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Short-term toxicity to aquatic invertebrates

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Reference
Endpoint:
short-term toxicity to aquatic invertebrates
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:
The supporting QMRF report has been attached
Qualifier:
according to guideline
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3 with log kow as the primary discriptors.
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)
Analytical monitoring:
not specified
Vehicle:
not specified
Test organisms (species):
Daphnia magna
Test type:
static
Water media type:
freshwater
Total exposure duration:
48 h
Hardness:
No data
Test temperature:
21 deg.C
pH:
7.9-8.1
Dissolved oxygen:
No data
Salinity:
No data
Conductivity:
No data
Nominal and measured concentrations:
No data
Details on test conditions:
No data
Reference substance (positive control):
not specified
Key result
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
173.69 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
other: Intoxication

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones 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-covalent interaction >> DNA intercalation >> Quinones 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 >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes 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) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 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 reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives 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 >> Polynitroarenes 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, 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 >> 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 >> Haloalkanes Containing Heteroatom 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 High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "g"

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: "h"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 17 - Halogens Br 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: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.892

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.992

Validity criteria fulfilled:
not specified
Conclusions:
The short term toxicity on Daphnia magna (aquatic invertebrates) was predicted for 1,3-thiazolidine-2,4-dione i.e 2,4-Thiazolidinedione using OECD QSAR toolbox version 3.3 and EC50 value was estimated to be 173.69 mg/l on Daphnia magna for 48 hrs duration considering Intoxication effects. Based on the value, 1,3-thiazolidine-2,4-dione i.e 2,4-Thiazolidinedione (Cas no. 2295-31-0) was considered to be non toxic to Daphnia magna (aquatic invertebrates), hence it can be considered to be not classified as per the CLP regulations.
Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic invertebrates was predicted for 1,3-thiazolidine-2,4-dione i.e 2,4-Thiazolidinedione (Cas no. 2295-31-0). Effect concentration i.e EC50 value was estimated to be 173.69mg/l for Daphnia magna for 48 hrs duration. Based on the effect value, 1,3-thiazolidine-2,4-dione i.e 2,4-Thiazolidinedione (Cas no. 2295-31-0) was likely to be non toxic to aquatic invertebrates, hence it can be considered to be not classified as per the CLP classification criteria for aquatic environment.

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic invertebrates was predicted for 1,3-thiazolidine-2,4-dione i.e 2,4-Thiazolidinedione (Cas no. 2295-31-0). Effect concentration i.e EC50 value was estimated to be 173.69 mg/l for Daphnia magna for 48 hrs duration. Based on the effect value, 1,3-thiazolidine-2,4-dione i.e 2,4-Thiazolidinedione (Cas no. 2295-31-0) was likely to be non toxic to aquatic invertebrates, hence it can be considered to be not classified as per the CLP classification criteria for aquatic environment.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates
Effect concentration:
173.69 mg/L

Additional information

Four studies including predicted data from validated tools and experimental data from peer reviewed journal also from authorative database for short term aquatic invertebrate’s endpoint of test chemical 1,3-thiazolidine-2,4-dione i.e 2,4-Thiazolidinedione (Cas no. 2295-31-0) with relevant read across which is structurally similar to target were summarised as follows:

 

First data from prediction using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, which indicate the short term toxicity on aquatic invertebrates was predicted for 1,3-thiazolidine-2,4-dione i.e 2,4-Thiazolidinedione (Cas no. 2295-31-0). Effect concentration i.e EC50 value was estimated to be 173.69 mg/l for Daphnia magna for 48 hrs duration.

Similarly prediction by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program suggest the LC 50 value for short term toxicity to aquatic invertebrates was predicted. On the basis of EPI suite, ECOSAR version 1.1, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 5083.027 mg/l for 1,3-thiazolidine-2,4-dione i.e 2,4-Thiazolidinedione in 48 hrs.

Above both predicted results of target assist by experimental result of read across chemical 2methyl 6,8-dideoxy-6-[(1-methyl-4-propyl-L-prolyl)amino]-1-thio-D-erythro-alpha-D-galacto-octopyranoside i.e Lincomycin (Cas no. 154-21-2) which suggest From peer reviewed journal- Ecotoxicology (2010) 19:662–669 an acute toxicity test was mentioned which indicate the acute lethal toxicity of Lincomycin (Cas no. 154-21-2) on freshwater invertebrate Daphnia magna for exposure period 48 hrs. Culture and maintenance of D. magna was performed at 20 ± 1 deg.C in 7-liter glass jars containing moderately hard water. White fluorescent light (12.1 lmol/m2/s) was provided to Daphnia during the culture and maintenance with 16:8 h light: dark photoperiod. Daphnia were fed with YCT (1:1:1 mixture of Yeast: Ceropyl: Tetramin) and algae (Selenastrum capricornutum). Three pH conditions of 7.4, 8.3 and 9.2 were chosen for experiment. And Data analysis has done by modified US EPA Probit analysis, the Spearman–Karber method, or the trimmed Spearman–Karber method. Thus based on the pH effect the Effective concentration to 50% (EC50) on test organism Daphnia magna was observed to be >500 mg/l.

One another read across 1-(4,6-dimethoxypyrimidin-2-yl)-3-(3-ethylsulfonyl-2-pyridylsulfonyl)urea (Cas no. 122931-48-0) from authorative database i.e ECOTOX database indicate Short term toxicity to aquatic invertebrates was performed in Daphnia magna (Water Flea) for 48 hrs with <24 hrs age. Test in fresh water media with static condition. During the experiment, the EC 50 value for 1-(4,6-dimethoxypyrimidin-2-yl)-3-(3-ethylsulfonyl-2-pyridylsulfonyl)urea i.e Rimsulfuron (Cas no.122931-48-0) was determined to be 360 mg/l on the basis of intoxication.

Thus based on the all available effect concentrations which is in the range of 173.69 mg/l to 5083.027 mg/l of target and read across chemicals come to the conclusion that test substance 1,3-thiazolidine-2,4-dione i.e 2,4-Thiazolidinedione (Cas no. 2295-31-0) was likely to be non toxic to aquatic invertebrates as it not exceed the classification criteria, hence it can be considered to be not classified as per the CLP regulation.