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Toxicological information

Genetic toxicity: in vitro

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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