N-hydroxyphthalimide

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

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:

OECD Guideline 201 (Alga, Growth Inhibition Test)

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.4 with logKow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- IUPAC name: 2-hydroxy-1H-isoindole-1,3(2H)-dione
- Molecular formula: C8H5NO3
- Molecular weight: 163.132 g/mol
- Smiles notation: c12c(C(=O)N(C1=O)O)cccc2
- InChl: 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

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

109.156 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

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" )  )

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 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 Non binder, impaired OH or NH2 group OR Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0495

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.54

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for 2-hydroxy-1H-isoindole-1,3(2H)-dione on Pseudokirchneriella subcapitata in a 72 hour study was estimated to be 109.15 mg/L on the basis of effects on growth rate.

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 algae and cyanobacteria was predicted for target substance 2-hydroxy-1H-isoindole-1,3(2H)-dione

 (CAS no. 524 -38 -9). EC50 value was estimated to be 109.15 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance 2-hydroxy-1H-isoindole-1,3(2H)-dione is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

 

Description of key information

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 algae and cyanobacteria was predicted for target substance 2-hydroxy-1H-isoindole-1,3(2H)-dione

 (CAS no. 524 -38 -9). EC50 value was estimated to be 109.15 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance 2-hydroxy-1H-isoindole-1,3(2H)-dione is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

 

Key value for chemical safety assessment

EC50 for freshwater algae:

109.15 mg/L

Additional information

Various predicted data for the target chemical 2-hydroxy-1H-isoindole-1,3(2H)-dione (CAS No. 524-38-9) and weight of evidence study for its read across substance were reviewed to summarize the following information:

Short term toxicity on aquatic algae and cyanobacteria of target chemical 2-hydroxy-1H-isoindole-1,3(2H)-dione(CAS No. 524-38-9) is predicted using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances (2017).EC50 value was estimated to be 109.15 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance 2-hydroxy-1H-isoindole-1,3(2H)-dione is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

 

In another prediction done using the EPI Suite ECOSAR version 1.10 (EPI Suite, 2017), the short term toxicity on green algae was predicted for test substance2-hydroxy-1H-isoindole-1,3(2H)-dione(CAS No. 524-38-9).On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 1101.824 mg/l for green algae for 96 hr duration. Based on this value, it can be concluded that the test chemical 2 -hydroxy-1H-isoindole-1,3(2H)-dione can be considered as non-toxic to green algae at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

 

In a weight of evidence study from authoritative database (J-CHECK, 2016) of the read across chemicalPhthalimide(CAS no. 85-41-6),short term toxicity to algae study was carried out for 72 hrs for evaluating the effects of the test compound Phthalimide on green algae in a static fresh water system. On the basis of effect on growth rate of the test organism green algae, the 72 hr EC50 and NOEC value was determined to be > 150 and 1.1 mg/l and on the basis of areas under the growth curves, the 72 hr EC50 and NOEC value was determined to be 62 and 6.5 mg/l, respectively. Thus, based on the EC50 value (> 150 mg/l), it can be concluded that the substance Phthalimide can be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP criteria.

 

For the same read across chemical Phthalimide(CAS no. 85-41-6),short term toxicity to Selenastrum capricornutum study was carried out for 72 hrs (OECD SIDS, 2005). The study was performed according to OECD Guideline 201 (Alga, Growth Inhibition Test). The study was based on the effects of the read across compound Phthalimide on Selenastrum capricornutum in a static fresh water system at an average temperature of 22.1°C. Test chemical conc. used for the study were 0, 10.6, 19.1, 34.3, 61.7, 111.1 and 200.0 mg/l, respectively. 300 mL net triangle conical glass flask was used as a test vessel. The flasks were incubated in a shaking water bath at 22.1 degrees C with continuous illumination at 4000 - 5000 lux. Based on the effect on growth rate of the test organism Selenastrum capricornutum, the 72 hrs ErC50 and NOEC value was determined to be 161 and 10.7 mg/l, respectively. Thus, based on EC50 value, it can be concluded that the substance Phthalimide can be considered as non-toxic to aquatic organisms and thus cannot be classifiedas hazardous as per the CLP criteria.

 

In an another weight of evidence study for read across chemical N-(Cyclohexylthio)phthalimide (CAS no. 17796-82-6) (HSDB and High Production Volume (HPV) Challenge Program; 2016), short term toxicity to Selenastrum capricornutum (green algae) study was carried out for 96 hrs. The study was based on the effects of the read across compound N-(Cyclohexylthio)phthalimide on Selenastrum capricornutum (green algae) in a static fresh water system. The test algae were obtained from the US EPA Environmental Research Laboratory in Corvallis, Oregon. Test chemical conc. used for the study were 0, 6, 10, 32, 56 and 100 mg/l, respectively. Initial cell density of algae was 2 × 104cells/ml. All tests were carried out in triplicates. Statistical analysis involved converting each test concentration to a logarithm, and the corresponding percentage decrease of in vivo chlorophyll a or cell numbers was converted to a probit. The EC50 and 95% confidence limits were then calculated by linear regression. The toxicity of the test substance to algae was similar throughout the 96 hr exposure. There was no significant difference between growth of the control and solvent control cultures after 96 hr of exposure by either measured parameter. Based on effect on biomass and growth of the test organism Selenastrum capricornutum (green algae), the 96 hr EC50 value was determined to be 21 mg/l and on the basis of chlorophyll measurement, the 96 hr EC50 value was determined to be 22 mg/l and NOEC value was 6 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance N-(Cyclohexylthio)phthalimide can be considered as toxic to aquatic organisms and thus can be classified as aquatic chronic category 3. Since the chemical is readily biodegradable in nature, chemical N-(Cyclohexylthio)phthalimide can be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP criteria.

 

Thus, based on the overall reported results for target chemical2-hydroxy-1H-isoindole-1,3(2H)-dione(OECD QSAR toolbox version 3.4 and EPI suite, 2017) and for its read across substance (from authoritative database J-CHECK, HSDB andsecondary sourceHigh Production Volume (HPV) Challenge Program; 2016), it can be concluded that the test substance2-hydroxy-1H-isoindole-1,3(2H)-dionecan be considered asnon-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.