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Additional information

For the target substance Undecylenamidopropyl Betaine, an in vitro gene mutation study in bacteria (Ames Test) is available. Further reliable, relevant and adequate data is available from in vitro gene mutation studies in bacteria conducted with the closely related source substances C8-18 and C18 unsatd. AAPB and Formamidopropylbetaine.

In vitro gene mutation tests in mammalian cells (mouse lymphoma L5178Y cells) were conducted with the source substances C8-18 AAPB and Formamidopropylbetaine. An vitro mammalian chromosome aberration test in Chinese hamster lung fibroblasts (V79) is available with the source substance Formamidopropylbetaine, and an  in vivo cytogenicity study (in vivo Mammalian Erythrocyte Micronucleus Test) was conducted with the source substance C8-18 and C18 unsatd. AAPB.

All tests were consistently negative. There is no evidence for a genotoxic potential of the target and source substances.

A justification for read-across is given below.

 

In vitro data

Ames tests

In a reverse gene mutation assay in bacteria according to OECD guideline 471 (adopted 21 July 1997) and EU method B.13/14 (30 May 2008), strains TA98, TA100, TA1535, and TA1537 of  Salmonella typhimurium  and  Escherichia coli  WP2 uvrA were exposed to Undecylenamidopropyl Betaine         

 (30.5% a.i. in aqueous solution) in deionized water at concentrations of 0 (control), 3, 10, 33, 100, 333, 1000, 2500 and 5000 μg/plate in the first experiment (plate incorporation assay) and 0 (control), 10, 33, 100, 333, 1000, 2500 and 5000 μg/plate in the second experiment (preincubation assay) in the presence and absence of mammalian metabolic activation (rat liver S9 mix). All concentrations were adjusted to purity.

The plates incubated with the test item showed normal background growth up to 5000 μg/plate with and without S9 mix in all strains used.

Toxic effects, evident as a reduction in the number of revertants (below the indication factor of 0.5), were absent in nearly all strains, only in strain TA 100 toxic effects were observed at 5000 μg/plate with and without S9 mix in experiment I and at 2500 and 5000 μg/plate in experiment II with and without S9 mix.

No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with the test item at any concentration level, neither in the presence nor absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.

Appropriate reference mutagens were used as positive controls. They showed a distinct increase in induced revertant colonies.

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

 

Similarly negative results were obtained with the source substances C8-18 and C18 unsatd. AAPB and Formamidopropylbetaine:

 

In a reverse gene mutation assay in bacteria according to EU Method B.14 (Version Commission Directive 92/69/EEC), strains TA1535, TA 1537, TA 1538, TA 98 and TA 100 of S. typhimurium were exposed to C8-18 and C18 unsatd. AAPB. Test was performed with concentrations up to and including cytotoxic concentrations in the absence and the presence of mammalian metabolic activation

No evidence of biologically significant mutagenic activity of the test item was found in the presence and absence of metabolic activation, up to and including its cytotoxic limit. The positive controls induced the appropriate responses in the corresponding strains and activity of metabolizing system was confirmed.

There was no evidence of induced mutant colonies over background.

 

The potential of Formamidopropylbetaine to induce mutations was investigated in a reverse gene mutation assay in bacteria according to OECD Guideline 471. The assay was performed in two independent experiments. Both took place as a plate incorporation test, using the Salmonella typhimurium strains T A 1535, TA 1537, TA 98, TA 100, TA 102. All experiments were in the absence and in the presence of a metabolic activation by an Aroclor 1254 induced rat liver post mitochondrial fraction (S9).

Experiment 1: 62, 185, 556, 1667, 5000 µg/plate

No mutagenic effects, evident as an elevation of the number of revertant colonies or toxic effects, evident as a reduction of the number of colonies occurred with or without metabolic activation with the test substance concentrations. Due to this, the concentrations of the second test were chosen as follows:

Experiment 2: 1000, 2000, 3000, 4000, 5000 µg/plate

No mutagenic or toxic effects occurred. Negative (solvent) and positive control treatments were included for all strains in both experiments. All mean numbers of revertant colonies on negative control plates fell within acceptable ranges and were significantly elevated by positive control treatments.

Based on the results of this study it is concluded that Formamidopropylbetaine is not mutagenic in the Salmonella typhimurium reverse mutation assay.

 

Mammalian cell gene mutation assays

In a mammalian cell gene mutation assay according to OECD Guideline 476 (1997) and EU Method B.17 (2008), the potential of C8 -18 AAPB to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y was tested.

The assay was performed in two independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 h. The second experiment was performed with a treatment period of 24 hours in the absence and 4 hours in the presence of metabolic activation.

The main experiments were evaluated at the following concentrations:

Experiment I:

without S9 mix: 2.4; 4.9; 9.8; 19.5; and 39.0 µg/mL

with S9 mix: 4.9; 9.8; 19.5; 39.0; and 78.0 µg/mL

Experiment II:

without S9 mix: 10; 20; 40; 50; and 60 µg/mL

with S9 mix: 40: 80; 100; 110; and 120 µg/mL

Relevant cytotoxic effects indicated by a relative total growth of less than 50% in both parallel cultures were observed in the absence of metabolic activation at 39 µg/mL in experiment I following 4 hour treatment and at 40 µg/mL and above in experiment II following 24 hours treatment. In the presence of metabolic activation toxic effects as described above occurred at 100 µg/mL and above in experiment II. No reproducible cytotoxic effects were noted in the first experiment with metabolic activation. The recommended toxic range of approximately 10-20 % relative total growth was covered in the second experiment with and without metabolic activation.

The isolated minor reduction of the relative total growth to 43.5% in the first culture of experiment I with metabolic activation was not considered a real toxic effect since no comparable reduction was observed in the parallel culture under identical conditions.

No substantial and reproducible dose dependent increase of the mutation frequency was observed with and without metabolic activation. The mutation frequency did not reproducibly reach or exceed the threshold of 126 above the mutation frequency of the corresponding solvent control in any of the experimental parts. An isolated increase exceeding the threshold was noted in the first culture of experiment I without metabolic activation at 19.5 µg/mL. However, this increase was judged as irrelevant fluctuation since it was not reproduced in the parallel culture under identical experimental conditions. Furthermore, the increase was not dose dependent as indicated by the lacking statistical significance. In experiment II the mutant frequency exceeded the range of the historical solvent control data at several test points without metabolic activation (both cultures) and at one test point with metabolic activation (culture I). However, the threshold described above was not reached at any test point of the second experiment and no dose dependent increase was indicated by statistical analysis.

A linear regression analysis (least squares) was performed to assess a possible dose dependent increase of mutant frequencies using SYSTAT11 statistics software. No significant dose dependent trend of the mutation frequency indicated by a probability value of <0.05 was determined in all experimental groups. In this study the range of the solvent controls was from 130 up to 164 mutant colonies per 106cells; the range of the groups treated with the test item was from 83 up to 275 mutant colonies per 106cells. The solvent controls remained within the range of the historical data. Methylmethanesulfonate (19.5 µg/mL in experiment I and 13.0 µg/mL in experiment II) and cyclophosphamide (3.0 µg/mL and 4.5 µg/mL in both main experiments) were used as positive controls and showed a distinct increase in induced total mutant colonies at acceptable levels of toxicity with at least one of the concentrations of the controls.

There was no concentration related positive response of induced mutant colonies over background.

 

In a mammalian cell gene mutation assay detecting forward mutations at the thymidine-kinase (TK) locus mouse lymphoma L5178Y cells cultured in vitro were exposed to Formamidopropylbetaine (37 %) at concentrations of 1, 3.3, 10, 33, 100, 333, 1000 and 1882 μg/mL in the presence and absence of mammalian metabolic activation (S9-mix). Formamidopropylbetaine was tested up to the limit concentration of 0.01 M (= 1882 µg/mL). The test was performed in 2 independent experiments: 

Experiment 1:

Without and with 8% (v/v) metabolic activation, 3 h treatment

Experiment 2:

Without metabolic activation, 24 h treatment

With 12% (v/v) metabolic activation, 3 h treatment

The numbers of small and large colonies in the treated cultures of both experiments were comparable to the numbers of small and large colonies of the solvent controls. Formamidopropylbetaine did not induce a significant increase in the mutation frequency in the presence or absence of mammalian metabolic activation. This result was confirmed in an independent repeat experiment with modifications in the concentration of the S9-mix and exposure period.

The positive controls did induce the appropriate response. There was no evidence of induced mutant colonies over background.

 

Chromosome aberration test

Formamidopropylbetaine (38.2% a.i.) was investigated for a possible potential to induce structural chromosomal aberrations in V79 cells of the Chinese hamster in vitro in the absence and presence of metabolic activation with S9 homogenate. The selection of the concentrations used in experiment I and II based on data from the solubility test and the pre-experiment according to the guidelines.

In experiment I with and without metabolic activation 5 µL/mL was selected as highest dose group for the microscopic analysis of chromosomal aberrations. In experiment II with and without metabolic activation 5 µL/mL was selected as highest dose group. The chromosomes were prepared 20 h after start of treatment with the test item. The treatment intervals were 4 h with and without metabolic activation (experiment I) and 4 h with and 20 h without metabolic activation (experiment II). Two parallel cultures were set up. At least 100 metaphases per culture were scored for structural chromosomal aberrations. The following concentrations were evaluated for microscope analysis: Experiment I: with and without metabolic activation: 1, 2.5 and 5 µL/mL Experiment II: without metabolic activation: 1, 2.5 and 5 µL/mL with metabolic activation: 2, 3, 4 and 5 µL/mL.

Precipitation: The test item was diluted in culture medium (MEM medium). No precipitation of the test item was noted in all dose groups evaluated.

Toxicity: In experiments I and II no toxic effects of the item (indicated by a decrease of the rel. mitotic index below 70 %) were noted in all dose groups evaluated with and without metabolic activation.

Clastogenicity: In experiment I without metabolic activation the aberration rate of the negative control (0.5 %) was within the historical control data of the negative control (0.0 % - 4.0 %). The number of aberrant cells found after treatment with the test item was within the historical control data range of the negative control. The mean values noted were 2.0 % (1 µL/mL) , 1.0 % (2.5 µL/mL) and 1.5 % (5 µL/mL). The number of aberrant cells found in the groups treated with the test item did not show a biologically relevant increase as compared to the corresponding negative control.

In experiment I with metabolic activation the number of aberrant cells noted for the negative control (l.5 %) was within the historical control data of the negative control (0.0 % - 4.5 %). The number of aberrant cells found after treatment with the test item was within the historical control data range of the negative control. The mean values noted were 1 % (1 µL/mL) , 3.5 % (2.5 µL/mL) and 1.5 % (5 µL/mL). The number of aberrant cells found in the groups treated with the test item did not show a biologically relevant increase as compared to the corresponding negative control.

In experiment II without metabolic activation the aberration rate of the negative control (0.5 %) was within the historical control data of the negative control (0.0 % - 4.0 %,). The number of aberrant cells found after treatment with the test item was within the historical control data range of the negative control. The mean values noted were 1.5 % (1 µL/mL) , 1 % (2.5 µL/mL) and 3 % (5 µL/mL). The number of aberrant cells found in the groups treated with the test item did not show a biologically relevant increase as compared to the corresponding negative control. In experiment II with metabolic activation the aberration rate of the negative control (1.5 %) was within the historical control data of the negative control (0.0 % - 4.5 %). The aberration rates of all dose groups treated with the test item were within the historical control data of the negative control. The mean values noted were 2.5 % (2 µL/mL), 3.5 % (3 µL/mL), 1.8 % (4 µL/mL) and 3 % (5 µL/mL). The number of aberrant cells found in the groups treated with the test item did not show a biologically relevant increase as compared to the corresponding negative control. Polyploid cells show the occurrence of polyploid metaphases. No biologically relevant increase in the frequencies of polyploid cells was found after treatment with the test item. EMS (400 and 900 µg/mL) and CPA (0.83 µg/mL) were used as positive controls and induced distinct and biologically relevant increases in cells with structural chromosomal aberration. In conclusion, it can be stated that during the described in vitro chromosomal aberration test and under the experimental conditions reported, Formamidopropylbetaine did not induce structural

chromosomal aberrations in the V79 Chinese hamster cell line. Therefore,

Formamidopropylbetaine is considered to be non-clastogenic.

 

In vivo data

The cytogenetic activity of Coco AAPB was tested in a OF1 (I. O. P. S. Caw) mouse bone marrow micronucleus assay, performed as described by W. Schmid - The Micronucleus test, Mutation Research, 31, 9-15 (1975). 5 male and 5 female animals were treated i. p. with Coco AAPB (30 % a. i). The test method by W. Schmidt is almost equivalent to the procedure described by OECD guideline 474. In a preliminary study the test animals were administered twice (in a 24 hours interval) each 100, 200, 500, 1000 and 2000 mg/kg bw/day by intraperitoneal injection. Clinical signs and mortality were observed up to 30 hours after the first administration. Clinical signs like piloerection and ptosis were seen at doses of ≥ 100 mg/kg bw/day. At doses ≥ 1000 mg/kg bw/day the mice died within 30 and 4 hours after the first administration. The tolerated doses were in the range of 100 to 500 mg/kg bw/day. Therefore, the dose of 200 mg/kg bw/day was selected as the high dose and 20 mg/kg bw/day (10 % of the high dose) as the low dose. As the test substance was applied twice with a 24 h interval (although only one timepoint was chosen for sacrifice), the result of the sacrifice 6h later may be regarded as a result of a 30h and a 6h treatment. The dose level of 200 mg/kg bw/day (corresponding to 60 mg active substance/kg bw/day) is considered to be sufficiently high based on the effects found in the preliminary study and due to the highly irritating properties of the compound.

The mean number of micronucleated erythrocytes/1000 polychromatic erythrocytes in males and female mice at 20 and 200 mg/kg bw/day were unaffected compared to the negative controls. The administration of 100 mg cyclophosphamide/kg bw serving as the positive control led to clearly elevated numbers of micronucleated erythrocytes.

It can be concluded, that Coco AAPB (30 % a. i) induced no clastogenic effect in this in vivo cytogenicity study on mice at dose levels of 20 and 200 mg/kg bw/day.

 

Conclusion

Reliable, relevant and adequate data on the genetic toxicity of the target substance and the source closely related source substances is available from in vitro gene mutation studies in bacteria (Ames Tests), in vitro gene mutation studies in mammalian cells (L5178Y/ TK Mouse Lymphoma assay), an in vitro chromosome aberration assay and one in vivo cytogenicity study (in vivo Mammalian Erythrocyte Micronucleus Test).

As fatty acids independently from their chain length and degree on unsaturation are generally considered to be not genotoxic, a variability in the fatty acid moiety is not expected to have any influence on the genotoxic activity of the substances.

 

In conclusion there is no evidence for genotoxic properties for the target substance Undecylenamidopropyl Betaine.

 

There are no data gaps for the endpoint genotoxicity. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans.

 

Justification for read-across

For details on substance identity and detailed toxicological profiles, please refer also to the general justification for read-across given at the beginning of the CSR and attached as pdf document to IUCLID section 13.

This read-across approach is justified based on structural similarities. The target and source substances contain the same functional groups. Thus a common mode of action can be assumed.

The only deviation within this group of substances is a variety in their carbon chain length, which obviously does not have a relevant impact on genetic toxicity as demonstrated by the available data on the target and source substances.

 

a. Structural similarity and functional groups

The target substance Undecylenamidopropyl Betaine is a monoconstituent substance manufactured from undecylenic acid and N, N-dimethylpropylenediamine (DMAPA) and further reacted with monochloroacetic acid.

 

The source substances C8-18 AAPB and C8-18 and C18 unsatd. AAPB are UVCB substances manufactured from natural fatty acids or oils with  N, N-dimethylpropylenediamine (DMAPA) and further reacted with sodium monochloroacetate. As their origin is from natural sources, the used fatty acids may have a mixed slightly varying composition with an even numbered chain length from C8 to C18, including unsaturated C18 chains.

 

The source substance Formamidopropylbetaine is a monoconstituent substance manufactured from formic acid and N, N-dimethylpropylenediamine (DMAPA) and further reacted with sodium monochloroacetate.

 

b. Differences

Differences in chemical and other intrinsic properties of the target and source substances could potentially arise from the following facts:

-Different amounts of different carbon chain lengths (carbon chain length distribution):

Higher amounts of higher chain lengths and corresponding lower amounts of lower chain length lead to a rising average lipophilicity as can be seen from the increasing log Kow from Formamidopropylbetaine (log Kow: -3.3), Undecylenamidopropyl Betaine (-1.38), C8-10 Alkylamidopropyl betaine (log Kow: 2.2), C12 AAPB (log Kow: 3.54), C8-18 AAPB (log Kow: 4.23).

However, based on the available toxicological data it is demonstrated, that this read-across approach is reliable.

There are clear trends in the physicochemical properties (with regard molecular weight, water solubility, log Kow and surface tension) as demonstrated below. As data on genotoxicity are available for the upper and lower end of this row similarly showing the absence of genotoxicity, the differences in C chain lengths obviously do not influence the intrinsic genotoxic activity. 

 

- Different amounts of unsaturated fatty ester moieties:

The source substance C8-18 and C18 unsatd. AAPB contains considerable amounts of unsaturated C18 chains, which represents a worst case with respect to some toxicological endpoints, mainly local effects (e.g. irritation, sensitisation) and reactivity. But in general, variability in the fatty acid moiety is not expected to be relevant to the genetic toxicity potentialof the substances.

 

The provided structural similarities and impurity profiles support the proposed read-across hypothesis with high confidence.

 

Comparison of genotoxicity data

 

Endpoints

Target substance

Source substances

 

Undecylenamidopropyl Betaine

C8-18 and C18 unsatd. AAPB

C8-18 AAPB

Formamido-propylbetaine

Genotoxicity

 

in vitro

Gene mutation in bacteria

key_Genetic toxicity in vitro: 98510-75-9 8.4.1_Evonik_2014_OECD471

 

OECD TG 471, gene mutation: bacterial reverse mutation assay (e.g. Ames test),
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation: with and without

cytotoxicity: only in strain TA 100 at 2500 and 5000 μg/plate;

vehicle controls valid: yes; negative controls valid: yes; positive controls valid: yes

 

Genotoxicity: negative

 

Reliability: 1 (reliable without restrictions), GLP

Sup_RA_Genetic toxicity in vitro: 147170-44-3_8.4.1_Zschimmer_1996_EEC 92_69


EU Method B.13/14
S. typhimurium TA 1535, TA 100, TA 1537, TA 1538 and TA 98

Metabolic activation: with and without

cytotoxicity: first evidence of toxicity at 10000 µg/plate with and without S9;

vehicle controls valid: yes; negative controls valid: yes; positive controls valid: yes

 

Genotoxicity: negative

 

Reliability: 2 (reliable with restrictions), no GLP

No data

sup_RA_Genetic toxicity in vitro: 120128-90-7_8.4.1_Evonik_2005_OECD471

 

OECD TG 471, gene mutation:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation: with and without

cytotoxicity: no;

vehicle controls valid: yes; negative controls valid: yes; positive controls valid: yes

 

Genotoxicity: negative

 

Reliability: 1 (reliable without restrictions), GLP

Gene mutation in mammalian cells

No data, read-across

No data

Key_RA_Genetic toxicity in vitro: 97862-59-4_8.4.3_MoLy_Evonik_2010_OECD-476

OECD TG 476,
mouse lymphoma L5178Y cells

Metabolic activation: with and without

cytotoxicity: yes;

vehicle controls valid: yes; positive controls valid: yes

 

Genotoxicity: negative

 

Reliability: 1 (reliable without restriction), GLP

key_RA_Genetic toxicity in vitro: 120128-90-7_8.4.3_Evonik_2012_OECD476

 

OECD TG 476,
mouse lymphoma L5178Y cells

Metabolic activation: with and without

cytotoxicity: no;

vehicle controls valid: yes; positive controls valid: yes

 

Genotoxicity: negative

 

Reliability: 1 (reliable without restriction), GLP

Chromosome aberration

No data, read-across

No data

No data

key_RA_Genetic toxicity in vitro: 120128-90-7_8.4.2_Evonik_2005_OECD473

 

OECD TG 473,
Chinese hamster lung fibroblasts (V79)

Metabolic activation: with and without

cytotoxicity: no;

vehicle controls valid: yes; positive controls valid: yes

 

Genotoxicity: negative

 

Reliability: 1 (reliable without restriction), GLP

Genotoxicity in vivo

No data, read-across

Key_Genetic toxicity in vivo: 61789-40-0_8.4.4_Goldschmidt_France_1987_micronucleus test in vivo
Study result type: experimental result

similar to OECD TG 474,mouse, intraperitoneal,100 mg/kg bw

 

toxicity: yes (in preliminary dose finding study lethal at doses >/= 1000 mg/kg bw);

vehicle controls valid: yes;

positive controls valid: yes


Genotoxicity negative

 

Reliability: 2 (reliable with restrictions), GLP

No data

No data

 

The target substance Undecylenamidopropyl Betaine was not mutagenic in the Ames test. Cytotoxicity was only observed in strain TA 100 at 2500 and 5000 μg/plate.Also the source substances Formamidopropylbetaine and C8-18 and C18 unsatd. AAPB were not mutagenic in the reverse gene mutation assay in bacteria and showed little or no signs of cytotoxicity.

Based on comparable results in the Ames test as well as on structural similarities, it is concluded that the outcome of the mutation assay in mammalian cells as well as the chromosome aberration assays conducted with the source substances Formamidopropylbetaine, C8-18 AAPB and C8-18 and C18 unsatd. AAPB is also relevant for the target substance Undecylenamidopropyl Betaine.

 

In a mammalian cell gene mutation assay according to OECD Guideline 476 the source substances Formamidopropylbetaine and C8-18 AAPB induced no concentration related positive response of induced mutant colonies over background when tested up limit or cytotoxic concentrations.

The source substance Formamidopropylbetaine did not induce chromosome aberrations in a chromosome aberration assay according to OECD Guideline 473 when tested up to limit concentrations.

The source substance C8-18 and C18 unsatd. AAPB was not clastogenic in a mouse bone marrow micronucleus assay.

 

Certain endpoints such as skin sensitisation and genotoxicity are characterised by covalent binding as a rate determining step or MIE (molecular initiating event). The consistency across endpoints - both, source substances and target substance were not sensitising - also helps to increase confidence in the read-across approach especially when MIEs are common for example, skin sensitisation and genotoxicity are underpinned by electrophilicity.

 

Quality of the experimental data of the analogues:

The available data are adequate and sufficiently reliable to justify the read-across approach.

The key studies were conducted according to EU Method B.13/14/OECD TG 471, OECD TG 476, OECD TG 473 or similar to OECD TG 474 and were reliable (RL1) or reliable with restrictions (RL2).

The test materials used in the respective studies represent the source substance as described in the hypothesis in terms of substance identity and minor constituents.

Overall, the study results are adequate for the purpose of classification and labelling and risk assessment.

 

Conclusion

As fatty acids independently from their chain length and degree on unsaturation are generally considered to be not genotoxic, a variability in the fatty acid moiety is not expected to have any influence on the genotoxic activity of the substances.

Based on the comparable negative outcome of the Ames test for the target and source substances as well as on structural similarities of the target and the source substanceas presented above and in more detail in the general justification for read across, it can be concluded that the available data on mammalian cell gene mutation and clastogenicity from the source substances Formamidopropylbetaine, C8-18 AAPB and C8-18 and C18 unsatd. AAPB are also valid for the target substance Undecylenamidopropyl Betaine.

There was no evidence of mutagenic or clastogenic intrinsic properties in any of the performed studies.

 

Further support is given by the lacking skin sensitisation potential for the target and source substances (see section “sensitisation”). The endpoint sensitisation is – similar to the endpoint genotoxicity – based on covalent binding of the substance itself or reactive metabolites to cellular macromolecules as rate determining step. The consistency across the endpoints increases the confidence in the conclusion that there is no concern for reactive metabolites. 


Justification for selection of genetic toxicity endpoint
No single key study was selected since all available studies (guideline studies or comparable to guidelines, RL1-2) were consistently negative.

Short description of key information:
All available tests were consistently negative:
- Ames test with S. typhimurium TA 98, TA 100, TA 1535, TA 1537, E coli WP2 uvrA (met. act.: with and without) (OECD TG 471, GLP, RL1)
- Mammalian cell gene mutation assay with mouse lymphoma L5178Y cells (TK) (met. act.: with and without) (OECD Guideline 476 and GLP); read across: C8-18 AAPB and Formamidopropylbetaine
- In vitro mammalian chromosome aberration test with Chinese hamster lung fibroblasts (met. act.: with and without) (OECD Guideline 473, GLP, RL1); read across: Formamidopropylbetaine
- in vivo, mouse micronucleus assay (similar to OECD Guideline 474, GLP, RL2), intraperitoneal, 100 mg/kg bw

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data, Undecylenamidopropyl Betaine does not need to be classified formutagenicityaccording to regulation (EC) 1272/2008. Thus, no labelling is required.