5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid

Endpoint summary

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:

key study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: predicted data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Species:

other: human reconstituted skin model (EpiDerm)

Type of coverage:

open

Preparation of test site:

other: not applicable

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

approx 25 mg

Duration of treatment / exposure:

60 minutes

Observation period:

incubation of 24 hours plus subsequent 18 ± 2 hours for post-incubation period

Number of animals:

not applicable

Details on study design:

three tissues were treated with the substance
- negative and positive controls (Sodium dodecylsulphate, CAS No. 151-21-3, solution in deionised H2O containing 5%) were run in parallel

Irritation / corrosion parameter:

other: other: cell viability

Remarks on result:

other: Basis: other: MTT reduction. Time point: 42 hours. Reversibility: other: not applicable. Remarks: not irritating. (migrated information)

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 "k" )  and "l" )  and ("m" and "n" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl OR Carboxylic acid OR Overlapping groups OR Pyrazolone OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Amide, aliphatic attach [-C(=O)N] OR Amino-carbonyl compound [NCC(=O)-C] OR Aromatic Carbon [C] OR Azomethine, aliphatic attach [-N=C] OR Carbonyl, aliphatic attach [-C(=O)-] OR Carbonyl, olefinic attach [-C(=O)-] 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: "d"

Referential boundary: The target chemical should be classified as Aromatic compound OR Carbonic acid derivative OR Carboxylic acid derivative OR Heterocyclic compound 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 OECD

Domain logical expression index: "f"

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 >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Extremely reactive (GSH) OR Extremely reactive (GSH) >> Maleimides (MA) OR Highly reactive (GSH) OR Highly reactive (GSH) >> Furamates (MA) by Protein binding potency

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 Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Amide, aliphatic attach [-C(=O)N] AND Amino-carbonyl compound [NCC(=O)-C] AND Aromatic Carbon [C] AND Azomethine, aliphatic attach [-N=C] AND Carbonyl, aliphatic attach [-C(=O)-] AND Carbonyl, olefinic attach [-C(=O)-] AND Hydrazine [>N-N<] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 6) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 2) ONLY

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.96

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= -1.31

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance Pyralozone T is estimated to be not irritating to human reconstituted skin model (EpiDerm).

Executive summary:

The skin irritation potential for Pyrazolone T is estimated using OECD QSAR toolbox version 3.3

The substance Pyralozone T is estimated to be not irritating to human reconstituted skin model (EpiDerm).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

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)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: predicted data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: der Lippischen Versuchstierzucht, Extertal, Germany
- Weight at study initiation: average 2.1 kg
- Housing: The animals were kept in individual cages
- Diet (e.g. ad libitum): animals received "mümmel z" (SSNIF, Soest, Germany) ad libitum.
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: 7 - 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18
- Humidity (%): 40
- Photoperiod (hrs dark / hrs light): 12h light- / 12h dark cycle

Vehicle:

unchanged (no vehicle)

Controls:

other: other eye acted as control

Amount / concentration applied:

100 µL

Duration of treatment / exposure:

8 days

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

6 male animals

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

5.2

Max. score:

110

Reversibility:

not specified

Remarks on result:

other: not irritating

Estimation method: Takes mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((((("a" or "b" or "c" or "d" )  and "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and "r" )  and "s" )  and ("t" and ( not "u") )  )  and "v" )  and "w" )  and ("x" and "y" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl OR Carboxylic acid OR Overlapping groups OR Pyrazolone OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Amide, aliphatic attach [-C(=O)N] OR Amino-carbonyl compound [NCC(=O)-C] OR Aromatic Carbon [C] OR Azomethine, aliphatic attach [-N=C] OR Carbonyl, aliphatic attach [-C(=O)-] OR Carbonyl, olefinic attach [-C(=O)-] 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: "d"

Referential boundary: The target chemical should be classified as Aromatic compound OR Carbonic acid derivative OR Carboxylic acid derivative OR Heterocyclic compound 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 Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "f"

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: "g"

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 11 - Trans.Metals Cu,Ag,Au OR Group 12 - Trans.Metals Zn,Cd,Hg OR Group 13 - Metals Al,Ga,In,Tl OR Group 14 - Metalloids Si,Ge OR Group 14 - Metals Sn,Pb OR Group 15 - Phosphorus P OR Group 17 - Halogens Cl OR Group 17 - Halogens F,Cl,Br,I,At OR Group 17 - Halogens I 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 9 - Trans.Metals Co,Rh,Ir by Chemical elements

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition OR Michael addition >> 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 Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-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 (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides by DNA binding by OECD

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures 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 AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines 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 carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related 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 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters 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: "l"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Extremely reactive (GSH) OR Extremely reactive (GSH) >> Maleimides (MA) OR Highly reactive (GSH) OR Highly reactive (GSH) >> Furamates (MA) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> 2-Vinylpyridine (MA) OR Moderately reactive (GSH) >> Alkyl 2-alkenoates (MA) OR Moderately reactive (GSH) >> Substituted 1-Alken-3-ones (MA) by Protein binding potency

Domain logical expression index: "n"

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: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aliphatic N-nitro group OR alpha,beta-unsaturated aliphatic alkoxy group OR Aromatic mono- and dialkylamine OR Heterocyclic Polycyclic Aromatic Hydrocarbons OR No alert found OR Primary aromatic amine, hydroxyl amine and its derived esters by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "r"

Similarity boundary:Target: OC(=O)C1CC(=O)N(c2ccc(S(O)(=O)=O)cc2)N=1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Butanedioic acid by OECD HPV Chemical Categories

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as days - weeks by Biodeg primary (Biowin 4) ONLY

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 5) ONLY

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.03

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.598

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance Pyrazolone T is estimated to be not irritating to eyes of New Zealand White rabbits.

Executive summary:

The eye irritation potential for Pyrazolone T is estimated using OECD QSAR toolbox version 3.3.

The substance Pyrazolone T is estimated to be not irritating to eyes of New Zealand White rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The skin irritation potential for Pyrazolone T is estimated using OECD QSAR toolbox version 3.3.The substance Pyralozone T is estimated to be not irritating to human reconstituted skin model (EpiDerm).

On the basis of available information for the target, the test substance can be considered as not irritating to the skin.

Eye irritation

The eye irritation potential for Pyrazolone T is estimated using OECD QSAR toolbox version 3.3.The substance Pyrazolone T is estimated to be not irritating to eyes of New Zealand White rabbits.

In other study by (S. D. GETTINGS et al., 1992) with similar substance (1934-21-0) was assayed in rabbit.Eye irritation test was conducted on 6 female and 6 male New Zealand White rabbits.30 μl of test chemical in aq. solution was administered into the right eye of rabbits and left eyes served as untreated controls. Ocular irritation was determined according to a modification of the Draize test. All animals were checked for viability twice daily. Ocular irritation was scored 24 h after each treatment and prior to the next instillation. On days 1, 3, 7, 14, and 21 the eyes were also evaluated 1 h after treatment. 24 h after each treatment. No significant signs of eye staining or particle depositions were observed. At ophthalmoscopic examinations, no ocular abnormities were noticed. Hence, tartrazine it is not expected to cause irritant effects following repeated treatment of eyes in a concentration of 3 % in aqueous solution.

In other study by (Mary Ann Liebert., 1992) with similar substance (86-92-0) was assayed in rabbits. Eye irritation test for Phenyl Methyl Pyrazolone was observed in three males and three females’ albino rabbits by the ocular irritation index. A volume of 0.1 ml of a 0.66% solution of PMP in propylene glycol was applied into the conjunctival sac of the right eye of each rabbit; the eyes were not rinsed. The left eye served as control. The eyes were examined for ocular lesions, using a cap lamp, after 24 h and on days 2, 3, 4, and 7; the eyes were also examined with a fluorescent lamp after injection of 2% sodium fluoresce in Solution. The ocular irritation index was 0.66/110 on day 1 and 0/110 on the remaining days. Phenyl Methyl Pyrazolone was non -irritating to the eyes of rabbits. Therefore Phenyl Methyl Pyrazolone was classified as non- irritant.

On the basis of available information for the target as well as read across substance and applying weight of evidence approach, the test substance can be considered as not irritating to the eye.

Justification for selection of skin irritation / corrosion endpoint:
The skin irritation potential for Pyrazolone T is estimated using OECD QSAR toolbox version 3.3.The substance Pyralozone T is estimated to be not
irritating to human reconstituted skin model (EpiDerm).

Justification for selection of eye irritation endpoint:
The eye irritation potential for Pyrazolone T is estimated using OECD QSAR toolbox version 3.3.The substance Pyrazolone T is estimated to be not
irritating to eyes of New Zealand White rabbits.

Justification for classification or non-classification

The substance Pyrazolone T is estimated not  to be irritating to both skin and eye.