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Toxicological information

Genetic toxicity: in vitro

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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

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1985
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

Constituent 1
Chemical structure
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.
Controlsopen allclose all
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
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
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
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.