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EC number: 251-410-3 | CAS number: 33229-34-4
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study performed according to OECD guideline 414 in compliance to GLP.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 005
- Report date:
- 2005
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2,2'-[[4-[(2-hydroxyethyl)amino]-3-nitrophenyl]imino]bisethanol
- EC Number:
- 251-410-3
- EC Name:
- 2,2'-[[4-[(2-hydroxyethyl)amino]-3-nitrophenyl]imino]bisethanol
- Cas Number:
- 33229-34-4
- Molecular formula:
- C12H19N3O5
- IUPAC Name:
- 2-({4-[bis(2-hydroxyethyl)amino]-2-nitrophenyl}amino)ethan-1-ol
- Details on test material:
- Test item : HC Blue No 2 (B037)
EC number : 251-410-3
Batch number : 3I394
Assay : 99.5% (titration)
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 0.5% carboxymethylcellulose in water
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- A satisfactory agreement was observed between the nominal and actual concentrations of the test item in the administered dosage forms since the deviations from nominal concentration remained within an acceptable range of +/-10%.
- Duration of treatment / exposure:
- Animals were treated from day 6 to day 19 post coitum inclusive.
- Frequency of treatment:
- Animals were treated once daily.
- Duration of test:
- Animals were sacrificed on day 20 post coitum.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day
- Dose / conc.:
- 300 mg/kg bw/day
- Dose / conc.:
- 1 000 mg/kg bw/day
- No. of animals per sex per dose:
- Twenty four
- Control animals:
- yes, concurrent vehicle
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Details on maternal toxic effects:
Mortality
No premature deaths occurred during the study.
Clinical signs
All females given HC Blue No2 had blue coloured urine from approximately day 7 post coitum until necropsy and blue coloured extremities (except in one female at 100 mg/kg bw/day) from approximately day 14 post coitum until necropsy. This finding was associated with blue coloured fur in the urogenital area of one female given 300 mg/kg bw/day and of 12/24 females given 1000 mg/kg bw/day towards the end of gestation. Excessive salivation (ptyalism) was observed in 10/24 females given 300 mg/kg bw/day and 17/24 females given 1000 mg/kg bw/day for a few days after start of dosing until the end of the treatment period. Other clinical signs (nodosities on the abdomen, masses on the mammary glands, abnormal growth of teeth) were randomly distributed within the groups and are commonly noted in rats of this strain and age.
Body weight
There was a slight, but statistically significant lower mean body weight gain from day 6 to day 9 post coitum for the group receiving 1000 mg/kg bw/day when compared to controls. Body weight gain for the remainder of the treatment period was similar to that of the controls. There were no effects on group mean maternal body weight or body weight gain for the groups receiving 100 or 300 mg/kg bw/day.The net body weight change was considered to be unaffected by treatment with HC Blue No 2.
Food consumption
Group mean food consumption was significantly lower from day 6 to day 9 post coitum for the group given 1000 mg/kg bw/day when compared to the controls. For the remainder of the treatment period, food intake for this group was similar to that of controls. There were no effects on group mean maternal food consumption at 100 or 300 mg/kg bw/day.
Necropsy findings
No findings recorded at maternal necropsy were considered to be related to treatment.
Gravid uterus weight
The differences noted for gravid uterus weight in the treated groups, when compared to controls were minor, not statistically significant and not dose related. They were not considered to be treatment related.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity : lower body weight gain and food consumption observed at the highest dose
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Details on embryotoxic / teratogenic effects:
Litter data
The mean number of corpora lutea, implantation sites and the percentage of pre-implantation loss were similar between treated and control groups. There were no effects on the group mean numbers of implantations or live fetuses or on the extent of post implantation loss for any group. There were no effects of treatment with HC Blue No 2 on group mean fetal weights or on the percentage of male fetuses; values were comparable with controls in all groups.
Soft tissue observation
No soft tissue malformations were observed in any group. The fetal soft tissue variations observed (hematoma in the cranial cavity, dilated renal pelvis, dilated ureters, enlarged atrial chamber, hemorrhage in abdominal cavity) were randomly distributed within the groups including the control.
Skeletal malformation
The only malformations observed (two fetuses with supernumerary lumbar vertebra at 100 mg/kg bw/day and one fetus with an absence of lumbar vertebra at 300 mg/kg bw/day) were not considered to be treatment related as they were not recorded in the high dose group.
Skeletal variation
At 1000 mg/kg bw/day there was a statistically significant increase in the fetal incidence of incomplete ossification of the interparietal when compared to controls (22 vs 11 in the control group). However this difference was not statistically significant when expressed as a mean percentage of affected fetuses and fell within the background control data range. Consequently it was not considered to be treatment related. At 1000 mg/kg bw/day the fetal incidence of incomplete ossification of the parietal was significantly greater when compared with the controls (6 vs 0 in the control group). This finding was not significant when expressed as a mean number of affected fetuses and fell within the background control data range. It was also not considered to be treatment related.
Effect levels (fetuses)
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Administration of HC Blue No 2 (B037) to pregnant female Sprague-Dawley rats from days 6 to 19 post-coitum inclusive at 100, 300 and 1000 mg/kg bw/day caused blue colouration of urine and extremities in all females. In addition, blue coloured fur was observed in many females given 1000 mg/kg bw/day. Ptyalism was also observed in females given 300 and 1000 mg/kg bw/day. Dosing at 1000 mg/kg bw/day caused maternal toxicity, shown by significantly lower body weight gains and food consumption, while there were no indications of any effects on the pregnancy parameters or embryo-fetal development. The NOAEL for maternal toxicity was 300 mg/kg bw/day and the NOEL for developmental toxicity was 1000 mg/kg bw/day.
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