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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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: 99.8%

Method

Target gene:
HPRT-locus
Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9-Mix
Test concentrations with justification for top dose:
1st Experiment
without S9 mix (4-hour exposure period)
0; 6.25; 12.5; 25.0; 50.0; 100.0; 150.0; 200.0 µg/mL
with S9 mix (4-hour exposure period)
0; 1.25; 2.5; 5.0; 10.0; 15.0; 20.0; 30.0 µg/mL
2nd Experiment (requirements of the OECD Guideline 476 were failed)
without S9 mix (24-hour exposure period)
0; 6.25; 12.5; 25.0; 50.0; 100.0; 150.0; 200.0 µg/mL
with S9 mix (4-hour exposure period)
0; 1.25; 2.5; 5.0; 10.0; 15.0; 17.5; 25.0 µg/mL
3rd Experiment
without S9 mix (24-hour exposure period)
0; 12.5; 25.0; 50.0; 100.0; 200.0; 300.0; 400.0 µg/mL
with S9 mix (4-hour exposure period)
0; 0.63; 1.25; 2.5; 5.0; 10.0; 15.0; 17.5; 20.0 µg/mL
Vehicle / solvent:
culture medium (Ham's F12)
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
3-methylcholanthrene
Details on test system and experimental conditions:
After an attachment period of 20 - 24 hours and a treatment period of 4 hours both with and without metabolic activation and 24 hours without metabolic activation, an expression phase of about 6 - 8 days and a selection period of about 1 week followed. The colonies of each test group were fixed with methanol, stained with Giemsa and counted.
Statistics:
Due to the clearly negative findings, a statistical evaluation was not carried out.

Results and discussion

Test results
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
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

Under the experimental conditions chosen, the conclusion is drawn that Propargyl alcohol highly conc. is not a mutagenic substance in the HPRT locus assay using CHO cells in the absence and the presence of metabolic activation.
Executive summary:

The substance Propargyl alcohol highly conc. was assessed for its potential to induce gene mutations at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in Chinese hamster ovary (CHO) cells in vitro. Three independent experiments were carried out, with and without the addition of liver S9 mix from induced rats (exogenous metabolic activation). The vehicle controls gave mutant frequencies within the range expected for the CHO cell line. Both positive control substances, EMS and MCA, led to the expected increase in the frequencies of forward mutations.

In this study, in the 1st and 3rd Experiment in the absence and presence of metabolic activation the highest concentrations tested for gene mutations were clearly cytotoxic.

On the basis from the results of the present study, the test substance did not cause any relevant increase in the mutant frequencies both either without S9 mix or after adding a metabolizing system in two valid experiments performed independently of each other.

Thus, under the experimental conditions of this study, the test substance Propargyl alcohol highly conc. is not mutagenic in the HPRT locus assay under in vitro conditions in CHO cells in the absence and the presence of metabolic activation.