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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
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3 ). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro. Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- Data is from OECD QSAR Toolbox version 3.3 and the supporting QMRF report has been attached.
- Qualifier:
- according to guideline
- Guideline:
- other: As mention below
- Principles of method if other than guideline:
- Prediction is done using OECD QSAR Toolbox version 3.3, 2017
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- Name - 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 - Target gene:
- Histidine
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not specified
- Cytokinesis block (if used):
- not specified
- Metabolic activation:
- with
- Metabolic activation system:
- S9 metabolic activation
- Test concentrations with justification for top dose:
- not specified
- Vehicle / solvent:
- not specified
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- not specified
- Details on test system and experimental conditions:
- not specified
- Rationale for test conditions:
- not specified
- Evaluation criteria:
- Prediction was done considering a dose dependent increase in the number of revertants/plate.
- Statistics:
- not specified
- Species / strain:
- S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- not specified
- Remarks on result:
- other: No mutagenic effect were observed.
- Conclusions:
- 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3 )was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.
- Executive summary:
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3 ). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with S9 metabolic activation system. 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro. Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.
Reference
The
prediction was based on dataset comprised from the following
descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain logical expression:Result: In Domain
(((((((("a"
or "b" or "c" )
and "d" )
and ("e"
and (
not "f")
)
)
and ("g"
and (
not "h")
)
)
and "i" )
and ("j"
and (
not "k")
)
)
and "l" )
and ("m"
and "n" )
)
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 >> Alkylation,
direct acting epoxides and related after cyclization AND SN2 >>
Alkylation, direct acting epoxides and related after cyclization >>
Nitrogen Mustards by DNA binding by OASIS v.1.3 ONLY
Domain
logical expression index: "e"
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: "f"
Referential
boundary: The
target chemical should be classified as Michael addition OR Michael
addition >> P450 Mediated Activation to Quinones and Quinone-type
Chemicals OR Michael addition >> P450 Mediated Activation to Quinones
and Quinone-type Chemicals >> Arenes OR Michael addition >> P450
Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic
(PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR
SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >>
Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Secondary
aromatic amine by DNA binding by OECD
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Non binder, without OH or NH2
group by Estrogen Receptor Binding
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as Non binder, impaired OH or NH2
group OR Non binder, MW>500 OR Non binder, non cyclic structure by
Estrogen Receptor Binding
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "j"
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: "k"
Referential
boundary: The
target chemical should be classified as Group CNHal log Kow > 3.8 by
Skin irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "l"
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: "m"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.967
Domain
logical expression index: "n"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 3.82
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Genetoxicity in vitro:
Prediction model based estimation and data from read across chemical have been reviewed to determine the mutagenic nature of 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3). The studies are as mentioned below
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3 ). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro. Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.
In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by National Institute of Technology and Evaluation (J-check, 2017) to determine the mutagenic nature of Chlorocyclohexane (542-18-7). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Bacterial reverse mutation test was performed to determine the mutagenic nature of Chlorocyclohexane. The study was performed as per the preincubation protocol using S. typhimurium TA 1535, TA 1537, TA 98, TA100 and E. coli WP2 in the presence and absence of S9 metabolic activation system. The test chemical was dissolved in DMSO and used at dose levels of 2.44, 4.88, 9.77, 19.5, 39.1, 78.1, 156 μg/plate (TA100, TA1535 strains), 9.77, 19.5, 39.1, 78.1, 156, 313 μg/plate (TA98, TA1537, WP2uvrA/pKM101 strains) without S9 and 9.77, 19.5, 39.1, 78.1, 156, 313 μg/plate (TA100, TA1535, TA98, TA1537 strains), 9.77, 19.5, 39.1, 78.1, 156, 313, 625 μg/plate (WP2uvrA/pKM101 strain) with S9. The plates were preincubated for 20 mins at 37°C and the exposure duration was 48 hrs. The plates were observed for dose-related and reproducible doubling of the mean number of revertant colonies per plate than that of the negative control. Chlorocyclohexane did not induce gene mutation in S. typhimurium TA 1535, TA 1537, TA 98, TA100 and E. coli WP2 in the presence and absence of S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.
In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by Rogelio Tornero-Velez et.al. (Drug Metabolism and Disposition,2Drug Metabolism and Disposition004) to determine the mutagenic nature of1, 3 Dichloropropane (142-28-9). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Gene mutation toxicity study was performed to determine the mutagenic nature of 1,3- dichloropropane. The study was performed using Salmonella typhimurium strainsTA98, TA100, TA104 TA1535, RSJ100, GSST1 in the presence and absence of S9 metabolic activation system. The chemical was dissolved in DMSO as solvent and used at dose levels 0.00, 0.01, 0.05, 0.10, 0.50, 1.00, 2.00 mg/plate. Concurrent solvent and positive controls were included in the study. 1, 3 Dichloropropane did not induce mutation in Salmonella typhimurium TA98, TA100, TA104 TA1535, RSJ100, GSST1 in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.
Based on the data available for the target chemical and its read across substance and applying weight of evidence 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3)does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.
Justification for classification or non-classification
Thus based on the above annotation and CLP criteria for the target chemical . 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (6441-82-3)does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.
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