N-potassium phthalimide

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

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.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): Potassium phthalimide
- Molecular formula (if other than submission substance): C8H5NO2.K
- Molecular weight (if other than submission substance): 185.223 g/mol
- Smiles notation (if other than submission substance): c12c(C(=O)[NH-]C1=O)cccc2.[K+]
- InChI: 1S/C8H5NO2.K/c10-7-5-3-1-2-4-6(5)8(11)9-7;/h1-4H,(H,9,10,11);/q;+1/p-1
- Substance type: Organic
- Physical state: solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Lepomis macrochirus

Test type:

static

Water media type:

freshwater

Total exposure duration:

96 h

Hardness:

No data

Test temperature:

26 deg.C

pH:

6.8

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:

96 h

Dose descriptor:

LC50

Effect conc.:

151.66 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Sublethal observations / clinical signs:

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Imides (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Imide by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Imide AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Amide, aromatic attach [-C(=O)N] AND Aromatic Carbon [C] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid derivative AND Cation AND Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 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 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 >> DNA Intercalators with Carboxamide Side Chain OR Radical 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 via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers 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 >> Nitroarenes with Other Active Groups OR SN2 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 >> 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 after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane 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: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.64

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.144

Validity criteria fulfilled:

not specified

Conclusions:

The Lethal concentration (LC50) value for Potassium phthalimide on Lepomis macrochirus in a 96 hrs. was estimated to be 151.66 mg/L in static freshwater system.

Executive summary:

The short-term toxicity of Potassium phthalimide (CAS no. 1074-82-4)to fish is predicted using QSAR toolbox version. 3.3.The prediction is based on the effects observed in a static freshwater system during a 96 hr exposure. The lethal concentration (LC50) for the substance is estimated to be 151.66 mg/L. Thus, based on lethal concentration value, it can be concluded that the test chemical Potassium phthalimide can be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP criteria.

Description of key information

The short-term toxicity of Potassium phthalimide (CAS no. 1074-82-4)to fish is predicted using QSAR toolbox version. 3.3.The prediction is based on the effects observed in a static freshwater system during a 96 hr exposure. The lethal concentration (LC50) for the substance is estimated to be 151.66 mg/L. Thus, based on lethal concentration value, it can be concluded that the test chemical Potassium phthalimide can be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP criteria.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

151.66 mg/L

Additional information

Four studies including Predicted data and experimental results for short term fish toxicity endpoint of the target chemical Potassium phthalimide (CAS no. 1074-82-4) with relevant read across chemical which is close to target chemical using log Kow as a primary descriptor were reviewed to summarize the following information:

 

First study indicate the 96 hrs aquatic toxicity was predicted to assess toxic effects of the test compound Potassium phthalimide (CAS no. 1074-82-4) using OECD QSAR toolbox ver.3.3;2017. The prediction was based on the effects of the test compound on fish species Lepomis macrochirus in a static fresh water system. The data suggests the median lethal concentration (LC50) for the test compound Potassium phthalimide (CAS no. 1074-82-4) was estimated to be 151.66 mg/l on the basis of mortality effect.

 Whereas another prediction using the EPI Suite ECOSAR version 1.10 (EPI Suite, 2017), the 96 hours LC50 was estimated to be 1818.541 mg/l on fish for target substance Potassium phthalimide (CAS no. 1074-82-4) with mortality effects.

 

Above both aquatic classification supported by experimental data (Spec.Sci.Rep.Fish.No.207, Fish Wildl.Serv., U.S.D.I., Washington, DC:157 p.; 1957) indicate in short term fish toxicity study the test substance Potassium phthalimide (Cas no. 1074-82-4) exposed to fish species Petromyzon marinus (Sea Lamprey) for 24 hrs. During experiment the 12.77 deg.C (55 Fahrenheit) test temp., 7.5 to 8.2 pH and 8.6 to 13.7 dissolved oxygen was maintained throughout the study. And test concentration used as 0.1, 1.0 and 5.0 mg/l. No observable effects including mortality was observed on test species Petromyzon marinus (Sea Lamprey) for 24 hrs.Thus NOEL (no observed effect level) was consider to be 5 mg/l for test substance Potassium phthalimide (Cas no. 1074-82-4).

 

Last study from experimental data source for read across chemical 1-(4,6-dimethoxypyrimidin-2-yl)-3-[2-dimethylcarbamoyl)phenylsulfamoyl]urea (Cas no. 213464-77-8) suggest the short term fish toxicity study on test species Lepomis macrochirus (Bluegill)of test substance1-(4,6-dimethoxypyrimidin-2-yl)-3-[2-dimethylcarbamoyl)phenylsulfamoyl]urea was determine for exposure period 96 hrs.In the experiment static condition maintained.

On the basis of mortality effect the lethal concentration (LC50) on fish Lepomis macrochirus (Bluegill) was observed to be >142 mg/l.

From all four studies the median lethal concentration (LC50) observed in the range of >142 to 1818.541 mg/l for 96 hrs and NOEC was 5 mg/l for 24 hrs.exposure period.

Thus based on the available results, it can be concluded that the test substance Potassium phthalimide (CAS no. 1074-82-4) can be considered as non toxic to fish and thus not consider for the aquatic classification as per the CLP criteria.