Disodium 4-[2-[2-[2-(dodecyloxy)ethoxy]ethoxy]ethyl] 2-sulphonatosuccinate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate. The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with S9 metabolic activation system. Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate did not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence is predicted to not likely classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from prediction database and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Prediction is done using OECD QSAR toolbox version 3.3

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of the test material: disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate
- IUPAC name: disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate
- Molecular formula: C22H42O10S2Na
- Molecular weight: 542.594 g/mol
- Smiles: [Na+].[Na+].C([C@@H](CC(=O)OCCOCCOCCOCCCCCCCCCCCC)S(=O)(=O)[O-])(=O)[O-]

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Details on mammalian cell type (if applicable):

No data

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

No data

Metabolic activation:

with

Metabolic activation system:

S9 metabolic activation system

Test concentrations with justification for top dose:

No data

Vehicle / solvent:

No data

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Details on test system and experimental conditions:

No data

Rationale for test conditions:

No data

Evaluation criteria:

The plates were observed for a dose dependent increase in the number of revertants/plate

Statistics:

No data

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

No data

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 10 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and "p" )  and ("q" and ( not "r") )  )  and ("s" and "t" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anionic Surfactants AND Esters (Acute toxicity) AND Nonionic Surfactants by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Anion OR Carbonic acid derivative OR Carboxylic acid derivative OR Carboxylic acid ester OR Carboxylic acid salt OR Cation OR Dialkylether OR Ether OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Carbonyl, aliphatic attach [-C(=O)-] OR Ester, aliphatic attach [-C(=O)O] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, aliphatic attach [-O-] OR Suflur {v+4} or {v+6} OR Sulphonate, aliphatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkoxy OR Carboxylic acid OR Carboxylic acid ester OR Ether OR Overlapping groups OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alkoxy OR Carboxylic acid OR Carboxylic acid ester OR Ether OR Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Radical OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion formation OR SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion formation >> N-Nitroso Compounds OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Sultones by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Sulfuranes by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized triple bond  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Radical reactions OR Radical reactions >> Free radical formation OR Radical reactions >> Free radical formation >> Hydroperoxides OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SN1 OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations >> Mercury compounds  OR SN2 OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Isothiazolone derivatives  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding by OASIS v1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> Furamates (MA) by Protein binding potency

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aliphatic nitriles (Hepatotoxicity) Rank B OR Carboxylic acids (Hepatotoxicity) No rank OR Perhexiline (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= -7.2

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.97

Conclusions:

Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate did not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence is predicted to not likely classify as a gene mutant in vitro.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate. The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with S9 metabolic activation system. Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate did not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence is predicted to not likely classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Gene mutation in vitro:

Prediction model based estimation and data from read across chemicals have been reviewed to determine the mutagenic nature of

Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate. The studies are discussed below:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate. The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate did not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence is predicted to not likely classify as a gene mutant in vitro.

Seifried et al (Chem. Res. Toxicol., 2006) discussed Ames mutagenicity test for 60 -70% structurally similar read across chemical Sodium lauroyl isethionate (RA CAS no 7381 -01 -3) to evaluate its genetoxic effects when exposed to Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 with dose concentration of 33-1600 µg/plate in plate incorporation assay. Based on the preliminary study conducted, the test compound was used at a five dose level from 33-1600 µg/plate. The plates were incubated for 48 h at 37±2 °C. Five doses of test chemical, together with the appropriate concurrent solvent and positive controls, were tested in triplicate on each tester strain without metabolic activation and also with activation by induced rat and hamster liver S9 preparations. For a test article to be considered positive, it had to induce at least a doubling (TA98, TA100, and TA1535) in the mean number of revertants per plate of at least one tester strain. This increase in the mean revertants per plate had to be accompanied by a dose response to increasing concentrations of the test chemical. Sodium lauroyl isethionate failed to induce mutation in the Salmonella typhirium TA98, TA100, TA1535, TA1537, and TA1538 both in the presence and absence of S9 activation system and hence is not likely to be a gene mutant.

In the same study by Seifried et al (2006), gene mutation study was conducted according to L5178Y TK+/- Mouse Lymphoma Mutagenicity Assay to determine the mutagenic nature of the test compound sodium lauroylisethionate (RA CAS no 7381 -01 -3; IUPAC name: sodium 2-(dodecanoyloxy)ethanesulfonate). The Cells at a concentration of 1.2 X 10⁷cells/mL were exposed for 4 h to a range of concentrations from16-149µg/mL. The cells were then washed, resuspended in growth medium, and incubated at 37°C for 48h to allow recovery and mutant expression. Cells in the cultures were adjusted to 3 X 10⁵/mL at 24 h intervals. They were then cloned (1 X 10⁶cells/plate for mutant selection and 200 cells/plate for viable count determinations) in soft agar medium containing Fischer’s medium, 20% horse serum, 2 mM sodium pyruvate, 0.02% pluronic F-68, and 0.23% granulated agar. Resistance to trifluorothymidine (TFT) was determined by adding TFT (final concentration, 3µg/mL) to the cloning medium for mutant selection. The 100X stock solution of TFT in saline was stored at -70 °C and was thawed immediately before use. Plates were incubated at 37 ( 1 °C in 5% CO2 in air for 10-12 days and then counted with an Artek automated colony Counter. Only colonies larger than ~ 0.2 mm in diameter were counted. Mutant frequencies were expressed as mutants per 10⁶surviving cells. Sodium lauroylisethionate failed to induce a doubling of the mutant frequency both in the presence and absence of S9 activation system and hence is not likely to be gene mutant in vitro.

In another study for 60 -70% structurally similar read across chemical, Ames mutagenicity test was conducted (J check) for Sodium 1-methoxy-1-oxohexadecane-2-sulfonate (RA CAS no 4016 -24 -4; IUPAC name: sodium 1-methoxy-1-oxohexadecane-2-sulfonate) to evaluate its genetoxic effects when exposed to Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 and E. coli WP 2 uvr A in preincubation assay. Based on the preliminary study conducted, the test compound was used at dose concentration of 0, 0.625, 1.25, 2.5, 3.13, 5, 6.25, 10, 12.5, 20, 25, 50, 100, 156, 313, 625, 1250, 2500 or 5000 µg/plate. The plates were preincubated for 20 mins and then exposure incubation was for 48 h at 37 °C. Appropriate concurrent solvent and positive controls, were tested in duplicate with three plates / dose on each tester strain without metabolic activation and also with activation. The case where the number of reversed mutant colonies (average value) in the test substance treated plate was more than twice the solvent control value and the dose dependence and the reproducibility of the result were observed was considered positive. Sodium 1-methoxy-1-oxohexadecane-2-sulfonatefailed to induce mutation in the Salmonella typhimuriumTA 98, TA 100, TA 1535, TA 1537 and E. coli WP 2 uvr A both in the presence and absence of S9 activation system and hence is not likely to be a gene mutant.

Based on the information available for target chemical and its read acorss, Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate does not exhibit gene mutation in vitro. Thus, the chemical is not likely to classify as a gene mutant in vitro as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the information available for target chemical and its read acorss, Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate does not exhibit gene mutation in vitro. Thus, the chemical is not likely to classify as a gene mutant in vitro as per the criteria mentioned in CLP regulation.