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Description of key information

Skin irritation

The skin irritation potential for test chemical 1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) was estimated to be not irritating to skin of New Zealand White Rabbits.

Based on the estimated result, 1,3-thiazolidine-2,4 -dione (CAS No: 2295-31-0) can be considered to be not irritating to skin and can be classified under the category “Not classified” as per CLP regulation.

Eye irritation

The eye irritation potential for test chemical 1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) was estimated to be not irritating to eyes of New Zealand White Rabbits.

Based on the estimated result, 1,3-thiazolidine-2,4 -dione (CAS No: 2295-31-0) can be considered to be not irritating to eyes and can be classified under the category “Not classified” 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 Toolbox version 3.3 and the QMRF report has been attached
Qualifier:
according to
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): 2,4-Thiazolidinedione
- Molecular formula: C3H3NO2S
- Molecular weight: 117.1277 g/mol
- Substance type: organic
- Physical state: Solid
- Smiles notation: C1C(=O)NC(=O)S1
- InChl: 1S/C3H3NO2S/c5-2-1-7-3(6)4-2/h1H2,(H,4,5,6)
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
no data
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
6
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Skin irritating effects were not observed in treated animals.

Estimation method: Takes mode value from the 8 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

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 >> Thiazolidinediones by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Dicarbonyl compounds OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives 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 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation >> Acyl transfer via nucleophilic addition reaction OR Acylation >> Acyl transfer via nucleophilic addition reaction >> Isocyanates, Isothiocyanates  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 >> Anhydrides (sulphur analogues of anhydrides)  OR Acylation >> Direct acylation involving a leaving group >> Azlactones and unsaturated lactone derivatives  OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents  OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Conjugated systems with electron withdrawing groups  OR Michael Addition >> Quinoide type compounds OR Michael Addition >> Quinoide type compounds >> Quinone methide(s)/imines; Quinoide oxime structure; Nitroquinones, Naphthoquinone(s)/imines  OR No alert found OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  OR SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> alpha-Activated haloalkanes  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Similarity boundary:Target: O=C1CSC(=O)N1
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.91

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.16

Interpretation of results:
other: not irritating
Conclusions:
1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) was estimated to be not irritating to skin of New Zealand White Rabbits.
Executive summary:

The skin irritation potential for test chemical 1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) was estimated to be not irritating to skin of New Zealand White Rabbits.

Based on the estimated result, 1,3-thiazolidine-2,4 -dione (CAS No: 2295-31-0) can be considered to be not irritating to skin and can be classified under the category “Not classified” as per CLP regulation.

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)
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 Version 3.3 and the QMRF report has been attached.
Qualifier:
according to
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): 2,4-Thiazolidinedione
- Molecular formula: C3H3NO2S
- Molecular weight: 117.1277 g/mol
- Substance type: organic
- Physical state: Solid
- Smiles notation: C1C(=O)NC(=O)S1
- InChl: 1S/C3H3NO2S/c5-2-1-7-3(6)4-2/h1H2,(H,4,5,6)
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
no data
Duration of treatment / exposure:
8 d
Observation period (in vivo):
8 d
Duration of post- treatment incubation (in vitro):
no data
Number of animals or in vitro replicates:
no data
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 8 d
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Eye irritating effects were not observed in treated animals

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

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

Domain logical expression index: "a"

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 >> Thiazolidinediones by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives 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 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives 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 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation >> Direct Acylation Involving a Leaving group >> Acyl halides (including benzyl and carbamoyl deriv.) OR Acylation >> Direct Acylation Involving a Leaving group >> Anhydrides OR Acylation >> Direct Acylation Involving a Leaving group >> Azlactone OR Acylation >> Direct Acylation Involving a Leaving group >> Dialkyl carbamoylhalides OR Acylation >> Isocyanates and Related Chemicals OR Acylation >> Isocyanates and Related Chemicals >> Isocyanates OR Michael addition OR Michael addition >> Acid imides OR Michael addition >> Acid imides >> Acid imides-MA OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-imine OR No alert found OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halocarbonyls OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "j"

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: "k"

Referential boundary: The target chemical should be classified as Moderately reactive (GSH) OR Moderately reactive (GSH) >> 2-Chloroacetamides (SN2) OR Moderately reactive (GSH) >> 2-Vinyl carboxamides (MA) OR Moderately reactive (GSH) >> Substituted 1-Alken-3-ones (MA) by Protein binding potency

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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: "n"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

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"

Similarity boundary:Target: O=C1CSC(=O)N1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.651

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.531

Interpretation of results:
other: not irritating
Conclusions:
The test substance1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) is estimated to be not irritating to eye of Vienna White Rabbits  over a 8 days observation period .
Executive summary:

An eye irritation potential for test chemical 1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) is estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The test substance1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) is estimated to be not irritating to eye of Vienna White Rabbits  over a 8 days observation period . Based on the estimated result, test chemical 1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) can be considered to be not irritating to eye and can be classified under the category “Not classified” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Various studieshas been investigated for the test chemical1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and humans for target chemical1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) and its structurally similar read across substances1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0), Tetrahydrothiophene (CAS No: 110-01-0) and 2-Pyrrolidone (CAS No: 616-45-5).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data which are summarized as below;

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0). The test substance1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) is estimated to be not irritating to skin of New Zealand White Rabbits when applied dermally at concentration of 500mg for 72 hours observation period.

The above result was supported by three skin irritation studies reported by Cosmetic Ingredient Review (Journal Of The American College Of Toxicology Volume 7, Number 3, 1988) in rabbits and human subjects for structurally similar read across substance1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0) as follow;

The primary irritation was assessed according to the protocol outlined in Title 16 parts 1500.3 (c)(4) and 1500.41 of the Code of Federal Regulations for chemical 1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0).According to this protocol, the test substance (volume, 0.5 ml) was applied to both abraded and intact clipped skin of albino rabbits (a minimum of 6) via a square patch made of surgical gauze (Table 6). The patches remained intact for 24 h, after which any reactions were evaluated. Subsequent evaluations were made 48 h after the initial ones. .No known signs of irritation was observed after skin evaluation. HenceThe chemical1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0)was considered to be not irritating to both abraded and intact clipped skin of albino rabbits.

The next skin irritation study of 1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0) was conducted on the facial skin of 53 panelists .In this test, 0.10% of test chemical was applied to the facial skin of 53 panelists at a concentration of 100% over a period of 4 weeks (Table 10). Applications were made with closed patches according to the standard 48-h method by Fregert. The test chemical failed to induce any adverse skin reactions. Thus the chemical 1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0) was considered to be not irritating to the facial skin of 53 panelists.

In the third study, the cumulative skin irritation potential of 1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0) was evaluated in 10 subjects (9 females, 1 male) according to the procedures of Lanman”” and Phillips et al. The test substance was applied (no patch cover) to the paraspinal region of each subject. A total of 21 consecutive applications were made, and each remained for 23 h. Scoring for cumulative irritation was done 24 h after application of the test substance; reapplication at the original site was done immediately afterward. Since there was no evidence of cumulative irritation in any of the subjects during the study, the chemical 1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0) was considered to be not irritating to 10 subjects.

U.S. National Library of Medicine(HSDB, 2016) performed a patch test in albino rabbits for anotherstructurally similar read across substanceTetrahydrothiophene (CAS No: 110-01-0) according to FHSA. The substance did not produce visible destruction or irreversible alterations in the tissue at the site of contact. Hence the test chemical Tetrahydrothiophene (CAS No: 110-01-0) was considered to be not irritating to the skin of albino rabbits.

The above results were further supported by experimental data reported by U.S. Environmental Protection Agency Hazard Characterization Document(2014) on anotherstructurally similar read across substance2-Pyrrolidone (CAS No: 616-45-5) inthree New Zealand white rabbits.Each rabbits were exposed to 500 mg of undiluted test chemical for 4 hours exposure period and skin reactions wereobserved up to 72 hours. The test site was washed after exposure. Slight erythema was exhibited by one rabbit, which resolved after 24 hours and no corrosion was observed. Therefore thetest chemical2-Pyrrolidone (CAS No: 616-45-5)was considered to be not irritatingto the skin ofthree New Zealand white rabbits.

Thus on the basis of the available data for the target substance 1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) and its structurally similar read across substances1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0), Tetrahydrothiophene (CAS No: 110-01-0) and 2-Pyrrolidone (CAS No: 616-45-5),it can be concluded thatchemical 1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) is unable to cause skin irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation

In different studies,the test chemical1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) has been investigated forpotential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) and its structurally similar read across substances1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0), Tetrahydrothiophene (CAS No: 110-01-0).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data which are summarized as below;

The prediction modelOECD QSAR toolbox version 3.3 with logPow as the primary descriptor, estimated an eye irritation potential for test chemical 1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0). The test substance 1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) is estimated to be not irritating to eye of Vienna White Rabbits over a 8 days observation period.

 

The above result was supported by two ocular irritation studies reported by Cosmetic Ingredient Review (Journal Of The American College Of Toxicology Volume 7, Number 3, 1988) in rabbits for structurally similar read across substance1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0) as follow;

The first eye irritation study was assessed in albino rabbits according to the procedures outlined in Title 16 parts 1500.3(c)(4) and 1500.42 of the Code of Federal Regulations for chemical 1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0).In this test, one-tenth milliliter of the test substance was placed in one eye of each of 6 albino rabbits. The untreated eyes served as controls. Grading for keratitis, iritis, and conjunctival redness was performed 24, 48, and 72 h after application. No known positive eye reactions were noted after evaluation. Hence the testmaterial1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0)was considerd to be not irritatingto the eye of six albino rabbits.

The next Ocular irritation study was conducted in New Zealand white rabbits according to the modified procedures outlined in Title 16 parts 1500.3(c)(4) and 1500.42 of the Code of Federal Regulations for 1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0).In this study, 1% (w/v) solution of the test substance in distilled water (effective DMDM Hydantoin concentration, 0.55%) was applied in 0.1 ml volumes to one eye of each of 9 New Zealand white rabbits. The contralateral eye served as the control. Fifteen seconds after administration of the solution, the treated eyes of 3 rabbits were rinsed with 30 ml of tap water.Reactions in rinsed and unrinsed eyes were graded for irritation on days 1, 2, and 3 after administration of the test substance according to the method of Draize et al.Since there were no signs of irritation noted for either rinsed or unrinsed eyes, the test material1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0) was considered to be not irritating to the eye of New Zealand white rabbits.

MAK Value Documentation (2012) performed an eye irritation potential of Tetrahydrothiophene (CAS No: 110-01-0) in six albino rabbits. In this test, 0.1 ml (100 mg) tetrahydrothiophene was instilled into the conjunctival sac of one of both eyes and later ocular lesions were noted. The instillation caused pain and blepharospasms. Severe inflammation, chemosis and slightly deepened folds of the iris were observed during the first four hours. Twenty-four hours after the treatment, only mild inflammation of the conjunctiva was still visible. Since the ocular lesions were not persisted after 24 hours, the test material Tetrahydrothiophene (CAS No: 110-01-0) was considered to be not irritating to the eye of six albino rabbits.

The above results were further supported by an eye irritation study conducted byU.S. National Library of Medicine(HSDB, 2016) according to FHSA in albino rabbits for anotherstructurally similar read across substanceTetrahydrothiophene (CAS No: 110-01-0). The test chemical did not elicit any local inflammatory reaction. Hencethe test chemicalTetrahydrothiophene (CAS No: 110-01-0)was considered to be not irritatingto the eye of albino rabbits.

Thus on the basis of the available data for the target substance 1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) and its structurally similar read across substances1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0), Tetrahydrothiophene (CAS No: 110-01-0) and 2-Pyrrolidone (CAS No: 616-45-5),it can be concluded thatchemical 1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) is unable to cause eye irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0) and its structurally similar read across substances1,3-Dimethylol-5,5-dimethylhydantoin (CAS No: 6440-58-0), Tetrahydrothiophene (CAS No: 110-01-0) and 2-Pyrrolidone (CAS No: 616-45-5) were observed in various studies. The results obtained from these studies indicates that the test chemical 1,3-thiazolidine-2,4-dione (CAS No: 2295-31-0)is not likely to cause skin and eye irritation. Hence2,2,2-trichloroacetaldehyde (CAS No: 75-87-6) can be classified under the category “Not Classified” for skin and eye as per CLP.