Dimethyl naphthalene-2,6-dicarboxylate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June to August 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study run to a detail method and to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

NDC, was tested in the GHO/HGPRT mutation assay in the absence and presence of metabolic activation with Aroclor-induced rat liver S-9. The assay was conducted at dose levels of 1000, 500, 250, 125 and 62.5 μg/mL both in the absence and in the presence of S-9 activation.

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl naphthalene-2,6-dicarboxylate

EC Number:

212-661-4

EC Name:

Dimethyl naphthalene-2,6-dicarboxylate

Cas Number:

840-65-3

Molecular formula:

C14H12O4

IUPAC Name:

2,6-dimethyl naphthalene-2,6-dicarboxylate

Test material form:

solid: flakes

Details on test material:

CAS number: 840-65-3

Method

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

62.5, 125, 250, 500 and 1000 μg/mL

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

in the non-activated study at a final concentration of 0.2 μL/mL

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

in the S-9 activated study at a final concentration of 4 μg/mL

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: 18-24 hours
- Exposure duration: 5 hours

NUMBER OF REPLICATIONS: 2

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency

OTHER EXAMINATIONS:
- Other: expression of the mutant phenotype and selection of the TG-resistant phenotype

No additional data

Evaluation criteria:

None stated

Statistics:

None stated

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: CHO cells were exposed to solvent alone and to nine concentrations of Dimethyl-2,6-naphthalene dicarboxylate ranging from 1000 to 0.1 µg/mL in the toxicity test in the absence and present of an S-9 reaction mixture. The osmolality of the highest concentration in treatment medium tested, 1000 µg/mL, was 446 mosm/kg, with a measured pH of 7.8. At this dose, the Dimethyl-2,6-naphthalene dicarboxylate was insoluble in solvent and formed a precipitate in treatment medium. Concentrations of 100 to 3 mg/mL were insoluble in solvent. The doses used in the initial assay were 1000, 500, 250, 125 and 62.5µg/mL in the absence and present of S-9. Doses selected for the confirmatory assay were 1000, 500, 250, 125 and 62.5 µg/mL both without and with metabolic activation. All doses were insoluble in treatment medium.

No additional data

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

In a study conducted similar to OECD 476, according to GLP, NDC is negative for gene mutation using Chinese Hamster Ovary (CHO) cells, with and without metabolic activation (S-9 mix). NDC, therefore, is considered non mutagenic in mammalian cells.