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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
Acute oral toxicity:
Acute oral toxicity dose (LD50) of 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was predicted based on OECD QSAR toolbox 3443mg/kg bw and different studies available on structurally similar read across substance 2-[2-[4-[(2-chloroethyl)methylamino]phenyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 3648-36-0) 2260 mg/kg bw and for the closely related read across substance 2,2-Dichloro-1-(3-methyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethanone (CAS no: 98730-04-2) 5000 mg/kg bw. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride can be classified as category V of acute oral toxicity.
Acute Inhalation toxicity:
Acute Inhalation toxicity dose (LC50) of 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was predicted based on OECD QSAR toolbox 22.9 mg/L air, and different studies available for the closely related read across substance Bromochloromethane (CAS no: 74-97-5) 12030 mg/m3 and Tris(2-chloro-1-methylethyl) phosphate (CAS no: 13674-84-5) >4600 mg/m3. All these studies concluded that the LC50 value is greater than 5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride can be classified as category V of acute inhalation toxicity.
Acute Dermal toxicity:
Acute Dermal toxicity dose (LD50) for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was predicted based on OECD QSAR toolbox 4242 mg/kg bwand differentstudies available on closely related read across substance3-Chloropropyl)triethoxysilane (CAS No. 5089-70-3) >2000 mg/kg bw and Tris(2-chloro-1-methylethyl) phosphate (13674-84-5) >2000 mg/kg bw. All these studies concluded that the LD50 value is>2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride can be classified as category V of acute dermal toxicity.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: estimated
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.3
- GLP compliance:
- not specified
- Test type:
- other: not specified
- Limit test:
- no
- 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:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- not specified
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Details on oral exposure:
- not specified
- Doses:
- 3443 mg/kg
- No. of animals per sex per dose:
- not specified
- Control animals:
- not specified
- Details on study design:
- not specified
- Statistics:
- not specified
- Preliminary study:
- not specified
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 3 443 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: 50% mortality observed
- Mortality:
- not specified
- Clinical signs:
- other: not specified
- Gross pathology:
- not specified
- Other findings:
- not specified
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- LD50 was estimated to be 3443 mg/kg bw when Sprague-Dawley female rats were treated with 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride by oral gavage route.
- Executive summary:
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride ( 6441-82-3). The LD50 was estimated to be 3443 mg/kg bw when Sprague-Dawley female rats were treated with 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride by oral gavage route.
Reference
The
prediction was based on dataset comprised from the following
descriptors: LD50
Estimation method: Takes average value from the 5 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 ("i"
and "j" )
)
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 Non binder, without OH or NH2
group by Estrogen Receptor Binding
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as Non binder, MW>500 OR Non
binder, non cyclic structure OR Very strong binder, OH group by Estrogen
Receptor Binding
Domain
logical expression index: "f"
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: "g"
Referential
boundary: The
target chemical should be classified as Acylation 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 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 >>
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: "h"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "i"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.878
Domain
logical expression index: "j"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 3.12
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 3 443 mg/kg bw
- Quality of whole database:
- Data is Klimisch 2 and from QSAR toolbox 3.3
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: estimated
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.3
- GLP compliance:
- not specified
- Test type:
- other: not specified
- Limit test:
- no
- 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:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- not specified
- Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- not specified
- Remark on MMAD/GSD:
- not specified
- Details on inhalation exposure:
- not specified
- Analytical verification of test atmosphere concentrations:
- not specified
- Duration of exposure:
- 4 h
- Remarks on duration:
- not specified
- Concentrations:
- 22.9 mg/L
- No. of animals per sex per dose:
- not specified
- Control animals:
- not specified
- Details on study design:
- not specified
- Statistics:
- not specified
- Preliminary study:
- not specified
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- 22.9 mg/L air
- Based on:
- test mat.
- Remarks on result:
- other: 50% mortality observed
- Mortality:
- not specified
- Clinical signs:
- other: not specified
- Body weight:
- not specified
- Gross pathology:
- not specified
- Other findings:
- not specified
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- LC50 was estimated to be 22.9 mg/L air, when Sprague-Dawley male and female rats were exposed with 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride for 4 h of exposure period.
- Executive summary:
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3). The LC50 was estimated to be 22.9 mg/L air, when Sprague-Dawley male and female rats were exposed with 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride for 4 h of exposure period.
Reference
The
prediction was based on dataset comprised from the following
descriptors: LC50
Estimation method: Takes average 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 ("g"
and (
not "h")
)
)
and ("i"
and (
not "j")
)
)
and ("k"
and "l" )
)
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 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 by Protein binding by OASIS v1.3
Domain
logical expression index: "f"
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: "g"
Referential
boundary: The
target chemical should be classified as Aliphatic Carbon [CH] AND
Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic
Nitrogen, one aromatic attach [-N] AND Aliphatic-C=N-Aliphatic AND
Amino, aliphatic attach [-N<] AND Aromatic Carbon [C] AND Chlorine,
aliphatic attach [-Cl] AND Olefinic carbon [=CH- or =C<] AND Tertiary
Carbon by Organic functional groups (US EPA)
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as 1,2-Oxaza compounds [N-C-O-] by
Organic functional groups (US EPA)
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Halogens AND Non-Metals by
Groups of elements
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Metalloids by Groups of elements
Domain
logical expression index: "k"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 1.43
Domain
logical expression index: "l"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 2.89
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 22 900 mg/m³ air
- Quality of whole database:
- Data is Klimisch 2 and QSAR toolbox 3.3.
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: estimated
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.3
- GLP compliance:
- not specified
- Test type:
- other: not specified
- Limit test:
- no
- 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
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- not specified
- Type of coverage:
- semiocclusive
- Vehicle:
- not specified
- Details on dermal exposure:
- not specified
- Duration of exposure:
- 24 h
- Doses:
- 4242 mg/kg
- No. of animals per sex per dose:
- not specified
- Control animals:
- not specified
- Details on study design:
- not specified
- Statistics:
- not specified
- Preliminary study:
- not specified
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 4 242 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: 50% mortality observed
- Mortality:
- not specified
- Clinical signs:
- other: not specified
- Gross pathology:
- not specified
- Other findings:
- not specified
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- LD50 was estimated to be 4242 mg/kg bw, when New Zealand White male and female rabbit was treated with 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride for 24 hours by dermal application semiocclusively.
- Executive summary:
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3). The LD50 was estimated to be 4242 mg/kg bw, when New Zealand White male and female rabbit was treated with 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride for 24 hours by dermal application semiocclusively.
Reference
The
prediction was based on dataset comprised from the following
descriptors: LD50
Estimation method: Takes average 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" )
)
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 No alert found 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 Inclusion rules not met by Skin
irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Halogenated alkanes by Skin
irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as (!Undefined)Group All Lipid
Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 4
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 AND Group CNHal Molecular
Weight > 380 g/mol by Skin irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as 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 Skin
irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "j"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 1.59
Domain
logical expression index: "k"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 2.89
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 4 242 mg/kg bw
- Quality of whole database:
- Data is Klimisch 2 and from QSAR toolbox 3.3
Additional information
Acute oral toxicity:
In different studies, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride along with the study available on structurally similar read across substance 2-[2-[4-[(2-chloroethyl)methylamino]phenyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 3648-36-0) and closely related read across substance 2,2-Dichloro-1-(3-methyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethanone (CAS no: 98730-04-2). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-[2-[4-[(2-chloroethyl) ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride ( 6441-82-3). The LD50 was estimated to be 3443 mg/kg bw when Sprague-Dawley female rats were treated with 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride by oral gavage route.
The above study supported by U.S. National Library of Medicine (ChemIDplus, 2017), for the structurally similar read across substance 2-[2-[4-[(2-chloroethyl)methylamino]phenyl] vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 3648-36-0).The acute oral toxicity was tested in rat at the dose concentration of 2260 mg/kg bw. Changes in Blood were observed in tested animals. 50% mortality was observed at 2260 mg/kg bw. Therefore, LD50 was considered to be 2260 mg/kg bw, when rats were treated with 2-[2-[4-[(2-chloroethyl) methylamino]phenyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CAS no: 3648-36-0) via oral route.
This study is further supported by U.S. National Library of Medicine (ChemIDplus, 2017), for the closely related read across substance2,2-Dichloro-1-(3-methyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethanone (CAS no: 98730-04-2).The acute oral toxicity was tested in rat at the dose concentration of 5000 mg/kg bw. No mortality was observed at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rats were treated with 2,2-Dichloro-1-(3-methyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethanone via oral route.
Thus, based on the above studies on 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3) and it’s read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride can be classified as category V of acute oral toxicity.
Acute Inhalation toxicity:
In different studies, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3) has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and mice for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride along with the study available on closely related read across substance Bromochloromethane (CAS no: 74-97-5) and Tris(2-chloro-1-methylethyl) phosphate (CAS no: 13674-84-5). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3). The LC50 was estimated to be 22.9 mg/L air, when Sprague-Dawley male and female rats were exposed with 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride for 4 h of exposure period.
The above study is supported by U.S. National Library of Medicine (ChemIDplus, 2017), for the closely related read across substance Bromochloromethane (CAS no: 74-97-5).The acute inhalation toxicity study was conducted in mouse at the concentration of12030 mg/m3. 50% mortality was observed at12030 mg/m3with clinical Symptoms like dyspnea and changes in lungs, thorax, muscle weakness and general anesthetic symptoms were observed, when exposed for 7 hours. Therefore, LC50 was considered to be 12030 mg/m3 when mouse was treated with Bromochloromethane by inhalation for 7 hours.
These results are further supported by GESTIS SUBSTANCE Database (2017), for the closely related read across substance Tris(2-chloro-1-methylethyl) phosphate (CAS no: 13674-84-5).The acute inhalation toxicity study was conducted in rat at the concentration of 4600 mg/m3. No mortality was observed at 4600 mg/m3.Therefore, LC50 was considered to be >4600 mg/m3 when rat was treated with Tris(2-chloro-1-methylethyl) phosphate by inhalation for 4 hours.
Thus, based on the above studies on 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3) and it’s read across substances, it can be concluded that LC50 value is greater than 5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride can be classified as category V of acute inhalation toxicity.
Acute Dermal toxicity:
In different studies, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats and rabbits for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride along with the study available on closely related read across substance 3-Chloropropyl)triethoxysilane (CAS No. 5089-70-3) and Tris(2-chloro-1-methylethyl) phosphate (13674-84-5). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3). The LD50 was estimated to be 4242 mg/kg bw, when New Zealand White male and female rabbit was treated with 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride for 24 hours by dermal application semiocclusively.
This study is supported by United Nations Environmental Programme (UNEP, 2010), for the closely related read across substance 3-Chloropropyl)triethoxysilane (CAS No. 5089-70-3). Acute Dermal toxicity study was conducted in male and female rats at the concentration of 2000 mg/kg bw. Test material (purity - 97.0%) was applied undiluted at 2000 mg/kg for 24 hours under a semi-occlusive dressing to the dorsal skin of 5 male and 5 female rats. The application volume was 2.00 cm3/kg body weight. The test substance was removed with warm water after the 24 hour exposure period. The animals were examined for clinical signs 30 minutes, 1, 2, 3, 4, 5, and 6 hrs post-dosing, and then once daily for two weeks. Body weight determinations were performed on the day of dosing, and days 7 and 14 (study termination). All animals were subject to a gross necropsy. The test substance with an applied dose of 2000 mg/kg body weight in 5 male and 5 female animals caused no lethality. Normal body weight gain was observed during the 14-day observation period. No signs of toxicity were observed in the male or female animals. Very slight erythema was observed in one male animal (48 and 72 hours after application) and two female animals (48 hours to day 5) at the site of application. By day 6, all skin irritation had subsided. No abnormalities were noted at necropsy. Therefore, LD50 was considered to be >2000 mg/kg bw, when male and female rats were treated with of 3-Chloropropyl)triethoxysilane by semi-occlusive dermal application.
The above study is further supported by National Industrial Chemicals Notification and Assessment Scheme (NICNAS, 2017) and EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID Dataset, 2000), for the closely related read across substance Tris(2-chloro-1-methylethyl) phosphate (13674-84-5). Acute Dermal toxicity study was conducted in male and female rabbits at the concentration of 2000 mg/kg bw. 3 male and 3 female rabbits dosed dermally for 24 hours. 2/3 application sites on the males and 1/3 on the females were abraded through the epidermis. Application sites were assessed for irritancy at 24 and 72 hours post treatment. No animals died. All animals showed some erythema and oedema formation at 24 hours but were normal at 72 hours. Therefore, LD50 was considered to be >2000 mg/kg bw, when male and female rabbits were treated with Tris(2-chloro-1-methylethyl) phosphate by dermal application to the abraded skin through the epidermis.
Thus, based on the above studies on 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3) and it’s read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride can be classified as category V of acute dermal toxicity.
Justification for classification or non-classification
Based on the above studies and prediction on 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3) and it’s read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw for acute oral and dermal toxicity and LC50 value is greater than 5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride can be classified as category V for acute oral, dermal and inhalation toxicity.
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