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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Method and results sufficient described, similar to OECD guideline 476

Data source

Reference
Reference Type:
publication
Title:
The mutagenic activity of unpolymerized resin monomers in Salmonella typhimurium and V79 cells
Author:
Schweikl H, Schmalz G, Rackebrandt K
Year:
1998
Bibliographic source:
Mutation Research 415: 119 - 130

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Principles of method if other than guideline:
In addition to the mutation test at the TK locus, analyses for chromosomal aberrations and induction of micronuclei in vitro were run.
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Methylmethacrylate (CAS: 80-62-6)
purchased from Merck
Purity analyzed HPLC and MS

Method

Target gene:
TK
Species / strain
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Details on mammalian cell type (if applicable):
V79B
Metabolic activation:
with and without
Metabolic activation system:
rat liver
Test concentrations with justification for top dose:
0, 10, 20 mM
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 1342 9,10-dimethyl 1,2-benzanthracene and ethyl methane sulfonate
Details on test system and experimental conditions:
1.5E+6 cells were plated onto cell culture plates with culture medium and incubated for 20-24 hours. Cells were exposed to varying concentrations of the test substance for 24 hrs in the absence of S9 mix or 4 hrs with or without S9 mix. The cells were subcultured after four days, cell numbers counted and expressed relative to cell counts in solvent control cultures or the plating efficiency. 3E+6 cells were subcultured for eight days and mutant isolation started on day 10 by replating the cells in selective media containing 6-thioguanidine, and the cloning efficiency determined.

Results and discussion

Test results
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
ambiguous
Remarks:
taking into account the range of control values
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
>20 mM/L
Positive controls validity:
valid
Additional information on results:
A very weak mutagenic response in V79 cells was observed at the concentrations tested after a direct exposure for 24 hours. Without metabolic activation, the mutant frequencies in the tested concentrations of 10 and 20 mM were 6 and 16 per million surviving cells, while in the control treatment 3 mutants per million surviving cells were observed. Other control data from parallel experiments reported in the same paper range from 2 to 10 mutants per million surviving cells. The cell numbers of the low and high dose treatment were 71 and 49% of the control, respectively. Data from the trial with metabolic activation were not reported in detail. The authors interpret the data as a very weakly positive finding. In the light of the range of control data, the result is interpreted as ambiguous.
Remarks on result:
other: other: V79B Chinese hamster fibroblasts
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
ambiguous without metabolic activation

The authors interpret the data as a very weakly positive finding. In the light of the range of control data reported in the paper (2 - 10 / mio cells), the result in the higher concentration (16 / mio. cells) is interpreted as ambiguous.
Executive summary:

A very weak mutagenic response in V79 cells was observed at the concentrations tested after a direct exposure for 24 hours. Without metabolic activation, the mutant frequencies in the tested concentrations of 10 and 20 mM were 6 and 16 per million surviving cells, while in the control treatment 3 mutants per million surviving cells were observed. Other control data from parallel experiments reported in the same paper range from 2 to 10 mutants per million surviving cells. The cell numbers of the low and high dose treatment were 71 and 49% of the control, respectively. Data from the trial with metabolic activation were not reported in detail. The authors interpret the data as a very weakly positive finding. In the light of the range of control data, the result is interpreted as ambiguous.