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EC number: 229-227-5 | CAS number: 6441-82-3
- 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 target chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) was assessedin various experimental studies which were conducted on rabbits and rats for target chemical2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) and its structurally similar read across substancesN, N-dimethyl-p-toluidine (CAS No: 99-97-8), 6-Hydroxy-1H-indole (CAS no: 2380-86-1)and N-Ethyl-N-(2-chloroethyl)aniline (CAS No: 92-49-9). The predicted data using QSAR toolbox has also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) is unable to cause skin irritation and thus 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
An ocular irritation potential of target chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) was assessedin various experimental studies which were conducted on rabbits for target chemical2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) and its structurally similar read across substancesN, N-dimethyl-p-toluidine (CAS No: 99-97-8) and 6-Hydroxy-1H-indole (CAS no: 2380-86-1). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) is unable to cause eye damage and thus can be considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.
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 3.4 and QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: as mentioned below
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.4
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- Name - 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride
Mol. formula: C24H30Cl2N2
Molecular Weight - 417.421 g/mole
InChI -1S/C24H30ClN2.ClH/c1-6-27(16-15-25)20-13-11-19(18(2)17-20)12-14-23-24(3,4)21-9-7-8-10-22(21)26(23)5;/h7-14,17H,6,15-16H2,1-5H3;1H/q+1;/p-1
SMILES:CCN(CCCl)c1ccc(C=CC2C(C)(C)c3ccccc3N{+}=2(C).Cl{-})c(C)c1 - Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- No data available
- Type of coverage:
- occlusive
- Preparation of test site:
- clipped
- Vehicle:
- not specified
- Controls:
- not specified
- Amount / concentration applied:
- No data available
- Duration of treatment / exposure:
- 4 hours
- Observation period:
- 72 hours
- Number of animals:
- 3
- Details on study design:
- No data available
- Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- 72 h
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- No skin irritation was observed in treated rabbits.
- Interpretation of results:
- other: not irritating
- Conclusions:
- The chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3)was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated results, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3)can be considered to be not irritating to skin.
- Executive summary:
The dermal irritation potential of 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3)was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor. The chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3)was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated results, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3)can be considered to be not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.
Reference
Estimation
method: Takes mode value from the 7 nearest neighbours
Domain logical expression:Result: In Domain
((((((((("a"
or "b" or "c" )
and ("d"
and (
not "e")
)
)
and ("f"
and (
not "g")
)
)
and ("h"
and (
not "i")
)
)
and ("j"
and (
not "k")
)
)
and ("l"
and (
not "m")
)
)
and "n" )
and ("o"
and (
not "p")
)
)
and ("q"
and "r" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as SN2 OR SN2 >> Alkylation, direct
acting epoxides and related after cyclization OR SN2 >> Alkylation,
direct acting epoxides and related after cyclization >> Nitrogen
Mustards by DNA binding by OASIS v.1.3 ONLY
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion
formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine
AND SN2 AND SN2 >> Episulfonium Ion Formation AND SN2 >> Episulfonium
Ion Formation >> Mustards by DNA binding by OECD
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as SN2 AND SN2 >> Nucleophilic
substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at
sp3 carbon atom >> Alkyl halides by Protein binding by OASIS v1.3
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as SN2 AND SN2 >> Nucleophilic
substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at
sp3 carbon atom >> Alkyl halides by Protein binding by OASIS v1.3
Domain
logical expression index: "e"
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 >> (Thio)Acyl and (thio)carbamoyl halides and
cyanides OR Acylation >> Direct acylation involving a leaving group >>
Carbamates 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 >> Conjugated systems with electron withdrawing groups
OR No alert found OR Nucleophilic addition OR Nucleophilic addition >>
Addition to carbon-hetero double bonds OR Nucleophilic addition >>
Addition to carbon-hetero double bonds >> Ketones OR SN2 >> Nucleophilic
substitution at sp3 carbon atom >> (Thio)Phosphates OR SN2 >>
Nucleophilic substitution at sp3 carbon atom >> alpha-Activated
haloalkanes OR SN2 >> Nucleophilic substitution on benzilyc carbon atom
OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >>
alpha-Activated benzyls OR SN2 >> Ring opening SN2 reaction OR SN2 >>
Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes by
Protein binding by OASIS v1.3
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as (!Undefined)Group All Lipid
Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility <
400 g/kg AND Group All Melting Point > 200 C AND Group CNHal Aqueous
Solubility < 0.1 g/L AND Group CNHal Molecular Weight > 370 g/mol by Eye
irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Group All Aqueous Solubility <
0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All
log Kow < -3.1 OR Group All log Kow > 9 OR Group All Molecular Weight >
650 g/mol OR Group CHal log Kow > 4.5 OR Group CHal Melting Point > 65 C
OR Group CHal Molecular Weight > 280 g/mol OR Group CHal Molecular
Weight > 370 g/mol by Eye irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as Halogens AND Non-Metals by
Groups of elements
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Metalloids by Groups of elements
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Not possible to classify
according to these rules (GSH) by Protein binding potency
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Slightly reactive (GSH) OR
Slightly reactive (GSH) >> Substituted haloacetamides (SN2) by Protein
binding potency
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as No alert found by DNA alerts for
AMES, MN and CA by OASIS v.1.3
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as AN2 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 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 Radical OR Radical >> Radical
mechanism via ROS formation (indirect) OR Radical >> Radical mechanism
via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR
Radical >> Radical mechanism via ROS formation (indirect) >>
Haloalcohols OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >>
Carbenium ion formation >> Alpha-Haloethers OR SN2 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 by epoxide
metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide
metabolically formed after E2 reaction >> Haloalcohols OR SN2 >>
Alkylation by epoxide metabolically formed after E2 reaction >>
Monohaloalkanes 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 >>
Monohaloalkanes OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >>
Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium
and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2
reaction with aziridinium and/or cyclic sulfonium ion formation
(enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution
after carbenium ion formation OR SN2 >> Nucleophilic substitution after
carbenium ion formation >> Monohaloalkanes 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
>> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >>
Alpha-Haloethers by DNA alerts for AMES, MN and CA by OASIS v.1.3
Domain
logical expression index: "n"
Similarity
boundary:Target:
CCN(CCCl)c1ccc(C=CC2C(C)(C)c3ccccc3N{+}=2(C).Cl{-})c(C)c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Alkene AND Alkyl arenes AND
Alkyl halide AND Ammonium salt AND Aromatic amine AND Aryl AND Indole/
Isoindole AND Overlapping groups by Organic Functional groups (nested)
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as Acetal by Organic Functional
groups (nested)
Domain
logical expression index: "q"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 2.17
Domain
logical expression index: "r"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 3.97
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 3.4 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 3.4
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of test material : 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride
- Molecular formula : C24H30Cl2N2
- Molecular weight : 417.421 g/mol
- Smiles notation : C1(=[N+](c2ccccc2C1(C)C)C)\C=C/c1c(cc(N(CCCl)CC)cc1)C.[ClH-]
- InChl : 1S/C24H30ClN2.ClH/c1-6-27(16-15-25)20-13-11-19(18(2)17-20)12-14-23-24(3,4)21-9-7-8-10-22(21)26(23)5;/h7-14,17H,6,15-16H2,1-5H3;1H/q+1;/p-1
- 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
- Duration of treatment / exposure:
- single application
- Observation period (in vivo):
- 72 hours
- Number of animals or in vitro replicates:
- 3
- Details on study design:
- No data available
- Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- 72 h
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- No eye irritation was observed in treated rabbits.
- Interpretation of results:
- other: not irritating
- Conclusions:
- The chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3)was estimated to be not irritating to the eyes of New Zealand White rabbits. Based on the estimated results, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) can be considered to be not irritating to eyes.
- Executive summary:
The ocular irritation potential of 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3)was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor. The chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3)was estimated to be not irritating to the eyes of New Zealand White rabbits. Based on the estimated results, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3)can be considered to be not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.
Reference
Estimation
method: Takes mode value from the 6 nearest neighbours
Domain logical expression:Result: In Domain
(((((((("a"
or "b" or "c" )
and ("d"
and (
not "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 SN2 OR SN2 >> Alkylation, direct
acting epoxides and related after cyclization OR SN2 >> Alkylation,
direct acting epoxides and related after cyclization >> Nitrogen
Mustards by DNA binding by OASIS v.1.3 ONLY
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion
formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine
AND SN2 AND SN2 >> Episulfonium Ion Formation AND SN2 >> Episulfonium
Ion Formation >> Mustards by DNA binding by OECD
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as SN2 AND SN2 >> Nucleophilic
substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at
sp3 carbon atom >> Alkyl halides by Protein binding by OASIS v1.3
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as (!Undefined)Group All Lipid
Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility <
400 g/kg AND Group All Melting Point > 200 C AND Group CNHal Aqueous
Solubility < 0.1 g/L AND Group CNHal Molecular Weight > 370 g/mol by Eye
irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as Group All Aqueous Solubility <
0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All
log Kow < -3.1 OR Group All log Kow > 9 OR Group All Molecular Weight >
650 g/mol OR Group C Melting Point > 55 C OR Group CHal log Kow > 4.5 OR
Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280
g/mol OR Group CHal Molecular Weight > 370 g/mol OR Group CNHal Aqueous
Solubility < 0.004 g/L OR Group CNHal log Kow > 3.8 by Eye
irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as Not possible to classify
according to these rules by Keratinocyte gene expression
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Very high gene expression OR
Very high gene expression >> alpha-Halobenzyls by Keratinocyte gene
expression
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as Inclusion rules not met by Skin
irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Aliphatic alpha-halogen-esters
OR Allyl halides,sulfonates OR Halogenated alkanes OR Ketones by Skin
irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "j"
Similarity
boundary:Target:
CCN(CCCl)c1ccc(C=CC2C(C)(C)c3ccccc3N{+}=2(C).Cl{-})c(C)c1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Alkyl chloride AND Alkyl halide
AND Amine AND Anion AND Aromatic compound AND Cation AND Halogen
derivative AND Heterocyclic compound AND Tertiary amine AND Tertiary
mixed amine by Organic functional groups, Norbert Haider (checkmol)
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Acyl chloride by Organic
functional groups, Norbert Haider (checkmol)
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Alkyl chloride AND Alkyl halide
AND Amine AND Anion AND Aromatic compound AND Cation AND Halogen
derivative AND Heterocyclic compound AND Tertiary amine AND Tertiary
mixed amine by Organic functional groups, Norbert Haider (checkmol)
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Primary alcohol by Organic
functional groups, Norbert Haider (checkmol)
Domain
logical expression index: "o"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 1.06
Domain
logical expression index: "p"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 3.35
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 chemical2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and rats for target chemical2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) and its structurally similar read across substancesN, N-dimethyl-p-toluidine (CAS No: 99-97-8), 6-Hydroxy-1H-indole (CAS no: 2380-86-1)and N-Ethyl-N-(2-chloroethyl)aniline (CAS No: 92-49-9).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 chemical2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) .The chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) is estimated to be not irritating to skin of rabbits.
Also the above result was supported by the experimental study conducted by (Sustainability Support Services (Europe) AB has the letter of access) in an OECD GLP laboratory for the structurally similar read across substanceN-dimethyl-p-toluidine (CAS No: 99-97-8) as per OECD guideline No. 404 in three healthy young adult female rabbits.During both studies, bodyweights were recorded on day 0 (prior to application) and at termination. Rabbits with good intact skin were selected for the study. The hairs of all the rabbits were clipped at contralateral sites, approximately 24 hours prior to treatment. A dose of 0.5 ml of test item (as such) was applied to the skin, over an area of approximately 6 x 6 cm clipped of hair on one side of rabbits. The other untreated side was kept as control area and 0.5 ml of distilled water was applied at this site. At the end of 4 hours, the gauze patch was removed and test item application site was wiped with water without altering the integrity of the epidermis. Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch. After 4 hours of exposure in animal no. 1, very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observation. At 24 hour very slight erythema (barely perceptible) and no oedema was observed. At 48 and 72 hours observation no erythema and no oedema was observed in animal no 1.Hence the confirmatory test was conducted after 24 hours on additional two rabbits (No. 2 and 3)to confirm the non irritant nature of the test item. Animal No. 2, revealed very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observation post patch removal. At 24 hour well defined erythema andvery slight oedema (barely perceptible) was observed. At 48 hour very slight erythema (barely perceptible) and no oedema was observed. At 72 hour no erythema and no oedema was observed. Animal No. 3, revealed very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observation post patch removal. At 24 hour very slight erythema (barely perceptible) and no oedema was observed. At 48 and 72 hour no erythema and no oedema was observed. The patch was removed after 4 hours and rabbits were observed for erythema and oedema at 1, 24, 48 and 72 hours after patch removal, evaluated and graded as per Draize method. The individual mean score at 24, 48 and 72 hours for animal nos. 1, 2 and 3 were 0.33, 1.00, 0.33 and 0.00, 0.33, 0.00, for erythema and oedema formation, respectively. Hence, under the experimental conditions tested it is concluded that the chemical N-dimethyl-p-toluidine (CAS No: 99-97-8) was Non-Irritating to the skin of female New Zealand White rabbits.
The Burnett CL et.al. {International Journal of Toxicology; Sep-Oct;33(3 Suppl):24S-35S, 2014} conducted skin irritation study of read across chemical 6-Hydroxy-1H-indole (CAS no: 2380-86-1) in three male New Zealand White Rabbits. Approximately, 500mg (0.5g) of 6-Hydroxy-1H-indole moistened with water was applied to an intact area skin under semi-occlusive condition. After 4 hours patches were removed and the remaining test substance was rinsed off and skin reactions were scored. A slight yellow staining was observed in 2 out of 3 rabbits with primary irritation score of 0.0 at all observation periods. Hence the chemical 6-Hydroxy-1H-indole (CAS no: 2380-86-1) was considered to be not irritating to the skin of three male New Zealand White Rabbits.
The above results were further supported by the experimental study reported by NTRL (1978)for the structurally similar read across substanceN-Ethyl-N-(2-chloroethyl)aniline (CAS No: 92-49-9) conducted on six New Zealand White rabbits under occlusive condition. In this study, the undiluted N-Ethyl-N-(2-chloroethyl)aniline was applied to the two clipped intact sites on saddle area of each of the six rabbits under a 1" x 1" 2-ply surgical gauze patch for 4 hours exposure period. Each patch was held in place with two strips of adhesive tape. At the end of the 4-hour exposure period, the patches were removed and any residual sample was gently sponged from the skin with a moistened towel. The reactions were scored immediately after removal of the patches (4-hour reading), and again at 24 and 48 hours after initial application. Following a 4-hour patch application to the intact skin of New Zealand White rabbits, no irritative effects were noted in five rabbits; one replacement rabbit exhibited erythema and edema prior to death; and a second replacement rabbit exhibited erythema, edema, and a leathery texture at both sites during the study. Therefore based on the observations N-Ethyl-N-(2-chloroethyl)aniline (CAS No: 92-49-9)was considered to be non-irritant to the skin of New Zealand White rabbits under occlusive condition by the DOT regulations.
Based on the available data for thetarget chemical2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) and its structurally similar read across substancesN, N-dimethyl-p-toluidine (CAS No: 99-97-8), 6-Hydroxy-1H-indole (CAS no: 2380-86-1)and N-Ethyl-N-(2-chloroethyl)aniline (CAS No: 92-49-9),it can be concluded thatchemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) 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 chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) has been investigated for potential for ocular irritati onto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) its structurally similar read across substances N-dimethyl-p-toluidine (CAS No: 99-97-8)and6-Hydroxy-1H-indole (CAS no: 2380-86-1).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 ocular irritation potential was estimated for test chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) .The chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) is estimated to be not irritating to eye of rabbits.
Also the above result was supported by the experimental studies conducted in an OECD GLP laboratory by (Sustainability Support Services (Europe) AB has the letter of access) for the structurally similar read across substance N-dimethyl-p-toluidine (CAS No: 99-97-8) as per OECD guideline No. 405 in New Zealand White female rabbit eyes. The eyes of all the rabbits were examined 24 hours prior to treatment. One eye of each rabbit served as control and other as treated. Control eye was left untreated whereas; 0.1 ml (as such, undiluted) of chemical was instilled in the other (treated) eye of each rabbit. The eye was observed at 1, 24, 48 and 72 hour after instillation. Ophthalmoscope was used for scoring of eye lesions. In the initial test, 0.1 ml of test item was applied into the conjunctival sac of the right eye of animal no.1 whereas the left eye of the rabbit served as the control. As animal no. 1 showed no severe ocular lesions a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3); 0.1 ml of chemical was instilled into the conjunctival sac of right eye of both the rabbits and left eye served as the control. Untreated eye of all the three rabbits was normal throughout the experimental period of 72 hours. Observation at 1 hour after instillation of chemical revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all the animals. Observation at 24 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae -Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in animal no. 2 whereas no swelling (normal) in animal no. 1 and 3. At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0% damage in all the animals. Observation at 48 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae -Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: No swelling (normal) was observed in all the animals. Observation at 72 hour after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Blood vessels normal in all the animals; Chemosis: No swelling (normal) was observed in all the animals. The individual mean score for animal nos. 1, 2 and 3at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.67, 0.00; 0.00, 0.00, 0.67, 0.33 and 0.00, 0.00, 0.67, 0.00 respectively and reversibility of effects on eyes of rabbits was observed within 72 hours. Hence, under the experimental conditions this it is concluded that N, N-dimethyl-p-toluidine is “Non Irritant” to New Zealand White female rabbit eyes.
The above studies were further supported by the experimental study conducted by Burnett CL et.al. {International Journal of Toxicology; Sep-Oct;33(3 Suppl):24S-35S, 2014} for read across chemical 6-Hydroxy-1H-indole (CAS no: 2380-86-1) in three female New Zealand White Rabbits. The 0.1ml of 5% 6-Hydroxy-1H-indole in 30% PEG-6 solution was instilled into the right eye of each rabbit whereas the other untreated eye served as control. Both the eyes were observed for ocular lesions at 1, 24, 48 and 72 hours post-treatment. Since none of the rabbits developed any ocular lesion, the chemical6-Hydroxy-1H-indole (CAS no: 2380-86-1) was considered to be not irritating to the eyes of three female New Zealand White Rabbits.
Based on the available data for thetarget chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) and its structurally similar read across substancesN-dimethyl-p-toluidine (CAS No: 99-97-8)and6-Hydroxy-1H-indole (CAS no: 2380-86-1),it can be concluded thatchemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) 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 chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicates that the chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) is unlikely to cause skin and eye irritation. Hence 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 6441-82-3) can be classified under the category “Not Classified” for skin and eye as per CLP.
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