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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Studies on genotoxicity are available for the following fatty acid category members:
in-vitro:
- Gene mutation in bacteria:
CAS# 142-62-1, C6: Ames: negative (Banduhn 1991)
CAS# 124-07-2, C8: Ames RL4: negative (Gloxhuber and Wallat 1981)
CAS# 90990-08-2, C8-18: Ames RL4: negative (Wallat 1982)
CAS# 67701-06-8, C12-18: Ames RL4: negative (Sterzel and Broschard 1999)
CAS# 143-07-7, C12: Ames RL4: negative (Gloxhuber and Wallat 1981)
CAS# 112-85-6, C22: Ames RL4: negative (Gloxhuber and Wallat 1981)
CAS# 112-85-6, C22: Ames: negative (Nakajima 2002)
- Gene mutation in mammalian cells:
CAS# 334-48-5, C10: Mouse Lymphoma Assay in-vitro: negative (Trenz 2010)
- Cytogenicity in mammalian cells:
CAS# 112-85-6, C22: Chromosomal Aberration test in-vitro: negative (Nakajima 2002)
in-vivo:
No data available.
All available data on genotoxicity showed that fatty acids are not genotoxic.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance CAS 112-85-6. In accordance to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Deviations:
no
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test
Target gene:
not applicable
Species / strain / cell type:
mammalian cell line, other: Chinese hamster lung (CHL) cells
Details on mammalian cell type (if applicable):
- Type and identity of media: Eagle-MEM liquid medium
- Properly maintained: yes
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 from rat liver, induced with phenobarbital and 5,6-benzoflavone
Test concentrations with justification for top dose:
-S9 mix (short-term exposure): 0, 875, 1750, 3500 µg/mL
+S9 mix (short-term exposure): 0, 875, 1750, 3500 µg/mL
-S9 mix (24-hour continuous exposure): 0, 350, 700, 1400, 2800 µg/mL
-S9 mix (48-hour continuous exposure): 0, 288, 575, 1150, 2300 µg/mL
Vehicle / solvent:
1.0 % Carboxymethylcellulose sodium
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: continuous exposure: Mitomycin C (0.05 µg/mL for 24 hours and 0.025 µg/mL for 48 hours); short-term exposure, Cyclophosphamide (12.5 µg/mL)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: 3 days
- Exposure duration: 6 (short-term exposure), 24, 48 hours

STAIN (for cytogenetic assays): Giemsa

NUMBER OF CELLS EVALUATED: 200

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

Evaluation criteria:
The frequency of polyploid cells or cells with abnormal structure of each test group were determined according to the criteria of Ishidate.
Species / strain:
mammalian cell line, other: Chinese hamster lung (CHL) cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: insoluble in water, soluble in alcohol, ether, chloroform and acetone
- Precipitation: observed on the slide of continuous exposure high dose group

RANGE-FINDING/SCREENING STUDIES: see 'Any other information on material and method incl. tables'

COMPARISON WITH HISTORICAL CONTROL DATA: this test was valid, since the frequency of chromosomal aberration in positive control was within background data.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Table 1: Results of growth inhibition test

Test item

Concentration

in µg/mL

Survival in %

Exposure period 24 h, without S9 mix

1% CMC▪Na

 

100

Test substance

272

97.7

454

95.2

756

96.5

1260

83.1

2100

62.1

3500

37.8

Exposure period 48 h, without S9 mix

1% CMC▪Na

 

100

Test substance

272

101.1

454

104.6

756

98.9

1260

89.7

2100

75.9

3500

1.3

Exposure period 6 h, without S9 mix

1% CMC▪Na

 

100

Test substance

272

109.6

454

93.7

756

102.5

1260

110.7

2100

89.8

3500

95.1

Exposure period 6 h, with S9 mix

1% CMC▪Na

 

100

Test substance

272

84.3

454

85.9

756

85.3

1260

86.5

2100

68.3

3500

76.3

Table 2: Results of chromosome aberration test

Test item

Concentration

Aberrant cells in %

Polyploid cells in %

 

in µg/mL

with gaps

without gaps

Exposure period 24 h, without S9 mix

1% CMC▪Na

 

0.5

0.5

0.0

MMC

0.05

56.0

52.5

0.5

Test substance

350

1.0

1.0

0.5

700

1.0

0.5

0.5

1400

0.5

0.0

0.0

2800

Toxic

Exposure period 48 h, without S9 mix

1% CMC▪Na

 

0.0

0.0

0.5

MMC

0.025

58.5

54.5

0.0

Test substance

288

1.0

1.0

0.0

575

0.5

0.0

0.5

1150

2.0

1.5

0.0

2300

Toxic

Exposure period 6 h, without S9 mix

1% CMC▪Na

 

1.5

0.5

0.5

CP

12.5

0.5

0.0

0.5

Test substance

875

0.5

0.5

0.0

1750

3.0

2.5

0.0

3500

1.0

0.5

0.5

Exposure period 6 h, with S9 mix

1% CMC▪Na

 

1.5

1.0

0.0

CP

12.5

63.5

61.5

0.0

Test substance

875

2.5

1.5

1.0

1750

2.0

2.0

0.0

3500

2.0

2.0

0.0

CMC▪Na: carboxymethylcellulose sodium (solvent)

MMC: Mitomycin C; CP: Cyclophosphamide (positive controls)

 

Conclusions:
Interpretation of results: negative

The test substance did not induce structural chromosomal aberrations in the absence or presence of an exogenous metabolic activation system.
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
09 Apr - 18 Apr 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance CAS 142-62-1. In accordance to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
TA 98: his D3052
TA 100: his G46
TA 1535: his G46
TA 1537: his C3076
TA 1538 his D3052
TA 1535, 1537 and TA 1538 contain rfa- and uvrB-; TA 98 and TA 100 contain rfa-, uvrB- and R+
Species / strain / cell type:
S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537 and TA 1538
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9 mix (Aroclor 1254-induced rat liver S9 fractions)
Test concentrations with justification for top dose:
First test: 8, 40, 200, 1000 and 5000 µg/ plate
Second test: 3.1, 12.5, 50, 200 and 800 µg/ plate
Vehicle / solvent:
- Vehicle/solvent used: bidist. water
Untreated negative controls:
yes
Remarks:
suspension medium Tween 80/ bidist. water and untreated fresh cell suspension
Negative solvent / vehicle controls:
yes
Remarks:
Buffer and Tween 80 / H2O
True negative controls:
yes
Positive controls:
yes
Positive control substance:
other: see remarks
Remarks:
sodium azide: strains TA 100 and TA 1535; 9-aminoacridine: TA 1537; 4-nitro-o-phenylendiamine: TA 98 and TA1538 without S9 mix and 2-aminoanthracene in all strains with S9 mix
Evaluation criteria:
A combination of the following criteria was considered as a positive result:
- The plate background of non-reverted bacteria did not show any growth reduction versus the respective negative controls
- The spontaneous mutation rates of each tester strain per plate were within the characteristic spontaneous mutation range
- As a rule, the positive controls showed mutation rates exceeding the control values of TA 100 at least by the factor 2.0 and those of the other tester strains at least by the factor 3.0
- At more than one dose tested, the test substance caused at least a 2.0-fold increase in comparison with the negative controls in the tester strain TA 100. For the other tester strains, an increase in the mutation rate of more than 3.0 above the corresponding negative controls was considered positive.
Species / strain:
S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537 and TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at the concentration of 800 µg / plate and higher
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Edenor C 6 98/100 did not induce any reverse mutations in the absence of rat liver enzymes (without S9-mix), nor did occur any induced reverse mutations in the presence of Aroclor 1254-induced S9-mix. Toxic effects were noted at the concentration of 800 µg / plate and higher.

In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test article did not induce point mutations by base-pair changes or frameshifts in the genome of the strains used.

Therefore, Edenor C 6 98/100 is not considered to be mutagenic in this Salmonella typhimurium reverse mutation assay.

Table 1. Test results of experiment 1 (plate incorporation)

 

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

TA 100

TA1535

TA1538

TA98

TA1537

Solvent: Tween 80/H2O

71 ± 6

12 ± 3

10 ± 3

25 ± 4

6 ± 1

8

78 ± 12

11 ± 4

9 ± 4

30 ± 2

9 ± 2

40

74 ± 6

8 ± 4

9 ± 4

26 ± 10

5 ± 1

200

69 ± 2

8 ± 2

12 ± 5

30 ± 3

8 ± 4

1000

37 ± 8 r

10 ± 3

2 ± 1 r

11 ± 4 r

2 ± 1 r

5000

I

I; PP

I

I

I

Positive controls, –S9

Name

SA

SA

4NPD

4NPD

9AA

Concentrations

(μg/plate)

2

2

40

40

80

Mean No. of colonies/plate

(average of 3 ± SD)

290 ± 40

477 ± 43

1517 ± 7

681 ± 38

610 ± 11

+

Solvent: Tween 80/H2O

76 ± 5

12 ± 5

22 ± 3

48 ± 3

8 ± 2

+

8

91 ± 15

11 ± 5

16 ± 4

41 ± 4

8 ± 3

+

40

85 ± 7

10 ± 2

17 ± 1

34 ± 6

6 ± 1

+

200

72 ± 5

11 ± 5

17 ± 2

35 ± 4

7 ± 1

+

1000

56 ± 5 r

9 ± 5

18 ± 3

12 ± 6 r

4 ± 1 r

+

5000

6 ± 5

I; PP

I; PP

I; PP

I; PP

Positive controls, +S9

Name

2AA

2AA

2AA

2AA

2AA

Concentrations

(μg/plate)

5

2.5

5

5

2.5

Mean No. of colonies/plate

(average of 3 ± SD)

783 ± 41

164 ± 34

968 ± 97

881 ± 55

77 ± 21

I: Complete inhibition of the bacterial background lawn

r: Partial inhibition of the bacterial background lawn

PP: Pin-point colonies

9AA = 9-aminoacridine

SA: Sodium azide

4NPD: 4-Nitro-o-phenylenediamine

2AA = 2-Aminoanthracene

 

Table 2. Test results of experiment 2 (plate incorporation)

 

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

TA 100

TA1535

TA1538

TA98

TA1537

Solvent: Tween 80/H2O

72 ± 7

10 ± 4

8 ± 2

31 ± 5

8 ± 2

3.1

65 ± 1

8 ± 1

7 ± 2

30 ± 4

8 ± 5

12.5

72 ± 4

15 ± 6

8 ± 1

32 ± 7

7 ± 3

50

67 ± 11

8 ± 3

7 ± 6

33 ± 1

7 ± 1

200

73 ± 9

10 ± 2

8 ± 5

29 ± 6

5 ± 3

800

45 ± 12 r

8 ± 5 r

5 ± 2 r

23 ± 4 r

4 ± 2 r

Positive controls, –S9

Name

SA

SA

4NPD

4NPD

9AA

Concentrations

(μg/plate)

2

2

40

40

80

Mean No. of colonies/plate

(average of 3 ± SD)

314 ± 22

499 ± 21

1659 ± 63

629 ± 10

739 ± 33

+

Solvent: Tween 80/H2O

79 ± 3

13 ± 2

16 ± 5

41 ± 7

12 ± 1

+

3.1

78 ± 7

10 ± 1

18 ± 3

38 ± 9

10 ± 1

+

12.5

70 ± 7

7 ± 1

15 ± 5

36 ± 8

10 ± 1

+

50

82 ± 15

12 ± 4

19 ± 2

33 ± 1

8 ± 4

+

200

78 ± 7

12 ± 3

20 ± 2

38 ± 8

10 ± 3

+

800

60 ± 13

11 ± 3 r

11 ± 1 r

26 ± 5

5 ± 2 r

Positive controls, +S9

Name

2AA

2AA

2AA

2AA

2AA

Concentrations

(μg/plate)

5

2.5

5

5

2.5

Mean No. of colonies/plate

(average of 3 ± SD)

862 ± 112

215 ± 2

1300 ± 212

1000 ± 46

88 ± 14

I: Complete inhibition of the bacterial background lawn

r: Partial inhibition of the bacterial background lawn

PP: Pin-point colonies

9AA = 9-aminoacridine

SA = Sodium azide

4NPD = 4-Nitro-o-phenylenediamine

2AA = 2-Aminoanthracene

 

Conclusions:
Interpretation of results: negative
Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
28 Jun - 23 Aug 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance CAS 334-48-5. In accordance to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
in vitro mammalian cell gene mutation tests using the thymidine kinase gene
Target gene:
Thymidine Kinase (TK)
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
- Type and identity of media: RPMI 1640 complete medium
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Phenobarbital (80 mg/kg bw) and beta-naphtoflavone (100 mg/kg bw)-induced rat liver S9 mix
Test concentrations with justification for top dose:
Pre-Test:
Experiment 1:
- with and without metabolic activation: 0.5, 2, 4, 6, 8, 10 mM
Experiment 2:
- without metabolic activation. 0.005, 0.05, 0.2, 0.7, 1.3, 2.0 mM

Main Test:
Experiment 1:
- with metabolic activation: 0.70, 0.82, 0.94, 1.06, 1.18, 1.30, 1.42, 1.54 mM
- without metabolic activation. 0.22, 0.46, 0.58, 0.70, 0.82, 0.94, 1.06, 1.18 mM
Experiment 2:
- with metabolic activation: 1.0, 1.12, 1.24, 1.36, 1.48, 1.60, 1.72, 1.84 mM
- without metabolic activation. 0.0005, 0.001, 0.002, 0.005, 0.01, 0.06, 0.18, 0.3 mM
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: RPMI cell culture medium
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
since medium was used as solvent, no further solvent control was necessary
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
without metabolic activation Migrated to IUCLID6: 200 and 500 µg/mL dissolved in medium
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
since medium was used as solvent, no further solvent control was necessary
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
without metabolic activation Migrated to IUCLID6: 10 µg/mL, dissolved in 0.9% NaCl
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
since medium was used as solvent, no further solvent control was necessary
True negative controls:
no
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
with metabolic activation Migrated to IUCLID6: 3.5 µg/mL, dissolved in DMSO (1% final concentration in medium)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 4 h (short-term exposure, Experiment 1 with and without metabolic activation, Experiment 2 with metabolic activation) or 24 h (long-term exposure, Experiment 2 without metabolic activation)
- Expression time (cells in growth medium): 72 h (short-term exposure) or 48 h (long-term exposure)
- Selection time (if incubation with a selection agent): 11 - 14 days

SELECTION AGENT (mutation assays): 5 µg/mL trifluorothymidine (TFT )

NUMBER OF REPLICATIONS:

NUMBER OF CELLS EVALUATED: ca. 2000/plate

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth; cloning efficiency; mitotic index
Evaluation criteria:
There are several criteria for a positive result:
- clear and dose-related increase in the mutant frequency
- biologically relevant response (at least a 2-fold increase of mutant frequencies related to the respective negative control values and higher than the historical range of negative controls) for at least one of the dose groups
- combined with a positive effect in the mutant frequency, an increased occurrence of small colonies (slow growth colonies) indicated by a low large/Small colonies ratio (1.5 times the ratio of clastogenic control MMS and/or B[a]P) is an indication for potential clastogenic effects and/or chromosomal aberrations.

The test substance is considered to be negative if there is no biologically relevant increase in the induction of mutant cells above concurrent control levels, at any dose level.
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 1.54 mM with metabolic activation and at 1.18 mM without metabolic activation in experiment 1, respectively; at 1.84 mM with metabolic activation and at 0.30 mM without metabolic activation in experiment 2, respectively.
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH:within the physiological range
- Effects of osmolality: within the physiological range
- Precipitation: in the pre-test with metabolic activation from concentrations of 4 mM and higher

RANGE-FINDING/SCREENING STUDIES:
All mutant values were found to be within the range of the historical control data of the test facility BSL Bioservice (about 51 to 170 mutants per 10^6 cells)

COMPARISON WITH HISTORICAL CONTROL DATA:
All mutant values were found to be within the range of the historical control data of the test facility BSL Bioservice (about 51 to 170 mutants per 10^6 cells)
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Colony sizing was performed for the highest concentrations of the test item and for the negative and positive controls. A mutation frequency above 2 in combination with an increased occurrence of small colonies (defined by slow growth and/or morphological alteration of the cell clone), indicated by a low large/small colony ratio (ratio of the clastogenic controls MMS and/or B[a]P with a coefficient of 1.5), is an indication for potential clastogenic effects and/or chromosomal aberrations.

 Although in experiment 1 with metabolic activation an increased number of small colonies was noted at doses of 1.30 mM and 1.42 mM (26 and 31small colonies, respectively, compared to 11 and 9 at control) all dose groups were considered as not clastogenic since no mutagenicity was found at these doses.

All other dose groups in the other experiments were also found not to be clastogenic, respectively.

Table 1: Experiment I - 4 h exposure - With Metabolic Activation

 

Concentration
[mM]

Cloning efficiency [%]

Relative Total Growth [%]

Mutants per 1E+06 surviving cells

Mutation factor

Colony Sizing

Quotient Large/Small

0

100

100

86.77

1

3.66

0.7

96.63

95.51

95.86

1.10

--

0.82

104.12

92.71

88.56

1.02

--

0.94

109.36

95.60

76.43

0.88

--

1.06

110.11

78.73

78.58

0.91

--

1.18

109.36

60.06

86.55

1.00

--

1.30

116.10

40.14

100.88

1.16

1.77

1.42

112.36

31.61

121.24

1.40

1.55

1.54

96.63

9.84

139.92

1.61

2.78

B[a]P, 3.5 µg/mL

99.63

69.03

623.89

7.19

1.24

B[a]P  Benzo[a]pyrene

Table 2: Experiment I - 4 h exposure - Without Metabolic Activation

 

Concentration
[mM]

Cloning efficiency [%]

Relative Total Growth [%]

Mutants per 1E+06 surviving cells

Mutation factor

Colony Sizing

Quotient Large/Small

0

100

100

79.39

1

2.75

0.22

100.33

90.09

78.53

0.99

--

0.46

86.38

79.76

124.63

1.57

--

0.58

91.03

79.70

77.88

0.98

--

0.70

98.34

89.53

70.89

0.89

--

0.82

98.34

71.30

69.28

0.87

--

0.94

95.02

64.50

62.74

0.79

1.60

1.06

99.00

47.66

74.59

0.94

3.17

1.18

91.69

11.04

97.49

1.23

1.12

EMS, 500 µg/mL

86.38

62.27

1337.77

16.85

--

MMS, 10 µg/mL

85.71

66.62

841.03

10.59

0.69

EMS   Ethyl methane sulphonate

MMS  Methyl methane sulphonate

Table 3: Experiment II - 4 h Exposure - With Metabolic Activation

 

Concentration
[mM]

Cloning efficiency [%]

Relative Total Growth [%]

Mutants per 1E+06 surviving cells

Mutation factor

Colony Sizing

Quotient Large/Small

0

100

100

82.64

1.00

2.07

1

96.97

85.91

82.23

1.00

--

1.12

101.68

89.08

61.54

0.74

--

1.24

98.99

86.20

86.92

1.05

--

1.36

99.66

83.65

75.75

0.92

--

1.48

90.91

64.04

118.05

1.43

--

1.60

96.07

35.51

70.23

0.85

2.38

1.72

91.58

38.25

84.77

1.03

2.13

1.84

98.99

19.98

98.81

1.20

4.73

B[a]P, 3.5 µg/mL

86.20

60.39

829.02

10.03

0.89

B[a]P  Benzo[a]pyrene

Table 4: Experiment II - 24 h exposure - Without Metabolic Activation

 

Concentration
[mM]

Cloning efficiency [%]

Relative Total Growth [%]

Mutants per 1E+06 surviving cells

Mutation factor

Colony Sizing

Quotient Large/Small

0

100

100

104.66

1

2.61

0.0005

95.24

94.64

76.34

0.73

--

0.001

101.36

103.58

68.22

0.65

--

0.002

94.56

95.29

66.56

0.64

--

0.005

101.36

105.73

52.63

0.50

--

0.01

102.04

98.98

64.06

0.61

--

0.06

102.72

96.75

61.54

0.59

3.30

0.18

96.60

55.56

91.91

0.88

2.24

0.30

91.16

19.77

99.26

0.95

1.94

EMS, 200 µg/mL

70.75

34.84

2516.55

24.05

--

MMS, 10 µg/mL

59.18

27.33

2625.00

25.08

0.81

EMS   Ethyl methane sulphonate

MMS  Methyl methane sulphonate

Conclusions:
Interpretation of results: negative
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only short abstract available
Principles of method if other than guideline:
Ames test according to Mutation Research 31, 347 - 364 (1975)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1538
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced rat liver S9 mix
Test concentrations with justification for top dose:
4, 20, 100, 500 and 2500 µg / plate
Vehicle / solvent:
- Vehicle/solvent used: DMSO
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 4-Nitro-o-phenylene diamine
Remarks:
without metabolic activation
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
without metabolic activation
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 2-Amino-anthracene
Remarks:
with metabolic activation
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:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Edenor C 12 98/100% did not induce reverse mutations in the absence or presence of S9 mix in the tester strains Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 and TA 1538.

Conclusions:
Interpretation of results: negative
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only short abstract available
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
limited data; only tested up to 2500 µg/plate
Principles of method if other than guideline:
Ames test according to Mutation Research 31, 347 - 364 (1975)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
his
Species / strain / cell type:
S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537 and TA 1538
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced rat liver S-9mix
Test concentrations with justification for top dose:
4, 20, 100, 500 and 2500 µg / plate
Vehicle / solvent:
- Vehicle/solvent used: Tween 80 / H2O bidist.
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 4-Nitro-o-phenylenediamine
Remarks:
without metabolic activation
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
without metabolic activation
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 2-Amino-anthracene
Remarks:
with metabolic activation
Species / strain:
S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537 and TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Edenor C 8 98/100% did not induce reverse mutations in the absence or presence of S-9 mix in the tester strains Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 and TA 1538.

Conclusions:
Interpretation of results: negative
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only short abstract available
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
limited data; only tested up to 1250 µg/plate
Principles of method if other than guideline:
Ames test according to Mutation Research 31, 347 - 364 (1975)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537 and TA 1538
Details on mammalian cell type (if applicable):
no data
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
4, 20, 100, 500, 1250 µg /plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Tween 80 / H20
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: without S9 mix: 4-Nitro-o-phenylene diamine and Sodium azide; with S9 mix: 2-Amino-anthracene
Species / strain:
S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537 and TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Edenor C 22 R did not induce reverse mutations in the absence or presence of S9 mix in the tester strains Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 and TA 1538.

Edenor C 22 R did not show mutagenic activity in vitro.

Conclusions:
Interpretation of results: negative
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance CAS 112-85-6. In accordance to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to guideline
Guideline:
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
his, trp operon
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
E. coli WP2 uvr A
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 mix from livers of male Sprague-Dawley rats; induced with phenobarbital and 5,6.benzoflavone
Test concentrations with justification for top dose:
156, 313, 625, 1250, 2500, 5000 µg/plate
Vehicle / solvent:
DMSO
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: -S9: 2-(2 Furyl)-3-(5-nitro-2-furyl)acrylamide (0.01 µg/plate); Sodium azide (0.5 µg/plate); Aminoacridine hydrochloride (80 µg/plate); +S9: 2-Aminoanthracene (1.0 µg/plate; TA100), (2 µg/plate; TA1535; TA1537), (10 µg/plate; WP2 uvrA), (0.5 µg/plate; TA9
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 minutes
- Exposure duration: 48 hours

NUMBER OF REPLICATIONS: 2 times (3 plates/concentration/test)

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth


Evaluation criteria:
An increase twice the number of revertant colonies in test concentration plates compared to the solvent control plates and an observable dose-dependency is considered as a positive result.
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, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
The test substance did not induce gene mutations in the S. typhimurium and E. coli strains. No toxicity was observed up to a concentration of 5000 µg/plate, with or without metabolic activation.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Table 1: Test Results of Experiment 1

 

EXPERIMENT 1 (Preincubation Test)

 

S9-Mix

Without

Test item (µg/plate)

TA 100

TA 1535

E. coli WP2 uvrA

TA 98

TA 1537

DMSO

95 ± 2

15 ± 1

25 ± 2

23 ± 3

9 ± 2

156*

94 ± 3

11 ± 1

27 ± 3

21 ± 2

8 ±3

313*

94 ± 4

12 ± 2

24 ± 1

21 ± 4

10 ± 2

625*

89 ± 2

14 ± 3

26 ± 1

18 ± 2

8 ± 1

1250*

82 ± 4

13 ± 1

25 ± 3

21 ± 3

8 ± 3

2500*

80 ± 2

11 ± 1

26 ± 1

17 ± 3

10 ± 4

5000*

78 ± 2

9 ± 2

28 ± 1

14 ± 4

10 ± 3

AF-2

687 ± 12

-

173 ± 10

460 ± 27

-

NaN3

-

422 ± 7

-

-

-

ACR

-

-

-

-

491 ± 28

 

S9-Mix

With

Test item (µg/plate)

TA 100

TA 1535

E. coli WP2 uvrA

TA 98

TA 1537

DMSO

112 ± 4

13 ± 1

31 ± 2

33 ± 2

7 ± 1

156*

103 ± 4

12 ± 3

27 ± 3

30 ± 3

10 ± 3

313*

106 ± 10

10 ± 4

26 ± 1

34 ± 4

11 ± 3

625*

97 ± 3

12 ± 2

27 ± 1

29 ± 4

10 ± 3

1250*

97 ± 5

12 ± 4

28 ± 5

30 ± 2

10 ± 1

2500*

98 ± 3

12 ± 3

27 ± 3

30 ± 2

10 ± 3

5000*

99 ± 9

9 ± 2

28 ± 2

29 ± 1

9 ± 1

2-AA

723 ± 12

383 ± 5

516 ± 5

366 ± 19

172 ± 8

* precipitation occurred at the end of the exposure

AF-2: 2-(2 furyl)-3-(5-nitro-2-furyl)acrylamide (0.01 µg/plate for TA 100 and E. coli WP2 uvrA; 0.1 µg/plate for TA 98)

NaN3: sodium azide (0.5 µg/plate)

ACR: 9-aminoacridine hydrochloride (80 µg/plate)

2-AA: 2-aminoanthracene (1 µg/plate for TA 100; 2 µg/plate for TA 1535 and TA 1537; 10 µg/plate for E. coli WP2 uvrA; 0.5 µg/plate for TA 98)

 

 

Table 2: Test Results of Experiment 2

 

EXPERIMENT 2 (Preincubation Test)

 

S9-Mix

Without

Test item (µg/plate)

TA 100

TA 1535

E. coli WP2 uvrA

TA 98

TA 1537

DMSO

95 ± 2

16 ± 2

26 ± 3

23 ± 2

5 ± 1

156*

94 ± 3

14 ± 1

25 ± 1

23 ± 3

6 ± 2

313*

95 ± 3

14 ± 3

26 ± 2

23 ± 4

6 ± 2

625*

90 ± 0

17 ± 1

24 ± 3

22 ± 2

7 ± 0

1250*

89 ± 5

15 ± 1

25 ± 3

21 ± 2

5 ± 2

2500*

85 ± 5

15 ± 2

23 ± 1

20 ± 1

7 ± 1

5000*

88 ± 3

15 ± 3

22 ± 2

20 ± 1

4 ± 1

AF-2

734 ± 14

-

128 ± 6

439 ± 7

-

NaN3

-

433 ± 3

-

-

-

ACR

-

-

-

-

503 ± 5

 

S9-Mix

With

Test item (µg/plate)

TA 100

TA 1535

E. coli WP2 uvrA

TA 98

TA 1537

DMSO

107 ± 3

15 ± 2

29 ± 2

26 ± 2

14 ± 1

156*

100 ± 2

15 ± 1

28 ± 1

29 ± 2

14 ± 2

313*

99 ± 4

13 ± 1

29 ± 3

30 ± 8

14 ± 1

625*

103 ± 3

14 ± 2

27 ± 2

30 ± 4

15 ± 2

1250*

101 ± 4

12 ± 2

28 ± 5

28 ± 2

13 ± 1

2500*

98 ± 2

13 ± 2

26 ± 2

26 ± 1

11 ± 1

5000*

96 ± 5

10 ± 1

26 ± 2

24 ± 1

12 ± 2

2-AA

678 ± 17

393 ± 5

521 ± 22

423 ± 31

173 ± 13

* precipitation occurred at the end of the exposure

AF-2: 2-(2 furyl)-3-(5-nitro-2-furyl)acrylamide (0.01 µg/plate for TA 100 and E. coli WP2 uvrA; 0.1 µg/plate for TA 98)

NaN3: sodium azide (0.5 µg/plate)

ACR: 9-aminoacridine hydrochloride (80 µg/plate)

2-AA: 2-aminoanthracene (1 µg/plate for TA 100; 2 µg/plate for TA 1535 and TA 1537; 10 µg/plate for E. coli WP2 uvrA; 0.5 µg/plate for TA 98)

 


Conclusions:
Interpretation of results: negative
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only short abstract available
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
limited data; only tested up to 2500 µg/plate
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay
Target gene:
his
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1538
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induce rat liver S-9 mix
Test concentrations with justification for top dose:
4, 20, 100, 500, 2500 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water/Tween 80
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:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results: negative
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only short abstract available
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
limited data; only 4 strains tested; only up to 2500µg/plate tested
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay
Target gene:
his
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1538
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Aroclor-induced rat liver S-9 mix
Test concentrations with justification for top dose:
4, 20, 100, 500, 2500 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water and propylene glycol (Tween 80)
- Justification for choice of solvent/vehicle: substance is not soluble in water
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 4-nitro-o-phenyldiamine
Remarks:
without metabolic activation
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
without metabolic activation
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
with metabolic activation
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:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results: negative
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Fatty acids are found in all living organisms fulfilling fundamental physiological functions within the body. Based on this role within the body, no potential of fatty acids for genotoxicity is expected as it could be demonstrated in-vitro with fatty acids C6, C8, C10, C12, and C22, as well as with fatty acids mixtures C8-18 and C12-18.

Two of the available studies on gene mutation in bacteria were conducted according to OECD guideline 471 and under GLP conditions with hexanoic acid and docosanoic acid, respectively (C6: Banduhn, 1991; C22: Nakajiama, 2002). In both studies bacteria strains S. typhimurium TA 98, TA 100, TA 1535, TA 1537 and TA 1538 were tested with the fatty acids at concentrations up to 5000 µg/plate with and without metabolic activation by rat liver S9-mix. C22 fatty acid was additionally tested with bacteria strain E. coli WP2 uvr A to detect DNA-cross linking. The test substances did not induce gene mutations in the S. typhimurium and E. coli strains. No toxicity was observed up to a concentration of 5000 µg/plate, with or without metabolic activation. The other available studies were insufficient for assessment due to limited documentation (C8: Gloxhuber and Wallat 1981; C8-18: Wallat 1982; C12-18: Sterzel and Broschard 1999; C12: Gloxhuber and Wallat 1981; C22: Gloxhuber and Wallat 1981). However, according to the authors, all these studies with fatty acids of different chain lengths gave negative results showing that fatty acids do not induce gene mutation in bacteria.

Regarding gene mutation in mammalian cells an in vitro mouse lymphoma assay was performed with decanoic acid under GLP according to OECD guideline 476 (Trenz, 2010). In two experiments, mouse lymphoma L5178Y cells were treated with decanoic acid at concentrations up to 1.54 mM with metabolic activation (phenobarbital and beta-naphtoflavone-induced rat liver S9-mix) and up to 1.18 mM without metabolic activation, respectively. Although cytotoxicity was observed , all mutant values were found to be within the range of the historical control data of the test facility, so that decanoic acid was not found to be mutagenic. In addition, colony sizing was performed for the highest concentrations used to detect potential clastogenic effects and/or chromosomal aberrations. As result, decanoic acid was not found to be clastogenic at all dose groups tested.

An in vitro mammalian chromosome aberration test was conducted with C22 fatty acid (docosanoic acid) in accordance with GLP and OECD guideline 473 and Japanese Guidelines for Screening Mutagenicity Testing of Chemicals (Nakajima, 2002). Properly maintained Chinese hamster lung (CHL) cells were treated with docosanoic acid dissolved in 1% carboxymethylcellulose sodium at concentrations of 875, 1750 and 3500 µg/mL with and without metabolic activation by S9 from Phenobarbital- and 5,6-benzoflavone-induced rat liver for 6 hours. In addition, the cells were incubated with 350, 700, 1400, 2800 µg/mL without metabolic activation for 24 hours and with 288, 575, 1150 and 2300 µg/mL without metabolic activation for 48 hours. No increase in chromosomal aberrations was found at all concentration tested.

Taking all the results together and based on a weight of evidence approach, the negative results for genetic toxicity, which were obtained with different members of the category do not provide any evidence that fatty acids are genotoxic.


Short description of key information:
Studies on genotoxicity are available for the following fatty acid category members:
in-vitro:
- Gene mutation in bacteria:
CAS# 142-62-1, C6: Ames: negative (Banduhn 1991)
CAS# 124-07-2, C8: Ames RL4: negative (Gloxhuber and Wallat 1981)
CAS# 90990-08-2, C8-18: Ames RL4: negative (Wallat 1982)
CAS# 67701-06-8, C12-18: Ames RL4: negative (Sterzel and Broschard 1999)
CAS# 143-07-7, C12: Ames RL4: negative (Gloxhuber and Wallat 1981)
CAS# 112-85-6, C22: Ames RL4: negative (Gloxhuber and Wallat 1981)
CAS# 112-85-6, C22: Ames: negative (Nakajima 2002)
- Gene mutation in mammalian cells:
CAS# 334-48-5, C10: Mouse Lymphoma Assay in-vitro: negative (Trenz 2010)
- Cytogenicity in mammalian cells:
CAS# 112-85-6, C22: Chromosomal Aberration test in-vitro: negative (Nakajima 2002)
in-vivo:
No data available.
All available data on genotoxicity showed that fatty acids are not genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to CLP (1272/2008/EC) classification criteria for genetic toxicity, fatty acids do not fulfill the criteria for classification and thus a non-classification is warranted for this endpoint.