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EC number: 265-499-1 | CAS number: 65138-66-1
- 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
Skin irritation:
The dermal irritation potential of 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.
Eye irritation:
The ocular irritation potential of 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- 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 QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: estimated data
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.3
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of test material (IUPAC name): 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium
- Molecular formula: C28H31N2O3.1/3C16H9N4O9S2
- Molecular weight: 1796.09 g/mol
- Smiles notation: c1(C)c(cc2[o+]c3c(c(c4c(cccc4)C(OCC)=O)c2c1)cc(C)c(NCC)c3)NCC.C1([C@@H](\N=N/c2ccc(cc2)S([O-])(=O)=O)C(=NN1c1ccc(S([O-])(=O)=O)cc1)C([O-])=O)=O.c1(cc2c([o+]c3c(c2c2ccccc2C(OCC)=O)cc(c(NCC)c3)C)cc1NCC)C.c1(cc2c([o+]c3c(c2c2ccccc2C(OCC)=O)cc(c(NCC)c3)C)cc1NCC)C
- InChl: 1S/3C28H31N2O3.C16H12N4O9S2/c3*1-6-29-23-15-25-21(13-17(23)4)27(19-11-9-10-12-20(19)28(31)32-8-3)22-14-18(5)24(30-7-2)16-26(22)33-25;21-15-13(18-17-9-1-5-11(6-2-9)30(24,25)26)14(16(22)23)19-20(15)10-3-7-12(8-4-10)31(27,28)29/h3*9-16,29-30H,6-8H2,1-5H3;1-8,13H,(H,22,23)(H,24,25,26)(H,27,28,29)/q3*+1;/p-3/b;;;18-17-
- Substance type: Organic
- Physical state: Solid - Species:
- other: rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- not specified
- Type of coverage:
- semiocclusive
- Preparation of test site:
- shaved
- Vehicle:
- not specified
- Controls:
- not specified
- Amount / concentration applied:
- not specified
- Duration of treatment / exposure:
- 4 hour
- Observation period:
- 7 days
- Number of animals:
- 3
- Details on study design:
- No data available
- Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- 7 d
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- no skin irritation was observed.
- Interpretation of results:
- other: not irritating
- Conclusions:
- The substance 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)was estimated to be not irritating to the skin of New Zealand White rabbits.
- Executive summary:
The dermal irritation potential of 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.
Reference
Estimation
method: Takes mode value from the 10 nearest neighbours
Domain logical expression:Result: In Domain
(((((((((("a"
or "b" or "c" or "d" )
and ("e"
and (
not "f")
)
)
and ("g"
and (
not "h")
)
)
and "i" )
and ("j"
and (
not "k")
)
)
and "l" )
and "m" )
and ("n"
and (
not "o")
)
)
and ("p"
and (
not "q")
)
)
and ("r"
and "s" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Esters (Chronic toxicity) AND
Not categorized by US-EPA New Chemical Categories
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as No alert found AND Non-specific
AND Non-specific >> Incorporation into DNA/RNA, due to structural
analogy with nucleoside bases AND Non-specific >> Incorporation into
DNA/RNA, due to structural analogy with nucleoside bases >> Specific
Imine and Thione Derivatives AND Radical AND Radical >> Radical
mechanism via ROS formation (indirect) AND Radical >> Radical mechanism
via ROS formation (indirect) >> Specific Imine and Thione Derivatives
AND SN1 AND SN1 >> Nucleophilic substitution on diazonium ions AND SN1
>> Nucleophilic substitution on diazonium ions >> Specific Imine and
Thione Derivatives by DNA binding by OASIS v.1.3
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as No alert found AND SN1 AND SN1
>> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >>
Secondary aromatic amine by DNA binding by OECD
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Esters OR Inorganic Compound OR
Schiff Bases-Azomethine OR Vinyl/Allyl Ethers by Aquatic toxicity
classification by ECOSAR ONLY
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.3
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as AN2 OR AN2 >> Carbamoylation
after isocyanate formation OR AN2 >> Carbamoylation after isocyanate
formation >> N-Hydroxylamines 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 >> Schiff base formation OR AN2 >> Schiff base formation
>> Dicarbonyl compounds OR AN2 >> Schiff base formation by aldehyde
formed after metabolic activation OR AN2 >> Schiff base formation by
aldehyde formed after metabolic activation >> Geminal Polyhaloalkane
Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2
>> Shiff base formation after aldehyde release >> Specific Acetate
Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base
formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >>
Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile
Halogen OR Non-covalent interaction OR Non-covalent interaction >> DNA
intercalation OR Non-covalent interaction >> DNA intercalation >>
Coumarins 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) >> Coumarins OR Radical >>
Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane
Derivatives OR Radical >> Radical mechanism via ROS formation (indirect)
>> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation
(indirect) >> p-Substituted Mononitrobenzenes OR SN1 OR SN1 >> Carbenium
ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR
SN1 >> Nucleophilic attack after carbenium ion formation 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 >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after
reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack
after reduction and nitrenium ion formation >> p-Substituted
Mononitrobenzenes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >>
Specific Acetate Esters OR SN2 >> Acylation involving a leaving group
OR SN2 >> Acylation involving a leaving group >> Geminal
Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group
>> Haloalkane Derivatives with Labile Halogen OR SN2 >> Acylation
involving a leaving group after metabolic activation OR SN2 >> Acylation
involving a leaving group after metabolic activation >> Geminal
Polyhaloalkane Derivatives OR SN2 >> Alkylation, nucleophilic
substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic
substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile
Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon
atom >> Sulfonates and Sulfates 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 >> Coumarins 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 >> Nucleophilic substitution at sp3 carbon atom after
thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at
sp3 carbon atom after thiol (glutathione) conjugation >> Geminal
Polyhaloalkane Derivatives OR SN2 >> Ring opening SN2 reaction OR SN2 >>
Ring opening SN2 reaction >> Sultones OR SN2 >> SN2 at an activated
carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline
Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon
atom >> Alpha-Haloethers by DNA binding by OASIS v.1.3
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Not possible to classify
according to these rules by DPRA Lysine peptide depletion
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as High reactive OR High reactive
>> Vinylene dicarboxylates by DPRA Lysine peptide depletion
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Class 5 (Not possible to
classify according to these rules) by Acute aquatic toxicity
classification by Verhaar (Modified) ONLY
Domain
logical expression index: "j"
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: "k"
Referential
boundary: The
target chemical should be classified as Group 15 - Phosphorus P OR Group
16 - Sulfur S OR Group 17 - Halogens Br OR Group 17 - Halogens Cl OR
Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At by Chemical
elements
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Not bioavailable by Lipinski
Rule Oasis ONLY
Domain
logical expression index: "m"
Similarity
boundary:Target:
CCNc1cc2c(cc1C)C(c1ccccc1C(=O)OCC)c1cc(C)c(NCC)cc1O2
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Not categorized by Repeated dose
(HESS)
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Aliphatic amines (Mucous
membrane irritation) Rank C OR Phthalate esters (Testicular toxicity)
Rank C by Repeated dose (HESS)
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as 1-phenoxy-benzene AND Aromatic
mono- and dialkylamine AND H-acceptor-path3-H-acceptor by in vivo
mutagenicity (Micronucleus) alerts by ISS
Domain
logical expression index: "q"
Referential
boundary: The
target chemical should be classified as alpha,beta-unsaturated aliphatic
alkoxy group OR Oxolane by in vivo mutagenicity (Micronucleus) alerts by
ISS
Domain
logical expression index: "r"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 6.15
Domain
logical expression index: "s"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 8.23
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- 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 QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: estimated data
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.3
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of test material (IUPAC name): 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium
- Molecular formula: C28H31N2O3.1/3C16H9N4O9S2
- Molecular weight: 1796.09 g/mol
- Smiles notation: c1(C)c(cc2[o+]c3c(c(c4c(cccc4)C(OCC)=O)c2c1)cc(C)c(NCC)c3)NCC.C1([C@@H](\N=N/c2ccc(cc2)S([O-])(=O)=O)C(=NN1c1ccc(S([O-])(=O)=O)cc1)C([O-])=O)=O.c1(cc2c([o+]c3c(c2c2ccccc2C(OCC)=O)cc(c(NCC)c3)C)cc1NCC)C.c1(cc2c([o+]c3c(c2c2ccccc2C(OCC)=O)cc(c(NCC)c3)C)cc1NCC)C
- InChl: 1S/3C28H31N2O3.C16H12N4O9S2/c3*1-6-29-23-15-25-21(13-17(23)4)27(19-11-9-10-12-20(19)28(31)32-8-3)22-14-18(5)24(30-7-2)16-26(22)33-25;21-15-13(18-17-9-1-5-11(6-2-9)30(24,25)26)14(16(22)23)19-20(15)10-3-7-12(8-4-10)31(27,28)29/h3*9-16,29-30H,6-8H2,1-5H3;1-8,13H,(H,22,23)(H,24,25,26)(H,27,28,29)/q3*+1;/p-3/b;;;18-17-
- Substance type: Organic
- Physical state: Solid - Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- No data available
- Vehicle:
- not specified
- Controls:
- not specified
- Amount / concentration applied:
- No data available
- Duration of treatment / exposure:
- 24 hours
- Observation period (in vivo):
- 7 days
- Duration of post- treatment incubation (in vitro):
- No data available
- Number of animals or in vitro replicates:
- 3
- Details on study design:
- No data available
- Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- 7 d
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- no eye irritation was observed.
- Interpretation of results:
- other: not irritating
- Conclusions:
- The substance 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)can be considered to be not irritating to eye.
- Executive summary:
The ocular irritation potential of 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.
Reference
Estimation
method: Takes mode value from the 9 nearest neighbours
Domain logical expression:Result: In Domain
(((((((("a"
or "b" or "c" or "d" )
and ("e"
and (
not "f")
)
)
and ("g"
and (
not "h")
)
)
and "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 Esters (Chronic toxicity) AND
Not categorized by US-EPA New Chemical Categories
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as No alert found AND Non-specific
AND Non-specific >> Incorporation into DNA/RNA, due to structural
analogy with nucleoside bases AND Non-specific >> Incorporation into
DNA/RNA, due to structural analogy with nucleoside bases >> Specific
Imine and Thione Derivatives AND Radical AND Radical >> Radical
mechanism via ROS formation (indirect) AND Radical >> Radical mechanism
via ROS formation (indirect) >> Specific Imine and Thione Derivatives
AND SN1 AND SN1 >> Nucleophilic substitution on diazonium ions AND SN1
>> Nucleophilic substitution on diazonium ions >> Specific Imine and
Thione Derivatives by DNA binding by OASIS v.1.3
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as No alert found AND SN1 AND SN1
>> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >>
Secondary aromatic amine by DNA binding by OECD
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Esters OR Inorganic Compound OR
Schiff Bases-Azomethine OR Vinyl/Allyl Ethers by Aquatic toxicity
classification by ECOSAR ONLY
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.3
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as AN2 OR AN2 >> Carbamoylation
after isocyanate formation OR AN2 >> Carbamoylation after isocyanate
formation >> N-Hydroxylamines 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 >> Schiff base formation by aldehyde formed after
metabolic activation OR AN2 >> Schiff base formation by aldehyde formed
after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2
>> Shiff base formation after aldehyde release OR AN2 >> Shiff base
formation after aldehyde release >> Specific Acetate Esters OR AN2 >>
Shiff base formation for aldehydes OR AN2 >> Shiff base formation for
aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base
formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR
Non-covalent interaction OR Non-covalent interaction >> DNA
intercalation OR Non-covalent interaction >> DNA intercalation >>
Coumarins 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) >> Coumarins OR Radical >>
Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane
Derivatives OR Radical >> Radical mechanism via ROS formation (indirect)
>> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation
(indirect) >> p-Substituted Mononitrobenzenes OR SN1 OR SN1 >> Carbenium
ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR
SN1 >> Nucleophilic attack after carbenium ion formation 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 >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after
reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack
after reduction and nitrenium ion formation >> p-Substituted
Mononitrobenzenes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >>
Specific Acetate Esters OR SN2 >> Acylation involving a leaving group
OR SN2 >> Acylation involving a leaving group >> Geminal
Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group
>> Haloalkane Derivatives with Labile Halogen OR SN2 >> Acylation
involving a leaving group after metabolic activation OR SN2 >> Acylation
involving a leaving group after metabolic activation >> Geminal
Polyhaloalkane Derivatives OR SN2 >> Alkylation, nucleophilic
substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic
substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile
Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon
atom >> Sulfonates and Sulfates 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 >> Coumarins 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 >> Nucleophilic substitution at sp3 carbon atom after
thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at
sp3 carbon atom after thiol (glutathione) conjugation >> Geminal
Polyhaloalkane Derivatives OR SN2 >> Ring opening SN2 reaction OR SN2 >>
Ring opening SN2 reaction >> Sultones OR SN2 >> SN2 at an activated
carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline
Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon
atom >> Alpha-Haloethers by DNA binding by OASIS v.1.3
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Non binder, without OH or NH2
group by Estrogen Receptor Binding
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as Non binder, impaired OH or NH2
group OR Non binder, MW>500 OR Non binder, non cyclic structure OR
Strong binder, OH group by Estrogen Receptor Binding
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as No superfragment by
Superfragments ONLY
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 Group 14 - Carbon C AND Group 15
- Nitrogen N AND Group 16 - Oxygen O by Chemical elements
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Group 16 - Sulfur S by Chemical
elements
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Aliphatic Carbon [CH] AND
Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic
Carbon, two phenyl attach [-C-] AND Aliphatic Nitrogen, one aromatic
attach [-N] AND Aliphatic Oxygen, two aromatic attach [-O-] AND Amino,
aliphatic attach [-N<] AND Aromatic Carbon [C] AND Carbonyl, olefinic
attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Ester,
aliphatic attach [-C(=O)O] AND Miscellaneous sulfide (=S) or oxide (=O)
AND Olefinic carbon [=CH- or =C<] AND Oxygen, two olefinic attach [-O-]
AND Tertiary Carbon by Organic functional groups (US EPA)
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as 2-Oxyalkyl-1,2-ethanediol deriv.
[HOCH2CH(OH)CO] OR Aliphatic 1,2,3-triol [-C(COH)(COH)C-OH] OR Aliphatic
Carbon [C] OR Aliphatic-C=N-Aliphatic OR Azomethine, aliphatic attach
[-N=C] OR Carbonyl, aliphatic attach [-C(=O)-] OR Ether-alcohols
[-OC(COH)CO-] OR Fused Aliphatic ring unit OR Hydroxy, aliphatic attach
[-OH] OR Imine, linear [-CH=NC-] OR Multi alcohol OR Oxygen, aliphatic
attach [-O-] OR Oxygen, one aromatic attach [-O-] by Organic functional
groups (US EPA)
Domain
logical expression index: "o"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 5.19
Domain
logical expression index: "p"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 9.37
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin irritation:
Various studieshas been investigated for the test chemical9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and humans for target chemical9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)and its structurally similar read across substancesIsopropyl myristate (CAS no: 110-27-0)andRhodamine B(CAS No: 81-88-9).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1) .The chemical 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)was estimated to be not irritating to skin of New Zealand White rabbits.
The JAMES E. FULTON, JR (1989) conducted a test by using a single rabbit ear to indicate the Comedogenicity and irritancy ofstructurally similar read across substanceRhodamine B(CAS No: 81-88-9). Rhodamine B was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control. The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. Rhodamine B falls under Grade 0 (no irritation observed). Hence it can be concluded that Rhodamine B(CAS No: 81-88-9).was not irritating to rabbit ears.
The above results were further supported by theprimary skin irritation study conducted bythe Cosmetic Ingredients Review(CIR) Expert Panel(1982)for structurally similar read across substanceIsopropyl myristate (CAS no: 110-27-0)in 15 subjects to assess the degree of skin irritancy caused by the chemical.In this study, each subject received undiluted Isopropyl myristate for 24 hours under occlusive condition and later observed for adverse skin effects.Since all the observations for skin irritation were negative, the chemical Isopropyl myristate (CAS no: 110-27-0)was considered as not irritatingto the human’s skin.
Thus on the basis of available data for thetarget chemical9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)and its structurally similar read across substancesIsopropyl myristate (CAS no: 110-27-0)andRhodamine B(CAS No: 81-88-9),it can be concluded thatchemical 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)is unable to cause skin irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.
Eye irritation:
In different studies,the test chemical9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)its structurally similar read across substancesBis(2-ethylhexyl)phthalate (CAS no: 117-81-7) and1,4-bis(2-ethylhexyl) benzene-1,4-dicarboxylate (CAS No: 6422-86-2).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1).The chemical 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1) was estimated to be not irritating to eye of New Zealand White rabbits.
The European Chemicals Bureau (2008) and HSDB (2016) examined thelocal eye irritative potential ofstructurally similar read across substanceBis(2-ethylhexyl)phthalate (CAS no: 117-81-7)in threemale Little White Russianrabbits’ eye in accordance with OECD guideline 405.During the study, each rabbit received volume of 0.1 ml of into the conjunctival sac of in the right eye. The left eye served as control. The ocular lesions were scored after 1, 24, 48, and 72 hours, and after 6 days of application, using the grading system of the OECD guideline.At 1 hour, the conjunctivae of all three rabbits showed mild redness and one rabbit showed mild discharge. No conjunctival reactions were observed at the later observation times. All observations for chemosis, corneal opacity and lesions of the iris were negative.Hence the chemical Bis(2-ethylhexyl)phthalate (CAS no: 117-81-7)can be considered as not irritatingto the threemale Little White Russianrabbits’ eye.
The above results were further supported by the experimental study reported byEuropean Chemicals Agency (ECHA, 2016) forstructurally similar read across substance1,4-bis(2-ethylhexyl) benzene-1,4-dicarboxylate (CAS No: 6422-86-2) in three (1 male and 2 female) New Zealand white rabbits according to OECD guideline 405.The undiluted1,4-bis(2-ethylhexyl) benzene-1,4-dicarboxylate was installed into the one eye of each rabbit for 4 hours and observations were made for 72 hours following application. No corneal opacity or iritis was observed during the study. Conjunctivitis and redness were reported up to 48 hours after administration. All reported effects were fully reversible within 72 hours. Since all the effects were cleared within 72 hours, the chemical 1,4-bis(2-ethylhexyl) benzene-1,4-dicarboxylate (CAS No: 6422-86-2) can be considered asnot irritatingto theNew Zealand whiterabbits’ eye.
Thus on the basis of available data for thetarget chemical9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)and its structurally similar read across substancesBis(2-ethylhexyl)phthalate (CAS no: 117-81-7) and1,4-bis(2-ethylhexyl) benzene-1,4-dicarboxylate (CAS No: 6422-86-2) is unable to cause eye irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.
Justification for classification or non-classification
The skin and eye irritation potential of test chemical9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)is unlikely to cause skin and eye irritation. Hence9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)can be classified under the category “Not Classified” for skin and eye as per CLP.
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