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EC number: 221-831-7 | CAS number: 3248-91-7
- 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
Effect on fertility:
No Observed Adverse Effect Level (NOAEL) was considered to be 10mg/kg/day and LOAEL was considered to be 50mg/kg bw . When female Sprague Dawley rats were treated with 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7) orally.
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data from secondary source
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Principles of method if other than guideline:
- Reproduction and developmental toxicity study 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloridewas performed on Sprague Dawley rats.
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- No data available
- Specific details on test material used for the study:
- - Name of test material: Basic Violet 2
- IUPAC name: 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride
- Molecular formula: C22H23N3ClH
- Molecular weight: 365.906 g/mol
- Substance type: Organic
- Physical state: No data
- Purity:No data
- Impurities (identity and concentrations): No data - Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- Hsd: SD strain
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- No data available
- Route of administration:
- oral: unspecified
- Vehicle:
- water
- Remarks:
- Distilled water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Test material dissolved in distilled water
DIET PREPARATION
- Rate of preparation of diet (frequency):No data available
- Mixing appropriate amounts with (Type of food )
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle: 2,10 and 50 mg/kg bw/day
- Amount of vehicle (if gavage): 10ml/kg bw/day
- Lot/batch no. (if required): No data available
- Purity: No data available - Details on mating procedure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 9 days ( from day 6 through day 15 gestation)
- Frequency of treatment:
- daily
- Details on study schedule:
- No data available
- Remarks:
- 2,10 and 50 mg/kg bw/day
- No. of animals per sex per dose:
- Total:72
2mg/kg bw/day:24
10mg/kg bw/day:24
50 mg/kg bw/day:24 - Control animals:
- not specified
- Details on study design:
- No data available
- Positive control:
- No data available
- Parental animals: Observations and examinations:
- Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: yes
DETAILED CLINICAL OBSERVATIONS: Yes
Time schedule:
BODY WEIGHT: Yes
Time schedule for examinations:
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes Food consumption was determined weekly.
Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
Time schedule for examinations: - Oestrous cyclicity (parental animals):
- No data available
- Sperm parameters (parental animals):
- No data available
- Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: [yes/no]
- If yes, maximum of [...] pups/litter ([...]/sex/litter as nearly as possible); excess pups were killed and discarded.
PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2 / F3] offspring:
[number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities, anogenital distance (AGD), presence of nipples/areolae in male pups, other:]foetuses were weighed, sexed and Number of implantation sites were observed.
GROSS EXAMINATION OF DEAD PUPS:: yes, subjected to external,soft tissue or skeletal examinations.
ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY:No data
ASSESSMENT OF DEVELOPMENTAL IMMUNOTOXICITY:No data - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals [describe when, e.g. as soon as possible after the last litters in each generation were produced.]
- Maternal animals: All surviving animals [describe when, e.g. after the last litter of each generation was weaned.]yes
GROSS NECROPSY: yes
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.] final body weight, uterus weight and corrected body weight were Observed
HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.No data - Postmortem examinations (offspring):
- SACRIFICE
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at [#?] days of age.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows:
GROSS NECROPSY
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]: No data
HISTOPATHOLOGY / ORGAN WEIGTHS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.:The foetuses were subjected to external, soft tissue or skeletal examinations - Statistics:
- No data available
- Reproductive indices:
- No data available
- Offspring viability indices:
- No data available
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Violet coloured faeces in 10mg/kg bw/day and 50mg/kg bw/day dose groups while Dyspnoea in 50mg/kg bw/day group were observed.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced body weight in 50mg/kg bw/day group from day 8
- 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:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- The number of implantations was decreased in 50mg/kg bw/day dose group.
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- clinical signs
- body weight and weight gain
- organ weights and organ / body weight ratios
- reproductive performance
- Remarks on result:
- other: No effect was observed at given dose
- Dose descriptor:
- LOAEL
- Effect level:
- 50 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- organ weights and organ / body weight ratios
- reproductive performance
- Remarks on result:
- other: toxic effects observed at given dose level
- Critical effects observed:
- not specified
- System:
- other: 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:
- effects observed, treatment-related
- Description (incidence and severity):
- Foetal weight was decreased in the 50mg/kg bw/day dose group
- 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
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- Foetal visceral exam and Foetal skeletal exam no treatment related effects was observed.
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 10 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- body weight and weight gain
- gross pathology
- other: Foetal visceral and skeletal finding
- Remarks on result:
- other: No effect was observed
- Dose descriptor:
- LOAEL
- Generation:
- F1
- Effect level:
- 50 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: effect on body weight was 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
- Reproductive effects observed:
- no
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- No Observed Adverse Effect Level (NOAEL) was considered to be 10mg/kg/day and LOAEL was considered to be 50 mg/kg bw.When female Sprague Dawley rats were treated with 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7) orally.
- Executive summary:
The reproduction and development toxicity study of 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7)was performed on female Sprague Dawley Hsd: SD strainrats. 72 rats were divided as 24 rats /dose group. The test materialdissolved in water were administers in dose concentration 0, 5, 10and 50 mg/kg bw/day from day 6 through day 15of gestationby oral gavage route. Animals were observed for clinical signs, Food consumption and body weight .On day 20 post-coitum, the dams were sacrificed and subjected to a macroscopic examination. The litter parameters like number of implantation sites. The foetuses were weighed and subjected to external, soft tissue or skeletal examinations.
Clinical sings like violet coloured faeces in 10mg/kg bw/day and 50mg/kg bw/day dose groups while dyspnoea in 50mg/kg bw/day group were observed.Body weightreduced in 50mg/kg bw/day group from day 8 and reductionin food consumptionwas observed during treatment. At necropsy final body weight, uterus weight and corrected body weight were decreased in 50mg/kg bw/day dose group in dams were noted. In litter the number of implantations was decreased in 50mg/kg bw/day dose group and foetal weight decrease in 50mg/kg bw/day dose group but no treatment related effects were observed in Foetal visceral and skeletal examination at any dose group. HenceNo Observed Adverse Effect Level (NOAEL) was considered to be 10mg/kg/day and LOAEL was considered to be 50mg/kg bw.When femaleSprague Dawley rats were treated with4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7)orally.
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEL
- 50 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 4 and from secondary source
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
The reproductive toxicity via oral route
In different studies, 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7) 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 rats for 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7)
This study published in a report by Scientific Committee on Consumer Safety (the Scientific Committee on Consumer Products, SCCS/1340/10,2011) The reproduction and development toxicity study of 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7)was performed on female Sprague Dawley Hsd: SD strain rats. 72 rats were divided as 24 rats /dose group. The test material dissolved in water were administers in dose concentration 0, 5, 10and 50 mg/kg bw/day from day 6 through day 15of gestation by oral gavage route. Animals were observed for clinical signs, Food consumption and body weight .On day 20 post-coitum, the dams were sacrificed and subjected to a macroscopic examination. The litter parameters like number of implantation sites. The foetuses were weighed and subjected to external, soft tissue or skeletal examinations.
Clinical sings like violet coloured faeces in 10mg/kg bw/day and 50mg/kg bw/day dose groups while dyspnoea in 50mg/kg bw/day group were observed. Body weight reduced in 50mg/kg bw/day group from day 8 and reduction in food consumption was observed during treatment. At necropsy final body weight, uterus weight and corrected body weight were decreased in 50mg/kg bw/day dose group in dams were noted. In litter the number of implantations was decreased in 50mg/kg bw/day dose group and foetal weight decrease in 50mg/kg bw/day dose group but no treatment related effects were observed in Foetal visceral and skeletal examination at any dose group. Hence No Observed Adverse Effect Level (NOAEL) was considered to be 10mg/kg/day and LOAEL was considered to be 50mg/kg bw .When female Sprague Dawley rats were treated with4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91 -7)orally.
This is further supported by experimental study conducted by Ryo Ohta, Atsuya Takagi, Hideo Ohmukai, Hideki Marumo, Atsushi Ono, Yuko Matsushima, Tohru Inoue, Hiroshi Ono, Jun Kanno (The Journal of Toxicological Sciences, Vol. 37, No. 5, 879-889, 2012) The reproductive toxicity study of New Fuchsin (3248-91-7)was performed on female C57BL/6Jrats.18 mice were divided as 6 rats /dose group.6 week old C57BL/6J ovariectomized mice were checked for vaginal smears 4 days before the start of the test. The animals were acclimatized for a period of 2 weeks. At 8 weeks of age, non-estrus mice were selected. The test material dissolved in water were administers in dose concentration 0,300mg/kg bw/day by oral gavage route of exposure at 24 hrs interval for 7 consecutive days. The dosing volume was 5ml/Kg were used .17α-ethynyl estradiol was used as the reference control. Vehicle control animals were also observed. Based on the dose range finding study performed highest dose 300mg/kg bw were selected. The animals were observed daily for clinical signs with the body weight recorded.24 hrs after the last treatment; the animals were euthanized by cervical dislocation. The uterus was carefully dissected at the level of the vaginal fornix, trimmed of fascia and fat under a stereomicroscope and weighed including the luminal fluid (wet weight), then pierced, gently blotted on moistened filter and weighed again for blot weight. Significant change in uterine weight was noted. Test material showed weak but significant agonistic and antagonistic effect at dose concentration 300mg/kg bw by oral route. Hence the Low Observed Effect Level (LOEL) was considered to be 300 mg/Kg/day. When femaleC57BL/6Jmice were treated with New Fuchsin (3248-91-7)orally.
So, based on the above mentioned studies for target substance 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7), reduction in body weight , food consumption , adverse effects on reproductive organ and decrease in number of implantations was observed at dose concentration 50mg/kg bw .Therefore, according to CLP criteria, the substance 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7) can be classified as“Category 2” for reproductive toxicity.
Effects on developmental toxicity
Description of key information
Developmental toxicity
No Observed Adverse Effect Level (NOAEL) was considered to be 10mg/kg/day and LOAEL was considered to be 50 mg/kg bw .When female Sprague Dawley rats were treated with 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7) orally.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data from secondary source
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- Prenatal developmental toxicity study 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloridewas performed on Sprague Dawley rats.
- GLP compliance:
- not specified
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of test material: Basic Violet 2
- IUPAC name: 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride
- Molecular formula: C22H23N3ClH
- Molecular weight: 365.906 g/mol
- Substance type: Organic
- Physical state: No data
- Purity:No data
- Impurities (identity and concentrations): No data - Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- Hsd: SD strain
- Details on test animals or test system and environmental conditions:
- No data available
- Route of administration:
- oral: unspecified
- Vehicle:
- water
- Remarks:
- Distilled water
- Details on exposure:
- Details on exposure
PREPARATION OF DOSING SOLUTIONS:
Test material dissolved in distilled water
DIET PREPARATION
- Rate of preparation of diet (frequency):No data available
- Mixing appropriate amounts with (Type of food )
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle: 2,10 and 50 mg/kg bw/day
- Amount of vehicle (if gavage): 10ml/kg bw/day
- Lot/batch no. (if required): No data available
- Purity: No data available - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- No data available
- Duration of treatment / exposure:
- 9 days ( from day 6 through day 15 gestation)
- Frequency of treatment:
- Daily
- Duration of test:
- 9 days ( from day 6 through day 15 gestation)
- Remarks:
- 2,10 and 50 mg/kg bw/day
- No. of animals per sex per dose:
- Total:72
2mg/kg bw/day:24
10mg/kg bw/day:24
50 mg/kg bw/day:24 - Control animals:
- not specified
- Details on study design:
- No data available
- Maternal examinations:
- Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: yes
DETAILED CLINICAL OBSERVATIONS: Yes
Time schedule:
BODY WEIGHT: Yes
Time schedule for examinations:
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes Food consumption was determined weekly.
Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
Time schedule for examinations:
OTHER: - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: No data
- Number of implantations: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data
- Other: - Fetal examinations:
- - External examinations: Yes:
- Soft tissue examinations: Yes:
- Skeletal examinations: Yes:
- Head examinations: Yes: - Statistics:
- No data available
- Indices:
- No data available
- Historical control data:
- No data available
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Violet coloured faeces in 10mg/kg bw/day and 50mg/kg bw/day dose groups while Dyspnoea in 50mg/kg bw/day group were observed.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- body weight reduced in 50mg/kg bw/day group from day 8
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Reduction in food consumption was observed during treatment
- 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:
- effects observed, treatment-related
- Description (incidence and severity):
- At necropsy final body weight, uterus weight and corrected body weight were decreased in 50mg/kg bw/day dose group
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- The number of implantations was decreased in 50mg/kg bw/day dose group.
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified - Changes in number of pregnant:
- not specified
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
- food consumption and compound intake
- gross pathology
- pre and post implantation loss
- Remarks on result:
- other: No effect observed in given dose
- Dose descriptor:
- LOAEL
- Effect level:
- 50 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- organ weights and organ / body weight ratios
- other: The number of implantations was decreased in 50mg/kg bw/day dose group.
- Remarks on result:
- other: Adverse effects was observed at given dose level
- Abnormalities:
- not specified
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Foetal weight was decreased in the 50mg/kg bw/day dose group
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified - Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- no effects observed
- Description (incidence and severity):
- no treatment related effects was observed in any dose group.
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- no treatment related effects was observed in any dose group.
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- no treatment related effects was observed in any dose group.
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- fetal/pup body weight changes
- external malformations
- skeletal malformations
- visceral malformations
- Remarks on result:
- other: No effect was observed
- Dose descriptor:
- LOAEL
- Effect level:
- 50 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- fetal/pup body weight changes
- Remarks on result:
- other: Decrease in body weight was observed at given dose level
- Abnormalities:
- not specified
- Developmental effects observed:
- no
- Treatment related:
- not specified
- Relation to maternal toxicity:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- No Observed Adverse Effect Level (NOAEL) was considered to be 10mg/kg/day and LOAEL was considered to be 50 mg/kg bw .When female Sprague Dawley rats were treated with 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7) orally.
- Executive summary:
Prenatal development toxicity study of with4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7)was performed on female Sprague Dawley Hsd: SD strainrats. 72 rats were divided as 24 rats /dose group. The test materialdissolved in water were administers in dose concentration 0, 5, 10and 50 mg/kg bw/day from day 6 through day 15of gestationby oral gavage route. Animals were observed for clinical signs, Food consumption and body weight .On day 20 post-coitum, the dams were sacrificed and subjected to a macroscopic examination. The litter parameters like number of implantation sites. The foetuses were weighed and subjected to external, soft tissue or skeletal examinations.Clinical sings like violet coloured faeces in 10mg/kg bw/day and 50mg/kg bw/day dose groups while dyspnoea in 50mg/kg bw/day group were observed.Body weightreduced in 50mg/kg bw/day group from day 8 and reductionin food consumptionwas observed during treatment. At necropsy final body weight, uterus weight and corrected body weight were decreased in 50mg/kg bw/day dose group in dams were noted. In litter the number of implantations was decreased in 50mg/kg bw/day dose group and foetal weight decrease in 50mg/kg bw/day dose group but no treatment related effects were observed in Foetal visceral and skeletal examination at any dose group. Hence No Observed Adverse Effect Level (NOAEL) was considered to be 10mg/kg/day and LOAEL was considered to be 50mg/kg bw.When female Sprague Dawley rats were treated with 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7) orally.
Reference
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEL
- 50 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 4 and from secondary source
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Developmental toxicity
In different studies, 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7) has been investigated for developmental 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 rats for 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7)
This study published in a report by Scientific Committee on Consumer Safety (the Scientific Committee on Consumer Products, SCCS/1340/10,2011) The reproduction and development toxicity study of 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7)was performed on female Sprague Dawley Hsd: SD strain rats. 72 rats were divided as 24 rats /dose group. The test material dissolved in water were administers in dose concentration 0, 5, 10and 50 mg/kg bw/day from day 6 through day 15of gestation by oral gavage route. Animals were observed for clinical signs, Food consumption and body weight .On day 20 post-coitum, the dams were sacrificed and subjected to a macroscopic examination. The litter parameters like number of implantation sites. The foetuses were weighed and subjected to external, soft tissue or skeletal examinations.
Clinical sings like violet coloured faeces in 10mg/kg bw/day and 50mg/kg bw/day dose groups while dyspnoea in 50mg/kg bw/day group were observed. Body weight reduced in 50mg/kg bw/day group from day 8 and reduction in food consumption was observed during treatment. At necropsy final body weight, uterus weight and corrected body weight were decreased in 50mg/kg bw/day dose group in dams were noted. In litter the number of implantations was decreased in 50mg/kg bw/day dose group and foetal weight decrease in 50mg/kg bw/day dose group but no treatment related effects were observed in Foetal visceral and skeletal examination at any dose group. Hence No Observed Adverse Effect Level (NOAEL) was considered to be 10mg/kg/day and LOAEL was considered to be 50mg/kg bw. When female Sprague Dawley rats were treated with4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7)orally.
So, based on the above mentioned study for target substance 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7),Foetal visceral and skeletal examination did not reveal teratogenic effects. Maternal toxicity and a delay of foetal development were observed at 50 mg/kg bw/day.Therefore, according to CLP criteria, the substance 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7) can be classified as“Category 2” for developmental toxicity.
Justification for classification or non-classification
Therefore, according to CLP criteria, the substance 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7) can be classified as“Category 2” for reproductive and developmental toxicity.
Additional information
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