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Description of key information

The skin sensitization potential of Thiazolidine-2,4-dione (2295-31-0) was estimated by SSS (QSAR) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Thiazolidine-2,4-dione(2295-31-0) was predicted to be non-sensitizing to the skin of female guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
Data is from OECD QSAR toolbox version.3.3 and QMRF report has been attached.
Qualifier:
according to guideline
Guideline:
other: Predicted data
Principles of method if other than guideline:
Prediction is done using OECD QSAR Toolbox version 3.3 with logKow as the primary descriptor.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Specific details on test material used for the study:
- Name of test material (as cited in study report): Thiazolidine-2,4-dione
- Molecular formula (if other than submission substance): C3H3NO2S
- Molecular weight (if other than submission substance): 117.126 g/mol
- Substance type: Organic
- Physical state: solid
- Purity: no data
- Impurities (identity and concentrations): no data
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
No data
No. of animals per dose:
Test group: 20Challenge control group: 5Positive control group: 5DNBC Challenge control group: 3
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
no data
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no irritation was observed
Remarks on result:
no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 6 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 ( not "q") )  )  and "r" )  and "s" )  and ("t" and "u" )  )

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) >> 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 >> 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 >> 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 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 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 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 Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams 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) >> Substituted 1-Alken-3-ones (MA) by Protein binding potency

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 No alert found by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group 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 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 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding alerts for skin sensitization by OASIS v1.3

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 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: "q"

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,Cl,Br,I,At OR Group 17 - Halogens I by Chemical elements

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Similarity boundary:Target: O=C1CSC(=O)N1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.852

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.662

Interpretation of results:
not sensitising
Conclusions:
Thiazolidine-2,4-dione was estimated to be not sensitizing to the skin of hartley female guines pig..
Executive summary:

The skin sensitization potential of Thiazolidine-2,4-dione was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Thiazolidine-2,4-dione was estimated to be not sensitizing to the skin of hartley female guinea pig.

Based on the estimated results, Thiazolidine-2,4-dione can be considered not sensitizing to skin and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In different studies, Thiazolidine-2,4-dione (2295-31-0) has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig for target chemical Thiazolidine-2,4-dione (2295-31-0) and its structurally similar read across substancesε-caprolactam (105-60-2). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of Thiazolidine-2,4-dione (2295-31-0) was estimated by SSS (QSAR) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. Thiazolidine-2,4-dione (2295-31-0) was predicted to be non-sensitizing to the skin of female guinea pig.

 

Supported by experimental study conducted byNational Technical Reports library (FAS DIVISION, Accession number: OTS0514817, 1987)to evaluate theskin sensitizing potential of read acrossε-caprolactam (105-60-2).Ten guinea were taken and on the left and right sides of each animal, an area of 25 cm2 was shaved. In induction after 4hrs the left side was cleaned and then it was painted with 50% solution of ε-caprolactam. The brushing was repeated three times, the painting was done each day (5 times per week, a total of 10 brushings. After a period of 14 days, during which time the skin effect on left side was disappeared, both side were shaved again. After 4hrs the right side, which had not been previously treated, was brushed one time crosswise with 50 %.Control test was carried out on three guinea pigs which had not been previously treated. The skin reaction was observed after 12 hrs of brushing. No sensitization could cause on the skin of guinea pigs by repeated application of ε-caprolactam in a 50 % solution in ether. ε-caprolactam is not a skin sensitizer.

It is further supported by experimental study conducted byNational Technical Reports library (FAS DIVISION, Accession number: OTS0514817, 1987)to evaluate theskin sensitizing potential of read acrossε-caprolactam (105-60-2).For the skin sensitization test ten guinea pig were injected intracutaneuosly in the skin of the back of the just above the buttock with 0.1 ml of 1% solution ofε-caprolactam in pure sodium chloride. After a delay of 13 days testing was undertaken by the crosswise brushing of the skin of the nape of the neck with 50% aqueous solution. After a further 12 days the same area was rubbed once crosswise 80% solution of ε-caprolactam. None of the guinea pig produced an inflammatory skin reaction by testing either at injection site or on the test area, hence can be concluded that theε-caprolactam is not a skin sensitizer.

Also supported by experimental study conducted byNational Technical Reports library (NTRL), (Springborn Laboratories, Accession number: OTS0529427, 1991)to evaluate theskin sensitizing potential of read acrossε-caprolactam (105-60-2).Ten guinea were taken and on the left and right sides of each animal, an area of 25 cm2 was shaved.

For the topical irritation screen, 4 concentrations (10, 25, 50 and 75% w/v in water, 4 animals/conc.) ofε-Caprolactam were applied to the clipped skin of each animal under occlusive conditions. Approximately 24 hours after dosing, patches were removed from each animal and the test sites wiped with gauze moistened with distilled water. Approximately 21 hours later, the test sites were shaved (if necessary) and three hours thereafter, the test sites were graded for irritation according to the Dermal Irritation Grading System. The grading was repeated approximately 24 hours later (48 hour scores).

For the intra-dermal irritation screen, 4 concentrations (0.1, 1.0, 3.0 and 5.0% w/v in water, 4 animals/conc.) ofε-Caprolactam were injected intradermally (0.1 ml/injection) to each animal. Approximately 24 and 48 hours later, the test sites were graded for irritation according to the Dermal Irritation Grading System as described for topical application:0 - No reaction± - Slight patchy erythema1 - Slight but confluent or moderate patchy erythema2 - Moderate confluent erythema3- Severe erythema with or without edema.The results indicated that a test article concentration of 3.0 % w/v would be appropriate for the intradermal induction since it was the highest dose that did not produce excessive ulceration of the test sites. A 75% w/v concentration ofε-Caprolactam was chosen for topical induction and challenge due to the minimal response noted at 24 hours post-dose and the complete resolution of the responses by 48 hour. Following challenge withε-Caprolactam in the maximisation test, dermal responses in the test group consisted of grade ± reactions (13/20) and grade 1 reactions (7/20). Slight edema were also observed at 7/20 test sites at the 24 hours interval. By 48 hours, a grade 1 reaction was noted in 1/20 test animals. Dermal responses in control group animals consisted of a grade 1 reaction (with slight edema) in 1/5 animals at 24 hours and of grade + to 0 reaction at all other control sites during the scoring intervals. The skin effects in the control group animals after challenge treatment are an indication of an irritation reaction to the test concentration used.

 

In conclusion, the use of the data for determining based on the concurrent reaction in the control animals and the decrease in the reaction after 24 to 48 hours,ε-Caprolactam is not considered to be a contact sensitizer under the test conditions chosen.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Thus, comparing the above annotations with the criteria of CLP regulation, Thiazolidine-2,4-dione (2295-31-0) can be considered as not classified for skin sensitization.