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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report similar or equivalent to OECD 476.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
GLP compliance:
yes
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MCP 917
- Physical state: pale yellow liquid

Method

Target gene:
Thymidine Kinase
Species / strain
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
- Type and identity of media: Fischer's medium supplemented with heat-inactivated horse serum (10%), sodium pyruvate (1mM) and Pluronic (0.1%)
- Properly maintained: yes
Additional strain / cell type characteristics:
other: subclone 3.7.2C
Metabolic activation:
with and without
Metabolic activation system:
S-9
Test concentrations with justification for top dose:
0.8 to 10 ul/ml
Vehicle / solvent:
acetone
Controls
Untreated negative controls:
yes
Remarks:
acetone
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
yes
Remarks:
two positive controls
Positive control substance:
ethylmethanesulphonate
Remarks:
EMS for non-activated culture, DMBA for the activated culture

Migrated to IUCLID6: DMBA
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: 65-72 hours
- Exposure duration: 3 hours
- Expression time (cells in growth medium): 48 hours

NUMBER OF CELLS EVALUATED: 2 x 10^5 cells per culture

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency and relative total growth

Results and discussion

Test results
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
not specified
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RANGE-FINDING/SCREENING STUDIES: There were no signs of toxicity at the highest soluble doses of the test material.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

The in vitro gene mutation assay in mammalian cells to assess the genotoxicity of the read-across substance, MCP 917, was non-mutagenic with or without activation. This finding does not warrant the classification of the submission substance as a genotoxin under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

The test material was examined for its potential to induce mutations in the mouse lymphoma L5178Y/TK+/- cell line, in both the presence and absence of an S9 metabolic system. The test material did not induce a statistically significant dose-dependent increase in gene mutation frequency with or without activation. Under the conditions of this study, the test material was non-mutagenic. This finding does not warrant the classification of the test material as a genotoxin under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.