Zinc bis(dibutyldithiocarbamate)

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

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

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

Test material information

Constituent 1

Reference substance name:

Zinc bis(dibutyldithiocarbamate)

EC Number:

205-232-8

EC Name:

Zinc bis(dibutyldithiocarbamate)

Cas Number:

136-23-2

Molecular formula:

C18H36N2S4Zn

IUPAC Name:

zinc bis(dibutyldithiocarbamate)

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 / concentrations

Doses / concentrations 1

Dose / conc.:

200 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

1 000 mg/kg bw/day

Doses / concentrations 3

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