Tetrahydro-2-methylfuran

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

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

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

Test material information

Constituent 1

Reference substance name:

Tetrahydro-2-methylfuran

EC Number:

202-507-4

EC Name:

Tetrahydro-2-methylfuran

Cas Number:

96-47-9

Molecular formula:

C5H10O

IUPAC Name:

2-methyltetrahydrofuran

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

Controls

Controls 1

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

Controls 2

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.