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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
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

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

Applicant's summary and conclusion