Potassium dimethyldithiocarbamate

Genetic toxicity: in vivo

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

Study period:

2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP - Guideline study, tested with the source substance sodium dimethyldithiocarbamate (CAS No. 128-04-1). In accordance to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on an read-across substance

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Sodium dimethyldithiocarbamate

EC Number:

204-876-7

EC Name:

Sodium dimethyldithiocarbamate

Cas Number:

128-04-1

IUPAC Name:

sodium dimethyldithiocarbamate

Details on test material:

- Name of test material (as cited in study report): SDDC
- Purity: 41.44%

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Ltd, Margate, Kent, UK
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 24-29 g

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

purified water

Duration of treatment / exposure:

2 applications (total volume: 20 mL/kg bw)

Frequency of treatment:

24 h interval

Post exposure period:

24 h

Doses / concentrations

Remarks:

Doses / Concentrations:
350, 700, 1400 mg/kg bw
Basis:
nominal conc.
concentration in vehicle: 17.5, 35, 70 mg/mL

No. of animals per sex per dose:

6

Control animals:

yes

Positive control(s):

Cyclophosphamide (CP), 40 mg/kg bw

Examinations

Tissues and cell types examined:

- Tissue: Femoral bone marrow
- Type of cells: Erythrocytes (2000 cells per animal)

Evaluation criteria:

- Parameters: Micronucleated cells, ratio of poly- to normochromatic erythrocytes

Statistics:

Chi-square test

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

CLINICAL SIGNS - Eye closure and lethargy in all mice treated with 700 and 1400 mg/kg/day. Additionally, abnormal breathing and two mortalities in animals dosed with 1400 mg/kg/day.

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Any other information on results incl. tables

Table 7.6.2-A1: Results for In Vivo Micronucleus Test Treatment group Dose [mg/kg/day] PCE Scored Mean Ratio PCE/NCE MN PCE MN PCE / 1000 cells ± sd^b Significance vehicle – 12000 1.07 8 0.67 ± 0.52 – SDDC 350 12000 0.75 6 0.50 ± 0.45 NS SDDC 700 12000 0.93 6 0.50 ± 0.55 NS SDDC 1400 8000^b 0.55 4 0.50 ± 0.58 NS Cyclophosphamide 40^a 12000 0.67 124 10.33 ± 3.83 p ≤ 0.05

^a administered as a single dose

^b animals found dead prior to dosing on day 2

sd standard deviation

MN micronucleated

NS not significant