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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames tests:

The structural analogue substance 9-octadecenoic acid was not mutagenic in a bacterial reverse mutation assay.

The structural analogue substance Octadecanoic acid was not mutagenic in a bacterial reverse mutation assay.

The structural analogue substance (cations) Ammonia was not mutagenic in a bacterial reverse mutation assay.

Based on the structural similarity of the target substance to the analogue substances, the read across study for genetic toxicity in vitro on chemically similar substance (Ames test: bacterial reverse mutation assay) and the weight of evidence approach, the target substance "Fatty acids, C14-18 and C16-18-unsatd., ammonium salts" is not considered to be classified for mutagenicity (Based on available data, the classification criteria are not met.).

Link to relevant study records

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Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Read-across justification / weight of evidence justification:
The target substance Fatty acids, C14-18 and C16-18-unsatd., ammonium salts consists of ammonium salts of the fatty acids Myristic Acid (C14 ), Palmitic acid (C16), Stearic acid (C18), Palmitoleic acid (C16:1), Oleic acid (C18:1), Linoleic acid (C18:2) and Linolenic acid (C18:3).
Information on genetic toxicity in vitro (Ames test: bacterial reverse mutation assay) of Oleic Acid (as representative of the unsaturated fatty acids and main constituent of fatty acids), Stearic acid (as representative of the saturated fatty acids) and Ammonia (as representative of the ammonium cation) is available. As results, this structural analogue substances were not mutagenic in a bacterial reverse mutation assay.
Therefore and based on the structural similarity of the target substance to the analogue substances, the results of the genetic toxicity in vitro of the source substances can be assigned to the target substance.
Based on these available data on genetic toxicity in vitro, the target substance "Fatty acids, C14-18 and C16-18-unsatd., ammonium salts" is not considered to be classified for mutagenicity.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Species / strain:
other: S. typhimurium TA98, TA100, TA1535, TA1537, TA1538, E. coli WP2 uvrA
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
growth inhibiton was observed in strains T 1537 and TA 1538 treated with 10, 50 and 100 µg of the analogue substance/plate without S9 mix.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
other: S. typhimurium TA98, TA100, TA1535, TA1537, TA1538, E. coli WP2 uvrA
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. Migrated from field 'Test system'.
Remarks:
Result of octadec-9-enoic acid.
Conclusions:
Based on read across study for genetic toxicity in vitro on chemically similar substance (Ames test: bacterial reverse mutation assay) and GHS criteria, the target substance "Fatty acids, C14-18 and C16-18-unsatd., ammonium salts" is not considered to be classified for mutagenicity (Based on available data, the classification criteria are not met.).
Based on read across study for genetic toxicity in vitro on chemically similar substance (Ames test: bacterial reverse mutation assay) and upon the DSD classification criteria (67/548/EEC), the target substance is not considered to be classified for mutagenicity (Based on available data, the classification criteria are not met.).
Executive summary:

Ames tests:

The structural analogue substance 9-octadecenoic acid was not mutagenic in a bacterial reverse mutation assay.

The structural analogue substance Octadecanoic acid was not mutagenic in a bacterial reverse mutation assay.

The structural analogue substance (cations) Ammonia was not mutagenic in a bacterial reverse mutation assay.

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Read-across (analogue): For justification of read-across see section 13.2.
Reason / purpose for cross-reference:
read-across source
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:
cytotoxicity
Remarks:
slight toxicity observed at the highest dose group
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'. Result of octadec-9-enoic acid.
Conclusions:
Based on read across study for genetic toxicity in vitro on chemically similar substance and GHS criteria, the target substance "Fatty acids, C14-18 and C16-18-unsatd., ammonium salts" is not considered to be classified for mutagenicity (Based on available data, the classification criteria are not met.).
Executive summary:

Ames test: The structural analogue substance 9 -octadecenoic acid was not mutagenic in a bacterial reverse mutation assay.

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study summary, acceptable for assessment with restrictions, no study available for review, only four strains tested.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
induced male Sprague Dawley rat liver S9 and induced male Syrian hamster liver S9
Test concentrations with justification for top dose:
0.1, 0.3, 1, 3.3, 10, 33, 100, 333 µg/plate
Vehicle / solvent:
- Vehicle/solvent used: DMSO
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation
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:
cytotoxicity
Remarks:
slight toxicity observed at the highest dose group
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Table 1: Results of the genetic toxicity study with oleic acid on Salmonella typhimurium strain TA100

Dose

[µg/plate]

No

activation

No

activation

10 % RLI

10 % RLI

10 % HLI

10 % HLI

0.1

147

105

 

 

 

 

0.3

126

98

 

 

 

 

1

132

98

 

 

 

 

3.3

142*

87*

128

106

143

102

10

115*

73*

136

116

136

108

33

 

 

133

115

133

100

100

 

 

141

102

133

92

333

 

 

117*

86*

127*

86*

Vehicle control

143

98

135

117

142

109

Positive control

1138

1060

895

774

1340

1082

*Slight toxicity observed

 

Table 2: Results of the genetic toxicity study with oleic acid on Salmonella typhimurium strain TA1535

Dose

[µg/plate]

No

activation

No

activation

10 % RLI

10 % RLI

10 % HLI

10 % HLI

0.1

20

17

 

 

 

 

0.3

25

15

 

 

 

 

1

23

14

 

 

 

 

3.3

22*

11*

13

16

10

11

10

18*

12*

14

8

11

11

33

 

 

11

11

13

13

100

 

 

11

11

10

10

333

 

 

9*

8*

7*

8*

Vehicle control

24

20

13

8

12

10

Positive control

894

760

64

72

84

76

*Slight toxicity observed

 

Table 3: Results of the genetic toxicity study with oleic acid on Salmonella typhimurium strain TA1537

Dose

[µg/plate]

No activation

No

activation

10 % RLI

10 % RLI

10 % HLI

10 % HLI

0.1

7

7

 

 

 

 

0.3

5

4

 

 

 

 

1

6

4

 

 

 

 

3.3

5

4

5

3

6

5

10

4*

5*

6

5

6

5

33

 

 

6

6

7

7

100

 

 

7

5

5

6

333

 

 

7*

4*

6*

6*

Vehicle control

4

6

7

4

5

10

Positive control

326

223

59

49

92

81

*slight toxicity observed

 

Table 4: Results of the genetic toxicity study with oleic acid on Salmonella typhimurium strain TA98

Dose

[µg/plate]

No

activation

No

activation

10 % RLI

10 % RLI

10 % HLI

10 % HLI

0.1

16

14

 

 

 

 

0.3

14

15

 

 

 

 

1

13

14

 

 

 

 

3.3

15

14

24

19

23

18

10

16

13

32

23

26

24

33

 

 

25

29

23

26

100

 

 

31

20

26

30

333

 

 

23*

24

29

25

Vehicle control

18

15

26

16

20

24

Positive control

1319

1263

386

792

819

1169

*slight toxicity observed

 

Conclusions:
Ames test: The substance 9-octadecenoic acid was not mutagenic in a bacterial reverse mutation assay.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

No adequate animal data are available and no epidemiological studies investigating the genotoxicity (in vitro) of the test (target) substance were identified. However, data from a structural analogue (read across substance) are available.  

The read across substance 9-octadecenoic acid (Oleic acid, CAS 112-80-1) was tested in a bacterial reverse mutation assay using 4 Salmonella typhimurium strains: strain TA98, TA100, TA1535 and TA1537. The substance was tested in the following concentrations: 0.1, 0.3, 1, 3.3, 10, 33, 100, 333 µg/plate. Besides that, the vehicle (DMSO) and a positive control were included in the test for each strain. The read across substance was tested without and with metabolic activation (induced male Sprague Dawley rat liver S9 and induced male Syrian hamster liver S9). The test results gave no indication for a mutagenic property of the tested substance in the bacterial reverse mutation assay.

Information on genetic toxicity in vitro (Ames test: bacterial reverse mutation assay) of Oleic Acid, Stearic acid and Ammonia is also available (publication) in which a bacterial reverse mutation assay using 6 bacterial strains (Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538 and Escherichia coli WP2 uvrA) and Oleic Acid, Stearic acid and Ammonia with and without rat liver S9 mix (induced with polychlorated biphenyls) is described. DMSO, Acetone and Air served as a vehicle. As positive controls, benzo(a)pyrene, 2-nitrofluorene, 9-aminoacridine, N-ethyl-N-nitro-N-nitrosoguanidine, 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide, 4-nitroquinoline-1-oxide and 2-aminoanthracene were used. The revertant colonies were counted using an automated colony counter. As results, this structural analogue substances were not mutagenic in a bacterial reverse mutation assay, neither with nor without metabolic activation.

The target substance Fatty acids, C14-18 and C16-18-unsatd., ammonium salts consists of ammonium salts of the fatty acids Myristic Acid (C14 ), Palmitic acid (C16), Stearic acid (C18), Palmitoleic acid (C16:1), Oleic acid (C18:1), Linoleic acid (C18:2) and Linolenic acid (C18:3). Oleic Acid (as representative of the unsaturated fatty acids and main constituent of fatty acids), Stearic acid (as representative of the saturated fatty acids) and Ammonia (as representative of the ammonium cation) are structurally similar to the target substance to the analogue substances. Therefore the results of the genetic toxicity in vitro of the source substances can be assigned to the target substance ( weight of evidence approach).

Justification for classification or non-classification

DSD (67/548/EEC):

The available study is considered reliable and suitable for classification purposes under 67/548/EEC. As a result the (target) substance is not considered to be classified for genetic toxicity under Directive 67/548/EEC.

CLP/GHS (Regulation (EC) No 1272/2008):

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for genetic toxicity under Regulation (EC) No 1272/2008.