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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No experimental data are available for the target substance C16 IOS-Na.


 


A negative Ames test according to OECD TG 471 is available for the closely related source substance 1 (C16-18 IOS-Na C16-rich).


 


In the two main tests, neither an increase in the number of revertant colonies (more than twice as many as that of the negative control) nor a dose-related response was observed at any doses in any strains of base-pair substitution type or frame-shift type, with or without metabolic activation. The revertant colonies of the positive controls showed an increase of more than twice that of the negative controls and they were within limit of controls (mean±3SD) in historical data, indicating that this study was performed correctly. From these results, mutagenicity of the test substance was judged negative.


 


 


 


A negative result in the bacterial reverse mutation assay is also available for the source substance 2 (C14-16 AOS-Na). Although there is only incomplete information available from a review article (Greim et al. 1994), the information supports that for the entire group of alpha-Olefin sulfonatesa genotoxic potential is not expected.


 


Also, the results of several in vitro studies (Bacterial Reverse Mutation Test and Mammalian Chromosome Aberration Test) with thea-olefin sulfonates were negative (Wibbertmann et al. 2011).


 


Alkyl sulfates with different chain lengths and counter ions were tested in variety of in vitro and in vivo test systems (Bacterial Reverse Mutation Test, Mammalian Cell Gene Mutation Test, Mammalian Chromosome Aberration Test, Rodent Dominant Lethal Test, Mammalian Erythrocyte Micronucleus Test and Mammalian Bone Marrow Chromosome Aberration Test) performed according to current standards and there was no indication for a genotoxic potential.


Based on the overall negative results in the genotoxicity assays with alkylsulfates anda-olefinsulfonates, the absence of structural elements indicating mutagenicity, and the overall data- base on different types of sulfonates which all tested negative in mutagenicity assays, alkane sulfonates are not expected to have genotoxic potential (Wibbertmann et al. 2011).


 


The result for source substance 1 can be also applied for the target substance because the minor structural differences between the target substance and source substances 1 and 2 (see details above) are not expected to have an impact on the genotoxic potential. 

Link to relevant study records

Referenceopen allclose all

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:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar (eco)toxicological properties because
Source and target substances share structural similarities (predominantly linear aliphatic hydrocarbon chain) with a common functional group: (polar sulfonate group). The molecular structure is almost identical.
They are manufactured from similar resp. identical precursors under similar conditions. Therefore, common breakdown products via physical and biological processes, which result in structurally similar chemicals are evident. Target and source substances are both a mixture of linear long chain Sulfonic acids, alkene, sodium salts and Sulfonic acids, alkane hydroxy, sodium salts and share an identical counter ion. A constant pattern in the changing of the potency of the properties across the target and source substances by chain-length and is not observed, because the distribution is too narrow.

Therefore, read-across from the existing toxicity studies on the source substance, is considered as an appropriate adaptation to the standard information requirements of Annex VII, 8.1, 8.2, 8.3, 8.4, 8.5 as well as 9.1 and 9.2 of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see cross reference to assessment report: Justification for read-across document attached to section 13

3. ANALOGUE APPROACH JUSTIFICATION
see cross reference to assessment report: Justification for read-across document attached to section 13

4. DATA MATRIX
see cross reference to assessment report: Justification for read-across document attached to section 13
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across: supporting information
Key result
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
It is concluded that Sulfonic acids, C16-alkane hydroxy and C16-alkene, sodium salts is not mutagenic in the bacterial reverse mutation assay carried out under the experimental conditions.
Executive summary:

This read-across is based on the hypothesis that source and target substances have similar (eco)toxicological properties because

Source and target substances share structural similarities (predominantly linear aliphatic hydrocarbon chain) with a common functional group: (polar sulfonate group). The molecular structure is almost identical.

They are manufactured from similar resp. identical precursors under similar conditions. Therefore, common breakdown products via physical and biological processes, which result in structurally similar chemicals are evident. Target and source substances are both a mixture of linear long chain Sulfonic acids, alkene, sodium salts and Sulfonic acids, alkane hydroxy, sodium salts and share an identical counter ion. A constant pattern in the changing of the potency of the properties across the target and source substances by chain-length and is not observed, because the distribution is too narrow.

Therefore, read-across from the existing bacterial reverse mutation assay on the source substance, is considered as an appropriate adaptation to the standard information requirements of Annex VII, 8.4 of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

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:
From 19th July 2013 to 12nd August 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
S. typhimurium TA98; hisD 3052_GC rfa uvrB pKM101c
S. typhimurium TA100; hisG 46_GC rfa uvrB pKM101
S. typhimurium TA1535; hisG 46_GC rfa uvrB
S. typhimurium TA1537; hisC 3076_GC rfa uvrB
E. coli WP2uvrA; trpE65_AT rfa uvrA
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
For the tests without metabolic activation, 0.5 mL of 0.1 M Na-phosphate buffer (pH 7.4) and 0.1 mL of each fresh bacterial culture were added to each tube containing 0.1 mL of the test solution. For the tests with metabolic activation, 0.5 mL of the S9 mix was added to each tube instead of the 0.1 M Na-phosphate buffer. The mixture was pre-incubated in a water bath at 37℃ for 20 minutes while shaking horizontally, and then 2.0 mL of top agar were added to the mixture, and the contents of each tube were poured over the surface of the minimal glucose agar plate. For the sterility test, 0.1 mL of the test solution of the highest dose and 0.5 mL of the S9 mix were put into each tube, 2.0 mL of top agar were then added to the tube, and the contents of each tube were poured over the surface of the minimal glucose agar plate. These operations were conducted under lamps with ultraviolet absorbent filter.All plates were incubated at 37℃ for 48 hours, and the number of revertant colonies was counted. Afterwards, growth inhibition of the test strains was checked using a stereoscopic microscope.
As top agar, a soft agar solution (0.6% Agar and 0.5% NaCl) with 1/10 by volume of the solution of 0.5 mM biotin-0.5 mM L-histidine and the same ratio of 0.5 mM L-tryptophan were used for the S. typhimurium TA strains and the E. coli strain, respectively. One minimal glucose agar plate was used for each dose level in the preliminary test and three minimal glucose agar plates were used for each dose level in two main tests which were performed at the same doses.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Water for injection (The Japanese Pharmacopoeia)
- Justification for choice of solvent/vehicle: From the result of the solubility test, the test substance was dissolved at 50 mg/mL in water, and neither exothermic reaction nor generation of gas was observed. Therefore water for injection was used as solvent for preparation.
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
benzo(a)pyrene
other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide, 2-Methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine.2HCl, 2-Aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: Preincubation
DURATION
- Preincubation period: 20 minutes
- Exposure duration: 48 hours
Evaluation criteria:
In the two main tests, if the number of revertant colonies on the test plates increased significantly in comparison with that on the control plates (based on twice as many as that of the negative control), and dose-response and reproducibility were also observed, the test substance was to be judged positive. The results at each concentration were demonstrated with the mean and the standard deviation.
Key result
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
It is concluded that Internal Olefin Sulfonate is not mutagenic in the bacterial reverse mutation assay carried out under the experimental conditions.
Executive summary:

In the two main tests, neither an increase in the number of revertant colonies (more than twice as many as that of the negative control) nor a dose-related response was observed at any doses in any strains of base-pair substitution type or frame-shift type, with or without metabolic activation. The revertant colonies of the positive controls showed an increase of more than twice that of the negative controls and they were within limit of controls (mean±3SD) in historical data, indicating that this study was performed correctly. From these results, mutagenicity of the test substance was judged negative.

The growth inhibition of the test strains by the test substance was observed at some doses. And the precipitate of the test substance on the plates was not observed either with or without metabolic activation. In the sterility test on the test solution and the S9 mix, no growth of bacteria was observed.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
not specified
Specific details on test material used for the study:
- Source: Hoechst AG
- Name of test material (as cited in study report): C14-16-alkane hydroxy and C14-16-alkene sulfonic acids sodium salts
- CAS 68439-57-6
- Analytical purity: No data
Target gene:
his-operon
Species / strain / cell type:
S. typhimurium, other: strains not specified
Metabolic activation:
not specified
Species / strain:
S. typhimurium, other: strain not specified
Metabolic activation:
not specified
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
True negative controls validity:
not specified
Positive controls validity:
not specified
Conclusions:
It is concluded that C14-16-alkane hydroxy and C14-16-alkene sulfonic acids sodium salts is not mutagenic in the bacterial reverse mutation assay.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

The test substance did not show any genotoxic intrinsic properties in the Ames-Test, and is therefore considered to be non-genotoxic.


Therefore the substance is not to be classified as “genotoxic” according to GHS Regulation EC No 1272/2008. No labelling is required.