Furan

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to an appropriate OECD test guideline but full details are not available. It was not compliant with GLP.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1985

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Furan

EC Number:

203-727-3

EC Name:

Furan

Cas Number:

110-00-9

Molecular formula:

C4H4O

IUPAC Name:

furan

Constituent 2

Reference substance name:

000110-00-9

Cas Number:

000110-00-9

IUPAC Name:

000110-00-9

Method

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat and hamster liver S9

Test concentrations with justification for top dose:

33.3, 100.0, 333.3, 1000.0 and 3333.3 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: DMSO was chosen as the chemical was not soluble in water or only soluble at a low concentration.

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA1535 and TA100 without metabolic activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylenediamine

Remarks:

TA98 without metabolic activation

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 9-aminoanthracene

Remarks:

TA1537 without metabolic activation

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

TA100, TA1535, TA1537, TA98 with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation

ACTIVATION: S9 mix contained glucose-6-phosphate and NADP as co-factors. 0.5 ml S9 mix containing 10% S9 was added to 2 ml top agar with 0.5mM L-histidine and 0.5mM D-biotin and 0.05 ml of test solution giving a final concentration of 10% S9 mix.

DURATION
- Preincubation period: 20 mins at 37C
- Exposure duration: 48 hours at 37C

SELECTION AGENT (mutation assays): histidine-deficient agar

NUMBER OF REPLICATIONS: triplicate plates, assay repeated

DETERMINATION OF CYTOTOXICITY
- Method: other: condition of background lawn



OTHER:

Evaluation criteria:

The criteria used for data evaluation are summarized as follows: 1) mutagenic response: a dose related, reproducible increase in the number of revertants over background, even if the increase was less than two-fold; 2) non-mutagenic response: when no increase in the number of revertants was elicited by the chemical; 3) questionable response: when there was an absence of a clear-cut dose related increase in revertants; when the dose-related increases in the number of revertants were not reproducible; or when the response was of insufficient magnitude to support the determination of mutagenicity.

Statistics:

None mentioned in report

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:

cytotoxicity

Remarks:

at 3333 in strains TA 1535 and TA 98 without activation

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Summary of results Trial 1 - revertants per plate (mean of 3 plates)

Treatment µg/plate	TA 100			TA 1535			TA 1537			TA 98
	-S9	+S9¹	+S9²	-S9	+S9¹	+S9²	-S9	+S9¹	+S9²	-S9	+S9¹	+S9²
Solvent control	91	104	82	11	5	7	7	7	18	24	33	36
100.0	102	103	93	15	10	10	5	7	19	29	28	33
333.0	93	93	102	12	7	11	5	5	17	25	31	36
1,000.0	83	88	98	13	8	8	5	5	18	19	25	34
3,333.0	79	89	105	6	7	10	5	4	16	10	20	33
10,000.0	73	63	105	3	6	7	4	4	7	1	13	38
Positive control	352	1482	338	285	404	211	312	466	83	529	1222	153

S9¹ = hamster liver S9

S9² = rat liver S9

Summary of results trial 2 – revertants per plate (mean of 3 plates)

Treatment µg/plate	TA 100			TA 1535			TA 1537			TA 98
	-S9	+S9¹	+S9²	-S9	+S9¹	+S9²	-S9	+S9¹	+S9²	-S9	+S9¹	+S9²
Solvent control	106	109	130	16	5	8	4	7	8	30	39	35
33.3	113	113	118	12	9	9	4	6	7	29	36	45
100.0	103	114	112	13	11	10	4	6	6	26	30	44
333.3	97	109	128	11	6	10	7	5	8	28	33	40
1000.0	113p	103p	109p	9p	8p	9p	7p	5p	10p	20p	23p	39p
3333.3	84p	89p	101p	7p	9p	6p	6p	6p	7p	12p	26p	31p
Positive control	237	2327	731	143	446	238	228	499	190	445	1725	578

p = precipitate present on plates

S9¹ = hamster liver S9

S9² = rat liver S9

Applicant's summary and conclusion

Conclusions:

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

Furan has been tested for mutagenicity to bacteria, in a study which was conducted according to a protocol that was similar to OECD 471, not compliant with GLP. No evidence of a test substance-related increase in the number of revertants was observed with or without activation in the initial or the repeat experiments. Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.