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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. There is no information on compliance with GLP.

Data source

Reference
Reference Type:
publication
Title:
A compilation of two decades of mutagenicity test results with the Ames Salmonella typhimurium and L5178Y mouse lymphoma cell mutation assays.
Author:
Seifried, H.E. et al
Year:
2006
Bibliographic source:
Chem. Res. Toxicol 19, 627-644

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
yes
Remarks:
the experiment was not repeated with a longer exposure time
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): 2-methyltetrahydrofuran, CAS 96-47-8

Method

Target gene:
thymidine kinase operon
Species / strain
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
- Type and identity of media: Fischer's medium for leukaemic cells of mice supplemented with 10% horse serum.
- Properly maintained: no data
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: no data
- Periodically "cleansed" against high spontaneous background: no data
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9;
Test concentrations with justification for top dose:
1500-5000 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: ethyltmethanesulphonate or methyltmethanesulphonate
Remarks:
without activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 3-methylcholanthrene or dimethylgenz[a]-anthracene with metabolic activation
Remarks:
with metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium;

DURATION
- Exposure duration: 4 hours
- Expression time (cells in growth medium): 48 hours
- Selection time (if incubation with a selection agent):
- Fixation time (start of exposure up to fixation or harvest of cells): 10-12 days

SELECTION AGENT (mutation assays): TFT

NUMBER OF REPLICATIONS: duplicate cultures

DETERMINATION OF CYTOTOXICITY
- Method: rate of growth

OTHER colony sizing was also performed
Evaluation criteria:
A positive result was obtained where there was doubling of mutant frequency over the concurrent solvent control, together with a dose response.

Results and discussion

Test results
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid

Any other information on results incl. tables

2-Methyltetrahydrofuran Mouse Lymphoma Test Data

      Non-Activated Cultures     S9-Activated Cultures
Solvent Dose (µg/ml) Average TFT Average VC Mut Freq RTG Dose (µg/ml) Average TFT Average VC  Mut Freq RTG
H2O 1500 to 5000                  
  1500 49 148 0.67 114 1500 45 221 0.4 142
    38 139 0.53 95   24 140 0.34 92
  2000 41 143 0.57 105 2000 62 132 0.93 77
    29 149 0.39 103   76 --- --- ---
  3000 39 199 0.39 135 3000 69 132 1.05 74
    44 151 0.58 104   77 129 1.19 82
  4000 38 160 0.48 92 4000 49 128 0.77 78
    49 155 0.63 108   58 132 0.88 81
  5000 50 145 0.7 87 5000 54 132 0.82 78
    32 163 0.39 97   39 132 0.6 77
  Solvent 39 17 0.58   Solvent 65 151 0.88  
  Positive 183 108 3.39 53 Positive 185 118 3.14 69

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with and without metabolic activation

An investigation into the mutagenicity of tetrahydro-2-methylfuran has been reported. The method used is similar to OECD TG 476. The authors of the publication report that the test substance was negative for mutagenicity to L5178Y cells without metabolic activation, but that the result with metabolic activation was inconclusive; however, the data presented do not include clear evidence of a substance-related, dose-dependent increase in mutant frequency, so it is the conclusion of the reviewer is that the test substance is negative for mutagenicity to mammalian cells under the conditions of the test.