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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
The skin sensitization 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 log Pow 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 sensitizing to the skin of guinea pigs. Based on the estimated result 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs and can be classified as non skin sensitizer.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation
- Remarks:
- 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
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- 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:
- guinea pig
- Strain:
- not specified
- Sex:
- not specified
- Details on test animals and environmental conditions:
- not specified
- Route:
- epicutaneous, occlusive
- Vehicle:
- water
- Concentration / amount:
- No data available
- Day(s)/duration:
- No data available
- Adequacy of induction:
- not specified
- Route:
- epicutaneous, occlusive
- Vehicle:
- water
- Concentration / amount:
- No data available
- Day(s)/duration:
- No data available
- Adequacy of challenge:
- not specified
- No. of animals per dose:
- 12
- Details on study design:
- No data available
- Challenge controls:
- No data available
- Reading:
- 1st reading
- Group:
- test chemical
- Dose level:
- No data available
- No. with + reactions:
- 0
- Total no. in group:
- 12
- Clinical observations:
- no skin sensitization was observed.
- Remarks on result:
- no indication of skin sensitisation
- Cellular proliferation data / Observations:
- no skin sensitization was observed.
- Interpretation of results:
- other: not sensitizing
- Conclusions:
- The substance 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.
- Executive summary:
The skin sensitization 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 log Pow 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 sensitizing to the skin of guinea pigs. Based on the estimated result 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.
Reference
The
prediction was based on dataset comprised from the following
descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 11 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 (
not "j")
)
)
and "k" )
and ("l"
and (
not "m")
)
)
and ("n"
and "o" )
)
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) >> Nitroarenes with Other Active Groups OR Radical >> Radical
mechanism via ROS formation (indirect) >> Single-Ring Substituted
Primary Aromatic Amines 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 diazonium or carbenium ion formation OR SN1 >>
Nucleophilic attack after diazonium or carbenium ion formation >>
Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after
metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after
metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >>
Nucleophilic attack after metabolic nitrenium ion formation >>
Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic
attack after reduction and nitrenium ion formation OR SN1 >>
Nucleophilic attack after reduction and nitrenium ion formation >>
Nitroarenes with Other Active Groups OR 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 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: "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, MW>500 OR Non
binder, non cyclic structure by Estrogen Receptor Binding
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as No alert found by Protein
binding by OECD
Domain
logical expression index: "j"
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 >> Acetates OR Acylation >> Direct Acylation
Involving a Leaving group >> Azlactone OR Michael addition OR Michael
addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes
>> Polarised alkene - esters OR SN2 OR SN2 >> SN2 reaction at sp3 carbon
atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and
related chemicals OR SNAr OR SNAr >> Nucleophilic aromatic substitution
OR SNAr >> Nucleophilic aromatic substitution >> Halo-pyrimidines by
Protein binding by OECD
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Not bioavailable by Lipinski
Rule Oasis ONLY
Domain
logical expression index: "l"
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: "m"
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-] by Organic functional groups (US EPA)
Domain
logical expression index: "n"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 5.18
Domain
logical expression index: "o"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 11.2
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
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 skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs 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 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;
The skin sensitization 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 log Pow 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 sensitizing to the skin of guinea pigs. Based on the estimated result 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.
The European Chemicals Bureau (2008) and HSDB (2016) conductedMagnusson-Kligman guinea pig maximization testofstructurally similar read across substanceBis(2-ethylhexyl)phthalate (CAS no: 117-81-7)in female albino Dunkin-Hartley guinea pigs to assess its skin sensitization potential.The induction procedure consisted of an intradermal injection of the test material followed by a topical application 7 days later. The guinea pigs received intradermal injection (actually 3 injections) of 0.1 ml Freund’s adjuvant alone, 0.1 ml 10% DEHP in paraffin oil, and 0.05 ml 10% DEHP in paraffin oil emulsified with 0.05 ml Freund’s adjuvant into the skin of the shoulder region. The control group received 2 injections of Freund’s adjuvant only. For the topical application, a 2.2 cm patch of filter paper was wetted with 50% DEHP in paraffin oil and applied for 48 hours to the pre-treated area. The control group was not subjected to topical application. After rest period of 14 days, the animals were challenged topically at higher non irritating concentration of concentrations 50% DEHP. A 2.2 cm patch wetted with 50% DEHP was applied to a challenge site (on the right flank) of all animals for 24 hours. The degree of response was assessed 24 hours after removal of the challenge patch and rated. Any animal showing erythema at the challenge site was considered to have shown a positive response. Since there were no positive responses, the chemical Bis(2-ethylhexyl)phthalate (CAS no: 117-81-7)can be considered as not skin sensitizing to the guinea pigs’ skin.
The above results were further supported bya Human Repeat Insult Patch Testreported by theEuropean Chemicals Agency (ECHA, 2016) forstructurally similar read across substance1,4-bis(2-ethylhexyl) benzene-1,4-dicarboxylate (CAS No: 6422-86-2) on skin of human volunteers (9/sex).Each volunteer were exposed to nine dermal applications of 0.5% DEHTP in acetone under semi-occlusive conditions over a three-week induction period. Following a two weeks rest period a challenge dose of 0.5% was applied to the skin. None of the volunteer showed any sign of skin sensitization. Hence the chemical 1,4-bis(2-ethylhexyl) benzene-1,4-dicarboxylate (CAS No: 6422-86-2) was considered to be not sensitizing to the skin of human volunteers.
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 skin sensitization and considered as non skin sensitizer.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
The skin sensitization potential of test substance 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1) and its structurally similar read across substances Bis(2-ethylhexyl)phthalate (CAS no: 117-81-7) and1,4-bis(2-ethylhexyl) benzene-1,4-dicarboxylate (CAS No: 6422-86-2) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (CAS No: 65138-66-1)is not likely to cause skin sensitization and hence can be classified as non skin sensitizer.
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