Disulfiram

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

23.08.85-01.05.86

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP - Guideline study, tested with the source substance tetramethylthiuram disulfide (CAS No. 137-26-8). 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 a read-across substance. (For detailed information on the justification of read-across, please refer to the analogue justification document attached in IUCLID section 13).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report Date:

1986

Materials and methods

Test guideline

Qualifier:

according to

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

yes

Remarks:

Chosen concentrations were too low as the relative cell survival did not reach 20%

GLP compliance:

yes

Remarks:

no attest of authority

Type of assay:

mammalian cell gene mutation assay

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): Thiram technical
- Analytical purity: 100 %
- Lot/batch No.: S94/06-85
- Physical state: white powder
- Impurities (identity and concentrations): Tetramethylthiuram monosulphide < 0.03 %, water 0.2 %, sodium sulphate 0.2 % and zinc 0.0124 %
- Stability under test conditions: active ingredient very stable during storage at 55 °C for 14 days; aqueous suspension is very stable at pH 6-7
- Storage condition of test material: at ambient temperature in the dark
- Melting point: 140 °C

Method

Target gene:

HGPRT

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Details on mammalian cell type (if applicable):

6-Thioguanine sensitive, heterozygous at hprt locus

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S9

Test concentrations with justification for top dose:

1, 3.3, 5.6 or 10 µg /ml without S9mix and at 10, 18, 33 or 56 µg/ml in the presence of S9mix for 2 h (S9 mix from Aroclor 1254 pretreated rats). Expression time: 7 days

Controls

Untreated negative controls:

yes

Remarks:

DMSO

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: Without S9-mix: Ethylmethane sulfonate (EMS); 6 mM With S9-mix: Dimethylnitrosamine (DMN); 4 and 8 mM

Results and discussion

Test results

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Chosen concentrations were too low as the cell survival did not reach 20%

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

A concentration of 10 µg/ml,without metabolic activation, reduced cloning efficiency by approximatively 50%. In the presence of S9 mix, cytotoxicity occurred only from 30 µg/ ml. In both experiments, none of the tested doses induced a significant increase in mutant frequency at the HPRT-locus. The addition of S9 mix did not influence these results.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative