity at 2000 mg/kg (maximum dose based on solubility of the test substance in corn oil.
Vehicle controls validity:
valid
Positive controls validity:
valid
Sex:
female
Genotoxicity:
negative
Toxicity:
no effects
Remarks:
Doses producing toxicity: No signs of toxicity at 2000 mg/kg (maximum dose based on solubility of the test substance in corn oil.
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: The small but statistically significant increase in the number of micronuclei in bone marrow of female mice at the 48-hour sampling time is considered to be not biologically significant, as the increase is just borderline.
Additional information on results:
Observations:
A small, but statistically significant increase in the number of micronuclei was observed in females at the 48-hour sampling time only. As the increase is borderline it is concluded that this result might not be biologically significant.
Control (cylophosphamide 50 mg/kg) showed toxic effects and significant increase in number of micronuclei.

RESULTS OF RANGE-FINDING STUDY
- Dose range: In a preliminary study 6 animals (3 males and 3 females) were dosed orally with 2000 mg/kg body weight.
- Solubility: Higher concentrations could not be dosed because of aggregates of the test substance in the suspension.
- Clinical signs of toxicity in test animals: The mice did not show any signs of reaction to treatment.
- Other: Based on the results of this pilot study 2000 mg/kg body weight was selected as an appropriate dose for the Micronucleus Test.

Applicant's summary and conclusion

Conclusions:
It is concluded that this test is valid and that TBzTD induced a small but statistically significant increase in the number of micronuclei, under the experimental conditions described in this report. However, as the increase is just borderline, this increase might be not biologically significant.
Executive summary:

Tetrabenzylthiuram disulfide (TBzTD) was tested in the Micronucleus Test in mice. Three groups (D to F), each comprising 5 males and 5 females, received a single oral dose of 2000 mg/kg body weight. Bone marrow was sampled at 24, 48 and 72 hours after dosing. Corresponding vehicle treated groups (A to C) served as negative controls. Bone marrow from a positive control group, treated with a single oral dose of cyclophosphamide (CP) at 50 mg/kg body weight, was harvested at 48 hours after dosing only. The test substance induced a statistically significant increase in the number of micronuclei in polychromatic erythrocytes in female mice at the 48 hour sampling time.

It is concluded that this test is valid and that TBzTD induced a small but statistically significant increase in the number of micronuclei, under the experimental conditions described in this report. However, as the increase is just borderline, this increase might be not biologically significant.

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