Fatty acids, C14-18 and C16-18-unsatd., ammonium salts

Endpoint summary

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

Reference

Reference 1

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.

Reference 2

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.

Reference 3

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.