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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 based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate OECD test guideline, with acceptable restrictions. The restrictions were that only four strains of bacteria were used. Read across to the registered substance is considered scientifically justified.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
1983
Deviations:
yes
Remarks:
only four strains of bacteria used
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Target gene:
Histidine operon
Species / strain
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
50, 158, 500, 1590 and 5000 µg/plate
Vehicle:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: none given in report
Controlsopen allclose all
Negative controls:
other: sterility checks of S9 and test substance, and bacteria plated alone
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
TA 1535 and TA 100 without metabolic activation
Negative controls:
other: sterility checks of S9 and test substance
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
TA 1535 with and without metabolic activation
Negative controls:
other: sterility checks of S9 and test substance
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
TA 1537 without metabolic activation
Negative controls:
other: sterility checks of S9 and test substance
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
TA 98 without metabolic activation
Negative controls:
other: sterility checks of S9 and test substance
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
TA 1537, TA 100 and TA 98 with metabolic activation
Details on test system and conditions:
ACTIVATION: S9 mix contained 10% S9, NADP and glucose-6-phosphate as cofactors.

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: none
- Exposure duration: 48 hours at 37°C

SELECTION AGENT (mutation assays): histidine deficient agar

NUMBER OF REPLICATIONS: triplicate plates, experiment repeated

DETERMINATION OF CYTOTOXICITY
Evaluation criteria:
None described in report
Statistics:
None described 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:
no, but tested up to limit concentrations
Remarks:
no cytotoxicity observed at any concentration.
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- none reported

RANGE-FINDING/SCREENING STUDIES: No toxicity was observed in the preliminary toxicity test, and no increase in revertant colonies occurred.

COMPARISON WITH HISTORICAL CONTROL DATA: no information

Any other information on results incl. tables

Table 1 Experiment 1 Plate incorporation: number of revertants per plate (mean of three plates)

Concentration (µg/plate)

TA 98

TA 100

TA 1535

TA 1537

+MA

-MA

+MA

-MA

+MA

-MA

+MA

-MA

None; sterility check

0

-

0

-

0

-

0

-

5000 (sterility check)

-

0

-

0

-

0

-

0

5000

28

22

110

111

13

9

4

3

1580

31

33

121

118

14

12

7

6

500

30

27

119

123

12

14

10

4

158

27

30

132

128

15

14

8

7

50

26

28

141

113

15

14

7

10

DMSO

34

31

126

116

18

16

7

8

Positive control 1

484

26

710

113

339

25

176

10

Positive control 2

-

149

-

948

-

799

-

1018

Culture only *

-

101

-

92

 

-

121

-

101

*10E-6 dilution of bacterial culture only; plated on nutrient: agar total colony counts 

 

Table 2 Experiment 2 Plate incorporation: number of revertants per plate (mean of three plates)

Concentration (µg/plate)

TA 98

TA 100

TA 1535

TA 1537

+MA

-MA

+MA

-MA

+MA

-MA

+MA

-MA

None; sterility check

0

-

0

-

0

-

0

-

5000 (sterility check)

-

0

-

0

-

0

-

0

5000

28

23

101

98

14

11

7

5

1580

28

26

110

100

13

15

6

8

500

27

26

99

94

16

19

9

7

158

26

27

102

100

16

13

7

6

50

25

27

120

97

19

15

6

6

DMSO

32

28

104

99

19

17

9

8

Positive control 1

541

24

775

105

211

22

150

4

Positive control 2

-

138

-

875

-

698

-

1243

Culture only *

-

100

-

102

-

111

-

102

*10E-6 dilution of bacterial culture only; plated on nutrient: agar total colony counts

Applicant's summary and conclusion

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

The C6-12 alcohol Linevol 79 did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at dose levels up to and including 5000 µg/plate. All positive controls gave an appropriate response. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.