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EC number: 240-005-7 | CAS number: 15876-39-8
- 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
Genetic toxicity in vitro
Description of key information
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2',4',5',7'-Tetrabromofluorescein aluminum salt. The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with S9 metabolic activation system. 2',4',5',7'-Tetrabromofluorescein aluminum salt was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.
Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- 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 from OECD QSAR Toolbox version 3.3 and the supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- Prediction is done using OECD QSAR Toolbox version 3.3, 2017
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- - Name of the test material: 2',4',5',7'-Tetrabromofluorescein aluminum salt
- IUPAC name: 2-(2,4,5,7-tetrabromo-3,6-dihydroxy-9H-xanthen-9-yl)benzoic acid
- Molecular formula: C20H8Br4O5.2/3Al
- Molceular weight: 1991.5992 g/mol
- Substance type: Organic - Target gene:
- Histidine
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not specified
- Cytokinesis block (if used):
- No data
- Metabolic activation:
- with
- Metabolic activation system:
- S9 metabolic activation system
- Test concentrations with justification for top dose:
- No data
- Vehicle / solvent:
- No data
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- not specified
- Positive control substance:
- not specified
- Details on test system and experimental conditions:
- No data
- Rationale for test conditions:
- No data
- Evaluation criteria:
- Prediction is done considering a dose depenednt increase in the number of revertants/plate
- Statistics:
- No data
- Species / strain:
- S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- not specified
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- No data
- Remarks on result:
- no mutagenic potential (based on QSAR/QSPR prediction)
- Conclusions:
- 2',4',5',7'-Tetrabromofluorescein aluminum salt was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.
- Executive summary:
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2',4',5',7'-Tetrabromofluorescein aluminum salt. The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with S9 metabolic activation system. 2',4',5',7'-Tetrabromofluorescein aluminum salt was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.
Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.
Reference
The
prediction was based on dataset comprised from the following
descriptors: "Gene mutation"
Estimation method: Takes highest mode 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 (
not "k")
)
)
and ("l"
and (
not "m")
)
)
and ("n"
and (
not "o")
)
)
and ("p"
and "q" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Phenols (Chronic toxicity) by
US-EPA New Chemical Categories
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Aryl OR Aryl halide OR
Carboxylic acid OR Fused carbocyclic aromatic OR Fused saturated
heterocycles OR Phenol OR Xanthene by Organic Functional groups ONLY
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Aryl OR Aryl halide OR
Carboxylic acid OR Overlapping groups OR Phenol OR Xanthene by Organic
Functional groups (nested) ONLY
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Acid, aromatic attach [-COOH] OR
Alcohol, olefinic attach [-OH] OR Aliphatic Carbon [CH] OR Aliphatic
Carbon, two phenyl attach [-C-] OR Aliphatic Oxygen, two aromatic
attach [-O-] OR Aromatic Carbon [C] OR Bromine, aromatic attach [-Br] OR
Bromine, olefinic attach [-Br] OR Carbonyl, olefinic attach [-C(=O)-] OR
Carbonyl, one aromatic attach [-C(=O)-] OR Hydroxy, aromatic attach
[-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon
[=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Oxygen, two
olefinic attach [-O-] OR Tertiary Carbon by Organic functional groups
(US EPA) ONLY
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as Aromatic compound OR Aryl
bromide OR Aryl halide OR Carbonic acid derivative OR Carboxylic acid OR
Carboxylic acid derivative OR Diarylether OR Ether OR Halogen derivative
OR Heterocyclic compound OR Hydroxy compound OR Phenol by Organic
functional groups, Norbert Haider (checkmol) ONLY
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.3
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as AN2 OR AN2 >> Michael-type
addition, quinoid structures OR AN2 >> Michael-type addition, quinoid
structures >> 3-Methylindole derivatives OR AN2 >> Michael-type
addition, quinoid structures >> Flavonoids OR AN2 >> Michael-type
addition, quinoid structures >> Quinoneimines OR AN2 >> Michael-type
addition, quinoid structures >> Quinones OR AN2 >> Carbamoylation after
isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation
>> N-Hydroxylamines OR AN2 >> Nucleophilic addition to alpha,
beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to
alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated
Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base
formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base
formation >> Dicarbonyl compounds OR AN2 >> Schiff base formation >>
Polarized Haloalkene Derivatives OR AN2 >> Shiff base formation after
aldehyde release OR AN2 >> Shiff base formation after aldehyde release
>> Specific Acetate Esters OR AN2 >> Thioacylation via nucleophilic
addition after cysteine-mediated thioketene formation OR AN2 >>
Thioacylation via nucleophilic addition after cysteine-mediated
thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR
AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated
thioketene formation >> Polarized Haloalkene Derivatives OR Michael
addition OR Michael addition >> Quinone type compounds OR Michael
addition >> Quinone type compounds >> Quinone methides OR Non-covalent
interaction OR Non-covalent interaction >> DNA intercalation OR
Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone,
Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA
intercalation >> Aminoacridine DNA Intercalators 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-covalent interaction >> DNA
intercalation >> Quinones OR Non-covalent interaction >> DNA
intercalation >> Triarylimidazole and Structurally Related DNA
Intercalators 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 reactive oxygen species OR Radical
>> Generation of reactive oxygen species >> Thiols OR Radical >> Radical
mechanism by ROS formation OR Radical >> Radical mechanism by ROS
formation (indirect) or direct radical attack on DNA OR Radical >>
Radical mechanism by ROS formation (indirect) or direct radical attack
on DNA >> Organic Peroxy Compounds OR Radical >> Radical mechanism by
ROS formation >> Acridone, Thioxanthone, Xanthone and Phenazine
Derivatives OR Radical >> Radical mechanism via ROS formation (indirect)
OR Radical >> Radical mechanism via ROS formation (indirect) >>
C-Nitroso Compounds OR Radical >> Radical mechanism via ROS formation
(indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism
via ROS formation (indirect) >> Flavonoids OR Radical >> Radical
mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic
Amines OR Radical >> Radical mechanism via ROS formation (indirect) >>
Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation
(indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS
formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS
formation (indirect) >> Specific Imine and Thione Derivatives OR Radical
>> ROS formation after GSH depletion OR Radical >> ROS formation after
GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion
(indirect) >> Quinoneimines OR Radical >> ROS formation after GSH
depletion >> Quinone methides 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 >> Acyclic Triazenes OR SN1 >> Nucleophilic attack after
carbenium ion formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic
attack after carbenium ion formation >> Specific Acetate Esters 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 >> N-Hydroxylamines OR SN1 >>
Nucleophilic attack after nitrenium and/or carbenium ion formation OR
SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion
formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic attack after
reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack
after reduction and nitrenium ion formation >> Conjugated Nitro
Compounds OR SN1 >> Nucleophilic substitution after glutathione-induced
nitrenium ion formation OR SN1 >> Nucleophilic substitution after
glutathione-induced nitrenium ion formation >> C-Nitroso Compounds OR
SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >>
Nucleophilic substitution on diazonium ions >> Specific Imine and Thione
Derivatives OR SN1 >> SN1 reaction at nitrogen-atom bound to a good
leaving group or on nitrenium ion OR SN1 >> SN1 reaction at
nitrogen-atom bound to a good leaving group or on nitrenium ion >>
N-Acyloxy(Alkoxy) Arenamides OR SN1 >> SN1 reaction at nitrogen-atom
bound to a good leaving group or on nitrenium ion >>
N-Aryl-N-Acetoxy(Benzoyloxy) Acetamides 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 >> Haloalkenes with
Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides
and related after P450-mediated metabolic activation >> Polycyclic
Aromatic Hydrocarbon Derivatives 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 >> Specific Acetate Esters OR SN2 >> SN2 at an activated
carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline
Derivatives OR SN2 >> SN2 at Nitrogen Atom OR SN2 >> SN2 at Nitrogen
Atom >> N-acetoxyamines OR SN2 >> SN2 at sp3 and activated sp2 carbon
atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized
Haloalkene Derivatives OR SN2 >> SN2 reaction at nitrogen-atom bound to
a good leaving group OR SN2 >> SN2 reaction at nitrogen-atom bound to a
good leaving group >> N-Acetoxyamines OR SN2 >> SN2 reaction at
nitrogen-atom bound to a good leaving group or nitrenium ion OR SN2 >>
SN2 reaction at nitrogen-atom bound to a good leaving group or nitrenium
ion >> N-Acyloxy(Alkoxy) Arenamides OR SN2 >> SN2 reaction at
nitrogen-atom bound to a good leaving group or nitrenium ion >>
N-Aryl-N-Acetoxy(Benzoyloxy) Acetamides by DNA binding by OASIS v.1.3
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OECD
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Acylation OR Acylation >> P450
Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >>
P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides
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 >> Alkyl
phenols OR Michael addition >> P450 Mediated Activation to Quinones and
Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated
Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR
Michael addition >> P450 Mediated Activation to Quinones and
Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs)
aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised
Alkenes-Michael addition OR Michael addition >> Polarised
Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael
addition >> Polarised Alkenes-Michael addition >> Alpha, beta-
unsaturated esters OR Michael addition >> Polarised Alkenes-Michael
addition >> Alpha, beta- unsaturated ketones OR Michael addition >>
Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and
Quinone-type Chemicals >> Quinones OR Schiff base formers OR Schiff base
formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base
formers >> Chemicals Activated by P450 to Mono-aldehydes >> Thiazoles OR
Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base
formers >> Direct Acting Schiff Base Formers >> Alpha-beta-dicarbonyl OR
SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation
>> Aliphatic N-Nitro OR SN1 >> Carbenium Ion Formation >> Allyl benzenes
OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic
(HACs) aromatic hydrocarbons-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 >> Primary (unsaturated) heterocyclic amine OR
SN1 >> Nitrenium Ion formation >> Primary 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 nitro OR SN2 OR SN2
>> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic
Alkenes >> Halogenated polarised alkenes OR SN2 >> P450 Mediated
Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 by DNA
binding by OECD
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Non binder, MW>500 by Estrogen
Receptor Binding
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Moderate binder, OH grooup OR
Non binder, impaired OH or NH2 group OR Non binder, non cyclic structure
OR Non binder, without OH or NH2 group OR Strong binder, OH group OR
Very strong binder, OH group OR Weak binder, OH group by Estrogen
Receptor Binding
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as No alert found by Protein
binding by OASIS v1.3
Domain
logical expression index: "m"
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 Acylation >> Ester aminolysis OR Acylation >> Ester
aminolysis >> Amides 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 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 by Protein binding by OASIS v1.3
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Halogens AND Non-Metals by
Groups of elements
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Metals OR Transition Metals by
Groups of elements
Domain
logical expression index: "p"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 7.2
Domain
logical expression index: "q"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 10.9
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2',4',5',7'-Tetrabromofluorescein aluminum salt. The study assumed the use of male and female mouse. 2',4',5',7'-Tetrabromofluorescein aluminum salt was predicted to not induce gene mutation in male and female mouse and hence, according to the prediction made, it is not likely to classify as a gene mutant in vivo.
Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- 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 from OECD QSAR Toolbox version 3.3 and the supporting QMRF report is attached
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- Prediction is done using OECD QSAR Toolbox version 3.3, 2017
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
- Specific details on test material used for the study:
- - Name of the test material: 2',4',5',7'-Tetrabromofluorescein aluminum salt
- IUPAC name: 2-(2,4,5,7-tetrabromo-3,6-dihydroxy-9H-xanthen-9-yl)benzoic acid
- Molecular formula: C20H8Br4O5.2/3Al
- Molceular weight: 1991.5992 g/mol
- Substance type: Organic - Species:
- mouse
- Strain:
- not specified
- Details on species / strain selection:
- No data
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data
- Route of administration:
- not specified
- Vehicle:
- No data
- Details on exposure:
- No data
- Duration of treatment / exposure:
- No data
- Frequency of treatment:
- No data
- Post exposure period:
- No data
- Remarks:
- No data
- No. of animals per sex per dose:
- No data
- Control animals:
- not specified
- Positive control(s):
- No data
- Tissues and cell types examined:
- No data
- Details of tissue and slide preparation:
- No data
- Evaluation criteria:
- Prediction was done considering chromosomal aberration in mammalian cell line used
- Statistics:
- No data
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- not specified
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- No data
- Conclusions:
- 2',4',5',7'-Tetrabromofluorescein aluminum salt was predicted to not induce gene mutation in male and female mouse and hence, according to the prediction made, it is not likely to classify as a gene mutant in vivo.
- Executive summary:
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2',4',5',7'-Tetrabromofluorescein aluminum salt. The study assumed the use of male and female mouse. 2',4',5',7'-Tetrabromofluorescein aluminum salt was predicted to not induce gene mutation in male and female mouse and hence, according to the prediction made, it is not likely to classify as a gene mutant in vivo.
Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.
Reference
The
prediction was based on dataset comprised from the following
descriptors: "chromosome aberration"
Estimation method: Takes highest mode value from the 8 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 (
not "l")
)
)
and ("m"
and (
not "n")
)
)
and ("o"
and "p" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Phenols (Chronic toxicity) by
US-EPA New Chemical Categories
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Aryl OR Aryl halide OR
Carboxylic acid OR Fused carbocyclic aromatic OR Fused saturated
heterocycles OR Phenol OR Xanthene by Organic Functional groups ONLY
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Aryl OR Aryl halide OR
Carboxylic acid OR Overlapping groups OR Phenol OR Xanthene by Organic
Functional groups (nested) ONLY
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Acid, aromatic attach [-COOH] OR
Alcohol, olefinic attach [-OH] OR Aliphatic Carbon [CH] OR Aliphatic
Carbon, two phenyl attach [-C-] OR Aliphatic Oxygen, two aromatic
attach [-O-] OR Aromatic Carbon [C] OR Bromine, aromatic attach [-Br] OR
Bromine, olefinic attach [-Br] OR Carbonyl, olefinic attach [-C(=O)-] OR
Carbonyl, one aromatic attach [-C(=O)-] OR Hydroxy, aromatic attach
[-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon
[=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Oxygen, two
olefinic attach [-O-] OR Tertiary Carbon by Organic functional groups
(US EPA) ONLY
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as Aromatic compound OR Aryl
bromide OR Aryl halide OR Carbonic acid derivative OR Carboxylic acid OR
Carboxylic acid derivative OR Diarylether OR Ether OR Halogen derivative
OR Heterocyclic compound OR Hydroxy compound OR Phenol by Organic
functional groups, Norbert Haider (checkmol) ONLY
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.3
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as AN2 OR AN2 >> Michael-type
addition, quinoid structures OR AN2 >> Michael-type addition, quinoid
structures >> Quinones OR AN2 >> Nucleophilic addition to alpha,
beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to
alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated
Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base
formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Shiff base
formation after aldehyde release OR AN2 >> Shiff base formation after
aldehyde release >> Specific Acetate Esters OR AN2 >> Thioacylation via
nucleophilic addition after cysteine-mediated thioketene formation OR
AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated
thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR
Michael addition OR Michael addition >> Quinone type compounds OR
Michael addition >> Quinone type compounds >> Quinone methides OR
Non-covalent interaction OR Non-covalent interaction >> DNA
intercalation OR Non-covalent interaction >> DNA intercalation >>
Quinones OR Radical OR Radical >> Radical mechanism by ROS formation
(indirect) or direct radical attack on DNA OR Radical >> Radical
mechanism by ROS formation (indirect) or direct radical attack on DNA >>
Organic Peroxy Compounds OR Radical >> Radical mechanism via ROS
formation (indirect) OR Radical >> Radical mechanism via ROS formation
(indirect) >> Quinones OR Radical >> ROS formation after GSH depletion
OR Radical >> ROS formation after GSH depletion >> Quinone methides 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 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 >>
Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation,
direct acting epoxides and related after P450-mediated metabolic
activation >> Polycyclic Aromatic Hydrocarbon Derivatives 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 >> Specific Acetate
Esters OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an
activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS
v.1.3
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OECD
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Acylation OR Acylation >> P450
Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >>
P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides
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 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 >> Arenes OR
Michael addition >> P450 Mediated Activation to Quinones and
Quinone-type Chemicals >> Hydroquinones OR Michael addition >> P450
Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic
(PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR
Michael addition >> Polarised Alkenes-Michael addition OR Michael
addition >> Polarised Alkenes-Michael addition >> Alpha, beta-
unsaturated amides OR Michael addition >> Polarised Alkenes-Michael
addition >> Alpha, beta- unsaturated esters OR SN1 OR SN1 >> Iminium Ion
Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines
OR SN2 OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation
of Aliphatic Alkenes >> Halogenated polarised alkenes by DNA binding by
OECD
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Not bioavailable by Lipinski
Rule Oasis ONLY
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Halogens AND Non-Metals by
Groups of elements
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Metalloids by Groups of elements
Domain
logical expression index: "m"
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: "n"
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 >> Anhydrides (sulphur analogues of
anhydrides) 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 >> Conjugated systems with electron withdrawing groups
by Protein binding alerts for skin sensitization by OASIS v1.3
Domain
logical expression index: "o"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 4.32
Domain
logical expression index: "p"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 10.9
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Gene mutation in vitro:
Prediction model based estimation and data from read across chemicals have been reviewed to determine the mutagenic nature of
2',4',5',7'-Tetrabromofluorescein aluminum salt (CAS no 15876-39 -8). The studies are as summarized below:
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2',4',5',7'-Tetrabromofluorescein aluminum salt. The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. 2',4',5',7'-Tetrabromofluorescein aluminum salt was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.
Salmonella/ mammalian-microsome test was performed by Muzall and Cook (Mutation Research, 1979) to evaluate the mutagenic nature of the read across chemicals D&C Red No. 21 (RA CAS no 15086 -94 -9; IUPAC name: 2-(2,4,5,7-tetrabromo-3,6-dihydroxy-9H-xanthen-9-yl)benzoic acid) and D & C Red No. 22 (RA CAS no 17372 -87 -1; IUPAC name: 2-(2,4,5,7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl)). The study was performed as per the plate incorporation method using Salmonella typhimurium strains TA98, TA1537, TA100, TA1535 with and without S9 metabolic activation system. The test material was dissolved in DMSO and used at dose levels from 10-250 mg. DMSO was used as the solvent control. The 2 ml of liquid top agar was cooled to 45°C and 0.1 ml of a broth culture of microorganism and test substance in volumes of ≤ 0.4 ml of DMSO was added prior to placing on minimal agar plates. After 48 h incubation at 37°C, the colonies which reverted to the prototroph were counted and compared to counts on the control plate (containing no test substance) to demonstrate mutagenicity or toxicity. Materials which caused a 2-fold increase of revertants, as compared to the number of spontaneous revertants on the control plates, were denoted as mutagens. Those which reduced the number of revertants were considered inhibitory. D & C Red no. 21 and D & C Red no. 22 did not induce gene mutation in Salmonella typhimurium TA98, TA1537, TA100, TA1535 in the presence and absence of S9 metabolic activation system and hence it is negative for gene mutation in vitro.
Brown et al (Mutation Research, 1979) performed Salmonella/mammalian microsome assay evaluate the mutagenic nature of D and C Red No. 27/ Phloxine B (RA CAS no 18472 -87 -2; IUPAC name: 2',4',5',7'-tetrabromo-4,5,6,7-tetrachloro-3',6'-dihydroxy-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one). The dye was dissolved in dimethylsulfoxide and up to 0.2 ml was introduced into 2.5 ml of the tempered top agar together with 0.1 ml Salmonella typhimuriumbroth suspension and 0.25 ml Aroclor 1254 induced rat liver S9. The mixtures was plated on 20 ml of Vogel-Bonner E bottom agar in the usual fashion and incubated for 3 days at 35°. Each agent was tested with all 5 basic tester strains (TA1535, TA100, TA1537, TA1538, TA98) with and without microsomal activation at concentrations of 0, 10, 50 or 100 µg/plate. Phloxine B did not show any mutagenic activity in the Salmonella typhimurium tester strains TA98, TA100, TA1535, TA1537 and TA1538 in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.
Gene mutation in vivo:
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2',4',5',7'-Tetrabromofluorescein aluminum salt. The study assumed the use of male and female mouse. 2',4',5',7'-Tetrabromofluorescein aluminum salt was predicted to not induce gene mutation in male and female mouse and hence, according to the prediction made, it is not likely to classify as a gene mutant in vivo.
In the in vivo micronucleus test performed by Hayashi et al (Food and Chemical Toxicology, 1988) for structurally similar read across chemical Acid Red 92 (Phloxine; RA CAS no 6441 -77 -6; IUPAC name: Dipotassium 3,6-dichloro-2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate). The chemical was investigated in male ddY mice for mutagenicity. The test chemical was administered by intraperitoneal injection once (at doses 0, 30, 60 or 120 mg/kg) or 4 times 24 hours apart (at a dose of 60 mg/kg/injection). Femoral marrow cells were flushed out with foetal bovine serum and smeared on clean glass slides. Cells were fixed with methanol for 5 min, and stained with Acridine Orange for the pilot experiment and with Giemsa for the full-scale test. One thousand polychromatic erythrocytes per mouse were scored using a light microscope. After treatment, the number of micronucleated polychromatic erythrocytes (MNPCEs) was recorded and the proportion of polychromatic erythrocytes (PCEs) among the total erythrocytes was evaluated. Based on the results, no mutagenic effects could be detected. Therefore, Acid Red 92 is considered to be non-mutagenic when male ddY mice were exposed to the test chemical.
Genetic toxicity in vivo study (SCCS, 2004) was performed for another structurally similar read across chemical Acid Red 92 (RA CAS no 18472 -87 -2; IUPAC name: 2',4',5',7'-tetrabromo-4,5,6,7-tetrachloro-3',6'-dihydroxy-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one) using male and female NMRI mice. Acid red 92 was injected intraperitoneally in mice and the number of micronucleus formed in the polychromatic erythrocytes was noted. The positive control (Cyclophosphamide) induced 2.030 % of MN in PCEs (0.08 % in the control animals: significance p 0.0040). In the treated animals with 100 mg/kg a percentage of MN 0.150 (24h) and 0.110 (48h) was observed: these values, although higher than the control, had a p > 0.34. A reduction of PCE was observed, thus indicating a cytotoxic effect of the test item in the bone marrow cells. Acid Red 92 did not induce micronucleus in the bone maroow polychromatic erthrocytes and hence it is non mutagenic in the In vivo Mammalian Erythrocyte Micronucleus Test performed
Based on the data available for the target chemical and its read across, 2',4',5',7'-Tetrabromofluorescein aluminum salt (CAS no 15876-39 -8) does not exhibit gene mutation in vitro and in vivo and hence does not classify for mutagenic effects as per the criteria mentioned in CLP regulation.
Justification for classification or non-classification
Based on the data available for the target chemical and its read across, 2',4',5',7'-Tetrabromofluorescein aluminum salt (CAS no 15876-39 -8) does not exhibit gene mutation in vitro and in vivo and hence does not classify for mutagenic effects as per the criteria mentioned in CLP regulation.
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