Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliance study report, available as unpublished report, no restrictions, adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Principles of method if other than guideline:
Method: other: Pharmakon Research International, Inc. method
GLP compliance:
yes (incl. certificate)
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Target gene:
Hypoxanthine-guanine phosphorybosil transferase (HGPRT)
Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
- Type and identity of media: Cells were plated in plastic tissue culture flasks in 5 mL of medium F12FCM5
- Properly maintained: yes
Metabolic activation:
with and without
Metabolic activation system:
S-9 fraction
Test concentrations with justification for top dose:
25, 50, 75, 100 and 300 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone
Controlsopen allclose all
Untreated negative controls:
yes
Remarks:
With and without metabolic activation
Negative solvent / vehicle controls:
yes
Remarks:
acetone
Remarks:
With and without metabolic activation
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
without metabolic activation
Positive controls:
yes
Positive control substance:
N-dimethylnitrosamine
Remarks:
With metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: 16-24 hours
- Exposure duration: 5 hours
- Expression time (cells in growth medium): 7 days
- Selection time (if incubation with a selection agent): 7 days

SELECTION AGENT (mutation assays): 6-thioguanine

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth (reduction in colony forming ability of the cells)

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 nor precipitates, but tested up to recommended limit concentrations
Remarks:
Cytotoxicity was not observed up to 1000 µg/ml.
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: insoluble
- Precipitation: a precipitation of the test article was apparent in the treatment media at all doses above 100 µg/mL.

RANGE-FINDING/SCREENING STUDIES:
Doses tested: 10, 50 and 100 µg/mL with and without metabolic activation.
There were no statistically significant increases in the mutation frequencies of the Terphenyl, hydrogenated treated cultures when compared to the negative controls at the doses and S-9 concentrations tested.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
Cytotoxicity was not observed up to 1000 µg/mL.
Remarks on result:
other: all strains/cell types tested

Applicant's summary and conclusion

Conclusions:
It is concluded that Terphenyl, hydrogenated failed to induce mutations in Chinese hamster Ovary (CHO) cells at 25, 50, 75, 100 and 300 μg/mL with and without metabolic activation.
Executive summary:

A key study was performed with Terphenyl, hydrogenated for the cell mutation assay in Chinese hamster Ovary (CHO) cells at 25, 50, 75, 100 and 300 μg/mL with and without metabolic activation. The study was conducted on the hypoxanthine-guanine phosphorybosil transferase (HGPRT) target gene. Cytotoxicity was not observed up to 1000 μg/mL, however precipitation of the test article was apparent in the treatment media at all doses above 100 μg/mL. There were no statistically significant increases in the mutation frequencies of the Terphenyl, hydrogenated treated cultures when compared to the negative controls at the doses and S-9 concentrations tested.