Registration Dossier

Skin Irritation:

The dermal irritation potential of4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was estimated to be not irritating to the skin of rabbits.

Based on the estimated results,4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate can be considered to be not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

The ocular irritation potential of4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results,4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate can be considered to be not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

Reference

Endpoint:

skin irritation: in vivo

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 OECD QSAR toolbox v3.3 and the QMRF report has been attached

Qualifier:

equivalent or similar to guideline

Guideline:

other: predicted data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Specific details on test material used for the study:

Name of test material (as cited in study report): disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate
- Molecular formula: C22H42O10S.2Na
- Molecular weight: 542.594 g/mol
- Smiles notation:[Na+].[Na+].C([C@@H](CC(=O)OCCOCCOCCOCCCCCCCCCCCC)S(=O)(=O)[O-])(=O)[O-]
-InChl (if other than submission substance): 1S/C22H42O10S.2Na/c1-2-3-4-5-6-7-8-9-10-11-12-29-13-14-30-15-16-31-17-18-32-21(23)19-20(22(24)25)33(26,27)28;;/h20H,2-19H2,1H3,(H,24,25)(H,26,27,28);;/q;2*+1/p-2
- Substance type: Organic
- Physical State: Liquid

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

500mg

Duration of treatment / exposure:

single treatment

Observation period:

72 hours

Number of animals:

3

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation was observed

Estimation method: Takes mode value from the 6 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 "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 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols 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 >> 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 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates 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 SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines 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 Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Anhydrides (sulphur analogues of anhydrides) OR 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 >> Conjugated systems with electron withdrawing groups 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 SN2 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 Alkali Earth AND Non-Metals by Groups of elements

Domain logical expression index: "m"

Referential boundary:The target chemical should be classified as Alkaline Earth OR Halogens OR Metalloids OR Metals OR Rare Earth OR Transition Metals by Groups of elements

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 14 - Carbon C AND Group 16 - Oxygen O AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "o"

Referential boundary:The target chemical should be classified as Group 15 - Nitrogen N OR Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Similarity boundary:Target: CCCCCCCCCCCCOCCOCCOCCOC(=O)CC(C(=O)O{-}.[Na]{+})S(=O)(=O)O{-}.[Na]{+}
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.27

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.166

Interpretation of results:

other: not irritating

Conclusions:

4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was estimated to be not irritating to the skin of rabbits.

Executive summary:

The dermal irritation potential of 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was estimated to be not irritating to the skin of rabbits.

Based on the estimated results,4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate can be considered to be not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

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 OECD QSAR toolbox v3.3 and the QMRF report has been attached

Qualifier:

equivalent or similar to guideline

Guideline:

other: predicted data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Specific details on test material used for the study:

Name of test material (as cited in study report): disodium 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate
- Molecular formula: C22H42O10S.2Na
- Molecular weight: 542.594 g/mol
- Smiles notation:[Na+].[Na+].C([C@@H](CC(=O)OCCOCCOCCOCCCCCCCCCCCC)S(=O)(=O)[O-])(=O)[O-]
-InChl (if other than submission substance): 1S/C22H42O10S.2Na/c1-2-3-4-5-6-7-8-9-10-11-12-29-13-14-30-15-16-31-17-18-32-21(23)19-20(22(24)25)33(26,27)28;;/h20H,2-19H2,1H3,(H,24,25)(H,26,27,28);;/q;2*+1/p-2
- Substance type: Organic
- Physical State: Liquid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

7 days

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

4

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation was observed

Estimation method: Takes 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(not "o")) ) and("p" and(not "q")) ) and("r" and(not "s")) ) and("t" and(not "u")) ) and("v" and(not "w")) ) and("x" and(not "y")) ) and("z" and(not "aa")) ) and("ab" and(not "ac")) ) and "ad") and "ae") and "af") and("ag" and "ah") )

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 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols 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 >> 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 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates 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 SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines 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 Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Anhydrides (sulphur analogues of anhydrides) OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR 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 >> Conjugated systems with electron withdrawing groups 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 SN2 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 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) >> 3-Alken-2-ones (MA) OR Highly reactive (GSH) >> Furamates (MA) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> Alkyl 2-alkenoates (MA) by Protein binding potency

Domain logical expression index: "p"

Referential boundary:The target chemical should be classified as Alkali Earth AND Non-Metals by Groups of elements

Domain logical expression index: "q"

Referential boundary:The target chemical should be classified as Alkaline Earth OR Halogens OR Metalloids OR Metals OR Rare Earth OR Transition Metals by Groups of elements

Domain logical expression index: "r"

Referential boundary:The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 14 - Carbon C AND Group 16 - Oxygen O AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "s"

Referential boundary:The target chemical should be classified as Group 15 - Nitrogen N OR Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "t"

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: "u"

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: "v"

Referential boundary:The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "w"

Referential boundary:The target chemical should be classified as alpha,beta-unsaturated aliphatic alkoxy group OR No alert found OR Oxolane by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "x"

Referential boundary:The target chemical should be classified as Inclusion rules not met by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "y"

Referential boundary:The target chemical should be classified as Organic sulphonic salts by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "z"

Referential boundary:The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "aa"

Referential boundary:The target chemical should be classified as Alpha-alkylcarboxylic acid derivatives (22c) OR Di-carboxylic acid derivatives (adipates) (22d) OR Di-substituted hydrocarbons (24b) OR Inorganic chemical OR Known precedent reproductive and developmental toxic potential OR Metal atoms were identified OR Not covered by current version of the decision tree OR Piperazine-, dioxane-, morpholine-, tetrahydrothiopyran-like derivatives and cyclohexanamine (17c) by DART scheme v.1.0

Domain logical expression index: "ab"

Referential boundary:The target chemical should be classified as Aliphatic acid [-C(=O)-OH] AND Aliphatic ether [C-O-C] AND -CH- [linear] AND -CH2- [linear] AND Ester [-C(=O)-O-C] AND Methyl [-CH3] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "ac"

Referential boundary:The target chemical should be classified as -C=CH [alkenyl hydrogen] OR Carbon with 4 single bonds & no hydrogens OR -CH - [cyclic] OR -CH2- [cyclic] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "ad"

Referential boundary:The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "ae"

Referential boundary:The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "af"

Referential boundary:The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (with extensions) ONLY

Domain logical expression index: "ag"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.96

Domain logical expression index: "ah"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.025

Interpretation of results:

other: not irritating

Conclusions:

4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results,4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate can be considered to be not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin Irritation:

In different studies,4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its structurally similar read across substance bis[2-(2-butoxyethoxy)ethyl] adipate [CAS: 141-13-7 ]and functionally similar read across substance Sodium formate[CAS : 141-53-7]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate. 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was estimated to be not irritating to the skin of rabbits.

This result is supported by the experimental study summarized in International Journal of Toxicology, 35(2_suppl), pp.41S-54S; 2016; for the functionallysimilar read across substance Sodium formate[CAS : 141-53-7]. The study was performed on 4 rabbits (3 male, 1 female). Sodium formate(in physiological saline) was applied to 4 abraded sites per rabbit (left, right and front, back) under an occlusive patch for 24 hours. The reactions were observed and scored at 72 hours after patch removal. Skin irritation was not observed in any of the rabbits after 72 hours of patch removal.

Hence, Sodium formate can be considered to be not irritating to skin.

The above results are further supported by the experimental study summarized in Robust summaries for bis[2-(2-butoxyethoxy)ethyl] adipate, submitted by PCA Services Inc, USA, 2011; for thestructurally similar read across substance bis[2-(2-butoxyethoxy)ethyl] adipate [CAS: 141-13-7].The study was conducted on6 New Zealand White rabbits according to EPA OTS 798.4470 (Acute Dermal Irritation) Guidelines.The hair of the mid-dorsal area of the trunk of each rabbit, between scapulae and pelvis, was shaved using an Oster small animal clipper with surgical head (#40). Care was taken to avoid abrasion of the skin during clipping. Prior to dose application, animals were placed into wooden restrainers. One (1) test site of approximately six (6) square centimeters was chosen on each animal. A single application of 0.5 ml of,bis[2-(2 -butoxyethoxy)ethyl] adipate was made to each site after which the area was covered with a two and one-half (2.5) centimeter square surgical gauze pad (Johnson & Johnson). This was held in place with three (3) inch Johnson & Johnson hypo-allergenic cloth tape, semi-occlusively. Animals were collared for the duration of the exposure to preclude access to the site. Wrappings and test article were removed after four (4) hours following application. Remaining test article was gently washed from the skin with water and paper towels. Each site was then individually examined and scored at 30 and 60 minutes following unwrapping for erythema and edema according to Draize. Observations continued at 24, 48 and 72 hours. Mean scores from the 24 and 72 hour reading were averaged to determine the primary irritation index. The animals did not exhibit any abnormal clinical signs for the duration of the study. The Primary Dermal Irritation Index (PDII) after 24 and 72 hours was 0.65.

Based on the PDII scores, bis[2-(2-butoxyethoxy)ethyl] adipate was assessed as minimal irritant to rabbit skin. Since the effects observed where completely reversible within 7 days of observation,bis[2-(2-butoxyethoxy)ethyl] adipate can be considered as not irritating to skin.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”

Eye Irritation:

In different studies,4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its structurally similar read across substance bis[2-(2-butoxyethoxy)ethyl] adipate [CAS: 141-13-7] and functionally similar read across substance Sodium formate[CAS : 141-53-7]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for4-oxo-2 -sulfonato-5,8,11,14-tetraoxahexacosan-1-oate. 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was estimated to be not irritating to the eyes of new Zealand White rabbits.

This result is supported by the experimental study summarized in International Journal of Toxicology, 35(2_suppl), pp.41S-54S; 2016; for the functionallysimilar read across substance Sodium formate [CAS : 141-53-7]. The study was performed on 6 New Zealand White rabbits (3 male, 3 female).Sodium formate (0.1 ml, powder) was instilled in the lower conjunctival sac of the left eye of the rabbits. The right eye remained untreated and served as control. Reactions were scored at 1, 24, 48 and 72 hours, and 7, 10, 14 and 17 days post-instillation. Moderate to severe conjunctival irritation was observed in all rabbits and conjunctival necrosis was observed in 4 of 6 rabbits. All reactions had cleared by 17 days.

Since the effects are fully reversible in 17 days, hence Sodium formate can be considered to be not irritating to eyes.

The above results are further supported by the experimental study summarized in Robust summaries for bis[2-(2-butoxyethoxy)ethyl] adipate, submitted by PCA Services Inc, USA, 2011; for thestructurally similar read across substance bis[2-(2-butoxyethoxy)ethyl] adipate [CAS: 141-13-7]. The study was conducted on6 New Zealand White rabbits according to EPAOTS 798.4500 (Acute Eye Irritation) guidelines. A dose of 0.1 mL (1/10 milliliter) of the test article was applied to one eye of 6 New Zealand White rabbits (3 male and 3 female) by gently pulling the lower lid away from the eyeball to form a cup into which the test article was dropped. The eyelids were then gently held together for one (1) second. The untreated eye served as control. The eyes remained unwashed. The Average Scores after 72 hours was 0.0

According to 40 CFR 798.4500 and under the conditions of this test, bis[2-(2-butoxyethoxy)ethyl] adipate elicited minimal irritation which was reversible within 72 hours (3 days). No fluorescein retention was recorded at any interval. Since the average scores were 0 after 72 hours and the effects were fully reversible in 72 hours, bis[2-(2 -butoxyethoxy)ethyl] adipate can be considered not irritating to eyes.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate was not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”

Available data for 4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate suggests that it is not likely to cause any irritation to eyes and skin.

4-oxo-2-sulfonato-5,8,11,14-tetraoxahexacosan-1-oate can be classified under the category “Not Classified” as per CLP regulation.