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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: as mentioned below
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.4 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-hydroxy-1H-isoindole-1,3(2H)-dione
- Molecular formula: C8 H5 N O3
- Molecular weight: 163.132 g/mol
- Smiles notation: c12c(C(=O)N(C1=O)O)cccc2
- InChI: 1S/C8H5NO3/c10-7-5-3-1-2-4-6(5)8(11)9(7)12/h1-4,12H
- Substance type: Organic
- Physical state: Solid
Test organisms (species):
Daphnia magna
Test type:
static
Water media type:
freshwater
Total exposure duration:
48 h
Test temperature:
21 ± 2 ºC
Dissolved oxygen:
6 mg/L
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
161.94 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 6 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 ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and ( not "p") )  )  and "q" )  and "r" )  and ("s" and "t" )  )

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 saturated heterocycles AND Hydroxamic acid AND Imide AND N-Hydroxylamine derivatives by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl AND Fused saturated heterocycles AND Hydroxamic acid 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 Hydroxy, nitrogen attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Oxygen, nitrogen attach [-O-] AND Oxygen-subtution at N on [-CO-N-CO-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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: "g"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> Miscellaneous Alkyl 2-halo alkenoates (SN2) OR 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: "h"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES by OASIS v.1.4

Domain logical expression index: "i"

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 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 by ROS formation OR Radical >> Radical mechanism by ROS formation >> Five-Membered Aromatic Nitroheterocycles OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR SN1 OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Conjugated Nitro Compounds OR SN2 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 OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom 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 by DNA alerts for AMES by OASIS v.1.4

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as alpha,beta-unsaturated carbonyls OR Aromatic N-acyl amine OR Hydrazine by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found OR Oxolane by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Biodegrades Fast by Biodeg probability (Biowin 1) ONLY

Domain logical expression index: "r"

Similarity boundary:Target: ON1C(=O)c2ccccc2C1=O
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.91

Validity criteria fulfilled:
not specified
Conclusions:
EC50 value for 2-hydroxy-1H-isoindole-1,3(2H)-dione(CAS: 524-38-9) was estimated to be 161.94 mg/l for Daphnia magna for 48 hrs duration. Thus based on this value it can be concluded that the substance was considered to be non-toxic to aquatic invertebrate 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 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for2-hydroxy-1H-isoindole-1,3(2H)-dione(CAS: 524-38-9). EC50 value was estimated to be 161.94 mg/l for Daphnia magna for 48 hrs duration. Thus based on this value it can be concluded that the substance was considered to be non-toxic to aquatic invertebrate and can be considered to be not classified as per the CLP regulations.

Description of key information

Short term toxicity to aquatic invertebrates

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for2-hydroxy-1H-isoindole-1,3(2H)-dione(CAS: 524-38-9). EC50 value was estimated to be 161.94 mg/l for Daphnia magna for 48 hrs duration.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates
Effect concentration:
161.94 mg/L

Additional information

Short term toxicity to aquatic invertebrates for2-hydroxy-1H-isoindole-1,3(2H)-dione(CAS: 524-38-9) was summaries with two predicted data and two experimental studies of two read across substances are as follows:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for2-hydroxy-1H-isoindole-1,3(2H)-dione(CAS: 524-38-9). EC50 value was estimated to be 161.94 mg/l for Daphnia magna for 48 hrs duration.

In another prediction done by EPI suite, ECOSAR version 1.1, the LC 50 value for short term toxicity to aquatic invertebrates was predicted. The LC50 value for short term toxicity to aquatic invertebrates was predicted to be 3010.80 mg/l for 2-hydroxy-1H-isoindole-1,3(2H)-dione in 48 hrs. Based on this value it can be concluded that the substance is considered to be not toxic to aquatic environment and can be considered to be not classified as per the criteria mentioned in CLP regulation.

 

Short term toxicity to aquatic invertebrates was performed for read across 1H-isoindole-1,3(2H)-dione (85-41-6) [J-check, 2010] which was 60-70 % structurally similar with target. The test was performed in Daphnia magna for 48 hrs in static fresh water system. The concentration ranges from 3.7, 6.7, 12.0, 21.6, 38.9, 70.0 mg/L along with control. Number of organisms per vessel was 20 per concentration i.e 5 per vessel. 16 hours light and 8 hour dark was the applied photoperiod. On the basis of experiment, the EC 50 value for 1H-isoindole-1,3(2H)-dione (85-41-6) was determined to be 20.8 mg/l. Based on the value the substance was considered to be toxic to aquatic invertebrates but as it was readily biodegradable, hence the 1H-isoindole-1,3(2H)-dione was considered to be not classified based on the CLP regulations.

 

For another read across N-Methylphthalimide (550-44-7) [HPVIS Robust summary, 2002] which was 80-90 % structurally similar with target , the test 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 EC50 value for 24 hrs of N-Methylphthalimide (550-44-7) was determined to be 112 mg/l.

Based on the above predicted data and studies of read across chemicals it can be considered that all the above studies supported the target classification, so based on the results it was considered that all weight of evidences supported the classifications and2-hydroxy-1H-isoindole-1,3(2H)-dione(CAS: 524-38-9) was considered to be non-toxic to aquatic invertebrates andcan be concluded to be not-classified as per the CLP regulations.