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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
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline study, published in peer-reviewed literature, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
Risk Assessments of Dithiocarbamate Accelerator Residues in Latex-based Medical Devices: Genotoxicity Considerations.
Author:
Tinkler J, Gott D and Bootman J
Year:
1998
Bibliographic source:
Food and Chemical Toxicology 36, 849-866

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Version / remarks:
UKEMS Basic Mutagenicity Test Guidelines, 1990
GLP compliance:
not specified
Type of assay:
other: micronucleus test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): zinc dibuthildithiocarbamate, ZDBC
- Physical state: fine white, aggregative powder
- Analytical purity: min. 98%
- Impurities (identity and concentrations): 28 ppm ZDMC, 17 pm ZDEC

Test animals

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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil
Duration of treatment / exposure:
Bone marrow from mice receiving the low and mid-level doses was collected at sacrifice 24 hours after dosing. Control and high-dose mice were sacrificed 24, 48 and 72 hours after dosing and bone marrow preparations were made at these times.
Frequency of treatment:
Single dose
Post exposure period:
24 hours for low and mid-level groups; 24, 48 and 72 hours for high dose and control test groups.
Doses / concentrationsopen allclose all
Dose / conc.:
200 mg/kg bw/day
Dose / conc.:
1 000 mg/kg bw/day
Dose / conc.:
5 000 mg/kg bw/day
No. of animals per sex per dose:
5/sex/dose
Control animals:
yes
Positive control(s):
- Positive control substance: clorambucil
- Justification for choice of positive control: known clastogen
- Route of administration: oral
- Doses / concentrations: 30 mg/kg bw

Examinations

Tissues and cell types examined:
A minimum of 2000 erythrocytes (polychromatic and mature) from the bone marrow of each animal were examined microscopically for the presence of micronuclei
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: Doses were selected following a preliminary toxicity test
Evaluation criteria:
The ratio of polychromatic to mature cells was calculated as an indicator of possible bone marrow toxicity, and the frequency of micronucleated polychromatic erythrocytes (per 1000) was determined as the critical indicator of chromosome-damaging effect.

Results and discussion

Test results
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
No significant adverse reactions were observed at any dose, there was no evidence of effect in the bone marrow. However, the maximum dose tested was both high and the maximum normally employed in studies of this type. No significant difference in frequency of micronucleated polychromatic erythrocytes between test and vehicle control animals was found at any of the dosages or times.

Any other information on results incl. tables

Frequencies of micronucleated polychromatic erythrocytes for the test substance ZDBC:

ZDBC, 24-hour kill

Sex

(30) CBC*

0

200 mg/kg

1000 mg/kg

5000 mg/kg

Male

66.0 +/- 11.7

0.6 +/- 0.5

0.9 +/- 1.1

0.9 +/- 1.2

1.1 +/- 0.8

Female

59.2 +/- 8.1

0.8 +/- 0.4

1.4 +/- 0.5

1.8 +/- 1.3

1.2 +/- 0.4

ZDBC, 48-hour kill

Sex

(30) CBC*

0

200 mg/kg

1000 mg/kg

5000 mg/kg

Male

Not tested

0.6 +/- 0.5

Not tested

Not tested

0.2 +/- 0.4

Female

Not tested

1.7 +/- 0.5

Not tested

Not tested

1.0 +/- 1.2

ZDBC, 72-hour kill

Sex

(30) CBC*

0

200 mg/kg

1000 mg/kg

5000 mg/kg

Male

Not tested

0.2 +/- 0.4

Not tested

Not tested

0.8 +/- 0.8

Female

Not tested

0.8 +/- 0.8

Not tested

Not tested

0.2 +/- 0.4

Applicant's summary and conclusion