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

Endpoint summary

Description of key information

Acute Oral Toxicity: 

In Acute oral toxicity ,LD50 value was predicted based on OECD QSAR toolbox for target substance m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) was estimated to be 2337.2 mg/kg bw,and for different studies available on the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (93-00-5) was considered to be 5000 mg/kg bw and for Pyrazolone T (118-47-8) was considered to be >22000 mg/kg bw in rat and mouse. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity: 

m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) has very low vapor pressure (2.58E-008 Pa.).So the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore the acute inhalation toxicity end point was considered for waiver.

Acute Dermal Toxicity:

In Acute dermal toxicity, LD50 value was predicted based on OECD QSAR toolbox for target substance m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) was estimated to be 2907.22 mg/kg bw,and for different studies available on structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (93-00-5) was considered to be >2000 mg/kg bw and for 4-amino benzenesulphonic acid (121-57-3)was considered to be >2000 mg/kg bw. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) cannot be classified for acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 predicted using OECD QSAR toolbox version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.4,2018

GLP compliance:

not specified

Test type:

other: estimated data

Limit test:

no

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:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data available

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

No data available

Doses:

2337.2 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 337.2 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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 ( not "l") )  )  and "m" )  and "n" )  and "o" )  and "p" )  and "q" )  and ("r" and "s" )  )

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 >> Nucleophilic addition reaction with cycloisomerization OR AN2 >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives 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 >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR Non-covalent interaction >> DNA intercalation >> Quinolone Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives 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 and Naphthalenediimide Derivatives OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines 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 nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine 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 of Heterocyclic Ring Systems >> Thiophenes-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 >> 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 OR SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines >> Ethenyl Pyridines OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) >> Heterocyclic Aromatic Amines OR Michael addition OR Michael addition >> Michael addition on polarised Alkenes OR Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  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 >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes 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 by OASIS v1.4

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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 ONLY

Domain logical expression index: "o"

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: "p"

Similarity boundary:Target: CC1CC(=N)N(c2cccc(S(O)(=O)=O)c2)N=1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.4

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.0124

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was estimated to be 2337.2 mg/kg bw,when male and female wistar rats were orally exposed with m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) via gavage.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor,the acute oral toxicity was estimated for m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5).The LD50 was estimated to be 2337.2 mg/kg bw,when male and female wistar rats were orally exposed with m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) via gavage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 337.2 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.4

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Quality of whole database:

Waiver

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 predicted using OECD QSAR toolbox version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.4,2018

GLP compliance:

not specified

Test type:

other: estimated data

Limit test:

no

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

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

No data available

Duration of exposure:

24 hours

Doses:

2907.22 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 907.22 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% Mortality was observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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 ( not "l") )  )  and "m" )  and "n" )  and "o" )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and "w" )  )

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 >> 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 >> 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 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 to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines >> Ethenyl Pyridines OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) >> Heterocyclic Aromatic Amines OR Michael addition OR Michael addition >> Michael addition on polarised Alkenes OR Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR Radical reactions OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical reactions >> 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 by OASIS v1.4

Domain logical expression index: "m"

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: "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 Bioavailable by Lipinski Rule Oasis ONLY

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 Halogens 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 Metalloids by Groups of elements

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Acidic [90,100] AND Basic [0,10) by Ionization at pH = 7.4

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as No pKa value by Ionization at pH = 7.4

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= -6.2

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.755

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was estimated to be 2907.22 mg/kg bw,when male and female new Zealand white rabbits were occlusively exposed with m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) by dermal application for 24 hours.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5).The LD50 was estimated to be 2907.22 mg/kg bw,when male and female new Zealand white rabbits were occlusively exposed with m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) by dermal application for 24 hours. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 907.22 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.4

Additional information

Acute Oral Toxicity: 

In different studies, m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5)  has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) along with the study available on the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (93-00-5) and Pyrazolone T (118-47-8). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor,the acute oral toxicity was estimated for m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5).The LD50 was estimated to be 2337.2 mg/kg bw,when male and female wistar rats were orally exposed with m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) via gavage.

The above study was further supported by Sustainability Support Services (Europe) AB (study number: 19166,2017) for the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5). The acute oral toxicity profile of 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5)in Sprague Dawley rats.1% aqueous Tween 80 was used as vehicle. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional three female animals were treated with the higher dose of  2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing.Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. Hence,The lethal concentration (LD50) valuefor acute oral toxicity testwas considered to be 5000mg/kg bw,when female Sprague Dawley rats were treated with 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5)orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

This is further supported by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) and RTECS (RTECS (registry of toxic effect of chemical substance database), 2017) for the structurally similar read across substance Pyrazolone T (118-47-8).Acute oral toxicity test was conducted on rat to evaluate the lethargic concentration of chemical Pyrazolone T. The lethal concentration was considered to be >22000 mg/kg in acute oral toxicity test of chemical Pyrazolone T exposed to rat by oral route.

The above experimental study was further supported by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) and RTECS (RTECS (registry of toxic effect of chemical substance database), 2017) for the structurally similar read across substance Pyrazolone T (118-47-8).Acute oral toxicity test was conducted on mouse to evaluate the lethargic concentration of chemical Pyrazolone T.The lethal concentration was considered to be >22000 mg/kg in acute oral toxicity test of chemical Pyrazolone T exposed to mouse by oral route.

Thus, based on the above studies on m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) and it’s structurally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity: 

m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) has very low vapor pressure (2.58E-008 Pa.).So the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore the acute inhalation toxicity end point was considered for waiver.

Acute Dermal Toxicity:

In different studies, m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5)has been investigated for acute dermal toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) along with the study available on structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) and4-amino benzenesulphonic acid (121-57-3). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5).The LD50 was estimated to be 2907.22 mg/kg bw,when male and female new Zealand white rabbits were occlusively exposed with m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) by dermal application for 24 hours. 

The above study was further supported by Sustainability Support Services (Europe) AB (study number: 19167,2017) for the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5).The acute dermal toxicity profile of 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5)in Sprague Dawley rats.The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days.Gross pathological examination did not reveal any abnormalities attributable to the treatment. Hence, The LD50 value was considered to be >2000 mg/kg bw,when male and female Sprague Dawley rats were semiocclusively treated with 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Also these results are further supported by INVENTORY MULTI-TIERED ASSESSMENT AND PRIORITISATION (IMAP) – NICNAS (HUMAN HEALTH TIER II ASSESSMENT FOR Sulfanilic acid and its sodium salt, INVENTORY MULTI-TIERED ASSESSMENT AND PRIORITISATION (IMAP) – NICNAS,2012) for the structurally similar read across substance4-amino benzenesulphonic acid (121-57-3).In acute dermal toxicity study,male and female Sprague Dawley rats were treated with Sulfanilic acid(121-57-3)in the concentration of 2000 mg/kg bw by dermal application. No mortality was observed in treated rats at dose 2000 mg/kg bw.Erythema, associated with dryness, was noted on the treatment site of two females on day 2 and of all females between day 3 and day 5.Therefore, LD50 value was considered to be >2000 mg/kg bw,when rats were treated with Sulfanilic acid(121-57-3)by dermal application as per OECD Guideline 402 (Acute Dermal Toxicity).

Thus, based on the above studies on m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) and it’s structurally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above experimental studies and prediction on m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) and it’s structurally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid (68083-38-5) cannot be classified for acute oral and dermal toxicity. For Acute inhalation toxicity wavier was added so, not possible to classify.