N-potassium phthalimide

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

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: as mentioned below

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: potassium 1,3-dioxo-1,3-dihydroisoindol-2-ide
- Molecular formula: C8 H5 N O2.K
- Molecular weight: 185.223 g/mol
- Smiles notation: c12c(C(=O)[NH-]C1=O)cccc2.[K+]
- InChl: 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

Vehicle:

no

Test organisms (species):

Daphnia magna

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

265 mg/L as CaCO3

Test temperature:

20 - 21 Dec C

pH:

7.50 - 7.98

Dissolved oxygen:

7.36 - 8.63 mg/L

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

161 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

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" 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" )  and ("o" and "p" )  )

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 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 >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups 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 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 >> 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 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline 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: "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 Michael addition OR Michael addition >> Acid imides OR Michael addition >> Acid imides >> Acid imides-MA 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 by Protein binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S OR Group 17 - Halogens Br OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "m"

Similarity boundary:Target: O=C1c2ccccc2C(=O)N{-}1.K{+}
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Similarity boundary:Target: O=C1c2ccccc2C(=O)N{-}1.K{+}
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.37

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.74

Validity criteria fulfilled:

not specified

Conclusions:

The short term toxicity on aquatic invertebrates was predicted for potassium 1,3-dioxo-1,3-dihydroisoindol-2-ide (CAS no 1074-82-4). EC50 value was estimated to be161.00mg/L on the basis of mobility for Daphnia magna for 48 hrs duration.As the 1,3-dioxo-1,3-dihydroisoindol-2-ide (CAS no 1074-82-4) was considered being non hazardous to aquatic invertebrates and 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 five closest read across substances, the short term toxicity on aquatic invertebrates was predicted forpotassium 1,3-dioxo-1,3-dihydroisoindol-2-ide (CAS no 1074-82-4). EC50 value was estimated to be161.00mg/L on the basis of mobility for Daphnia magna for 48 hrs duration.As the 1,3-dioxo-1,3-dihydroisoindol-2-ide (CAS no 1074-82-4) was considered being non hazardous to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.

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 five closest read across substances, the short term toxicity on aquatic invertebrates was predicted forpotassium 1,3-dioxo-1,3-dihydroisoindol-2-ide (CAS no 1074-82-4). EC50 value was estimated to be161.00mg/L on the basis of mobility for Daphnia magna for 48 hrs duration.As the 1,3-dioxo-1,3-dihydroisoindol-2-ide (CAS no 1074-82-4) was considered being non hazardous to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

161 mg/L

Additional information

Short term toxicity to aquatic invertebrates for potassium 1,3-dioxo-1,3-dihydroisoindol-2-ide (CAS no 1074-82-4) was summarised with two estimated data for target and two experimental study with read across substances N-Methylphthalimide (550-44-7) which has 60-70 % structural similarity with target and N,N’–ethylenebis[N–acetylacetamide] (10543-57-4) which has functionally similar.

 Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for potassium 1,3-dioxo-1,3-dihydroisoindol-2-ide (CAS no 1074-82-4). EC50 value was estimated to be 161.00mg/L on the basis of mobility for Daphnia magna for 48 hrs duration. As the 1,3-dioxo-1,3-dihydroisoindol-2-ide (CAS no 1074-82-4) was considered being non hazardous to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.

Prediction using EPI suite, ECOSAR version 1.1, 2017, based on the effects observed in 48 hr exposure. The lethal concentration (LC50) for the 1, 3-dioxo-1, 3-dihydroisoindol-2-ide (CAS no 1074-82-4) was estimated to be 1232.557 mg/l. Hence, 1, 3-dioxo-1, 3-dihydroisoindol-2-ide (CAS no 1074-82-4) was considered being non hazardous to aquatic invertebrates and can be considered to be not classified as per the CLP regulations. 

 

A study on read across chemical N-Methylphthalimide (550-44-7) which has 60-70 % structural similarity with target (201-14220 B, Robust summary, 30 December 2002), short term toxicity to aquatic invertebrates was performed in Daphnia magna for 24 hrs in static test condition. Nominal and measured test concentrations were used, in which the nominal concentration were used for test. The culture vessels were incubated in a temperature controlled room at 20 + 1ºC, under an 8-hour dark and 16-hour light photoperiod. The light intensity at the water surface was 400 to 800 lux. Daphnia in stock culture were fed with green alga and solution of yeast. At test initiation, dissolved oxygen, temperature, pH, and conductivity ranged from 8.3 to 9.1 mg/L, 19.5 to 20.7 ᵒC, 6.7 to 7.9 units, and 342 to 348 μS/cm respectively. At test termination, dissolved oxygen, temperature, and pH ranged from 8.3 to 9.1 mg/L, 19.5 to 20.7 ºC, and 7.0 to 7.7 units, respectively. General observations on behavior were made at test initiation, and at 30 minutes and 24 hours of exposure. Based on experimental result, the EC 50 value for 24 hrs of N-Methylphthalimide (550-44-7) was determined to be 112 mg/l. On the basis of result, the N-Methylphthalimide (550-44-7) was considered to be non- toxic to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.

 Another study on N,N’–ethylenebis[N–acetylacetamide] (10543-57-4)toxicity to aquatic invertebrates was performed in daphnia magna for 24 and 48 hrs. The EC 50 value for Daphnia magna was determined to be >500 and >800 mg/l for N,N’–ethylenebis[N–acetylacetamide] (10543-57-4).Based on the value the N,N’–ethylenebis[N–acetylacetamide](10543-57-4) was considered to be non-toxic to aquatic invertebrates and can be considered to be non-classified as per the CLP regulations.

 On the basis of predicted results for toxicity to aquatic invertebrates from target and study from read across all weight of evidences has supported the classification hence it can be considered that 1,3-dioxo-1,3-dihydroisoindol-2-ide(CAS no 1074-82-4)was likely to be non-toxic to aquatic invertebrates at environmentally relevant concentrations and can be considered to be not classified as per the criteria of CLP regulation.