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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 241-034-8 | CAS number: 16961-83-4
- 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
Neurotoxicity
Administrative data
- Endpoint:
- neurotoxicity
- Remarks:
- subchronic
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Published peer-reviewed study
Data source
Reference
- Reference Type:
- publication
- Title:
- Neurotoxicity of sodium fluoride in rats
- Author:
- Mullenix PJ, Denbesten PK, Schunior A & Kernan WJ
- Year:
- 1 995
- Bibliographic source:
- Neurotoxicology and Teratology, 17(2): 169-177
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Behavioural neurotoxicity study in rats exposed either prenatally, as weanlings, or as adults.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Sodium fluoride
- EC Number:
- 231-667-8
- EC Name:
- Sodium fluoride
- Cas Number:
- 7681-49-4
- Molecular formula:
- FNa
- IUPAC Name:
- sodium fluoride
- Details on test material:
- Sodium fluoride (NaF) was the test substance, and the authors were looking at the effects of fluoride.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Pathogen free Sprague-Dawley rats obtained from Charles River Laboratories. Rats were randomly assigned to treatment groups and housed 2/cage/treatment and sex. Light was provided on a 12 h light:dark cycle, and food and deionised water were offered ad libitum except during behavioural testing.
Pregnant dams were obtained on gestation day 8, and housed individually throughout gestation and lactation. Dams were fed Purina Rat Chow (Formulab), and pups were fed Certified Purina Rat Chow (5002) after weaning.
Weanlings were obtained (with dams) at 19 days of age. The pups were weaned on gestation day 21 and maintained on a low fluoride diet (<10ppm fluoride, Purina 5010 or Teklad L356).
Adult rats were obtained at 10 weeks of age, and exposures began at 12 weeks of age. They were maintained on the same low fluoride diet as the weanlings.
Administration / exposure
- Route of administration:
- other: one group received subcutaneous injections, the other groups received NaF in their drinking water
- Vehicle:
- other: saline (s.c.) or distilled water (oral)
- Details on exposure:
- Prenatal exposures: On gestational days 14-18, or 17-19, dams were given subcutaneous injections of 0.13 mg/kg sodium fluoride in saline, two or three times daily, at least 4 hours apart. Controls received an equal volume/body weight s.c. injection of saline alone on days to match the treated group. Beyond the prenatal period the pups received no further NaF treatment.
Weanling exposures: From gestation day 21 (weaning) the rats were exposed to NaF in their drinking water at concentrations of 0, 75, 100, 125, or 175ppm. Each fluoride treatment group had matching controls that received deionised water only. The 175ppm was studied only in females, and resulted in mortalities within 10 days of exposure. The survivors in this group received water only for the remainder of the study. Rats were exposed for 6 or 20 weeks.
Adult exposures: male and female rats aged 12 weeks old were exposed to 0 or 100ppm NaF in their drinking water for 5 to 6 weeks. - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No information available.
- Duration of treatment / exposure:
- Prenatal exposure: 5 or 3 days.
Weanling exposure: 6 or 20 weeks.
Adult exposure: 5 or 6 weeks. - Frequency of treatment:
- Prenatal exposure: 2 or 3 times daily.
Weanling and adult exposure: daily.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 ppm
- Remarks:
- nominal in water
- Dose / conc.:
- 75 ppm
- Remarks:
- nominal in water
- Dose / conc.:
- 100 ppm
- Remarks:
- nominal in water
- Dose / conc.:
- 125 ppm
- Remarks:
- nominal in water
- Dose / conc.:
- 175 ppm
- Remarks:
- nominal in water; 175ppm was discontinued due to excessive mortality
- Dose / conc.:
- 0.13 other: mg/kg
- Remarks:
- nominal conc., nominal in saline
- No. of animals per sex per dose:
- Prenatal exposures: 7 dams were treated on gestational days 14-18, 9 dams were treated on gestational days 17-19, 13 dams served as controls. Litters were culled to 10 pups per litter.
Weanling exposures: 19-27/sex/dose.
Adult exposures: 21-24/sex/dose. - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Doses were selected based on published data that showed 100 ppm fluoride in drinking water produces dental fluorosis without overt toxicity.
Examinations
- Observations and clinical examinations performed and frequency:
- Body weights were recorded at various points during the study.
- Specific biochemical examinations:
- Blood samples were collected by cardiac puncture under CO2 anaesthesia at study termination (satellite groups were used where blood samples were required prior to behavioural testing). Plasma fluoride concentrations were determined using an ion-specific electrode following the hexamethyldisiloxane diffusion method.
Brain fluoride concentrations were determined for two treatment groups in the weanling or adult exposure studies. Brains were removed and chilled, 7 sections were dissected, individually lyophilised and weighed, and the fluoride content measured following diffusion of ionic fluoride. - Neurobehavioural examinations performed and frequency:
- Except for adult exposures, behaviour was tested at 9 weeks of age, and repeated at 14 and 19 weeks depending on exposure period. Tests were conducted in an isolated observation room at the same time each day. Video cameras were used to record rat behaviour at a rate of 1 frame/s. Spontaneous behaviour in a novel environment was recorded. The novel environment was a clear Plexiglass box, where the control and treated rats were separated by a clear partition with small holes allowing them to see and smell each other during exploration. The video signals were transferred to a computer for pattern analysis and behavioural classification. The behaviours identified by the computer were 5 major body positions, and the specific activity i.e. grooming, sniffing etc.
Measures of behaviour were: calculation of behavioural initiations , calculation of behavioural total time, and calculation of behavioural time structure. - Sacrifice and (histo)pathology:
- Brain weights were recorded in the animals used for brain fluoride content analysis.
- Other examinations:
- No other examinations were made.
- Positive control:
- Not examined.
- Statistics:
- t-tests were used to compare the number of behavioural initiations and behavioural total time per groups between groups. The behavioural time structure was analysed using K functions and RS statistics.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Clinical biochemistry findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- effects observed, treatment-related
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Other effects:
- not examined
- Description (incidence and severity):
- Migrated information from 'Further observations for developmental neurotoxicity study'
Details on results (for developmental neurotoxicity):Prenatal exposures: Prenatal NaF exposure altered behavioural outcomes in male offspring when exposure occurred on gestation days 17-19. The effect was in time structure changes. (migrated information) - Details on results:
- Weanling exposures: At 125ppm body weight was reduced throughout 20 weeks exposure in both sexes. The survivors of the 175ppm had stunted growth compared to matched controls, however the effects were ameliorated by 18 weeks of age. Plasma fluoride levels were significantly increased in all exposed animals; at doses of 75 and 100 ppm for 6 weeks plasma fluoride increased with dose. At 125ppm for 6 weeks plasma fluoride was increased compared to controls but not in a dose dependent fashion. Behaviour was altered in both sexes, dependent on duration and concentration of exposure. In females, 6 weeks exposure to 100 or 125ppm affected behaviour, in males 11 weeks exposure to 125ppm affected behaviour. A relationship between behavioural effects and plasma fluoride was observed in females expoed for 6 weeks to 75, 100 or 125 ppm. A common pattern amongst behavioural disturbances, irrespective of sex, exposure duration or fluoride concentration, developed.
Adult exposures: male and female rats given 100ppm for 6 weeks had significantly increased plasma fluoride levels with no effect on body weight. Behaviour was only affected in females. Compared to females exposed at weaning, females exposed as adults had a lower plasma fluoride level associated with significant behavioural changes.
Fluoride exposure elevated fluoride levels in the brain. In male and female rats exposed to 125ppm for 20 weeks starting at weaning fluoride levels were increased in all 7 brain regions examined. In rats exposed to 100 ppm for 6 weeks starting at 3 months of age fluoride levels increased in the medulla oblongata in both sexes, and in the hippocampus of females.
Any other information on results incl. tables
Fluoride exposure caused sex and dose specific behavioural disruption (as measured by computer pattern recognition in a novel environment), with a common pattern. Males were most sensitive to prenatal day 17 -19 exposure, whereas females were more sensitive to weanling and adult exposures. After fluoride ingestion, the severity of the effect on behaviour increased directly with plasma F levels and F concentrations in specific brain regions.
Applicant's summary and conclusion
- Conclusions:
- Fluoride exposure caused sex and dose specific behavioural disruption (as measured by computer pattern recognition in a novel environment), with a common pattern.
- Executive summary:
The study was designed to assess the neurotoxicity of sodium fluoride (NaF) in Sprague-Dawley rats. Rats were exposed prenatally, as weanling, or adults. Prenatal exposure - dams were injected subcutaneously with 0.13 mg/kg NaF or saline on gestational days 14 -18 or 17 -19. Weanlings were exposed to NaF in their drinking water at 0, 75, 100 or 125 ppm for 6 to 20 weeks. 3 month old adults received water containing 100 ppm for 6 weeks. Fluoride exposure caused sex and dose specific behavioural disruption (as measured by computer pattern recognition in a novel environment), with a common pattern. Males were most sensitive to prenatal day 17 -19 exposure, whereas females were more sensitive to weanling and adult exposures. After fluoride ingestion, the severity of the effect on behaviour increased directly with plasma F levels and F concentrations in specific brain regions.
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.