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

Endpoint summary

Description of key information

The skin sensitization potential of Disodium 4-oxo-2-sulfonato-5, 8, 11, 14-tetraoxahexacosan-1-oate (40754-59-4) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Disodium 4-oxo-2-sulfonato-5, 8, 11, 14-tetraoxahexacosan-1-oate (40754-59-4) was predicted to be non sensitizing to the skin of male and femaleDunkin-Hartley guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 QSAR toolbox 3.3.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3.

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

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-]

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Centre d'élevage Lebeau, 78950 Gambais,
France- Age at study initiation: no data
- Weight at study initiation: 404 +/- 26 g for males and 410 +/- 20 g for females
- Housing: individually in polycarbonate cages
- Diet (ad libitum): Guinea-pigs sustenance reference 106 diet, UAR, France
- Water (e.g. ad libitum): filtered tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes: non-recycled and filtered
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal and epicutaneous

Vehicle:

physiological saline

Concentration / amount:

0.5 ml of a 10% solution

Day(s)/duration:

48 hour

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Concentration / amount:

0.5 ml of a 10% solution

Day(s)/duration:

48 hour

No. of animals per dose:

10 animals

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: No data available.
- Exposure period: 48 hour
- Test groups: yes
- Control group:
- Site: No data available.
- Frequency of applications: No data available.
- Duration: 48 hours
- Concentrations: 0.5 ml of a 10% solution

B. CHALLENGE EXPOSURE
- No. of exposures: No data available.
- Day(s) of challenge: No data available.
- Exposure period: No data available.
- Test groups: yes
- Control group: No data available.
- Site: Left Flank
- Concentrations: 0.5 ml of a 10% solution
- Evaluation (hr after challenge): 48 hours

Positive control substance(s):

yes

Remarks:

DCNB

Statistics:

No data available.

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5 ml of a 10% solution

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No sensitization effect were observed.

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "S W A N"
Estimation method: Takes highest mode value from the 5 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 "o" )  )

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 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters 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 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters 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 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 by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Isothiazolinone derivatives OR Low reactive OR Low reactive >> Alicyclic ketones by DPRA Cysteine peptide depletion

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha, beta - Unsaturated Carboxylic Acids and Esters by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.33

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.903

Interpretation of results:

other: Negative

Conclusions:

The skin sensitization potential of Disodium 4-oxo-2-sulfonato-5, 8, 11, 14-tetraoxahexacosan-1-oate (40754-59-4) was estimated using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Disodium 4-oxo-2-sulfonato-5, 8, 11, 14-tetraoxahexacosan-1-oate (40754-59-4) was predicted to be non sensitizing to the skin of male and femaleDunkin-Hartley guinea pig.

Executive summary:

The skin sensitization potential of Disodium 4-oxo-2-sulfonato-5, 8, 11, 14-tetraoxahexacosan-1-oate (40754-59-4) was estimated using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Disodium 4-oxo-2-sulfonato-5, 8, 11, 14-tetraoxahexacosan-1-oate (40754-59-4) was predicted to be non sensitizing to the skin of male and femaleDunkin-Hartley guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

In different studies, Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate ( 40754-59-4)has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction and studies are based on in vivo experiments in guinea for target chemical disodium Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate ( 40754-59-4) and its structurally similar read across substances Acetone (67-64-1)and sodium 2-(dodecyloxy)-2-oxoethanesulfonate(1847-58-1). The predicted data using the OECD QSAR toolbox and DANISH QSAR have also been compared with the experimental data.

The skin sensitization potential of Disodium 4-oxo-2-sulfonato-5, 8, 11, 14-tetraoxahexacosan-1-oate (40754-59-4) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Disodium 4-oxo-2-sulfonato-5, 8, 11, 14-tetraoxahexacosan-1-oate (40754-59-4) was predicted to be non sensitizing to the skin of male and femaleDunkin-Hartley guinea pig.

 Another Prediction done by Danish QSAR (2017), to evaluate the skin sensitization potential of Disodium 4-oxo-2-sulfonato-5, 8, 11, 14-tetraoxahexacosan-1-oate (40754-59-4).Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for Disodium 4-oxo-2-sulfonato-5, 8, 11, 14-tetraoxahexacosan-1-oate (40754-59-4) estimated to be not sensitizing when applied to human and guinea pig skin.

Further supported by experimental data conducted by Nakamura A et al.(Contact Dermatitis, 1994) )on structurally similar read across substance Acetone (67-64-1)on female Hartley guinea pigs.The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on skin sensitization from the analogue substance. Skin sensitization study for Acetone was conducted on female Hartley guinea pigs by guinea pig Maximization test. A group of 10 female Hartley guinea pigs were used for the skin sensitization test (protocol of Magnusson and Kligman with modified scale for Scoring of skin responses). Induction was performed by intradermal injection and topical application of 100 %acetone. 21 days later the animals were challenged by topical application of 100 μl acetone on the shavedflank of 10 animals. No positive skin sensitization effect was observed in any animal. Therefore Acetone was considered to be non skin sensitizing in female Hartley guinea pigs.

It is further supported by an experimental study conducted  by Mary Ann Liebert, (JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY, 1987)on structurally similar read across substance sodium 2-(dodecyloxy)-2-oxoethanesulfonate(1847-58-1)on female Hartley guinea pigs.Skin sensitization test forsodium 2-(dodecyloxy)-2oxoethanesulfonate (1847-58-1) was observed in female guinea pigs by guinea pigs maximization test (modified method of Buehler and Griffith). A 10% aqueous dilution of the cream shampoo was topically administered under occlusive patches in 0.5 ml doses to the shaved backs of 10 healthy female Hartley guinea pig. Three inductive patches were applied at weekly intervals. While challenge patches were applied 2 and 3 weeks after the last inductive patch. The sites were scored after 24 hour after each application. No erythema was observed after any inductive orchallenge patches. Therefore sodium 2-(dodecyloxy)-2oxoethanesulfonate was considered to be not sensitizing in female Hartley guinea pigs.

Thus based on the above predictions on Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate ( 40754-59-4) as well as its read across substances and applying weight of evidence, it can be concluded that Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate ( 40754-59-4)can be considered as not classified for skin sensitization effects.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation, Disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate ( 40754-59-4)can be considered as not classified for skin sensitization effects.