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EC number: 208-358-1 | CAS number: 524-38-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
LD50 was estimated to be 2201 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with 2-hydroxy-1H-isoindole-1,3(2H)-dione.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- 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:
- Data is predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.4
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of the test material: N-Hydroxyphthalimide
- IUPAC name: 2-hydroxy-1H-isoindole-1,3(2H)-dione
- Molecular formula: C8H5NO3
- Molecular Weight: 163.132 g/mole
- Substance type: Organic
- Smiles: c12c(C(=O)N(C1=O)O)cccc2 - Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data available
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- No data available
- Doses:
- 2201 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- No data available
- Statistics:
- No data available
- Preliminary study:
- No data available
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 2 201 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: 50 % mortality observed
- Mortality:
- No data available
- Clinical signs:
- other: No data available
- Gross pathology:
- No data available
- Other findings:
- No data available
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- LD50 was estimated to be 2201 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with 2-hydroxy-1H-isoindole-1,3(2H)-dione.
- Executive summary:
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-hydroxy-1H-isoindole-1,3(2H)-dione. The LD50 was estimated to be 2201 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with 2-hydroxy-1H-isoindole-1,3(2H)-dione.
Reference
The
prediction was based on dataset comprised from the following
descriptors: LD50
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 ("l"
and (
not "m")
)
)
and ("n"
and (
not "o")
)
)
and "p" )
and ("q"
and (
not "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 No alert found by DNA binding by
OECD
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Acylation OR Acylation >> Direct
Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl
Halide >> Acyl halide OR Michael addition OR Michael addition >> P450
Mediated Activation of Heterocyclic Ring Systems OR Michael addition >>
P450 Mediated Activation of Heterocyclic Ring Systems >> Furans OR
Michael addition >> P450 Mediated Activation of Heterocyclic Ring
Systems >> Thiophenes-Michael addition OR Michael addition >> P450
Mediated Activation to Quinones and Quinone-type Chemicals OR Michael
addition >> P450 Mediated Activation to Quinones and Quinone-type
Chemicals >> 5-alkoxyindoles OR Michael addition >> P450 Mediated
Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR
Michael addition >> P450 Mediated Activation to Quinones and
Quinone-type Chemicals >> Arenes OR SN1 OR SN1 >> Iminium Ion Formation
OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >>
Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic
azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >>
Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion
formation >> Primary (unsaturated) heterocyclic amine OR SN1 >>
Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium
Ion formation >> Tertiary (unsaturated) heterocyclic amine OR SN1 >>
Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium
Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> Direct
Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related
>> Epoxides OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated
Epoxidation >> Thiophenes-SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2
>> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as No alert found by Protein
binding by OASIS v1.4
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Acylation OR Acylation >>
Acylation involving an activated (glucuronidated) carboxamide group OR
Acylation >> Acylation involving an activated (glucuronidated)
carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation
involving an activated (glucuronidated) ester group OR Acylation >>
Acylation involving an activated (glucuronidated) ester group >>
Arenecarboxylic Acid Esters OR Acylation >> Acylation involving an
activated (glucuronidated) sulfonamide group OR Acylation >> Acylation
involving an activated (glucuronidated) sulfonamide group >>
Arenesulfonamides OR Acylation >> Direct acylation involving a leaving
group OR Acylation >> Direct acylation involving a leaving group >>
Anhydrides (sulphur analogues of anhydrides) OR Acylation >> Direct
acylation involving a leaving group >> Carbamates OR Acylation >>
Direct acylation involving a leaving group >> Carboxylic Acid Amides OR
Acylation >> Direct acylation involving a leaving group >>
N-Acylloxysuccinimides OR Acylation >> Direct acylation involving a
leaving group >> N-Haloacylamides OR Acylation >> Ester aminolysis OR
Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis
or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated
aryl esters OR Acylation >> Ester aminolysis or thiolysis >> Carbamates
OR AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >>
Michael addition to activated double bonds >> alpha,beta-Unsaturated
Carbonyls and Related Compounds OR AN2 >> Michael addition to activated
double bonds in heterocyclic ring systems OR AN2 >> Michael addition to
activated double bonds in heterocyclic ring systems >> Pyrazolone and
Pyrazolidine Derivatives OR AN2 >> Michael-type addition to quinoid
structures OR AN2 >> Michael-type addition to quinoid structures >>
Carboxylic Acid Amides OR AN2 >> Michael-type addition to quinoid
structures >> N-Substituted Aromatic Amines OR AN2 >> Michael-type
addition to quinoid structures >> Substituted Phenols OR AN2 >>
Nucleophilic addition at polarized N-functional double bond OR AN2 >>
Nucleophilic addition at polarized N-functional double bond >>
Arenesulfonamides OR AN2 >> Nucleophilic addition to pyridonimine
tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized)
OR AN2 >> Nucleophilic addition to pyridonimine tautomer of
aminopyridoindoles or aminopyridoimidazoles (hypothesized) >>
Heterocyclic Aromatic Amines OR AN2 >> Schiff base formation with
carbonyl compounds (AN2) OR AN2 >> Schiff base formation with carbonyl
compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives OR Michael
addition OR Michael addition >> Michael addition on conjugated systems
with electron withdrawing group OR Michael addition >> Michael addition
on conjugated systems with electron withdrawing group >>
alpha,beta-Carbonyl compounds with polarized double bonds OR
Nucleophilic addition OR Nucleophilic addition >> Addition to
carbon-hetero double bonds OR Nucleophilic addition >> Addition to
carbon-hetero double bonds >> Ketones OR Radical reactions OR Radical
reactions >> ROS generation and direct attack of hydroxyl radical to the
C8 position of nucleoside base OR Radical reactions >> ROS generation
and direct attack of hydroxyl radical to the C8 position of nucleoside
base >> Heterocyclic Aromatic Amines OR Schiff base formation OR Schiff
base formation >> Direct acting Schiff base formers OR Schiff base
formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and
1,3-Dicarbonyls OR Schiff base formation >> Schiff base on pyrazolones
and pyrazolidinones OR Schiff base formation >> Schiff base on
pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones OR SE
reaction (CYP450-activated heterocyclic amines) OR SE reaction
(CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium
cation to the C8 position of nucleoside base OR SE reaction
(CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium
cation to the C8 position of nucleoside base >> Heterocyclic Aromatic
Amines OR SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR
SN2 >> Nucleophilic substitution at sp3 carbon atom >> alpha-Activated
haloalkanes OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2
Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters
OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl
and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution
on activated aryl and heteroaryl compounds >> Activated aryl and
heteroaryl compounds OR SR reaction (peroxidase-activated heterocyclic
amines) OR SR reaction (peroxidase-activated heterocyclic amines) >>
Direct attack of arylnitrenium radical to the C8 position of nucleoside
base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct
attack of arylnitrenium radical to the C8 position of nucleoside base >>
Heterocyclic Aromatic Amines by Protein binding by OASIS v1.4
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 Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Non-Metals by Groups of elements
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Halogens by Groups of elements
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Group 14 - Carbon C AND Group 15
- Nitrogen N AND Group 16 - Oxygen O by Chemical elements
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Group 16 - Sulfur S by Chemical
elements
Domain
logical expression index: "p"
Similarity
boundary:Target:
ON1C(=O)c2ccccc2C1=O
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "q"
Referential
boundary: The
target chemical should be classified as Not known precedent reproductive
and developmental toxic potential by DART scheme v.1.0
Domain
logical expression index: "r"
Referential
boundary: The
target chemical should be classified as ARA inhibitors, Candesartan-like
chemicals (5c-3) OR ARA inhibitors, Candesartan-like chemicals (5c-3) >>
Candesartan-like ARA inhibitors OR Known precedent reproductive and
developmental toxic potential by DART scheme v.1.0
Domain
logical expression index: "s"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -1.22
Domain
logical expression index: "t"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 1.3
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 201 mg/kg bw
- Quality of whole database:
- Data is Klimisch 2 and from OECD QSAR toolbox
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Acute oral toxicity:
In different studies, 2-hydroxy-1H-isoindole-1,3(2H)-dione has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats for 2-hydroxy-1H-isoindole-1,3(2H)-dione along with the study available on structurally similar read across substance 2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione (CAs no 133-07-3) and phthalimide (CAS no 85-14-6). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-hydroxy-1H-isoindole-1,3(2H)-dione. The LD50 was estimated to be 2201 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with 2-hydroxy-1H-isoindole-1,3(2H)-dione.
In another experimental study conducted by Greene et al (Toxicology and Applied Pharmacology 51, 197-199 (1979)) on structurally similar read across substance 2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione (CAs no 133-07-3), Sprague-Dawley male rats were treated with 2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione in the concentration of 1000, 3000, 3500, 4000, 8000 and 12000 mg/kg orally by gavage and observed for 14 days. At 4000, 8000 and 12000 mg/kg, All animals died on day 0 and Day 1, except one animal at 4000 mg/kg which died on Day 3. Salivation, decreased activity, bloody nasal discharge, and ataxia at 3000 and 3500 mg/kg and, in addition, decreased respiration, in coordination, and gasping at 4000, 8000 and 12000 mg/kg With the exception of salivation and incoordination which disappeared within 24 hr, these signs persisted for several days. In addition, In lungs, liver and gastrointestinal tract toxicity was observed at all doses, the lungs were dark and mottled and the gastrointestinal tract was vascularized. The liver was pale or pale and mottled at 3500 and 3000 mg/kg, respectively, and dark or dark and mottled at 4000, 8000 and 12000 mg/kg. Therefore, LD50 was considered to be 4700 mg/kg bw when Sprague-Dawley male rats were treated with 2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione orally by gavage.
Also it is further supported experimental study given by Environmental Protection Agency, Washington, DC. Office of Toxic (OTS05336499, U.S. Environmental Protection Agency, April 20, 1998) on structurally similar read across substance 2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione (CAs no 133-07-3), Crl:CD(SD)BR male rats were treated with 2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione in the concentration of 3000, 5000 and 6000 for male and 1500, 3000 and 5000 mg/kg for female orally by gavage and observed for 14 days. At 5000 mg/kg bw, all male and 2 female rats died. At 3000 mg/kg bw, 2 male and 2 female rats died. At 6000 mg/kg 4 female rats died. At 1500 mg/kg bw, 1 female rats died. Ataxia and abnormal gait at 5000 mg/kg bw in male rats and ataxia, abnormal gait and tremors were observed at 3000 mg/kg bw in female rats. Therefore, LD50 was considered to be 4156 mg/kg bw for male and 2636 mg/kg bw when Crl:CD(SD)BR male rats were treated with 2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione orally by gavage.
It is further supported experimental data given by J check (2017) on structurally similar read across phthalimide (CAS no 85-14-6), Crj:CD (SD) male and female rats were treated with phthalimide in the concentration of 2000 mg/kg bw in 1 % Carboxymethylcellulose sodium orally to gauge the acute oral toxicity in single dose study. No mortality was observed in treated male and female rats at 2000 mg/kg bw. Similarly, No effects on general appearance and Body weight of treated male and female rats were observed at 2000 mg/kg bw. In addition, No gross pathological and histopathological changes were observed in treated male and female rats at 2000 mg/kg bw Therefore, LD50 was considered to be > 2000 mg/kg bw when rat were treated phthalimide orally by gavage.
In addition to above experimental data study given by OECD SIDS (2005) for similar read across, male and female rats were treated with phthalimide in the concentration of 501, 794, 1260, 2000, 3160, 5000, 7940, 10000 mg/kg bw as a 20% suspension in corn oil orally by gavage. One female died at 10000 mg/kg bw and No mortality was observed in treated male and female rats at 501, 794, 1260, 2000, 3160, 5000, 7940 mg/kg bw. Reduced appetite, reduced activity, and slight lethargy for two to three days were observed in surviving animals. No gross pathological changes were observed in viscera of treated male and female rats. Therefore, LD50 was considered to be > 10000 mg/kg bw when rat were treated phthalimide orally.
Thus based on the above predictions and studies on 2-hydroxy-1H-isoindole-1,3(2H)-dione and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus comparing this value with the criteria of CLP regulation, 2-hydroxy-1H-isoindole-1,3(2H)-dione can be not classified for acute oral toxicity.
Justification for classification or non-classification
Based on the above predictions and studies on 2-hydroxy-1H-isoindole-1,3(2H)-dione and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus comparing this value with the criteria of CLP regulation, 2-hydroxy-1H-isoindole-1,3(2H)-dione can be not classified for acute oral toxicity.
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