Reaction products of 2-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-hydroxyphenol with ((C10-16, rich in C12-13 alkyloxy)methyl)oxyrane

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:

1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented, GLP and guideline conform, some information to test material are not given (storage, expiration date of the batch), read across substance

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-(4,6-diphenyl-1,3,5-triazin-2-yl)-5-((hexyl)oxy)phenol

EC Number:

411-380-6

EC Name:

2-(4,6-diphenyl-1,3,5-triazin-2-yl)-5-((hexyl)oxy)phenol

IUPAC Name:

411-380-6

Method

Target gene:

HGPRT

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Metabolic activation system:

Rat liver S-9 microsomal activation system

Test concentrations with justification for top dose:

0, 18.52, 55.56, 166.67 and 500 microg/ml

Vehicle / solvent:

DMSO

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

N-dimethylnitrosamine

Remarks:

without metabolic activation

Migrated to IUCLID6: DMN, 1.0 microliter/ml

Controls 2

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

with metabolic activation

Migrated to IUCLID6: 0.3 microliter/ml

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: with metabolic activation for 5 hours and in the experiment without metabolic activation for 21 hours

SELECTION AGENT (mutation assays): 6-Thioguanine

NUMBER OF REPLICATIONS: two

NUMBER OF CELLS EVALUATED: all colonies were counted

DETERMINATION OF CYTOTOXICITY
Cytotoxicity test
In the part with metabolic activation, at the highest concentration of 500 microg/ml an acute growth inhibiting effect of 55.15% could be seen. Withoutmetabolic activation treatment was growth inhibiting by 39.42% at the highest concentration of 500 microg/ml. Accordingly, 500 microg/ml was chosen as the highest concentration for the first mutagenicity assay with and without metabolic activation. Precipitates of the test compound were visible in the cultures down to the concentration of 62.5 ng/ml.

OTHER
The cells have a stable karyotype with a modal chromosome number of 22±1. All stock cells were checked for mycoplasma contamination, using the Hoechst- Dye staining method or the 6-MPDR method, before being frozen.

Evaluation criteria:

All mutant frequencies are normalized to a virtual cloning efficiency of 100% at the end of the expression
period. If the cloning efficiency of the viability cultures is lower than 15%, the corresponding
mutant frequency is usually not calculated, owing to the high statistical insignificance of the
result. For every concentration a mean mutant factor, which is defined as the ratio of the mean mutant
frequencies of the treated cultures with the mean mutant frequencies of the solvent control cultures,
will be calculated.

Statistics:

Statistical significance of mutant frequencies was carried out according to the UKEMS guidelines

Results and discussion

Test results

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Precipitates of the test compound were visible in the cultures down to the concentration of 62.5 microg/ml.

RANGE-FINDING/SCREENING STUDIES:

COMPARISON WITH HISTORICAL CONTROL DATA: Historical control data from gene mutation tests with Chinese Hamster Cells V79

ADDITIONAL INFORMATION ON CYTOTOXICITY: In the part with metabolic activation, at the highest concentration of 500 microg/ml an acute growth inhibiting effect of 55.15% could be seen. Without metabolic activation treatment with the test item was growth inhibiting by 39.42% at the highest concentration of 500 microg/ml. Accordingly, 500 microg/ml was chosen as the highest concentration for the first mutagenicity assay with and without metabolic activation.

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

Based on the results of two independently performed experiments and under the given experimental conditions, it is concluded that the test item and its metabolites did not show any mutagenic activity in this forward mutation system.