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EC number: 432-550-6 | CAS number: 243858-01-7
- 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:
- July 08, 1999 to Aug. 19, 1999
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 000
- Report date:
- 2000
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:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 432-550-6
- EC Name:
- -
- Cas Number:
- 243858-01-7
- Molecular formula:
- Hill formula: C25H22FN7Na4O16S5 CAS formula: C25H26FN7O16S5.4Na
- IUPAC Name:
- tetrasodium 2-({4-fluoro-6-[methyl({2-[2-(sulfonatooxy)ethanesulfonyl]ethyl})amino]-1,3,5-triazin-2-yl}amino)-5-hydroxy-6-[2-(4-methyl-2-sulfonatophenyl)diazen-1-yl]naphthalene-1,7-disulfonate
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Name of test material (as cited in study report): Reaktiv Orange F97-0318
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: HARLAN WINKELMANN, Gartenstr. 27, 33178 Borchen, SPF breeding colony
- Age at study initiation: approximately 6 weeks
- Housing: in makrolon cages (type 4) on soft wood granulate in groups of 5 animals
- Diet: ssniffl R/M-H (V 1534), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50 ±20%
- Photoperiod: 12 h light/12 h dark
IN-LIFE DATES: From: July 08, 1999 To: Aug. 19, 1999
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- yes
- Remarks:
- first and last week of treatment
- Details on analytical verification of doses or concentrations:
- HPLC of samples from all dose groups
- Duration of treatment / exposure:
- 28 d
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 62.5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 250 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
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Acute oral toxicity testing of the test substance at a dose of 2000 mg/kg in the rat (only this dose was tested) showed that the LD50 is above 2000 mg/kg bw in both male and female animals. The dose of 2,000 mg/kg was tolerated by all the animals without signs of intoxication.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL EXAMINATION: Yes
- Time schedule: Once before the first treatment and thereafter once a week
FOOD CONSUMPTION: Yes
- Time schedule: 2 times per week
WATER CONSUMPTION: Yes
- Time schedule: once weekly
BODY WEIGHT: Yes
- Time schedule for examinations: before the start of the study and then twice weekly
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the termination of the study and after the recovery period,
- Anaesthetic used for blood collection: Yes ((intraperitoneal injection of 67 + 6. 7 mg/kg bw Ketamine-Hydrochloride + Xylazine).
- Animals fasted: No
- Hematology investigations included erythrocyte count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin {MCH), mean corpuscular hemoglobin concentration (MCHC), leukocyte count, thrombocyte count, differential leukocyte count and red cell morphology,reticulocyte count, Heinz bodies, coagulation time.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the termination of the study and after the recovery period
- Animals fasted: No
- How many animals: 5/sex/dose
- Clinical chemistry parameters evaluated consisted of sodium, potassium, inorganic phosphorus, uric acid, bilirubin total, bilirubin direct, creatinine, glucose, urea, calcium, chloride, aspartate aminotransferase (ASA T/GOT), alanine aminotransferase (ALA T/GPT), alkaline phosphatase CAP),
gamma-alutamvltranspeptidase (GGT), cholesterol, triglycerides, total protein and albumin.
URINALYSIS: Yes
- Time schedule for collection of urine: Day 27 for treatment groups and Day 41 for recovery groups
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Urinalysis consisted of following investigations: appearance, color, volume, specific weight, pH, hemoglobin, protein, glucose, bilirubin, urobilinogen, ketone bodies and sediment.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: At the termination of the study.
- Dose groups that were examined: all
- Battery of functions tested: sensory activity / grip strength / motor activity / other: sensory reactivity to stimuli of different types (auditory, visual, and proprioceptive), presence and absence of pupillary constriction, measurement of motor activity, and forelimb and hindlimb grip strength. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes. skin, orifices, eyes, feeth, oral mucosa and internal organs.
HISTOPATHOLOGY: Yes. Brain, adrenal glands, ovaries, heart, stomach, uterus, lungs, jejunum, lymph nodes (iliac), trachea, colon, lymph nodes (mandibular), thymus, urinary bladder, thyroid with parathyroid glands, liver, testes, bone marrow (sternum), spleen, epididymides, N. ischiadicus , kidneys,prostate gland, spinal cord (cervical). - Other examinations:
- ORGAN WEIGHTS: The following organs were weighed and the organ to body weight ratios calculated: heart, liver, kidneys, adrenal glands, spleen, testes, epididymides, thymus and brain.
- Statistics:
- Treatment group values were compared statistically with the control group values at the level of significance p = 0.05
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- At necropsy of the final and recovery value some animals of the intermediate and nearly all animals of the high dose group showed red or brown-red discolored kidneys. Additionally, all males of the terminal and three males of the recovery high-dose group showed light red discolored testes.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Histopathological examinations revealed intratubular deposition of yellow-red pigment in the kidneys of nine and three animals of the high-dose terminal sacrifice and recovery groups, respectively. This finding was a result of deposition of test material in the tubular cells, particularly in the high dose terminal sacrifice group. This substance deposition did not cause morphological changes in the kidneys, consequently, it was considered to be of no toxicological relevance. In the stomach dose dependent submucosal mixed cellular infiltrations were found in all animals of the terminal sacrifice high-dose group, and in a lower degree in eight intermediate-dose rats. This was considered to be the result of a topical but reversible acute irritation caused by the high salt load administered with the test substance.
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY: No clinical signs were observed. No mortality occured throughout the study.
BODY WEIGHT AND WEIGHT GAIN: Body weight development remained unaffected by the administration of the test substance in all groups.
FOOD CONSUMPTION: Food consumption of all animals remained unaffected by the administration of the test substance throughout the study.
WATER CONSUMPTION: There was no alteration for water consumption throughout the study.
HAEMATOLOGY: A significant increase of the platelets in males of the high dose group was observed. This finding was not considered to be treatment related as it was not accompanied by a statistically significant decrease in coagulation time, occurred in one sex only, and could not be observed in the recovery group. All other hematological parameters remained unaffected.
CLINICAL CHEMISTRY: Clinical chemistry analysis revealed that the serum was discolored orange in all animals of both sexes from the high-dose group. This discoloration was believed to impair the measurement of total bilirubin and total protein and consequently, caused a false significant deviation from the control group. The clinical chemistry also revealed statistically significant increase in serum calcium and cholesterol in female animals of the high dose group. Total protein and albumin was also indicated to be increased in females of the intermediate and/or low dose groups, respectively. Additionally, a decrease in potassium, triglycerides, and glucose was noted in intermediate and high-dose females. Low dose females also had low glucose level. The analyses at the end of the recovery period indicated a statistically significant increase of sodium, potassium, phosphorus, total protein, and albumin in females and sodium, chloride, creatinine, and ASA T in males of the high-dose group. A decrease was noted in the glucose value in males. The increase in serum calcium, cholesterol, and albumin in after 28 d of treatment was considered to be not related to the administration of the test substance. These apparent statistical significances were caused by the lower values of the control animals compared to the historical control data. The apparently increased parameters were found to be inside the physiological ranges and correspond with the historical control data. The decrease in potassium, triglycerides, and glucose in treated animals were also considered incidental findings as all values were in the physiological range of the historical control data.
Consequently, the changes in serum parameter were considered to be of no biological significance and not to be substance related. This was also confirmed taking into consideration that there were no corresponding findings in the recovery group.
URINALYSIS: The urine examination did not show any compound-related effect, sediments were inconspicuous.
NEUROBEHAVIOUR: Neurotoxicological measurements including 'open field' observations, assessment, of sensory function, and forelimb and hindlimb grip strength were not influenced by the administration of the test compound in all groups. As a result of the lower standard deviation of this group, the statistical evaluation revealed an increased motor activity in females of the high dose group. However, this finding was considered not to be treatment-related, as it occurred in one sex only, on average activity of the females was lower in the high than in the intermediate dose group, and the historic control values of males and females were about in the same range.
ORGAN WEIGHTS: At the end of the 28 d treatment period, the statistical evaluation revealed a significant increase of the absolute liver weight of intermediate and high dose females. In relative organ weights a statistically significant increase in spleen weight or kidney weights was noted in males or females, respectively. In males of the high-dose recovery group an increase of the relative liver weight was found. The apparent changes in mean organ weight were considered to be incidental and mainly caused by the lower terminal mean body weight of concerned groups.
GROSS PATHOLOGY: At necropsy of the final and recovery value some animals of the intermediate and nearly all animals of the high dose group showed red or brown-red discolored kidneys. Additionally, all males of the terminal and three males of the recovery high-dose group showed light red discolored testes.
HISTOPATHOLOGY: NON-NEOPLASTIC: Histopathological examinations revealed intratubular deposition of yellow-red pigment in the kidneys of nine and three animals of the high-dose terminal sacrifice and recovery groups, respectively. This finding was a result of deposition of test material in the tubular cells, particularly in the high dose terminal sacrifice group. This substance deposition did not cause morphological changes in the kidneys, consequently, it was considered to be of no toxicological relevance. In the stomach dose dependent submucosal mixed cellular infiltrations were found in all animals of the terminal sacrifice high-dose group, and in a lower degree in eight intermediate-dose rats. This was considered to be the result of a topical but reversible acute irritation caused by the high salt concentration administered with the test substance. Further, sporadic findings were observed in various organs of different animals, which correlated to the gross pathology findings (pigment deposits in the lymph nodes); type and incidence of these changes were not relevant for the assessment of the toxicity of the test substance.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- systemic effects
- Effect level:
- > 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Dose descriptor:
- NOEL
- Effect level:
- 62.5 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
Target system / organ toxicity
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- Under the test conditions, No Observed Adverse Effect Level (NOAEL) for systemic effects, No Observed Adverse Effect Level (NOAEL) for local effects and No Observed Effect Level (NOEL) were determined to be 1000 mg/kg bw, 62.5 mg/kg bw and 62.5 mg/kg bw, respectively.
- Executive summary:
A 28 d oral (gavage) repeated dose toxicity study was conducted in Sprague Dawley rats according to OECD guideline 407 and EU method B.7 in compliance with GLP.
Four groups of animals (5/sex/dose) received the test substance at the dose of 0.0, 62.5, 250.0 and 1,000.0 mg/kg bw/day by oral gavage for a period of 28 d. 14 d recovery groups (control and high dose) were also included in the study. No clinical signs and no mortality occurred throughout the duration of study. No test substance related effects were seen for body weight, food and water consumption, organ weights, hematology, clinical chemistry and urinanalysis investigations. Histopathology rexamination revealed reversible dose dependent, slight acute topical irritations in the submucosa of the stomach in intermdeiate and high dose animals. No systemic effects were observed.
Under the test conditions, No Observed Adverse Effect Level (NOAEL) for systemic effects, No Observed Adverse Effect Level (NOAEL) for local effects and No Observed Effect Level (NOEL) were determined to be 1000 mg/kg bw, 62.5 mg/kg bw and 62.5 mg/kg bw, respectively.
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