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EC number: 208-096-8 | CAS number: 509-34-2
- 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
Repeated
dose toxicity: oral
Since
no compound related adverse effects on rats are observed, the no
observed adverse effect level (NOAEL) relating to repeated dose for the
given test material
3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one is
estimated to be 742.11 mg/kg/day via oral route of administration.
Repeated dose toxicity: inhalation
A short-term toxicity study does not need to be conducted because
exposure of humans via inhalation in production and/or use is not likely
as based on the provided thorough and rigorous exposure assessment.
Repeated
dose toxicity: dermal
The
acute toxicity value for substance
3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (as
provided in section 7.2.3) is >2000 mg/kg body weight. The substance was
also found to be not irritating to skin. Also, given the use of the
chemical as dye compound; repeated exposure by the dermal route is
unlikely. Thus, it is expected that substance
3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one shall
not exhibit 28 day repeated dose toxicity by the dermal route. In
addition, there is no dermal absorption data as well as no data
available that suggests that substance
3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one shall
exhibit repeated dose toxicity by the dermal route. Hence this end point
was considered for waiver.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose 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 by OECD QSAR Toolbox version 3.3. The supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: as mentioned below
- Principles of method if other than guideline:
- Data is predicted by OECD QSAR Toolbox version 3.3.
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of the test material: 3',6'-bis(diethylamino)spiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one
- Molecular formula: C28H30N2O3
- Molecular weight: 442.556 g/mol
- Substance type: Organic
- Smiles: C12(c3c(Oc4c1ccc(c4)N(CC)CC)cc(N(CC)CC)cc3)c1c(cccc1)C(O2)=O - Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- oral: unspecified
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Frequency of treatment:
- not specified
- Remarks:
- not specified
- Control animals:
- not specified
- Details on study design:
- not specified
- Positive control:
- not specified
- Observations and examinations performed and frequency:
- not specified
- Sacrifice and pathology:
- not specified
- Other examinations:
- not specified
- Statistics:
- not specified
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 742.12 mg/kg bw/day (actual dose received)
- Based on:
- not specified
- Sex:
- not specified
- Basis for effect level:
- body weight and weight gain
- clinical signs
- Critical effects observed:
- not specified
- Conclusions:
- Since no compound related adverse effects on rats are observed, the no observed adverse effect level (NOAEL) relating to repeated dose for the given test material 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one is estimated to be 742.11 mg/kg/day via oral route of administration.
- Executive summary:
The repeated dose toxicity of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one to rats was estimated using QSAR Toolboox version 3.3. Since no compound related adverse effects on rats are observed, the no observed adverse effect level (NOAEL) relating to repeated dose for the given test material 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one is estimated to be 742.11 mg/kg/day via oral route of administration.
Reference
The
prediction was based on dataset comprised from the following
descriptors: NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain
((((((("a"
or "b" )
and ("c"
and (
not "d")
)
)
and ("e"
and (
not "f")
)
)
and "g" )
and "h" )
and "i" )
and ("j"
and "k" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion
formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine
by DNA binding by OECD
Domain
logical expression index: "b"
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: "c"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.3
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as AN2 OR AN2 >> Michael-type
addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >>
Michael-type addition on alpha, beta-unsaturated carbonyl compounds >>
Four- and Five-Membered Lactones OR AN2 >> Shiff base formation after
aldehyde release OR AN2 >> Shiff base formation after aldehyde release
>> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent
interaction >> DNA intercalation OR Non-covalent interaction >> DNA
intercalation >> DNA Intercalators with Carboxamide Side Chain OR
Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary
Aromatic Amines OR Non-specific OR Non-specific >> Incorporation into
DNA/RNA, due to structural analogy with nucleoside bases OR
Non-specific >> Incorporation into DNA/RNA, due to structural analogy
with nucleoside bases >> Specific Imine and Thione 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 via ROS formation (indirect) OR Radical >> Radical mechanism
via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR
Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes
with Other Active Groups OR Radical >> Radical mechanism via ROS
formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines
OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific
Imine and Thione Derivatives 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 carbenium
ion formation OR SN1 >> Nucleophilic attack after carbenium ion
formation >> Specific Acetate Esters 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 metabolic nitrenium ion
formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion
formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic
attack after metabolic nitrenium ion formation >> Single-Ring
Substituted Primary Aromatic Amines 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 SN1 >> Nucleophilic substitution on diazonium ions OR
SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and
Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >>
Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and
related OR SN2 >> Alkylation, direct acting epoxides and related >>
Epoxides and Aziridines 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 >>
Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening
SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting
epoxides formed after metabolic activation OR SN2 >> Direct acting
epoxides formed after metabolic activation >> Quinoline Derivatives 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 >>
Specific Acetate Esters 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: "e"
Referential
boundary: The
target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion
formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine
by DNA binding by OECD
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as 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 >> Alkyl phenols OR Michael addition >> P450
Mediated Activation to Quinones and Quinone-type Chemicals >>
Hydroquinones OR No alert found OR SN1 >> Iminium Ion Formation OR SN1
>> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >>
Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion
formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >>
Unsaturated heterocyclic azo by DNA binding by OECD
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as No superfragment by
Superfragments ONLY
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as Not bioavailable by Lipinski
Rule Oasis ONLY
Domain
logical expression index: "i"
Similarity
boundary:Target:
CCN(CC)c1ccc2c(c1)Oc1cc(N(CC)CC)ccc1C21c2ccccc2C(=O)O1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "j"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.642
Domain
logical expression index: "k"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 8.73
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 742.11 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is of k2 reliability and predicted by QSAR toolbox.
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Data waiving:
- exposure considerations
- Justification for data waiving:
- a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Data waiving:
- other justification
- Justification for data waiving:
- other:
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated
dose toxicity: oral
The
predicted data for target substance
3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (CAS
509-34-2) and the experimental study for its read across substance
disodium 3-oxo-3H-spiro[2-benzofuran-1,9'-xanthene]-3',6'-diolate (CAS
518-47-8)has
been investigated for potential of toxicity following repeated exposure
via oral route and is presented below as a weight of evidence approach
for classification of the target substance:
The repeated toxicity of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one to rats was estimated using QSAR Toolboox version 3.3. Since no compound related adverse effects on rats are observed, the no observed adverse effect level (NOAEL) relating to repeated dose for the given test material 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one is estimated to be 742.11 mg/kg/day via oral route of administration.
In a short term toxicity study, CD Sprague-Dawley female rats were treated with structurally similar substance D&C YELLOW NO. 8 (CAS No. 518-47-8) in the concentration of 0, 100, 500 and 1500 mg/kg body weight/ day by oral gavage (Fd Chem. Toxic, Vol. 24, No. 8, pp. 819 823, 1986). Six rats died during the dosing period at 1500 mg/kg bw/day and Orange discoloration of the urine was observed in all the treated rats as compared to control. Similarly, green discoloration of the amniotic fluid and green colored small intestines were observed at 1500 mg/kg bw/day and green discoloration of the amniotic fluid was observed at 100 and 500 mg/kg bw/day treated rats as compared to control. There were slight reductions in body-weight gains in the high-dose group, compared with controls, throughout the dosing period. Therefore, NOAEL was considered to be 500 mg/kg body weight /day when CD Sprague-Dawley female rats were treated repeatedly with D&C YELLOW No. 8 orally by gavage from day 6 to 19 of gestation.
Yet in another study for the same structurally similar substance and from same source (Fd Chem. Toxic, Vol. 24, No. 8, pp. 819 823, 1986), Dutch Belted female Rabbits were treated with D&C YELLOW NO. 8 (CAS No. 518 -47 -8) in the concentration of 0, 30, 100 and 250 mg/kg body weight/ day by oral gavage.One rabbits died each in 30 and 250 mg/kg bw/day including control. One rabbit was aborted on day 28 of gestation at 250 mg/kg bw/day as compared to control. Pneumonia was observed in three rabbit which were died. Orange discoloration of the urine was observed in all the treated rabbits between days 7 and 28 of gestation as compared to control. In addition, no effects were observed on body weight and body weight gain and gross pathology of treated rabbits as compared to control. There were no biologically meaningful or statistically significant differences in the mean numbers of corpora lutea, total implantations+ early or late resorptions, viable foetuses, foetal sex distribution or mean foetal body weight in any of the treated groups as compared to the control group. At 30 and 100 mg/kg bw/day, malformations were observed in two foetuses from two litters. However, these values fell within the ranges of historical control data. Therefore, NOAEL was considered to be 250 mg/kg body weight /day when Dutch Belted female Rabbits were treated repeatedly with D&C YELLOW NO. 8 orally by gavage from day 6 to 27 of gestation.
On the basis of evidence from above studies, it can be presumed that there is no potential of target substance to be harmful to rat/rabbit following repeated exposure. Also, the substance didn’t show any specific target organ toxicity. Hence, based on the above study summarized with oral routes and by applying weight of evidence approach it can be concluded that 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one is not classified as toxic on Repeated dose exposure via oral route.
Repeated
dose toxicity: inhalation
A
short-term toxicity study does not need to be conducted because exposure
of humans via inhalation in production and/or use is not likely as based
on the provided thorough and rigorous exposure assessment.
Repeated
dose toxicity: dermal
The
acute toxicity value for substance
3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (as
provided in section 7.2.3) is >2000 mg/kg body weight. The substance was
also found to be not irritating to skin. Also, given the use of the
chemical as dye compound; repeated exposure by the dermal route is
unlikely. Thus, it is expected that substance
3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one shall
not exhibit 28 day repeated dose toxicity by the dermal route. In
addition, there is no dermal absorption data as well as no data
available that suggests that substance
3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one shall
exhibit repeated dose toxicity by the dermal route. Hence this end point
was considered for waiver.
Justification for classification or non-classification
Based on the above study summarized with oral routes and by applying weight of evidence approach it can be concluded that 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one is not classified as toxic on Repeated dose exposure via oral route.
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