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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 419-370-3 | CAS number: 84632-66-6
- 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:
- 1995-02-01 to 1995-02-28
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP and guideline study. Not allrecommended organs were weighed and not all tissues/organs examined histopathologically. No FOR was performed (no 90-day study available.)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Version / remarks:
- 92/69/EEC, 31-Jul-1992
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- adopted May 12, 1981
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Revised Japanese Chemical Substance Law (1987) according to the notification of Dec. 9, 1986 by EA, Environmental Agency (No. 700); MHW, Ministry of Health and Welfare (No. 1039) and MITI, Ministry of International Trade and Industry (No. 1014)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wolferstrasse 4, 4414 Fuellinsdorf/Switzerland
- Age at study initiation: 6 weeks
- Weight at study initiation: Males: 137.4 - 152.8 g, Females: 113.3 - 126.7 g
- Fasting period before study: no
- Housing: Individually in Makrolon type-3 cages with autoclaved standard softwood bedding ('Lignocel', Schill AG, CH-4132 Muttenz).
- Diet: Pelleted standard Kliba no. 343, Batch nos. 82/94 and 84/94 rat maintenance diet ('Kliba', Klingentalmuehle AG, CH-4303 Kaiseraugst) ad libitum.
- Water: Community tap-water from Fullinsdorf was available ad libitum.
- Acclimation period: From 25-JAN-1995 to 31-JAN-1995 under laboratory conditions, after health examination.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 46-66
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 1995-01-25 To: 1995-03-15
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test article was weighed into a glass beaker on a tared Mettler PM 480 balance and the vehicle was added. The mixture (w/v) was prepared using a homogenizer. Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer.
- Rate of preparation: Daily prior to each application
VEHICLE
- Justification for use and choice of vehicle: Standard vehicle for studies of this type, recommended in the guidelines.
- Amount of vehicle: 10 mL/kg bw per treatment day - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentration, homogeneity and stability of the test article/vehicle mixtures were determined in samples taken during acclimatization and during week 3 of the treatment. The analyses were performed according to a photometrical method.
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- Once daily, 7 days per week for a total of 28 days.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 50, 200 and 1000 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- Dose groups:
5 males and 5 females in each group.
Recovery groups:
5 males and 5 females (0 and 1000 mg/kg bw/day) - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on acute oral test
- Post-exposure recovery period in satellite groups: yes (0 and 1000 mg/kg bw/day), 14 days - Positive control:
- none
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule:
Observations for mortality/viability and clinical signs of toxicity were recorded once daily.
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations:
The body weights were recorded weekly and twice during week 4 of treatment and week 2 of the recovery period.
FOOD CONSUMPTION:
The food consumption was recorded once during the acclimatization period and weekly thereafter.
FOOD EFFICIENCY: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations:
at 4 weeks (on all animals) and at 6 weeks (on all recovery animals)
- Examinations:
A description of any abnormality was recorded. 10 - 90 minutes after the application of a mydriatic solution (Dispersa AG, CH-8442 Hettlingen) the cornea, lens, anterior chamber, vitreous body and ocular fundus of both eyes were examined under dimmed light using a Heine BETA 200 Ophthalmoscope (Eisenhut Vet. AG, CH-4123 Allschwil).
HAEMATOLOGY: Yes
- Time schedule for collection of blood:
at 4 weeks: all animals
at 6 weeks: all recovery animals
- Anaesthetic used for blood collection: Yes (light ether anesthesia)
- Animals fasted: Yes
- How many animals: all animals
- Parameters checked:
Erythrocyte count
Hemoglobin
Hematocrit
Mean corpuscular volume
Mean corpuscular hemoglobin
Mean corpuscular hemoglobin concentration
Platelet count
Reticulocyte count
Reticulocyte fluorescence ratios
Nucleated erythrocytes (normoblasts)
Heinz bodies
Methemoglobin
Total leukocyte count
Differential leukocyte count
Red cell morphology
Coagulation: Thromboplastin time
Activated partial thromboplastin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood:
at 4 weeks: all animals
at 6 weeks: all recovery animals
- Animals fasted: Yes
- How many animals: all animals
- Parameters checked:
Glucose
Urea
Creatinine
Uric acid
Bilirubin, total
Cholesterol, total
Triglycerides
Phospholipids
Aspartate aminotransferase
Alanine aminotransferase
Lactate dehydrogenase
Creatine kinase
Alkaline phosphatase
Gamma-glutamyltransferase
Calcium
Phosphorus
Sodium
Potassium
Chloride
Albumin
Protein, total
Globulin
Albumin/Globulin ratio
URINALYSIS: Yes
- Time schedule for collection of urine: Urine was collected during the 18-hours fasting period into a specimen vial.
- Metabolism cages used for collection of urine: yes (model K. Ehret & Co., Emmendingen, Germany)
- Animals fasted: Yes
- Parameters checked:
Volume (18-hour)
Specific gravity
Osmolairity
Color
Appearance
pH
Protein
Glucose
Ketone
Bilirubin
Blood
Urobilinogen
Urine Sediment
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- NECROPSY
after 4 weeks - all animals
after 6 weeks - recovery group
All animals were weighed and necropsied and descriptions of all macroscopic abnormalities were recorded. At the end of the treatment or recovery period the animals were anesthetized by intraperitoneal injection of NARCOREN (Rhone Merieux GmbH, D-88471 Laupheim) at a dose of 2.0 mL/kg bw (equivalent to 320 mg sodium pentobarbitone/kg body weight), weighed and sacrificed by exsanguination.
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Tissues collected: Adrenals; aorta; bone (sternum, femur); bone marrow (sternum, femur); brain; cecum; colon; duodenum; epididymides; esophagus; eyes with optic nerve and Harderian gland; femur including joint; heart; ileum; jejunum; kidneys; larynx; lacrimal gland, exorbital; liver; lung; lymph nodes (mandibular, mesenteric); mammary gland area; nasal cavity; ovaries; pancreas; pituitary gland; prostate gland; rectum; salivary gland (mandibular, sublingual); seminal vesicles; sciatic nerve; skeletal muscle; skin; spinal cord (cervical, midthoracic, lumbar); spleen; stomach; testes; thymus; thyroid incl. parathyroid gland; tongue; trachea; urinary bladder infused with formalin; uterus; vagina and gross lesions.
Tissues examined: Slides of adrenals, heart, kidneys, liver, lungs, spleen, stomach and testes collected at terminal sacrifice from the animals of the control and high-dose groups were examined by a pathologist. The same applied to the testes from males of 50 and 200 mg/kg bw/day treatment groups and to all gross lesions from all animals.
ABSOLUTE AND RELATIVE ORGAN WEIGHTS
The following organ weights were recorded on the scheduled dates of necropsy:
Adrenals, brain, heart, kidneys, liver, ovaries, pituitary, spleen, testes, thyroid including parathyroid gland.
The organ to terminal body weight ratios as well as the organ to brain weight ratios were determined. - Other examinations:
- none
- Statistics:
- The following statistical methods were used to analyze the body weights, food consumption, organ weights and all ratios and clinical laboratory data :
When the variables could be assumed to follow a normal distribution, the Dunnett-test (many to one t-test) based on a pooled variance estimate was applied for the comparison between the treated groups and the control groups for each sex. The Steel-test (many-one rank test) was applied when the data could not be
assumed to follow a normal distribution. The Fisher's exact test was applied to the ophthalmoscopy data.
Results and discussion
Results of examinations
- Details on results:
- CLINICAL SIGNS AND MORTALITY
All animals survived their assigned study period.
No clinical signs of toxicity were observed in any group. The only finding of note was a discoloration of the feces which occurred in animals of all treated groups during the treatment period.
BODY WEIGHT AND WEIGHT GAIN
There was no effect on body weight in any group. The body weight gain was similar in all groups and no statistically significant differences occurred during the study.
FOOD CONSUMPTION
The ranges for individual food consumption were similar in treated and control rats. There were no treatment-related significant differences in mean absolute and relative food consumption noted for any treated group when compared with the vehicle control group.
OPHTHALMOSCOPIC EXAMINATION
There were no treatment-related ophthalmoscopic findings noted for any group.
HAEMATOLOGY
The assessment of hematology data indicated no changes of toxicological significance at termination of the treatment nor at the end of the treatment-free period.
CLINICAL CHEMISTRY
The assessment of clinical biochemistry data indicated no changes of toxicological significance at termination of the treatment nor at the end of the treatment-free period.
URINALYSIS
The assessment of urinalysis data indicated no changes of toxicological significance at termination of the treatment nor at the end of the treatment-free period.
ORGAN WEIGHTS
No treatment-related changes of organ weights, organ to body weight and organ to brain weight ratios were observed during the study.
GROSS PATHOLOGY
The reddish discoloration of the mucosa of various segments of the gastrointestinal tract of animals primarily of group 3 (200 mg/kg bw/day) and 4 (1000 mg/kg bw/day) was considered to be due to deposits of the test article.
HISTOPATHOLOGY: NON-NEOPLASTIC
Minimal to slight seminiferous tubular atrophy was noted in the testes of three rats of the high dose group (1000 mg/kg bw/day) at the end of the main study period. This finding was no longer in evidence following the recovery period.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no test item-related adverse effects up to and including the high dose level of 1000 mg/kg bw/day
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
ANALYSIS OF DOSE FORMULATIONS:
Adequate homogenicity of the test item in the dose formulations and adequate accuracy of preparations were confirmed by the analytical results.
Applicant's summary and conclusion
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.
Hoewel ECHA veel materiaa in uw taal online heeft, is een deel van deze pagina in het Engels. Meer informatie van ECHA over meertaligheid.
Welkom op de ECHA-website. In Internet Explorer 7 (en vroegere versies) wordt deze site niet volledig ondersteund. U schakelt het best op een recentere versie van Internet Explorer over.
Deze website maakt gebruik van cookies om het surfen zo aangenaam mogelijk te maken.
Lees meer over hoe wij cookies gebruiken.