m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid

Endpoint summary

Description of key information

Skin Irritation:

The dermal irritation potential of 3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor.

3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid was estimated to be irritating to the skin of New Zealand White rabbits.

Based on the estimated result; 3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid can be considered irritating to skin and can be classified under the category “Category 2” as per CLP.

Eye Irritation:

The ocular irritation potential of 3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor.

3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid was estimated to be irritating to the eyes of rabbits.

Based on the estimated results, 3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid can be considered irritating to eyes and can be classified under the category “Category 2” as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

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 toolobox v3.4 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 v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid
- IUPAC name: 3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid
- Molecular formula: C10H11N3O3S
- Molecular weight: 253.281 g/mole
- Smiles: O=S(=O)(O)c1cccc(N2N=C(CC2=N)C)c1
- Inchl: 1S/C10H11N3O3S/c1-7-5-10(11)13(12-7)8-3-2-4-9(6-8)17(14,15)16/h2-4,6,11H,5H2,1H3,(H,14,15,16)
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

0.5ml

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Signs of irritation observed

Estimation method: Takes mode value from the 5 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 ("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 ( not "ae") )  )  and ("af" and ( not "ag") )  )  and ("ah" and ( not "ai") )  )  and ("aj" and ( not "ak") )  )  and ("al" and ( not "am") )  )  and ("an" and ( not "ao") )  )  and ("ap" and ( not "aq") )  )  and ("ar" and ( not "as") )  )  and ("at" and ( not "au") )  )  and ("av" and ( not "aw") )  )  and ("ax" and "ay" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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 Aromatic Carbon [C] OR Azomethine, aliphatic attach [-N=C] OR Hydrazine [>N-N<] OR Hydroxy, sulfur attach [-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen, two or tree olefinic attach [>N-] 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: "c"

Referential boundary: The target chemical should be classified as Amidine OR Aryl OR Overlapping groups OR Sulfonic acid OR Unsaturated heterocyclic amine OR Unsaturated heterocyclic fragment by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Amidine OR Aryl OR Sulfonic acid OR Unsaturated heterocyclic amine OR Unsaturated heterocyclic fragment by Organic Functional groups ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinone methides OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR Radical 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 (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines 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 and Naphthalenediimide Derivatives OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after 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 and Naphthalenediimide 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.1.4

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 of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans 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 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo 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 Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aldehydes OR Aromatic amines OR Esters of organic sulfonic or sulfuric esters OR Ketones OR Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Transition Metals by Groups of elements

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Rare Earth by Groups of elements

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Metalloids by Groups of elements

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Halogens by Groups of elements

Domain logical expression index: "t"

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: "u"

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

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Group C Vapour Pressure < 0.0001 Pa OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as (N/A) by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Amidine AND Aryl AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Alcohol OR Alkene by Organic Functional groups

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as Amidine AND Aryl AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "ag"

Referential boundary: The target chemical should be classified as Alkyl by Organic Functional groups

Domain logical expression index: "ah"

Referential boundary: The target chemical should be classified as Amidine AND Aryl AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "ai"

Referential boundary: The target chemical should be classified as Benzimidazole OR Benzothiazole/ Benzoisothiazole by Organic Functional groups

Domain logical expression index: "aj"

Referential boundary: The target chemical should be classified as Amidine AND Aryl AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "ak"

Referential boundary: The target chemical should be classified as Cycloalkene by Organic Functional groups

Domain logical expression index: "al"

Referential boundary: The target chemical should be classified as Amidine AND Aryl AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "am"

Referential boundary: The target chemical should be classified as Fused saturated heterocycles by Organic Functional groups

Domain logical expression index: "an"

Referential boundary: The target chemical should be classified as Amidine AND Aryl AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "ao"

Referential boundary: The target chemical should be classified as Naphtalene by Organic Functional groups

Domain logical expression index: "ap"

Referential boundary: The target chemical should be classified as Amidine AND Aryl AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "aq"

Referential boundary: The target chemical should be classified as Thioalcohol OR Triazine by Organic Functional groups

Domain logical expression index: "ar"

Referential boundary: The target chemical should be classified as Amidine AND Aryl AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "as"

Referential boundary: The target chemical should be classified as Surfactants - Anionic by Organic Functional groups

Domain logical expression index: "at"

Referential boundary: The target chemical should be classified as Amidine AND Aryl AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "au"

Referential boundary: The target chemical should be classified as Sulfonamide by Organic Functional groups

Domain logical expression index: "av"

Referential boundary: The target chemical should be classified as Amidine AND Aryl AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "aw"

Referential boundary: The target chemical should be classified as No functional group found by Organic Functional groups

Domain logical expression index: "ax"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.41

Domain logical expression index: "ay"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.64

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid was estimated to be irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of 3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor.

3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid was estimated to be irritating to the skin of New Zealand White rabbits.

Based on the estimated result; 3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid can be considered irritating to skin and can be classified under the category “Category 2” as per CLP.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

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 v3.4 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 v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid
- IUPAC name: 3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid
- Molecular formula: C10H11N3O3S
- Molecular weight: 253.281 g/mole
- Smiles: O=S(=O)(O)c1cccc(N2N=C(CC2=N)C)c1
- Inchl: 1S/C10H11N3O3S/c1-7-5-10(11)13(12-7)8-3-2-4-9(6-8)17(14,15)16/h2-4,6,11H,5H2,1H3,(H,14,15,16)
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

50 mg

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3

Details on study design:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

signs of irritation observed

Estimation method: Takes mode value from the 5 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 ("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 "u" )  and ("v" and ( not "w") )  )  and ("x" and ( not "y") )  )  and ("z" and ( not "aa") )  )  and ("ab" and ( not "ac") )  )  and ("ad" and ( not "ae") )  )  and ("af" and ( not "ag") )  )  and ("ah" and ( not "ai") )  )  and ("aj" and ( not "ak") )  )  and ("al" and ( not "am") )  )  and ("an" and ( not "ao") )  )  and ("ap" and ( not "aq") )  )  and ("ar" and ( not "as") )  )  and ("at" and ( not "au") )  )  and "av" )  and ("aw" and ( not "ax") )  )  and ("ay" and "az" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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 Aromatic Carbon [C] OR Azomethine, aliphatic attach [-N=C] OR Hydrazine [>N-N<] OR Hydroxy, sulfur attach [-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen, two or tree olefinic attach [>N-] 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: "c"

Referential boundary: The target chemical should be classified as Amidine OR Aryl OR Overlapping groups OR Sulfonic acid OR Unsaturated heterocyclic amine OR Unsaturated heterocyclic fragment by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Amidine OR Aryl OR Sulfonic acid OR Unsaturated heterocyclic amine OR Unsaturated heterocyclic fragment by Organic Functional groups ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Aldehydes OR Aromatic amines OR Epoxides(=oxiranes) OR Esters of organic sulfonic or sulfuric esters OR Ketones OR Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "g"

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: "h"

Referential boundary: The target chemical should be classified as Organic sulphonic salts OR Substituted indoles OR Subststituted pyrazoles OR Thiazoles and thiazolidines by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Metalloids by Groups of elements

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Rare Earth by Groups of elements

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Transition Metals by Groups of elements

Domain logical expression index: "r"

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: "s"

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

Domain logical expression index: "t"

Similarity boundary:Target: CC1CC(=N)N(c2cccc(S(O)(=O)=O)c2)N=1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "u"

Similarity boundary:Target: CC1CC(=N)N(c2cccc(S(O)(=O)=O)c2)N=1
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Amineptine (Hepatotoxicity) Alert OR Aromatic hydrocarbons (Liver enzyme induction) Rank C by Repeated dose (HESS)

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Group C Vapour Pressure < 0.0001 Pa OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ag"

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

Domain logical expression index: "ah"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ai"

Referential boundary: The target chemical should be classified as (N/A) by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "aj"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "ak"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles >> Heterocyclic Aromatic Amines OR Radical mechanism OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "al"

Referential boundary: The target chemical should be classified as Not classified by Oncologic Primary Classification

Domain logical expression index: "am"

Referential boundary: The target chemical should be classified as Aromatic Amine Type Compounds by Oncologic Primary Classification

Domain logical expression index: "an"

Referential boundary: The target chemical should be classified as Hydrazine by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "ao"

Referential boundary: The target chemical should be classified as alpha,beta-unsaturated aliphatic alkoxy group by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "ap"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All Melting Point > 200 C AND Group CNS Melting Point > 200 C AND Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "aq"

Referential boundary: The target chemical should be classified as Group C Aqueous Solubility < 0.0005 g/L by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ar"

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: "as"

Referential boundary: The target chemical should be classified as Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "at"

Referential boundary: The target chemical should be classified as Aromatic-H AND -CH2-  [cyclic] AND Methyl  [-CH3] AND Sulfonic acid / salt -> aromatic attach by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "au"

Referential boundary: The target chemical should be classified as Aliphatic ether  [C-O-C] OR Aromatic-CH by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "av"

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

Domain logical expression index: "aw"

Referential boundary: The target chemical should be classified as Aromatic-H AND Benzene AND -CH2-  [cyclic] AND Methyl  [-CH3] AND Sulfonic acid / salt -> aromatic attach by Bioaccumulation - metabolism alerts

Domain logical expression index: "ax"

Referential boundary: The target chemical should be classified as N-Alkane (linear) ... < C22 by Bioaccumulation - metabolism alerts

Domain logical expression index: "ay"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.18

Domain logical expression index: "az"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.614

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid was estimated to be irritating to the eyes of rabbits.

Executive summary:

The ocular irritation potential of 3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor.

3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid was estimated to be irritating to the eyes of rabbits.

Based on the estimated results, 3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid can be considered irritating to eyes and can be classified under the category “Category 2” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

In different studies,3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acidhas 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 substances, 4­Aminobenzenesulfonic acid[CAS: 121-57-3] and p-toluenesulphonic acid[CAS: 104-15-4].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 v3.4 with log kow as the primary descriptor, the skin irritation potential was estimated for3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid.3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acidwas estimated to be irritating to the skin of New Zealand White rabbits.  

This is supported by the experimental study summarized in GESTIS Substance Database (Information System in Hazardous Substance of the Berufsgenossenscheftn), 2016; for the structurally similar read across substance, 4­Aminobenzenesulfonic acid [CAS: 121-57 -3]. 500mg of test sample was applied on rabbit skin and the rabbits were observed for signs of irritation till 24 hours.Since the rabbits produced slight irritation reactions within 24 hours, 4-Aminobenzenesulfonic acid (CAS No: 121­57­3) was considered as irritating on rabbit skin.

The above results are supported by the experimental study summarized in U.S. Environmental Protection Agency; High Production Volume (HPV) Challenge; p-Toluenesulfonic acid (p-TSA), 2017; for the structurally similar read across substance, p-toluenesulphonic acid[CAS: 104-15-4]. The study was performed as per OECD 404 Guidelines. 500 mg wetted with 0.1 ml 0.9% saline was applied to an area of 6.25sqcm of skin of New Zealand White rabbit under semi-occlusive conditions for 4 hours. The treated sites were washed with water after the exposure period. The test sites were observed and scored according to Draize method 30-60 minutes, 24, 48 and 72 hours, and 7 days after exposure for 4 hours exposure only.

The average erythema and edema scores (24-72 hours) were 3.7 and 2 respectively. Dry, fissured skin, eschar formation, brown discolouration; scar formation and open wound after 7 days were some effects observed in rabbits. These effects were not reversible within 7 days. Hence, 4-methyl benzenesulphonic acid was considered to be corrosive to rabbit skin.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,2-methyl-4-nitroanilinewas not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Category 2”.

 

Eye Irritation:

In different studies,3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acidhas 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 substances, , 4­Aminobenzenesulfonic acid[CAS: 121-57-3] and p-toluenesulphonic acid[CAS: 104-15-4].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 v3.4 with log kow as the primary descriptor, the eye irritation potential was estimated for3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid.3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acidwas estimated to be irritating to the eyes of rabbits.

This is supported by the experimental study summarized in US Environmental Protection Agency Office of Pollution Prevention and Toxics (OPPT), 2013; for the structurally similar read across substance, p-toluenesulphonic acid[CAS: 104-15-4].The study was performed as per OECD 405 Guidelines.

Undiluted 4-methyl benzenesulphonic acid was instilled in the eyes of 9 rabbits for 5,10 or 30 seconds (3 animals for each duration). The rabbits were observed till 14 days for signs of irritation. The ocular reactions were scored with maximum score being 110.The overall irritation scores were 83.6, 110,110 for the 5,10 and 30 second exposures respectively. The effects observed were not fully reversible within 14 days.

Based on the scores and observations, 4-methyl benzenesulphonic acid can be considered to be corrosive to rabbit eyes.

 These results are further supported by the experimental study summarized in Chemosphere, Vol. 28, No. 12, pp. 2203.2236, 1994; for the structurally similar read across substance, 4­Aminobenzenesulfonic acid [CAS: 121-57-3].100 mg of the test chemical was instilled into the eyes of rabbits and effects were observed for 24 hours. Moderate irritation effects were observed after 24 hours of instillation of the test chemical. Therefore, sulphanilic acid was considered to be moderately irritating to eyes.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acidwas irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Category 2”.

Justification for classification or non-classification

Available data for 3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid indicates that it is likely to cause irritation or corrosion to skin and eyes.

Hence, 3-(5-imino-3-methyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-1-sulfonic acid can be classified under the category “Category 2” as per CLP regulation.