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EC number: 235-468-7 | CAS number: 12237-62-6 This substance is identified in the Colour Index by Colour Index Constitution Number, C.I. 42535:3.
- 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
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Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- 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 is from peer reiviewed journal
Data source
Reference
- Reference Type:
- publication
- Title:
- Teratogenicity and embryotoxicity study in rats
- Author:
- S. A. CLODE
- Year:
- 1 987
- Bibliographic source:
- Food Chemical Toxicology, 1987
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: as mentioned below
- Principles of method if other than guideline:
- Teratogenicity and embryotoxicity study of the test chemical was performed on rats
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Hydrogen [4-[4-(dimethylamino)-α-(2-hydroxy-3,6-disulphonato-1-naphthyl)benzylidene]cyclohexa-2,5-dien-1-ylidene]dimethylammonium, monosodium salt
- EC Number:
- 221-409-2
- EC Name:
- Hydrogen [4-[4-(dimethylamino)-α-(2-hydroxy-3,6-disulphonato-1-naphthyl)benzylidene]cyclohexa-2,5-dien-1-ylidene]dimethylammonium, monosodium salt
- Cas Number:
- 3087-16-9
- Molecular formula:
- C27H26N2O7S2.Na
- IUPAC Name:
- Hydrogen [4-[4-(dimethylamino)-α-(2-hydroxy-3,6-disulphonato-1-naphthyl)benzyli dene]cyclohexa-2,5-dien-1-ylidene]dimethylammonium, monosodium salt
- Test material form:
- solid
- Details on test material:
- - Name of test material (as cited in study report): Hydrogen [4-[4-(dimethylamino)-α-(2-hydroxy-3,6-
disulphonato-1-naphthyl)benzylidene]cyclohexa-2,5-dien-1-ylidene]dimethylammonium, monosodium
salt
- Molecular formula :C27H26N2O7S2.Na
- Molecular weight: 576.623 g/mol
- Substance type:Organic
- Physical state:Solid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Specified-pathogen-free colony (Olac (1976) Ltd, Bicester, Oxon)
- Age at study initiation: No data available
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: Animals were housed in five per caged till 7 weeks and then individually.
- Diet (e.g. ad libitum): Spratt's Laboratory Diet No. 5, ad libitum
- Water (e.g. ad libitum): Tap-water, ad libitum
- Acclimation period: 7 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2°C
- Humidity (%): 40-60%
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
IN-LIFE DATES: From: To: No data available
Administration / exposure
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The dosing solutions were prepared at concentrations 0, 250, 500 and 1000 mg/kg such that a volume of 10 ml/kg was administered daily.
DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): Water
- Concentration in vehicle: 0, 250, 500 and 1000 mg/kg/day
- Amount of vehicle (if gavage): 10 ml/kg
- Lot/batch no. (if required): No data available
- Purity: No data available - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - M/F ratio per cage: 1 : 1 ratio
- Length of cohabitation: Overnight
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy Sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged (how): Individually
- Any other deviations from standard protocol: This procedure was repeated over several consecutive days until at least 30 females had been allocated to each treatment group. - Duration of treatment / exposure:
- 19 days
- Frequency of treatment:
- Daily
- Duration of test:
- 19 days
Doses / concentrations
- Remarks:
- 0, 250, 500 and 1000 mg/kg bw/day
- No. of animals per sex per dose:
- Total: 120
0 mg/kg/day: 30 female
250 mg/kg/day: 30 female
500 mg/kg/day: 30 female
1000 mg/kg/day: 30 female - Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data available
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes / No / No data:
- Time schedule:
- Cage side observations checked in table [No.?] were included.
DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:
BODY WEIGHT: Yes / No / No data: yes
- Time schedule for examinations:Each animal was weighed on alternate days, commencing on day 0 of pregnancy.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes / No / No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / No data
- Time schedule for examinations:
POST-MORTEM EXAMINATIONS: Yes / No / No data: yes
- Sacrifice on gestation day # : On day 20 of pregnancy, 30 females from each group were killed by cervical dislocation and a postmortem examination was carried out
- Organs examined: a postmortem examination was carried out, during which the gross appearance of the maternal tissues was noted and the foetuses were removed. The numbers of corpora lutea and implantation sites and the numbers and positions of the sites with dead, live or resorbed foetuses were recorded.
OTHER: At 7 wk of age vaginal smears were prepared and examined for each female. Those females in pro-oestrus (indicated by the presence of mainly cornified and epithelial cells) were caged
individually overnight with a mature male. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes / No / No data: yes
Examinations included:
- Gravid uterus weight: Yes / No / No data: yes
- Number of corpora lutea: Yes / No / No data: yes
- Number of implantations: Yes / No / No data: yes
- Number of early resorptions: Yes / No / No data: yes
- Number of late resorptions: Yes / No / No data: yes - Fetal examinations:
- - External examinations: Yes: [all per litter / half per litter / #? per litter ] / No / No data: yes
- Soft tissue examinations: Yes: [all per litter / half per litter / #? per litter ] / No / No data: tes
- Skeletal examinations: Yes: [all per litter / half per litter / #? per litter ] / No / No data: yes
- Head examinations: Yes: [all per litter / half per litter / #? per litter ] / No / No data: no data available - Statistics:
- No data available
- Indices:
- Viability of fetuses were observed.
- Historical control data:
- No data available
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- There were no statistically significant differences in body weight between treated and control females
- 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:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At autopsy, all the maternal animals given the test chemical were found to have colouring in the gastro-intestinal tract and the placental tissue also appeared to the slightly green. Apart from this,
no abnormalities were found in the tissues of the maternal animals. - Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- There were no differences between the control and treated groups in the results of the examination of the reproductive system and the foetuses
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- no effects observed
- Description (incidence and severity):
- No effect were observed on number of corpora lutea, implantation sites, Pre-implantation losses, early resorptions, late resorptions and post-implantation losses of treated female rats as compared to control.
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- No effect were observed on number of corpora lutea, implantation sites, Pre-implantation losses, early resorptions, late resorptions and post-implantation losses of treated female rats as compared to control.
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- No effect were observed on the number of Pre-implantation and post-implantation losses of treated female rats as compared to control.
- Total litter losses by resorption:
- not specified
- Description (incidence and severity):
- no data available
- Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- No effect were observed on number of early resorptions, late resorptions of treated female rats as compared to control.
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- No effect were observed on number of corpora lutea, implantation sites, Pre-implantation losses, early resorptions, late resorptions and post-implantation losses of treated female rats as compared to control.
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Other effects:
- not specified
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- dead fetuses
- early or late resorptions
- gross pathology
- maternal abnormalities
- necropsy findings
- number of abortions
- pre and post implantation loss
- total litter losses by resorption
Maternal abnormalities
- Abnormalities:
- not specified
- Localisation:
- not specified
Results (fetuses)
- Fetal body weight changes:
- 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):
- a lack of teratogenic effect was indicated by the absence of any gross malformations of severe defects in the examination of the skeletal or soft parts.
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- a lack of teratogenic effect was indicated by the absence of any gross malformations of severe defects in the examination of the skeletal parts.
- Visceral malformations:
- no effects observed
- Other effects:
- not specified
- Description (incidence and severity):
- Ossification of proximal phalanges and fourth metacarpals of Skeletal tissue were observed in 500 and 1000 mg/kg/day treated fetuses as compared to contorl. Despite this association with treatment, the nature of the finding does not indicate an adverse effect.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reduction in number of live offspring
- fetal/pup body weight changes
- external malformations
- skeletal malformations
Fetal abnormalities
- Abnormalities:
- not specified
- Localisation:
- other: not specified
Overall developmental toxicity
- Developmental effects observed:
- no
- Treatment related:
- no
Any other information on results incl. tables
Table 1.Results of the examination of the reproductive system and foetuses of female rats given 0-1000mg/kg/day test chemical in aqueous solution, by oral intubation, throughout pregnancy
|
Mean no. (value)/pregnant female given doses (mg/kg/day) of: |
|||
Observation |
0 |
250 |
500 |
1000 |
Corpora lutea |
12.13 |
11.57 |
11.67 |
12.03 |
Implantations |
10.60 |
10.93 |
10.13 |
10.83 |
Pre-implantation losses |
1.57 |
0.64 |
1.54 |
1.20 |
Early resorptions |
0.50 |
0.60 |
0.40 |
0.57 |
Late resorptions |
0.03 |
0.13 |
0.17 |
0.13 |
Post-implantation losses |
0.53 |
0.73 |
0.57 |
0.70 |
Live foetuses |
10.07 |
10.20 |
9.53 |
10.13 |
Litter weight (g) |
34.2 |
34.7 |
33.6 |
35.9 |
Mean foetal weight (g) |
3.40 |
3.42 |
3.49 |
3.53 |
The results are means for groups of 30 females. There were no significant differences between the control and test groups (the exact test of Fisher, 1934): P > 0.05.
Table 2. Incidence of statistically significant findings in rat pups from females given 0-1000mg/kg/day test chemicalin aqueous solution, by oral intubation, throughoutpregnancy
Finding |
Dose level (mg/kg/day)... |
No. of pups affected |
|||
|
|
0 |
250 |
500 |
1000 |
Visceral findings
|
|
|
|
|
|
No. of pups examined... |
|
138 |
137 |
133 |
136 |
Mucus in tracea |
|
3 |
11* |
13** |
13** |
Skeletal findings |
|
|
|
|
|
No. of pups examined... |
|
131 |
134 |
129 |
135 |
Proximal phalanges ossified |
|
23 |
19 |
35 |
38* |
Metacarpals ossified |
|
53 |
56 |
71* |
82*** |
Values marked with asterisks differ significantly (chi-square test) from those of the control: *P <0.05; **P < 0.01; ***P < 0.001.
Applicant's summary and conclusion
- Conclusions:
- NOAEL was considered to be 1000 mg/kg/day for P and F1 generation when Wistar female rats treated with the test chemical
- Executive summary:
Teratogenicity and embryotoxicity study of the test chemical was performed on rats. Daily oral doses of 0 (control), 250, 500 or 1000 mg/kg body weight were given to groups of 30 pregnant Wistar rats on days 0-19 of pregnancy.The dosing solutions were prepared at concentrations such that a volume of 10ml/kg was administered daily. The controls received water. Each animal was weighed on alternate days, commencing on day 0 of pregnancy. On day 20 of pregnancy, 30 females from each group were killed by cervical dislocation and a postmortem examination was carried out, during which the gross appearance of the maternal tissues was noted and the foetuses were removed. The numbers of corpora lutea and implantation sites and the numbers and positions of the sites with dead, live or resorbed foetuses were recorded. The live foetuses were weighed and examined for gross abnormalities.This treatment did not adversely influence maternal body weight, the numbers of implanations, pre- or post-implantation losses or of live foetuses, the sex ratio or the weight of the litters or foetuses. No definite abnormalities were seen and the only finding in the examination of stained skeletons was a slightly more advanced ossification of the forelimbs of the offspring from females given 500 or 1000 mg /kg/day. More foetuses with mucus in the trachea were found in the treated groups than in the controls but this was not considered to be a teratogenic effect. Thus no embryotoxic or teratogenic effects were detected with doses of up to 1000 mg/kg/day throughout pregnancy. NOAEL was considered to be 1000 mg/kg/day for P and F1 generation when Wistar female rats treated with the test chemical
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