1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-coco acyl derivs., hydroxides, inner salts

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 January, 2018 - 15 February, 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

Batch: DSP-001.
Purity: 97%.
Expiry Date: 15 August 2018.

Species / strain / cell type:

S. typhimurium TA 1537

Remarks:

his C 3076; rfa-; uvrB-:

Details on mammalian cell type (if applicable):

Obtained from Trinova Biochem GmbH on 27 June 2017.

Species / strain / cell type:

S. typhimurium TA 98

Remarks:

his D 3052; rfa-; uvrB-;R-factor

Details on mammalian cell type (if applicable):

Obtained from Trinova Biochem GmbH on 27 June 2017.

Species / strain / cell type:

S. typhimurium TA 1535

Remarks:

his G 46; rfa-; uvrB-:

Details on mammalian cell type (if applicable):

Obtained from Trinova Biochem GmbH on 27 June 2017.

Species / strain / cell type:

S. typhimurium TA 100

Remarks:

his G 46; rfa-; uvrB-;R-factor

Details on mammalian cell type (if applicable):

Obtained from Trinova Biochem GmbH on 27 June 2017.

Species / strain / cell type:

E. coli WP2 uvr A

Remarks:

trp-; uvrA-:

Details on mammalian cell type (if applicable):

Obtained from British Industrial Biological Research Association on 17 August 1987.

Metabolic activation:

with and without

Test concentrations with justification for top dose:

The maximum concentration was 5000 µg/plate (the maximum recommended dose level).
Eight concentrations of the test item (1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate) were assayed in triplicate against each tester strain, using the direct plate incorporation method.

Vehicle / solvent:

The vehicle control used was as follows:
Identity: Sterile distilled water.
Supplier: Baxter.
Batch number (purity): 17H09BA1A (N/A), Expiry: 07/2020.

Untreated negative controls:

yes

Remarks:

triplicate

Negative solvent / vehicle controls:

yes

Remarks:

triplicate

Positive controls:

yes

Remarks:

triplicate

Positive control substance:

4-nitroquinoline-N-oxide

benzo(a)pyrene

other: N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG); 9-Aminoacridine (9AA); 2-Aminoanthracene (2AA).

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation
- Number of cells (x 10 9 /mL) for each treated and control culture:
TA100: Experiment 1 = 2.7; Experiment 2 = 1.5
TA1535: Experiment 1 = 1.2; Experiment 2 = 1.9
WP2uvrA: Experiment 1 = 3.2; Experiment 2 = 2.3
TA198: Experiment 1 = 3.1; Experiment 2 = 1.9
TA1537: Experiment 1 = 1.3; Experiment 2 = 1.5

DURATION
- Preincubation period:
- Exposure duration:
- Expression time (cells in growth medium):
- Selection time (if incubation with a selection agent):
- Fixation time (start of exposure up to fixation or harvest of cells):

Evaluation criteria:

There are several criteria for determining a positive result.
Any, one, or all of the following can be used to determine the overall result of the study:
1. A dose-related increase in mutant frequency over the dose range tested (De Serres and Shelby, 1979).
2. A reproducible increase at one or more concentrations.
3. Biological relevance against in-house historical control ranges.
4. Statistical analysis of data as determined by UKEMS (Mahon et al., 1989).
5. Fold increase greater than two times the concurrent solvent control for any tester strain (especially if accompanied by an out-of-historical range response (Cariello and Piegorsch, 1996)).

A test item will be considered non-mutagenic (negative) in the test system if the above criteria are not met.

Statistics:

Statistical significance was confirmed by using Dunnetts Regression Analysis (* = p < 0.05) for those values that indicate statistically significant increases in the frequency of revertant colonies compared to the concurrent solvent control.

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES:
The dose range used for Experiment 2 was determined by the results of Experiment 1 and was as follows:
Salmonella strains TA100, TA1535 and TA1537 (with and without S9): 0.5, 1.5, 5, 15, 50, 150, 500, 1500 µg/plate;
Salmonella strain TA98 (with and without S9): 1.5, 5, 15, 50, 150, 500, 1500, 5000 µg/plate;
E.coli strain WP2uvrA (with and without S9): 5, 15, 50, 150, 500, 1500, 5000 µg/plate.

HISTORICAL CONTROL DATA
- Positive historical control data,Year: 2017
Range across all strains with and without S9: 95-4357.
Mean across all strains with and without S9: 186-2379.

Conclusions:

1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-coco acyl derivs., hydroxides, inner salts was considered to be non-mutagenic under the conditions of this test.

Executive summary:

A GLP compliant bacterial reverse mutation test was performed on the substance in accordance with OECD Test Guideline 471.

Several strains of bacteria were treated with the test item using both Ames plate incoporation and pre-incubation methods at doses ranging from 0.5 to 5000 µg/plate, with and without S9 -mix.

Sterile distilled water was used as the vehicle as the test item is soluble in water.

There were no increases in the frequency of revertant colonies observed for any of the bacterial strains, at any of the doses, with or without metabolic activation in the plate incorporation or pre-incubation experiments. All controls were valid.

Under the conditions of this test, 1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-coco acyl derivs., hydroxides, inner salts was found to be non-mutagenic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)