3-(1-(4-amino-3-methyl-5-sulphonatophenyl)-1-(4-amino-3-sulphonatophenyl)methylene)cyclohexa-1,4-dienesulphonic acid

Endpoint summary

Description of key information

The skin sensitization potential of 2-amino-5-[(4-amino-3-sulfonatophenyl)(3-sulfocyclohexa-2,5-dien-1-ylidene)methyl]-3-methylbenzenesulfonate was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. 2-amino-5-[(4-amino-3-sulfonatophenyl)(3-sulfocyclohexa-2,5-dien-1-ylidene)methyl]-3-methylbenzenesulfonate was predicted to be non sensitizing to the skin of female Hartley guinea pigs

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

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:

according to guideline

Guideline:

other: Estimated 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: Acid fuchsin
- IUPAC name: 2-amino-5-[(4-amino-3-sulfonatophenyl)(3-sulfocyclohexa-2,5-dien-1-ylidene)methyl]-3-methylbenzenesulfonate
- Molecular formula: C20H20N2O9S3
- Molecular weight: 585.5443 g/mole
- Smiles : C1(S(=O)(=O)O)=C\C(=C(\c2cc(S(=O)(=O)[O-])c(c(c2)C)N)c2cc(S(=O)(=O)[O-])c(cc2)N)C=CC1=N.[Na+].[Na+]
- Inchl: 1S/C20H19N3O9S3.2Na/c1-10-6-13(9-18(20(10)23)35(30,31)32)19(11-2-4-14(21)16(7-11)33(24,25)26)12-3-5-15(22)17(8-12)34(27,28)29 ;;/h2-9,21H,22-23H2,1H3,(H,24,25,26)(H,27,28,29)(H,30,31,32);;/q;2*+1/p-2/b19-11+,21-14?;;
- Substance type: Organic
- Physical state: Solid crystalline powder (Olive to dark olive-green)

Species:

guinea pig

Strain:

Hartley

Sex:

female

Details on test animals and environmental conditions:

no data available

Route:

epicutaneous, occlusive

Vehicle:

not specified

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

20

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Vehicle:

not specified

Concentration:

no data available

No. of animals per dose:

no data available

Details on study design:

no data available

Statistics:

no data available

Positive control results:

no data available

Other effects / acceptance of results:

no data available

Reading:

1st reading

Group:

test chemical

Dose level:

no data available

Clinical observations:

no data available

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

no data available

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkene OR Alkyl arenes OR Allyl OR Aniline OR Aryl OR Cycloalkene OR Dianilines OR Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkene OR Alkyl arenes OR Allyl OR Cycloalkene OR Dianilines OR Overlapping groups OR Sulfonic acid by Organic Functional groups (nested) 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 Aliphatic Nitrogen, one aromatic attach [-N] OR Alkenyl sufide [-S=C] OR Aromatic Carbon [C] OR Hydroxy, sulfur attach [-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Suflur {v+4} or {v+6} OR Sulfinic acid [-S(=O)OH] OR Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Amine OR Aromatic compound OR Primary amine OR Primary aromatic amine OR Sulfonic acid OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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 Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyridines by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group  3 - Lanthanoids OR Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 14 - Metalloids Si,Ge OR Group 15 - Phosphorus P OR Group 16 - Selennm Se OR Group 17 - Halogens Br OR Group 17 - Halogens Cl OR Group 17 - Halogens F,Cl,Br,I,At OR Group 2 - Alkaline Earth Be,Mg,Ca,Sr,Ba,Ra OR Group 4 - Trans.Metals Ti,Zr,Hf OR Group 5 - Trans.Metals V,Nb,Ta OR Group 6 - Trans.Metals Cr,Mo,W OR Group 7 - Trans.Metals Mn,Tc,Re OR Group 8 - Trans.Metals Fe,Ru,Os OR Group 9 - Trans.Metals Co,Rh,Ir by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as weeks - months by Biodeg ultimate (Biowin 3) ONLY

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "o"

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: "p"

Similarity boundary:Target: Cc1cc(C(=C2C=CCC(S(O)(=O)=O)=C2)c2ccc(N)c(S(O)(=O)=O)c2)cc(S(O)(=O)=O)c1N
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.38

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.28

Interpretation of results:

other: Negative

Conclusions:

2-amino-5-[(4-amino-3-sulfonatophenyl)(3-sulfocyclohexa-2,5-dien-1-ylidene)methyl]-3-methylbenzenesulfonate was predicted to be non sensitizing to the skin of female Hartley guinea pigs

Executive summary:

The skin sensitization potential of 2-amino-5-[(4-amino-3-sulfonatophenyl)(3-sulfocyclohexa-2,5-dien-1-ylidene)methyl]-3-methylbenzenesulfonate was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. 2-amino-5-[(4-amino-3-sulfonatophenyl)(3-sulfocyclohexa-2,5-dien-1-ylidene)methyl]-3-methylbenzenesulfonate was predicted to be non sensitizing to the skin of female Hartley guinea pigs

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studies have been investigated for assessing the dermal sensitization potential of 2-amino-5-[(4-amino-3-sulfonatophenyl)(3-sulfocyclohexa-2,5-dien-1-ylidene)methyl]-3 -methylbenzenesulfonate to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs along with predicted data for target chemical and its closely related read across substances, Aminoiminomethanesulphinic acid [CAS: 1758-73-2] and Methanesulfonic acid [CAS: 75-75-2]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The skin sensitization potential of 2-amino-5-[(4-amino-3-sulfonatophenyl)(3-sulfocyclohexa-2,5-dien-1-ylidene)methyl]-3-methylbenzenesulfonate was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. 2-amino-5-[(4-amino-3-sulfonatophenyl)(3-sulfocyclohexa-2,5-dien-1-ylidene)methyl]-3 -methylbenzenesulfonate was predicted to be non sensitizing to the skin of female Hartley guinea pigs.

This result is supported by the experimental study summarized in Hazardous Substances Data Bank (HSDB) for Methanesulfonic acid, U.S National Library of Medicine, 2010; for the closely related read across substance, Methanesulfonic acid [CAS: 75-75-2]. The irritation potential of methane sulphonic acid 70% at levels of undiluted, 50%, 25%, 10%, 5%, 2.5%, 1% and 0.5% was evaluated in two groups of four animals each prior to the sensitization study.The 50% concentration from the preliminary study was chosen for use at induction for the test group, since it caused no greater than mild to moderate primary irritation. Moreover, the 25% concentration was selected for challenge, because it caused no more than slight irritation.

20 Hartley guinea pigs (10/sex) were induced by 50% of methane sulphonic acid. On day 1, dermal application of 0.3 ml of test substance (treated group) or with the vehicle (control group) was performed on the left shoulder. On day 7, the same region received another topical application. On day 14, this same site was treated by a last topical application. All these applications lasted approximately 6 hours. On day 28, all the animals were challenged with 0.3 ml of the test substance at the concentration of 25% in their right flank. The challenge exposure lasted for 24 hours. Water served as vehicle control and 5guinea pigs/sex were used in the control group. The dermal reactions were observed and scored 24 hours after the challenge exposure.

20 guinea-pigs were induced by 50% of methane sulphonic acid 70% solution (i.e. 35% of methane sulphonic acid) and challenged by 25% of methane sulphonic acid 70% solution (i.e. 17.5% of methane sulphonic acid). None of the test animals responded with a skin grade that would have been suggestive of sensitization.

Hence, methane sulphonic acid can be considered to be not sensitizing to the skin of Hartley guinea pigs.

These results are further supported by the experimental study summarized in Methanesulfinic Acid, Aminoimino - SIDS Initial Assessment Report , United Nations Environmental Programme (UNEP),2005; for the closely related read across substance, Aminoiminomethanesulphinic acid [CAS: 1758-73-2]. Aminoiminomethanesulphinic acid was injected daily for 10 days intracutaneously into the hair-clipped skin of guinea pigs.The doses of the test com-pound injected were selected to produce no local reactions, and the place of injection was altered daily. After further 10 days without treatment the test compound was again injected intracutaneously on 2 subsequent days, and 24 and 48 hours later local reactions were registered. There were no reactions observed exceeding those of physiological saline which served as negative control.

Hence, it was considered that Aminoiminomethanesulphinic acid had no sensitizing effect on guinea pig skin under the conditions of the study.

Based on the available data for the target and read across substances and applying the weight of evidence approach, 2-amino-5-[(4-amino-3-sulfonatophenyl)(3-sulfocyclohexa-2,5-dien-1-ylidene)methyl]-3-methylbenzenesulfonate can be considered to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available data for 2-amino-5-[(4-amino-3-sulfonatophenyl)(3-sulfocyclohexa-2,5-dien-1-ylidene)methyl]-3-methylbenzenesulfonate suggests that it is not likely to cause any dermal sensitization to guinea pig skin.

2-amino-5-[(4-amino-3-sulfonatophenyl)(3-sulfocyclohexa-2,5-dien-1-ylidene)methyl]-3-methylbenzenesulfonate can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.