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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:
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

Constituent 1
Chemical structure
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

Controlsopen allclose all
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
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.