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Diss Factsheets
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EC number: 234-666-0 | CAS number: 12021-95-3
- 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
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Endpoint summary
Administrative data
Description of key information
In rodents, repeated exposure to fluoride salts, such as sodium fluoride, causes alteration of teeth at daily doses of 4 mg NaF/kg bw/day or greater. Higher repeated doses of 10 and 25 mg NaF/kg bw/day increase dental effects as well as cause toxic effects in bone and the stomach. The severity of the toxic effects is related to increasing dose and duration of exposure. In a life-time chronic exposure study in the rats, an extremely high concentration of 175 ppm sodium fluoride in drinking water was associated with an increased incidence of osteosclerosis in female rats and equivocal evidence of osteosarcoma in male rats.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEL
- 8.2 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
Additional information
Subacute Toxicity:
A 28-day repeated oral toxicity study (Proctor & Gamble, Co., 1991) was conducted to characterize the systemic toxicity of sodium fluoride. Weanling male and female Sprague-Dawley rats were dosed by gavage at concentrations of 2.5, 25 or 250 ppm sodium fluoride. The NOEL was 25 ppm. The following effects were observed at 250 ppm; hematology - significant depression in mean cell volume of males and females and mean cell hemoglobin of males; clinical chemistry - significant decrease in total protein of males and females and significant increase in alanine aminotransferase, potassium and chloride of females only; several changes in the mineral analysis of teeth and bone; and increased absolute and relative stomach weights.
Subchronic Toxicity:
The U.S. National Toxicology Program (NTP, 1990) evaluated the toxicological effects of continuous exposure to 0, 30, 100 or 300 ppm sodium fluoride in drinking water on F344 male and female rats for a 6-month period. Sodium fluoride caused weight loss at 300 ppm, fluorosis of the teeth at 100 and 300 ppm, minimal hyperplasia of the gastric mucosa of the stomach at 100 and 300 ppm (however, one high dose rat of each sex had an ulcer), a dose-related increase in fluoride content of bone and urine with increasing fluoride concentration in the drinking water, and a significant increase in fluoride content in the plasma at 300 ppm. No significant signs of toxicity were observed at concentrations of 10 or 30 ppm.
The U.S. National Toxicology Program (NTP, 1990) evaluated the toxicological effects of continuous exposure to 0, 10, 50, 100, 200, 300 or 600 ppm sodium fluoride in drinking water of male and female B6C3F1 mice for a 6-month period. Sodium fluoride caused death in some animals at 600 ppm and in a single male animal at 300 ppm, weight loss at 200 to 600 ppm, fluorosis of the teeth at 100, 200, 300 and 600 ppm, acute nephrosis and/or lesions in the liver and myocardium in mice that died early, minimal alterations in bone growth/remodeling in the long bones at 50 to 600 ppm, a dose-related increase in fluoride content of bone and urine with increasing fluoride concentration in the drinking water, and a possible dose-related increase in fluoride content in the plasma. No signs of toxicity were observed at the low dose of 10 ppm sodium fluoride.
Chronic Toxicity
The U.S. National Toxicology Program (NTP, 1990) evaluated the toxicological and carcinogenic effects of continuous exposure to 0, 25, 100 or 175 ppm sodium fluoride in drinking water on male and female F344/N rats for a 2 -year period. Survival and weight gains of the male and female rats were not affected by fluoride treatment. Rats receiving sodium fluoride developed effects typical of dental fluorosis at 25, 100 and 175 ppm, and female rats had increased osteosclerosis at the high-dose of 175 ppm.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Key study. In the registration dossier for KF and NaF, a LOAEL of 10 mg/kg/by, based on NaF was selected from a chronic study as the relevant effect level. This is re-calculated to 8.2 mg/kg/day based on H2ZrF6, based on the fluoride content of both substances.
Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: stomach; other: bone
Justification for classification or non-classification
Based on the results described above, classification for repeated dose toxicity is not warranted.
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.
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