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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: genome mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was conducted by a GLP accredited laboratory using OECD Testing Guideline 471. The study was conducted on 6-[(p-Tosyl)amino]hexanoic acid, which is the carboxylic acid component of the registered substance i.e. tosyl salt.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
Tosyl carboxylic acid
IUPAC Name:
Tosyl carboxylic acid
Constituent 2
Reference substance name:
6-[(p-Tosyl)amino]hexanoic acid
IUPAC Name:
6-[(p-Tosyl)amino]hexanoic acid
Constituent 3
Reference substance name:
6-[[(4-methylphenyl)sulphonyl]amino]hexanoic acid
EC Number:
278-934-5
EC Name:
6-[[(4-methylphenyl)sulphonyl]amino]hexanoic acid
Cas Number:
78521-39-8
IUPAC Name:
6-{[(4-methylphenyl)sulfonyl]amino}hexanoic acid
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): ASC PLUS, dried
- Physical state: white powder, odourless
- Analytical purity: 99.24%
- Lot/batch No.: 110526S
- Expiration date of the lot/batch: 26-05-2016
- Storage condition of test material: ambient temperature (15-25°C)
- Other: soluble in DMSO

Method

Target gene:
TA100: his G46
TA98: his D3052
TA97: his D6610
TA102: his G428 (pAQ1)
TA1535: his G46
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 100
Additional strain / cell type characteristics:
other: Strain is histidine-dependent
Species / strain / cell type:
S. typhimurium TA 98
Additional strain / cell type characteristics:
other: Strain is histidine-dependent
Species / strain / cell type:
S. typhimurium TA 97
Additional strain / cell type characteristics:
other: Strain is histidine-dependent
Species / strain / cell type:
S. typhimurium TA 1535
Additional strain / cell type characteristics:
other: Strain is histidine-dependent
Species / strain / cell type:
S. typhimurium TA 102
Additional strain / cell type characteristics:
other: Strain is histidine-dependent
Metabolic activation:
with and without
Metabolic activation system:
Mammalian liver post-mitochondrial fraction (S9), prepared from Sprague Dawley male rats.
Test concentrations with justification for top dose:
Range-Finding: 7 concentrations in the range of 0.01-5.0 mg/plate
Definitive assay: 8 concentrations in the range of 0.000001-1 mg/plate
Confirmatory assay with preincubation: 0.000000-0.5 mg/plate
Appropriate amount of test item was weighted and diluted in DMSO not earlier than 30 min prior to test start. For dilution of final doses, sterile DMSO was used.
Vehicle / solvent:
- Vehicle/solvent used: DMSO
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
mitomycin C
other: 2-acetamidofluorene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48-72 hr

NUMBER OF REPLICATIONS: 3
Evaluation criteria:
- concentration-related increase over the tested range and reproducible increase at one or more concentrations in the number of revertant colonies per plate in at least one strain with or without metabolic activation
- mutation factor >2
Statistics:
Student's t-test was used

Results and discussion

Test resultsopen allclose all
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 97
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 102
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
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

No significant increase in the mutant frequency was observed for the 5 tested strains, neither in the standard plate incorporation nor in the preincubation assays with or without metabolic activation.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

The test substance is considered to be non-mutagenic in the bacterial gene mutation test system.
Executive summary:

The genetic toxicity of the test substance was determined in accordance with the OECD Guideline for Testing of Chemicals 471. The test substance was dissolved in DMSO and tested with the 5 strains of Salmonella typhimurium: TA100, TA98, TA97, TA102 and TA1535. There was no induction of metabolic activity either with or without metabolic activation with S-9 mix. Adequate positive and negative control substances were included in the test system. In conclusion, up to and including concentrations of 5000 µg/plate the test substance did not increase the mutation frequency of the 5 tested strains and is therefore considered to be non-.mutagenic. The test substance was the carboxylic acid component of the registered substance. Read-across between the tosyl salt carboxylic acid (6-[(p-Tosyl)amino]hexanoic acid) and the registered substance is considered justified as the registered substance is manufactured directly from 6-[(p-Tosyl)amino]hexanoic acid by simple neutralisation with triethanolamine (TEA). Other than ionization of the carboxylic acid group, the 6-[(p-Tosyl)amino]hexanoic acid remains chemically unchanged upon salt formation. In water, the acid and amine components of 6-[(p-Tosyl)amino]hexanoic acid, compound with 2,2’,2’’-nitrilotriethanol (1:1) dissociate completely and behave essentially as independent substances. Since TEA can be considered non-hazardous, it is the acid component of the salt that will have a more significant impact on the outcome of any (eco)toxicological or environmental tests. The pKa of the carboxylic acid group in 6-[(p-Tosyl)amino]hexanoic acid (pKa = 4.90) is the same in the free acid as it is in the TEA salt. As a result, 6-[(p-Tosyl)amino]hexanoic acid will respond to changes of pH in the same way whether it is in the salt form or as the parent carboxylic acid and hence it’s bioavailability will be the same.