Tetrakis(phenylmethyl)thioperoxydi(carbothioamide)

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Version / remarks:

Adopted on 26 May 1983

Deviations:

no

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

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:

C30-H28-N2-S4

IUPAC Name:

N,N-dibenzyl[(dibenzylcarbamothioyl)disulfanyl]carbothioamide

Test material form:

solid

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

Corn oil

Duration of treatment / exposure:

one administration

Frequency of treatment:

one administration

Post exposure period:

72h

Doses / concentrations

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 time: 24 hours
Female: 0 mg/kg; No. of animals: 5; Sacrifice time: 48 hours
Female: 0 mg/kg; No. of animals: 5; Sacrifice time: 72 hours
Female 2000 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
Female 2000 mg/kg; No. of animals: 5; Sacrifice time: 48 hours
Female 2000 mg/kg; No. of animals: 5; Sacrifice time: 72 hours

Control animals:

yes, concurrent vehicle

Positive control(s):

yes, cylophosphamide 50 mg/kg

Examinations

Tissues and cell types examined:

Bone marrow

Details of tissue and slide preparation:

Bone marrow was sampled at 24, 48 and 72 hours after dosing.

Statistics:

yes

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

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.

Positive control (cylophosphamide 50 mg/kg) showed toxic effects and significant increase in number of micronuclei.

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, 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.