Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 700-936-6 | 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2013-03-22 to 2013-05-17
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Deviations:
- no
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- tetrasodium 4-[(E)-2-[2-(carbamoylamino)-4-[(2,6-difluoropyrimidin-4-yl)amino]phenyl]diazen-1-yl]benzene-1,3-disulfonate 4-[(E)-2-[2-(carbamoylamino)-4-[(4,6-difluoropyrimidin-2-yl)amino]phenyl]diazen-1-yl]benzene-1,3-disulfonate
- EC Number:
- 700-936-6
- Molecular formula:
- C17H11F2N7Na2O7S2
- IUPAC Name:
- tetrasodium 4-[(E)-2-[2-(carbamoylamino)-4-[(2,6-difluoropyrimidin-4-yl)amino]phenyl]diazen-1-yl]benzene-1,3-disulfonate 4-[(E)-2-[2-(carbamoylamino)-4-[(4,6-difluoropyrimidin-2-yl)amino]phenyl]diazen-1-yl]benzene-1,3-disulfonate
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Test System
Species/strain: healthy Wistar rats, Crl: WI(Han) (Full Barrier)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: male and female; the female animals were non-pregnant and nulliparous.
Age at the start of the treatment period: 8 - 9 weeks old
Body weight at the allocation of the animals to the experimental groups: males: 165 – 185 g (mean: 177.08 g, ± 20% = 141.67 – 212.50 g)
females: 140 – 160 g (mean: 148.25 g, ± 20% = 118.60 – 177.90 g)
The animals were derived from a controlled full-barrier maintained breeding system (SPF).
According to Art. 9.2, No. 7 of the German Act on Animal Welfare the animals were bred for experimental purposes.
Housing and Feeding Conditions:
- Full barrier in an air-conditioned room
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/-10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 0902)
- Free access to tap water, sulphur acidified to a pH of approximately 2.8 (drinking water, municipal residue control, microbiological
controls at regular intervals)
- The animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin saw fiber bedding (lot no. 011012).
- Certificates of food, water and bedding are filed at BSL BIOSERVICE.
- Adequate acclimatisation period (at least five days)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- The test item formulation and vehicle were administered at a single dose to the animals by oral gavage.
The application volume for all groups was 5 mL/kg body weight.
For each animal the individual dosing volume was calculated on the basis of the body weight most recently measured.
In consultation with the sponsor the following doses (Table 1) were selected for the 3 dose groups (LD = low dose, MD = medium dose, HD = high dose) and 1 control group (C).
Control: 0 mg/kg body weight
Low Dose: 100 mg/kg body weight
Medium Dose: 300 mg/kg body weight
High Dose: 1000 mg/kg body weight
The animals were treated with the test item or vehicle on 7 days per week for a period of 14 days. - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- The animals were treated with the test item or vehicle on 7 days per week for a period of 14 days.
- Frequency of treatment:
- The animals were treated once daily.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
100 mg/kg bw, 300 mg/kg bw and 1000 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 24 animals (12 males and 12 females) were used for the study (3 male and 3 female animals per group).
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Rationale for animal assignment: random
- Section schedule rationale : alle male animals together and all female animals together
Examinations
- Observations and examinations performed and frequency:
- Body Weight and Food Consumption
The body weight was recorded once before assignment to the experimental groups and on study days 1, 8 and 14 during the
treatment period as well as on the day of necropsy.
Food consumption was measured on study days 1, 8 and 14 for each animal.
Clinical Observations
All Animals were observed for clinical signs during the entire treatment period of 14 days.
General clinical observations were made at least once a day, approximately at the same time each day and considering the peak period of
anticipated effects after dosing. The health condition of the animals was recorded. Twice daily all animals were observed for morbidity
and mortality except on weekends and public holidays when observations were made once daily.
Detailed cage side observations considering spontaneous activity, lethargy, recumbent position, convulsions, tremors, apnoea, asphyxia,
vocalisation, diarrhoea, changes in skin and fur, eyes and mucous membranes (salivation, discharge), piloerection and pupil size were made
outside the home cage in a standard arena once before the first administration and at least once a week thereafter.
Haematology
Haematological parameters (HCT, HB, RBC, PLT, WBC) were examined at the end of the treatment prior to or as part of the sacrifice of the animals.
After overnight fasting, blood from the abdominal aorta of the animals was collected in EDTA-coated tubes. - Sacrifice and pathology:
- Pathology
On study day 15, all surviving animals of the study were sacrificed using anesthesia (ketamine, Pharmanovo, lot no: 24139, expiry date: 06/2014
and xylazin, Serumwerk, lot no. 00512, expiry date: 07/2014) and were subjected to a detailed gross necropsy which included careful examination
of the external surface of the body, all orifices and the cranial, thoracic and abdominal cavities and their contents.
Organ Weight
No organ weights were taken in this study. - Statistics:
- According to OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results. Due to the small size of groups a statistical evaluation of the results was not performed in this study.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- Mortality
No mortality occurred in the control or any of the dose groups during the treatment period of this study.
Clinical Observations
No signs of toxicity were observed in any animal during the whole observation period.
Body Weight Development
Throughout the treatment period, body weights were within the normal range of variation for this strain and no difference could be found
between C and treatment groups.
Food Consumption
In correlation to the body weight and body weight change, the food consumption in both males and females increased with the progress
of the study in all groups.
No considerable effect of Reactive Golden Yellow HF-RN 1331 on food consumption was found in any of the treatment groups of male female animals.
Haematology
No difference in haematological parameters was found for male animals at the end of the treatment period.
In female animals values of WBC were slightly decreased in MD (-22%) and HD (-33 %) groups. This could be test item related.
However, since no finding was found in male animals and since the standard deviation was relatively high (due to a low number of animals),
a clear statement cannot be given. A gender related difference is unlikely but cannot be excluded.
Pathology
No gross pathological changes were recorded for any animal of any group.
Effect levels
- Basis for effect level:
- other: see 'Remark'
- Remarks on result:
- not measured/tested
- Remarks:
- Effect level not specified (migrated information)
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the present study, the repeated oral application of the test item Reactive Golden Yellow HF-RN 1331 to male
and female Wistar rats at doses of 100, 300 and 1000 mg/kg body weight for 14 days was associated with no signs of toxicity or mortality.
Based on the data generated from this dose range finding study, dose levels of 100 300, and 1000 mg/kg body weight per day are suggested
for the subsequent main study with Reactive Golden Yellow HF-RN 1331. - Executive summary:
The aim of this study was to assess the possible health hazards which could arise from repeated exposure of Reactive Golden Yellow HF-RN 1331
via oral administration to rats over a period of 14 days.
The test item was administered daily in graduated doses to 3 groups of test animals, one dose level per group for a treatment period of 14 days.
Animals of an additional control group were handled identically as the dose groups but received aqua ad injectionem, the vehicle used in this study.
The 4 groups comprised 3 male and 3 femaleWistarrats.
During the period of administration, the animals were observed precisely each day for signs of toxicity.
Body weight and food consumption were measured weekly. At the conclusion of the treatment period, all animals were sacrificed and subjected to necropsy.
The following doses were evaluated:
Control: 0 mg/kg body weight; Low Dose: 100 mg/kg body weight; Medium Dose: 300 mg/kg body weight; High Dose: 1000 mg/kg body weight
The test item formulation was prepared freshly on each day of administration. The test item was dissolved in aqua ad injectionem and administered daily during
a 14-day treatment period to male and female animals. Dose volumes were adjusted individually based on weekly body weight measurement.
Summary Results
All animals survived until the end of the study without showing any signs of toxicity.
No mortality occurred in the control or any of the dose groups during the treatment period of this study.
No signs of toxicity were observed in any animal during the whole observation period.
Throughout the treatment period, body weights were within the normal range of variation for this strain and no difference could be found between C and treatment groups.
No considerable effect ofReactive Golden Yellow HF-RN 1331on food consumption was found in any of the treatment groups of male female animals.
No difference in haematological parameters was found for male animals at the end of the treatment period.
In female animals values of WBC were slightly decreased in MD (-22%) and HD (-33 %) groups.
No gross pathological changes were recorded for any animal of any group.
Conclusion
Under the conditions of the present study, the repeated oral application of the test item Reactive Golden Yellow HF-RN 1331 tomale and female Wistarrats at doses of 100, 300 and 1000 mg/kg body weight for 14 days was associated with no signs of toxicity or mortality.
Based on the data generated from this dose range finding study, dose levels of 100 300, and 1000 mg/kg body weight per dayaresuggested for the subsequent main study withReactive Golden Yellow HF-RN 1331.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.