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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:
27-Mar-1996 to 23-May-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 was that no cross linking strain was used.

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)
Deviations:
yes
Remarks:
(no TA102 or E. coli WP2 uvrA; 2-AA only positive control with S9)
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Kalcohl 6098 (1-hexadecanol)
- Substance type: white granular solid
- Physical state: solid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: 2439
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: room temperature in the dark

Method

Target gene:
histidine
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:
S9 from Aroclor 1254-induced male rat livers
Test concentrations with justification for top dose:
50, 150, 500, 1500 and 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: not stated
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Remarks:
without S9, 3 µg/plate for TA100, 5 µg/plate for TA1535
Positive control substance:
N-ethyl-N-nitro-N-nitrosoguanidine
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Remarks:
without S9, 80 µg/plate for TA1537
Positive control substance:
9-aminoacridine
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Remarks:
without S9, 5 µg/plate for TA1538
Positive control substance:
other: 4-nitro-o-phenylenediamine
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Remarks:
without S9, 0.2 µg/plate for TA98
Positive control substance:
4-nitroquinoline-N-oxide
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Remarks:
with S9, all strains, 0.5, 1 or 2 µg/plate
Positive control substance:
other: 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in agar (plate incorporation)

DURATION
- Preincubation period: not applicable
- Exposure duration: 48 hours

NUMBER OF REPLICATES: duplicate test, each performed with triplicate plates

DETERMINATION OF CYTOTOXICITY
- Method: growth of bacterial lawn
Evaluation criteria:
For a substance to be considered positive, it should have induced a concentration-related and statistically significant increase in mutation rate in one or more starins of bacteria in the presence and/or absence of S9 in both experiments at sub-toxic concentrations. To be considered negative the number of induced revertants compared to spontaneous revertants should be less than two-fold at each concentration employed.
Statistics:
Methods recommended by the United Kingdom Environmental Mutagen Society and normally Dunnett's method of linear regression

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 nor precipitates, but tested up to recommended limit concentrations
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 nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: no data
- Water solubility: no data
- Precipitation: at 5000 mg/plate, but this did not interfere with scoring of revertant colonies
- Other confounding effects: no data

RANGE-FINDING/SCREENING STUDIES: yes, non-toxic up to 5000 ug/plate in TA100

COMPARISON WITH HISTORICAL CONTROL DATA: vehicle control results said to be "within the normal range"

ADDITIONAL INFORMATION ON CYTOTOXICITY: no further data
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

STATISTICAL RESULTS: Dunnetts test was used and showed no statistically significant differences between test and control plates.

Table 1 Experiment 1 Revertants per plate (mean of 3 plates)

Concentration      µg/plate

TA 100

TA 100

TA 1535

TA 1535

TA 1538

TA 1538

TA 98

TA 98

TA 1537

TA 1537

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

0

107

99

33

19

15

21

19

34

8

12

50

91

85

34

12

14

25

24

34

11

10

150

92

89

27

15

17

28

25

35

11

11

500

88

86

23

15

20

29

25

43

10

13

1500

95

98

30

16

16

19

25

40

9

13

5000

95

95

29

18

16

26

23

39

6

12

Positive control

419

672

137

171

544

235

148

236

277

209

 

Table 2 Experiment 2 Revertants per plate (mean of 3 plates)

Concentration      µg/plate

TA 100  

TA 100

TA 1535   

TA 1535    

TA 1538   

TA 1538   

TA 98       

TA 98     

TA 1537   

TA 1537   

 - MA

 + MA

 - MA

 + MA

 - MA

 + MA

 - MA

 + MA

 - MA

 + MA

0

90

113

20

11

14

11

17

27

7

12

50

82

111

21

12

19

14

18

26

8

9

150

87

102

25

12

10

13

17

32

9

8

500

81

107

14

15

13

13

17

27

8

7

1500

89

104

19

14

8

9

17

24

9

10

5000

74

90

15

11

8

11

17

28

9

10

Positive control

530

600

171

195

589

196

152

305

496

206

 

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

In a reliable study, performed according to OECD guideline 471, the C16 alcohol Kahlcol 6098 did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at concentrations up to 5000 µg/plate. This concentration was not cytotoxic. The study was performed in compliance with GLP.