Tetrahydro-3-methylfuran

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to valid and internationally recognized test procedures.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1986

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

The Salmonella preincubation assay, a modification of the standard plate incorporation assay as used by the National Toxicology Program (NTP) . Salmonella typhimurium tester strains TA97, TA98, TA100, TA1535, and TA1537 were incubated (preincubation) with concentrations of 100 to 10,000 microg/plate of tetrahydrofuran (3 replicates/concentration) either with or without metabolic activation (Aroclor 1254-induced male rat and Syrian hamster S-9.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Tetrahydrofuran

EC Number:

203-726-8

EC Name:

Tetrahydrofuran

Cas Number:

109-99-9

IUPAC Name:

tetrahydrofuran

Details on test material:

Tetrahydrufuran was received from Radian Corporation (Austin, TX, USA) as a coded aliquot.

The purity of the tetrahydrofuran was approximately 99%.

Method

Target gene:

Histidine requiring strains.

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Details on mammalian cell type (if applicable):

Also including TA97

Test concentrations with justification for top dose:

100, 333, 1000, 333, and 10000 microgr/plate

Vehicle / solvent:

Water was used as solvent in all cases where solubility allowed.

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

water

True negative controls:

yes

Remarks:

Potassium chloride

Positive controls:

yes

Positive control substance:

other: sodium azide (TA1535 and TA100), 4-nitro-o-phenylenediamine (TA98), and 9-aminoacridine (TA97 and TA1535)

Details on test system and experimental conditions:

METHOD OF APPLICATION:
A modification of the standard plate incorporation method was employed. Tests were conducted in the presence or absence of S9. Five dose levels and control were tested up to and including 10,000 microg/plate at approximately half-log intervals. All testes were performed in triplicate and the entire assay conducted twice (at separate laboratories).
- Preincubation Mixture: To a series of tubes were added 0.5 ml of S-9 mix or 0.1 M PO4 buffer (pH4), 0.05 ml of the overnight culture, and 0.05 ml of the solvent or test chemical mixture. These were allowed to incubate without shaking at 37 deg C.
- Exposure: To the preincubation tubes were added either 2.0 or 2.5 ml of top agar supplemented with 0.05 mM L-histidine and 0.5 mM d-biotin was added, and the contents of the resulting tubes mixed and poured onto minimal glucose agar plates. After solidification, plates were inverted and incubated at 37 deg C for 48 hours.


DURATION
- Preincubation period: 20 minutes
- Exposure duration: 48 hours


NUMBER OF REPLICATIONS:
3 replicates/strain


DETERMINATION OF CYTOTOXICITY
Cytotoxicity was evidenced by one or more of the following phenomena: appearance of his- pinpoint colonies, reduced numbers of revertant colonies per plate, or thinning or absence of the bacterial lawn. Nontoxic chemicals were tested up to 10,000 microg/plate, or to a level determined by their solubility.

Evaluation criteria:

A positive response is defined as a reproducible, dose-related increase in histidine-independent (revertant) colonies in any one strain/activation combinations. An equivocal response is defined as an increase in revertants that is not dose-related, not reproducible, or not of sufficient magnitude to support a determination of mutagenicity. A negative response is obtained when no increase in revertant colonies is observed following chemical treatment. There is no minimum percentage or fold increase required for a chemical to be judged positive or weakly positive.

Statistics:

Results reported as the means +/- one standard deviation.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and 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 examined

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

Tetrahydrofuran was negative for mutagenicity when tested in Salmonella sp. up to a limiting plate incorportation level of 10,000 microg/plate.