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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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
strain with AT base pair as primary mutation site missing, only 4 test concentrations up to 4000 µg/plate tested
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
6-O-α-D-glucopyranosyl-D-fructose
EC Number:
237-282-1
EC Name:
6-O-α-D-glucopyranosyl-D-fructose
Cas Number:
13718-94-0
Molecular formula:
C12H22O11
IUPAC Name:
6-O-alpha-D-glucopyranosyl-D-fructose
Details on test material:
- Name of test material (as cited in study report): isomaltulose
- Physical state: white, crystalline powder
- Analytical purity: no data
- Reference No.: 571/271105/UK
- Storage condition of test material: stored in a cool, dry place

Method

Target gene:
his operon
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
S. typhimurium TA 1538
Metabolic activation:
with and without
Metabolic activation system:
cofactor supplemented post-mitochondrial fraction (10% S9 in S9 mix), prepared from the livers of Fischer 344 rats treated with Aroclor 1254 (500 mg/kg bw for 5 days)
Test concentrations with justification for top dose:
100, 500, 1000 and 4000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: sodium azide (SA; 1 µg/plate, -S9, TA 100 and TA 1535); 9-aminoacridine (9AA; 50 µg/plate, -S9, TA 1537); 2-nitrofluorene (2NF; 0.5 µg/plate, -S9, TA 1538 and TA 98); 2-aminoanthracene (2AA; 2µg/plate, +S9, all strains)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 h

DETERMINATION OF CYTOTOXICITY
- Method: other: reduction in the background lawn on the plates

Number of replications: triplicates each in one (TA 1535, TA 98, TA 100) or two (TA 1537, TA 1538) independent experiments
Statistics:
Mean values and standard deviations were calculated for each treatment. Analysis of variance were performed on each set of data to give the F-statistic. As no F-statistic was biologically significant, no further analysis were carried out.

Results and discussion

Test resultsopen allclose all
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
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
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'.

Any other information on results incl. tables

Table 1. Test results for Isomaltulose (experiment I)

 

With or without S9-Mix

Test substance concentration

(μg/plate)

Mean number of revertant colonies per plate (average of 3 plates) ± standard deviation

Base-pair substitution type

Frameshift type

TA100

TA1535

TA98

TA1537

TA1538

water

159.3 ± 3.8

18 ± 2.6

18.7 ± 8.7

7.7 ± 4.7

22.7 ± 4.0

100

173.7 ± 8.1

15.7 ± 5.0

20.0 ± 5.2

6.0 ± 4.4

19.0 ± 10.5

500

150.3 ± 12.5

23.3 ± 9.6

19.0 ± 2.0

4.0 ± 0.0

21.0 ± 2.6

1000

165.7 ± 13.9

16.0 ± 3.0

20.7 ± 3.2

6.0 ± 2.6

11.7 ± 5.5

4000

139.3 ± 4.0

20.7 ± 9.1

19.7 ± 1.5

7.0 ± 6.2

14.0 ± 6.0

Positive controls

(concentrations (µg/plate))

SA

(1)

SA

(1)

2NF

(0.5)

9AA

(50)

2NF

(0.5)

Mean No. of colonies/plate (average of 3 plates) ± SD

909.3 ± 112.0

626.7 ± 68.5

104.5 ± 7.5a

343.0 ± 16.1

241.7 ± 17.2

+

water

144.0 ± 24.6

15.7 ± 5.5

37.7 ± 2.3

15.7 ± 4.7

29.7 ± 8.0

+

100

130.0 ± 10.6

21.0 ± 3.6

36.3 ± 6.7

12.3 ± 1.2

30.7 ± 3.5

+

500

116.0 ± 18.7

20.0 ± 4.6

33.0 ± 8.9

14.7 ± 4.0

26.3 ± 3.2

+

1000

135.7 ± 5.8

18.0 ± 3.6

29.7 ± 8.1

14.0 ± 2.6

21.0 ± 7.0

+

4000

112.0 ± 3.6

17.7 ± 2.5

32.0 ± 4.4

11.3 ± 0.6

31.7 ± 1.2

+

Positive controls

(concentrations (µg/plate))

2AA

(2)

2AA

(2)

2AA

(2)

2AA

(2)

2AA

(2)

Mean No. of colonies/plate (average of 3 plates) ± SD

490.3 ± 84.7

62.3 ± 13.0

375.5 ± 117.5a

58.3 ± 8.3

330 ± 22.6

a: The mean was calculated based on two plates (one plate lost)

SA = sodium azide

9AA = 9-aminoacridine

2NF = 2-nitrofluorene

2AA = 2-aminoanthracene

SD = standard deviation

 

Table 2. Test results for Isomaltulose (experiment II)

 

With or without S9-Mix

Test substance concentration

(μg/plate)

Mean number of revertant colonies per plate (average of 3 plates) ± standard deviation

Frameshift type

TA1537

TA1538

water

5.3 ± 1.2

6.0 ± 2.6

100

6.7 ± 1.5

7.0 ± 1.0

500

4.7 ± 1.5

6.7 ± 2.1

1000

4.0 ± 2.0

9.0 ± 4.6

4000

5.3 ± 1.5

10.7 ± 3.8

Positive controls

(concentrations (µg/plate))

9AA

(50)

2NF

(0.5)

Mean No. of colonies/plate (average of 3 plates) ± SD

100.0 ± 37.5

333.7 ± 35.3

+

water

7.3 ± 0.6

20.0 ± 3.5

+

100

6.7 ± 2.3

24.0 ± 4.6

+

500

12.3 ± 1.5

22.0 ± 2.6

+

1000

5.3 ± 1.5

16.3 ± 6.1

+

4000

6.3 ± 1.5

21.3 ± 2.3

+

Positive controls

(concentrations (µg/plate))

2AA

(2)

2AA

(2)

Mean No. of colonies/plate (average of 3 plates) ± SD

72.3 ± 25.4

602.7 ± 99.9

9AA = 9-aminoacridine

2NF = 2-nitrofluorene

2AA = 2-aminoanthracene

SD = standard deviation

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative