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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 911-915-8 | 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:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 975
- Report date:
- 1975
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 452 (Chronic Toxicity Studies)
- GLP compliance:
- no
- Limit test:
- no
Test material
Test animals
- Species:
- dog
- Strain:
- Beagle
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Marshall Research Animals, Inc. North Rose, New York
- Age at study initiation: 5-6 months
- Weight at study initiation: males 8.8-11.8 kg, females 7.4-12.1 kg
- Housing: individually in elevated cages
- Diet (e.g. ad libitum): standard laboratory diet presented daily
- Water: ad libitum
- other: animals were immunized against distemper, hepatitis and leptospirosis (pretest by supplier)
Administration / exposure
- Route of administration:
- other: oral intubation
- Vehicle:
- other: 0.25 % Methocel 90 (R) HG Premium 15000 CPS (DOW Chemical)
- Details on oral exposure:
- Preparation:
Appropriate amounts of compound (adjusted by most recent weekly body weight) were suspended in the vehicle weekly. The suspension was shaken thoroughly before each use.
Storage:
Suspensions were refrigerated when not in use.
Volume:
1 cm³/kg bw days 1-6 ; 3 cm³/kg bw day 7-termination - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 740-749 days
- Frequency of treatment:
- - daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 10 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- - 6
- Control animals:
- yes
- Details on study design:
- For the first five weeks , the highest dose was 25.0 mg/kg bw/d.
During the 6th week, the high-dose dogs were not dosed to allow them to recover from emesis, diarrhoea and anorexia. During the 7th week, the high dose dogs received placebo treatment (vehicle) in an attempt to decondition dogs from salivating in anticipation of dosing. Dosing was assumed at the beginning of the 8th week at the reduced dose level of 10 mg/kg bw/d.
Examinations
- Observations and examinations performed and frequency:
- General:
- daily for physical appearance, signs of local systemic toxicity, pharmacologic effects or mortality
Body weight:
- once pretest, weekly and terminally (after fasting)
Food consumption:
- estimated pretest and 4 times weekly thereafter
Ophtalmoscopic examinations:
- pretest and months 6, 12 and 24
Laboratory studies:
- twice pretest and months 1, 3, 6, 9, 12, 20 and 24 (all animals)
Hematology
-hemoglobin, hematocrit, erythrocytes, reticulocytes, total and differential leukocytes, erythrocyte morphology, bone marrow differential, prothrombin time
Clinical chemistry:
- SGOT, SGPT, alkaline phosphatase, blood urea nitrogen, fasting glucose, cholesterol (months 12+24), triglycerides (months 12+24), total protein, creatinine (months 12+24), uric acid (months 12+24), sodium, potassium, calcium, phosphorus, chloride
Urinalysis:
- bilirubin, glucose, gross appearance, ketones, occult blood, pH, protein, specific gravity - Sacrifice and pathology:
- - Animals Dying spontaneously: necropsy performed
- Interim necropsy examination: month 6 , No of animals 16 (2/sex/group)
- Sacrifice method: exsanguinated under sodium pentobarbital anaesthesia
- Organs weighed: liver, kidneys, adrenals, thyroid
- Tissues fixed: adrenal, bone rib junction, mandible with teeth, head of femur, bone marrow, sternal, brain, eyes with optic nerve, gall bladder, heart with coronary vessels, colon, duodenum, ileum, jejunum, kidney, liver lungs, lymph node (mesenteric), mammary gland, ovaries, pancreas, parathyroid, pituitary, prostate, salivary gland, skeletal muscle, spleen, stomach, testes, thyroid, urinary bladder, uterus, gross lesions, tissue masses - Statistics:
- Body weight, food consumptions, haematology and clinical chemistry parameters, organ weights and organ/body weight ratios were analyzed.
Compound treated groups were compared to control at each time interval.
Results and discussion
Results of examinations
- Details on results:
- At the original high-dose level (25.0 mg/kg bw/d for the first 5 weeks of test), a decrease in body weight and food consumption occurred, with excessive salivation before and after dosing and increased incidences of diarrhoea and emesis in both sexes were noted. These effects gradually disappeared after the high-dose was reduced from 25.0 to 10 mg/kg bw/d.
After 24 months slightly lower serum phosphorus levels were noted at 10 mg/kg bw/d in both sexes and at 1.0 and 5.0 mg/kg bw/d in the females. Lower phosphorus levels were also noted in the high-dose females at twenty months.
Yellow discoloration and reticoloendothelial cell hyperplasia and hypertrophy of mesenteric lymph nodes occurred in dogs receiving 5.0 and 10.0 mg/kg bw/d.
There were no other microscopic or macroscopic tissue alterations considered attributable to the administration of amine fluorides 297/242.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- gross pathology
- Dose descriptor:
- LOAEL
- Effect level:
- 5 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- gross pathology
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
After 5 weeks, the high dose (25 mg/kg bw/day) was reduced to 10 mg/kg bw/day because of intolerance.
Applicant's summary and conclusion
- Executive summary:
In a chronic toxicity study Amine fluorides (1.315 % Olaflur as leading substance and 0.347 % Hetaflur) were administered orally per intubation to 6 Beagle dogs per sex per dose at dose levels of 0, 1, 5 or 25 (10) mg/kg bw/day for a period of 2 years (Menley & James Laboratories, 1975). The NOEL was considered to be 1 mg/kg bw/day for both males and females.
After 5 weeks, the high dose (25 mg/kg bw/day) was reduced to 10 mg/kg bw/day because of intolerance. Animals of the high and middle dose group showed reduced body weight gains. At the end of treatment slightly lower serum phosphate levels were determined as compared to the controls. On dissection, a yellowish discoloration and hyperplasia/hypertrophy of the reticulo-endothelial system was seen. No other macroscopic or microscopic changes were found in the organs and tissues.
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.