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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
Key value for chemical safety assessment
Effects on fertility
Description of key information
Toxicity
to reproduction
Since
no compound related adverse effects on rats are observed, the no
observed adverse effect level (NOAEL) relating to reproductive function
for the given test material
3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one is
estimated to be 720 mg/kg/day via oral route of administration.
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- 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: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- no
- Frequency of treatment:
- No data
- Remarks:
- No data
- Control animals:
- not specified
- Parental animals: Observations and examinations:
- Not specified
- Oestrous cyclicity (parental animals):
- Not specified
- Sperm parameters (parental animals):
- Not specified
- Litter observations:
- Not specified
- Postmortem examinations (parental animals):
- Not specified
- Postmortem examinations (offspring):
- Not specified
- Statistics:
- Not specified
- Reproductive indices:
- Not specified
- Offspring viability indices:
- Not specified
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- 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
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 720 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- clinical signs
- reproductive function (sperm measures)
- reproductive performance
- Remarks on result:
- other: not specified
- Critical effects observed:
- not specified
- Reproductive effects observed:
- not specified
- Conclusions:
- Since no compound related adverse effects on rats are observed, the no observed adverse effect level (NOAEL) relating to reproductive function for the given test material 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one is estimated to be 720 mg/kg/day via oral route of administration.
- Executive summary:
The reproductive 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 reproductive function for the given test material 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one is estimated to be 720 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 ("f"
and (
not "g")
)
)
and "h" )
and "i" )
and ("j"
and (
not "k")
)
)
and ("l"
and "m" )
)
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-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)
>> Nitroarenes with Other Active Groups 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
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 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 No superfragment by
Superfragments ONLY
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as No alert found by Protein
binding alerts for skin sensitization by OASIS v1.3
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Acylation OR Acylation >> Direct
acylation involving a leaving group OR Acylation >> Direct acylation
involving a leaving group >> Azlactones and unsaturated lactone
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 Schiff base formation OR Schiff
base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff
base formation >> Pyrazolones and Pyrazolidinones derivatives >>
Pyrazolones and Pyrazolidinones by Protein binding alerts for skin
sensitization by OASIS v1.3
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=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as No alert found by rtER Expert
System ver.1 - USEPA
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Salicylates by rtER Expert
System ver.1 - USEPA
Domain
logical expression index: "l"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.643
Domain
logical expression index: "m"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 7.68
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 720 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is of K2 reliability and predicted by QSAR toolbox.
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Toxicity to reproduction:
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 to reproduction via oral route and is presented below as a weight of evidence approach for classification of the target substance:
The reproductive toxicity of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one to rats was estimated using QSAR Toolbox version 3.3. Since no compound related adverse effects on rats are observed, the no observed adverse effect level (NOAEL) relating to reproductive function for the given test material 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one is estimated to be 720 mg/kg/day via oral route of administration.
In a Reproductive/Teratogenic toxicity study, CD Sprague-Dawley female rats were treated with structurally similar substance D&C Yellow no. 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 and 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. No effect on Post-implantation loss/dam, Total implantations/dam, Corpora lutea/dam and There were no biologically meaningful or statistically significant differences in the number of litters and Foetal sex of treated rats were observed as compared to control. In addition, No effect on viability of foetuse, number of fetuses with malformations, number of foetuses or litters with developmental variations were observed in any of the treated groups.Slight increase in the number of litters with unossified sternebrae (sternebrae nos 1-6) and rudimentary 14thrib(s) was observed in feotus of 1500 mg/kg bw/day treated rats as compared to control, but the observed effect fell within the ranges of historical control data. Therefore, Reproductive NOAEL was considered to be 1500 mg/kg body weight /day for F0 and F1 generation when CD Sprague-Dawley female rats were treated with D&C Yellow no. 8.
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 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 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. No effect on body weight and body weight gain and No effect on Post-implantation loss/dam, Total implantations/dam and Corpora lutea/dam were observed in treated rabbits as compared to control. Similarly, there were no biologically meaningful or statistically significant differences in the number of litters, Foetal sex and gross pathological changes were observed in treated rabbits as compared to control. In addition, No effect on viability of foetus, foetal body weight and sex of foetus were observed as compared to control. At 30 and 100 mg/kg be/day, malformations were observed in two foetuses from two litters. However, these values fell within the ranges of historical control data. There were no biologically meaningful or statistically significant differences in number of fetuses with malformations,number of foetuses or litters with developmental variations were observed in foetuses of any of the treated groups. Therefore, Reproductive NOAEL was considered to be 250 mg/kg body weight /day for F0 and F1 generation when Dutch Belted female rabbits were treated with D&C YELLOW NO. 8 orally by gavage from day 6 to 27 of gestation.
Based on the above mentioned studies for target substance and to its read across substance and by comparing these with the CLP criteria, it can be concluded that no adverse effects on reproductive performance was observed. Therefore by applying weight of evidence approach the substance3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one is considered to be not classified as Reproductive toxic chemical.
Justification for classification or non-classification
On the basis of evidence from above studies in, it can be presumed that there is no potential of the targert substance to be harmful to rat for reproductive toxictiy.
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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