Sodium dimethyldithiocarbamate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

yes

Remarks:

According to OECD 473 the highest concentration should show a mitotic index greater than 50%. With mitotic indices of 46 and 48%, this criterion was barely missed.

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian chromosome aberration test

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

Molecular formula:

C3H7NS2.Na

IUPAC Name:

sodium dimethyldithiocarbamate

Method

Species / strain

Species / strain / cell type:

lymphocytes: human

Metabolic activation:

with and without

Metabolic activation system:

S9 mix from livers of male Sprague-Dawley rats treated with phenobarbitone (80 mg/kg bw) and -naphthoflavone (100 mg/kg bw). (3 daily oral doses). Livers were prepared 24 h after the doses.

Test concentrations with justification for top dose:

±S9: 0 – 268.5 µg/mL

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: none

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: –S9: Mitomycin C (MMC, 0.2-0.4 µg/mL, dissolved in MEM) +S9: Cyclophosphamide (CP, 10 µg/mL, dissolved in DMSO)

Details on test system and experimental conditions:

DURATION:
- Exposure duration: 4, 24 h
- Harvest time: 24 h from beginning of treatment

NUMBER OF CELLS EVALUATED:
100 per culture, 2 cultures per concentration

Results and discussion

Test results

Species / strain:

lymphocytes: human

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

GENOTOXICITY:
The test material did not induce any significant dose-related increases in the frequency of cells with chromosome aberrations or in the number of polyploid cells in the absence or presence of metabolic activation.

CYTOTOXICITY:
Clear toxic effects were observed after 4 h treatment with 89.5 µg/mL in the absence and presence of S9 mix. At the 24-hours exposure without S9 the toxic level was already reached at 22.38 µg/mL.

Any other information on results incl. tables

Table 7.6.1-B1 Results of Chromosome Aberration Test – Experiment 1 without metabolic activation (4 h exposure to SDDC, harvest 24 h after start of exposure)
total incidences in 100 cells scored			MMC 0.4 µg/mL		Solvent control		SDDC [µg/mL]
							89.5		134.28		268.5
Replicate			A	B	A	B	A	B	A	B	A	B
Cytotoxicity   (Mitotic inhibition > 50 %)			Yes		No		No		No		No
	Gaps		10	13	1	1	1	1	2	1	0	0
Chromatid- aberrations	Breaks		18	24	1	2	0	1	0	3	1	1
	Exchanges		19	23	0	0	0	1	0	0	0	0
Chromosome- aberrations	Breaks		2	1	0	0	0	0	0	0	0	0
	Exchanges		0	1	0	0	0	0	0	0	0	0
	Others		0	0	0	0	0	0	0	0	0	0
Mitotic index [% mitotic nuclei]			2.30	1.95	4.45	4.60	3.50	2.85	2.60	2.45	2.25	2.60
Total Numbers of aberrations, including gaps			49	62	2	3	1	3	2	4	1	1
Total Numbers of aberrations, excluding gaps			39	49	1	2	0	2	0	3	1	1
Frequency of Aberrant Cells, including gaps [%]			32	41	2	3	1	2	2	4	1	1
Frequency of Aberrant Cells, excluding gaps [%]			27^a	36^a	1	2	0	2	0	3	1	1
^asum of replicates: p < 0.001
Table 7.6.1 -B2 Results of Chromosome Aberration Test – Experiment 1 with metabolic activation (4 h exposure to SDDC, harvest 24 h after start of exposure, 1% S9)
total incidences in 100 cells scored			CP 10 µg/mL		Solvent control		SDDC [µg/mL]
							44.75		89.5		134.28
Replicate			A	B	A	B	A	B	A	B	A	B
Cytotoxicity   (Mitotic inhibition > 50 %)			Yes		No		No		No		Yes
	Gaps		7	17	2	4	2	0	3	0	3	1
Chromatid- aberrations	Breaks		12	19	0	0	0	0	2	0	3	0
	Exchanges		4	3	0	0	0	0	0	0	0	0
Chromosome- aberrations	Breaks		3	3	1	0	0	0	0	1	1	0
	Exchanges		0	1	0	0	0	0	0	0	0	0
	Others		0	0	0	0	0	0	0	0	0	0
Mitotic index [% mitotic nuclei]			1.70	1.75	3.65	3.70	2.90	3.55	2.05	1.90	1.55	1.40
Total Numbers of aberrations, including gaps			26	43	3	4	2	0	5	1	7	1
Total Numbers of aberrations, excluding gaps			19	26	1	0	0	0	2	1	4	0
Frequency of Aberrant Cells, including gaps [%]			19	32	3	4	1	0	5	1	7	1
Frequency of Aberrant Cells, excluding gaps [%]			16^a	19^a	1	0	0	0	2	1	4	0
^asum of replicates: p < 0.001

Table 7.6.1 -B3 Results of Chromosome Aberration Test – Experiment 2 without metabolic activation (24 h continuous exposure to SDDC prior to cell harvest)
total incidences in 100 cells scored		MMC^a 0.2 µg/mL		Solvent control		SDDC [µg/mL]
						11.19		16.79		22.38		44.75^b
Replicate		A	B	A	B	A	B	A	B	A	B	A	B
Cytotoxicity   (Mitotic inhibition > 50 %)		Yes		No		No		No		No		Yes
	Gaps	8	8	0	1	0	0	1	1	2	0	–	–
Chromatid- aberrations	Breaks	20	18	0	0	1	1	3	1	0	0	–	–
	Exchanges	15	12	0	0	0	0	0	0	2	0	–	–
Chromosome- aberrations	Breaks	3	3	0	0	1	0	0	1	1	1	–	–
	Exchanges	0	0	0	0	0	0	0	0	0	0	–	–
	Others	0	0	0	0	0	0	0	0	0	0	–	–
Mitotic index [% mitotic nuclei]		1.90	2.30	4.95	6.55	5.15	4.40	3.35	6.20	2.80	3.20	1.05	1.30
Total Numbers of aberrations, including gaps		46	41	0	1	2	1	4	3	5	1	–	–
Total Numbers of aberrations, excluding gaps		38	33	0	0	2	1	3	2	3	1	–	–
Frequency of Aberrant Cells, including gaps [%]		34	25	0	1	2	1	4	3	4	1	–	–
Frequency of Aberrant Cells, excluding gaps [%]		29^d	23^d	0	0	2	1	3^c	2^c	3	1	–	–
^aslide evaluation terminated at 50 cells because approximately 50% cells with aberrations had been observed ^btoxic ^csum of replicates: p < 0.05 ^dsum of replicates: p < 0.001

Table 7.6.1 -B4 Results of Chromosome Aberration Test – Experiment 1 with metabolic activation (4 h exposure to SDDC, harvest 24 h after start of exposure, 2% S9)
total incidences in 100 cells scored		CP 10 µg/mL		Solvent control		SDDC [µg/mL]
						11.19		22.38		44.75		89.5
Replicate		A	B	A	B	A	B	A	B	A	B	A	B
Cytotoxicity   (Mitotic inhibition > 50 %)		Yes		No		No		No		No		Yes
	Gaps	15	6	0	0	0	1	3	4	1	2	1	2
Chromatid- aberrations	Breaks	25	15	0	1	0	0	0	0	0	0	2	0
	Exchanges	17	9	0	0	0	0	0	0	0	0	0	0
Chromosome- aberrations	Breaks	6	0	0	1	1	0	5	3	1	0	0	0
	Exchanges	0	1	0	0	0	0	0	0	0	0	0	0
	Others	0	0	0	0	0	0	0	0	0	0	0	0
Mitotic index [% mitotic nuclei]		1.85	1.50	5.60	6.95	5.10	5.45	6.25	5.30	3.80	2.75	2.15	1.55
Total Numbers of aberrations, including gaps		63	31	0	2	1	1	8	7	2	2	3	2
Total Numbers of aberrations, excluding gaps		48	25	0	2	1	0	5	3	1	0	2	0
Frequency of Aberrant Cells, including gaps [%]		41	18	0	2	1	1	6	5	2	2	3	2
Frequency of Aberrant Cells, excluding gaps [%]		31^a	15^a	0	2	1	0	3	1	1	0	2	0
^asum of replicates: p < 0.001

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative