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EC number: 947-399-6 | CAS number: -
- 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

Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data from handbook or collection of data
Data source
Reference
- Reference Type:
- review article or handbook
- Title:
- Toxicological evaluation of certain veterinary drug residues in food
- Author:
- FAO/WHO Expert Committee on Food Additives (JECFA)
- Year:
- 2 004
- Bibliographic source:
- FAO/WHO Expert Committee on Food Additives (JECFA),2004
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- The three-generation reproductive toxicity study of test material was performed in Fischer 344 rats.
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- No data available
Test material
- Reference substance name:
- [4-[4,4'-bis(dimethylamino)benzhydrylidene]cyclohexa-2,5-dien-1-ylidene]dimethylammonium chloride
- EC Number:
- 208-953-6
- EC Name:
- [4-[4,4'-bis(dimethylamino)benzhydrylidene]cyclohexa-2,5-dien-1-ylidene]dimethylammonium chloride
- Cas Number:
- 548-62-9
- Molecular formula:
- C25H30N3.Cl
- IUPAC Name:
- (4-(4,4'-Bis(dimethylamino)benzhydrylidene)cyclohexa-2,5-dien-1-ylidene)dimethylammonium, chloride
- Test material form:
- solid
- Details on test material:
- - Name of test material (as cited in study report):Gentian violet
- IUPAC name: N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride
- Molecular formula : C25H30N3.Cl
- Molecular weight : 407.986 g/mol
- Smiles notation: C(\c1ccc(N(C)C)cc1)(c1ccc(N(C)C)cc1)=C1\C=C\C(=[N+](/C)C)C=C1.[ClH-]
- InChl:1S/C25H30N3.ClH/c1-26(2)22-13-7-19(8-14-22)25(20-9-15-23(16-10-20)27(3)4)21-11-17-24(18-12-21)28(5)6;/h7-18H,1-6H3;1H/q+1;/p-1
- Substance type: Organic
- Physical state: Solid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Details on species / strain selection:
- No data available
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data available
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: Feed
- Details on exposure:
- No data available
- Details on mating procedure:
- - M/F ratio per cage:No data available
- Length of cohabitation: 14 days
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy:No data available
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.No data available
- Further matings after two unsuccessful attempts: [no / yes (explain)]No data available
- After successful mating each pregnant female was caged (how): single
- Any other deviations from standard protocol:No data available - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data available
- Duration of treatment / exposure:
- total:280-294
F0 generation :at least 80days
F1b generation:100-140 days
F2b generation:100-140 days
F3a generation:up to weaning - Frequency of treatment:
- Daily
- Details on study schedule:
- - F1 parental animals not mated until [...] weeks after selected from the F1 litters.
After at lest 80 daysfrom start of study, In F0 generation male and female rats of same dose group were caged together for 14 days for mating .Pups from this mating F1a generation used for separate study while F0 generation animals were mating second times in same dose group following birth of F1b generation
- Selection of parents from F1 generation when pups were [...] days of age.:
At 100-140 days of age, one male and one female from each litter were randomly selected to produce F2a generation. Same procedure was used to produce F2b generation
- Age at mating of the mated animals in the study: [...] weeks
After 100-140 days, F3a generation were produce as result of mating one male and one female animal per litter from F2b generation.
Doses / concentrations
- Remarks:
- 0, 5,15 and 30 mg /kg bw /day
- No. of animals per sex per dose:
- Total :450
Control group:180
Male :90
female 90
treated group:270
5mg/kg bw/day:45male and 45 female
15mg/kg bw/day:45male and 45 female
30mg/kg bw/day:45male and 45 female - Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data available
- Positive control:
- No data available
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: No data
- Time schedule:
- Cage side observations checked in table [No.?] were included.
DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule:
BODY WEIGHT: Yes
- Time schedule for examinations:
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations:
OTHER:No data - 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]: No data available
- If yes, maximum of [...] pups/litter ([...]/sex/litter as nearly as possible); for F1b and F2a generation one male and one female from each litter were seleted and 2 male and 2 female per litter for F3a generation were selected excess pups were killed and discarded.
PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2 / F3] offspring:yes
[number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, were observed
GROSS EXAMINATION OF DEAD PUPS:
[no / yes, for external and internal abnormalities; possible cause of death was/was not determined for pups born or found dead.]No data available
ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY:No data available
ASSESSMENT OF DEVELOPMENTAL IMMUNOTOXICITY:No data available - 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.]No data available
- Maternal animals: All surviving animals [describe when, e.g. after the last litter of each generation was weaned.] No data available
GROSS NECROPSY
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]No data available
HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.: yes in F3a generations were observed - 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: No data available
GROSS NECROPSY
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]No data available
HISTOPATHOLOGY / ORGAN WEIGTHS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively. yes in F3a generation - Statistics:
- No data available
- Reproductive indices:
- No data available
- Offspring viability indices:
- No data available
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- No dose related effect on mortality was observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The dose related effect in body weight was observed at dose 30mg/kg bw /day group compared to control and lower 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
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- No effect observed on fertility index and stillborn animals ,sex ratio, number of pups per litter .
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 30 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive performance
- Remarks on result:
- other: No effect observed on reproductive performance
Target system / organ toxicity (P0)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Results: P1 (second parental generation)
General toxicity (P1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Description (incidence):
- not dose related mortality was observed,
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The dose related effect in body weight was observed at dose 30mg/kg bw /day group compared to control and lower 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
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P1)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- No effect observed on fertility index and stillborn animals ,sex ratio, number of pups per litter .
Effect levels (P1)
- Dose descriptor:
- NOAEL
- Effect level:
- 30 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive performance
- Remarks on result:
- other: No effect observed on reproductive performace
Target system / organ toxicity (P1)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Results: F1 generation
General toxicity (F1)
- 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:
- no effects observed
- Description (incidence and severity):
- No dose related effects on incidence of gross deformities were noted
- Histopathological findings:
- not specified
- Other effects:
- not specified
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not specified
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- other: F2b
- Effect level:
- 30 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: gross deformities
- Remarks on result:
- other: No effect observed at dose 30mg/kg bw
Target system / organ toxicity (F1)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Results: F2 generation
General toxicity (F2)
- 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:
- effects observed, treatment-related
- Description (incidence and severity):
- Dose related trend for focal dilatation of the renal cortex and tubules ,for necrosis of the thymus and inverse dose-response relationship for red pulp haematopoietic cell proliferation of the spleen
- Other effects:
- not specified
Developmental neurotoxicity (F2)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not specified
Effect levels (F2)
- Dose descriptor:
- LOAEL
- Generation:
- other: F3a
- Effect level:
- 5 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
- Remarks on result:
- other: Dose related effect observed
Target system / organ toxicity (F2)
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 5 mg/kg bw/day (nominal)
- Organ:
- kidney
- spleen
- thymus
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
Overall reproductive toxicity
- 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
Applicant's summary and conclusion
- Conclusions:
- NOAEL for reproductive toxicity was considered to be 30 mg/kg bw/day for P, P1 and F2b generation and LOAEL was considered to be 5mg/kg bw/day for F3a generation when male and female Fischer 344 rats were treated with test material orally.
- Executive summary:
In three generation reproductive toxicity study, Total 450 male and female Fischer 344 rats were used in the study separated in two group i.e. control group and treated group.90 animals of each sex were used in control group. Test material was given in feed at dose concentration 0, 5, 15 and 30 mg /kg bw /day.45 animals of each sex were used for each dose concentration in F0 generation.
In F0 generation male and female rats of same dose group were caged together for 14 days for mating .Pups from this mating F1ageneration used for separate study while F0 generation animals were mating second times in same dose group following birth of F1bgeneration. At 100-140 days of age, one male and one female from each litter were randomly selected to produce F2ageneration. Same procedure was used to produce F2bgeneration .After 100-140 days, F3a generation were produce as result of mating one male and one female animal per litter from F2b generation. Pups from all generations were examined for gross deformities while at weaning, 2male and 2 female per litter of F3a generation were randomly selected for histopathology of organs and tissues.
The dose related effect in body weight was observed at dose 30mg/kg bw /day dose group, as animals in this group had lower body weight compared to control and lower dose group. No dose related effects were observed on reproductive performance as number of pups per litter, fertility index and numbers of stillborn animals were not affected across the generation or dose group.Also No dose related effects were observed on gross deformities in each generation.
The only significant histopathological changes noted in F3ageneration were dose related trend for focal dilation of renal cortex and tubules and statistically significant dose related trend for necrosis of thymus (p<0.012 for male and p<0.0001 for female).Also statistically significant inverse dose response relationship for red pulp hematopoietic cell proliferation of spleen (p<0.001 for male and p<0.00001 for female).
Hence, NOAEL for reproductive toxicity was considered to be 30mg/kg bw/day for P, P1 and F2b generation and LOAEL w as considered to be 5mg/kg bw/day for F3a generation when male and female Fischer 344 rats were treated with test material orally.
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