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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
Effects on fertility
Description of key information
The NOAEL was estimated to be 96.2 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride.
Based on the above predictions on 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride, it can be concluded that NOAEL value is 96.2 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride can be Not classified for reproductive toxicity.
Link to relevant study records
- Endpoint:
- toxicity to reproduction
- 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: as below
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.3
- GLP compliance:
- not specified
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of test material (IUPAC name): 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3- trimethyl-3H-indolium chloride
- Common name: Astrazonrot 6B
- Molecular formula: C24H30ClN2Cl
- 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:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- not specified
- Route of administration:
- oral: feed
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- not specified
- Details on exposure:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 2 years
- Frequency of treatment:
- Daily
- Dose / conc.:
- 96.2 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- not specified
- Control animals:
- yes
- Details on study design:
- not specified
- Positive control:
- not specified
- Parental animals: Observations and examinations:
- not specified
- Oestrous cyclicity (parental animals):
- not specified
- Sperm parameters (parental animals):
- not specified
- Litter observations:
- not specified
- Postmortem examinations (parental animals):
- not specified
- Postmortem examinations (offspring):
- not specified
- Statistics:
- not specified
- Reproductive indices:
- not specified
- Offspring viability indices:
- not specified
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 96.2 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- gross pathology
- histopathology: non-neoplastic
- Remarks on result:
- other: No effect observed
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- other: not specified
- Generation:
- other: not specified
- Based on:
- not specified
- Sex:
- not specified
- Basis for effect level:
- other: not specified
- Remarks on result:
- other: not specified
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- other:
- Based on:
- not specified
- Sex:
- not specified
- Basis for effect level:
- other: not specified
- Remarks on result:
- other: not specified
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- NOAEL was estimated to be 96.2 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride.
- 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. The NOAEL was estimated to be 96.2 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride.
Reference
The
prediction was based on dataset comprised from the following
descriptors: NOAEL
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" )
)
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 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 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: "g"
Referential
boundary: The
target chemical should be classified as Dihydroxyl group by Organic
Functional groups (nested)
Domain
logical expression index: "h"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 1.82
Domain
logical expression index: "i"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 7.75
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 96.2 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is Klimisch 2 and from OECD QSAR toolbox
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Reproductive toxicity:
In different studies, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in mice and 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 substance1,2-dichloroethane(CAS no 107-06-2). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.
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. The NOAEL was estimated to be 96.2 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride.
In a another experimental study conducted by Sweeney et al (Regulatory Toxicology and Pharmacology 81 (2016) 468e479) on structurally similar read across1,2-dichloroethane(CAS no 107-06-2), Crl:CD (Sprague-Dawley) male and female rats treated with 1,2-dichloroethane in the concentration of 0 (vehicle), 50, 150, and 300 mg/kg bw/day orally by drinking water as per OECD 443. Decrease in body weight and body weight gain was observed in treated rats in P generation. As EDC in drinking water to have poor palatability; drinking water consumption was generally decreased, relative to Controls, in a dose-related manner. Similarly, No effect was observed on estrous cycle, sperm evaluation, Fertility, gestation, vaginal opening and preputial separation of treated P male and female rats as compared to control. In addition, Change in relative liver weight was observed in F0 female rats. As no significant histological findings were identified in the liver (or any other tissue), the organ weight change may be considered non adverse. No gross pathological and Histopathological changes were observed in treated male and female P rats. No Reproductive/developmental effects (Cohort 1), neurodevelopmental effects (Cohort 2), and developmental immune effects (Cohort 3) were observed in F1 male and female rats. Therefore, NOAEL was considered to be 155 mg/kg/day for male and 182 mg/kg bw for female P generation and 184 mg/kg/day for male and 169 mg/kg bw for female F1 generation when Crl:CD (Sprague-Dawley) male and female rats treated with 1,2-dichloroethane orally by drinking water.
Father supported by experimental study given byWorld health organization (IARC MONOGRAPHS VOLUME 71, (1987a)) on structurally similar read across1,2-dichloroethane(CAS no 107-06-2),ICR Swiss male and female mice treated with 1,2-dichloroethane in the concentration of 0, 5, 15 or 50 mg/kg bw orally by drinking water. No effect on Fertility, gestation and lactation indices of treated P rats were observed. In addition, No effect on survival and body weight of treated pups were observed. Therefore, NOAEL was considered to be 50 mg/kg/day P and F1 generation when ICR Swiss male and female mice treated with 1,2-dichloroethane orally by drinking water.
Thus, based on the above studies and predictions on 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride and its read across substances, it can be concluded that NOAEL value is 96.2 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride can be Not classified for reproductive toxicity.
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the above studies and predictions on 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride and its read across substances, it can be concluded that NOAEL value is 96.2 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride can be Not classified for reproductive toxicity.
Additional information
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