Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The restrictions were that the range of strains does not comply with current guidelines. Read-across to the registered substance is considered scientifically justified

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
range of strains does not comply with current guidelines
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 / cell type:
S. typhimurium, other: TA 98; TA 100;TA 1535; TA 1537; TA 1538
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
Toxicity test: 33, 100, 333, 1000, 3333, 10000 µg/plate; Main experiment: 1.5, 5, 15, 50, 150, 500 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO was used in preliminary toxicity test, and high levels of toxicity demonstrated. At the concentrations used for the mutation assay, acetone was used as solvent as the levels of test substance could not be detected accurately in analysis when DMSO was the solvent.

- Justification for choice of solvent/vehicle: none given in report
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:
TA 1535 and TA 100 without metabolic activation: 2-aminoanthracene
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
TA 1537 without metabolic activation
Untreated negative controls:
other:
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
TA 1538 and TA 98 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:
all strains with metabolic activation
Details on test system and experimental conditions:
ACTIVATION; Aroclor induced rat liver S9; NADP and glucose-6-phosphate as co-factors; 0.5 ml 10% S9 in 2.7 ml agar and test material and test strains.
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION

- Preincubation period: none

- Exposure duration: 2 days

- Expression time (cells in growth medium): 2 days


SELECTION AGENT (mutation assays): histidine-poor agar

NUMBER OF REPLICATIONS: triplicate plates, two independent experiments

DETERMINATION OF CYTOTOXICITY
- Method: other: condition of bacterial lawn
Evaluation criteria:
A positive response was recorded if there was a reproducible, dose dependent increase in the number of revertants to at least twice control values for TA 1535, TA 98, TA 1537 and TA 1538, and 1.5 times for strain TA 100.
Statistics:
Mean and standard deviation.

Results and discussion

Test results
Key result
Species / strain:
S. typhimurium, other: TA 98; TA 100;TA 1535; TA 1537; TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
500 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid

Any other information on results incl. tables

Table 1 Experiment 1: Reversions per plate (mean of 3 plates)

Concentration µg/plate

TA 1535

TA 1537

TA 1538

TA 98

TA 100

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

0*

18

23

10

14

23

19

26

39

124

132

Positive control

245

250

1334

150

286

569

186

522

747

598

1.5

18

15

14

16

18

14

24

31

121

145

5

17

17

18

17

19

21

32

35

147

136

15

15

21

16

14

18

20

25

36

130

115

50

14

15

8

16

18

13

22

33

121

110

150

14

19

8

16

13

20

23

27

119

118

500

10

13

2

6

3

7

7

20

58

89

* solvent control acetone

Table 2 Experiment 2: Reversions per plate (mean of 3 plates)

Concentration µg/plate

TA 1535

TA 1537

TA 1538

TA 98

TA 100

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

0*

14

16

11

11

20

26

30

31

129

123

Positive control

262

178

1331

166

235

252

224

247

557

523

1.5

13

15

8

10

19

24

28

28

125

112

5

20

12

14

14

19

21

28

34

136

121

15

19

17

14

14

20

25

26

35

137

111

50

21

17

14

7

18

17

21

25

129

105

150

18

16

11

8

13

18

24

27

112

109

500

-

12

-

5

-

6

-

23

-

59

* solvent control acetone

Applicant's summary and conclusion

Conclusions:
Fatty alcohol blend was tested in a bacterial reverse mutation assay according to a protocol that is similar to OECD 471 and under GLP in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538. No increase in the number of revertants per plate was observed with or without activation in either the initial assay or the independent repeat assay. Solvent and positive controls gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.
Executive summary:

Fatty alcohol blend was tested in a bacterial reverse mutation assay according to a protocol that is similar to OECD 471 and under GLP in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538. No increase in the number of revertants per plate was observed with or without activation in either the initial assay or the independent repeat assay. Solvent and positive controls gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

The in vitro and in vivo data available for members of the category and supporting substances indicate that the C6-24 alcohols are not genotoxic. In addition, the category of LCAAs under consideration does not contain any structural elements that are of concern for potential mutagenic activity.