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EC number: 279-317-3 | CAS number: 79828-43-6
- 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:
- 1994
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- not specified
- Principles of method if other than guideline:
- None
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Pentasodium bis[5-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-hydroxy-3-[(2-hydroxy-5-nitrophenyl)azo]naphthalene-2,7-disulphonato(4-)]chromate(5-)
- EC Number:
- 279-317-3
- EC Name:
- Pentasodium bis[5-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-hydroxy-3-[(2-hydroxy-5-nitrophenyl)azo]naphthalene-2,7-disulphonato(4-)]chromate(5-)
- Cas Number:
- 79828-43-6
- Molecular formula:
- C38H18Cl2CrN16O20S4.5Na
- IUPAC Name:
- Pentasodium bis[5-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-hydroxy-3-[(2-hydroxy-5-nitrophenyl)azo]naphthalene-2,7-disulphonato(4-)]chromate(5-)
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- None
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: SPF breeding VELAZ Černý Vůl
- Age at study initiation: 6-8 weeks
- Housing: 2-3 rats of the same sex in one plastic cage containing dry and sterilized clean shavings of soft wood.
- Diet (e.g. ad libitum): standard complete pelleted diet ST1 (supplier Bergman, Jesenice u Prahy)
- Water (e.g. ad libitum): free access to drinking water
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature: 23 ±-3 °C
- Humidity: 40-60 %
- Photoperiod: 12-hour light/12-hour dark cycle
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: water with addition of 0.5 % methylcellulose
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: daily just before administration. The concentrations of suspensions at each dose levels were adjusted, so that the administration would ensure the equals 1 mL per 100 g of body weight of the test animal and the volume was constant for each dose levels. During the application, the suspension was permanent mixed by electric stirrer.
- Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- None
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 5 males and 5 females per dose
- Control animals:
- yes, concurrent no treatment
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on the results of the dose-range finding experiment
- Post-exposure recovery period in satellite groups: 14 days - Positive control:
- None
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: in 7-days intervals
BODY WEIGHT: Yes
- Time schedule for examinations: in 7-days intervals
FOOD CONSUMPTION:
- Food consumption for each animal determined: Yes
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time x 100 calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
- Time schedule for examinations:
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Before the start of the study and than in the 28th and the 42nd day of the study. In satellite groups was the examination performed in the 42nd day.
- Anaesthetic used for blood collection: Yes - ether
- Animals fasted: Yes (18 h)
- How many animals: all animals
- Parameters examined: Haemoglobin, Total count of Erythrocytes, Haematokrit , MCV (the mean corpuscular volume), Total count of Leucocytes, Thrombocytes, Differential leukocyte count
BIOCHEMICAL EXAMINATION
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: in the 28th and the 42nd day of the study
- Animals fasted: Yes (18 h)
- How many animals: all animals
- Parameters examined: Total protein, Glucose, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Total bilirubin, Creatinine, Urea, Albumin, Alkaline phosphatase (ALP), Na+, K+, Ca2+, Cl-
URINALYSIS: Yes
- Time schedule for collection of urine: in the 28th and the 42nd day of the study
- Metabolism cages used for collection of urine: Yes
- Parameters examined: quantity of erythrocytes, haemoglobin, ketones, bilirubin, urobilinogen, glucose, protein and pH.
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- macroscopic revision of thoracic, abdominal and cranial cavity
- selected organs were collected for weighing and further histological examination
- the absolute weights of liver, adrenal glands, kidneys, brain, and in males also of testes were recorded
- somatic indexes were calculated
HISTOPATHOLOGY: Yes
- brain, lungs, heart, liver, spleen, pancreas, adrenal glands, kidneys, esophagus, stomach, small and large intestine, testes, epididymides, uterus and ovary - Other examinations:
- None
- Statistics:
- The non-parametric Mann-Whitney test was used for statistical analysis of results.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- 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:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- effects observed, treatment-related
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not specified
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Changes in the stool consistence were observed in some animals during the clinical observation. An increased restlessness and different coloration of the auricles, nostrils and fingers were found in animals at the highest dose level.
HAEMATOLOGY
The dose level - 100 mg/kg: The values of total leucocytes count in treated animals were on the upper limit of physiological norms. Other haematological values were in the physiological range.
The dose level - 500 mg/kg: All of haematological values were in the physiological range.
The dose level - 1000 mg/kg: The haematological examination of animals showed changes in the differential leukocyte count with occurrence of young developmental forms especially myelocytes and metamyelocytes. In most of animals at the highest dose level occurrence of stomatocytes were observed in the microscopic examination of blood smears. Increasing of total number of leukocytes above limit of physiological norms was observed in males. In females, the value of MCV (mean corpuscular volume) was in the physiological range and haemoglobin was at the lower limit.
CLINICAL CHEMISTRY
Values of urea concentration, potassium and chloride ions were statistically significantly increased in males at the lowest dose level (100 mg/kg), but the values of concentration of sodium and calcium ions were decreased. In females at the highest dose level, increased values of cholesterol and concentration of potassium were recorded. Although the parameters were statistically significant, all of them were within physiological range.
Values of activity of AST were recorded statistically significantly increased and concentrations of creatinine, sodium and calcium ions were statistically significantly decreased in males at middle dose level (500 mg/kg). In females, increased values of concentration of potassium ion and activity of ALT, AST, ALP were recorded. Albumin and sodium ions concentration were decreased. Nevertheless all of biochemical parameters were within the physiological range.
Statistically significantly decreased concentrations of creatinine and sodium ions were recorded in animals at the highest dose level (1000 mg/kg) Decreased activity of ALP and concentration of sodium ions and increased concentration of total bilirubin and concentration of potassium ions were recorded in females. Although the parameters were statistically significant, all of monitored values were within physiological range. Increased concentration of chloride ions above physiological range was recorded in both sexes at the highest dose level. Concentration of sodium ions decreased below the limit of physiological range.
In males from the satellite group, significantly statistically increasing of concentrations of total protein and urea were recorded. The albumin and calcium concentration was decreased. In females were recorded decreased values of urea, AST, total bilirubin, sodium and calcium ions. Although the parameters were statistically significant, all of monitored values were within the physiological range.
GROSS PATHOLOGY
Bluish coloration of tail skin was observed in males at middle dose level (500 mg/kg), who were sacrificed at the end of application period. Two males and one female at the highest dose level (1000 mg/kg) showed also stomach mucous membrane coloration. Enlargement of spleen was observed in two males and four females at the highest dose level and testes reducing was observed in one male.
HISTOPATHOLOGY: NON-NEOPLASTIC
The significant histopathological changes - macroscopically enlarged spleen, were found at the highest dose level (1000 mg/kg). In the histological examination was evident enlargement of a red pulp with dilatation of the sinuses with erythrocytes and numerous of scavenger cells with a rusty pigment. Particles of pigment were also situated freely. The affect with this character was in two males and one female. The kidney cortex with a round-cell infiltration was observed in three males. There were observed advanced degree of dystrophy of the germinal epithelium of testes with a total disappearance of all layers of this epithelium (maintenance of the Sertoli cell only) in one male. The dark-blue pigment residues in the stomach mucous membrane were recorded in two females at the highest dose level. The fatty droplets were found only in the interstitium of the renal papilla in one male.
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 500 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: The changes of the haematological parameters and increased erythrocyte haemolysis, which caused damage of spleen tissue and reversible changes of the biochemical parameters.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
DISCUSSION
Changes in the stool consistence were observed in some animals during the clinical observation. An increased restlessness and different coloration of the auricles, nostrils and fingers were found in animals at the highest dose level. The body weight increment of treated animals was not significantly different in comparison with the animals from the control group. Although the results of biochemical parameters were statistically significant, most of monitored values were within the physiological range. Only the concentration of chloride ions was on the upper limit of physiological norms and oppositely, the concentration of sodium ions was on the lower limit. The concentrations of ions returned on physiological range in satellite groups. The spleen oedema was found during the histopathological examination in seven animals (in two males and five females) at the highest dose level and in three females at satellite group administered by the highest dose level of the test substance. It was apparent, that there was no inflammatory – septic splenomegaly. The occurrence of the russet pigment in the scavenger cells or freely placed as a particles in the red pulp, is probably associated with occurrence of the stomatocytes in blood smears, when the inverted shape of erythrocytes were caused by poor membrane. So the occurrence of haemolysis of erythrocytes was increased. Other haematological parameters correspond to this pathological status, especially decreased concentration of haemoglobin and increased volume of erythrocytes. The reaction of the tissue was not in any case caused by macroscopically and microscopically detectable residues of dark-blue pigment on the mucous membrane of stomach. Also the small nodular clusters of the mononuclear cells in liver were also occurred in limited number of animals at all dose levels. Their character did not demonstrate the toxic effect of the test substance, because the occurrence of alteration of liver cells is missing, nor the results of biochemical examination did not indicate the toxic effect. With increasing dose level, any increased frequency or intensity of mentioned affections were recorded. The consequence of the quantitative differential in the quantity of neutral lipids in the plasma of hepatocytes is given by individual difference of lipids metabolism. In all cases it was finely droplet or irregular steatosis, not dystrophic steatosis with character of dying liver cells. The other pathomorphological affection has not integral character (spermatic granuloma in epididymides, advanced dystrophy of testes and occurrence of non-septic nephritis of interstitium) in animals at the highest dose level. It may be classified like a spontaneous and occasional. After the examinations may be stated, the test substance had a negative effect in dependence of sexes and doses, because it caused a dose dependent hard harm in females at the highest dose level (1000 mg/kg).
Applicant's summary and conclusion
- Conclusions:
- The mid dose of 500 mg/kg may be considered as NOEL (no-observed-effect level).
- Executive summary:
The test substance Ostazin Black H-N was tested in the 28-days study according to the guideline OECD No. 407 (OECD, 1981). The test substance was administered to Wistar rats as a suspension in water using a stomach tube. The concentrations of suspensions were 100, 500 and 1000 mg/kg of the body weight. During the study, checking of the health status was performed daily. The detailed clinical observation, food consumption and record of the body weight were performed weekly. At the same time interval (weekly), test substance volume was adjusted according to the body weight of the animals. Haematological and biochemical analysis and the urinalysis were performed of the 28th and 42nd day of study. At the end of application period of the test substance or the observation period, gross necropsy of animals with the macroscopic revision of the thoracic, abdominal and cranial cavity was performed. The selected organs for histopathology examinations were removed. The test substance at the lowest (100 mg/kg) dose level and at the middle dose level (500 mg/kg) did not affect a behaviour of the test animals and body weight increment and did not cause changes in haematological and biochemical parameters with a deviation from physiological norms. Also the results of histopathological examinations did not demonstrate changes depending on the test substance either. Therefore the middle dose level (500 mg/kg) may be considered as NOEL (no-observed-effect level). The test substance at the highest dose level (1000 mg/kg) caused changes in behaviour of the test animals and stool consistency. Changes in the haematological parameters were detected. There was a change in the differential leukocyte count with occurrence of young developmental forms, especially myelocytes and metamyelocytes. An occurrence of the stomatocytes was observed in a microscopic examination of blood smears. Increased total number of leukocytes above the limit of physiological norms was observed in males. In females, the value of MCV (the mean corpuscular volume) was increased above the limit of physiological ranges and haemoglobin was at a lower limit. Biochemical parameters showed increasing concentration of Cl- ions above the limit of physiological norms and the concentration of Na+ions decreased below the limit of physiological norms. The histopathological examination of the animals at the highest dose level revealed enlargement of the spleen with russet pigment and numerous scavenger cells in a red pulp. In the satellite groups the haematological and biochemical values returned to the physiological range, however increased total number of leukocytes were still seen in males only. Histopathological changes at the highest dose level (1000 mg/kg bw/day) persisted in both sexes, especially in females. Based on the above findings, it can be said that this substance (or metabolites) caused changes dependent on dose levels and sex of the animals. The changes of the haematological parameters and increased erythrocyte haemolysis, which caused damage of spleen tissue, were recorded. The test substance also caused reversible changes of the biochemical parameters. With respect to the results of the study, the middle dose level 500 mg/kg may be considered as NOEL (no-observed-effect level).
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