Zinc methacrylate

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:

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.